bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics of oxcarbazepine active metabolite in Chinese paediatric patients with epilepsy: Model‐based dose optimization
Authors: Wu Wei , Yang Wen‐sheng , Xu Xiao‐yong , Ge Xi‐lin , Lu Jinmiao , Wang Guang‐fei , Wang Yi , Li Zhi‐ping 
Published: March 2024

AbstractThe pharmacological activity of oxcarbazepine (OXC) is primarily exerted through its active 10‐monohydroxy metabolite (MHD). Nonetheless, there is limited pharmacokinetic information available regarding paediatric patients with epilepsy treated with OXC, especially in infants and toddlers. Concurrently, this drug exhibits substantial variability in pharmacokinetics and therapeutic response across different individuals. We aimed to develop a model to quantitatively investigate factors that affect MHD pharmacokinetics to formulate a dosage guideline for OXC in Chinese paediatric patients. A total of 297 MHD trough concentrations were obtained from 287 epileptic children. Six body weight (BW)‐based allometric models were used for population pharmacokinetic modelling, while investigating the impact of other covariates on the apparent clearance. The one‐compartment model and age cut‐off model for the apparent clearance (CL/F) were established to describe the pharmacokinetics of MHD. The probability to obtain target trough concentration ranges (TTCRs) of MHD between 3 and 35 mg/L was determined by Monte Carlo simulations for doses ranging from 8 to 90 mg/kg/day. A new dose optimization strategy combining the dosage guidelines and Bayesian method provides a tailored approach for Chinese paediatric epileptic patients based on their individual BW and desired TTCRs of MHD, and also supports current dose recommendations, with the exception of children weighing ≤5 kg.
Online decision aid for patients with prostate cancer evaluated by 11 290 patients and 91 urologists in Germany
Authors: Huber Johannes , Karschuck Philipp , Valdix Johanna , Thomas Christian , Koch Rainer , Ihrig Andreas , Hölscher Tobias , Krones Tanja , Kessler Elke , Kliesch Sabine , Linné Clemens , Enders Paul , Michel Maurice‐Stephan , Wülfing Christian , Groeben Christer 
Published: March 2024

ObjectiveTo evaluate the nationwide online decision aid ‘Entscheidungshilfe Prostatakrebs’ (established in 2016, >11.000 users and 60 new users/week) for patients with non‐metastatic prostate cancer (PCa), from the perspective of patients and urologists.Patients and MethodsTo provide personalised information, the tool collects most of the International Consortium for Health Outcomes Measurement standard set, personal preferences, psychological features, and a validated rating of the tool. To evaluate urologists’ opinions, we developed a structured two‐page questionnaire. All data were collected anonymously.ResultsFrom June 2016 to December 2020, 11 290 patients used the PCa decision aid. Their median (interquartile range [IQR]) age was 67 (61–72) years. The median (IQR) time from initial diagnosis to using the tool was 4 (3–7) weeks. In all, 87.7% of users reported high satisfaction. In a multivariable model, predictors for considering observation were higher knowledge, using the decision aid alone, lower oncological risk, normal erectile function, and respective personal preferences. Of 194 urologists, 91 (47%) had implemented the decision aid in their clinical practice. The urologists’ mean (SD) satisfaction score (1 ‘very good’; 6 ‘unsatisfactory’) with it was 1.45 (0.55), and 92% recommended it. Half of the urologists reported time savings.ConclusionPatients and urologists report a very high level of acceptance and satisfaction with this online tool. It offers advantages in shared decision‐making and time efficiency. The usage of the decision aid might improve the adoption of active surveillance and watchful waiting when indicated.
Advances in the study of S100A9 in cardiovascular diseases
Authors: Chen Fengling , He Ziyu , Wang Chengming , Si Jiajia , Chen Zhu , Guo Yuan 
Published: March 2024

AbstractCardiovascular disease (CVD) is a group of diseases that primarily affect the heart or blood vessels, with high disability and mortality rates, posing a serious threat to human health. The causative factors, pathogenesis, and characteristics of common CVD differ, but they all involve common pathological processes such as inflammation, oxidative stress, and fibrosis. S100A9 belongs to the S100 family of calcium‐binding proteins, which are mainly secreted by myeloid cells and bind to the Toll‐like receptor 4 and receptor for advanced glycation end products and is involved in regulating pathological processes such as inflammatory response, fibrosis, vascular calcification, and endothelial barrier function in CVD. The latest research has found that S100A9 is a key biomarker for diagnosing and predicting various CVD. Therefore, this article reviews the latest research progress on the diagnostic and predictive, and therapeutic value of S100A9 in inflammatory‐related CVD such as atherosclerosis, myocardial infarction, and arterial aneurysm and summarizes its molecular mechanisms in the progression of CVD, aiming to explore new predictive methods and to identify potential intervention targets for CVD in clinical practice.
Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?
Authors: Clemmensen Tor Skibsted , Hjort Baatrup Johanne , Bjerre Kamilla Pernille , Lichscheidt Emil , Nielsen Pernille Koefoed , Eiskjaer Hans 
Published: March 2024

