bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing clinical development for neuronopathic Hunter syndrome through a quantitatively‐driven reverse translation framework
Authors: Latzman Robert D. , Campagne Olivia , Modi Meera E. , Karas Marta , Malanga C. J. , Whiteman David A. H. 
Published: March 2024

AbstractA quantitatively‐driven evaluation of existing clinical data and associated knowledge to accelerate drug discovery and development is a highly valuable approach across therapeutic areas, but remains underutilized. This is especially the case for rare diseases for which development is particularly challenging. The current work outlines an organizational framework to support a quantitatively‐based reverse translation approach to clinical development. This approach was applied to characterize predictors of the trajectory of cognition in Hunter syndrome (Mucopolysaccharidosis Type II; MPS‐II), a rare X‐linked lysosomal storage disorder, highly heterogeneous in its course. Specifically, we considered ways to refine target populations based on age, cognitive status, and biomarkers, that is, cerebrospinal fluid glycosaminoglycans (GAG), at trial entry. Data from a total of 138 subjects (age range 2.5 to 10.1 years) from Takeda‐sponsored internal studies and external natural history studies in MPS‐II were included. Quantitative analyses using mixed‐effects models were performed to characterize the relationships between neurocognitive outcomes and potential indicators of disease progression. Results revealed a specific trajectory in cognitive development across age with an initial progressive phase, followed by a plateau between 4 and 8 years and then a variable declining phase. Additionally, results suggest a faster decline in cognition among subjects with lower cognitive scores or with higher cerebrospinal fluid GAG at enrollment. These results support differences in the neurocognitive course of MPS‐II between distinct groups of patients based on age, cognitive function, and biomarker status at enrollment. These differences should be considered when designing future clinical trials.
Generic substitution of amlodipine is not associated with increased risk of mortality or adverse cardiovascular events: An observational cohort study
Authors: Zhao Boya , Wu Jing , Lu Chengzhi , Feng Xing Lin 
Published: March 2024

AbstractThis study aims to assess clinical outcomes following switching from originator to generic amlodipine. This population‐based, matched, cohort study included users of originator amlodipine using claims data during 2018–2020 from a health system in Tianjin, China, in which usage of generic amlodipine was promoted by a drug procurement policy, the national volume‐based procurement. Non‐switchers refer to those remained on originator after the policy, while pure‐switchers were those who switched to and continued using generic amlodipine, and back‐switchers were those switched to generic amlodipine but then back to the originator. Propensity score matching generates comparable non‐switchers and pure‐switchers pairs, and non‐switchers and back‐switchers pairs. The primary outcome was major adverse cardiovascular events (MACEs), defined as all‐cause mortality, stroke, and myocardial infarction during follow‐up (April 1, 2019 to December 30, 2020). Secondary outcomes included heart failure, atrial fibrillation, and adherence to amlodipine. The hazard ratio (HR) for each clinical outcome was assessed through Cox proportional hazard regression. In total, 5943 non‐switchers, 2949 pure‐switchers, and 3061 back‐switchers were included (mean age: 62.9 years; 55.5% men). For the matched pairs, pure‐switchers (N = 2180) presented no additional risks of clinical outcomes compared to non‐switchers (N = 4360) (e.g., MACEs: 2.86 vs. 2.95 events per 100 person‐years; HR = 0.97 [95%CI: 0.70–1.33]). Back‐switchers (N = 1998) also presented no additional risk compared to non‐switchers (N = 3996) for most outcomes except for stroke (HR = 1.55 [95%CI: 1.03–2.34]). Pure‐switchers and back‐switchers all had better amlodipine adherence than non‐switchers. Generic substitution of amlodipine is not associated with increased risk of cardiovascular events or all‐cause mortality, but improves medicine adherence.
Limited complementarity of functional and taxonomic diversity in Chilean benthic marine invertebrates
Authors: Pino Loreto , Webb Thomas J. 
Published: March 2024

