bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absolute and Relative Agreement Between Radiographic and Sonographic Calcaneal Ossification Staging: A Pilot Study
Authors: DeJong Lempke Alexandra F. , Whitney Kristin E. , Jackson Sarah S. , Le Hung M. , Hanlon Shawn L. 
Published: February 2025

Background: Radiographic evaluations are commonly used to determine calcaneal ossification staging throughout pediatric development. Sonographic imaging may offer a less expensive, noninvasive, clinically feasible option for calcaneal developmental assessments. Here, we assessed (1) inter-rater agreement of radiographic and sonographic calcaneal ossification staging of children and adolescent patients with Sever’s disease and (2) agreement between radiographic and sonographic calcaneal ossification staging scores. Hypothesis: There would be substantial agreement of radiographic and sonographic calcaneal ossification staging across raters, and between imaging measures. Study Design: Retrospective cohort study. Level of Evidence: Level 3. Methods: Adolescent patients (<18 years of age) with physician-diagnosed Sever’s disease who had complete calcaneal sonographic and radiographic imaging available on a retrospective chart review were included. Three independent reviewers with advanced training in musculoskeletal ultrasound each separately assessed radiographic and sonographic imaging data and assigned calcaneal calcification stages (0-5) to blinded images based on established criteria. Fleiss’ Kappa analyses were used to determine inter-rater staging agreement for both imaging approaches. Cohen’s Kappa analyses were used to determine the agreement between radiographic and sonographic staging. Absolute agreement, and relative agreement within each stage were assessed for both analyses. Results: Data from 19 patients (13 female, 6 male; 12.2 ± 2.3 years) were included. Absolute inter-rater agreement for radiographic and sonographic calcaneal ossification staging was comparable across the 3 raters (radiographs, κ = 0.692, z = 9.02; P < .01; sonographs, κ = 0.713, z = 7.95; P < .01), and perfect relative agreement (κ = 1.0, z = 10.6; P < .01). Consensus scores for radiographic and sonographic staging had moderate (κ = 0.535, z = 4.2; P < .01, and perfect relative (100% relative agreement, z = 6.22; P < .01) agreement. Conclusion: Sonographic evaluations of calcaneal ossification staging was comparable across assessors, and similar to radiographic staging. Clinical Relevance: Clinicians may consider incorporating ultrasound imaging for calcaneal ossification staging for young patients.
Incident prescriptions for common cardiovascular medications: comparison of recent versus pre-2020 medication adherence and discontinuation in three universal health care systems
Authors: McNaughton Candace D. , Austin Peter C. , Jackevicius Cynthia A. , Chu Anna , Holodinsky Jessalyn K. , Hill Michael D. , Norris Colleen M. , Kumar Mukesh , Kamal Noreen , Lee Douglas S. , Khan Nadia , Vyas Manav V. , Joundi Raed A. , Kapral Moira K. , Yu Amy Y. X. 
Published: February 2025

Abstract

Background
Health system disruptions since onset of the COVID-19 pandemic may have adversely impacted adherence to medications for common cardiovascular risk factors.

Methods
We examined adherence to and discontinuation of incident prescriptions for medications treating hypertension, dyslipidemia, diabetes, and atrial fibrillation in Ontario, Alberta, and Nova Scotia, Canada. We compared the recent period (April 1, 2020 through most recently available follow-up: September 30, 2021 for Ontario; March 31, 2021 for Alberta; and March 31, 2022 for Nova Scotia) to the baseline, pre-pandemic period (April 1, 2014 through March 31, 2019). In each province, people aged ≥66 years with a valid health number and corresponding incident prescription were included. For each medication class, adherence in the recent period, defined as ≥ 0.80 proportion-of-days-covered (PDC), was compared to the pre-pandemic period using modified Poisson regression with robust error variance, adjusted for patient characteristics. Similarly adjusted Cox proportional hazards models compared hazard of discontinuation over one year of follow-up between the two time periods.

