bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and safety of cenobamate, a novel antiseizure medication, in healthy Japanese, and an ethnic comparison with healthy non‐Japanese
Authors: Yang Eunsol , Sunwoo Jung , Huh Ki Young , Kim Yu Kyong , Lee SeungHwan , Jang In‐Jin , Yu Kyung‐Sang 
Published: October 2021

AbstractCenobamate (XCOPRI and ONTOZRY) is a novel antiseizure medication for the treatment of focal‐onset seizures. Nonetheless, there is limited information on the pharmacokinetics (PKs), safety, and efficacy of cenobamate in Asian people, including Japanese people. This study aimed to evaluate the PKs and safety of cenobamate after a single oral dose in healthy Japanese subjects and to compare the PKs with that reported in non‐Japanese subjects. A randomized, double‐blind, placebo‐controlled, single ascending dose study was conducted at four dose levels of 50, 100, 200, and 400 mg. Subjects were randomly assigned to cenobamate or placebo in a 6:2 ratio. Cenobamate was rapidly absorbed, reaching its maximum plasma concentration (Cmax) in 0.75 to 2.25 h, and was eliminated with a mean half‐life of 37.0 to 57.7 h. The Cmax increased dose proportionally, whereas area under the concentration‐time curve increased more than dose proportionally, which was consistent with the findings in non‐Japanese subjects. The systemic exposure of cenobamate was comparable between Japanese and non‐Japanese subjects at all dose levels evaluated. All adverse events were mild in severity, and their incidence did not show dose‐dependent trends. Furthermore, there were no clinically significant issues in safety parameters, including sedation tests, neurologic examinations, and Columbia Suicide Severity Rating Scale interviews. In conclusion, the systemic exposure of cenobamate after a single dose in Japanese subjects increased by dose, which was similar to the pattern in non‐Japanese subjects. In addition, a single dose of cenobamate was well‐tolerated in the dose range of 50 to 400 mg in healthy Japanese subjects.
Incidental findings in UK healthy volunteers screened for a COVID‐19 vaccine trial
Authors: Hodgson Susanne H. , Iveson Poppy , Larwood Jessica , Roche Sophie , Morrison Hazel , Cosgrove Catherine , Galiza Eva , Ikram Sabina , Lemm Nana‐Marie , Mehdipour Savviz , Owens Daniel , Pacurar Mihaela , Schumacher Michael , Shaw Robert H. , Faust Saul N. , Heath Paul T. , Pollard Andrew J. , Emary Katherine R. W. , Pollock Katrina M. , Lazarus Rajeka 
Published: October 2021

AbstractThe safety of novel therapeutics and vaccines are typically assessed in early phase clinical trials involving “healthy volunteers.” Abnormalities in such individuals can be difficult to interpret and may indicate previously unrecognized medical conditions. The frequency of incidental findings (IFs) in healthy volunteers who attend for clinical trial screening is unclear. To assess this, we retrospectively analyzed data for 1838 “healthy volunteers” screened for enrolment in a UK multicenter, phase I/II severe acute respiratory syndrome‐coronavirus 2 (SARS‐COV‐2) vaccine trial. Participants were predominantly White (89.7%, 1640/1828) with a median age of 34 years (interquartile range [IQR] = 27–44). There were 27.7% of participants (510/1838) who had at least one IF detected. The likelihood of identifying evidence of a potential, new blood‐borne virus infection was low (1 in 238 participants) compared with identification of an elevated alanine transaminase (ALT; 1 in 17 participants). A large proportion of participants described social habits that could impact negatively on their health; 21% consumed alcohol in excess, 10% were current smokers, 11% described recreational drug use, and only 48% had body weight in the ideal range. Our data demonstrate that screening prior to enrollment in early phase clinical trials identifies a range of IFs, which should inform discussion during the consent process. Greater clarity is needed to ensure an appropriate balance is struck between early identification of medical problems and avoidance of exclusion of volunteers due to spurious or physiological abnormalities. Debate should inform the role of the trial physician in highlighting and advising about unhealthy social habits.
The print media's construction of the ‘drug problem’ in Victorian newspapers: The case of North Richmond Community Health's medically supervised injecting room
Authors: Whiteside Bianca , Dunn Matthew 
Published: October 2021