AbstractAimPatterns of benthic biodiversity at the macroecological scale remain poorly characterised throughout the Chilean latitudinal gradient, in part due to the lack of integrated databases, uneven sampling effort, and the use of species richness alone to quantify biodiversity. Different diversity measures, encompassing taxonomic and functional components, may give us extra information on biodiversity relevant to conservation planning and management. Thus, evaluating the spatial complementarity of these measures is essential.LocationCoast and continental shelf of Chile.MethodsThe latitudinal gradient of Chile was divided into five ecoregions according to the Marine Ecosystems of the World classification. Using a 55 × 55 km equal area grid, we estimated the incidence coverage‐based estimator (ICE), taxonomic distinctness (Δ+) and three measures of functional diversity: functional richness (FRic), functional evenness (FEve) and functional divergence (FDiv). For each measure, we described spatial patterns, identified hotspots, evaluated hotspot congruence and evaluated complementarity between measures.ResultsDiversity patterns varied between ecoregions and over the latitudinal gradient. ICE and Δ+ peaked in the Chiloense and Channels and Fjords ecoregions. Δ+ and FRic present a similar pattern at mid‐latitudes. FEve showed a contrary pattern, principally with FRic. Areas with high numbers of hotspots differed spatially according to each metric, and three latitudinal bands were observed. ICE, Δ+ and FRic were positively correlated, but the hotspot overlap at the grid cell level was more limited.Main ConclusionsThe complementarity between taxonomic and functional diversity measures is limited when we observe the overlap between grid cells representing hotspots. However, some regions are consistently identified as highly diverse, with the Magellanic Province (Chiloense and Channels and Fjords ecoregions) being the most important for the richness, taxonomic and functional diversity of benthos. Confirmation of the importance of this region can help prioritise conservation efforts.
A Historical Introduction to Continental Pedagogics from a North American Perspective
Authors: Kraus Anja , Ylimaki Rose 
Published: March 2024

AbstractThis article aims to serve as an introductory discussion of the European Continental tradition of pedagogics, specifically from a North American perspective. It begins with an overview of the Continental tradition and its main figures. Here, we find a philosophical and, thus, language‐sensitive attitude toward the human, the child; and a specific pedagogical terminology, i.e., descriptions and interpretations about the reality of education, such as educational practices, goals, norms, and organizational forms of educational institutions. John Dewey's educational theories exemplify the North American perspective on Continental pedagogics and its study of the fundamental nature of knowledge, reality, and existence. Dewey's writings diverge notably from this tradition, as he integrated into his work American pragmatism and an interest in the scientific method, an interest that plays a role in today's policy trends in the United States and elsewhere. Then again, Dewey took a critical stand toward instrumentalizing pedagogics for political aims. On this point, the German‐born political philosopher Hannah Arendt agreed with him. As Arendt can be seen as an example of a Continental perspective on philosophy that includes a strong warning to separate politics and education, she relates to Dewey's argument against instrumentalization. Thus, this article also features some of her work. The overall intention is to contribute to a renewal of a language for pedagogics by delineating a historical‐philosophical perspective on this specific field of professional practice.
Transformations of Choice and Diversity in Education: Bildung from Wilhelm von Humboldt through John Stuart Mill to Milton Friedman
Authors: Price Todd Alan , Mattig Ruprecht 
Published: March 2024

AbstractThere is fierce controversy in the United States over whether parents should be able to choose their children's schools and/or curriculum. To discuss the pedagogical arguments inherent in this question, Todd Alan Price and Ruprecht Mattig begin with the classical concept of Bildung as developed by Wilhelm von Humboldt around 1800. Next, they compare Humboldt's ideas with the ideas of John Stuart Mill and Milton Friedman, who stand in the tradition of liberal thought, as Mill was strongly influenced by Humboldt and Friedman, in turn, by Mill. Finally, they consider Friedman's role as a central figure in the school choice movement, and are thus able to trace a line of thought from Humboldt to actual controversies. Price and Mattig's analysis here shows that the liberalism of Humboldt, Mill, and Friedman revolves around diversity and choice in education. Moreover, it traces that in the process of translating, translocating, and transcontextualizing Humboldt's original thought through Mill to Friedman, the complexity of arguments about education and the role of parents and the state in a liberal society has been unduly reduced. The authors conclude the paper by proposing a principle for thinking about the relationship between different educational institutions in democracies.
Rediscovery of Forgotten Dimensions of Pedagogical Practice from a Continental Perspective
Authors: Pfrang Agnes , Castner Daniel J. 
Published: March 2024

AbstractThis article critically assesses contemporary empirical educational research, directing attention toward overlooked facets of pedagogical practice. Here, Agnes Pfrang and Daniel Castner raise questions about predominant psychological approaches to empirical educational research, instead advocating for a holistic viewpoint that encompasses the subtleties of educational situations and experiences. They highlight the learning atmosphere and pedagogical relationships as crucial dimensions often neglected by researchers. By delving into the historical evolution of the relationship between educational research and empirical pedagogy, the article underscores the ramifications of an increasing emphasis on evidence‐based approaches. It contends that conventional control measures, focused on performance metrics and rankings, inadequately encapsulate the essence of pedagogy. Pfrang and Castner call for a paradigm shift, urging a more comprehensive and context‐sensitive framework in both educational research and practice. This article serves as a rallying cry for a nuanced understanding that embraces the multifaceted nature of educational interactions, advocating for a move away from traditional metrics and toward more inclusive perspectives.
General neurology: Current challenges and future implications
Authors: Bassetti Claudio Lino Alberto , Accorroni Alice , Arnesen Astri , Basri Hamidon Bin , Berger Thomas , Berlit Peter , Boon Paul , Charway‐Felli Augustina , Kruja Jera , Lewis Steven , Markowski Michael , Medina Marco Tulio , McCombe Pamela , Moro Elena , Ozturk Serefnur , Smith Phil , Vuletic Vladimira 
Published: March 2024

