bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the contribution of genetic variants to high sunitinib exposure in patients with cancer
Authors: Giraud Eline L. , Krens Stefanie D. , Böhringer Stefan , Desar Ingrid M. E. , Vermeulen Sita H. , Kiemeney Lambertus A. , Huitema Alwin D. R. , Steeghs Neeltje , van Erp Nielka P. , Swen Jesse J. 
Published: August 2024

AimsSunitinib exhibits considerable interindividual variability in exposure. While the target total plasma concentration of sunitinib and its active metabolite is 50–87.5 ng/mL for the intermittent dosing schedule, ~10–21% of patients experience higher exposures (>87.5 ng/mL), correlated with an increased risk for toxicity. Previous research identified single nucleotide variants (SNVs) in genes from the sunitinib pharmacokinetic pathway to be associated with efficacy and toxicity. However, significant interindividual variability in exposure remains unexplained. Our aim was to identify genetic variants associated with supratherapeutic exposure of sunitinib.MethodsThis was a genome‐wide association study. Cases were identified during routine therapeutic drug monitoring and consisted of patients with dose‐normalized sunitinib plasma concentrations >87.5 ng/mL (intermittent dosing) or >75 ng/mL (continuous dosing). Controls were sampled from the historical cohort EuroTARGET who tolerated the standard dose of 50 mg in an intermittent schedule. SNVs were tested for an association with sunitinib exposure. A P‐value ≤5 × 10−8 was considered significant and a P‐value between 5 × 10−8 and 5 × 10−6 was considered suggestive.ResultsSixty‐nine cases and 345 controls were included for association analysis. One SNV (rs6923761), located on the gene glucagon‐like peptide 1 receptor, was significantly associated with increased sunitinib exposure (P = 7.86 × 10−19). Twelve SNVs were suggestive for an association with sunitinib exposure (P ≤ 5 × 10−6).ConclusionsWhile rs6923761 is associated with high sunitinib exposure, the underlying mechanism is not yet clarified and warrants further investigation. [Corrections made on 23 September 2024, after first online publication: In the preceding sentence, identifier rs6923671 has been changed to rs6923761 in this version.] We could not confirm the earlier found associations between SNVs in candidate genes involved in the pharmacokinetic pathway of sunitinib and its efficacy and toxicity.
Revisiting the full blood count: Circulating blood cells and their role in coagulation
Authors: Schofield Jeremy , Yong Jun , Toh Cheng‐Hock 
Published: August 2024

SummaryThere has been an expansion in our understanding of the multifaceted roles of circulating blood cells in regulating haemostasis and contributing to thrombosis. Notably, there is greater recognition of the interplay between coagulation with inflammation and innate immune activation and the contribution of leucocytes. The full blood count (FBC) is a time‐honoured test in medicine; however, its components are often viewed in isolation and without consideration of their haemostatic and thrombotic potential. Here, we review how the individual components of the FBC, that is, haemoglobin, platelets and leucocytes, engage with the haemostatic system and focus on both their quantitative and qualitative attributes. We also explore how this information can be harnessed into better management of people with multiple long‐term conditions because of their higher risk of adverse clinical events.
ADO09, a co‐formulation of pramlintide and insulin A21G, lowers body weight versus insulin lispro in type 1 diabetes
Authors: Andersen Grit , Eloy Rosy , Heise Tim , Gaudier Martin , Mégret Claire , Seroussi Cyril , Chan You‐Ping , Soula Olivier , Riddle Matthew , DeVries J. Hans 
Published: August 2024

AbstractAimTo study safety, efficacy and weight loss with ADO09, a co‐formulation of insulin A21G and pramlintide, in type 1 diabetes.Materials and MethodsA randomized, two‐arm ambulatory 16‐week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment.ResultsA significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed.ConclusionsThese results extend previous observations on the efficacy and safety of this insulin/pramlintide co‐formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia.
Efficacy, adherence and persistence of various glucagon‐like peptide‐1 agonists: nationwide real‐life data
Authors: Kassem Sameer , Khalaila Buthaina , Stein Nili , Saliba Walid , Zaina Adnan 
Published: August 2024

