bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating reference conditions using baseline vegetation data to inform large‐scale ecosystem restoration efforts
Authors: Guilfoyle Colin , de Eyto Elvira , Graham Conor T. , Birch Sam , Lally Heather T. 
Published: July 2024

AbstractAimsEcological restoration is informed by established guidelines, including the use of reference ecosystems to direct restoration objectives and quantify progress. Despite their importance, the use of reference conditions in restoration projects has been inconsistent, particularly where habitat degradation has occurred at landscape scales. Here we use baseline vegetation data and the relationship between vegetation communities and environmental conditions to identify and select positive reference sites within a proposed landscape‐scale restoration project. In addition, we demonstrate the use of positive references in monitoring through an adjacent post‐restoration case study area.LocationWild Nephin National Park, Mayo, Ireland.MethodsVegetation communities at sites (n = 230) within a large (4700 ha) proposed restoration area were surveyed using quadrats. Positive reference sites were identified following community classification within the Irish Vegetation Classification (IVC). The environmental determinants of positive references were assessed through redundancy analysis. Based on these determinants, sites with similar environmental conditions were identified though k‐medoids clustering, enabling positive references to be spatially designated. Ordination and Ellenberg's indicator values were used to demonstrate the use of positive references in restoration monitoring.ResultsA total of 49 positive reference sites were identified for the study area. Altitude, soil type, subsoil type, soil depth and topographical position were identified as significant determinants of communities within positive reference sites. K‐medoids clustering with 11 clusters accurately grouped environmentally similar regions of the study area and enabled positive reference sites to be determined and designated spatially based on the cluster groupings.ConclusionsOverall, the study demonstrates with a practical example how landscape‐scale restoration can be informed and monitored through the identification of appropriate positive reference sites within the restoration area, based on the relationship between existing non‐degraded plant communities and their environmental determinants, derived from baseline habitat data.
Big ideas that changed the world of disability: Exploring theory with self‐advocates
Authors: Grove Nicola , Richards Simon , Rice Simon , Magwood Claudia , Collis Bryan , Martick Steffen , Schuppener Saskia , Kremsner Gertraud , Tilley Elizabeth , Walmsley Jan 
Published: July 2024

AbstractBackgroundInclusive research has sidelined discussion of theoretical issues with researchers with intellectual/learning disabilities. This is a situation which the Big Ideas initiative sought to change. Between 2021 and 2023, the Open University, Leipzig University and the University of Koblenz organised nine workshops to explore influential theories in disability research. The objective was to share a theory (Big Idea) that sheds light on disability with self‐advocates and discuss how it relates to their experience. By making theories accessible and discussing how they relate to lived experience, we aimed to inform self‐advocates and activist researchers about key concepts in disability, deepen their capacity for research and campaigning, and better equip them to activate for change.MethodsThe online workshops were evaluated by observers. These observations were used by an inclusive group of activist researchers as the basis for an overall evaluation of the project.FindingsPeople with learning disabilities can engage with complex theories if these are presented accessibly alongside opportunities for reflective discussion. Input from self‐advocates helps to broaden and deepen theoretical understanding.An unanticipated but important finding was that the Big Ideas workshops created a new space in which academics and self‐advocates could learn together as equals.ConclusionsMaking theory accessible and easier to understand is both possible and valuable.
Ticagrelor increases its own potency at the P2Y12 receptor by directly changing the plasma membrane lipid order in platelets
Authors: Pyrshev Kyrylo , Allemand Florentin , Rabani Vahideh , Yesylevskyy Semen , Davani Siamak , Ramseyer Christophe , Lagoutte‐Renosi Jennifer 
Published: July 2024

