bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once‐weekly dosing for the treatment of patients with diabetes
Authors: Heise Tim , Chien Jenny , Beals John M. , Benson Charles , Klein Oliver , Moyers Julie S. , Haupt Axel , Pratt Edward John 
Published: December 2022

AbstractAimTo assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of basal insulin Fc (BIF; LY3209590), a fusion protein combining a novel single‐chain insulin variant together with human IgG2 Fc domain, following single and multiple once‐weekly BIF administration.Materials and MethodsThe single ascending dose, 15‐day study assessed four BIF doses (5‐35 mg) in healthy participants and people with type 2 diabetes (T2D). In the 6‐week multiple ascending dose study, people with T2D, previously treated with basal insulin, received insulin glargine daily or a one‐time loading dose of BIF followed by 5 weeks of once‐weekly dosing (1‐10 mg). Safety, tolerability and PK and glucose PD were examined.ResultsMean ages of people with T2D (N = 57) and healthy participants (N = 16) in the single‐dose study were 58.4 and 35.8 years, respectively; mean body mass index values were 29.5 and 26.1 kg/m2. BIF had a PK half‐life of approximately 17 days, which led to a sustained, dose‐dependent decrease in fasting blood glucose for 5 days or longer. No severe hypoglycaemia was observed. The 6‐week ascending dose study included 33 people with T2D aged 40‐69 years. BIF showed a low peak‐to‐trough ratio of 1.14 after the last dose at week 6 (steady state). Over 6 weeks, BIF seven‐point glucose profiles remained constant and were similar to insulin glargine. Rates and duration of BIF hypoglycaemic events were similar to insulin glargine.ConclusionsBIF was well tolerated and the PK/PD profile enabled once‐weekly dosing with minimal variation in exposure in a treatment interval of 1 week. The findings suggest BIF is suitable for further development as a weekly basal insulin in people with diabetes.
More than just charts and graphs: What to teach in a data visualization course
Authors: Camm Jeffrey D. , McCray Gordon E. , Roehm Michelle L. 
Published: December 2022

AbstractBased on our experience developing and delivering a highly successful data visualization course within a Master of Science in Business Analytics program, we present a taxonomy for data visualization courses and recommend content and pedagogical features for each type of data visualization course therein. We also discuss the interdependence between data visualization and business communication as a critical consideration in course design.
Class II composite restoration technique teaching: A randomised controlled crossover laboratory‐based trial involving a novel ringless sectional matrix technique
Authors: Bailey Oliver , Shand Bonnie , Ellis Ian 
Published: December 2022

AbstractIntroductionObjectives were to assess how different techniques (including a novel ringless sectional matrix approach) affect students' restorative outcomes, and their preferences for and preparedness to clinically implement new techniques with the aim of introducing appropriate techniques to the undergraduate curriculum.Materials and MethodsStudents performed two class II composite restorations in plastic teeth using two sectional matrix techniques (separating ring vs. without [ringless]), and two composite restorative techniques (incremental vs. injection‐moulded bulk‐fill). Restorations were assessed on multiple parameters which were combined to rate them as “good” or not. Online surveys assessed students' preferences for and preparedness to clinically implement new techniques.ResultsContact area concavity (OR = 106, p < .001) and cervical marginal overhang (OR = 7.4, p < .001) were much more likely with the separating ring compared to the ringless sectional matrix technique. “Good” restorations were 29.5 times more likely when using ringless compared to separating ring techniques and 3.3 times more likely when using the injection‐moulding bulk‐fill compared to layered composite technique. A majority of students preferred the ringless to separating ring sectional matrix technique and the injection‐moulding bulk‐fill to layered composite technique. Large majorities felt prepared to implement the new techniques clinically with no or minimal guidance.ConclusionsA classic sectional matrix technique with separating ring resulted in a much greater occurrence of contact area concavity and cervical marginal overhang than a novel ringless approach. When allied with student preferences and clinical preparedness, inclusion of the novel ringless approach in the undergraduate curriculum can be supported alongside bulk‐fill injection‐moulding techniques.
Spatio‐temporal dynamics of oscillatory brain activity during the observation of actions and interactions between point‐light agents
Authors: Friedrich Elisabeth V. C. , Zillekens Imme C. , Biel Anna Lena , O'Leary Dariusz , Singer Johannes , Seegenschmiedt Eva Victoria , Sauseng Paul , Schilbach Leonhard 
Published: December 2022