AbstractIntroductionThe media's influence on policy has been widely documented. This study sought to investigate how Melbourne's medically supervised injecting room (MSIR) was represented in the print media.MethodsA qualitative discourse analysis of Victorian print media (n = 441 items) representation of MSIR was conducted. Constructivist Grounded Theory guided the sampling strategy and coding while the discourse analysis was informed by Bacchi's approach to policy analysis, ‘What's the problem represented to be?’. Print news media was gathered from Factiva and Newsbank databases from January 2016 to June 2020.ResultsThe media's representation of the ‘drug problem’ of overdose was identified by a range of actors in support and opposition of the facility. In attributing the concept of ‘drug use’ to the ‘drug problem’ items most frequently suggest it is the ‘choice’ of the individual to inject illicit drugs. The voices of people who inject drugs (PWID) were largely silenced in the print news media and to re‐conceptualise the ‘drug problem’ to be a ‘health problem’ would aid in the support for the harm reduction strategy. The research highlighted ‘dividing practices’ (residents vs. PWID) and the portrayal of PWID that translate to the lived effects of PWID.Discussion and ConclusionsThe print news media did not directly influence the establishment of the Melbourne MSIR. However, the representation of PWID in the print media must be further investigated for the successful establishment of future harm reduction strategies.
Hohe Prävalenz und geringes Bewusstsein bei Patienten mit chronisch‐entzündlichen Hauterkrankungen und genitaler Beteiligung
Authors: Staubach Petra , Plavic‐Radeka Natascha , Peveling‐Oberhag Adriane , Sohn Anna , Zimmer Sebastian , Weyer‐Elberich Veronika , Lang Berenice Mareen 
Published: October 2021

ZusammenfassungHintergrundEine genitale Beteiligung bei Patienten mit chronisch‐entzündlichen Hauterkrankungen ist zwar häufig, wird jedoch nicht ausreichend erkannt.ZielDie Beurteilung der Prävalenz genitaler Symptome bei Patienten mit Psoriasis und chronischer Urtikaria, der Effekte auf die Lebensqualität, die Arzt‐Patienten‐ Beziehung sowie des Krankheitsmanagements.Patienten und MethodenEs wurden 100 Patienten mit Psoriasis und 100 Patienten mit chronischer Urtikaria aus unserer ambulanten Abteilung sowie 50 gesunde Kontrollen in die Studie aufgenommen. Die Datenerhebung erfolgte mittels Fragebögen, die von dermatologischen Experten entwickelt wurden.Ergebnisse74 % der 250 Teilnehmer litten schon einmal an genitalen Symptomen – 70 % der Psoriasis‐Patienten und 58 % der Urtikaria‐Patienten. Sieben von zehn Teilnehmern klagten sogar über eine wiederholte genitale Beteiligung. 50 % der Psoriasis‐Patienten und 41 % der Urtikaria‐Patienten berichteten von einem Einfluss auf die Lebensqualität. Bei 41 % war genitaler Pruritus das Hauptsymptom, wobei einer von drei Patienten eine bessere Behandlung für dieses spezifische Problem erwartete. Darüber hinaus beklagten 74 % mangelndes Bewusstsein der Ärzte: 79 % der Urtikaria‐Patienten und 58 % der Psoriasis‐Patienten gaben an, niemals von ihren Ärzten zu genitalen Symptomen befragt worden zu sein.SchlussfolgerungenDer Großteil der Patienten mit Psoriasis und chronischer Urtikaria leidet an einer genitalen Beteiligung und dadurch an einer Beeinträchtigung der Lebensqualität. Die Therapiebeurteilungen von Patienten und Ärzten sollten genitale Symptome als Einflussfaktor auf die Lebensqualität enthalten.
Screening auf Depression bei Psoriasis‐Patienten während einer dermatologischen Konsultation: ein erster Schritt in Richtung Behandlung
Authors: Kromer Christian , Mohr Johannes , Celis Daniel , Poortinga Sietske , Gerdes Sascha , Mössner Rotraut , Wilsmann‐Theis Dagmar 
Published: October 2021