AbstractBackgroundWe aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality.MethodsThe study population comprises 193 consecutive long‐term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow‐up or right censuring on the 30th of June 2023.ResultsDSAs were detected in 50 patients using a cut‐off at MFI ≥1000 and 45 patients using a cut‐off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0–14.4]. DSA positive patients had poorer graft function and higher values of NT‐proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow‐up of five years [4.7–5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI .6–2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5–4.8)ConclusionsRoutine screening reveals DSA in approximately 25% of long‐term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.
Lessons for future clinical trials in adults with Becker muscular dystrophy: Disease progression detected by muscle magnetic resonance imaging, clinical and patient‐reported outcome measures
Authors: De Wel Bram , Iterbeke Louise , Huysmans Lotte , Peeters Ronald , Goosens Veerle , Dubuisson Nicolas , van den Bergh Peter , Van Parijs Vinciane , Remiche Gauthier , De Waele Liesbeth , Maes Frederik , Dupont Patrick , Claeys Kristl G. 
Published: March 2024

AbstractBackground and purposeBecause Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials.MethodsMuscle magnetic resonance imaging, patient‐reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed‐function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow‐up.ResultsProton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32‐item Motor Function Measurement (MFM‐32) scale (−1.3%, p = 0.017), North Star Ambulatory Assessment (−1.3 points, p = 0.010) and patient‐reported activity limitations scale (−0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6‐min walk distance (−28.7 m, p = 0.042), 10‐m walking test (−0.1 m/s, p = 0.032), time to climb four stairs test (−0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (−4.6 N m, p = 0.014) and hamstrings (−5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM‐32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15).DiscussionIt is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow‐up. Finally, significant changes are reported in a wide range of clinical and patient‐reported outcome measures, of which the MFM‐32 appeared to be the most sensitive to change in adults with BMD.
Outcomes and outcome measures
Authors: Castaman Giancarlo , Jimenez‐Yuste Victor , Gouw Samanta , D'Oiron Roseline 
Published: March 2024

AbstractIntroductionAdvances in haemophilia treatment have resulted in a near‐normal life expectancy, lower burden of bleeding and treatment, and improved quality of life in high‐income countries. Bleeding rate is approaching zero and novel parameters should be evaluated to assess the efficacy of treatment not only from the clinical point of view by using new methodologies (e.g. joint health assessment), but also from the patient's perspective (e.g. pain, quality of life, treatment satisfaction).Methods and resultsThis approach should be aimed at combining objective clinical methodologies and patient‐reported outcomes (PROs). However, some instruments used for assessing PROs are still suboptimal and not properly validated. Recent evidence suggests that these tools can take advantage from a more personalized designed approach and could be effectively improved and serve to facilitate the patient's self‐evaluation. For other congenital bleeding disorders (BDs), a set of patient‐relevant outcomes has been also defined that overlap substantially those of haemophilia, including bleeding, side effects and complications, and PROs, such as pain, physical functioning, impact on daily life including school and work and mental health. There is a growing focus on addressing women‐specific outcomes in BDs, reflecting an increased awareness of the unique challenges faced by women in this context. However, the development of tailored tools is imperative to further advance the progress in managing women with BDs, ensuring more accurate monitoring and personalized care.ConclusionsHow incorporating these outcome measures in the process of approval of novel treatments for these disorders by regulatory authorities remains to be established.
Sialic acid in the regulation of blood cell production, differentiation and turnover
Authors: Irons Eric Edward , Gc Sajina , Lau Joseph T. Y. 
Published: March 2024

AbstractSialic acid is a unique sugar moiety that resides in the distal and most accessible position of the glycans on mammalian cell surface and extracellular glycoproteins and glycolipids. The potential for sialic acid to obscure underlying structures has long been postulated, but the means by which such structural changes directly affect biological processes continues to be elucidated. Here, we appraise the growing body of literature detailing the importance of sialic acid for the generation, differentiation, function and death of haematopoietic cells. We conclude that sialylation is a critical post‐translational modification utilized in haematopoiesis to meet the dynamic needs of the organism by enforcing rapid changes in availability of lineage‐specific cell types. Though long thought to be generated only cell‐autonomously within the intracellular ER‐Golgi secretory apparatus, emerging data also demonstrate previously unexpected diversity in the mechanisms of sialylation. Emphasis is afforded to the mechanism of extrinsic sialylation, whereby extracellular enzymes remodel cell surface and extracellular glycans, supported by charged sugar donor molecules from activated platelets.
Does location matter in IS research? A developing country perspective from India
Authors: Seetharaman Priya , Mathew Saji K. , De' Rahul 
Published: March 2024

