bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dioscin pretreatment ameliorates ferroptosis in cardiomyocytes after myocardial infarction via inhibiting endoplasmic reticulum stress
Authors: Wu Chang , Shen Xueping , Lou Pan , Song Dongyan 
Published: January 2025

Abstract

Background
Myocardial infarction (MI) remains a leading cause of mortality globally, often resulting in irreversible damage to cardiomyocytes. Ferroptosis, a recently identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a significant contributor to post-MI cardiac injury. The endoplasmic reticulum (ER) stress response has been implicated in exacerbating ferroptosis.

Methods
Here, we investigated the potential of Dioscin, a natural compound known for its diverse pharmacological properties, in mitigating ferroptosis in cardiomyocytes following MI by targeting ER stress.

Results
In animal models subjected to MI, administration of Dioscin notably improved cardiac function, reduced infarct size by approximately 24%, and prevented adverse remodeling, highlighting its therapeutic potential. Through in vitro and in vivo models of MI, we demonstrated that Dioscin treatment significantly attenuates ferroptosis in cardiomyocytes, as evidenced by a decrease in lipid peroxidation by about 19% and preserved mitochondrial integrity. Moreover, Dioscin exerted its protective effects by inhibiting ER stress markers, such as the phosphorylation levels of PERK and eIF2α proteins, and the expression levels of BIP and ATF4 proteins, thus disrupting the ER stress-mediated signaling cascade associated with ferroptosis.

Conclusion
Overall, our findings suggested that Dioscin holds promise as a therapeutic agent against post-MI cardiac injury by mitigating ferroptosis via the suppression of ER stress. Further investigations into the precise molecular mechanisms and clinical translation of Dioscin’s cardioprotective effects are warranted, offering a potential avenue for novel therapeutic interventions in MI-related cardiac complications.

Graphical Abstract
Is the treatment of ankle osteoarthritis changing over time in Italy? Analysis of temporal trends for fusion and arthroplasty in a population-based study from 2001 to 2022 on the National Hospital Discharge Record database
Authors: Cuccu Adriano , Samaila Elena Manuela , Ciminello Enrico , Alfieri Montrasio Umberto , Cortese Fabrizio , Ceccarelli Stefania , Falcone Tiziana , Torre Marina 
Published: January 2025

Abstract

Background
Treatment of ankle osteoarthritis by total ankle replacement (TAR) is increasing worldwide. The aim of the study was to present the overall temporal trends of TAR throughout 22 years (2001–2022) in Italy, analyzing the distributions of hospitals by volume of activity and patients by age and sex, drawing on the National Hospital Discharge Record database. Furthermore, as a secondary aim, we compared these trends with those of ankle fusions.

Materials and methods
International Classification of Diseases, 9th Revision, Clinical Modification (ICD9-CM) codes of interest were identified to browse the Italian National Hospital Discharge Record database. Surgical volumes, trends over time, classes of hospital activity volume, sex and age of patients, and population incidence rates were described. The statistical significance of time series trends was assessed by the Cox–Stuart test with randomness as a null hypothesis.

Results
20,248 ankle procedures (total ankle replacements 8853 and ankle fusions 11,395) were extracted from 231,601,523 admissions registered nationally from 2001 to 2022. The yearly total number of TARs significantly increased almost tenfold from 96 to 996 (p < 0.05), while the number of fusions exhibited a stationary behavior (p > 0.05). The increased trend in TAR procedures was concentrated mostly in the North of Italy, with predominantly males between 55 and 64 years of age. The analysis of the number of procedures performed on inhabitants by region and that performed by all the hospitals in the region showed a different pattern across Italy.

Conclusions
The substantial increase in TARs may be owing to improved implant designs and innovative surgical technologies, which allow the treatment of more severe cases and deformities, previously untreated or treated by a fusion. This trend highlights the need to invest in implementing high quality registries by promoting surgeons’ participation in data collection.

Level of evidence: population based study, level 1 evidence.
Modeling and simulation of distribution and drug resistance of major pathogens in patients with respiratory system infections
Authors: Yang Li , Liang Ermin , Gao Yali 
Published: January 2025

Abstract

Background
Respiratory tract infections (RTIs) are one of the leading causes of morbidity and mortality worldwide. The increase in antimicrobial resistance in respiratory pathogens poses a major challenge to the effective management of these infections.

