bluuebunny/crossref_metadata_2025_split huggingface dataset:
12‐month outcomes of ranibizumab versus aflibercept for macular oedema in central retinal vein occlusion: data from the FRB! registry
Authors: Niedzwiecki Mateusz , Hunt Adrian , Nguyen Vuong , Mehta Hemal , Creuzot‐Garcher Catherine , Gabrielle Pierre‐Henry , Guillemin Martin , Fraser‐Bell Samantha , Arnold Jennifer , McAllister Ian L. , Gillies Mark , Barthelmes Daniel 
Published: September 2021

AbstractPurposeTo compare 12‐month treatment outcomes of eyes receiving aflibercept or ranibizumab for macular oedema secondary to central retinal vein occlusion (CRVO) in routine clinical practice.Methods296 treatment‐naïve eyes receiving either aflibercept (171 eyes, 2 mg) or ranibizumab (125 eyes, 0.5 mg) for macular oedema secondary to CRVO were recruited retrospectively from centres using the prospectively designed FRB! registry. The primary outcome measure was the mean change in LogMAR letter scores of visual acuity (VA). Secondary outcomes included change in central subfield thickness (CST), injections and visits, time to first grading of inactivity, switching and non‐completion from baseline to 12 months.ResultsBaseline VA (SD) was somewhat better in aflibercept‐ versus ranibizumab‐treated eyes (42.5 ± 25.5 letters versus 36.9 ± 26 letters; p = 0.07) with similar CST (614 (240) μm versus 616 (234) μm: p = 0.95). The 12‐month adjusted mean (95%CI) VA change was +16.6 (12.9, 20.4) letters for aflibercept versus +9.8 (5.5, 14.1) letters for ranibizumab (p = 0.001). The mean (95%CI) adjusted change in CST was significantly greater in aflibercept‐ versus ranibizumab‐treated eyes: −304 (−276, −333) µm versus −252 (−220, −282) µm (p < 0.001). Both groups had a median (Q1, Q3) of 7 (5, 9) injections and 10 (8,13) visits. Aflibercept‐treated eyes became inactive sooner than ranibizumab (p = 0.02). Switching occurred more commonly from ranibizumab (26 eyes, 21%) than from aflibercept (9 eyes, 5%) (p < 0.001).ConclusionBoth aflibercept and ranibizumab improved VA and reduced CST in eyes with CRVO in routine clinical practice, with aflibercept showing significantly greater improvements in this comparative analysis.
A stakeholders' attributions approach to integrating normative, descriptive, and instrumental corporate social responsibility
Authors: Perrault Elise , Shaver Kelly 
Published: September 2021

AbstractAlthough there is an extensive body of research that empirically examines the antecedents and outcomes of corporate social responsibility (CSR), much less attention has been accorded to theory development that would suggest why firms engage in CSR, when, and how these initiatives pay off. In this paper, we propose an integrated model of the relationships among the ethical base for engaging in CSR, the pragmatic reality of business–society relationships, and firm strategic outcomes (e.g., normative, descriptive, and instrumental CSR, respectively). Specifically, we consider that a firm's ethical approach to CSR informs the actions and practices through which the firm pragmatically interacts with society. We argue that stakeholders interpret a firm's social performance as reaffirming, repairing, reinforcing, or reducing their perceptions of the firm's reputation—leading to attributions of trust/suspicion that affect firm outcomes. We conclude with the implications of our framework for future research and managerial practice.
Evaluation of the drug‐drug interaction potential of treosulfan using a physiologically‐based pharmacokinetic modelling approach
Authors: Schaller Stephan , Martins Frederico S. , Balazki Pavel , Böhm Sonja , Baumgart Joachim , Hilger Ralf A. , Beelen Dietrich W. , Hemmelmann Claudia , Ring Arne 
Published: September 2021