AbstractPredicting actions from non‐verbal cues and using them to optimise one's response behaviour (i.e. interpersonal predictive coding) is essential in everyday social interactions. We aimed to investigate the neural correlates of different cognitive processes evolving over time during interpersonal predictive coding. Thirty‐nine participants watched two agents depicted by moving point‐light stimuli while an electroencephalogram (EEG) was recorded. One well‐recognizable agent performed either a ‘communicative’ or an ‘individual’ action. The second agent either was blended into a cluster of noise dots (i.e. present) or was entirely replaced by noise dots (i.e. absent), which participants had to differentiate. EEG amplitude and coherence analyses for theta, alpha and beta frequency bands revealed a dynamic pattern unfolding over time: Watching communicative actions was associated with enhanced coupling within medial anterior regions involved in social and mentalising processes and with dorsolateral prefrontal activation indicating a higher deployment of cognitive resources. Trying to detect the agent in the cluster of noise dots without having seen communicative cues was related to enhanced coupling in posterior regions for social perception and visual processing. Observing an expected outcome was modulated by motor system activation. Finally, when the agent was detected correctly, activation in posterior areas for visual processing of socially relevant features was increased. Taken together, our results demonstrate that it is crucial to consider the temporal dynamics of social interactions and of their neural correlates to better understand interpersonal predictive coding. This could lead to optimised treatment approaches for individuals with problems in social interactions.
Tool use and tooling in ravens (Corvus corax): A review and novel observations
Authors: Jacobs Ivo , Osvath Mathias 
Published: December 2022

AbstractCorvids are known for their cognitive flexibility, and many have innovated various forms of tool use. Here, we review tool use and tooling in common ravens (Corvus corax) and describe additional observations. In total, they have used tools in 10 submodes and 11 modes. Of these modes, four were observed in captivity only, four in the wild only and three in both contexts. Five of these modes constitute tooling. When they manufactured tools, it was through detachment or subtraction. The purpose of most tool use was apparent, except when they used containers to transport small amounts of food that could be held in their bill and antelingual pouch (estimated to hold at least 16.2 ml). The small number of tool‐using individuals per mode and the lack of detailed descriptions limit further interpretation and generalizability. Nonetheless, ravens are likely customary tool users in three modes and show the capacity for diverse tool use, which should be examined in dedicated future experiments.
The effect of PPAR isoform (de)activation on the lipid composition in full‐thickness skin models
Authors: Helder Richard W. J. , Rousel Jannik , Boiten Walter A. , Gooris Gerrit S. , Nadaban Andreea , El Ghalbzouri Abdoelwaheb , Bouwstra Joke A. 
Published: December 2022

AbstractHuman skin equivalents (HSEs) are 3D‐cultured human skin models that mimic many aspects of native human skin (NHS). Although HSEs resemble NHS very closely, the barrier located in the stratum corneum (SC) is impaired. This is caused by an altered lipid composition in the SC of HSEs compared with NHS. One of the most pronounced changes in this lipid composition is a high level of monounsaturation. One key enzyme in this change is stearoyl‐CoA desaturase‐1 (SCD1), which catalyses the monounsaturation of lipids. In order to normalize the lipid composition, we aimed to target a group of nuclear receptors that are important regulators in the lipid synthesis. This group of receptors are known as the peroxisome proliferating activating receptors (PPARs). By (de)activating each isoform (PPAR‐α, PPAR‐δ and PPAR‐γ), the PPAR isoforms may have normalizing effects on the lipid composition. In addition, another PPAR‐α agonist Wy14643 was included as this supplement demonstrated normalizing effects in the lipid composition in a more recent study. After PPAR (ant)agonists supplementation, the mRNA of downstream targets, lipid synthesis genes and lipid composition were investigated. The PPAR downstream targets were activated, indicating that the supplements reached the keratinocytes to trigger their effect. However, minimal impact was observed on the lipid composition after PPAR isoform (de) activation. Only the highest concentration Wy14643 resulted in strong, but negative effects on CER composition. Although the novel tested modifications did not result in an improvement, more insight is gained on the nuclear receptors PPARs and their effects on the lipid barrier in full‐thickness skin models.
Macrosystem community change in lake phytoplankton and its implications for diversity and function
Authors: Weigel Benjamin , Kotamäki Niina , Malve Olli , Vuorio Kristiina , Ovaskainen Otso 
Published: December 2022

