bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resected EGFR-mutated non-small-cell lung cancers: incidence and outcomes in a European population (GFPC Exerpos Study)
Authors: Auliac Jean-Bernard , Thomas Pascal-Alexandre , Bylicki Olivier , Guisier Florian , Curcio Hubert , AlainVegnenègre  , Swalduz Aurelie , Wislez Marie , Le Treut Jacques , Decroisette Chantal , Basse Victor , Falchero Lionel , De Chabot Gonzague , Moreau Diane , Huchot Eric , Lupo Mansuet Audrey , Blons Helene , Chouaïd Christos , Greillier Laurent 
Published: March 2024

Background: Few epidemiological data are available on surgically treated Caucasian patients with non-small-cell lung cancers (NSCLCs) harboring epidermal growth factor receptor ( EGFR) mutations. The main objective of this study was to describe, in the real-world setting, these patients’ incidence, clinical, and tumoral characteristics. Methods: The participating centers included all consecutive localized non-squamous NSCLC patients undergoing surgery between January 2018 and December 2019 in France. EGFR status was determined retrospectively when not available before surgery. Results: The study includes 1391 no squamous NSCLC patients from 16 centers; EGFR status was determined before surgery in 692 (49.7%) of the cases and conducted as part of the study for 699 (50.3%); 171 (12.3%) were EGFR mutated; median age: 70 (range: 36–88) years; female: 59.6%; never smokers: 75.7%; non-squamous histology 97.7%, programmed death ligand-1 expression 0%/1–49%/⩾50 in 60.5%/25.7%/13.8%, respectively. Surgery was predominantly lobectomy (81%) or segmentectomy (14.9%), with systematic lymph node dissection in 95.9%. Resection completeness was R0 for 97%. Post-surgery staging was as follows: IA: 52%, IB: 16%, IIA: 4%, IIB: 10%, IIIA: 16%, and IIIB: 0.05%; EGFR mutation exon was Del19/exon 21 ( L858R)/20/18 in 37.4%/36.8%/14%, and 6.4% of cases, respectively; 31 (18%) patients received adjuvant treatment (chemotherapy: 93%, EGFR tyrosine kinase inhibitor: 0%, radiotherapy: 20%). After a median follow-up of 31 (95% confidence interval: 29.6–33.1) months, 45 (26%) patients relapsed: 11/45 (24%) locally and 34 (76%) with metastatic progression. Median disease-free survival (DFS) and overall survival were not reached and 3-year DFS was 60%. Conclusion: This real-world analysis provides the incidence and outcomes of resected EGFR-mutated NSCLCs in a European patient cohort.
Treatment of External Fixator Pin Tract Deep Infections With an Antibiotic “Sparkler”
Authors: Hlad Lee M. , Rizkalla Jacob N. , So Eric , Herzenberg John E. 
Published: March 2024

Pin tract infections are virtually universal complications with the use of external fixation. While most are superficial and respond to oral antibiotics and local care, septic loosening may occur at the bone–pin interface, which may lead to instability of the fixator, catastrophic failure, fracture, and long-term osteomyelitis. Classification systems and prevention protocols have been developed to address this ubiquitous complication. Treatment of severe pin tract infections often requires debridement, parenteral antibiotics, and removal of the offending pin or the entire external fixator. In cases of osteomyelitic pin tracks, a sizable cavity is often present. We describe a simple technique for treatment of deep bone pin tract infection through the use of debridement, irrigation, and an antibiotic “sparkler,” which is a specially prepared percutaneous implant of antibiotic laden bone cement. Levels of Evidence: Level 5
Association between high levels of nitrogen dioxide and increased cumulative incidence of lung cancer in patients with idiopathic pulmonary fibrosis
Authors: Yoon Hee-Young , Kim Sun-Young , Song Jin Woo 
Published: March 2024

