bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of cardio-renal biomarkers and mortality in the U.S.: a prospective cohort study
Authors: Yang Fan , Wang Mingsi , Chen Yuzhu , Wu Jianjun , Li Yilan 
Published: September 2023

Abstract
Objective
Diabetes poses a significant threat to human health. There is a lack of large-scale cohort studies to explore the association between mortality risk and indicators beyond blood glucose monitoring in diabetic populations.

Methods
Multivariable Cox proportional hazards regression models were performed to investigate the association of 13 blood biomarkers with mortality risk in the National Health and Nutrition Examination Survey (NHANES) and biomarker levels were log-transformed and correlated with mortality.

Results
During a median follow-up of 7.42 years, 1783 diabetic patients were enrolled. Compared to traditional risk factors, the addition of hs-cTnT, hs-cTnI, NT-proBNP, creatinine, cystatin C, and β-2 microglobulin biomarkers increased the predictive ability for all-cause mortality by 56.4%, 29.5%, 38.1%, 18.8%, 35.7%, and 41.3%, respectively. However, the inclusion of blood glucose monitoring had no impact on the prediction of all-cause mortality. Compared with the 1st quartiles of creatinine and Cystatin C, the risk of diabetes mortality were higher in the highest quartiles (HR: 5.16, 95% CI: 1.87–14.22; HR: 10.06, 95% CI: 4.20-24.13).

Conclusions
In the diabetic population, elevated plasma levels of hs-cTnT, hs-cTnI, NT-proBNP, creatinine, cystatin C, and β-2 microglobulin serve as robust and straightforward predictors of long-term mortality compared to blood glucose levels and HbA1c values. Creatinine and cystatin C stand out as more precise markers for predicting diabetes mortality prior to blood glucose monitoring.
Item response theory-based psychometric analysis of the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) among adolescents in the UK
Authors: Hanzlová Radka , Lynn Peter 
Published: September 2023

Abstract
Background
Middle and late adolescence is the period in a person's life that is most vulnerable to mental health problems. To enable an evidence base that can support policies to prevent such problems, it is crucial to have good quality, reliable, and accurate measurement tools for mental well-being. One of them is the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS). This study aimed to test the psychometric properties of the SWEMWBS on a large sample of adolescents aged 16 to 19 from the United Kingdom (UK) (N = 8,090). Data were from four waves of the longitudinal panel study Understanding Society.

Methods
The analysis was conducted using Item Response Theory (IRT), which is the most appropriate method for testing psychometric properties. The Graded Response Model (GRM) was applied to the data. The reliability and criterion validity of the SWEMWBS were also examined.

Results
The presented results confirm the very good psychometric properties of the SWEMWBS amongst adolescents aged 16 to 19 years. The assumptions for the use (unidimensionality, local non-independence, monotonicity) of IRT were met. The results of GRM showed very high discriminant power for all items. The five-category response scale performed optimally; however, differences were found between points on the response scale both between and within items. In general, the scale as a whole showed very good functioning, but particularly in the negative values of mental well-being.

Conclusions
The SWEMWBS was confirmed as a concise, reliable, and valid instrument for measuring mental well-being among older UK adolescents.
Constructing founder sets under allelic and non-allelic homologous recombination
Authors: Bonnet Konstantinn , Marschall Tobias , Doerr Daniel 
Published: September 2023

AbstractHomologous recombination between the maternal and paternal copies of a chromosome is a key mechanism for human inheritance and shapes population genetic properties of our species. However, a similar mechanism can also act between different copies of the same sequence, then callednon-allelic homologous recombination (NAHR). This process can result in genomic rearrangements—including deletion, duplication, and inversion—and is underlying many genomic disorders. Despite its importance for genome evolution and disease, there is a lack of computational models to study genomic loci prone to NAHR. In this work, we propose such a computational model, providing a unified framework for both (allelic) homologous recombination and NAHR. Our model represents a set of genomes as a graph, where haplotypes correspond to walks through this graph. We formulate two founder set problems under our recombination model, provide flow-based algorithms for their solution, describe exact methods to characterize the number of recombinations, and demonstrate scalability to problem instances arising in practice.
Do women with high-risk HPV E6/E7 mRNA test positivity and NILM cytology need colposcopy?
Authors: Liu Ying , Jin Xiu , Gong Yingying , Ma Yingying , Du Beibei , Yang Linqing , Wang Yunfei , Zhu Weipei 
Published: September 2023

Abstract
Purpose
This study aimed to assess the value of an HPV E6/E7 mRNA assay and HPV 16 18/45 genotype assay combined with age stratification for triaging women negative for intraepithelial lesions or malignancy (NILM) cytology.