AbstractAimWe use lake phytoplankton community data to quantify the spatio‐temporal and scale‐dependent impacts of eutrophication, land‐use and climate change on species niches and community assembly processes while accounting for species traits and phylogenetic constraints.LocationFinland.Time period1977–2017.Major taxaPhytoplankton.MethodsWe use hierarchical modelling of species communities (HMSC) to model metacommunity trajectories at 853 lakes over four decades of environmental change, including a hierarchical spatial structure to account for scale‐dependent processes. Using a “region of common profile” approach, we evaluate compositional changes of species communities and trait profiles and investigate their temporal development.ResultsWe demonstrate the emergence of novel and widespread community composition clusters in previously more compositionally homogeneous communities, with cluster‐specific community trait profiles, indicating functional differences. A strong phylogenetic signal of species responses to the environment implies similar responses among closely related taxa. Community cluster‐specific species prevalence indicates lower taxonomic dispersion within the current dominant clusters compared with the historically dominant cluster and an overall higher prevalence of smaller species sizes within communities. Our findings denote profound spatio‐temporal structuring of species co‐occurrence patterns and highlight functional differences of lake phytoplankton communities.Main conclusionsDiverging community trajectories have led to a nationwide reshuffling of lake phytoplankton communities. At regional and national scales, lakes are not single entities but metacommunity hubs in an interconnected waterscape. The assembly mechanisms of phytoplankton communities are strongly structured by spatio‐temporal dynamics, which have led to novel community types, but only a minor part of this reshuffling could be linked to temporal environmental change.
Agrobacterium‐mediated transformation via establishment of stable tissue culture system inZoysia matrella(L.) Merrill ‘Wakaba’
Authors: Ng Hwan May , Gondo Takahiro , Ushiyama Mari , Cho Shin , Maemura Soko , Hashiguchi Masatsugu , Tanaka Hidenori , Akashi Ryo 
Published: December 2022

AbstractZoysia matrella(L.) Merrill is a perennial C4 warm‐season turfgrass grown for landscapes, golf courses, sports fields and recreation parks. To create a new breeding method by genome editing, an efficient genetic transformation system is essential. In this study, we report the efficient protocol ofAgrobacterium‐mediated transformation through the establishment of a stable tissue culture system forZ. matrella‘Wakaba’. The embryogenic callus was induced from shoot apices of nodal segments incubated in Murashige and Skoog (MS) medium containing 2 mg/l 2,4‐dichlorophnoxyacetic acid (2,4‐D), 0.1 mg/l 6‐benzylaminopurine (BAP) and 5 μM CuSO4(MS‐DBC). Repeated subculture of compact high‐quality callus in MS‐DBC medium produced a highly regenerative callus with dense pre‐embryogenic clusters, and it was used as a transformation target.Agrobacteriumstrain EHA105 harboring pANIC8B vector containing the β‐glucuronidase gene (GUS) and hygromycin B phosphotransferase gene was used.Agrobacterium‐infected calli were cocultured for 5 days with 100 μM acetosyringone and then subjected to selection pressure of 50 mg/l hygromycin. This optimized protocol yielded transformation efficiencies of up to 6.6%. Southern blot analysis verified one to three copies of theGUSgene in different independent transgenic plants. All transgenic plants were morphologically normal, and the GUS expressions were stable. Our optimizedin vitroand transgenic system will facilitate the new breeding technology of genome editing in zoysiagrass.
Trends in three major histological subtypes of cutaneous melanoma in the Netherlands between 1989 and 2016
Authors: van Niekerk Catharina C. , Otten J. Hans D. M. , van Rossum Michelle M. , van den Reek Juul M. P. A. , Brummelkamp Erik , Mol Martijn , Groenewoud J. Hans M. M. , Verbeek André L. M. 
Published: December 2022

