bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of adaptive scaffolding on performance, cognitive load and engagement in game-based learning: a randomized controlled trial
Authors: Faber Tjitske J. E. , Dankbaar Mary E. W. , van den Broek Walter W. , Bruinink Laura J. , Hogeveen Marije , van Merriënboer Jeroen J. G. 
Published: August 2024

Abstract
Background
While game-based learning has demonstrated positive outcomes for some learners, its efficacy remains variable. Adaptive scaffolding may improve performance and self-regulation during training by optimizing cognitive load. Informed by cognitive load theory, this study investigates whether adaptive scaffolding based on interaction trace data influences learning performance, self-regulation, cognitive load, test performance, and engagement in a medical emergency game.

Methods
Sixty-two medical students from three Dutch universities played six game scenarios. They received either adaptive or nonadaptive scaffolding in a randomized double-blinded matched pairs yoked control design. During gameplay, we measured learning performance (accuracy, speed, systematicity), self-regulation (self-monitoring, help-seeking), and cognitive load. Test performance was assessed in a live scenario assessment at 2- and 6–12-week intervals. Engagement was measured after completing all game scenarios.

Results
Surprisingly, the results unveiled no discernible differences between the groups experiencing adaptive and nonadaptive scaffolding. This finding is attributed to the unexpected alignment between the nonadaptive scaffolding and the needs of the participants in 64.9% of the scenarios, resulting in coincidentally tailored scaffolding. Exploratory analyses suggest that, compared to nontailored scaffolding, tailored scaffolding improved speed, reduced self-regulation, and lowered cognitive load. No differences in test performance or engagement were found.

Discussion
Our results suggest adaptive scaffolding may enhance learning by optimizing cognitive load. These findings underscore the potential of adaptive scaffolding within GBL environments, cultivating a more tailored and effective learning experience. To leverage this potential effectively, researchers, educators, and developers are recommended to collaborate from the outset of designing adaptive GBL or computer-based simulation experiences. This collaborative approach facilitates the establishment of reliable performance indicators and enables the design of suitable, preferably real-time, scaffolding interventions. Future research should confirm the effects of adaptive scaffolding on self-regulation and learning, taking care to avoid unintended tailored scaffolding in the research design.

Trial registration
This study was preregistered with the Center for Open Science prior to data collection. The registry may be found at https://osf.io/7ztws/.
From admission to discharge: a systematic review of clinical natural language processing along the patient journey
Authors: Klug Katrin , Beckh Katharina , Antweiler Dario , Chakraborty Nilesh , Baldini Giulia , Laue Katharina , Hosch René , Nensa Felix , Schuler Martin , Giesselbach Sven 
Published: August 2024

AbstractBackgroundMedical text, as part of an electronic health record, is an essential information source in healthcare. Although natural language processing (NLP) techniques for medical text are developing fast, successful transfer into clinical practice has been rare. Especially the hospital domain offers great potential while facing several challenges including many documents per patient, multiple departments and complex interrelated processes.MethodsIn this work, we survey relevant literature to identify and classify approaches which exploit NLP in the clinical context. Our contribution involves a systematic mapping of related research onto a prototypical patient journey in the hospital, along which medical documents are created, processed and consumed by hospital staff and patients themselves. Specifically, we reviewed which dataset types, dataset languages, model architectures and tasks are researched in current clinical NLP research. Additionally, we extract and analyze major obstacles during development and implementation. We discuss options to address them and argue for a focus on bias mitigation and model explainability.ResultsWhile a patient’s hospital journey produces a significant amount of structured and unstructured documents, certain steps and documents receive more research attention than others. Diagnosis, Admission and Discharge are clinical patient steps that are researched often across the surveyed paper. In contrast, our findings reveal significant under-researched areas such as Treatment, Billing, After Care, and Smart Home. Leveraging NLP in these stages can greatly enhance clinical decision-making and patient outcomes. Additionally, clinical NLP models are mostly based on radiology reports, discharge letters and admission notes, even though we have shown that many other documents are produced throughout the patient journey. There is a significant opportunity in analyzing a wider range of medical documents produced throughout the patient journey to improve the applicability and impact of NLP in healthcare.ConclusionsOur findings suggest that there is a significant opportunity to leverage NLP approaches to advance clinical decision-making systems, as there remains a considerable understudied potential for the analysis of patient journey data.
Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study
Authors: Lejawa Mateusz , Goławski Marcin , Fronczek Martyna , Osadnik Tadeusz , Paneni Francesco , Ruscica Massimiliano , Pawlas Natalia , Lisik Małgorzata , Banach Maciej 
Published: August 2024

Abstract
Background
Numerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D.

Methods
Independent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MR‒Egger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger.