AbstractAimThe management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP‐1RAs in efficacy, adherence and persistence.Materials and MethodsWe conducted a retrospective cohort study using the electronic medical database from Clalit Health Services. Adults with type 2 diabetes mellitus who purchased any GLP‐1RA between 2009 and 2021 were included. The Index Date was defined as the date of the first purchase of any GLP‐1RA. We evaluated the adherence, persistence and glycaemic control after GLP‐1RAs initiation. Baseline glycaemic and post‐treatment glycaemic controls were analysed.ResultsIn total, 70 654 patients were included. The mean age was 11.7 ± 60.4, and 51% were females. A significant reduction in glycated haemoglobin (HbA1c) was observed in all patients who received GLP‐1RAs. However, the percentage of changes in the HbA1c was higher among weekly GLP‐1RA than daily initiators (14.6% vs. 10.2%, p < 0.001). The proportion of subjects with any decrease in HbA1c was higher among the once‐weekly compared with the daily dose (82.4% vs. 74.7%) and mainly patients initiated semaglutide or dulaglutide, with 16.0% and 14.7% reduction. The frequency of good adherence (the proportion of days covered ≥80%) was significantly higher among the weekly group odds ratio = 1.25 (95% confidence interval 1.21–1.28). Good adherence was reported in older age, female gender, Jewish ethnicity and high socio‐economic status (p < 0.001).ConclusionsWeekly GLP‐1RAs initiators were more adherent, persistent to therapy and achieved better glycaemic control. Epidemiological variables might play a role in achieving this goal.
Real‐world smartphone data can trace the behavioural impact of epilepsy: A case study
Authors: van Nieuw Amerongen Arthur R. , Meppelink Anne Marthe , Ghosh Arko , Thijs Roland D. 
Published: August 2024

AbstractBackgroundNeurobehavioural comorbidities have a detrimental effect on the quality of life of people with epilepsy, yet tracking their impact is challenging as behaviour may vary with seizures and anti‐seizure medication (ASM) side effects. Smartphones have the potential to monitor day‐to‐day neurobehavioural patterns objectively. We present the case of a man in his late twenties with drug‐resistant focal epilepsy in whom we ascertained the effects of ASM withdrawal and a convulsive seizure on his touchscreen interactions.MethodsUsing a dedicated app, we recorded over 185 days the timestamps of 718,357 interactions. We divided the various smartphone behaviours according to the next‐interval dynamics of the interactions by using a joint interval distribution (JID). During two ASM load transitions, namely before versus during tapering and tapering versus restarting medication, we used cluster‐based permutation tests to compare the JIDs. We also compared the JID of the seizure day to the average of the previous 3 days.ResultsThe cluster‐based permutation tests revealed significant differences, with accelerated next‐interval dynamics during tapering and a reversal upon medication restart. The day of the convulsion exhibited a marked slowing of next‐interval dynamics compared to the preceding 3 days.ConclusionOur findings suggest that the temporal dynamics of smartphone touchscreen interactions may help monitor neurobehavioural comorbidities in neurological care.
Family social support for college students with disabilities
Authors: Daly‐Cano Meada , Ruise Brandis L. , Moore Adam , Vaccaro Annemarie , Newman Barbara M. , Newman Philip R. 
Published: August 2024