Results
In the recent period, PDC ranged from 48.9% for dyslipidemia medications in Alberta to 82.2% for anticoagulants in Nova Scotia. Adherence was not different between periods, with the following exceptions: higher adherence in the recent period for antihypertensives (adjusted risk ratios [aRR] 1.08, 95% CI 1.06–1.10) and dyslipidemics (aRR 1.07, 95% CI 1.04–1.09) in Nova Scotia, and for antihyperglycemics (aRR 1.10, 95% CI 1.08–1.14) and anticoagulants (1.15, 95% CI 1.12, 1.18) in Alberta. Adherence was lower in the recent period only for antihypertensives in Alberta (aRR 0.95, 95% CI 0.93, 0.97). One-year rates of discontinuation ranged from 20.9% for anticoagulants in the Alberta recent period to 56.7% for antihypertensives in the Ontario baseline period. The adjusted hazard of discontinuation was lower or unchanged in the recent period for all medication classes.

Conclusions
Despite significant health system disruptions since 2020, recent adherence to incident cardiovascular prescriptions was similar or better than before and rates of medication discontinuation were lower. However, interventions are still needed to improve existing, suboptimal adherence.
A population-based study on the burden of hospitalized pediatric pneumococcal disease in Taiwan before and after the introduction of 13-valent pneumococcal conjugate vaccine into the childhood immunization program in 2015
Authors: Yen Ting-An , Wu Jhong-Lin , Wang Chi-Chuan , Huang Ling-Ya , Yeo See-Hwee , Patel Dony , Lim Cindy Thiow Koon , Lin Hung-Wei , Yamada Eriko , Sukarom Isaya 
Published: February 2025

Abstract

Background
To estimate the burden of invasive pneumococcal disease, non-bacteremic pneumococcal pneumonia, and acute otitis media before and after inclusion of the 13-valent pneumococcal vaccine (PCV13) into Taiwan’s Childhood Immunization Program in 2015.

Methods
Episodes of eligible children aged < 18 years hospitalized with invasive pneumococcal disease, non-bacteremic pneumococcal pneumonia, or acute otitis media between 1 January 2011 and 31 December 2019 were identified from the National Health Insurance Research Database. Annual hospitalized incidence rate, case fatality rate, and healthcare resource utilization and costs were estimated. Incidence time trends were assessed with interrupted time series analyses.

Results
1,284 invasive pneumococcal disease episodes, 25,074 non-bacteremic pneumococcal pneumonia episodes, and 23,139 acute otitis media episodes were identified. The overall annual incidence rates of invasive pneumococcal disease, non-bacteremic pneumococcal pneumonia, and acute otitis media were 3.31, 64.61, and 59.62 episodes per 100,000 person-years, respectively. Interrupted time series analyses results showed a significantly lower baseline incidence rate (incidence rate ratio [IRR]:0.58, p-value = 0.001) for invasive pneumococcal disease, and significantly higher baseline incidence rate (IRR:1.17, p-value < 0.001) for non-bacteremic pneumococcal pneumonia in the post-PCV13 period. Baseline incidence rates between the two periods were comparable for acute otitis media. A significant increase in trend of incidence rate was observed for all three diseases. Case fatality rate was 1.79%, 0.09%, and 0.00% for invasive pneumococcal disease, non-bacteremic pneumococcal pneumonia, and acute otitis media, respectively. Median length of hospitalization per inpatient visit was comparable between the two periods for invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia, but significantly shorter in the post-PCV13 period for acute otitis media. In the post-PCV13 period, average total costs per episode was lower for invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia, but higher for acute otitis media.

Conclusions
Residual clinical and economic burden of pneumococcal diseases remained substantial after PCV13 inclusion into Taiwan’s Childhood Immunization Program. To further reduce the disease burden among children, additional research to investigate the cause of increasing trends of hospitalized invasive pneumococcal disease, non-bacteremic pneumococcal pneumonia and acute otitis media in the post-PCV13 era will be required.
Donafenib combined with sintilimab for advanced hepatocellular carcinoma: a single arm phase II trial
Authors: Hong Xiaoyang , Guo Yongjian , Shi Wenbo , Zhu Kangshun , Liang Licong , Lin Liteng , Chen Ye , Zhou Jingwen , Huang Jingjun , Huang Jiabai , Wu Yaozhu , Huang Wensou , Cai Mingyue 
Published: February 2025

Abstract

Background
Previous studies evaluating antiangiogenic agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma (HCC) have shown encouraging results. This study was conducted to investigate the efficacy and safety of donafenib combined with sintilimab (Don-Sin) for advanced HCC.