Results
Genetically predicted fasting insulin levels were negatively associated with Lp(a) levels (β = − 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (β = − 0.26, SE = 0.07, P = 0.0002), but not MR‒Egger (β = − 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a).

Conclusion
Our MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.
The assessment of bone health in children with juvenile idiopathic arthritis; comparison of different imaging-based methods
Authors: Augdal Thomas , Angenete Oskar , Zadig Pia , Lundestad Anette , Nordal Ellen , Shi Xieqi , Rosendahl Karen 
Published: August 2024

Abstract
Background
Osteoporosis is increasingly being recognized in children, mostly secondary to systemic underlying conditions or medication. However, no imaging modality currently provides a full evaluation of bone health in children. We compared DXA, a radiographic bone health index (BHI (BoneXpert) and cone-beam CT for the assessment of low bone mass in children with juvenile idiopathic arthritis (JIA).

Methods
Data used in the present study was drawn from a large multicentre study including 228 children aged 4–16 years, examined between 2015 and 2020. All had a radiograph of the left hand, a DXA scan and a cone-beam CT of the temporomandibular joints within four weeks of each other. For the present study, we included 120 subjects, selected based on DXA BMD and BoneXpert BHI to secure values across the whole range to be tested.

Results
One hundred and twenty children (60.0% females) were included, mean age 11.6 years (SD 3.1 years). There was a strong correlation between the absolute values of BHI and BMD for both total body less head (TBLH) (r = 0.75, p < 0.001) and lumbar spine (L1-L4) (r = 0.77, p < 0.001). The correlation between BHI standard deviation score (SDS) and BMD TBLH Z-scores was weak (r = 0.34) but significant (0 = 0.001), varying from weak (r = 0.31) to moderate (r = 0.42) between the three study sites.
Categorizing BHI SDS and DXA BMD Z-scores on a 0–5 scale yielded a weak agreement between the two for both TBLH and LS, with w-kappa of 0.2, increasing to 0.3 when using quadratic weights. The agreement was notably higher for one of the three study sites as compared to the two others, particularly for spine assessment, yielding a moderate kappa value of 0.4 – 0.5.
For cone-beam CT, based on a 1–3 scale, 59 out of 94 left TMJ’s were scored as 1 and 31 as score 2 by the first observer vs. 87 and 7 by the second observer yielding a poor agreement (kappa 0.1).

Conclusions
Categorizing DXA LS and automated radiographic Z-scores on a 0–5 scale gave a weak to moderate agreement between the two methods, indicating that a hand radiograph might provide an adjuvant tool to DXA when assessing bone health children with JIA, given thorough calibration is performed.
Diagnostic challenges and outcome of fatty acid oxidation defects in a tertiary care center in Lebanon
Authors: Daher Rose T. , Taoum Katia El , Samaha Jinane , Karam Pascale E. 
Published: August 2024

AbstractBackgroundFatty acid oxidation defects are rare autosomal recessive disorders with variable clinical manifestations and outcome. Early detection by systematic neonatal screening may improve their prognosis. Long-term outcome studies of these disorders in the Middle East and North Africa region are limited. The purpose of this study is to report the diagnostic challenges and outcome of fatty acid oxidation defects in a major tertiary care center in Lebanon, a resource-constrained country in the Middle East.MethodsA retrospective review of charts of all fatty acid oxidation defects sequential patients diagnosed and followed at our center was conducted. Collected data included: parental consanguinity, age at diagnosis, clinical presentation, biochemical profile, confirmatory diagnosis, treatment and outcome. A genotype–phenotype correlation was also performed, when available.ResultsSeven types of fatty acid oxidation defects were identified in a total of 34 patients from 21 families. Most families (79%) were consanguineous (first-degree cousins). The majority were diagnosed when clinically symptomatic (78%), at various ages between 10 days and 19 years (average: 2 years). Follow-up duration spanned between 2 months and 15 years (average: 5 years). The remainder of the patients were detected while still asymptomatic by systematic neonatal screening (9%) or due to positive family history (9%). The most common defect was carnitine transporter deficiency (50%) with an exclusive cardiac presentation related to a founder variant c.981C > T, (p.Arg254*) in theSLC22A5gene. Medium chain acyl-CoA dehydrogenase deficiency was found in 13% only, which could be explained by the absence of systematic neonatal screening. Rare gene variants were detected in very long chain and multiple acyl-CoA dehydrogenase deficiency. The worse prognosis was observed in very long chain acyl-CoA dehydrogenase deficiency. The overall survival at last follow-up reached 75% with a complete reversal of symptoms with treatment in most patients (63%), despite their late diagnosis.ConclusionsOur experience highlights the diagnostic challenges and outcome of fatty acid oxidation defects in a resource-constrained country with high consanguinity rates. Physicians’ awareness and systematic neonatal screening are key for diagnosis. Larger genotype–phenotype studies are still needed to understand the natural history of these rare diseases and possibly improve their outcome.
CCT3/ACTN4/TFRC axis protects hepatocellular carcinoma cells from ferroptosis by inhibiting iron endocytosis
Authors: Zhu Huihui , Liu Qiuhong , Meng Qinna , Zhang Lingjian , Ju Siwei , Lang Jiaheng , Zhu Danhua , Chen Yongxia , Aishan Nadire , Ouyang Xiaoxi , Zhang Sainan , Jin Lidan , Xiao Lanlan , Wang Linbo , Li Lanjuan , Ji Feiyang 
Published: August 2024

