bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asia‐inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler
Authors: Lu Hong , Klopp‐Schulze Lena , Mukker Jatinder Kaur , Li Dandan , Kuroki Yoshihiro , Bolleddula Jayaprakasam , Terranova Nadia , Goteti Kosalaram , Gao Wei , Strotmann Rainer , Dong Jennifer , Venkatakrishnan Karthik 
Published: October 2024

AbstractWith the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guidelines in effect from 2018, the design of Asia‐inclusive multiregional clinical trials (MRCTs) has been streamlined, thereby enabling efficient simultaneous global development. Furthermore, with the recent regulatory reforms in China and its drug administration joining the ICH as a full regulatory member, early participation of China in the global clinical development of novel investigational drugs is now feasible. This would also allow for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E5 and E17. Herein, we describe recent case examples of model‐informed Asia‐inclusive global clinical development in the EMD Serono portfolio, as applied to the ataxia telangiectasia and Rad3‐related inhibitors, tuvusertib and berzosertib (oncology), the toll‐like receptor 7/8 antagonist, enpatoran (autoimmune diseases), the mesenchymal–epithelial transition factor inhibitor tepotinib (oncology), and the antimetabolite cladribine (neuroimmunological disease). Through these case studies, we illustrate pragmatic approaches to ethnic sensitivity assessments and the application of a model‐informed drug development toolkit including population pharmacokinetic/pharmacodynamic modeling and pharmacometric disease progression modeling and simulation to enable early conduct of Asia‐inclusive MRCTs. These examples demonstrate the value of a Totality of Evidence approach where every patient's data matter for de‐risking ethnic sensitivity to inter‐population variations in drug‐ and disease‐related intrinsic and extrinsic factors, enabling inclusive global development strategies and timely evidence generation for characterizing benefit/risk of the proposed dosage in Asian populations.
Performance of ChatGPT and Dental Students on Concepts of Periodontal Surgery
Authors: Li Chen , Zhang Jinmei , Abdul‐Masih John , Zhang Sihan , Yang Jingmei 
Published: October 2024

ABSTRACTIntroductionAs a large language model, chat generative pretrained transformer (ChatGPT) has provided a valuable tool for various medical scenarios with its interactive dialogue‐based interface. However, there is a lack of studies on ChatGPT's effectiveness in handling dental tasks. This study aimed to compare the knowledge and comprehension abilities of ChatGPT‐3.5/4 with that of dental students about periodontal surgery.Materials and MethodsA total of 134 dental students participated in this study. We designed a questionnaire consisting of four questions about the inclination for ChatGPT, 25 multiple‐choice, and one open‐ended question. As the comparison of ChatGPT‐3.5 and 4, the question about the inclination was removed, and the rest was the same. The response time of ChatGPT‐3.5 and 4 as well as the comparison of ChatGPT‐3.5 and 4′ performances with dental students were measured. Regarding students' feedback on the open‐ended question, we also compared the outcomes of ChatGPT‐4′ and teacher's review.ResultsOn average, ChatGPT‐3.5 and 4 required 3.63 ± 1.18 s (95% confidence interval [CI], 3.14, 4.11) and 12.49 ± 7.29 s (95% CI, 9.48, 15.50), respectively (p < 0.001) for each multiple‐choice question. For these 25 questions, the accuracy was 21.51 ± 2.72, 14 and 20 for students, ChatGPT‐3.5 and 4, respectively. Furthermore, the outcomes of ChatGPT‐4's review were consistent with that of teacher's review.ConclusionsFor dental examinations related to periodontal surgery, ChatGPT's accuracy was not yet comparable to that of the students. Nevertheless, ChatGPT shows promise in assisting students with the curriculum and helping practitioners with clinical letters and reviews of students' textual descriptions.
Genital and sexual alterations in regular cyclists: A urological point of view
Authors: Giraldo Gómez Mariana , Nieva‐Posso Daniel Andrés , García‐Perdomo Herney Andrés 
Published: October 2024