Methods
This was a single-center, single-arm phase II trial recruiting patients with BCLC stage C HCC. A safety run-in cohort was planned with the first 6 patients receiving oral donafenib 200 mg twice daily and intravenous sintilimab 200 mg once every 3 weeks. Dose-limiting toxicities (DLTs) were evaluated to determine the recommended dose of donafenib for those enrolled thereafter. The primary endpoint of this study was progression-free survival (PFS) per mRECIST.

Results
30 patients were enrolled. As 3 patients (50.0%) experienced DLTs during safety run-in, the initial dose of donafenib was adjusted to 200 mg once daily for subsequent patients. The primary endpoint was met with a median PFS of 6.2 (95% confidence interval [CI], 4.4-8.0) months per mRECIST (6.3 [95% CI, 5.4–7.2] months per RECIST 1.1). The objective response rate was 23.3% per mRECIST and 16.7% per RECIST 1.1, while the disease control rate reached 76.7% per mRECIST/RECIST 1.1. The median overall survival was 16.0 (95% CI, 13.5–18.5) months. Treatment-related adverse events (TRAEs) occurred in 28 patients (93.3%) and grade 3 TRAEs were observed in 9 patients (30.0%).

Conclusions
Don-Sin showed promising antitumor effects with an acceptable safety profile in patients with advanced stage HCC. The preliminary findings need to be further evaluated in phase III randomized controlled trials.

Trial registration
ClinicalTrials.gov (identifier: NCT05162352; date of registration: December 4, 2021).
The relationship between vision status and its influencing factors among primary and secondary school students: The masking effect of physical activity level and the moderating effect of academic stress
Authors: Xu Jiyan , Li Yanjun , Ma Siyuan , Dai Shimeng , Xu Weiwei , Sang Mengjiao , Feng Kaijie 
Published: February 2025

Abstract

Background
The global youth myopia rate continues to rise, and the vision health of primary and secondary school students has become a global concern. This cross-sectional study aims to explore the vision status of primary and secondary school students in the Ningxia Hui Autonomous Region, China, and its internal relationship with influencing factors under regional characteristics.

Methods
A survey was conducted among 1,670 primary and secondary school students in the Ningxia Hui Autonomous Region of China using a snapshot method and random sampling techniques from September to October 2023. The survey instruments included vision examination, the International Physical Activity Questionnaire, the Lifestyle Behavior Scale, and the Student Academic Stress Questionnaire. The data was tested with descriptive statistics, difference test, correlation analyses, regression analyses, and so on using SPSS 25.0 and SPSSAU, and the target model was established and tested for the goodness-of-fit with AMOS 23.0.

Results
There was a significant negative correlation between vision status and lifestyle behaviors (r=-0.360, p < 0.01), physical activity level (r=-0.058, p < 0.05). The physical activity level played a significant masking effect between lifestyle behaviors and vision status (a*b = 0.002, c’=-0.044), and academic stress played a moderating role in the process of lifestyle behaviors affecting physical activity level and vision status. A moderated mediator model was constructed and fitted well (RMSEA = 0.028, CFI = 0.953, NFI = 0.934).

Conclusions
The prevalence rate of myopia among primary and secondary school students in Ningxia Hui Autonomous Region is lower than the national average, and its prevalence is related to lifestyle behaviors, physical activity level, and academic stress. The impact of lifestyle behaviors on vision status is controlled by physical activity level and academic stress. A strategy of coordinated education involving families, schools, and communities should be implemented. Parents should avoid having excessive expectations and additional academic burdens on their children and encourage them to actively participate in sports; schools should fully implement the ‘’Double Reduction’’ policy, making myopia prevention and control an important part of health education; communities should carry out publicity work for myopia prevention and control, raising adolescents’ awareness of eye health.
Effect of different ceramic materials and dentin sealing on occlusal veneers bond strength and fracture resistance
Authors: Nasr Dina Mohamed , AboElHassan Rewaa Gaber 
Published: February 2025

Abstract

Background
The effect of immediate dentin sealing (IDS) or delayed dentin sealing (DDS) on bond strength of different ceramic occlusal veneer restorations, was not examined yet, but the digital quantification of surface area of preparations helped in the calculation of the actual bond strength of these restorations, besides that, dentin sealing could influence the fracture resistance values of different ceramic occlusal veneer restorations.

This study aimed to examine the effect of different dentin sealing strategies and different restorative materials on the debonding forces, bond strength and fracture resistance of occlusal veneer restorations.

