bluuebunny/crossref_metadata_2025_split huggingface dataset:
Former long‐term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: A prospective, population‐based cohort study
Authors: Mosorin Maria‐Elina , Ollila Meri‐Maija , Nordström Tanja , Jokelainen Jari , Piltonen Terhi , Auvinen Juha , Morin‐Papunen Laure , Tapanainen Juha 
Published: August 2023

AbstractIntroductionCurrent use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial.Material and methodsThis was a prospective, longitudinal birth cohort study with long‐term follow‐up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2‐h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin‐only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253).ResultsCompared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6–9.2) but not of type 2 diabetes mellitus. Former progestin‐only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol‐lowering medication.ConclusionsFormer long‐term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.
A field study on the effects of inactivated bacteria vaccine for respiratory diseases in Japanese Black calves
Authors: Otomaru Konosuke , Fujimura Yu , Miyahara Takuro , Saita Hiroto , Usa Amane , Waki Hitoshi 
Published: August 2023

AbstractThis study evaluated the effects of vaccination for Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni in young Japanese Black calves at an ordinal farm, where respiratory diseases frequently occur at a young age. In total, 105 calves were divided into the vaccination group (n = 52), which received inactivated combined vaccine at 0 and 2 weeks of age, and the control group (n = 53), which received no vaccine. From both groups, eight calves each were randomly selected to determine the antibody titers. And, the incidence of respiratory disease and medical costs (treatment plus vaccination costs) were recorded for each group from birth to 16 weeks of age. In the vaccination group, the antibody titers against P. multocida, M. haemolytica, and H. somni were significantly higher than those in the control group after 8, 12, and 4 weeks of age, respectively (p < 0.05). The incidence of respiratory disease was significantly lower in the vaccination group compared to the control group (p < 0.01), and the medical costs per calf in the vaccination group were 46.4% lower than in the control group. These results might contribute to establishing an effective vaccination program against respiratory diseases in calves at each farm.
A new population pharmacokinetic model for recombinant factor IX‐Fc fusion concentrate including young children with haemophilia B
Authors: Koopman Sjoerd F. , Goedhart Tine M.H.J. , Bukkems Laura H. , Mulders Trevor M. , Leebeek Frank W.G. , Fijnvandraat Karin , Coppens Michiel , Mathias Mary , Collins Peter W. , Tait R. Campbell , Bagot Catherine N. , Curry Nicola , Payne Jeanette , Chowdary Pratima , Cnossen Marjon H. , Mathôt Ron A.A. ,   for the OPTI‐CLOT study group and SYMPHONY consortium
Published: August 2023

AbstractAimsRecombinant factor IX Fc fusion protein (rFIX‐Fc) is an extended half‐life factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients aged ≥12 years. The aim was to externally evaluate the predictive performance of the published rFIX‐Fc population PK model for patients of all ages and develop a model that describes rFIX‐Fc PK using real‐world data.MethodsWe collected prospective and retrospective data from patients with haemophilia B treated with rFIX‐Fc and included in the OPTI‐CLOT TARGET study (NTR7523) or United Kindom (UK)‐EHL Outcomes Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A new population PK model was constructed using nonlinear mixed‐effects modelling.ResultsReal‐world data were obtained from 37 patients (median age: 16 years, range 2–71) of whom 14 were aged <12 years. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction error of −48.8%. The new model showed a lower median prediction error (3.4%) and better described rFIX‐Fc PK, especially for children aged <12 years. In the new model, an increase in age was correlated with a decrease in clearance (P < .01).ConclusionsThe published population PK model significantly underpredicted FIX activity levels. The new model better describes rFIX‐Fc PK, especially for children aged <12 years. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population.
Adverse drug events caused by three high‐risk drug–drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study
Authors: Klopotowska Joanna E. , Leopold Jan‐Hendrik , Bakker Tinka , Yasrebi‐de Kom Izak , Engelaer Frouke M. , de Jonge Evert , Haspels‐Hogervorst Esther K. , van den Bergh Walter M. , Renes Maurits H. , de Jong Bas T. , Kieft Hans , Wieringa Andre , Hendriks Stefaan , Lau Cedric , van Bree Sjoerd H. W. , Lammers Hendrick J. W. , Wierenga Peter C. , Bosman Rob J. , de Jong Vincent M. , Slijkhuis Mirjam , Franssen Eric J. F. , Vermeijden Wytze J. , Masselink Joost , Purmer Ilse M. , Bosma Liesbeth E. , Hoeksema Martin , Wesselink Elsbeth , de Lange Dylan W. , de Keizer Nicolette F. , Dongelmans Dave A. , Abu‐Hanna Ameen 
Published: August 2023