Methods
From January 2017 to December 2021, a total of 162,309 eligible women underwent cervical cancer screening at the Affiliated Hospital of Jining Medical University, China. Excluding those with negative HPV E6/E7 mRNA, abnormal and unsatisfactory cytology, and those who failed to undergo colposcopy, 6,845 women were ultimately included in our study. We analysed the triage guidance for different subtypes of HPV in the presence of NILM cytology.

Results
Among 162,309 women, 19,834 (12.2%) were positive for HPV E6/E7 mRNA. Of the 6,845 women included in the study, 1,941 (28.4%), 561 (8.2%), 55 (0.8%) and 4,288 (62.6%) tested positive for HPV 16, HPV 18/45, HPV16/18/45 or other HR-HPV genotypes, respectively. The proportions of LSIL+ (including LSIL, HSIL and ICC) and HSIL+ (including HSIL and ICC) pathological results in the HPV 16/18/45 + group were 57% and 34.1%, respectively, higher than 36.3% and 11% in the other HR-HPV + group (χ2 = 653.214, P < 0.001). The percentages of LSIL + and HSIL + in the HPV16 + group (61.3% and 42.8%, respectively) and HPV16+/18/45 + group (76.3% and 41.9%, respectively) were much higher than those in the HPV18 + group (40.6% and 13.1%, respectively) (P < 0.001). However, there was no significant difference in the percentage of histopathological results between the HPV16 + group and HPV16+/18/45 + groups (P > 0.05). The above results were consistent after stratification according to age.

Conclusion
The rate of histopathological abnormalities was still high for the other HR-HPV subtypes with NILM cytology, although the rate of histopathological abnormalities was much higher for the HPV 16/18/45 positive subtypes. Therefore, colposcopy should be performed in women with HPV E6/E7 mRNA positivity and NILM cytology, regardless of age and HPV genotype.
Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction
Authors: Jakobsson Gabriel , Papareddy Praveen , Andersson Henrik , Mulholland Megan , Bhongir Ravi , Ljungcrantz Irena , Engelbertsen Daniel , Björkbacka Harry , Nilsson Jan , Manea Adrian , Herwald Heiko , Ruiz-Meana Marisol , Rodríguez-Sinovas Antonio , Chew Michelle , Schiopu Alexandru 
Published: September 2023

Abstract
Background and Aims
The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD.

Methods
The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9−/− mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice.

Results
In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9−/− mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9−/− mice, confirming target specificity.

Conclusion
Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis.

Graphical Abstract
Core and penumbra estimation using deep learning-based AIF in association with clinical measures in computed tomography perfusion (CTP)
Authors: Bal Sukhdeep Singh , Yang Fan-pei Gloria , Chi Nai-Fang , Yin Jiu Haw , Wang Tao-Jung , Peng Giia Sheun , Chen Ke , Hsu Ching-Chi , Chen Chang-I 
Published: September 2023

Abstract
Objectives
To investigate whether utilizing a convolutional neural network (CNN)-based arterial input function (AIF) improves the volumetric estimation of core and penumbra in association with clinical measures in stroke patients.

Methods
The study included 160 acute ischemic stroke patients (male = 87, female = 73, median age = 73 years) with approval from the institutional review board. The patients had undergone CTP imaging, NIHSS and ASPECTS grading. convolutional neural network (CNN) model was trained to fit a raw AIF curve to a gamma variate function. CNN AIF was utilized to estimate the core and penumbra volumes which were further validated with clinical scores.

Results
Penumbra estimated by CNN AIF correlated positively with the NIHSS score (r = 0.69; p < 0.001) and negatively with the ASPECTS (r =  − 0.43; p < 0.001). The CNN AIF estimated penumbra and core volume matching the patient symptoms, typically in patients with higher NIHSS (> 20) and lower ASPECT score (< 5). In group analysis, the median CBF < 20%, CBF < 30%, rCBF < 38%, Tmax > 10 s, Tmax > 10 s volumes were statistically significantly higher (p < .05).

Conclusions
With inclusion of the CNN AIF in perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke.

Critical relevance statement
With CNN AIF perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke.

Graphic abstract
Stable isotope labeling and ultra-high-resolution NanoSIMS imaging reveal alpha-synuclein-induced changes in neuronal metabolism in vivo
Authors: Spataro Sofia , Maco Bohumil , Escrig Stéphane , Jensen Louise , Polerecky Lubos , Knott Graham , Meibom Anders , Schneider Bernard L. 
Published: September 2023