AimsThe aim of this work is the development of a mechanistic physiologically‐based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug‐drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P‐glycoprotein (P‐gp) substrates.MethodsA PBPK model for treosulfan was developed de novo based on literature and unpublished clinical data. The PBPK DDI analysis was conducted using the U.S. Food and Drug Administration (FDA) DDI index drugs (probe substrates) midazolam, omeprazole and digoxin for CYP3A4, CYP2C19 and P‐gp, respectively. Qualified and documented PBPK models of the probe substrates have been adopted from an open‐source online model database.ResultsThe PBPK model for treosulfan, based on both in vitro and in vivo data, was able to predict the plasma concentration‐time profiles and exposure levels of treosulfan applied for a standard conditioning treatment. Medium and low potentials for DDI on CYP3A4 (maximum area under the concentration‐time curve ratio (AUCRmax = 2.23) and CYP2C19 (AUCRmax = 1.6) were predicted, respectively, using probe substrates midazolam and omeprazole. Treosulfan was not predicted to cause a DDI on P‐gp.ConclusionMedicinal products with a narrow therapeutic index (eg, digoxin) that are substrates for CYP3A4, CYP2C19 or P‐gp should not be given during treatment with treosulfan. However, considering the comprehensive treosulfan‐based conditioning treatment schedule and the respective pharmacokinetic properties of the concomitantly used drugs (eg, half‐life), the potential for interaction on all evaluated mechanisms would be low (AUCR < 1.25), if concomitantly administered drugs are dosed either 2 hours before or 8 hours after the 2‐hour intravenous infusion of treosulfan.
9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial
Authors: Gerhard‐Hartmann Elena , Goergen Helen , Bröckelmann Paul J. , Mottok Anja , Steinmüller Tabea , Grund Johanna , Zamò Alberto , Ben‐Neriah Susana , Sasse Stephanie , Borchmann Sven , Fuchs Michael , Borchmann Peter , Reinke Sarah , Engert Andreas , Veldman Johanna , Diepstra Arjan , Klapper Wolfram , Rosenwald Andreas 
Published: September 2021

SummaryHigh programmed cell death 1 ligand 1 (PD‐L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin‐ and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti‐PD‐1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD‐L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti‐PD‐1‐based first‐line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced‐stage or r/r cHL. All but two cases (97%) showed PD‐L1 expression by the tumour cells in variable amounts. While MHC‐I was rarely expressed in >50% of HRSC, MHC‐II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD‐L1 and MHC‐I/II expression on early response to the highly effective anti‐PD‐1‐based NIVAHL first‐line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti‐PD‐1 first‐line cHL treatment.
Local disconnects in global discourses—The unintended consequences of marine mammal protection on small‐scale fishers
Authors: Davis Katrina J. , Alfaro‐Shigueto Joanna , Arlidge William N.S. , Burton Michael , Mangel Jeffrey C. , Mills Morena , Milner‐Gulland E.J. , Palma‐Duque José , Romero‐de‐Diego Cristina , Gelcich Stefan 
Published: September 2021

AbstractGlobal commitments prioritize protection of wildlife and improvements to human wellbeing. Local disconnects in these commitments are rarely acknowledged—or their implications assessed—preventing the development of effective solutions. National and international efforts to protect marine mammals along South America's west coast have contributed to species recovery, but also to conflict between sea lions and small‐scale fisheries. To understand the concerns ultimately motivating this conflict, we assessed how 301 coastal small‐scale fishers perceive their interactions with South American sea lions (Otaria flavescens). We then reviewed the terrestrial human–wildlife literature to identify potential management solutions to resolve the conflict. We find that fishers are chiefly concerned with increases in sea lion populations, perceive that sea lion interactions have significantly increased over the past 80 years, and report sea lion‐driven catch and income losses of ≥26%. We propose solutions to manage conflict that are sensitive to heterogeneity among fisher groups.
δ‐Tocotrienol sensitizes and re‐sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK‐mediated apoptosis
Authors: Fontana Fabrizio , Marzagalli Monica , Raimondi Michela , Zuco Valentina , Zaffaroni Nadia , Limonta Patrizia 
Published: September 2021