AimsKnowledge about adverse drug events caused by drug–drug interactions (DDI‐ADEs) is limited. We aimed to provide detailed insights about DDI‐ADEs related to three frequent, high‐risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential.MethodsWe extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e‐triggers) to preselect patients with potential DDI‐ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI‐ADEs using internationally prevailing standards.ResultsIn total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e‐triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI‐ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI‐INR+ e‐trigger (0.76), followed by DDI‐AKI e‐trigger (0.57).ConclusionThe highly preventable nature and severity of DDI‐ADEs, calls for action to optimize ICU patient safety. Use of e‐triggers proved to be a promising preselection strategy.
How teachers conceptualise shared control with an AI co‐orchestration tool: A multiyear teacher‐centred design process
Authors: Lawrence LuEttaMae , Echeverria Vanessa , Yang Kexin , Aleven Vincent , Rummel Nikol 
Published: August 2023

AbstractArtificial intelligence (AI) can enhance teachers' capabilities by sharing control over different parts of learning activities. This is especially true for complex learning activities, such as dynamic learning transitions where students move between individual and collaborative learning in un‐planned ways, as the need arises. Yet, few initiatives have emerged considering how shared responsibility between teachers and AI can support learning and how teachers' voices might be included to inform design decisions. The goal of our article is twofold. First, we describe a secondary analysis of our co‐design process comprising six design methods to understand how teachers conceptualise sharing control with an AI co‐orchestration tool, called Pair‐Up. We worked with 76 middle school math teachers, each taking part in one to three methods, to create a co‐orchestration tool that supports dynamic combinations of individual and collaborative learning using two AI‐based tutoring systems. We leveraged qualitative content analysis to examine teachers' views about sharing control with Pair‐Up, and we describe high‐level insights about the human‐AI interaction, including control, trust, responsibility, efficiency, and accuracy. Secondly, we use our results as an example showcasing how human‐centred learning analytics can be applied to the design of human‐AI technologies and share reflections for human‐AI technology designers regarding the methods that might be fruitful to elicit teacher feedback and ideas. Our findings illustrate the design of a novel co‐orchestration tool to facilitate the transitions between individual and collaborative learning and highlight considerations and reflections for designers of similar systems.
Practitioner notesWhat is already known about this topic:

Artificial Intelligence (AI) can help teachers facilitate complex classroom activities, such as having students move between individual and collaborative learning in unplanned ways.
Designers should use human‐centred design approaches to give teachers a voice in deciding what AI might do in the classroom and if or how they want to share control with it.
What this paper adds:

Presents teacher views about how they want to share control with AI to support students moving between individual and collaborative learning.
Describes how we adapted six design methods to design AI features.
Illustrates a complete, iterative process to create human‐AI interactions to support teachers as they facilitate students moving from individual to collaborative learning.
Implications for practice:

We share five implications for designers that teachers highlighted as necessary when designing AI‐features, including control, trust, responsibility, efficiency and accuracy.
Our work also includes a reflection on our design process and implications for future design processes.
Fetal and neonatal alloimmune thrombocytopenia: No evidence of systemic inflammation as a modulator of disease severity. Could placental inflammation be key?
Authors: Böhm David , Wienzek‐Lischka Sandra , Cooper Nina , Berghöfer Heike , Müller Katja , Bayat Behnaz , Bein Gregor , Sachs Ulrich J. 
Published: August 2023