AbstractIn Parkinson’s disease, pathogenic factors such as the intraneuronal accumulation of the protein α-synuclein affect key metabolic processes. New approaches are required to understand how metabolic dysregulations cause degeneration of vulnerable subtypes of neurons in the brain. Here, we apply correlative electron microscopy and NanoSIMS isotopic imaging to map and quantify 13C enrichments in dopaminergic neurons at the subcellular level after pulse-chase administration of 13C-labeled glucose. To model a condition leading to neurodegeneration in Parkinson’s disease, human α-synuclein was unilaterally overexpressed in the substantia nigra of one brain hemisphere in rats. When comparing neurons overexpressing α-synuclein to those located in the control hemisphere, the carbon anabolism and turnover rates revealed metabolic anomalies in specific neuronal compartments and organelles. Overexpression of α-synuclein enhanced the overall carbon turnover in nigral neurons, despite a lower relative incorporation of carbon inside the nucleus. Furthermore, mitochondria and Golgi apparatus showed metabolic defects consistent with the effects of α-synuclein on inter-organellar communication. By revealing changes in the kinetics of carbon anabolism and turnover at the subcellular level, this approach can be used to explore how neurodegeneration unfolds in specific subpopulations of neurons.
Increased paclitaxel recovery from Taxus baccata vascular stem cells using novel in situ product recovery approaches
Authors: Santoyo-Garcia Jorge H. , Valdivia-Cabrera Marissa , Ochoa-Villarreal Marisol , Casasola-Zamora Samuel , Ripoll Magdalena , Escrich Ainoa , Moyano Elisabeth , Betancor Lorena , Halliday Karen J. , Loake Gary J. , Rios-Solis Leonardo 
Published: September 2023

AbstractIn this study, several approaches were tested to optimise the production and recovery of the widely used anticancer drug Taxol® (paclitaxel) from culturable vascular stem cells (VSCs) of Taxus baccata, which is currently used as a successful cell line for paclitaxel production. An in situ product recovery (ISPR) technique was employed, which involved combining three commercial macro-porous resin beads (HP-20, XAD7HP and HP-2MG) with batch and semi-continuous cultivations of the T. baccata VSCs after adding methyl jasmonate (Me-JA) as an elicitor. The optimal resin combination resulted in 234 ± 23 mg of paclitaxel per kg of fresh-weight cells, indicating a 13-fold improved yield compared to the control (with no resins) in batch cultivation. This resin treatment was further studied to evaluate the resins’ removal capacity of reactive oxygen species (ROS), which can cause poor cell growth or reduce product synthesis. It was observed that the ISPR cultivations had fourfold less intracellular ROS concentration than that of the control; thus, a reduced ROS concentration established by the resin contributed to increased paclitaxel yield, contrary to previous studies. These paclitaxel yields are the highest reported to date using VSCs, and this scalable production method could be applied for a diverse range of similar compounds utilising plant cell culture.
Graphical Abstract
S-Nitrosylation in endothelial cells contributes to tumor cell adhesion and extravasation during breast cancer metastasis
Authors: Koning T. , Cordova F. , Aguilar G. , Sarmiento J. , Mardones G. A. , Boric M. , Varas-Godoy M. , Lladser A. , Duran W. N. , Ehrenfeld P. , Sanchez F. A. 
Published: September 2023

Abstract
Background
Nitric oxide is produced by different nitric oxide synthases isoforms. NO activates two signaling pathways, one dependent on soluble guanylate cyclase and protein kinase G, and other where NO post-translationally modifies proteins through S-nitrosylation, which is the modification induced by NO in free-thiol cysteines in proteins to form S-nitrosothiols. High levels of NO have been detected in blood of breast cancer patients and increased NOS activity has been detected in invasive breast tumors compared to benign or normal breast tissue, suggesting a positive correlation between NO biosynthesis, degree of malignancy and metastasis. During metastasis, the endothelium plays a key role allowing the adhesion of tumor cells, which is the first step in the extravasation process leading to metastasis. This step shares similarities with leukocyte adhesion to the endothelium, and it is plausible that it may also share some regulatory elements. The vascular cell adhesion molecule-1 (VCAM-1) expressed on the endothelial cell surface promotes interactions between the endothelium and tumor cells, as well as leukocytes. Data show that breast tumor cells adhere to areas in the vasculature where NO production is increased, however, the mechanisms involved are unknown.

Results
We report that the stimulation of endothelial cells with interleukin-8, and conditioned medium from breast tumor cells activates the S-nitrosylation pathway in the endothelium to induce leukocyte adhesion and tumor cell extravasation by a mechanism that involves an increased VCAM-1 cell surface expression in endothelial cells. We identified VCAM-1 as an S-nitrosylation target during this process. The inhibition of NO signaling and S-nitrosylation blocked the transmigration of tumor cells through endothelial monolayers. Using an in vivo model, the number of lung metastases was inhibited in the presence of the S-nitrosylation inhibitor N-acetylcysteine (NAC), which was correlated with lower levels of S-nitrosylated VCAM-1 in the metastases.