AbstractCycling is one of the leading sports activities practiced in the Western world; its promotion, even from political spaces, as a non‐polluting transportation alternative in urban spaces has led to its frequent practice among men and women. Our objective was to review the association between regular cycling and the development of urological and sexual disorders in men and women. The intensity of cycling, the number of hours invested, the positioning of the seat, and the body position can lead to the development of urological and sexual disorders that can affect the quality of life. As for male cyclists, the intense practice of this sport has been associated with prostatic disturbances and pelvic pain. Sexual disorders have been identified with genital numbness and the development of injuries, and it is still controversial, although most of the literature does negate the development of erectile dysfunction. In women, it has been associated more frequently with dysuria and recurrent urinary infections; as for sexual disorders, it has been associated with chronic pelvic pain, genital numbness, and, more regularly, the development of genital sores. Regular and high‐intensity cycling practice has urological and sexual effects in both men and women, but more studies are needed to reach better decisions.
Adult penicillin allergy programmes in Australian hospitals: a practical guide from the National Antibiotic Allergy Network
Authors: Hannah Rory , Mitri Elise , Katelaris Constance H. , O'Hern Jennifer , Avent Minyon , Valoppi Glenn , Rawlins Matthew , Frith Catherine , McMullan Brendan , Kong David , Chua Kyra , Legg Amy , James Rod , Janson Sonja , Hawkins Carolyn , Randall Katrina , Ierano Courtney , Thursky Karin , Trubiano Jason A. 
Published: October 2024

AbstractPenicillin allergy is a significant burden on patient, prescribing and hospital outcomes. There has been increasing interest in the incorporation of penicillin allergy testing (i.e. delabelling) into antimicrobial stewardship (AMS) programmes to reduce the burden of penicillin allergy labels and improve prescribing. In particular, there has been a focus on point‐of‐care penicillin allergy assessment and direct oral challenge for low‐risk phenotypes. The National Antibiotic Allergy Network has provided a guide to assist AMS clinicians with the incorporation of penicillin allergy programmes, in particular direct oral challenge, into Australian hospitals.
Mitogen‐activated protein kinase kinase kinase 1 facilitates the temozolomide resistance and migration of GBM via the MEK/ERK signalling
Authors: Wu Sicheng , Xue Senrui , Tang Yuchen , Zhao Wenyu , Zheng Maojin , Cheng Zhixuan , Hu Xin , Sun Jinmin , Ren Jing 
Published: October 2024

AbstractMitogen‐Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is overexpressed in gliomas; however, its clinical significance, biological functions, and underlying molecular mechanisms remain unclear. Abnormal overexpression of MAP3K1 in glioma is strongly associated with unfavourable clinicopathological characteristics and disease progression. MAP3K1 could potentially serve as a reliable diagnostic and prognostic biomarker for glioma. MAP3K1 silencing suppressed the migration but had no effect on the proliferation and cell death of Glioblastoma Multiforme (GBM) cells. MAP3K1 knockdown exacerbated the temozolomide (TMZ) induced inhibition of glioma cell proliferation and death of GBM cells. In addition, MAP3K1 knockdown combined with TMZ treatment significantly inhibited the growth and increased cell death in organoids derived from GBM patients. MAP3K1 knockdown reversed TMZ resistance of GBM in intracranial glioma model. In terms of molecular mechanisms, the phosphorylation level of ERK was significantly decreased by MAP3K1 silencing. No significant change in the JNK pathway was found in MAP3K1‐silenced GBM cells. Inhibition of ERK phosphorylation suppressed the migration and enhanced the TMZ sensibility of GBM cells. MAP3K1 was correlated with the immune infiltration in glioma. MAP3K1 could facilitate the migration and TMZ resistance of GBM cells through MEK/ERK signalling.
From Stream to Bloom: Exploring the Potential Role of Aquatic Insects for Pollination in Wetland Environments
Authors: Murail Cassandre , Baude Mathilde , Bergerot Benjamin , Geslin Benoit , Legay Nicolas , Villalta Irene , Greulich Sabine 
Published: October 2024