AbstractBackground and purposeIn the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future.MethodsThe European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN.ResultsThe TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future.ConclusionsGN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost‐effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN.
Playful personnel selection: The use of traditional versus game‐related personnel selection methods and their perception from the recruiters’ and applicants’ perspectives
Authors: Ohlms Marie L. , Melchers Klaus G. , Kanning Uwe P. 
Published: March 2024

AbstractGame‐related assessments (GRAs) are increasingly gaining interest in practice and research. However, little is known about how recruiters view these methods. This study examined recruiters’ (N = 158) reasons for using GRAs, the influence of their characteristics on their use of these methods, and recruiters’ perceptions of GRAs compared to those of potential applicants (N = 144). Results indicated that perceived ease of use, perceived usefulness, innovativeness in IT, and video game pursuit partly explained recruiters’ intentions to use GRAs, which then predicted actual usage. The expected positive impact on the organizational image and applicant reactions were among the most important reasons for using GRAs. Recruiters and potential applicants perceived GRAs as more enjoyable and modern than traditional assessment methods.
K33 only mutant ubiquitin augments bone marrow‐derived dendritic cell‐mediated CTL priming via PI3K‐Akt pathway
Authors: Liang Yi Yun , Liao Xiao Yan , Jia Jun Jun , Yin Yi Zhen , Zhang Yue Hua , Gao Feng Guang 
Published: March 2024

AbstractTo explore the effect of K33 only mutant ubiquitin (K33O) on bone marrow‐derived dendritic cells' (BMDCs') maturity, antigen uptake capability, surface molecule expressions and BMDC‐mediated CTL priming, and further investigate the role of PI3K‐Akt engaged in K33O‐increased BMDC maturation, antigen uptake and presentation, surface molecule expressions and BMDC‐based CTL priming. BMDCs were conferred K33O and other ubiquitin mutants (K33R, K48R, K63R‐mutant ubiquitin) incubation or LY294002 and wortmannin pretreatment. PI3K‐Akt phosphorylation, antigen uptake, antigenic presentation and CD86/MHC class I expression in BMDC were determined by western blot or flow cytometry. BMDC‐based CTL proliferation and priming were determined by in vitro mixed lymphocyte reaction (MLR), ex vivo enzyme‐linked immunospot assay (Elispot) and flow cytometry with intracellular staining, respectively. The treatment with K33O effectively augmented PI3K‐Akt phosphorylation, BMDCs' antigen uptake, antigenic presentation, CD86/MHC class I and CD11c expressions. MLR, Elispot and flow cytometry revealed that K33O treatment obviously enhanced CTL proliferation, CTL priming and perforin/granzyme B expression. The pretreatment with PI3K‐Akt inhibitors efficiently abrogated K33O's effects on BMDC. The replenishment of K33 only mutant ubiquitin augments BMDC‐mediated CTL priming in bone marrow‐derived dendritic cells via PI3K‐Akt signalling.
Research progress of the netrins and their receptors in cancer
Authors: Gao Xing , Ye Jiazhou , Huang Xi , Huang Shilin , Luo Wenfeng , Zeng Dandan , Li Shizhou , Tang Minchao , Mai Rongyun , Li Yongqiang , Lin Yan , Liang Rong 
Published: March 2024

AbstractNetrins, a family of secreted and membrane‐associated proteins, can regulate axonal guidance, morphogenesis, angiogenesis, cell migration, cell survival, and tumorigenesis. Four secreted netrins (netrin 1, 3, 4 and 5) and two glycosylphosphatidylinositols‐anchored membrane proteins, netrin‐G1 and G2, have been identified in mammals. Netrins and their receptors can serve as a biomarker and molecular therapeutic target for pathological differentiation, diagnosis and prognosis of malignant cancers. We review here the potential roles of the netrins family and their receptors in cancer.
Role of the gut microbiota and innate immunity in polycystic ovary syndrome: Current updates and future prospects
Authors: Zhou Min , Yu Jing , Li Xuewei , Ruan Zheng , Yu Shaohui 
Published: March 2024