SummaryIn fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti‐HPA‐1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies. Concentrations of C‐reactive protein, soluble CD14, procalcitonin, and sFlt‐1 did not differ between the two cohorts. There was no correlation between C‐reactive protein or soluble CD14 and the platelet count, but a negative correlation between procalcitonin concentrations and the neonatal platelet count in both cohorts. sFlt‐1 concentration and the platelet count were correlated in FNAIT cases exclusively. None of the inflammatory markers was statistically different between cases with and without intracranial haemorrhage. We were unable to identify systemic inflammation as a relevant factor for thrombocytopenia in FNAIT. The antiangiogenic enzyme sFlt‐1, released by the placenta, did correlate with the platelet count in FNAIT cases. Our findings may give rise to the hypothesis that placental inflammation rather than systemic inflammation modulates disease severity in FNAIT.
Structural properties and immune‐enhancing activities of galactan isolated from red seaweed Grateloupia filicina
Authors: Ma Nan , Palanisamy Subramanian , Yelithao Khamphone , Talapphet Natchanok , Zhang Yutong , Dae‐Hee Lee , Shin Il‐Shik , Lee Dong‐Jin , You SangGuan 
Published: August 2023

AbstractA water‐soluble polysaccharide (GFP) was isolated from Grateloupia filicina and fractionated using a DEAE Sepharose Fast Flow column to evaluate immunostimulatory activity. Carbohydrates (62.0%–68.4%) and sulfates (29.3%–34.3%) were the major components of GFP and its fractions (GFP‐1 and GFP‐2), with relatively lower levels of proteins (4.5%–15.4%) and uronic acid (1.4%–3.9%). The average molecular weight (Mw) for GFP and its fractions was calculated between 98.2%–243.7 kDa. The polysaccharides were composed of galactose (62.1%–87.2%), glucose (4.5%–33.2%), xylose (3.1%–5.3%), mannose (1.4%–2.2%), rhamnose (1.2%–2.0%), and arabinose (0.9%–1.7%) units connected through →3)‐Galp‐(1→, →4)‐Galp‐(1→, →2)‐Galp‐(1→, →6)‐Galp‐(1→, →3,4)‐Galp ‐(1→, →3,6)‐Galp‐(1→, →4,6)‐Galp‐(1→, →3,4,6)‐Galp‐(1→, →2,3)‐Galp‐(1→, →2,4)‐Galp‐(1→, →4)‐Glcp‐(1→, →6)‐Glcp‐(1→ and →4,6)‐Glcp‐(1→residues. The isolated polysaccharides effectively induced RAW264.7 murine macrophages by releasing nitric oxide (NO) and various cytokines via nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) and mitogen‐activated protein kinase (MAPK) signaling pathways. Further, the expression of toll‐like receptor‐2 (TLR‐2) and TLR‐4 in RAW264.7 cells indicated their activation through TLR‐2 and TLR‐4 binding receptors. Among the polysaccharides, GFP‐1 highly stimulated the activation of RAW264.7 cells, which was mainly constituted of (→1) terminal‐D‐galactopyranosyl, (1→3)‐linked‐ᴅ‐galactopyranosyl, (1→4)‐linked‐ᴅ‐galactopyranosyl and (1→3,4) ‐linked‐ᴅ‐galactopyranosyl residues. These findings demonstrate that GFP‐1 from G. filicina are effective at stimulating the immune system and this warrants further investigation to determine potential biomedical applications.
Epidermal biomarkers of the skin barrier in atopic and contact dermatitis
Authors: de Boer F. L. , van der Molen H. F. , Kezic S. 
Published: August 2023