ABSTRACTThe substantial loss of insects we are experiencing today has been highlighted all over the world. There is a growing concern about the global decline of pollinators and its impact on terrestrial and agricultural ecosystems, but the focus of scientists towards bees remains the rule. Therefore, the role of other insect taxa in pollination is still overlooked. Our review focused on some of these neglected pollinating taxa, the winged aquatic insects, i.e., insects with an aquatic larval stage such as Ephemeroptera, Trichoptera, Plecoptera (ETP), Megaloptera and some aquatic Diptera. We first documented the visitors of aquatic and wetland flowering plants, anticipating a greater presence of aquatic insects on these plants compared to terrestrial pollinators. Secondly, we documented plant visits, pollen found in gut contents and pollen transfers performed by aquatic insects. Our results revealed a surprisingly low proportion of aquatic insects visiting both aquatic and wetland plants, suggesting a potential gap in the literature. The scarcity of articles dedicated to pollen transfer by aquatic insects also indicates that they are fewly considered in ecological studies. While the role of aquatic insects in pollination is not well documented in the literature, records of their flower visits and pollen found on them or in their gut contents do exist and are promising clues to consider them as effective pollinators. Future research is needed to provide new insights into the importance of winged aquatic insects for the reproductive success of plants, which could also be an argument for the importance of wetland conservation.
Haematological and Biochemical Reference Intervals Towards a Proactive Health Monitoring Approach in Norwegian Atlantic Salmon Farming
Authors: Keitel‐Gröner Frederike , Hoel Eirik , Husebø Christina , Le Hoang Thi My Dung , Bjerkestrand Kristine Marie , Lagos Leidy , Sandstad Margunn , Knudsen David Lausten , Rennemo Johan , Berge Kjetil 
Published: October 2024

ABSTRACTHaematological and plasma parameters are used in veterinary medicine as a diagnostic tool, allowing for the early detection of potential health and welfare issues. For the implementation of monitoring strategies, reference intervals (RIs) are needed to know when deviations in those parameters become clinically relevant. Here, haematological and plasma biochemical RIs of Norwegian Atlantic salmon (Salmo salar Linnaeus) are presented for 29 biomarkers. Two subgroups were defined from the reference population based on water type, referred to as pre‐adult (freshwater, 166.8 ± 118.4 g, N = 979) and adult (seawater, 2655 ± 2883 g, N = 4941), collected at 93 fish farms along the Norwegian coast. While the influence of various pre‐analytical variables on RIs is well documented, aquaculture practitioners cannot always control those variables in the field. Here, RIs were calculated from blood samples collected based on local pre‐analytical practices and then further processed under standardised conditions (analytical phase). RIs are therefore considered highly relevant for the application in the field. Finally, when taking blood samples in the field, it is advised to centrifuge whole blood as soon as possible, while plasma parameters investigated were stable for 168 h at 4°C or 72 h at room temperature.
Has the Euro Paid Off? A Study of the Trade‐Induced Welfare Effects of the EMU
Authors: Esteve‐Pérez Silviano , Gil‐Pareja Salvador , Llorca‐Vivero Rafael , Paniagua Jordi 
Published: October 2024

AbstractThis paper aims to provide policy‐relevant insights into the effect of the euro on trade. It uses a new data set of bilateral international and intranational manufacturing trade flows for 69 countries over the period 1986−2016. A general equilibrium gravity model is estimated to quantify the welfare effect of the euro and its impact on consumer prices and producer prices within countries (i.e., distributional effects). The results of three counterfactual experiments indicate that the euro has successfully increased welfare for the Economic and Monetary Union (EMU) and non‐EMU member countries. The results suggest that a two‐speed euro design would have further increased welfare, with some heterogeneity within countries. The growth effects of the euro are mainly driven by trade creation outside the EMU. This finding raises questions over the cohesiveness of the euro area as an optimum currency area.
Support for a Weight‐Inclusive Curriculum? Exploring Partner Perspectives and Influences on Nutrition Education in Vermont High Schools
Authors: Hinchey Deborah , Garnett Bernice Raveche , Gamble Janet , Pope Lizzy 
Published: October 2024