ZusammenfassungHintergrund und ZieleDepression ist bei Psoriasis‐Patienten eine Begleiterkrankung mit hoher Prävalenz. Das Ziel dieser prospektiven Studie war die Nachbeobachtung von Psoriasis‐Patienten mit Depressionsrisiko und die Beurteilung individueller Wege zu psychosozialer Versorgung sowie der Wirksamkeit eines Depressions‐Screenings in einem realen Umfeld.Patienten und MethodenIn dieser prospektiven multizentrischen Studie wurden 355 Patienten mit Psoriasis anhand des Beck‐Depressions‐Inventars (BDI‐II) auf Symptome einer Depression untersucht. Hausärzte von Patienten mit Depressionsrisiko wurden um weitere Beurteilung gebeten. Ein Jahr später wurden Informationen zur psychosozialen Versorgung erfasst.Ergebnisse130 Patienten wurden positiv auf Symptome einer Depression untersucht und 71 Patienten wurden nachbeobachtet (Nachverfolgungsrate: 54,6 %). Eine psychiatrische Behandlung wurde 28,2 % der Patienten empfohlen und von 23,9 % akzeptiert. Parameter der Krankheitsaktivität der Psoriasis (PASI: 3,1, ∆: –1,7, P = 0,018), der Lebensqualität (dermatologischer Lebensqualitätsindex [DLQI]: 6,5, ∆: –2,8, P = 0,005) und Depressionssymptome (BDI‐II: 13,2, ∆: –8.3, P < 0,001) verbesserten sich signifikant. Die Abnahme des BDI‐II‐Wertes war bei Patienten mit starker Abnahme des PASI deutlicher.SchlussfolgerungenScreening nach Depressionssymptomen führte zu erhöhter Inanspruchnahme von psychosozialer Versorgung und einer Verbesserung der Psoriasis, der depressiven Symptome und der Lebensqualität. Daher sollte ein Depressions‐Screening in die Routinebehandlung integriert werden, um die Patientenversorgung zu optimieren.
Komplikationsrisiken im Zusammenhang mit Antithrombotika bei Hautoperationen: Systematischer Review und Metaanalyse
Authors: Scherer Fabian David , Dressler Corinna , Avila Valles Gabriela , Nast Alexander 
Published: October 2021