AbstractSorafenib is widely used in treating advanced hepatocellular carcinoma (HCC). However, its effectiveness in prolonging patient survival is limited by the development of drug resistance. To systematically investigate the resistance mechanisms of Sorafenib, an integrative analysis combining posttranslational modification (PTM) omics and CRISPR/Cas9 knockout library screening was conducted. This analysis identified ubiquitination at lysine 21 (K21) on chaperonin-containing TCP1 subunit 3 (CCT3) as being associated with Sorafenib resistance. Transcriptomic data from HCC patients treated with Sorafenib revealed that CCT3 expression was lower in responders compared to non-responders. Experimentally, inhibiting the expression of CCT3 sensitized HCC cells to Sorafenib and enhanced Sorafenib-induced ferroptosis. Additionally, CCT3 was found to interact with ACTN4, hindering the recycling of transferrin receptor protein 1 (TFRC) to the cell membrane, thus obstructing iron endocytosis. Mechanistically, the inhibition of ferroptosis by CCT3 depends on the deubiquitination of K6-linked non-degradative ubiquitination at its K21, which occurs upon Sorafenib treatment. Moreover, CCT3 knockdown enhanced the anti-tumor effects of Sorafenib in nude mice. In summary, we have identified a novel function of the chaperone protein. Targeting the CCT3/ACTN4/TFRC axis offers a promising strategy to enhance ferroptosis and overcome Sorafenib resistance in HCC.
Policy Brief – Survivorship is cancer survivorship the poor cousin of cancer control within the EBCP?
Authors: Mbengi Régine Kiasuwa , Schittecatte Gabrielle , Theys Sofie 
Published: August 2024

Abstract
Background
There is an increasing number of cancer survivors, including children, adolescents, young adults, individuals of working age, and the elderly, within the Belgian and European population. Yet, survivorship care and rehabilitation are often treated as an afterthought in care organisation. This not only directly affects the quality of life of survivors and carers, but also puts the sustainability of the healthcare and social security systems at risk.

Methods
We analysed the ongoing Europe Beating Cancer Plan (EBCP) to identify the actions supporting survivorship (care) developments, then compared their weight in the EBCP to the other domains of cancer control. Following this analysis, and comparison with related ongoing projects, and current infrastructure in Belgium, several unmet needs were identified.

Conclusion
To better address these unmet needs, we recommend that Belgium incorporates survivorship care and long-term follow-up in clinical guidelines and care pathways, and considers including indicators related to cancer survivorship in the planning and design of quality insurance schemes, including certification of comprehensive cancer centres. Furthermore, we suggest further investment and support for research and knowledge exchange in the field of survivorship.
Nurses’ contribution to antimicrobial stewardship: business as usual?
Authors: Bos Maria , de Bot Cindy , Vermeulen Hester , Hulscher Marlies , Schouten Jeroen 
Published: August 2024

Abstract
Background
Antimicrobial Stewardship (AMS), the set of actions to ensure appropriate antimicrobial use, is increasingly considered a multidisciplinary endeavour. However, it is unclear how Dutch hospital-based nurses envision their contribution to AMS.

Objective
To explore the views and visions of Dutch bedside nurses on their role regarding appropriate antimicrobial use.

Methods
A qualitative study using semi-structured interviews was conducted. Fourteen bedside nurses in nine different Dutch hospitals participated. Data were analysed using a thematic content analysis.

Results
Nurses considered their role regarding appropriate use of antibiotics as an integral part of their daily nursing practice. They envisioned their future role as an expansion of their current practice, improving or intensifying this contribution. Prompting review of antimicrobial treatment by nurses was seen as regular practice. Ward rounds were considered the best moment to exert their nursing role, by showing leadership in communicating about different aspects of AMS. Patient advocacy (“striving for the best possible care for their patient”) appears to be a driver of the nursing contribution. Nurses perceived a shared responsibility with prescribers on certain aspects of the antimicrobial treatment and wished for a clarification of this role. Education and cognitive reminders such as antibiotic checklist to be used in ward rounds, can support the uptake of the nurses’ role.