AbstractObjectiveThe purpose of this work was to provide insight into the complex processes through which families support their children with disabilities as they move into and through college.BackgroundStudents with disabilities, like all traditional‐age college students, must adapt to increased levels of freedom, opportunities for autonomous decision‐making, and expectations of self‐directed behavior. However, students continue to need social support as they adapt to the new demands of college environments and to changing postsecondary contexts where family roles are more limited.MethodConstructivist grounded theory methods were used to examine the qualitative narratives from a study of 59 college students with disabilities in the United States. Using grounded theory constant comparative analysis (Charmaz, 2014), emergent themes related to perceived family support surfaced.ResultsStudents described familial support in ways that expanded on the common types of family support documented in prior literature. Findings are organized into five sections with examples of the following: instrumental support, informational support, emotional support, support by resilience modeling, and support by reframing disability.ConclusionFindings suggest that students with disabilities experience various types of family support during college.ImplicationsPolicy‐informed implications for families and educators are discussed. Recommendations are made for parents and college educators about recognizing the variety of types of familial support to foster effective support for youth with disabilities as they transition away from home and into college.
Lineage tracing using Wnt2b‐2A‐CreERT2 knock‐in mice reveals the contributions of Wnt2b‐expressing cells to novel subpopulations of mesothelial/epicardial cell lineages during mouse development
Authors: Takahashi Masanori , Isagawa Takayuki , Sato Tatsuyuki , Takeda Norihiko , Kawakami Kiyoshi 
Published: August 2024

AbstractMesothelial and epicardial cells give rise to various types of mesenchymal cells via epithelial (mesothelial)‐to‐mesenchymal transition during development. However, the genes controlling the differentiation and diversification of mesothelial/epicardial cells remain unclear. Here, we examined Wnt2b expression in the embryonic mesothelium and epicardium and performed lineage tracing of Wnt2b‐expressing cells by using novel Wnt2b‐2A‐CreERT2 knock‐in and LacZ‐reporter mice. Wnt2b was expressed in mesothelial cells covering visceral organs, but the expression was restricted in their subpopulations. Wnt2b‐expressing cells labeled at embryonic day (E) 10.5 were distributed to the mesothelium and mesenchyme in the lungs, abdominal wall, stomach, and spleen in Wnt2b2A‐CreERT2/+;R26RLacZ/+ mice at E13.0. Wnt2b was initially expressed in the proepicardial organ (PEO) at E9.5 and then in the epicardium after E10.0. Wnt2b‐expressing PEO cells labeled at E9.5 differentiated into a small fraction of cardiac fibroblasts and preferentially localized at the left side of the postnatal heart. LacZ+ epicardium‐derived cells labeled at E10.5 differentiated into a small fraction of fibroblasts and smooth muscle cells in the postnatal heart. Taken together, our results reveal novel subpopulations of PEO and mesothelial/epicardial cells that are distinguishable by Wnt2b expression and elucidate the unique contribution of Wnt2b‐expressing PEO and epicardial cells to the postnatal heart.
Correlation of FUT3 and FUT6 Gene Polymorphisms With Helicobacter pylori Infection
Authors: Zhou Shihang , Zheng Ziwei , Wang Liying , Song Wenqian , Xia Yuexin , Shao Linnan , Liang Xiaohua 
Published: August 2024

ABSTRACTBackgroundHelicobacter pylori infection is a significant pathogen in gastrointestinal diseases. Previous studies have identified single‐nucleotide polymorphisms (SNPs) are factors associated with H. pylori infection. Notably, Leb and Sialyl‐Lex antigens, regulated by the FUT3 and FUT6 genes, play a crucial role in H. pylori infection. This study aimed to investigate the correlation between FUT3 and FUT6 gene polymorphisms and H. pylori infection in the Han population of northern China.Materials and MethodsAn immunoturbidimetric assay was employed to detect H. pylori infection, categorizing subjects into infected and noninfected groups. Gene variants were identified through sequencing. Finally, FUT3 and FUT6 gene polymorphisms were analyzed to assess their association with H. pylori infection.ResultsThe frequency of the T allele (rs778805) and the G allele (rs61147939) in the infection group was significantly higher than that in the noninfection group (63.4% vs. 55.1%, p = 0.045; 55.2% vs. 47.0%, p = 0.042, respectively). In the infection group, the frequency of the AA genotype (rs3745635) in the recessive model, the TT genotype (rs778805) in the recessive model, and the GG genotype (rs61147939) in the recessive model were significantly higher than the noninfection group (5.8% vs. 2.3%, p = 0.042; 41.9% vs. 29.3%, p = 0.022; 34.9% vs. 20.5%, p = 0.0068, respectively). The frequency of the A13 haplotype and the A13/A13 diplotype of the FUT6 gene was significantly higher in the infection group than in the noninfection group (55.56% vs. 46.32%, p = 0.019; 34.94% vs. 20.30%, p = 0.045, respectively). The rs778805‐rs17855739‐rs28362459‐rs3745635 combination was identified as the best interaction model (p < 0.05).ConclusionsThis study suggests that FUT3 and FUT6 gene polymorphisms are significantly associated with H. pylori infection in the Han Chinese from northern China.
Update on occupational dermatitis: reviewing toxic substances from OSHA standards
Authors: Lee Juwon , Lin Rachel , Maderal Andrea 
Published: August 2024