AbstractBackgroundThe weight‐normative approach to nutrition education dominates health education programming across the United States, despite evidence that this paradigm contributes to negative outcomes including weight cycling, bias and stigma, the development of disordered eating behaviors, and weight‐based bullying.MethodsThis study investigates perspectives of 10 potential partners with interest in and potential to influence nutrition education. Through qualitative interviews and document analysis, researchers explored support for a weight‐inclusive curriculum and factors that influence high school nutrition curricular content and implementation.ResultsFindings indicate that partners hold both weight‐inclusive and weight‐normative values, guidance around nutrition curricular content is lacking, and state‐level policy is crucial to the valuing and implementation of consistent curricula.Implications for School Health Policy, Practice, and EquityLack of guidance or mandated curricular content contributes to inequities across the state. Weight‐inclusive curricular materials are needed. Administration must take an active role in providing access to professional development and state policy support for curricular implementation is essential.ConclusionsWeight‐inclusive curriculum could serve to improve health outcomes for adolescents. However, successful implementation of, or changes to, health and nutrition curricula will require support and engagement from partners at all ecological levels.
From oppressive to affirmative: Situating the health and well‐being of LGBTIQ+ people as impacted by systemic and structural transitions in Russia, Turkey, Pakistan, and India
Authors: Ahuwalia Diana Cherian , Singh Purnima , Jami Humaira , Ummak Esra , Osin Evgeny 
Published: October 2024

AbstractInequity in health and well‐being is driven by systemic, political, and structural forces that, along with social factors, influence the allocation, access, and impact of health resources across communities based on religion, gender, caste, sexuality, and ability. Lesbian, gay, bisexual, transgender, intersex, queer/questioning, and plus (LGBTIQ+) communities, marginalized for subverting cis‐gender norms, face heightened risks of poor health, well‐being, and limited psycho‐social, medical, and legal support. Understanding the challenges and triumphs of LGBTIQ+ individuals navigating oppressive and discriminatory legal, social, and structural forces can significantly contribute to improving their health and well‐being. Additionally, such insights can inform public policy and legal structures to be more inclusive. This paper offers a commentary on the health and psycho‐social well‐being of LGBTIQ+ individuals, focusing on the systemic transitions in Russia, Turkey, Pakistan, and India. The unique, intersectional identities of queer individuals make them particularly vulnerable to stigma and discrimination. While Pakistan has laws to protect transgender rights and India has decriminalized same‐sex behavior, LGBTIQ+ individuals in these countries still face discrimination in housing, careers, and healthcare, similar to the experiences in Turkey and Russia, where no legal protections exist. The paper emphasizes the need to view queer experiences through an intersectional lens, acknowledging that advancements in one area alone may not suffice to transform their experiences from marginalization to inclusion.
‘No es la democracia que míster superman quiere imponernos desde Washington’: An analysis of populist attitudes on democracy from Latin American legislators
Authors: Marenghi Patricia , Montero Mercedes García 
Published: October 2024

AbstractIn studies on Populism, extensive discussion has mounted around whether the phenomenon represents a threat to democracy or a corrective force. In line with this concern, we examine whether the populist attitudes held by legislators are related to their opinions on the functioning of and satisfaction with three central aspects of governance: (I) democracy itself; (II) its institutions; and (III) the separation of powers. Using the ideational approach and survey information collected for the PELA‐USAL database, we first measure the populist attitudes of legislators in 12 Latin American countries. We then test through multivariate analysis two theoretical arguments: (1) that populism is relatively hostile to democracy and its institutions; and (2) that ideological extremism and the situation of the legislator in the government/opposition dynamic serve as moderators (enhancers) of that hostility. The results suggest that the populist attitudes of these legislators are indeed significantly connected to lower levels of trust and satisfaction with democracy and its institutions and that populism in combination with ideological extremism sharpens that critical perspective, while a legislator's affiliation with the ruling party or coalition in government tends to temper it.
MHC Class II Supertypes Affect Survival and Lifetime Reproductive Success in a Migratory Songbird
Authors: Canal David , Roved Jacob , Lara Antonio , Camacho Carlos , Potti Jaime , Santoro Simone 
Published: October 2024