AbstractDysfunction of the skin barrier plays a critical role in the initiation and progression of inflammatory skin diseases, such as atopic dermatitis and contact dermatitis. Epidermal biomarkers can aid in evaluating the functionality of the skin barrier and understanding the mechanisms that underlay its impairment. This narrative review provides an overview of recent studies on epidermal biomarkers associated with the function and integrity of the skin barrier, and their application in research on atopic dermatitis and contact dermatitis. The reviewed studies encompass a wide spectrum of molecular, morphological and biophysical biomarkers, mainly obtained from stratum corneum tape strips and biopsies. Lipids, natural moisturizing factors, and structural proteins are the most frequently reported molecular biomarkers. Additionally, corneocyte surface topography and elasticity show potential as biomarkers for assessing the physical barrier of the skin. In contact dermatitis studies, biomarkers are commonly employed to evaluate skin irritation and differentiate between irritant and allergic contact dermatitis. In atopic dermatitis, biomarkers are primarily utilized to identify differences between atopic and healthy skin, for predictive purposes, and monitoring response to therapies. While this overview identifies potential biomarkers for the skin barrier, their validation as epidermal biomarkers for atopic dermatitis and contact dermatitis has yet to be established.
Investigation of vertical margin involvement in endoscopic resection for T1 colorectal cancer
Authors: Kano Yuki , Yamamoto Yoichi , Ikematsu Hiroaki , Sasabe Maasa , Minakata Nobuhisa , Watanabe Takashi , Yamashita Hiroki , Mitsui Tomohiro , Inaba Atsushi , Sunakawa Hironori , Nakajo Keiichiro , Murano Tatsuro , Kadota Tomohiro , Shinmura Kensuke , Yano Tomonori 
Published: August 2023

ObjectivesThe resection of vertical margin‐negative submucosally invasive colorectal cancer (CRC) relies on the pathological risk assessment of lymph node metastasis. However, no large‐scale study has clarified the endoscopic resection (ER) outcome for submucosally invasive CRC, focusing on the vertical margin status. This retrospective study aimed to examine vertical margin involvement in ER for submucosally invasive CRC and explore the treatment consequences associated with vertical margin status.MethodsWe analyzed 395 submucosally invasive CRC cases in 389 patients who underwent ER at our hospital between 2008 and 2020. The presence of residual tumors and simultaneous lymph node metastasis in patients who underwent additional surgery was assessed and compared between the vertical incomplete ER and the vertical margin‐negative groups.ResultsAmong the patients, 270 were men, with a median age of 69 years. The vertical incomplete ER rate was 21.5%, with positive vertical margins and unclear vertical margins identified in 12.2% and 9.3% of the cases, respectively. Among 154 patients who underwent additional surgery after ER, the vertical incomplete ER group had a significantly higher residual tumor rate than the vertical margin‐negative group (P = 0.001). The vertical incomplete ER group had a significantly higher lymph node metastasis rate than the vertical margin‐negative group (P = 0.029).ConclusionThis study clarified the substantial risk of vertical incomplete ER in submucosally invasive CRC and revealed the high risk of residual tumor and lymph node metastasis in vertical incomplete ER for submucosal CRC.
Advanced biomedical imaging for accurate discrimination and prognostication of mediastinal masses
Authors: Mahmoudi Scherwin , Gruenewald Leon D. , Eichler Katrin , Martin Simon S. , Booz Christian , Bernatz Simon , Lahrsow Maximilian , Yel Ibrahim , Gotta Jennifer , Biciusca Teodora , Mohammed Hanin , Ziegengeist Nicole Suarez , Torgashov Katerina , Hammerstingl Renate M. , Sommer Christof M. , Weber Christophe , Almansour Haidara , Bucolo Giuseppe , D'Angelo Tommaso , Scholtz Jan‐Erik , Gruber‐Rouh Tatjana , Vogl Thomas J. , Koch Vitali 
Published: August 2023