AbstractThis paper examines the question of doing information systems (IS) research from a location, particularly from a developing country like India. Our analysis reveals that IS publications from India are relatively few in number, though increasing in recent years; hardly focussed on context‐specific issues and concerns; and are largely in lower‐ranked journals. Using neo‐institutional theory, we show that the reasons are dominantly coercive (measuring up to rankings and accreditation agencies) and mimetic (following leaders). Normative (influence of professional bodies) forces appear to counterbalance this by necessitating continuous improvement in research outputs and emphasising location‐specific, impactful research. Institutional responses to these forces manifest in policies and mechanisms to operationalise them, such as resource availability, balancing teaching load with research expectations, promotion and tenure policies amongst others. We examine the paths by which more rigorous and relevant research, responsible to a location can be achieved, based on the insights from a series of talks given by eminent IS scholars. We opine that there is a need to consciously seek out such paths, perhaps by actively seeking collaboration with other disciplines and practitioners; establishing programmes of research; and building contextualised theories. We conclude with a relook at the underlying dynamics of the various institutional responses, recommended paths and some policy implications of our findings.
Peer perspectives on friendships among peers with and without intellectual and developmental disabilities: A pilot mixed methods study
Authors: Shikarpurya Sehrish , Fogarty Melissa , Gilson Carly B. , Benzel Megan , Fletcher Katherine E. , Osburn Courtney , Villarreal Alexis , Tassin Abigail 
Published: March 2024

AbstractBackgroundThe benefits of friendships among peers with and without intellectual and developmental disabilities are well supported by research. However, little is known about the nature of these inclusive friendships in inclusive college courses.MethodWe explored the perspectives of peers on the development of authentic friendships among peers with and without intellectual and developmental disabilities in inclusive college courses in the United States. We used a sequential, explanatory, transformative mixed methods‐grounded theory research design. We integrated quantitative (N = 44) and qualitative (N = 8) findings using blended analysis to inform a preliminary grounded theory of inclusive and reciprocal friendships.ResultsQuantitative findings suggest two relationships and one predictor of peers' perceived social engagement. Qualitative findings resulted in five themes that promote friendships.ConclusionsWe propose that the context for developing inclusive friendships could be fostered using the preparation and actions stages of the grounded theory model.
Behavioural, developmental and psychological characteristics in children with germline PTEN mutations: a carer report study
Authors: Cummings K. , Dias R. P. , Hart R. , Welham A. 
Published: March 2024

AbstractBackgroundPTEN is primarily known as a tumour suppressor gene. However, research describes higher rates of difficulties including intellectual disability and difficulties relating to autism spectrum conditions (ASCs) in people with germline PTEN mutations. Other psychological characteristics/experiences are less often reported and are explored in this study.MethodsThe parents of 20 children with PTEN mutations completed an online survey exploring adaptive behaviour, ASC‐associated behaviours, anxiety, mood, hypermobility, behaviours that challenge, sensory experiences, quality of life and parental wellbeing. Published normative data and data from groups of individuals with other genetic neurodevelopmental conditions were used to contextualise findings.ResultsOverall levels of adaptive behaviour were below the ‘typical’ range, and no marked relative differences were noted between domains. Higher levels of ASC‐related difficulties, including sensory experiences, were found in comparison with ‘typically developing’ children, with a possible peak in restrictive/repetitive behaviour; ASC and sensory processing atypicality also strongly correlated with reported joint hypermobility. A relative preservation of social motivation was noted. Anxiety levels were found to be elevated overall (and to relate to sensory processing and joint hypermobility), with the exception of social anxiety, which was comparable with normative data. Self‐injurious behaviour was common.ConclusionsResults suggest a wide range of possible difficulties in children with PTEN mutations, including elevated anxiety. Despite elevated ASC phenomenology, social motivation may remain relatively strong. Firm conclusions are restricted by a small sample size and potential recruitment bias, and future research is required to further explore the relationships between such characteristics.
Long‐term effects of environmental dynamic lighting on sleep–wake rhythm, mood and behaviour in older adults with intellectual disabilities
Authors: Böhmer M. N. , Oppewal A. , Bindels P. J. E. , van Someren E. J. W. , Festen D. A. M. 
Published: March 2024