AbstractBackgroundTime trend analysis of cutaneous melanoma (CM) mortality in fair skin populations shows both a gradual decrease and/or an increase. To explain these differences, we analyzed long‐term time trends in the incidence of the most common histological subtypes of CM: superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM), and nodular melanoma (NM).MethodsUsing data from the Netherlands Cancer Registry and Statistics Netherlands, the number and rates of cases diagnosed with SSM, LLM, and NM from 1989 to 2016 were analyzed by age, calendar period, and birth cohort of people born in successive periods from 1925 to 1973.ResultsPrimary CM was diagnosed in 52,000 men and 66,588 women in the study period. The annual age‐standardized incidence rate increased three‐fold from 14 to 42 per 100,000 person‐years. The most common subtype was SSM (50%), followed by LMM (23%) and NM (14%). Age‐specific subtype rates showed an upward trend over time for both men and women. Younger birth cohorts had higher rates of SSM and LMM diagnosis than older birth cohorts. This birth cohort pattern was not observed for NM.ConclusionsWe observed a strong increase in the melanoma epidemic curves in the light‐skinned Dutch population over the last three decades. This increase is explained by younger generations having higher rates of SSM and LMM than older generations.
Rectovaginal Constriction in Jersey Cattle: Ultrastructural Features
Authors: Troykr D. , Woollen N. E. , Leipold H.W. 
Published: December 2022

SummaryTissue sections taken from layers involved in the inelastic constricting band within the anal canal of Jersey cattle affected with rectovaginal constriction (RVC) were studied with transmission and scanning electron microscopy and compared to the same tissues from normal animals. The affected tissues revealed a tangled meshwork of fine fibers on scanning electron micrographs, and a distinct linger‐print‐like pattern of collagen fibers on transmission electron microscopy. There were also randomly organized, small‐diameter fibers present within RVC tissue.
Ossifikationsvarianten am Gliedmaßenskelett des Hundes: II. Persistierende Ossifikationszonen
Authors: Mayrhofer Elisabeth 
Published: December 2022

SummaryOssification Variants of the Limb Skeleton of the Dog. II. Persisting Ossification ZonesPhysiological fusion of secondary ossification centres can be disturbed in growing dogs. On radiographs they look like isolated small bone shadows, located at the border of the glenoid cavity, acetabulum and olecranon. They are not to be mixed up with traumatic or degenerative changes. Diagnosis depends on the age of the dog.
Ovarian Serotonin During Oocyte Development and Ovulation in the Domestic Hen (Gallus Domesticus)*
Authors: Paczoska‐Eliasiewicz H. , Rząsa J. 
Published: December 2022

SummaryTire results indicate that serotonin concentration in the follicle wall decreases as the follicle grows and maturates. Moreover, a high negative correlation (r = ‐0.9297) between follicle diameter and serotonin concentration was found. In the post‐ovulatory follicle, 2h after ovulation, the serotonin concentration (210.2 ng/g wet wt.) was significantly lower than in the preovulatory follicle (524.7 ng/g) 0.5 h before ovulation. It seems likely that serotonin plays a role in follicular maturation and ovulation in the domestic hen.
Biosimilars of anti‐vascular endothelial growth factors for ophthalmic disease – Clinical trial status 2022
Authors: McFadyen James , Votruba Marcela , Muenzberg Michael , Cornes Paul 
Published: December 2022

AbstractPurpose: Diabetic Macular Œdema (DME) and Age‐related Macular Degeneration (nAMD) are the leading causes of vision loss in developed nations. Anti‐Vascular Endothelial Growth Factor (aVEGF) has revolutionized the treatment of both conditions, but access is limited by costs. Biosimilars of aVEGF can cut costs, but prescriber concerns over the lack of clinical data can slow uptake. This paper reports all biosimilar aVEGF in development for Europe and the USA, and pools the results of clinical confirmatory trials to provide statistically greater reassurance in the similarity of outcomes.Methods: Biosimilars in the clinical development phase were identified from US and EU trial registries.Results: There are 13 biosimilars of ranibizumab and aflibercept in final clinical comparative trial stage of development in Europe and the USA, recruiting 6126 patients. Five studies of intravitreal bevacizumab biosimilars are recruiting 772 patients. Equivalence outcomes are typically based on Best‐Corrected Visual Acuity (BCVA) with 90% confidence limits of −3 to +3 letters between reference and biosimilar medicines. Completed trials to date with 1166 participants analysed together show BCVA outcomes of ≤1 letter between Originator Reference Products and Biosimilars; for serious adverse events the risk ratio is 1.17, with 95% confidence intervals of 0.85–1.63, p = 0.32.Conclusions: Biosimilars of aVEGF are expected soon. There are likely sufficient brands expected to create meaningful price competition. To date, the EU/US regulatory pathway is delivering biosimilars with close equivalence of safety and efficacy outcomes.
Capsular bag distension syndrome after uneventful DMEK for Fuchs corneal endothelial dystrophy
Authors: Weber Adrian , Reinhold Aja , Massa Horace , Gugleta Konstantin , Gatzioufas Zisis 
Published: December 2022

