bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats
Authors: Costain Will J. , Haqqani Arsalan S. , Hussack Greg , Faassen Henk van , Lessard Etienne , Ling Binbing , Brunette Eric , Ly Dao , Fang Hung , Bultinck Jennyfer , Geysens Steven , Pynaert Gwenda , Piens Kathleen , Ryckaert Stefan , Fudalej Franck , Vervecken Wouter , Stanimirovic Danica 
Published: November 2024

Abstract

Background
Iduronate-2-sulfatase (IDS) deficiency (MPS II; Hunter syndrome) is a disorder that exhibits peripheral and CNS pathology. The blood brain barrier (BBB) prevents systemic enzyme replacement therapy (ERT) from alleviating CNS pathology. We aimed to enable brain delivery of systemic ERT by using molecular BBB-Trojans targeting endothelial transcytosis receptors. Methods: Single-domain antibody (sdAb)-enzyme fusion protein constructs were prepared in Yarrowia lipolytica. sdAb affinity and BBB permeability were characterized using SPR and an in vitro rodent BBB assay, respectively. In vivo PK analysis was performed in rats. Quantification of fusion protein amounts were performed using LC-MS.
Results
Fusion proteins consisting of IDS and BBB-transmigrating sdAbs, albumin binding sdAbs or human serum albumin (HSA) were evaluated for their in vitro BBB permeability. IGF1R3H5-IDS was selected for in vivo pharmacokinetics (PK) analysis in rats. IDS and IGF1R3H5-IDS exhibited very short (< 10 min) serum half-life (t1/2α), while constructs containing either HSA or anti-serum albumin sdAbs (R28 or M79) showed 8–11 fold increases in the area under the curve (AUC) in serum. CSF analysis indicated that IGF1R3H5 increased brain exposure by 9 fold (AUC) and constructs containing HSA or R28 exhibited 42–52 fold increases. Quantitation of brain levels confirmed the increased and sustained delivery of IDS to the brain of HSA- and R28-containing constructs. Lastly, analysis of brain fractions demonstrated that the increases in brain tissue were due to parenchymal delivery without fusion protein accumulation in brain vessels.
Conclusions
These results demonstrate the utility of IGF1R-targeting sdAbs to effect brain delivery of lysosomal enzymes, as well as the utility of serum albumin-targeting sdAbs in t1/2 extension, to increase brain delivery of rapidly cleared enzymes.
Sustainable steel-concrete composite beams with novel demountable shear connections under positive bending moments: Experimental behavior and analytical model
Authors: Xiong Liquan , Liu Yuoguo , Li Song , Li Yajuan , Wang Xinyong , Tang Daomin , Chen Xiaojian 
Published: November 2024

Abstract

Sustainable structures or structural components as one of the frontiers in civil engineering can solve the problem of construction and demolition waste and also enhance the reuse of structural components at the end of their service life or after damage. In terms of sustainable assessment, steel-concrete composite beams with or without novel demountable shear connectors were performed in this work. Structural configuration and mechanical properties of proposed sustainable steel-concrete composite beams were firstly presented and then the nonlinear analysis of this composite beams using the Abaqus software was validated. Three specimens with different types of shear connectors were designed and tested under two-point loading to investigate the flexural behavior and deconstructability. Results from this research showed that these composite beams exhibited a flexure-shear or flexural behavior, presenting the typical failure modes of yielding of steel beam, slab concrete split or concrete crushing of plug. Compared to that of traditional composite beam with embedded welded bolts, specimens with demountable shear bolts and demountable shear connections experienced reduced initial flexural stiffness (about 29.8% and 37.2%), yield strength (by about 18.3% and 32.1%) and ultimate strength (about 12.9% and 24.9%) due to the relative slip between the steel beam and precast concrete slab, respectively. Whereas these of composite beams developed a better deformation capacity and ductility coefficient. Additionally, sustainable steel-concrete composite beam with demountable shear connections could easily allow for easy installment and disassemble to achieve the recycle of these structural members and also replacement with new plugs to permit a quick seismic rehabilitation after earthquake damage. Finally, some suggestions of this sustainable composite beam and demountable shear connections were proposed to provide references for the design in practice.
Inhibition of LOX-1 ameliorates coagulation and inflammation in sepsis by suppressing the JAK2/STAT3 pathway
Authors: Wang Ying , Zhang Rongrong , Zhou Chen , Huang Yueyue , Zhou Aiming , Luo Shuang , Liang Chenglong , Pan Jingye 
Published: November 2024

