bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD34 as a potential prognostic indicator for camrelizumab response in advanced non-small-cell lung cancer: insights from digital spatial profiling
Authors: Huang Xinyi , Tian Baoqing , Ren Ziyuan , Zhang Jingxin , Yan Weiwei , Mo You , Yuan Jupeng , Ma Yujiao , Wang Ruiyang , Liu Rufei , Chen Minxin , Yu Jinming , Chen Dawei 
Published: October 2024

Background:Given that only a small subset of patients with advanced non-small-cell lung cancer (aNSCLC) benefit from immune checkpoint inhibitors (ICIs), the effectiveness of ICIs is often compromised by the complex interplay within the tumor microenvironment (TME).Objectives:To identify predictive biomarkers associated with ICI resistance at a multi-omics spatial level.Design:A total of eight aNSCLC patients who received first-line anti-programmed cell death protein-1 (PD-1) monoclonal antibody camrelizumab at Shandong Cancer Hospital and Institute between 2021 and 2022 were included in the discovery cohort. An additional validation cohort of 45 samples from camrelizumab-treated aNSCLC patients was also enrolled.Methods:NanoString GeoMx®digital spatial profiling was conducted at the transcriptomic and proteomic level within pan-cytokeratin (panCK+), CD45+, and CD68+compartments. For validation, multiplex immunofluorescence (mIF) staining was performed.Results:Distinct spatial expression patterns and levels of immune infiltration were observed between tumor and leukocyte compartments. Higher CD34 expression in the macrophage compartment correlated with poorer prognosis and response to camrelizumab ( p < 0.05). mIF validation confirmed the association of elevated CD34 expression level with reduced progression-free survival (PFS; hazard ratio (HR) = 5.011, 95% confidence interval: 1.057–23.752, p = 0.042), outperforming traditional tumor markers in predictive accuracy.Conclusion:Our findings identify CD34 as a novel spatial biomarker for anti-PD-1 therapy efficacy, potentially guiding the selection of aNSCLC patients who are more likely to benefit from ICI treatment.Trial registration:ChiCTR2000040416.
Counting the costs: a nationwide study on healthcare use following an adalimumab biosimilar switch in >1300 inflammatory arthritis patients
Authors: Nabi Hafsah , Ibsen Rikke , Ibsen Michael , Kjellberg Jakob , Hetland Merete Lund , Glintborg Bente 
Published: October 2024

Background: In Denmark, cost savings motivate mandatory biosimilar switches. In 2018, patients switched from originator to biosimilar adalimumab, that is, to GP2017 in Eastern and to SB5 in Western Denmark. However, concerns were raised about additional costs covering, that is, an increased number of outpatient visits due to patient education, treatment monitoring, and patient concerns. Objectives: To investigate whether the switch led to increased total healthcare costs, defined as costs related to in- and outpatient contacts in hospitals and the primary sector and use of prescription medicine (excluding biological treatment). Design: Observational cohort study with geographical cluster pseudo-randomization. Methods: Patients with rheumatoid arthritis, psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA), who switched were identified in the nationwide DANBIO registry. Total healthcare costs 9 months before and after the switch were captured from the National Patient and Prescription registries. The difference between pre- and post-switch costs was estimated by a generalized estimation equations (GEE) model. Results: Overall, 1316 patients switched to GP2017 ( n = 621) or SB5 ( n = 695). Total healthcare costs were mainly driven by hospital costs. The monthly fluctuations of hospital costs 9 months before and after the switch were largely similar or decreased. In the adjusted analyses (GEE), hospital costs decreased after the switch (by approximately 15%) for GP2017 switchers, especially PsA (estimate = 0.83; 95% CI 0.75–0.92) and AxSpA patients (estimate = 0.85; 0.77–0.93), with no significant changes for SB5 switchers. Conclusion: We found no increase in total healthcare costs in 9 months following a nationwide mandatory adalimumab originator to biosimilar switch. Our findings were strengthened by similar results for GP2017 and SB5.
Prognostic Factors of Hearing Improvement for EES and MES in Attic Cholesteatoma
Authors: Gao Minqian , Zeng Nan , Kang Weibiao , Lin Yong , Li Peng , Tao Yuan , Lu Yongtian , Zhao Wei , Chen Xiangwei , Jiang Zebin , Gao Jinliang , Yu Youjun , Liang Wanshan , Zhai Sijia , Yang Qiong , Yang Haidi 
Published: October 2024