Conclusion
Nurses envision their future role in AMS as an enhanced, elaborated and empowered version of their current daily practice. Education, formal acknowledgment and increased awareness of the nursing role, may advance the contributing role nurses already have.
Automated subway touch button detection using image process
Authors: An Junfeng , Lu Mengmeng , Li Gang , Liu Jiqiang , Wang Chongqing 
Published: August 2024

AbstractSubway button detection is paramount for passenger safety, yet the occurrence of inadvertent touches poses operational threats. Camera-based detection is indispensable for identifying touch occurrences, ascertaining person identity, and implementing scientific measures. Existing methods suffer from inaccuracies due to the small size of buttons, complex environments, and challenges such as occlusion. We present YOLOv8-DETR-P2-DCNv2-Dynamic-NWD-DA, which enhances occlusion awareness, reduces redundant annotations, and improves contextual feature extraction. The model integrates the RTDETRDecoder, P2 small target detection layer, DCNv2-Dynamic algorithm, and the NWD loss function for multiscale feature extraction. Dataset augmentation and the GAN algorithm refine the model, aligning feature distributions and enhancing precision by 6.5%, 5%, and 5.8% in precision, recall, and mAP50, respectively. These advancements denote significant improvements in key performance indicators.
Comparison between imidacloprid effects on AChE and nAChRα1 in target Aphis craccivora and non-target Apis mellifera: experimental and theoretical approaches
Authors: Ali Hussein M. , Abdel-Aty Basma , El-Sayed Walaa , Mariy Faiza M. , Hegazy Gamal M. 
Published: August 2024

Abstract
Background
Neonicotinoids are widespread insecticides because of their potent effects against aphids and other piercing-sucking insects in addition to having high selectivity toward insects rather than vertebrates. However, they affect severely some non-target insects, mainly honeybee in a phenomenon called colony collapse disorder (CCD).

Results
Effects of imidacloprid (IMI), most used neonicotinoids, on aphid acetylcholinesterase (AChE), in vivo and in vitro were examined; besides, molecular modeling was used to investigate similarities and differences of AChE and nicotinic acetylcholine receptors α1-subunit (nAChRα1) in aphids, target insect, and honeybees, non-target insect. Results showed that aphid AChE was inhibited in vitro, with IC50 108.6 mg/L but not affected in vivo while the mortality was concentration-dependent with high toxicity (LC50 9.50 mg/L); in addition, aphid AChE was more inhibited, in vitro, but with much less effects, in vivo, than that of honeybees. These results indicate that AChE is not the main cause of the observed mortality, but it still has a role in insect resistance system with different responses in both insects. Molecular modeling showed high similarity in primary and secondary structures of AChE indicated by high identity (67%) and low gaps (1%); besides, the same template for both enzymes was auto-selected for homology. In addition, similar positions of the triad amino acids were found in AChE of both insects indicating high similarity. Conversely, the similarity in nAChRα1 in both insects is lower (50% identity and 9% gaps). These gaps (50 amino acids) are found in the intracellular large loop between TM3 and TM4 and account for the observed differences in the nAChRα1 binding sites of in both insects.

Conclusion
These observed variations in nAChRα1 structures and binding sites in different insect species can be used as good bases in designing new neonicotinoids that express high effects on target insects with better selectivity to minimize adverse effects on non-target organisms.

Graphical Abstract
Elevated level of extracellular vimentin is associated with an increased fibrin formation potential in sepsis: ex vivo swine study
Authors: Martinez-Vargas Marina , Saini Arun , Pradhan Subhashree , Gardea Luis , Stoll Barbara , Didelija Inka C. , Vijayan K. Vinod , Nguyen Trung C. , Cruz Miguel A. 
Published: August 2024

Abstract
Background
Sepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy.

Results
We employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma vimentin level at 70 h post-MRSA inoculation was on average twofold higher compared to pre-infection (0 h) level in the same animal. Anti-vimentin antibody effectively reduced fibrin formation ex vivo and increased porosity in the fibrin clot structure generated from septic piglet plasma. In contrast to plasma at 0 h, the size-exclusion chromatography revealed that phosphorylated vimentin was in-complex with fibrinogen in septic piglet plasma.

Conclusions
Thus, our swine model of sepsis-induced coagulopathy, reproduced increased extracellular circulating vimentin and subsequent potentiation of fibrin formation, often observed in septic patient. These outcomes validate the use of large animal models to investigate the dysregulated host immune response to infection leading to coagulopathy, and to develop new therapies for sepsis-induced disseminated microvascular thrombosis.