Abstract

Lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) is a transmembrane protein that belongs to the C-type lectin family and plays a significant role in various diseases by promoting the release of inflammatory mediators and enhancing cellular responses to oxidative stress. Studies have demonstrated that in sepsis, activation of LOX-1 promotes a procoagulant phenotype in endothelial cells. The aim of this study was to investigate whether inhibition of LOX-1 could ameliorate coagulation dysfunction and the inflammatory response in sepsis by modulating the JAK2/STAT3 signaling pathway. We utilized LPS-induced C57BL/6 mice to establish an in vivo animal model and assessed the activity of the JAK2/STAT3 signaling pathway, along with coagulation-related factors and inflammatory factors.In the in vitro experiments, human umbilical vein endothelial cells (HUVECs) were exposed to LPS after either LOX-1 knockdown or no treatment. We subsequently measured the expression of tissue factor (TF) and inflammatory factors, as well as changes in the JAK2/STAT3 signaling pathway. The results indicated that LOX-1 blockade improved coagulation dysfunction and the inflammatory response, leading to enhanced survival in septic mice. In vitro, LOX-1 knockdown suppressed the expression of TF and inflammatory factors in LPS-induced HUVECs. Both in vivo and in vitro experiments confirmed that inhibition of LOX-1 ameliorated sepsis by suppressing the JAK2/STAT3 signaling pathway.
IntroductionInvestigating the educational needs of mothers to prevent the occurrence of contractures in burned children
Authors: Alipour Negar Abdul , Roshan FatemehSadat SeyedNematollah , Sahbaei Faezeh 
Published: November 2024

Abstract

Background: Burns in children are one of the most common injuries and often cause appearance changes, contractures, disturbances in the normal movements of joints, social isolation, and depression. Since mothers, as the main caregivers, have a unique and essential role in providing physical care and also improving psychosocial functioning, follow-up treatment, and taking care of the complications of burns in their children, the present study aims to investigate the educational needs of mothers of children with burns to prevent contracture.
Methods: This descriptive-cross-sectional study was conducted in Motahhari Burn Center from January to September 2024. 150 mothers of burned children were selected through convenient sampling. The data collection tool included a demographic information questionnaire and a 40-item questionnaire to assess the educational needs of mothers. Data were analyzed using SPSS version 26 software.
Results: Educational need in the cause and predisposing factors of contracture in the dimensions of not doing physical therapy (3.22), motivational and spiritual factors (3.02), not using anti-scar devices (3.22), and financial problems (3.06) were at an average level. Also, mothers' educational needs in the care and prevention field in the nutrition dimension (3.77) were at a medium level. In the dimensions of wound care (2.95), proper dressing (2.85), positioning of burned limbs (2.88), and physical therapy (2.64), the use of anti-scar devices (2.87), and mobility and activity (2.87) were at a high level. 44% of mothers in the contracture causes section, 47.4% in the burn care, and 62.6% in the prevention of contracture section had a severe educational need. No correlation was observed between demographic variables and the educational needs of mothers in the mentioned three sections (p ≥ 0.05).
Conclusions: Mothers have a high educational need regarding the prevention of contracture in children with burns, and to provide proper care from mother to child, the educational needs of mothers must be met. Considering that no meaningful relationship was found between demographic information such as mother's and father's occupation and academic level, it can be concluded that education should be given the same for all parents regardless of academic level and occupation.
Effect of Liquid Density, Ultrasonic Velocity, and Gas Flow Rate on the Formation of Air Bubbles in Aqueous Methanol at Temperature 293.15K, 303.15K &amp; 313.15 K
Authors: Mall P. K. , Paliwal H. K. , Medhavi Amit , Kumar Shailendra 
Published: November 2024