BackgroundLung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. However, the association between individual exposure to air pollutants and lung cancer development in patients with IPF is unknown. This study aimed to assess the effect of individual exposure to nitrogen dioxide (NO2) on lung cancer development in patients with IPF.MethodsWe enrolled 1085 patients from an IPF cohort in the Republic of Korea (mean age 65.6 years, males 80.6%). We estimated individual-level long-term exposures to NO2at the patients' residential addresses using a national-scale exposure prediction model based on data from air quality regulatory monitoring stations. To evaluate the association between NO2levels and lung cancer development in IPF, we used an individual- and area-level covariates adjusted model as our primary model.ResultsThe estimated average annual NO2concentration was 23.1 ppb. During a median follow-up of 4.3 years, 86 patients (7.9%) developed lung cancer. NO2concentration was associated with lung cancer development in an unadjusted model (HR 1.219; p=0.042), while a marginal association was found in the primary model (HR 1.280; p=0.084). When NO2concentration was stratified by the median value (21.0 ppb), exposure to high NO2levels (≥21.0 ppb) was associated with a 2.0-fold increase in the risk of lung cancer development (HR 2.023; p=0.047) in the primary model.ConclusionIndividual exposure to high NO2levels may increase the risk of lung cancer development in patients with IPF.
Motivation and preferences for learning of patients with COPD or asthma and their significant others in pulmonary rehabilitation: a qualitative study
Authors: Muijsenberg Anouk J.L. , Haesevoets Sarah , Houben-Wilke Sarah , Tatousek Jan , Lacroix Joyca , Spruit Martijn A. , Janssen Daisy J.A. 
Published: March 2024

IntroductionAn in-depth understanding of educational needs from the perspective of learners in pulmonary rehabilitation is lacking. To improve learning in pulmonary rehabilitation, understanding of factors that induce or enhance intrinsic motivation in both patients and their significant others is needed. Therefore, this study aims to gain in-depth understanding of what motivates patients with COPD or asthma referred for pulmonary rehabilitation and their significant others to learn and what their preferences are for education.MethodsFor this qualitative study, a sample was taken from a previous quantitative study. Data was collected through one-time face-to-face semi-structured interviews. The interviews were transcribed and independently analysed by two researchers using thematic analyses.ResultsTwelve patients and four significant others (56% female; age: 63±11 years) were interviewed. Participants expressed a variety of information needs and learning preferences. Subthemes that emerged within the theme of motivation for learning were: 1) curiosity, such as knowledge gaps and hope for new information; and 2) values and goals, such as own health, caring for loved ones and spending time with family.DiscussionTo enhance intrinsic motivation for learning within pulmonary rehabilitation, autonomy of individuals should be supported by offering several learning topics and education adapted to preferences, while curiosity should be fostered by targeting information needs. Moreover, health education programmes should match with the personal values and goals of individuals, such as own health, caring for loved ones and spending time with family.
Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice
Authors: Wang Bo , Zhu Sheng , Guo Miao , Ma Run-Dong , Tang Ya-Ling , Nie Ya-Xiong , Gu Hong-Feng 
Published: March 2024

Abstract
Background
Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region.

Methods
STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe2+ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively.

Results
Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin.

Conclusion
Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.

Graphical Abstract
Associations of resistance training levels with low muscle mass: a nationwide cross-sectional study in Korea
Authors: Park Jae Ho , Lim Nam-Kyoo , Park Hyun-Young 
Published: March 2024

Abstract
Background
Low muscle mass is associated with adverse health outcomes such as functional decline and all-cause mortality. This study investigated the relationship between the risk of low muscle mass and the training period and/or frequency of resistance training (RT).

Methods
We included 126,339 participants (81,263 women) from nationwide cohorts in Korea. Low muscle mass was defined based on the fat-free mass index. To investigate the presence of an inverse dose–response relationship between RT levels and the risk of low muscle mass, the training period (months) and frequency (per week) of RT were used. Multiple logistic regression models were used to assess the risk of low muscle mass according to the RT levels.

Results
Prevalence rates for low muscle mass in our study population were 21.27% and 6.92% in men and women, respectively. When compared with not performing RT, performing RT for 3–4 days/week and ≥5 days/week decreased the risk of low muscle mass by 22% and 27%, respectively, and performing RT for 12–23 months and ≥24 months decreased the risk by 19% and 41%, respectively. When simultaneously considering both training period and frequency, performing RT for either 3–4 days/week or ≥5 days/week was significantly related to risk reduction, provided that the training period was at least 1 year. Importantly, performing RT for more than 2 years resulted in an additional risk reduction. However, there was no additional effect of performing RT for ≥5 days/week compared to 3–4 days/week, regardless of whether the RT duration was 1–2 years or more than 2 years.