AbstractOccupational dermatitis (OD) is an inflammatory skin disease stemming from exposure to specific substances within a work setting. As the second most prevalent occupational health concern in 2020, affecting 1.8 per 10,000 workers, OD poses a significant challenge to workforce well‐being and imposes a substantial economic burden through lost wages, decreased productivity, and increased healthcare spending. Dermatologists emerge as pivotal figures in recognizing risk factors and delivering essential care to individuals with OD. This review focuses on chemical hazards and toxic substances regulated by the Occupational Safety and Health Administration across general industry, maritime, and construction sectors. It explores the background of each hazard, pathophysiology to dermatitis, and human cases reported between 2017 and 2023 for formaldehyde, chromium, vinyl chloride, and cadmium.
Effect of different cooking oils and methods on physicochemical, nutritional, and microbial safety for mixed vegetables focusing on Bangladesh
Authors: Molla Mohammad Mainuddin , Dey Biddut Chandra , Khan Md. Hafizul Haque , Sabuz Ashfak Ahmed , Chowdhury Md. Golam Ferdous , Pervin Shahnaj , Alam Mahfujul , Khatun Anjumanara , Pathan Md. Hasib , Shaikh Md. Aftab Ali 
Published: August 2024

SummaryCooking is an essential aspect of everyday life. Cooking oils and methods exert enormous effects on the nutritional, physicochemical, microbial qualities, and bioactive compounds of vegetables. Most of them are either directly or indirectly related to human health. Hence, the present investigation was undertaken to find out the effect of two cooking methods (traditional and steam cooking) and four selected culinary oils (soybean oil, mustard oil, extra virgin olive oil, and extra virgin coconut oil) on the cooked vegetables. The results indicated that steam‐cooked mixed vegetables retained more nutrients than traditional ones. The traditional cooking method of preparing mixed vegetables with soybean oil revealed higher amounts of crude fat, 26.90 ± 0.10%, whereas steam cooking and traditionally cooked vegetables without oils showed lower amounts of crude fat, 1.21 ± 0.04%, and 1.94 ± 0.04%, respectively. The highest crude fibre from 5.68 ± 0.20 to 6.48 ± 0.02% was recorded by the steam‐cooked vegetables in comparison with traditionally prepared mixed vegetables. Traditionally cooked vegetables with mustard oil showed a higher crude protein (13.30 ± 0.10%). The mixed vegetables that were steam‐cooked using extra virgin olive oil revealed a decreased percent of carbohydrates, 49.42 ± 0.03%. Most of the essential minerals especially for the human body like Ca, Mg, Fe, Cu, and Zn were found notable in both traditional and steam‐cooking processes using extra virgin olive oil, and mustard oil. The leading bioactive compound ß‐carotene 67.04 ± 0.04 mg/100 g was noted by the steam‐cooked vegetables with mustard oil. The highest anthocyanin 32.69 ± 0.02 mg/100 g and ascorbic acid 42.31 ± 0.01 mg/100 g were recorded in the steam‐cooked vegetables without culinary oils. Steam‐cooking with extra virgin coconut and olive oil resulted in high total carotenoid and phenolic content (31.60 ± 0.05 and 3.11 ± 0.04 mg/100 g, respectively). However, the findings suggest that culinary oils used in the present study retained more essential minerals and bioactive compounds than soybean oil. Only sufficient amount of edible oil may be used for vegetables cooking and proper functioning of fat‐soluble vitamins.
Traditional Chinese‐version reliability test of the Pieper‐Zulkowski pressure ulcer knowledge: Psychometric and assessment
Authors: Chao Wen‐Yi , Hsu Mei‐Yu , Chen Su‐Ru , Wu Tzu‐Ling , Kuo Yu‐Chen , Huang Zih‐Chun , Wu Yu‐Lin 
Published: August 2024