AbstractPurpose: Capsular bag distension syndrome or capsular block syndrome is a rare complication of cataract surgery characterized by accumulation of fluid between the intraocular lens and the posterior lens capsule, leading to visual deterioration. A small continuous curvilinear capsulorhexis, residual cortical lens material, as well as residual viscoelastic material behind the intraocular lens are associated with increased risk of fluid entrapment. Capsular bag syndrome usually occurs in the early postoperative period, but it has also been described as late as 14 years after cataract surgery. Nd‐YAG laser posterior capsulotomy is the treatment of choice in most cases, facilitating the drainage of the fluid in the vitreous cavity. Late‐onset capsular block syndrome is often associated with Propionibacterium acnes, requiring surgical management.Methods: Hereby we report a case of a 72‐year‐old female patient with Fuchs corneal endothelial dystrophy, who developed a capsular block syndrome after an uneventful endothelial keratoplasty (DMEK).Results: In the early postoperative period after the DMEK, we observed the development of capsular block syndrome OS. The patient was subjected to bilateral cataract surgery 6 years ago. After intensive follow‐up examination for excluding Propionibacterium acnes‐related endophthalmitis, we proceeded with Nd‐YAG capsulotomy, which resulted in drainage of the fluid in the vitreous cavity and immediate visual recovery.Conclusions: To our knowledge this is the first report of capsular bag syndrome after DMEK and therefore anterior segment surgeons should be aware of this rare complication.
Menopausal hormone therapy and the risk of cataract in postmenopausal women in South Korea
Authors: Sim Haeun , Jeong Jeonga , Kang Min Ji , Hwang Jehyung 
Published: December 2022

AbstractPurpose: Postmenopausal women have a higher prevalence of cataract than similar‐aged men. This study aimed to evaluate the effects of menopausal hormone therapy on lens opacity in postmenopausal women.Methods: This retrospective cohort study analysed population‐based health insurance data in South Korea collected from 2002 to 2019. To determine the risk factors associated with cataract, postmenopausal women (N = 2 506 271) were grouped according to postmenopausal hormone therapy use. The treatment group was further divided into the following subgroups: tibolone, combined oestrogen plus progestin by manufacturer, oral oestrogen, combined oestrogen plus progestin by physician, and topical oestrogen groups. The main outcome measure was the prevalence of cataract.Results: The control group comprised 463 151 postmenopausal women who had never used menopausal hormone therapy after menopause, while the treatment group included 228 033 postmenopausal women who had used menopausal hormone therapy continuously for at least 6 months. The treatment group had a higher incidence of cataract than the control group based on Cox proportional hazards ratio analysis. Low socioeconomic status and high parity were identified as risk factors for cataract, and reduced risk of cataract was associated with living in rural areas and drinking.Conclusions: Women undergoing postmenopausal hormone therapy, including tibolone, had a higher incidence of cataract than those who were not. Old age, low socioeconomic status, and high parity were risk factors for cataract. Our findings may help physicians identify postmenopausal women at a greater risk of developing cataract.References1. Eisner A & Luoh SW. Breast cancer medications and vision: effects of treatments for early‐stage disease. Curr Eye Res 36, 867–885 (2011).2. Spinelli MG. Depression and hormone therapy. Clin Obstet Gynecol 47, 428–436 (2004).3. Freedman RR. Physiology of hot flashes. Am J Hum Biol 13, 453–464 (2001).4. Abraham S, Perz J, Clarkson R & Llewellyn‐Jones D. Australian women's perceptions of hormone replacement therapy over 10 years. Maturitas 21, 91–95 (1995).