Objective
To investigate the distribution of major pathogens of RTIs and their antimicrobial resistance patterns in a tertiary care hospital and to develop a mathematical model to explore the relationship between pathogen distribution and antimicrobial resistance.

Methods
Five hundred patients with RTIs were included in the study and 475 bacterial strains were isolated from their respiratory specimens. Antimicrobial susceptibility testing and analysis of influencing factors were performed. A mathematical model was developed to simulate the relationship between pathogen distribution and drug resistance.

Results
The most common pathogens were Streptococcus pneumoniae (30%), Haemophilus influenzae (20%), Pseudomonas aeruginosa (15%), Staphylococcus aureus (10%) and Klebsiella pneumoniae (10%). The distribution of pathogens varied according to age group and type of RTIs, with higher proportions of Pseudomonas aeruginosa and Staphylococcus aureus in hospital-acquired and ventilator-associated pneumonia. Isolated pathogens showed high and increasing rates of resistance to commonly used antibiotics. Model simulations suggest that a shift in the distribution of pathogens toward more resistant strains may lead to a significant increase in overall resistance rates, even if antibiotic use patterns remain unchanged.

Conclusion
This study emphasizes the importance of regular monitoring of respiratory pathogen distribution and antimicrobial resistance patterns and the need for a comprehensive approach to managing RTIs, including implementation of antibiotic stewardship programs, infection control measures, and development of new therapies.
Methodological considerations for estimating indirect costs in children and adolescents with chronic conditions: a scoping review
Authors: Kitschen Anne , Asegu Lulseged M. , Sauerland Dirk 
Published: January 2025

Abstract

Background
In children and adolescents, the prevalence of chronic diseases, e.g., obesity, asthma, and attention-deficit/hyperactivity disorder (ADHD), has increased in the last decades. These diseases have negative effects on patients and their families and pose a significant economic burden. Indirect costs related to caregivers’ lost workdays or children’s and adolescents’ missed education are likely to be high. However, there are no guidelines for measuring and valuing indirect costs in this population. Thus, this scoping review aims to examine methods in published articles, compare these approaches, and analyze benefits and shortcomings.

Methods
The systematic literature search was conducted in Medline, PsycINFO, Embase, NHS EED, and the HTA Database considering all articles from inception until 16 October 2024. Two researchers independently screened title, abstract, and full text. Cost-of-illness studies (COIs) reporting indirect costs for obesity, asthma, or attention-deficit/hyperactivity disorders (ADHD) in children and adolescents up to 24 years were included. Only studies published in English or German were considered. Methodological characteristics, measurement of indirect costs, cost components, data source, and costing methods were extracted.

Results
The literature search revealed 45 studies. Thirty-two articles on asthma, eight on ADHD, and five on obesity were included. While all studies included absenteeism, only a few assessed and valued unpaid work (31.1%) or presenteeism (13.3%). Overall, 88.9% of the studies considered indirect costs for caregivers. Additionally, 51.1% considered productivity losses for children and adolescents, with 47.8% of these studies assigning a monetary value to these losses. The largest share of studies (53.3%) considered indirect costs by measuring and valuing caregivers’ lost work time.

Discussion
In conclusion, various methodologies were used to consider indirect costs for chronic diseases in children and adolescents, underlining the need for standardization. This scoping review presents methodologies for incorporating indirect costs in COIs and other types of economic evaluations, which focus on children and adolescents and adopt a societal perspective. These indirect costs include both paid and unpaid activities, as well as absenteeism and presenteeism, not only for caregivers but also for children and adolescents themselves.
Institutional, neighborhood, and life stressors on loneliness among older adults
Authors: Tsuchiya Kazumi , Thierry Amy Danielle , Taylor Harry Owen 
Published: January 2025

Abstract

Background
Loneliness is a public health epidemic in the United States (US), with older adults being vulnerable to experiencing loneliness. Predictors of loneliness are less understood among racial/ethnic groups of US older adults, and few studies have included perceived institutional discrimination (PID), stressful life events (SLE), and perceived neighborhood characteristics (PNC) as antecedent stressors of loneliness in diverse older adult samples. Our study assessed the relationship between these stressors and loneliness among specific racial/ethnic groups of older adults.