ZusammenfassungHintergrund und Zielsetzung: Unser Ziel war es, das Komplikationsrisiko bei Operationen an der Haut beim perioperativen Pausieren im Vergleich zum Fortführen von Antithrombotika und beim perioperativen Bridging von Vitamin‐K‐Antagonisten mit Heparin im Vergleich zum Fortführen der Vitamin‐K‐Antagonisten zu evaluieren.Methodik: Wir führten einen systematischen Review durch und haben drei Datenbanken nach einschlussfähigen Studien durchsucht. Die Methodik folgte dem Cochrane Handbook. Wir verwendeten RoB 2 und ROBINS‐I, um das Verzerrungsrisiko zu bewerten. Die Qualität der Evidenz wurde bewertet (GRADE) und fixed‐effect‐Metaanalysen wurden durchgeführt.Ergebnisse: Zwei randomisierte kontrollierte Studien und 19 prospektive Kohortenstudien wurden eingeschlossen. Es ist unklar, ob das perioperative Fortführen von Acetylsalicylsäure das Risiko signifikanter postoperativer Blutungen (SPB) im Vergleich zum Pausieren erhöht (Risikodifferenz (RD) 0,004, 95 %‐Konfidenzintervall (KI) –0,003 bis 0,019).Im Vergleich zum perioperativen Pausieren kann das Fortführen von Phenprocoumon das Risiko für SPB erhöhen (RD 0,02, 95 %‐KI 0,00 bis 0,05). Im Vergleich zum perioperativen Fortführen kann das Bridging von Phenprocoumon mit Heparin das Risiko für SPB erhöhen (RD 0,07, 95 %‐KI 0,01 bis 0,22). Für direkte orale Antikoagulantien wurde keine Evidenz hinsichtlich der Blutungsrisiken gefunden.Schlussfolgerungen: Es wurden keine eindeutigen Hinweise für erhebliche Blutungsrisiken beim perioperativen Fortführen von Antithrombotika bei kleineren Operationen an der Haut gefunden. Allerdings war die Qualität der Evidenz sehr niedrig.
Incidence, hospitalization and mortality and their changes over time in people with a first ever diabetic foot ulcer
Authors: Røikjer Johan , Werkman Nikki C. C. , Ejskjaer Niels , van den Bergh Joop P. W. , Vestergaard Peter , Schaper Nicolaas C. , Jensen Morten Hasselstrøm , Klungel Olaf , de Vries Frank , Nielen Johannes T. H. , Driessen Johanna H. M. 
Published: October 2021

AbstractAimsA diabetic foot ulcer (DFU) is a severe condition associated with morbidity and mortality. Population‐based studies are rare and limited by access to reliable data. Without this data, efforts in primary prevention cannot be evaluated. Therefore, we examined the incidence and changes over time for the first DFU in people with diabetes. We also examined hospitalization and all‐cause mortality and their changes over time.MethodsFrom the UK primary care CPRD GOLD database (2007–2017), we identified 129,624 people with diabetes by a prescription for insulin or a non‐insulin anti‐diabetic drug. DFUs were identified using Read codes and expressed as incidence rates (IRs). Changes over time were described using Poisson and logistic regression and expressed as incidence rate ratios (IRRs) and odds ratios (ORs) respectively.ResultsThe mean IR of first registered DFUs was 2.5 [95% CI: 2.1–2.9] per 1000 person‐years for people with type 2 diabetes and 1.6 [1.3–1.9] per 1000 person‐years for people with type 1. The IRs declined for people with type 2 diabetes (IRR per year: 0.97 [0.96–0.99]), while no changes were observed for people with type 1 diabetes (IRR per year: 0.96 [0.89–1.04]). Average hospitalization and 1‐year mortality risk for people with type 2 diabetes were 8.2% [SD: 4.7] and 11.7% [SD: 2.2] respectively. Both declined over time (OR: 0.89 [0.84, 0.94] and 0.94 [0.89, 0.99]).ConclusionThe decline in all IRs, hospitalizations and mortality in people with type 2 diabetes suggests that prevention and care of the first DFU has improved for this group in primary care in the UK.
A case of variant parachute mitral valve associated with mitral annular disjunction arrhythmic syndrome
Authors: Datta Ishita , Dawdy John , Afonso Luis 
Published: October 2021

AbstractParachute mitral valve (PMV) is a rare congenital cardiac valvular anomaly often associated with other congenital cardiac defects, particularly Shone's complex, but may infrequently occur in isolation. PMV and its variants are predominantly associated with mitral stenosis (MS) or rarely mitral regurgitation (MR). We present the case of a middle‐aged female who was evaluated for a syncopal episode and found to have an atypical variant PMV with disproportionately long anterior mitral leaflet, bileaflet mitral valve prolapse, and mitral annular disjunction, without associated MS or MR. This is the first case report to highlight this particular constellation of findings.
Soil pH drives poplar rhizosphere soil microbial community responses to ozone pollution and nitrogen addition
Authors: Li Pin , Yin Rongbin , Zhou Huimin , Yuan Xiangyang , Feng Zhaozhong 
Published: October 2021