AbstractBackground and PurposeAlthough the amphiphilic nature of the widely used antithrombotic drug Ticagrelor is well known, it was never considered as a membranotropic agent capable of interacting with the lipid bilayer in a receptor‐independent way. In this study, we investigated the influence of Ticagrelor on plasma membrane lipid order in platelets and if this modulates the potency of Ticagrelor at the P2Y12 receptor.Experimental ApproachWe combined fluorescent in situ, in vitro and in silico approaches to probe the interactions between the plasma membrane of platelets and Ticagrelor. The influence of Ticagrelor on the lipid order of the platelet plasma membrane and large unilamellar vesicles was studied using the advanced fluorescent probe NR12S. Furthermore, the properties of model lipid bilayers in the presence of Ticagrelor were characterized by molecular dynamics simulations. Finally, the influence of an increased lipid order on the dose‐response of platelets to Ticagrelor was studied.Key ResultsTicagrelor incorporates spontaneously into lipid bilayers and affects the lipid order of the membranes of model vesicles and isolated platelets, in a nontrivial composition and concentration‐dependent manner. We showed that higher plasma membrane lipid order in platelets leads to a lower IC50 value for Ticagrelor. It is shown that membrane incorporation of Ticagrelor increases its potency at the P2Y12 receptor, by increasing the order of the platelet plasma membrane.Conclusion and ImplicationsA novel dual mechanism of Ticagrelor action is suggested that combines direct binding to P2Y12 receptor with simultaneous modulation of receptor‐lipid microenvironment.
Synthesis, biological evaluation and mechanism of action of benzothiazole derivatives with aromatic hydrazone moiety, a new class of antileishmanial compounds
Authors: Coimbra Elaine Soares , Antinarelli Luciana M. R. , de Oliveira Lemos Ari Sérgio , da Silva Neto Adolfo Firmino , Pinheiro Alessandra Campbell , de Souza Marcus Vinícius Nora 
Published: July 2024

AbstractLeishmaniasis is a disease caused by protozoa Leishmania spp., considered as a significant and urgent public health problem mainly in developing countries. In the absence of an effective vaccine, the treatment of infected people is one of the most commonly prophylactic measures used to control this disease. However, the therapeutic arsenal is reduced to a few drugs, with serious side effects and variability in efficacy. Attempting to this problem, in this work, a series of benzothiazole derivatives was synthetized and assayed against promastigotes and intracellular amastigotes of L. amazonensis, as well as the toxicity on macrophages. In addition, studies about the mechanism of action were also performed. Among the synthesized molecules, the substitution at position 4 of the aromatic ring appears to be critical for activity. The best compound exhibited IC50 values of 28.86 and 7.70 μM, against promastigotes and amastigotes of L. amazonensis, respectively, being more active than miltefosine, used as reference drug. The in silico analysis of physicochemical and pharmacokinetic (ADMET) properties of this compound suggested a good profile of oral bioavailability and safety. In conclusion, the strategy of using benzothiazole nucleous in the search for new antileishmanial agents was advantageous and preliminar data provide information about the mechanism of action as well as in silico parameters suggest a good profile for preclinical studies.
Investigating potential mechanisms of vitamin D against thyroid cancer via network pharmacology and experimental validation
Authors: Liu Bin , Hou Bowen , Zhao Yu , Gao Fengyi , Dong Xiaoyin , He Jiageng 
Published: July 2024

AbstractThyroid cancer (TC) is one of the most common endocrine malignancies worldwide. Increasing evidence suggests that vitamin D (VD) has potential benefits in the treatment of TC. However, evidence regarding the targets and molecular mechanisms of VD in TC remains limited. In this study, we conducted network pharmacology, molecular docking, and experimental evaluation to explore the target genes, biological functions, and signaling pathways involved in this process. Network analysis revealed 77 potential target genes of VD against TC, and four hub target genes were identified: ESR1, KIT, CCND1, and PGR. Furthermore, we identified the biological processes (BP) and signaling pathways involving these potential target genes, and then determined the possible interaction between the hub targets and VD through molecular docking. Finally, through in vitro experiments, we found that VD effectively inhibits the proliferation of TC cells and downregulates the expression of the ESR1 gene. In conclusion, the effects of VD against TC involve multiple biological targets, BP, and signaling pathways. These findings provide scientific evidence for the application of VD in the treatment of TC.
Factor structure of FUNDES‐Child‐SE measuring the participation and independence of children with disabilities
Authors: Gothilander Jennifer , Axelsson Anna Karin , Danielsson Henrik , Almqvist Lena , Ullenhag Anna 
Published: July 2024