AbstractObjectivesAmong gynaecologic malignancies, ovarian cancer (OC) represents the leading cause of death for women worldwide. Current OC treatment involves cytoreductive surgery followed by platinum‐based chemotherapy, which is associated with severe side effects and development of drug resistance. Therefore, new therapeutic strategies are urgently needed. Herein, we evaluated the anti‐tumour effects of Vitamin E‐derived δ‐tocotrienol (δ‐TT) in two human OC cell lines, IGROV‐1 and SKOV‐3 cells.Materials and MethodsMTT and Trypan blue exclusion assays were used to assess δ‐TT cytotoxicity, alone or in combination with other molecules. δ‐TT effects on cell cycle, apoptosis, ROS generation and MAPK phosphorylation were investigated by flow cytometry, Western blot and immunofluorescence analyses. The synergism between δ‐TT and chemotherapy was evaluated by isobologram analysis.ResultsWe demonstrated that δ‐TT could induce cell cycle block at G1‐S phase and mitochondrial apoptosis in OC cell lines. In particular, we found that the proapoptotic activity of δ‐TT correlated with mitochondrial ROS production and subsequent JNK and p38 activation. Finally, we observed that the compound was able to synergize with cisplatin, not only enhancing its cytotoxicity in IGROV‐1 and SKOV‐3 cells but also re‐sensitizing IGROV‐1/Pt1 cell line to its anti‐tumour effects.Conclusionsδ‐TT triggers G1 phase cell cycle arrest and ROS/MAPK‐mediated apoptosis in OC cells and sensitizes them to platinum treatment, thus representing an interesting option for novel chemopreventive/therapeutic strategies for OC.
Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
Authors: Schaefer Krista R. , Avey Jaedon P. , Todd Michael R. , Beans Julie A. , Dillard Denise A. , Shireman Laura M. , Thornton Timothy A. , Tyndale Rachel F. , Thummel Kenneth E. , Robinson Renee F. , Claw Katrina G. 
Published: September 2021

AbstractPrevalence of smoking is higher in Alaska Native and American Indian (ANAI) populations living in Alaska than the general US population. Genetic factors contribute to smoking and cessation rates. The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. ANAI (N = 151) people trying to quit smoking were recruited. DNA samples were genotyped for CYP2A6 variants *1X2A, *1B, *2, *4, *9, *10, *12, and *35. Multiple nicotine metabolites were measured in plasma and urine samples, including cotinine and 3′‐hydroxycotinine used to determine CYP2A6 activity (e.g., nicotine metabolite ratio [NMR]). We calculated summary statistics for all of the genotypes and metabolites and assigned CYP2A6 activity scores based on known information. We studied the association of CYP2A6 variants with the NMR and smoking histories. The overall frequency of the CYP2A6*1B gain of function allele was high in the ANAI versus non‐ANAI populations in other studies. Both *4 null and *9 decrease of function alleles had frequencies similar to previous studies of ANAI populations. In a multivariate analysis, the genotype‐inferred CYP2A6 activity score was associated with both plasma and urine NMR (p value = 8.56E‐08 and 4.08E‐13, respectively). Plasma NMR was also associated with duration of smoking (p value < 0.01) but not urinary total nicotine equivalents uncorrected for creatinine (TNE9uc) or biological sex. Urine NMR was significantly associated (p value < 0.01) with TNE9uc. Variation in NMR in this ANAI population is explained in part by CYP2A6 genetic variation.
Pigmented epidermotropic breast cancer metastases: A rare variant with a particularly unusual feature
Authors: Torre‐Castro Juan , Moya‐Martínez Cristina , Haya‐Martínez Lara , Mendoza‐Cembranos María Dolores , Eraña‐Tomás Itziar , Requena Luis 
Published: September 2021

AbstractPigmented epidermotropic breast cancer metastases are a rarity, often clinically misdiagnosed as melanocytic lesions. Histopathologically, they show a dermal proliferation of neoplastic metastatic cells that extend to the overlying epidermis in a pattern identical to that seen in primary Paget disease (PD). Differential diagnosis should be established with entities with a similar presentation, such as pigmented mammary PD and malignant melanoma. Immunohistochemistry may be useful for this purpose. We present a new case of pigmented epidermotropic breast cancer metastases with a particularly unusual feature: the absence of dermal infiltration by neoplastic cells, thus considered as pure epidermotropic metastatic involvement.
Participant experiences in the Diabetes REmission Clinical Trial (DiRECT)
Authors: Rehackova Lucia , Rodrigues Angela Margarete , Thom George , Brosnahan Naomi , Barnes Alison C. , McCombie Louise , Leslie Wilma S. , Zhyzhneuskaya Sviatlana , Peters Carl , Adamson Ashley J. , Lean Michael E.J. , Taylor Roy , Sniehotta Falko F. 
Published: September 2021