AbstractGround‐level ozone (O3) pollution frequently coincides with the deposition of anthropogenic nitrogen (N), and both factors can influence the structure and functionality of both above‐ and belowground ecosystems. Elevated O3 levels have been shown to adversely impact plants in many prior reports, but the interacting effects of high O3 levels and N addition on exposed plants remain to be clearly defined, and the changes in rhizosphere microbial community composition in this context have yet to be studied. The direct and indirect mechanisms and interactions among plants, microbes, and the soil that shape these O3 and N responses are also poorly understood. Herein, we explored the interactive effects of O3 exposure (five levels) and soil N (four levels) on the composition of rhizosphere soil microbial communities associated with poplar trees (Populus euramericana cv. ‘74/76’). In these analyses, exposure to higher levels of O3 was linked to significant decreases in bacteria, fungi, arbuscular mycorrhizal fungi, and to a reduction in the ratio of fungi‐to‐bacteria, whereas soil N addition had no impact on these parameters. No interactive effects between O3 and N were observed in the context of alterations in soil microbial community composition, and equivalent performance was observed for concentration‐based (AOT40, cumulative exposure to hourly O3 concentrations >40 ppb) and flux‐based [POD1 and POD7, cumulative stomatal uptake of O3 > 1 or 7 nmol O3 m−1 PLA (projected leaf area) s−1] dose–response analyses. Structural equation modelling revealed that changes in the composition of the microbial community were attributable to changes in soil pH but unrelated to plant characteristics. Overall, these findings indicated that increased O3 levels can induce soil alkalinisation and thereby influence soil microbial communities such that soil pH is a reliable predictor of O3 pollution‐related changes in these communities.Highlights
Elevated O3 exhibited an overall negative influence on microorganisms.
AOT40‐, POD1‐ and POD7‐based dose–responses performed equally well.
Soil pH is a reliable predictor of O3 pollution‐related changes in microbial communities.
N addition failed to affect O3 effects on soil microbial community.
Impact of adhesive primer and light‐curing on polymerization kinetics of self‐adhesive resin cement in association with free radical reaction
Authors: Ozaki Akane , Shishido Shunichi , Nakamura Keisuke , Harada Akio , Katsuda Yusuke , Kanno Taro , Egusa Hiroshi 
Published: October 2021

AbstractThis study analyzed the impact of adhesive primer and light‐curing on the polymerization kinetics of urethane dimethacrylate‐based self‐adhesive resin cement combined with free radical reaction. Specimens were prepared by mixing the cement paste with or without adhesive primer. Subsequently, specimens were light‐cured or set without light‐curing. The degree of conversion (DC), Vickers hardness (Hv), and free radical concentrations were repeatedly measured up to 168 h after the curing initiation. Irrespective of the curing procedures, DC, Hv, and free radical concentration rapidly increased during the initial 30 min of curing. The specimens cured with adhesive primer and/or light‐curing generally showed higher values of DC, Hv, and radical concentration than those set by chemical curing alone, especially during the initial polymerization phase. Kinetic analysis using a linear mixed model revealed that the adhesive primer had a higher coefficient estimate than light‐curing, indicating that the former had a higher impact on the polymerization. Additionally, the adhesive primer alleviated the Hv reduction caused by water and air during the initial polymerization phase, although light‐curing hardly prevented the polymerization inhibition. Therefore, we suggest that application of adhesive primer is beneficial to achieve higher degree of conversion and better mechanical properties of self‐adhesive resin cements by enhancing free radical reactions.
No increased risk of Kaposi sarcoma relapse in patients with controlled HIV‐1 infection after switching protease inhibitor‐based antiretroviral therapy
Authors: Lajaunie Rébecca , Cuzin Lise , Palich Romain , Makinson Alain , Bani‐Sadr Firouzé , Duvivier Claudine , Arvieux Cedric , Rey David , Poizot‐Martin Isabelle , Delpierre Cyril , Delobel Pierre , Martin‐Blondel Guillaume ,   And The Dat’AIDS study group
Published: October 2021