Conclusions
S-Nitrosylation in the endothelium activates pathways that enhance VCAM-1 surface localization to promote binding of leukocytes and extravasation of tumor cells leading to metastasis. NAC is positioned as an important tool that might be tested as a co-therapy against breast cancer metastasis.
Handling orthodontic complaints
Authors: Lewis Kevin 
Published: September 2023

This article explains some proven strategies for successful complaints handling across different areas of orthodontic practice, while stressing the need to recognise and understand the subtleties often encountered when managing complaints about orthodontic care and treatment, and the importance of taking them into account. It will also suggest some ‘upstream’ strategies for making complaints less likely. CPD/Clinical relevance: This paper aims to give orthodontic practitioners clinical insight into complaints handling procedures across private and NHS practice.
Cotton on to the problems: a visual aid for mimicking maxillary advancement surgery chairside
Authors: Dewshi Claire , Brierley Catherine 
Published: September 2023

When planning orthognathic surgery for patients with a mild Class III skeletal relationship, it may be challenging for orthodontists to predict soft tissue changes in a way that is meaningful to patients. A simple tip is to place two damp cotton wool rolls under the patient's upper lip to mimic anterior repositioning of the maxilla. While dermal fillers are becoming increasingly popular, they can complicate facial assessment as a result of the altered soft tissue profile. Patients should be encouraged not to use dermal fillers at any point along the orthognathic pathway, or delay facial assessment in multidisciplinary clinics until these fillers have dissolved. CPD/Clinical relevance: This article describes a quick and easy chairside aid to help patients and clinicians visualise the facial changes with maxillary advancement surgery by placing two damp cotton wool rolls under the upper lip to mimic anterior repositioning of the maxilla.
Stakeholder Perspectives on Interprofessional Primary Care for Adults With Intellectual and Developmental Disabilities in Ontario, Canada
Authors: Bobbette Nicole J. , Lysaght Rosemary , Ouellette-Kuntz Hélène , Tranmer Joan , Donnelly Catherine 
Published: September 2023

Abstract
Access to high-quality primary care has been identified as a pressing need for adults with intellectual and developmental disabilities (IDD). Interprofessional primary care teams offer comprehensive and coordinated approaches to primary care delivery and are well-positioned to address the needs of adults with IDD. The overall aim of this article is to describe the current provision of interprofessional primary care for adults with IDD from the perspectives of patients, caregivers, and health providers. Results provide important insights into the current state of practice and highlight a critical need for further work in the field to develop processes to engage in team-based care and demonstrate the value of the approach for this population.
Reading Lessons Planning With Students With Intellectual and Developmental Disabilities in Mind: Needs-Based Assessment Proposal
Authors: Sánchez-Gómez Victoria , López-Cruz Mauricio , Amor Antonio M. 
Published: September 2023

Abstract
This study addresses the need to reinforce the reading learning of students with intellectual and developmental disabilities (IDD) in general education classrooms. A standardized way of assessing support needs in reading (SNr) from the teachers’ perspective is proposed. The objectives were (i) to develop an instrument and evaluate its properties and (ii) to preliminarily assess the support needs in reading of students with IDD. Participants were 86 Chilean elementary school teachers who responded about the support needs of their own students. The instrument assesses three dimensions (i.e., representation, engagement, and action and expression). Analyses showed excellent preliminary evidence of validity and reliability. Preliminarily identified support needs suggest that students need more support in representation. Practical and research implications are discussed.
The application of blended learning in mathematics teacher education: Protocol for a systematic review
Authors: Tong Duong Huu , Uyen Bui Phuong , Ngan Lu Kim 
Published: September 2023

Introduction
In recent decades, especially in higher education, blended learning has become the most commonly used active teaching strategy. Because of the COVID-19 pandemic, blended learning, which combines face-to-face and online components, is believed to overcome the shortcomings of conventional teaching methods, particularly in face-to-face interactions. Based on PRISMA guidelines, this study follows the protocol for a systematic review of blended learning applications in mathematics teacher education. This systematic review study aims to comprehend the potential of blended learning for various mathematical topics, the common blended learning models, and the benefits and challenges this teaching approach presents for educational stakeholders.

Methods
Searches will be performed in various electronic databases, including Scopus, ScienceDirect, Taylor & Francis Online, Mendeley, Google Scholar, and ERIC. Selected studies that satisfy the inclusion criteria will document the use of various blended learning models in a range of mathematical topics as well as the advantages and disadvantages of this method of instruction. The data extraction process will be carried out independently by various authors, and the results of the data synthesis will be reported per the chosen studies, methodological considerations, and key findings.

Discussion
This review will provide information about the application of blended learning and its benefits and challenges in mathematics teacher education to support educational stakeholders in mathematics teacher education.