AbstractIntroductionThe Diabetes REmission Clinical Trial (DiRECT) has shown that sustained remission of type 2 diabetes in primary care is achievable through weight loss using total diet replacement (TDR) with continued behavioural support. Understanding participants’ experiences can help optimise the intervention, support implementation into healthcare, and understand the process of behaviour change.MethodsThirty‐four DiRECT participants were recruited into this embedded qualitative evaluation study. In‐person and telephone interviews were conducted before the TDR; at week 6–8 of the TDR; 2 weeks into food reintroduction (FR); and at 1 year, to learn about participant experiences with the programme. Transcribed narratives were analysed thematically, and we used interpretation to develop overarching themes.ResultsInitiation of the TDR and transition to FR were challenging and required increased behavioural support. In general, adhering to TDR proved easier than the participants had anticipated. Some participants chose the optional extension of TDR. Rapid weight loss and changes in diabetes markers provided ongoing motivation. Further weight loss, behavioural support and occasional use of TDR facilitated weight loss maintenance (WLM). A process of behaviour adaptation to change following regime disruption was identified in three stages: (1) expectations of the new, (2) overcoming difficulties with adherence, and (3) acceptance of continuous effort and establishment of routines.ConclusionsThe DiRECT intervention was acceptable and regularity, continuity, and tailoring of behavioural support was instrumental in its implementation in primary care. The adaptation process accounts for some of the individual variability of experiences with the intervention and highlights the need for programme flexibility.
Movement of Red Shiner during a regulated, intentional surface‐flow recession
Authors: Archdeacon Thomas P. , Gonzales Eric J. , Thomas Lyle I. 
Published: September 2021

AbstractUnderstanding how fish respond to drought and streamflow intermittency is important for designing effective conservation actions. Fish could move to refuge areas prior to intermittency, or be trapped in nearby habitats at the onset. We used mechanical pumps to simulate streamflow intermittency in the Rio Grande, New Mexico. We conducted a 5‐week before–after impact‐only experiment. We seined at 10 sites each week to observe changes in Red Shiner Cyprinella lutrensis abundance and distribution in a 35‐km reach. We conducted two surveys prior to any flow reduction. Next, we reduced flows each week to simulate streamflow intermittency and repeated surveys to identify changes in distribution that would suggest large‐scale movement of Red Shiner to refuge areas. During the first survey, we marked Red Shiner with elastomeric tags to observe movement. In a separate effort, we surveyed all isolated pools that formed after flow reductions for tagged Red Shiner. We observed no patterns that suggested large‐scale movement to refuge areas. Instead, numbers remained steady or increased at all sites in surveys 1 through 4 and declined sharply when sites dried. Tagged fish also supported this conclusion: dispersal models estimated 56% remained within ~0.5 km of the tagging location. We suggest Red Shiner is resilient to drought because of their opportunistic life history and potential for rapid recolonisation, rather than resistant to drought through population‐scale movements to refuge areas. Conservation actions to benefit species threatened by drought must consider the mechanisms of persistence, including both behaviour and life‐history strategy, to be effective.
Innate right in Kant—A critical reading
Authors: Flikschuh Katrin 
Published: September 2021

AbstractA now influential reading of Kant's statement of innate right in the Doctrine of Right interprets it as affirming a basic right of each to freedom of choice and action. This reading treats the innate right as foundational to Kant's entire philosophy of right—all other rights are said to be derived from the innate right. I call this the ‘free choice’ reading of innate right; while it enjoys considerable intuitive appeal, it is contestable on textual and systematic grounds. I show that the free choice reading (a) conflates Kantian external freedom with liberal negative freedom and (b) that its foundationalist assumptions about innate right conflict with Kant's critical method of justification. I go on to offer an alternative interpretation of innate right as conditionally affirming subjects' capacity for legal accountability, the real possibility of which depends on that of acquired right. Far from supplying the basis of acquired right, the possibility of innate right thus depends on that of acquired right. I close with some remarks on the merits of reading Kant's innate right critically and hence, counter‐intuitively.
Timing and magnitude of climatic extremes differentially elevate mortality but enhance recovery in a fish population
Authors: Chiu Ming‐Chih , Chang Shih‐Hsun , Yen Yu‐Ting , Liao Lin‐Yan , Lin Hsing‐Juh 
Published: September 2021