AbstractBackgroundFUNDES‐Child‐SE is a proxy rating questionnaire for measuring participation and independence in children with disabilities in a Swedish context. It includes the components of frequency of attendance, engagement and independence. The original, Taiwanese FUNDES‐Child 7.0, has previously been found to have a four‐factor structure for frequency of participation and a two‐factor structure for independence. The aim of this study was to test the factor structure in FUNDES‐Child‐SE. The factor structure is an important part of construct validity.MethodsCaregivers of 163 children with disabilities aged 6–18 years participated in this cross‐sectional study. Exploratory factor analysis was used to find the factor structure for Engagement. Confirmatory factor analysis was used to test the factor structure for all three components.ResultsThe proposed factor structure for frequency of participation (daily living participation frequency, mobility participation frequency, learning participation frequency and community participation frequency) and independence (daily living independence and social participation independence) fit with data from FUNDES‐Child‐SE after excluding three to five items and adding two to five covariances of residuals. In the engagement component, two factors, named engagement in informal activities and engagement in formal activities, were found. After excluding one item and adding 10 covariances of residuals, the factor structure had an acceptable fit to data.ConclusionsDifferences in components' factor structure indicate that attendance and engagement are separate aspects of participation. Before using numeric scores from FUNDES‐Child‐SE in clinical settings, responsiveness and interpretability should be evaluated.
“Still work?” Design and effect of interventions used to modify feeding problems in children with autism: A systematic review of studies employing group designs
Authors: Chung Louisa Ming Yan , Fang Yuan , Or Peggy Pui Lai , Sun Fenghua , Poon Eric Tsz Chun , Chan Carmen Ka Man 
Published: July 2024

AbstractBackgroundFeeding problems in children with autism jeopardize the well‐being of both children with autism and their families. Mixed findings were reported from previous interventions, which were mostly evaluated by single subject research design (SSRD) studies. Moreover, feasibility assessment and social validity measurement were unaddressed by these SSRD studies. To fill this substantial knowledge gap, the present review systematically summarized and evaluated feeding interventions implemented in children with autism, which were assessed by studies employing group designs.MethodAn extensive literature search in eight established online databases was conducted, and a total of 17 eligible studies published in 2009–2021 were included for further analysis. A descriptive account of the features of the investigations is provided, including assessment of study quality.ResultsA total of 449 children with autism and 203 parents/caregivers participated in the included studies. The multiple use of five strategic intervention components were highlighted in this review, including nutrition education/consultations, environmental modifications, sensory exposure, cognitive components, and behaviour interventions. The reviewed interventions showed a preliminarily positive effect for modifying feeding problems in children with autism. Furthermore, the evaluation based on the RE‐AIM framework (reach, efficacy, adoption, implementation, and maintenance) demonstrated that an interdisciplinary multi‐component intervention strategy may achieve high effectiveness and feasibility in improving feeding problems in a wide range of children with autism.ConclusionsThis review found that interventions achieved and maintained a positive effect on modification of feeding problems in groups of children with autism. Information and gaps identified and summarized in the implementation process may assist both researchers and stakeholders to further support these vulnerable children.
A new Urbacodon (Theropoda, Troodontidae) from the Upper Cretaceous Iren Dabasu Formation, China: Implications for troodontid phylogeny and tooth biology
Authors: Wang Shuo , Ding Nuo , Tan Qingwei , Yang Rui , Zhang Qiyue , Tan Lin 
Published: July 2024