Abstract

The current study describes a numerical and experimental study on the formation, growth, and detachment of gas bubbles in aqueous methanol. The process of bubble formation and growth is significant in many industrial applications where gas bubbles disperse within a liquid medium. Experimental measurements of fluid properties, such as density and ultrasonic velocity, of aqueous methanol were conducted over a range of concentrations (0 to 1) and at temperatures of 293.15 K, 303.15 K, and 313.15 K under atmospheric pressure. The study focuses on experimentally analyzing the bubble size distribution (BSD) within a bubble column. The study examines the effects of air flow rate, density, and ultrasonic velocity on bubble diameter in an aqueous methanol solution. As the air flow rate increases from 3 L/min to 4 L/min, bubble diameter consistently increases, with higher densities also contributing to larger bubbles. At a density of 7914 kg/m³, the bubble diameter increases from 0.0048 mm to 0.0054 mm, and at 9981 kg/m³, it rises from 0.0075 mm to 0.0086 mm.Higher ultrasonic velocities similarly result in larger bubbles. At a flow rate of 3 L/min, bubble diameter increases from 0.0046 mm at 1052.5 m/s to 0.0074 mm at 9222 m/s. The findings indicate that an increase in ultrasonic velocity flow rate and an increase in liquid density lead to larger bubble sizes before detachment.
Online personalized normative feedback to foster intention to change and treatment- seeking in pathological gamblers and investors: protocol for a randomized controlled trial among young adults
Authors: Coloma-Carmona Ainhoa , Carballo José Luis , Miró-Llinares Fernando , Pérez-Jover Virtudes 
Published: November 2024

Abstract

Background: Despite the availability of treatment options, the percentage of individuals with gambling problems seeking help remains low. To reach a broader population of those affected by disordered gambling, online or self-guided interventions have been developed, with personalized normative feedback (PNF) being one of the most widely used strategies in preventing gambling issues among young adults. However, most studies on the efficacy of PNF focus only on its impact on the intensity and severity of gambling behavior, without exploring its potential effect on increasing intention to change and help-seeking behaviors. Furthermore, no studies have assessed the efficacy of PNF in addressing emerging online gambling-like behaviors, such as betting within video games or excessive financial trading of high-risk assets (e.g., cryptocurrencies), which have been linked to pathological gambling.
Method/Design:This project has two main objectives: (1) to quantify intention to change and the prevalence of help-seeking behaviors in young adults in Spain with disordered gambling or trading behaviors, and (2) to assess the efficacy of online personalized normative feedback (PNF) in increasing these behaviors. A randomized controlled trial with a Solomon three-group design will be conducted, including a sample of at least 472 men and women aged 18-30 years. The study will include three assessments: a pre-test, an immediate post-test, and a 12-week follow-up assessment. The intervention will consist of online PNF, delivered to participants in two intervention groups. The impact of PNF on gambling and trading behavior (including intensity, frequency, and severity) and the longitudinal trajectory of these behaviors will be also evaluated. Additionally, individual, interpersonal, and contextual factors will be assessed to identify the profile of individuals most likely to benefit from this intervention.
Discussion: This study is innovative in evaluating the efficacy of online PNF in promoting behavior change and help-seeking in young adults with gambling and trading disorders. The findings will offer valuable insights into the psychological and social impacts of these behaviors, informing future prevention and treatment strategies.
Trial registration: ClinicalTrials.gov Identifier: NCT06681103; Date of Registration: November 7, 2024.
Evaluation of an artificial intelligence model for identification of obstructive hydrocephalus on computed tomography of the head
Authors: Hillis James , Ghatak Ankita , Newbury-Chaet Isabella , Mercaldo Sarah , Chin John , Halle Madeleine , L'Italien Eric , MacDonald Ashley , Schultz Alex , Buch Karen , Conklin John , Mehan William , Pomerantz Stuart , Rincon Sandra , Bizzo Bernardo 
Published: November 2024