AbstractPolycystic ovary syndrome (PCOS) is one of the modern intractable reproductive diseases. The female irregular menstruation, infertility, obesity, and so forth caused by PCOS have become a hot issue affecting family harmony and social development. The aetiology of PCOS is complex. In recent years, many scholars have found that its pathogenesis was related to the imbalance of gut microbiota. Gut microbiota can form two‐way communication with the brain through the ‘gut‐brain axis’ and affect the host's metabolism. Current research has confirmed that the gut microbiota can interfere with glucose and lipid metabolism, insulin sensitivity, hormone secretion and follicular development in women by altering intestinal mucosal permeability and secreting metabolites. In addition, the diversity and composition of gut microbiota of PCOS patients changed, which may affect the metabolic function of the gut microbiota and the ability to produce metabolites, and may also directly or indirectly affect the endocrine function. This study reviewed recent research advances about the role of gut microbiota in PCOS. In order to provide basis for prevention and treatment of PCOS based on gut microbiota.
Bond pairs and the term structure
Authors: Diaz Antonio , Livingston Miles 
Published: March 2024

AbstractIn the US Treasury bond market, the existence of a bond pair (two bonds with the same maturity but different coupons) is shown to allow the computation of the zero‐coupon interest rate for that maturity directly from the bond prices, as well as the zero‐coupon interest rates for adjacent maturity bonds with the same number of coupon payments. Since the 2008–2009 financial crisis, the number of bond pairs has increased, allowing for the direct estimation from bond prices of the zero‐coupon interest rates for an average of 180 individual maturities for bond maturities between 6 months and 30 years. The bond pairs approach outperforms popular yield‐curve‐fitting models in accurately reproducing original bond prices.
Variant‐specific in vitro neuronal network phenotypes and drug sensitivity in SCN2A developmental and epileptic encephalopathy
Authors: Jia Linghan , Li Melody , Pachernegg Svenja , Sedo Alicia , Jancovski Nikola , Burbano Lisseth Estefania , Dalby Kelley , Nemiroff Alex , Reid Christopher , Maljevic Snezana , Petrou Steven 
Published: March 2024

AbstractDe novo variants in the NaV1.2 voltage‐gated sodium channel gene SCN2A are among the major causes of developmental and epileptic encephalopathies (DEE). Based on their biophysical impact on channel conductance and gating, SCN2A DEE variants can be classified into gain‐of‐function (GoF) or loss‐of‐function (LoF). Clinical and functional data have linked early seizure onset DEE to the GoF SCN2A variants, whereas late seizure onset DEE is associated with the loss of SCN2A function. This study aims to assess the impact of GoF and LoF SCN2A variants on cultured neuronal network activity and explore their modulation by selected antiseizure medications (ASM). To this end, primary cortical cultures were generated from two knock‐in mouse lines carrying variants corresponding to human GoF SCN2A p.R1882Q and LoF p.R853Q DEE variant. In vitro neuronal network activity and responses to ASM were analyzed using multielectrode array (MEA) between 2 and 4 weeks in culture. The SCN2A p.R1882Q neuronal cultures showed significantly greater mean firing and burst firing. Their network synchronicity was also higher. In contrast, the SCN2A p.R853Q cultures showed lower mean firing rate, and burst firing events were less frequent. The network synchronicity was also lower. Phenytoin and levetiracetam reduced the excitability of GoF cultures, while retigabine showed differential and potentially beneficial effects on cultures with both GoF and LoF variants. We conclude that in vitro neuronal networks harboring SCN2A GoF or LoF DEE variants present with distinctive phenotypes and responses to ASM.image
A new nonsurgical combination approach for skin tightening and remodeling; Endoskin—A comparative study
Authors: Benar Hasan , Benar Elif Burcu 
Published: March 2024

AbstractIntroductionThis article introduces a novel nonsurgical skin tightening and remodeling approach termed Endoskin, which combines internal laser therapy (1470 nm Diode laser) with injectable poly‐L‐lactic acid (PLLA). The internal laser targets the superficial fat layer, stimulating collagen production and cellular rejuvenation, leading to gradual skin tightening and improved elasticity. Simultaneously, PLLA promotes collagen synthesis, strengthening the skin's foundation and restoring volume. This comprehensive exploration delves into Endoskin's mechanisms, clinical applications, and its differentiation from traditional methods.MethodsThe study encompassed 234 participants, categorized into two groups: Group A received internal laser treatment and Group B received the combined Endoskin treatment. Patient satisfaction, assessed using a Likert scale unveiled significantly higher levels in Group B. Dermatologists, blinded to treatment details, also expressed greater satisfaction with the combination treatment outcomes.DiscussionThe ensuing discussion emphasizes the synergistic effects of internal laser therapy and PLLA, presenting a multifaceted approach to skin rejuvenation. The study results underscore Endoskin's efficacy, safety, and its potential as a nonsurgical option for skin tightening and remodeling. The gradual and harmonious transformation aligns with natural aging, positioning Endoskin as an appealing choice for those seeking subtle yet impactful changes.ConclusionIn conclusion, Endoskin demonstrates notable efficacy, reliability, and safety in achieving skin rejuvenation. Although further research is warranted to assess its long‐term effects, the current findings position Endoskin as a promising option with a significantly higher level of overall patient and dermatologist satisfaction compared to internal laser treatment alone.