AbstractTooth attachment and replacement play significant roles in the feeding ecology of polyphyodont vertebrates, yet these aspects have remained largely unexplored in non‐avialan paravians including troodontids. Here, we describe a new troodontid species, Urbacodon norelli sp.n., recovered from the Upper Cretaceous Iren Dabasu Formation of Inner Mongolia, China, based on an incomplete right dentary and 12 associated replacement teeth. Urbacodon norelli is distinguished from all other known troodontids, including its relative U. itemirensis from Uzbekistan, by several features: the presence of paired dentary symphyseal foramina, the presence of a relatively steep anterior margin of the dentary, the absence of a dentary chin, the presence of a common groove hosting the anterior 12 dentary teeth, and the presence of relatively larger dentary teeth. Phylogenetic analysis places both species of Urbacodon as sister taxa to Zanabazar junior, confirming their status as later‐diverging troodontids. Radiographs revealed an alternating tooth replacement pattern in U. norelli, with a maximum Zahnreihen‐spacing estimated to be 3. During tooth replacement, the anteriorly inclined interdental septa, which wedge between anterior dentary teeth, underwent frequent remodelling as the developing tooth moved upwards, particularly anterolabially. This rapid turnover left insufficient time for an interdental plate to form, resulting in the absence of such structures in this specimen. The frequent remodelling of periodontal tissues accompanying tooth replacement is likely to account for the absence of interdental plates. The discovery of this new troodontid expands our understanding of paravian theropods from the Upper Cretaceous Iren Dabasu Formation and provides valuable insights into troodontid tooth biology.
How debunking biases in research and development decisions could lead to more equitable healthcare?
Authors: Weber Benjamin , Zineh Issam , Lalonde Richard , Visser Sandra A. G. 
Published: July 2024

AbstractDecades of research have demonstrated that a variety of cognitive biases can affect our judgment and ability to make rational decisions in personal and professional environments. The lengthy, risky, and costly nature of pharmaceutical research and development (R&D) makes it vulnerable to biased decision‐making. Moreover, cognitive biases can play a role in regulatory and clinical decision‐making, the latter impacting diagnostic and treatment decisions in the therapeutic use of medicines. These inherent and/or institutionalized biases (e.g., in assumptions, data, or decision‐making practices) could conceivably contribute to health inequities. In this mini‐review, we provide a broad perspective on how cognitive biases can affect pharmaceutical R&D, regulatory evaluation, and therapeutic decision‐making. Example approaches to mitigate the effect of common biases in the development, approval, and use of new therapeutics, such as quantitative decision criteria, multidisciplinary reviews, regulatory and treatment guidelines, and evidence‐based clinical decision support systems are illustrated. Mitigating the impact of cognitive biases could increase pharma R&D efficiency, change the perspective and prioritization of unmet medical needs, increase representativeness and quality of evidence generated through clinical trials and real‐world research, leading to higher quality insights and more effective medication use, and as such could eventually contribute to more equitable healthcare.
Epigenetic markers of tooth eruption – DNA methylation and histone acetylation
Authors: Westerlund Anna , Shikhan Asal , Sabel Nina , Asa'ad Farah , Larsson Lena 
Published: July 2024

AbstractThe present study aimed to evaluate whether epigenetic markers are expressed in the dental follicles surrounding ectopically erupting teeth. Twenty‐one dental follicles were collected in 20 adolescent children through surgical exposure of ectopic teeth. The epigenetic modifications of DNA methylation and histone acetylation were evaluated by immunohistochemistry. The results showed cells positive for DNA‐methyltransferase 1 (DNMT1), DNA methyltransferase 3 beta (DNMT3B), ten‐eleven translocation‐2 (TET2), acetyl‐histone H3 (AcH3), acetyl‐histone H4 (AcH4), 5‐methylcytosine (5mC), and 5‐hydroxymethylcytosine (5hmC) were present in all the samples. The levels of epigenetic markers representing active chromatin (5hmC, AcH3, AcH4, and TET2) were statistically significantly higher than those of markers representing inactive chromatin (5mC, DNMT3B, DNMT1). In conclusion, follicles in ectopic teeth display major epigenetic modifications. In the follicles, epigenetic markers associated with the activation of bone‐related genes are more abundant than markers associated with the inactivation of bone‐related genes.
Disruption of adenosine metabolism increases risk of seizure‐induced death despite decreased seizure severity
Authors: Purnell Benton , Bhasin Jayant , Rust Brian , George Steven , Bah Kadiatou , Lu Tracy , Fedele Denise , Boison Detlev 
Published: July 2024