Objective The surgical strategy of cholesteatomas is still controversial. This study aimed to compare the hearing improvement and determine the prognostic factors between endoscopic and microscopic ear surgery for attic cholesteatoma via a multicenter retrospective study. Methods This retrospective study included 169 patients with attic cholesteatoma who received endoscopic ear surgery (EES) or microscopic ear surgery (MES) from 12 otorhinolaryngology centers. Hearing improvement between EES and MES was evaluated, including the postoperative pure tone average (PTA) and air-bone gap (A-B Gap), as well as the hearing threshold across the low-, mid-, and high-frequency. The success rate of grafts was collected. Linear regression was performed to access the prognostic value of preoperative PTA and A-B Gap. Patients were followed up for at least 3 years. Results The graft success rate of EES was 89.66% (78/87) versus 80.49% (66/82) for MES. The postoperative PTA and A-B Gap demonstrated significant improvement in EES compared to MES (Post-PTA: t = 3.281, P = .001; Post-A-B Gap: t = 2.197, P = .029). In the EES group, there were 59 ears (67.82%) with a postoperative A-B Gap ≤20 dB HL, which revealed a higher rate of successful hearing outcomes in EES as opposed to MES (χ2 = 9.904, P = .019). There were significantly better hearing improvement, shorter surgical times, and lower hospital stays in EES for epitympanic cholesteatoma without stapes superstructure involvement. The preoperative AC ≤79 dB and/or preoperative A-B Gap ≤52 dB was associated with a better prognosis in EES for epitympanic cholesteatoma with stapes superstructure involvement. Conclusions EES showed higher graft success rate, better hearing improvement, shorter surgical times and hospital stays for attic cholesteatoma, particularly without stapes superstructure involvement. The range of preoperative PTA and A-B Gap have shown the prognostic value, which maybe a favorable surgical indication for EES or MES.
Head-to-Head Comparison Between 18F-FDG PET and Leukocyte Scintigraphy to Monitor Treatment Responses in Necrotizing Otitis Externa
Authors: Hurstel Moïra , Vasseur Alice , Melki Saifeddine , Veran Nicolas , Imbert Laetitia , Nguyen Duc Trung , Rumeau Cécile , Verger Antoine 
Published: October 2024

Background Necrotizing otitis externa (NOE) is a rare disease associated with high morbidity and mortality, and there is currently no available accurate biomarker to assess treatment responses. The aim of the current study was to evaluate and directly compare the diagnostic performances of 18-Fluoro-deoxyglucose positron emission tomography (18F-FDG PET) and labeled leukocyte scintigraphy (LS) to monitor treatment responses in NOE. Methods Consecutive patients with NOE who underwent 18F-FDG PET at the end of antibiotic therapy and planar as well as single photon emission computed tomography-labeled leukocyte scintigraphy after completing the initial antibiotic treatment were retrospectively included. Semiquantitative analyses were performed to determine the ratios of affected/nonaffected sides for PET and 4 hour and 24 hour LS acquisitions as well as the kinetic PET ratios (at diagnosis and post-treatment) and LS (4 and 24 hours). The final treatment responses were assessed by 2 experienced ENT physicians based on clinical, otoscopic, and biological data and subsequent 3-month follow-up. Results Seventeen patients (74.0 ± 10.6 years old, 5 women) were included. The best diagnostic performances were obtained with the PET maximum standardized uptake value (SUVmax)-lesion-to-background ratio and the tomographic LS lesion-to-background ratio at the 4-hour acquisition timepoint (thresholds of 4.1 and 1.19, yielding accuracies of 100% and 88%, respectively). In the multivariate analysis, the PET SUVmax-lesion-to-background ratio was the only predictive factor of recovery when associated with all clinical parameters ( P < .001). Conclusion 18F-FDG PET is the first-line imaging modality for evaluating NOE treatment responses, with excellent diagnostic performances. LS with only 4-hour acquisitions appeared to suffice to evaluate NOE treatment responses. Both biomarkers constitute early prognostic biomarkers for predicting antibiotic treatment response in patients with NOE. Trial registration The institutional ethics committee (Comité d’Ethique du CHRU de Nancy) approved the evaluation of retrospective patient data, and the trial was registered at ClinicalTrials.gov (n°2023PI003-404).
Predicting the Risk of Adverse Neonatal Outcomes in Women With Insulin-Treated Diabetes: Is It Time for a Pregnancy-Specific Glycemic Risk Index (GRI)?
Authors: Citro Fabrizia , Bianchi Cristina , Belcari Tommaso , Galleano Federico , Venturi Caterina , Battini Lorella , Marchetti Piero , Bertolotto Alessandra , Aragona Michele 
Published: October 2024