ABSTRACTThe major histocompatibility complex (MHC) plays a critical role in the immune response against pathogens. Its high polymorphism is thought to be mainly the consequence of host‐pathogen co‐evolution, but elucidating the mechanism(s) driving MHC evolution remains challenging for natural populations. We investigated the diversity of MHC class II genes in a wild population of pied flycatchers Ficedula hypoleuca and tested its associations with two key components of individual fitness: lifetime reproductive success and survival. Among 180 breeding adults in our study population, we found 182 unique MHC class II exon 2 alleles. The alleles showed a strong signal of positive selection and grouped into nine functional supertypes based on physicochemical properties at the inferred antigen‐binding sites. Three supertypes were found in > 98% of the sampled individuals, indicating that they are nearly fixed in the population. We found no rare supertypes in the population, as all supertypes were present in > 70% of individuals. Three supertypes were related to different components of individual fitness: two were associated with lower offspring production over time, while the third was positively associated with survival. Overall, the substantial allelic and functional diversity and the relationship between specific supertypes and fitness are in accordance with the notion that balancing selection maintains MHC class II diversity in the study population, possibly with fluctuating selection as the underlying mechanism. The absence of rare supertypes in the population suggests that the balancing selection is not driven by rare‐allele advantage.
Building Resilient Communities by Fostering Social Equity in Public Administration: Analyzing the Influence of Social Capital on COVID‐19 Vaccination Rates in Communities With Varying Social Vulnerabilities
Authors: Lofaro Ryan J. , Entress Rebecca , Liu Gao 
Published: October 2024

ABSTRACTWe draw from the Theory of Fundamental Causes to examine social equity and community resilience in public administration. We analyze the effect of social capital and social vulnerability on COVID‐19 vaccination rates in United States' counties, as well as social capital's influence in counties with varying social vulnerabilities. Findings show that bonding social capital and socioeconomic status (SES) vulnerability negatively predict vaccine uptake. Bonding's negative association is most pronounced in counties with minority status and language (MS&L) vulnerabilities, and specifically, Hispanic communities, with its influence disappearing in high SES vulnerability counties and Black communities. Linking social capital increases vaccination rates in Black communities and those with SES vulnerability, but not in Hispanic communities or those with MS&L vulnerabilities. The article highlights the nuances of social connections as a resource to enhance resilience. Variations across communities of color and those with varying social vulnerabilities demonstrate the complexity of social equity.
High diversity of Phytophthora species in natural ecosystems and nurseries of Portugal: Detrimental side effect of plant introductions from the age of discovery to modern globalization
Authors: Horta Jung Marília , Maia Cristiana , Mora‐Sala Beatriz , Abad‐Campos Paloma , Schena Leonardo , Mosca Saveria , Carella Giuseppe , Moricca Salvatore , Nechwatal Jan , Dionísio Lídia , Cravador Alfredo , Jung Thomas 
Published: October 2024

AbstractBetween 2010 and 2015, an extensive survey of Phytophthora diversity was performed across Portugal. Baiting and direct isolation tests obtained 48 Phytophthora taxa in 62 of 70 forest stands (89%) from 148 of 302 rhizosphere soil samples (49%) and 25 of 29 tree species (86%), and from bark cankers of Alnus lusitanica and Fagus sylvatica; from 33 of 34 rivers and forest streams (97%); and in 12 of 13 forest nurseries (92%) from 54 of 87 root ball samples (61%) and 16 of 21 tree species (76%). The 799 Phytophthora isolates belonged to 28 known and three recently described species; one designated and two new non‐hybrid taxa; and five designated and nine new hybrid taxa. The majority, 34 Phytophthora taxa (71%), are introduced aliens in Europe while nine (19%) and five (10%) taxa are of cryptic and native origin, respectively. Phytophthora cinnamomi was the most common species in forests (56%) and forest nurseries (61%). Multiple first records for Portugal and partly Europe of both Phytophthora taxa and tree declines and new host–Phytophthora associations were found. Isolation rates from forest soil differed considerably between declining (65%) and healthy trees (10%), regardless of the tree species. The widespread infestations of nurseries with aggressive wide‐host range pathogens like P. cinnamomi, P. pseudocryptogea, P. ×cambivora, P. multivora and P. plurivora, and host‐specific pathogens like P. alticola, P. quercetorum and P. quercina, will inevitably cause their further spread to the wider environment, exacerbating pathogen threats to forest ecosystems and thus weakening their resilience to climatic extremes.