Conclusions
Since performing RT for 5 days/week or more did not yield any additional effects on the risk of low muscle mass, performing RT for 3–4 days/week was sufficient to prevent low muscle mass. The effectiveness of this preventive measure can be further enhanced by engaging in long-term RT, specifically for more than 2 years.
Nano-enabled pesticides: a comprehensive toxicity assessment of tebuconazole nanoformulations with nematodes at single species and community level
Authors: Eghbalinejad Mahleh , Hofman Jakub , Kotouček Jan , Grillo Renato , Hochmanová Bílková Zuzana , Reiff Nicola , Höss Sebastian 
Published: March 2024

AbstractThere is an increasing imperative to explore safer alternatives for pesticides due to their indiscriminate use and consequential health impacts on the environment and humans. Nanoformulations of pesticides are being developed as potential alternatives due to their beneficial properties, including enhanced solubility, targeted delivery to the site of action, improved stability and efficacy and reduced non-target effects. Nevertheless, a comprehensive assessment is necessary for these emerging nanopesticides compared to existing formulations, aiming to ascertain whether their "nano" characteristics exacerbate toxicity for non-target organisms. This study investigated the toxicity of tebuconazole (TBZ) in different formulations, including nanoformulations (poly-ε-caprolactone [PCL] and nanostructured lipid carrier [NLC] loaded with TBZ), as well as a commercial formulation, on the reproduction of the nematode Caenorhabditis elegans in both aqueous and soil matrices. Additionally, the impact of the correspondent nanocarriers without TBZ on C. elegans was examined. In water, TBZ in the form of nano and commercial formulations exhibited higher toxicity on the nematodes' reproduction than the TBZ (a.s.) attributable to higher freely dissolved concentrations of TBZ, which resulted in a toxicity order, ranging from the most to the least toxic as follows: NLC-TBZ > PCL-TBZ > commercial formulation > TBZ (a.s.). For NLC-TBZ, the excess toxicity could be clearly explained by combined toxicity of TBZ (a.s.) and nanocarriers, with the effect addition of the separate single compounds matching the observed effects of the nanoformulation. For PCL-TBZ, effects were stronger than expected from the effect addition of TBZ (a.s.) and PCL nanocarriers, potentially due to enhanced bioavailability of encapsulated TBZ in the gut of the nematodes. In soil, NLC with and without loaded TBZ showed higher toxicity than other tested compounds, while PCL nanocarriers without TBZ did not exhibit negative effects on the reproduction of C. elegans. Microcosm experiment, where long-term effects on native soil nematode fauna were tested, confirmed that TBZ-nanoformulations act via combined toxic effects of TBZ and nanocarriers. These findings contribute valuable insights to understanding nanopesticides' ecotoxicity and underscore the need for harmonized regulatory assessments to evaluate these novel formulations adequately.
Unlocking potential biomarkers bridging coronary atherosclerosis and pyrimidine metabolism-associated genes through an integrated bioinformatics and machine learning approach
Authors: Bu Fanli , Qin Xiao , Wang Tiantian , Li Na , Zheng Man , Wu Zixuan , Ma Kai 
Published: March 2024

Abstract
Background
This study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS.

Methods
A set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets.

Results
This investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results.

Conclusion
In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis.
Applying Sydney Triage to Admission Risk Tool (START) to improve patient flow in emergency departments: a multicentre randomised, implementation study
Authors: Berendsen Russell Saartje , Seimon Radhika V , Dixon Emma , Murphy Margaret , Vukasovic Matthew , Bohlken Nicole , Taylor Sharon , Cooper Zoe , Scruton Jennifer , Jain Nitin , Dinh Michael M 
Published: March 2024

Abstract
Background
To determine the effectiveness of applying the Sydney Triage to Admission Risk Tool (START) in conjunction with senior early assessment in different Emergency Departments (EDs).