AbstractBackgroundSleep–wake problems and depressive symptoms are common in people with intellectual disabilities (IDs) and are thought to be related to the unstable sleep–wake rhythm in this population. Previously, we showed that after increasing environmental light exposure, mid‐sleep and sleep onset advanced, and mood improved over a period of 14 weeks after installing environmental dynamic light installations in the living room of people with IDs. We invited participants of that short‐term study to take part in the current study on sleep–wake rhythm, mood and behaviour in older adults with IDs 1 year after installing environmental dynamic light installations in the common living rooms of six group homes.MethodsA pre–post study was performed from October 2017 to February 2019. We included 45 participants (63.5 ± 8.5 years, 67% female) from six group home facilities who provided data at baseline (9, 4 and 1 weeks prior to installing light installations), short term (3, 7 and 14 weeks after installing light installations) and 1 year (54 weeks after installing light installations). Wrist activity was measured with actigraphy (GENEActiv) to derive the primary outcome of interdaily stability of sleep–wake rhythms as well as sleep estimates. Mood was measured with the Anxiety, Depression and Mood Scale. Behaviour was measured with the Aberrant Behaviour Checklist.ResultsOne year after installing dynamic lighting, we did not find a change in interdaily stability. Total sleep time decreased (β = −25.40 min; confidence interval: −10.99, −39.82), and sleep onset time was delayed (β = 25.63 min; confidence interval: 11.18, 40.08). No effect on mood or behaviour was found.ConclusionsWe did not find a change in sleep–wake rhythm, mood or behaviour in older persons with IDs living in care facilities 1 year after installing the light. We did find evidence for a long‐term effect on sleep duration and sleep timing. The results have to be interpreted with care as the current study had a limited number of participants. The need for more research on the long‐term effects of enhancing environmental light in ID settings is evident.
Comparison of ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants: An updated meta‐analysis
Authors: Paik Haerin , Jee Byung Chul 
Published: March 2024

AbstractAimThe purpose of the study was to compare the ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants (HSs).MethodsWe performed a meta‐analysis of studies in which post‐cystectomy serum anti‐Müllerian hormone (AMH) values were compared between bipolar coagulation and suture method or between bipolar coagulation and HSs. Through a literature search, we retrieved 14 articles which met inclusion criteria and were eligible for final analysis. The articles included 10 randomized trials, 3 prospective studies, and 1 retrospective study (n = 1435). The primary outcome was post‐cystectomy serum AMH values.ResultsBoth bipolar coagulation and suture methods showed significantly lower post‐cystectomy AMH values at 3, 6, and 12 months. However, post‐cystectomy serum AMH values at 12 months were significantly higher in the suture method group compared to the bipolar coagulation (weighted mean difference [WMD]: −1.10, 95% confidence interval [CI]: −1.83, −0.38, p = 0.003, I2 = 89, n = 3). The suture method also showed a lower decline rate at 3 months post‐cystectomy compared to the bipolar coagulation group (WMD: −25.13%, 95% CI: −49.56 to −0.70, p = 0.04, I2 = 95%, n = 2). Overall, pregnancy rates were similar between the two groups. Between the bipolar coagulation and HSs group, serum AMH values at 3 months post‐cystectomy were similar (WMD: −0.46, 95% CI: −1.04 to 0.13, p = 0.13, I2 = 0%, n = 3). However, the HSs group showed a less decline rate at 3 months post‐cystectomy compared to the bipolar coagulation group (WMD: −17.02%, 95% CI: −22.81, −11.23, p < 0.00001, I2 = 0%, n = 3).ConclusionsBoth the suture method and HSs may have potential benefits in the preservation of ovarian reserve over the bipolar coagulation method when cystectomy for ovarian endometrioma is performed.
A bloody mess? UK regulation of menopause discrimination and the need for reform
Authors: WESTWOOD SUE 
Published: March 2024

AbstractThis article considers the regulation of menopause‐related discrimination in the workplace. Many menopausal women experience profound workplace inequalities, often connected with the intersection of ageism and sexism. The United Kingdom Parliament's Women and Equalities Committee (WEC) recently recommended that the government consult about a new protected characteristic, ‘menopause’, and that Section 14 of the Equality Act 2010 (EqA) on dual discrimination be brought into force. The government has rejected these recommendations, asserting that menopausal women are sufficiently protected under the EqA's existing provision. This article presents an alternative perspective, arguing that there is insufficient legal protection from menopause discrimination, with it fitting poorly within age, sex, and/or disability discrimination, and there being no facility for intersectional claims. The WEC is correct: Section 14 should be implemented, ‘menopause’ should be a protected characteristic, and, beyond that, the EqA needs wider reform to provide greater protections from discrimination, beyond inflexible identity categories that fail to allow for complex intersecting structural oppressions.