Methods
We used the Health and Retirement Study data (n = 9,904) to examine whether PID, SLE, and PNC were associated with loneliness. Loneliness was measured using the 11-item UCLA Loneliness Scale. PID included unfairly not hired for a job, unfairly prevented from moving into a neighborhood, and unfairly treated by the police. SLE included moving to a worse neighborhood/residence, being robbed or burglarized, and unemployed/looking for a job. PNC were measured as discohesion and disorder. Lagged multivariate linear regression models regressed loneliness (2014/2016 HRS waves) on PID, SLE and PNC (2010/2012 HRS waves) measured as cumulative totals and individual items. Models were stratified by Black (BOAs), Hispanic/Latinx (HOAs), and White (WOAs) older adults.

Results
Cumulative totals of PID, SLE, and neighborhood discohesion were associated with loneliness among BOAs while only discohesion was associated with loneliness among HOAs. Cumulative totals for PID, SLE, and PNC were associated with loneliness among WOAs. Individual stressors predicting loneliness for BOAs were moving to a worse residence and being robbed/burglarized. For HOAs, being prevented from moving to a neighborhood was associated with greater loneliness while being robbed/burglarized was associated with less loneliness. Individual stressors predicting greater loneliness for WOAs were being unfairly not hired for a job, receiving unfair treatment during police encounters, and moving to a worse residence.

Conclusions
Our study finds racial/ethnic variation in psychosocial stressors predicting loneliness four years later. Nevertheless, neighborhood discohesion was the most salient stressor and was associated with greater loneliness across all racial/ethnic groups. Future research and interventions should consider the differing stress appraisal processes across groups and to support the development of resources and policies to ameliorate loneliness among diverse older adults.
Game-thinking; utilizing serious games and gamification in nursing education – a systematic review and meta-analysis
Authors: Nylén-Eriksen Mats , Stojiljkovic Marko , Lillekroken Daniela , Lindeflaten Katrin , Hessevaagbakke Elisabeth , Flølo Tone Nygaard , Hovland Olav Johannes , Solberg Ada Marie Svarstad , Hansen Sylvia , Bjørnnes Ann Kristin , Tørris Christine 
Published: January 2025

Abstract

Background
The digital shift in higher education is moving from teacher-focused models to active learning with digital technologies, including the integration of game-based learning strategies. We aim to identify, assess, and summarize the findings of evidence and determine the effectiveness of game-thinking on learning outcomes in nursing education.

Methods
A comprehensive search for relevant literature was conducted between April and May 2022 Seven databases ERIC, Scopus, ProQuest Education Source, MEDLINE, CINAHL, Web of Science, and Embase were utilized to locate original, peer-reviewed papers published in English. The review was conducted and reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.

Results
Overall, 3302 studies were initially screened based on their titles and abstract. From this selection 281 studies were then assessed for full-text eligibility. In the end, 70 studies, consisting of 27 Randomized Controlled Trials (RCTs) and 43 Quasi-experimental studies were included in the review. These studies encompassed data from a total of 8348 participants. The results from the narrative synthesis of the results revealed consistencies across the included studies and their findings. The meta-analysis suggested that game-thinking could be beneficial in nursing education, notably improving students’ academic achievement (Pooled ES = 0.99, [95%CI 0.53, 1.44]). The most significant effect of game-thinking on academic achievement was observed in the academic knowledge performance of nursing students (Pooled ES = 1.06, [95%CI 0.55, 1.57]), followed by academic skill performance (Pooled ES = 0.54, [95%CI 0.06, 1.03]).

Conclusions
The systematic review and meta-analysis provide evidence supporting the effectiveness of game-thinking in nursing education. The findings highlight the potential of game-based learning in enhancing nursing education through knowledge acquisition, albeit with a nuanced effect on skill development. As nursing education continues to adapt to the digital era, integration of game-thinking strategies could serve as a valuable method for creating engaging and effective learning experiences for nursing students.
Factors affecting the prolongation of mechanical ventilation in patients after cardiac surgery
Authors: Kermani Mahdieh Sharifzadeh , Dehesh Tania , Pouradeli Shiva , Esmaili Bahareh Soltani 
Published: January 2025

Abstract

Background
This study aimed to investigate the major predictive factors associated with prolonged mechanical ventilation(PMV) following cardiac surgery.