Abstract

Introduction:
Obstructive hydrocephalus is a critical radiographic finding requiring emergent treatment. Its identification on head computed tomography (CT) by an artificial intelligence (AI) model could facilitate sooner life-saving interventions, although there are common co-occurring findings including intracranial hemorrhage that can confound this interpretation. This study assessed the accuracy of an AI model (Annalise Enterprise CTB) at identifying obstructive hydrocephalus including in the presence or absence of other findings.
Methods
This retrospective cohort included 177 thin (≤ 1.5mm) series and 194 thick (> 1.5 and ≤ 5mm) series from 200 non-contrast head CT cases. These cases were obtained from patients aged ≥ 18 years at 5 hospitals in the United States. Each case was interpreted independently by up to three neuroradiologists. Each series was then interpreted by the AI model.
Results
The AI model performed with area under the curve 0.988 (95% confidence interval (CI): 0.971 to 0.998) on thin series and 0.986 (95% CI: 0.969 to 0.997) on thick series. These results were broadly maintained in subgroups for the presence or absence of intracranial hemorrhage, parenchymal abnormality and ventricular drain, and across demographic and scanner manufacturer subgroups.
Conclusions
The AI model accurately identified obstructive hydrocephalus in this dataset. Its performance in subgroup analyses reflected its robustness.
Thalamocortical Hodology to Personalize Electrical Stimulation for Focal Epilepsy
Authors: Gonzalez-Martinez Jorge , Damiani Arianna , Nouduri Sirisha , Ho Jonathan , Salazar Steven , Jegou Aude , Reedy Eliza , Ikegaya Naoki , Sarma Sridevi , Aung Thandar , Pirondini Elvira 
Published: November 2024

Abstract

Targeted electrical stimulation to specific thalamic regions offers a therapeutic approach for patients with refractory focal and generalized epilepsy who are not candidates for resective surgery. However, clinical outcome varies significantly, in particular for focal epilepsy, influenced by several factors, notably the precise anatomical and functional alignment between cortical regions generating epileptic discharges and the targeted thalamic stimulation sites. Here we hypothesized that targeting thalamic nuclei with precise anatomical and functional connections to epileptic cortical areas (an approach that we refer to as hodological matching) could enhance neuromodulatory effects on focal epileptic discharges. To investigate this, we examined three thalamic subnuclei (pulvinar nucleus, anterior nucleus, and ventral intermediate nucleus/ventral oral posterior nuclei) in a retrospective study involving 32 focal epilepsy patients. Specifically, we first identified hodologically organized thalamocortical fibers connecting these nuclei to individual seizure onset zones (SOZs), combining neuroimaging and electrophysiological techniques. Further, analysis of 216 spontaneous seizures revealed the critical role of matched thalamic nuclei in seizure development and termination. Importantly, electrical stimulation of hodologically-matched thalamic nuclei immediately suppressed intracortical interictal epileptiform discharges, contrasting with ineffective outcomes from stimulation of unmatched targets. Finally, we retrospectively evaluated 7 patients with a chronic hodologically-matched neurostimulation system, which led to a clinically relevant reduction in seizure frequency (median reduction 86.5%), that outstands the current clinical practice of unmatched targets (39%). Our results underscore the potential of hodological thalamic targeting to modulate epileptiform activity in specific cortical regions, highlighting the promise of precision medicine in thalamic neuromodulation for focal refractory epilepsy.
Demonstrating the value for money of implementing evidence-based treatment: the case for further investment in magnesium sulphate as a neuroprotectant for preterm births
Authors: Sillero-Rejon Carlos , Edwards Hannah B , Opmeer Brent C. , Hollingworth William , Pithara-McKeown Christalla , de Vocht Frank , Redwood Sabi , Odd David , Luyt Karen , McLeod Hugh 
Published: November 2024

Abstract

Background:
Effective and cost-effective treatments are not always optimally implemented. The benefit forgone due to sub-optimal implementation is often not considered or estimated. We use the economic concept of ‘incremental net monetary benefit’ (INMB) to demonstrate how this can be valued. This approach can inform decision-making when used to estimate the value for money of potential future quality improvement (QI) programmes. We illustrate these analyses using the case of antenatal magnesium sulphate (MgSO4), a cost-effective treatment for the prevention of cerebral palsy in preterm births. We estimate the optimal implementation of MgSO4, the INMB lost due to sub-optimal implementation, and the value of future implementation initiatives to increase the use of MgSO4.
Methods:
We estimated MgSO4 treatment implementation for babies under 32 weeks’ gestation using routine data on its uptake between 2014 and 2022 in England, Scotland, and Wales. The optimal uptake level of MgSO4 was estimated using clinical judgment. The societal lifetime INMB of MgSO4 for the prevention of cerebral palsy in preterm births was obtained from the literature. The INMB of sub-optimal implementation over time was estimated as the difference between optimal and actual uptake over time in each country. We estimated the cost-effectiveness of a hypothetical future QI programme based on different scenarios of implementation effectiveness and costs.
Results:
The optimal uptake of MgSO4 was 95%. The INMB forgone associated with sub-optimal MgSO4 uptake has reduced over time, as uptake has increased. However, in 2022, the societal lifetime INMB forgone was still £18.2m in England, £3.7m in Scotland, and £1.0m in Wales. A future QI programme across all three countries achieving a 5% increase in MgSO4 uptake over one year, and costing £987,500 to implement, would be cost-effective; generating £7.5m in INMB. Future implementation initiatives are likely to be cost-effective within a range of different implementation effectiveness and costs.
Conclusions:
The case of MgSO4 treatment for preterm birth illustrates how sub-optimal implementation of evidence-based interventions can be associated with high opportunity costs measured as INMB forgone. This approach provides valuable quantification of the value for money of future QI programmes to improve the implementation of these interventions.
WITHDRAWN: Algorithm Development for Measuring CDOM and Secchi from Hue Angle Using Satellite Images: A Study in Lake Peipsi, Estonia
Authors: Rahman Mizanur , Alikas Krista , Ansper-Toomsalu Ave , Aunap Raivo 
Published: November 2024