Methods
This multicentre implementation study, conducted in two metropolitan EDs, used a convenience sample of ED patients. Patients who were admitted, after presenting to both EDs, and were assessed using the existing senior ED clinician assessment, were included in the study. Patients in the intervention group were assessed with the assistance of START, while patients in the control group were assessed without the assistance of START. Outcomes measured were ED length of stay and proportion of patients correctly identified as an in-patient admission by START.

Results
A total of 773 patients were evaluated using the START tool at triage across both sites (Intervention group n = 355 and control group n = 418 patients). The proportion of patients meeting the 4-hour length of stay thresholds was similar between the intervention and control groups (30.1% vs. 28.2%; p = 0.62). The intervention group was associated with a reduced ED length of stay when compared to the control group (351 min, interquartile range (IQR) 221.0–565.0 min versus 383 min, IQR 229.25–580.0 min; p = 0.85). When stratified into admitted and discharged patients, similar results were seen.

Conclusion
In this extension of the START model of care implementation study in two metropolitan EDs, START, when used in conjunction with senior early assessment was associated with some reduced ED length of stay.
Novel CAD gene mutations in a boy with developmental and epileptic encephalopathy 50 with dramatic response to uridine therapy: a case report and a review of the literature
Authors: Duan Lifen , Ye Lei , Yin Runxiu , Sun Ying , Yu Wei , Zhang Yi , Zhong Haiyan , Bao Xinhua , Tian Xin 
Published: March 2024

Abstract
Background
Developmental and epileptic encephalopathy-50 (DEE-50) is a rare clinical condition believed to be caused by a mutation in the CAD gene and is associated with a bleak prognosis. CAD-related diseases have a wide range of clinical manifestations and other symptoms that may be easily overlooked. Like other rare diseases, the clinical manifestations and the treatment of DEE-50 necessitate further investigation.

Case presentation
A 1-year-old male patient presented with developmental delay, seizures, and anaemia at 3 months of age. He further developed refractory status epilepticus (SE), rapid deterioration of cognitive and motor function, and even became comatose at 5 months of age. Whole-exome sequencing of trios (WES-trios) revealed a compound heterozygous variant in the CAD gene, with one locus inherited from his father (c.1252C>T: p.Q418* nonsense mutation) and one from his mother (c.6628G>A: p.G2210S, missense mutation). This compound heterozygous CAD variant was unreported in the Human Gene Mutation Database. After uridine treatment, his cognitive faculties dramatically improved and he remained seizure-free.
Forty two cases with CAD gene mutation reported in the literatures were reviewed. Among them, 90% had onset before 3 years of age, with average of 1.6±1.8 years old. The average age of diagnosis was 7.7 ± 10 years. The mortality rate was approximately 9.5%, with all reported deaths occurring in patients without uridine treatment. The clinical entity could be improved dramatically when the patient treated with uridine.

Conclusions
We present a boy with DEE 50 caused by novel CAD gene mutations and reviewed the clinical features of 42 patients reported previously. DEE 50 has early onset, refractory seizures, even status epilepticus leading to death, with favorable response to treatment with oral uridine. Early uridine treatment is recommended if CAD defect is suspected or genetically diagnosed. This study enhances the knowledge of DEE 50 and expands the spectrum of CAD gene mutations.
Practical implications of ICD-11 personality disorder classifications
Authors: Pan Bing , Wang Wei 
Published: March 2024

AbstractPersonality disorders (PDs) are associated with an inferior quality of life, poor health, and premature mortality, leading to heavy clinical, familial, and societal burdens. The International Classification of Diseases-11 (ICD-11) makes a thorough, dramatic paradigm shift from the categorical to dimensional diagnosis of PD and expands the application into adolescence. We have reviewed the recent literature on practical implications, and severity and trait measures of ICD-11 defined PDs, by comparing with the alternative model of personality disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), by mentioning the relevance in forensic and social concerns, and by referencing the developmental implication of life span, especially in adolescence. Study results strongly support the dimensional utility of ICD-11 PD diagnosis and application in adolescence which warrants early detection and intervention. More evidence-based research is needed along the ICD-11 PD application, such as its social relevance, measurement simplification, and longitudinal design of lifespan observation and treatment.