Methods
This retrospective, cross-sectional, descriptive-analytical study was conducted from September 2021 to March 2022, involving 244 patients who underwent cardiac surgery. PMV was defined as mechanical ventilation for more than 24 h. Potential risk factors before, during, and after surgery were examined and recorded. Logistic regression analysis was performed to assess the relationship between demographic, clinical variables, and prolonged mechanical ventilation. A significance level of 0.05 was used for data analysis.

Results
The study population consisted of 68.4% male and 31.6% female patients, with 86.9% undergoing CABG surgery. PMV was observed in 13.1% of the patients. The findings revealed that the incidence of postoperative pneumonia increased the likelihood of PMV by more than 7 times [OR = 7.24, 95% CI=(5.12,8.14), P-value = 0.001]. Similarly, respiratory failure was associated with a 7.5-fold increase in the odds of PMV [OR = 7.56, 95% CI=(4.48,8.77), P-value = 0.042]. Drainage of one liter of blood on the first postoperative day increased the risk of PMV by 2.2 times [OR = 2.21, 95% CI=(1.98,2.46), P-value = 0.032], and the use of epinephrine was associated with a 2.73-fold increase in the odds [OR = 2.73, 95% CI=(2.24,3.11), P-value = 0.022]. Risk of PMV in the patients who had cardiac dysfunctin increased by more than 2 times.[OR = 2.58, 95%; CI = (1.33.2.87); P-value = 0.042]. In the patients need an Intra Aortic Balloon Pump(IABP) risk of PMV increased by more than 2 times. (OR = 2.74,95%,CI = 1.36,5.47: Pvalue = 0.03). The risk of PMV in the patients who had cerebrovascular accident(CVA) increased by more than three times [OR = 3.75, 95% CI = 1.26,4.84; P-value = 0.044]. For each unit increase in Euro Score 2 the chance of PMV increased by 1.38 TIMES. Furthermore ICU Mortality had a significant relationship with PMV.(Pvalue < 0.001).

Conclusion
The study identified postoperative complications, such as pneumonia, respiratory failure, high drainage, need to an IABP, higher EURO Score 2, Cardiac dysfunction, CVA and the use of epinephrine, as independent risk factors for PMV following cardiac surgery.
Avascular necrosis in pediatric rheumatic diseases: an Italian retrospective multicentre study
Authors: Taietti Ivan , Zini Federico , Conti Emilio Amleto , Cristini Enrica , Borzani Irene , Ramponi Giulia , Bracaglia Claudia , Pecoraro Raffaele , Papa Riccardo , Tibaldi Jessica , Pastore Serena , Simonini Gabriele , Cattalini Marco , Meini Antonella , Marino Achille , Lanni Stefano , Minoia Francesca , Filocamo Giovanni 
Published: January 2025

Abstract

Background
Atraumatic avascular necrosis (AVN) is a severe condition that may complicate the course of rheumatic diseases and contribute to long-term damage. However, there is a lack of evidence on this rare event in pediatric rheumatology. The aim of our study was to evaluate the occurrence of avascular necrosis in the context of rheumatologic diseases in Italy and to describe the main demographic and clinical features of AVN patients, with a particular focus on treatment background.

Methods
All centres part of the Italian Society of Pediatric Rheumatology were invited to participate in a retrospective case collection of children with rheumatic diseases complicated by a pediatric-onset AVN. Demographic, clinical, laboratory and imaging data were recorded, together with outcome and treatment background, particularly steroid exposure. Population collected was further evaluated according to the different underlying rheumatologic disease and to the time of AVN onset.

Results
Fourteen patients (SLE = 7; JIA = 4; others = 3) were collected from 7 centres. Females were predominantly affected (71%) with a median age at AVN diagnosis of 14.3 years. Multifocal involvement was mostly reported (93%), mainly involving femoral heads (44%) and knees (28%). All patients had a severe rheumatologic background and received systemic glucocorticoids with a median cumulative prednisone equivalent dose of 457.5 mg/kg. In all patients but one imaging showed persistence of abnormalities, despite the complete resolution of symptoms in 6 of them. Bisphosphonates were the most used therapeutic approach; orthopedic surgery was required in 2 cases.