Abstract

Depending on the illumination condition and water composition, watercolor differs from one water source to another around the globe. The In-situ-based water monitoring systems are traditionally expensive, time-consuming, and sometimes limited because of extreme weather events. It also doesn't reflect the CDOM and Secchi of the whole waterbody because of limited data collection stations in the large waterbody. However, for optically complex water like Lake Peipsi, it is important to monitor water quality parameters like Secchi and CDOM spatially and regularly. Remote sensing could allow monitoring lakes on a large scale with the possibility of frequently getting information from non-accessible water bodies. Sentinel-3 OLCI has a high temporal, spectral, and spatial resolution for estimating water quality parameters. This study developed an algorithm to compare in-situ data and satellite data to calculate the Hue angle to investigate the relationship between the color of the water and water quality parameters such as CDOM and water transparency. The relations are expressed in the quadratic equation to calculate CDOM and Secchi. This study found the equation for CDOM is y = 21.7 - 0.647x + 0.00521x² and Secchi depth y= 0.638 + 0.0183x + 0.000346x² with the correlation values 0.67 and 0.52, respectively. To develop the algorithm, this study considered various meteorological and environmental parameters such as Cloudiness, sun, wave height, and wind speed collected from 2016 to 2022 from 23 stations in Peipsi and also validated the result using the in-situ data collected from the same stations from May to September 2023. This study found a CDOM ranging from 1.618 to 8.822 m⁻¹ and a Secchi depth ranging from 0.031 to 2.097 m. The study shows promising results for using remote sensing hue angle to estimate water quality parameters in the optically complex Lake Peipsi.
Inclusivity of Indigenous Knowledge Systems in Fisheries Management
Authors: Moffat Keshia , Snook Jamie , Paul Kenneth , Frid Alejandro 
Published: November 2024

Abstract

Indigenous Peoples have developed knowledge systems that foster respectful and reciprocal relations between human and other-than-human beings, supporting resilient ecosystems and societies. Despite the impacts of colonization, Indigenous Knowledge Systems (IKS) endure in many parts of the world and there is growing recognition that IKS can strongly improve fisheries management. During the last five years, Fisheries and Oceans Canada (DFO), the federal institution responsible for managing Canada's fisheries, released policies and strategies intended to make fisheries management more inclusive of IKS. To measure progress in their implementation, we applied 13 semiquantitative indicators and qualitative analyses of IKS inclusivity to a sample of 88 public documents produced or co-produced by DFO to advise management decisions. Of these documents, ≈ 89% did not meaningfully include IKS in the research processes and outcomes that they reported, while 10% showed a range of limited IKS inclusion in scientific processes initiated and driven by DFO. In the latter cases, IKS appeared to be considered as an afterthought or in ways that served a pre-determined scientific methodology. Only one advice document balanced the complementary strengths of IKS and science. The indicators that we developed in a Canadian context can be used, with locally appropriate revisions, to gauge the extent to which state governments in other countries are inclusive of IKS in fisheries management, thereby identifying shortcomings in law, policy, and practice and informing mitigation measures. Strengthening the inclusivity of IKS would enable more holistic approaches to fisheries management and benefit global conservation.