Materials and methods
Human mandibular molars (N = 64/test) were prepared for occlusal veneer restorations fabricated from Lithium disilicate ceramic (LS) (control group), Zirconia-reinforced lithium Silicate ceramic (ZLS), High translucent zirconia ceramic (HZ), and Resin nano ceramic (LU) (n = 16). Each material was subdivided according to IDS or DDS application, (n = 8). Bond strength testing and fracture resistance values were measured using universal testing machine. Two-way ANOVA was performed to investigate the effects of the two variables, dentin sealing and material selection, and their interaction (α = 0.05), followed by One-way ANOVA and post hoc or Student t-test for further determination of significance.

Results
For debonding forces and bond strength testing there were significant differences regarding different materials and dentin sealing strategies, while for fracture resistance, the material selection had a significant effect on it with no significant effects of dentin sealing strategies. The interaction between materials and dentin sealing showed no significant differences concerning all tests. For debonding forces and bond strength there was a higher result related to IDS application than DDS (p < 0.001*), and there was a significant effect of material selection on them (LS > ZLS > HZ > LU), (p = 0.001*). Regarding the fracture resistance there was significant increase of all studied materials than LU (p = 0.002*).

Conclusion
Immediate dentin sealing increased the required debonding forces of occlusal veneers made of different materials and their bond strength without significant effect on their fracture resistance, however this improvement was found to be material dependant. All the used materials can withstand lateral and occlusal forces higher than the values recommended for restoring posterior teeth.
Healthcare trajectories of aging individuals during their last year of life: application of process mining methods to administrative health databases
Authors: Bosson-Rieutort Delphine , Langford-Avelar Alexandra , Duc Juliette , Dalmas Benjamin 
Published: February 2025

Abstract

Context
World is aging and the prevalence of chronic diseases is raising with age, increasing financial strain on organizations but also affecting patients’ quality of life until death. Research on healthcare trajectories has gained importance, as it can help anticipate patients’ needs and optimize service organization. In an overburdened system, it is essential to develop automated methods based on comprehensive and reliable and already available data to model and predict healthcare trajectories and future utilization. Process mining, a family of process management and data science techniques used to derive insights from the data generated by a process, can be a solid candidate to provide a useful tool to support decision-making.

Objective
We aimed to (1) identify the healthcare baseline trajectories during the last year of life, (2) identify the differences in trajectories according to medical condition, and (3) identify adequate settings to provide a useful output.

Methods
We applied process mining techniques on a retrospective longitudinal cohort of 21,255 individuals who died between April 1, 2014, and March 31, 2018, and were at least 66 years or older at death. We used 6 different administrative health databases (emergency visit, hospitalisation, homecare, medical consultation, death register and administrative), to model individuals’ healthcare trajectories during their last year of life.

Results
Three main trajectories of healthcare utilization were highlighted: (i) mainly accommodating a long-term care center; (ii) services provided by local community centers in combination with a high proportion of medical consultations and acute care (emergency and hospital); and (iii) combination of consultations, emergency visits and hospitalization with no other management by local community centers or LTCs. Stratifying according to the cause of death highlighted that LTC accommodation was preponderant for individuals who died of physical and cognitive frailty. Conversely, services offered by local community centers were more prevalent among individuals who died of a terminal illness. This difference is potentially related to the access to and use of palliative care at the end-of-life, especially home palliative care implementation.

Conclusion
Despite some limitations related to data and visual limitations, process mining seems to be a method that is both relevant and simple to implement. It provides a visual representation of the processes recorded in various health system databases and allows for the visualization of the different trajectories of healthcare utilization.
Targeting the G-quadruplex as a novel strategy for developing antibiotics against hypervirulent drug-resistant Staphylococcus aureus
Authors: Sultan Maria , Razzaq Maria , Lee Joohyun , Das Shreyasi , Kannappan Shrute , Subramani Vinod Kumar , Yoo Wanki , Kim Truc , Lee Hye-Ra , Chaurasia Akhilesh K. , Kim Kyeong Kyu 
Published: February 2025

Abstract

Background
The rapid emergence of multiple drug-resistant (MDR) bacterial pathogens and the lack of a novel antibiotic pipeline pose a serious threat to global healthcare. The limited number of established targets further restricts the identification of novel antibiotics to treat life-threatening MDR infections caused by Staphylococcus aureus strains. Therefore, novel targets for developing antibiotics are urgently required. In this study, we hypothesized that the G-quadruplex (G4)-binding ligands can be used as novel antibiotics as their binding can possibly downregulate/block the expression of vital genes.