AbstractObjectiveRespiratory arrest plays an important role in sudden unexpected death in epilepsy (SUDEP). Adenosine is of interest in SUDEP pathophysiology due to its influence on seizures and breathing. The objective of this investigation was to examine the role of adenosine in seizure severity, seizure‐induced respiratory disruption, and seizure‐induced death using mouse models. Understanding adenosinergic contributions to seizure cessation and seizure‐induced death may provide insights into how SUDEP can be prevented while avoiding increased seizure severity.MethodsOur approach was to examine: (1) seizure severity and seizure‐induced death after 15 mA electroshock seizures and during repeated pentylenetetrazol (PTZ) administration in wild‐type mice (Adk
+/+) and transgenic mice with reduced adenosine metabolism (Adk
+/−); (2) the postictal hypercapnic ventilatory response (HCVR) in wild‐type mice (the postictal HCVR could not be examined in Adk
+/− mice due to their high mortality rate); and (3) the effects of adenosinergic drugs on seizure severity and seizure‐induced death following maximal electroshock (MES).Results
Adk
+/− mice were more vulnerable to seizure‐induced death in the 15 mA electroshock and repeated PTZ models. Despite increased mortality, Adk
+/− mice had comparable seizure severity in the PTZ model and reduced seizure severity in the 15 mA electroshock model. Breathing and HCVR were suppressed by 15 mA electroshock seizures in wild‐type mice. Pharmacological inhibition of adenosine metabolism decreased MES seizure severity but did not increase mortality. A1 selective and nonselective adenosine receptor antagonists increased seizure‐induced death following MES.SignificanceAdenosine has opposing effects on seizure severity and seizure‐induced death. On the one hand, our seizure severity data highlight the importance of adenosine in seizure suppression. On the other hand, our mortality data indicate that excessive extracellular adenosine signaling can increase the risk of seizure‐induced respiratory arrest.
The use of hysteroscopy to identify and treat reproductive tract abnormalities in the mare
Authors: Eaton Sarah 
Published: July 2024

SummaryHysteroscopy is a complementary tool to the traditional transrectal palpation and ultrasonography commonly performed by equine practitioners. Once mastered, it is a quick and useful diagnostic tool for the general and targeted evaluation of the endometrium and provides real time information about potential causes of subfertility. Samples of intrauterine fluid and the endometrium can be taken via transendoscopic catheters or infusion pipettes or via the use of traditional endometrial biopsy forceps. In addition to being a useful diagnostic tool, treatments can often be performed at the same time the pathologies are identified, providing mare owners with information and resolution of problems. With the development of additional technologies, hysteroscopy allows for optical biopsies to be performed, which will likely increase in use as the software moves from the research laboratories to clinical practice. Hysteroscopy is an easily learned, useful clinical skill for the identification of abnormalities in the mares' reproductive tract.
Medical negligence under pressure: obligations of clinicians and healthcare services in the setting of resource limitations
Authors: Panaccio Danielle C. , Farmer Caitlin C. , Pang Sam C. , Dean Jessica M. , Mahar Patrick D. , Kevat Dev A. 
Published: July 2024

AbstractHealthcare provision takes place in a variety of contexts, with variations of resources available to practitioners and their patients. Effects from the COVID‐19 pandemic superimposed on existing system demands have driven increasing concern about resource limitations, particularly in rural and remote settings. This article explores the legal liability of medical practitioners and healthcare services with respect to actions in negligence arising from harm to patients suffered, either partly or wholly, as a result of resource limitations.