AbstractThis study was to translate the Pieper–Zulkowski pressure ulcer knowledge test (PZ‐PUKT) into Traditional Chinese and evaluate its psychometric properties as well as identify the predictors of knowledge on pressure injury. The PZ‐PUKT was translated into Traditional Chinese (TC‐PZ‐PUKT), and its content validity was evaluated. A total of 296 nurses participated in this study and completed the 72‐item TC‐PZ‐PUKT online. The reliability of the TC‐PZ‐PUKT was analysed by evaluating its internal consistency and test–retest reliability. Hierarchical regression was used to determine factors associated with TC‐PZ‐PUKT scores. Content validity was achieved with a score of 0.986. Internal consistency was observed to be reliable, with a Cronbach's alpha of 0.858. The mean knowledge score on the TC‐PZ‐PUKT was 72.5%, with a 1‐week test–retest reliability of r = 0.849. Education level, certification as a wound specialist and self‐learning through reading articles, books or guidelines on pressure injury were significantly associated with TC‐PZ‐PUKT scores. The TC‐PZ‐PUKT is a valid and reliable tool. Education level, certification as a wound specialist and self‐learning regarding pressure injury are related to knowledge of pressure injury.
Creativity, Practical Ability, Self‐Identity: Public Art Practice with Primary School Students in China
Authors: Song Haiou , Chen Shuai , Mustafa Muhizam 
Published: August 2024

AbstractPublic art is increasingly recognised for its pedagogical value, especially in higher education, where it enhances institutions’ educational outcomes and expands students’ learning experiences. However, its potential in basic education remains under‐exploited. This study aims to bridge the gap by investigating how public art is effectively integrated into school curriculums and the educational benefits it offers students in their learning journey. Researchers, therefore, designed a student‐centred public art intervention project, Dreams and Hopes, at a Chinese nonprofit primary school incorporating the school's educational goals. The project recruited 5th and 6th graders to create a giant mosaic mural for the campus’ public space during the school's club and regular curriculum. To determine the educational benefits of the public art practice, researchers collected qualitative data using ethnographic methods in the project. The results showed that students at different stages (design, making, exhibition) gained competencies in three key themes: creativity (divergence, convergence, expression), practical ability (operation, innovation, collaboration), and self‐identity (satisfaction, achievement, confidence). These competencies align with the school's educational goals and enhance students’ learning experience. Problem‐based guidance, a relaxed and enjoyable atmosphere, effective communication and a connection to reality are essential to these critical competencies. The study reveals that public art may support educational goals and benefit students. It also enhances the practical experience of public art in basic education and provides a model of intervention to educators. The study recommends that schools actively collaborate with external resources, emphasise the art practice's educational value, and provide platforms for student arts participation.
A Convincing Narrative to Control the Crisis Response? The Role of the President of the European Commission During the COVID‐19 Pandemic
Authors: Camisão Isabel , Maior Paulo Vila 
Published: August 2024

AbstractSense‐making and meaning‐making are fundamental tasks of crisis management. They entail the construction of a persuasive crisis narrative for guaranteeing that the public understands and supports crisis responses. Building on a combination of literature on crisis management and policy narratives, we analysed von der Leyen's speeches on the pandemic (March 2020–December 2022) to answer one central research question: was the President of the Commission able to construct a compelling narrative to support the crisis response at the supranational level? Our findings suggest that she was able to create a convincing crisis narrative that helped to back the Commission's co‐ordination role and the crisis response devised at the supranational level.