Methods
To test this, first we screened the antibiotic properties of representative G4-binding ligands against hypervirulent and MDR S. aureus USA300 and determined the in vitro and in vivo antibacterial activity; and proposed the mechanism of action by applying various microbiological, infection, microscopic, and biophysicochemical techniques.

Results
Herein, among screened G4-binding ligands, N-methyl mesoporphyrin IX (NMM) showed the highest antibacterial activity against S. aureus USA300. NMM exhibited a minimum inhibitory concentration (MIC) of 5 μM against S. aureus USA300, impacting cell division and the cell wall by repressing the expressions of genes in the division cell wall (dcw) gene cluster. Genome-wide bioinformatics analysis of G4 motifs and their mapping on S. aureus genome, identified the presence of G4-motif in the promoter of mraZ, a conserved master regulator of the dcw cluster regulating the coordinated cell division and cell wall synthesis. Physicochemical assessments using UV–visible, circular dichroism, and nuclear magnetic resonance spectroscopy confirmed that the G4-motif present in the mraZ promoter formed an intramolecular parallel G4 structure, interacting with NMM. In vivo reporter followed by coupled in vitro transcription/translation (IVT) assays confirmed the role of mraZ G4 as a target interacting NMM to impose extreme antibacterial activity against both the gram-positive and -negative bacteria. In-cell and in vivo validation of NMM using RAW264.7 cells and Galleria mellonella; respectively, demonstrated that NMM exhibited superior antibiotic activity compared to well-established antibiotics, with no observed cytotoxicity.

Conclusions
In summary, the current study identified NMM as a broad-spectrum potent antibacterial agent and elucidated its plausible mechanism of action primarily by targeting G4-motif in the mraZ promoter of the dcw gene cluster.
Extracellular vimentin is a damage-associated molecular pattern protein serving as an agonist of TLR4 in human neutrophils
Authors: Suprewicz Łukasz , Fiedoruk Krzysztof , Skłodowski Karol , Hutt Evan , Zakrzewska Magdalena , Walewska Alicja , Deptuła Piotr , Lesiak Agata , Okła Sławomir , Galie Peter A. , Patteson Alison E. , Janmey Paul A. , Bucki Robert 
Published: February 2025

Abstract

Background
Vimentin is a type III intermediate filament protein that plays an important role in cytoskeletal mechanics. It is now known that vimentin also has distinct functions outside the cell. Recent studies show the controlled release of vimentin into the extracellular environment, where it functions as a signaling molecule. Such observations are expanding our current knowledge of vimentin as a structural cellular component towards additional roles as an active participant in cell signaling.

Methods
Our study investigates the immunological roles of extracellular vimentin (eVim) and its citrullinated form (CitVim) as a damage-associated molecular pattern (DAMP) engaging the Toll-like receptor 4 (TLR4) of human neutrophils. We used in vitro assays to study neutrophil migration through endothelial cell monolayers and activation markers such as NADPH oxidase subunit 2 (NOX2/gp91phox). The comparison of eVim with CitVim and its effect on human neutrophils was extended to the induction of extracellular traps (NETs) and phagocytosis of pathogens.

Results
Both eVim and CitVim interact with and trigger TLR4, leading to increased neutrophil migration and adhesion. CitVim stimulated the enhanced migratory ability of neutrophils, activation of NF-κB, and induction of NET formation mainly mediated through reactive oxygen species (ROS)-dependent and TLR4-dependent pathways. In contrast, neutrophils exposed to non-citrullinated vimentin exhibited higher efficiency in favoring pathogen phagocytosis, such as Escherichia coli and Candida albicans, compared to CitVim.

Conclusions
Our study identifies new functions of eVim in its native and modified forms as an extracellular matrix DAMP and highlights its importance in the modulation of immune system functions. The differential effects of eVim and CitVim on neutrophil functions highlight their potential as new molecular targets for therapeutic strategies aimed at regulation of neutrophil activity in different pathological conditions. This, in turn, opens new windows of therapeutic intervention in inflammatory and immunological diseases characterized by immune system dysfunction, in which eVim and CitVim play a key role.