AbstractObjectivesOur aim was to assess if switching from a protease inhibitors (PI)‐based regimen to a PI‐free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication.MethodsIn a retrospective analysis of the prospectively collected Dat’AIDS database we selected patients who both had a past KS history and a HIV‐1 viral load below 200 copies/mL while being PI‐treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI‐free regimen.ResultsAmong the 216 patients with past KS event and a history of HIV‐1 infection efficiently treated by a PI‐based regimen, 148 patients (68.5%) later switched to a PI‐sparing regimen. Their baseline characteristics were not different from non‐switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI‐treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/μL (range 225–560) for switching patients, compared with 362 and 136 cells/μL for the other two patients.ConclusionsIn this large cohort of PLHIV with a history of KS and ART‐controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI‐containing ART regimen has been switched to a PI‐free regimen. Our results do not support a specific effect of PI on KS.
IL1R2 polymorphisms and their interaction are associated with osteoporosis susceptibility in the Chinese Han population
Authors: Rong Kai , Liang Zhiquan , Xiang Wenyuan , Wang Zhan , Wen Fengli , Lu Laijin 
Published: October 2021

AbstractAimsInterleukin 1 (IL‐1) inhibitory receptor type 2 (IL1R2) serves as a negative regulator of IL‐1 signalling and is involved in the pathogenesis of osteoporosis. This study aimed to determine the correlation between IL1R2 polymorphism and osteoporosis susceptibility in the Chinese Han population.MethodsWe recruited 594 osteoporosis patients and 599 healthy controls. Six single nucleotide polymorphisms (SNPs) in IL1R2 were selected for genotyping using the Agena MassARRAY platform. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis with adjustment for age and sex. Linkage disequilibrium analysis was plotted using Haploview v4.2. Multifactor dimension reduction (MDR) was performed to estimate the SNP‐SNP interactions of IL1R2 variants.ResultsRs11674595 (OR = 1.86, p = 0.020), rs2072472 (OR = 1.26, p = 0.019) and rs4851527 (OR = 0.78, p = 0.007) were related to the risk of osteoporosis. Moreover, the contribution of IL1R2 polymorphisms to osteoporosis risk was associated with age, sex and body mass index. We found the relationships of Trs11674595Ars4851527 (OR = 0.80, p = 0.015), Crs11674595Grs4851527 (OR = 1.22, p = 0.043) and Ars3218977Grs2072472 (OR = 1.25, p = 0.022) haplotypes to osteoporosis occurrence, and a potential accumulated effect of IL1R2 SNPs (testing accuracy = 0.5783 and cross validation consistency = 10/10) on osteoporosis susceptibility.ConclusionIL1R2 polymorphisms (rs11674595, rs4851527, rs2072472 and rs3218977) may contribute to osteoporosis risk in the Chinese Han population. Our findings may increase our understanding of the effects of IL1R2 polymorphisms on the predisposition to osteoporosis.
Challenges and Opportunities: Creative Approaches to Museum and Gallery Learning during the Pandemic
Authors: Noble Kate 
Published: October 2021

AbstractDuring the pandemic many museums and galleries pivoted from onsite, in‐person delivery to develop a remote offer and to create digital learning resources and activity packs for children and young people. In this article, I draw upon my experience as practitioner researcher on the schools and teachers’ programme at the Fitzwilliam Museum to consider different approaches to supporting participatory creative pedagogies while the museum was closed. After discussing how the work built on and extended existing programming for this audience, I consider effective strategies for facilitating authentic and inclusive encounters with objects and artworks remotely. While some were empowered to take part and to engage, others were locked out through the ever widening social and digital divide. How can we overcome these challenges and make the most of the opportunities which this work has revealed? What are the implications of this work for our understanding of the role, function and future of museum and gallery learning?