AbstractBackgroundTo investigate the potential of radiomic features and dual‐source dual‐energy CT (DECT) parameters in differentiating between benign and malignant mediastinal masses and predicting patient outcomes.MethodsIn this retrospective study, we analysed data from 90 patients (38 females, mean age 51 ± 25 years) with confirmed mediastinal masses who underwent contrast‐enhanced DECT. Attenuation, radiomic features and DECT‐derived imaging parameters were evaluated by two experienced readers. We performed analysis of variance (ANOVA) and Chi‐square statistic tests for data comparison. Receiver operating characteristic curve analysis and Cox regression tests were used to differentiate between mediastinal masses.ResultsOf the 90 mediastinal masses, 49 (54%) were benign, including cases of thymic hyperplasia/thymic rebound (n = 10), mediastinitis (n = 16) and thymoma (n = 23). The remaining 41 (46%) lesions were classified as malignant, consisting of lymphoma (n = 28), mediastinal tumour (n = 4) and thymic carcinoma (n = 9). Significant differences were observed between benign and malignant mediastinal masses in all DECT‐derived parameters (p ≤ .001) and 38 radiomic features (p ≤ .044) obtained from contrast‐enhanced DECT. The combination of these methods achieved an area under the curve of .98 (95% CI, .893–1.000; p < .001) to differentiate between benign and malignant masses, with 100% sensitivity and 91% specificity. Throughout a follow‐up of 1800 days, a multiparametric model incorporating radiomic features, DECT parameters and gender showed promising prognostic power in predicting all‐cause mortality (c‐index = .8 [95% CI, .702–.890], p < .001).ConclusionsA multiparametric approach combining radiomic features and DECT‐derived imaging biomarkers allows for accurate and noninvasive differentiation between benign and malignant masses in the anterior mediastinum.
Evaluation of high‐density lipoprotein‐bound long non‐coding RNAs in subjects with familial hypercholesterolaemia
Authors: Scicali Roberto , Bosco Giosiana , Scamporrino Alessandra , Di Mauro Stefania , Filippello Agnese , Di Giacomo Barbagallo Francesco , Spampinato Salvatore , Pavanello Chiara , Ossoli Alice , Di Pino Antonino , Calabresi Laura , Purrello Francesco , Piro Salvatore 
Published: August 2023

AbstractBackgroundLong non‐coding RNAs (lncRNAs) could be attractive circulating biomarkers for cardiovascular risk stratification in subjects at high atherosclerotic cardiovascular disease risk such as familial hypercholesterolaemia (FH). Our aim was to investigate the presence of lncRNAs carried by high‐density lipoprotein (HDL) in FH subjects and to evaluate the associations of HDL‐lncRNAs with lipoproteins and mechanical vascular impairment assessed by pulse wave velocity (PWV).MethodsThis was a retrospective observational study involving 94 FH subjects on statin treatment. Biochemical assays, HDL purification, lncRNA and PWV analyses were performed in all subjects.ResultsLncRNA HIF1A‐AS2, LASER and LEXIS were transported by HDL; moreover, HDL‐lncRNA LEXIS was associated with Lp(a) plasma levels (p < .01). In a secondary analysis, the study population was stratified into two groups based on the Lp(a) median value. The high‐Lp(a) group exhibited a significant increase of PWV compared to the low‐Lp(a) group (9.23 ± .61 vs. 7.67 ± .56, p < .01). While HDL‐lncRNA HIF1A‐AS2 and LASER were similar in the two groups, the high‐Lp(a) group exhibited a significant downregulation of HDL‐lncRNA LEXIS compared to the low‐Lp(a) group (fold change −4.4, p < .0001). Finally, Lp(a) and HDL‐lncRNA LEXIS were associated with PWV (for Lp(a) p < .01; for HDL‐lncRNA LEXIS p < .05).ConclusionsLncRNA HIF1A‐AS2, LASER and LEXIS were transported by HDL; moreover, significant relationships of HDL‐lncRNA LEXIS with Lp(a) levels and PWV were found. Our study suggests that HDL‐lncRNA LEXIS may be useful to better identify FH subjects with more pronounced vascular damage.