Conclusions
Despite its rarity, AVN may be a severe complication of pediatric rheumatic diseases. Active monitoring is crucial to promptly identify patients and to prevent long-term damage. Prospective large sample studies are required to better understand the impact of steroid exposure and its complex interplay with other potential contributing factors.
TAD-SIE: sample size estimation for clinical randomized controlled trials using a Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator
Authors: Lala Sayeri , Jha Niraj K. 
Published: January 2025

Abstract

Background
Phase-3 clinical trials provide the highest level of evidence on drug safety and effectiveness needed for market approval by implementing large randomized controlled trials (RCTs). However, 30–40% of these trials fail mainly because such studies have inadequate sample sizes, stemming from the inability to obtain accurate initial estimates of average treatment effect parameters.

Methods
To remove this obstacle from the drug development cycle, we present a new algorithm called Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator (TAD-SIE) that powers a parallel-group trial, a standard RCT design, by leveraging a state-of-the-art hypothesis testing strategy and a novel trend-adaptive design (TAD). Specifically, TAD-SIE uses synthetic intervention (SI) to estimate individual treatment effects and thereby simulate a cross-over design, which makes it easier for a trial to reach target power within trial constraints (e.g., sample size limits). To estimate sample sizes, TAD-SIE implements a new TAD tailored to SI given that using it violates assumptions under standard TADs. In addition, our TAD overcomes the ineffectiveness of standard TADs by allowing sample sizes to be increased across iterations without any condition while controlling significance level with futility stopping. Our TAD also introduces a hyperparameter that enables trial designers to trade off between accuracy and efficiency (sample size and number of iterations) of the solution.

Results
On a real-world Phase-3 clinical RCT (i.e., a two-arm parallel-group superiority trial with an equal number of subjects per arm), TAD-SIE obtains operating points ranging between 63% to 84% power and 3% to 6% significance level in contrast to baseline algorithms that get at best 49% power and 6% significance level.

Conclusion
TAD-SIE is a superior TAD that can be used to reach typical target operating points but only for trials with rapidly measurable primary outcomes due to its sequential nature. The framework is useful to practitioners interested in leveraging the SI algorithm for their study design.
Quantifying impacts of two ENSO patterns on South China sea summer monsoon onset
Authors: Zhang Lianyi , Lin Junshu , Chen Zesheng , Shi Yanping , Du Yan 
Published: January 2025

Abstract
The onset of the South China Sea (SCS) Summer Monsoon (SCSSM) is usually in May, strongly influencing the beginning of the wet season over the surrounding regions, such as South China and the Philippine Islands. The onset date is significantly affected by the El Niño-Southern Oscillation (ENSO), which manifests as two major types: the Eastern-Pacific (EP) and Central-Pacific (CP) patterns. However, the impacts of these patterns on the SCSSM onset await quantification. Here, using a novel statistical metric, binary combined linear regression, we find a dominant role of the CP pattern rather than the EP pattern, as a moderate CP El Niño/La Niña tends to cause SCSSM onset delay/advance by around 4.7/5.1 days in its decaying year. The anomalous SST structure of CP El Niño leads to persistent anomalous anti-cyclonic winds over the western North Pacific from April to June, suppressing the local convection and impeding the SCSSM winds. In comparison, the EP El Niño impact decays quickly in May and hardly affects the SCSSM onset. This, hence, weakens the relationship between the SCSSM onset and ENSO. These results help improve the SCSSM onset prediction by involving diverse ENSO impacts.
History of the Organisation for Economic Co-operation and Development (OECD) test guidelines for non-animal test methods in Japan
Authors: Kojima Hajime 
Published: January 2025

Abstract
The number of alternatives to animal tests (non-animal test methods) for human health developed globally account for more than 40% of the test methods in the Organisation for Economic Co-operation and Development (OECD) Guidelines for the Testing of Chemicals (TGs). Within the TGs, the National Institute of Health Sciences (NIHS) has standardized 16 OECD TGs for human health, implemented four major revisions, and developed one test method for the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) S10 guidelines on photosafety. This review describes trends in the OECD and Japan that mainly focus on international standardizations of non-animal test methods for human health. Drawing from this experience, I hope Japan will advance new approach methodologies for detecting systemic toxicity, which are in global demand.