AbstractThe countervailing effects of disturbances (e.g., high mortality and enhanced recovery) on population dynamics can occur through demographic processes under rapidly increasing climatic extremes. Across an extreme‐event gradient, we mechanistically demonstrated how dramatic changes in streamflow have affected the population persistence of endangered salmon in monsoonal Taiwan over a three‐decade period. Our modeling indicated that the dynamics of the age‐structured population were attributed to demographic processes, in which extensive mortality was characterized as a function of climatic extremes and vulnerability in the young stage of fish. In the stochastic simulations, we found that the extensive mortality and high proportion of large fish resulted from extreme flooding, which caused high values of postimpact population recovery. Our empirical evidence suggests that the magnitudes and timing of disturbance can explain the population persistence when facing climatic extremes and thereby challenges the understanding of the mechanistic drivers of these countervailing phenomena under changing environmental conditions.
Participation preferences of health service users in health care decision‐making regarding rehabilitative care in Germany—A cross‐sectional study
Authors: Baumann Lisa A. , Brütt Anna L. 
Published: September 2021

AbstractBackgroundInvolving patients and citizens in health care decision‐making is considered increasingly important in Germany. Participatory structures have been implemented, especially in rehabilitative care. However, it is unknown whether and to what extent German patients and citizens want to participate in decisions that exceed their own medical treatment.ObjectiveThis study aimed to survey participation preferences and associated factors of health service users in decisions regarding rehabilitative care at micro, meso and macro levels.MethodsA questionnaire was sent to 3872 former rehabilitants. We collected participation preferences using the Control Preference Scale or an adapted form. Possible influencing factors were examined using logistic regression models.ResultsThe response rate was 5.7% (n = 217). At all decision‐making levels, joint decision‐making was preferred. At the macro level, preferences for actively participating were the highest. Preferences were significantly interrelated between decision‐making levels. At the micro level, an orthopaedic indication significantly decreased the desire for participation compared to psychosomatic indications (odds ratio = 0.44, p = .019).DiscussionParticipants wanted to be equally involved in decision‐making as experts. Higher preferences for active participation at the macro level might be due to dissatisfaction with the current health care organisation and lack of trust in politicians. Compared to the general public, our study sample was older (73.3% between 50 and 69 years) and more often chronically ill—factors associated with increased participation preferences in the literature.ConclusionContrary to the identified preferences, participation opportunities in the German health care system are rare. Further research on participation preferences and structures that enable meaningful involvement are needed.
Component fraction effect on microstructure and properties of CoFe2O4−K0.5Na0.5NbO3 composites
Authors: Yeh Chi‐Chimg , Li Jhe‐Wei , Tu Guo‐Sen , Qi Xiaoding 
Published: September 2021

AbstractCoFe2O4−K0.5Na0.5NbO3 (CFO−KNN) composites were sintered in air at 1100°C for 2 h. The relative density of sintered CFO−KNN varied with the KNN/CFO ratio and when the volume fraction of KNN reached 50% or more, the sintered composites had a relative density higher than both of the components (i.e., individually sintered KNN and CFO). The highest relative density (94%) was obtained with the composites of 80 vol% KNN. Transmission electron microscopy did not observe any secondary phase at the interface between CFO and KNN grains. However, elemental analyses showed traces of interdiffusion of Na, K, Co, and Fe ions, which were within the solubility limit of both lattices so that no segregation of other phase occurred. Nevertheless, the interdiffusion altered grain growth kinetics for both phases, resulting in the changes in grain sizes for both KNN and CFO in the composites. The composites of higher CFO content showed lower piezoelectric d33 due to a higher DC conductivity that resulted in an incomplete poling of samples. The attainable magnetoelectric voltage coefficient was 3.6 mV cm−1 Oe−1, which was measured with the composites of 50 vol% KNN.