Background: The Glycemia Risk Index (GRI) describes the quality of glycemic control, emphasizing extreme hypoglycemia and hyperglycemia more than less extreme values. However, a pregnancy-specific GRI (pGRI), tailored to the tighter target glucose range required during pregnancy, has not been established. Methods: We retrospectively evaluated clinical, metabolic, and Continuous Glucose Monitoring (CGM) data across pregnancy in women with insulin-treated diabetes, managed between September 2021 and March 2024 at the University Hospital of Pisa. First and second levels of hyperglycemia (TAR1: 140-180 mg/dL, TAR2: >180 mg/dL) and hypoglycemia (TBR1: 63-54 mg/dL, TBR2: <54 mg/dL) were used to calculate the pGRI at each trimester. Logistic regression analysis investigated the association between pGRI and risk of at least one adverse neonatal outcome (among preterm delivery, macrosomia, large for gestational age, small for gestational age, neonatal hypoglycemia, neonatal jaundice, and neonatal intensive care unit admission). Results: Of 45 pregnant women, 25 (56%) experienced at least one adverse neonatal outcome. In the third trimester, women with adverse outcomes had significantly higher total TAR (26 [12-32]% vs 10 [4-23]%, P = .018) and lower TIR (71 [64-83]% vs 88 [75-92]%, P = .007). Specifically, the difference was notable in TAR2 (6 [2-15]% vs 1 [0-4]%, P = .004), whereas TAR1 was comparable between the 2 groups. Accordingly, third trimester pGRI was higher in women with adverse neonatal outcomes (38 [18-49]% vs 18 [10-31]%, P = .013) and, at logistic regression, slightly but significantly increased the risk of adverse neonatal outcomes (1.044 [1.004-1.086], P = .024). Conclusions: Pregnant women with insulin-treated diabetes reporting adverse neonatal outcomes spent more time in hyperglycemia, particularly in extreme hyperglycemia. Therefore, the level of hyperglycemia should always be assessed during pregnancy. The pGRI, emphasizing extreme hyperglycemia, may be a novel comprehensive tool for assessing the risk of adverse neonatal outcomes.
Adverse events of topical ocular prostaglandin medications for glaucoma treatment: a pharmacovigilance study based on the FAERS database
Authors: Wu Shi-Nan , Huang Caihong , Wang Yu-Qian , Li Xiang , Zhang Si-Qi , Chen Xiao-Dong , Qin Dan-Yi , Zhu Linfangzi , Wen Jia-Yi , Luo Na-Chuan , Hu Jiaoyue , Liu Zuguo 
Published: October 2024

Background: As prostaglandin medications, crucial in glaucoma treatment, become more widely used, their local adverse events are increasingly observed. Objectives: To evaluate the common adverse events of four clinically commonly used prostaglandin F (FP) receptor agonists in the treatment of glaucoma in the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Design: We screened and analyzed the generic and brand names of latanoprost, bimatoprost, travoprost, and tafluprost in the FAERS database and summarized and cleaned the baseline information of subjects receiving the above-mentioned drugs. Methods: Perform descriptive statistical analysis on the baseline information of subjects using the drugs. Conduct disproportionality analysis of drug-related adverse events. The criteria for positive signals of adverse events are established by simultaneously meeting the thresholds set by four methods: the ratio of reported odds, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. Additionally, assess the cumulative risk curves for drug-induced time of the aforementioned drugs and use one-way ANOVA to compare differences in drug-induced time across different groups. Results: The study included 1567 latanoprost, 1517 bimatoprost, 696 travoprost, and 82 tafluprost subjects. Adverse events mainly affected eye disorders, with significant issues in iris hyperpigmentation, ocular pemphigoid, corneal endothelial cell loss, periorbital fat atrophy, corneal irritation, eyelash growth, and ocular hyperemia. The time to onset varied among drugs, with latanoprost showing the longest (mean days = 344.37) and bimatoprost the shortest duration (mean days = 155.65; p < 0.001). Conclusion: Although signal detection analysis based on the FAERS database cannot establish a definitive causal relationship, our study found that FP receptor agonists used in glaucoma can cause various adverse events. Assessing their clinical suitability and potential side effects is crucial for providing personalized treatment and ensuring medication safety.
An integrative systematic review of nurses’ involvement in medication deprescription in long-term healthcare settings for older people
Authors: Vaismoradi Mojtaba , Mardani Abbas , Crespo Manuel Lillo , Logan Patricia A. , Sak-Dankosky Natalia 
Published: October 2024

Background: Deprescription of medications for older people in long-term care settings is crucial to enhance medication safety by reducing polypharmacy and minimizing related adverse events. Nurses as the member of the multidisciplinary healthcare team can support deprescription initiatives, but there is a gap in comprehensive knowledge about their roles. Objectives: To investigate the role and contribution of nurses in deprescribing medications within the multidisciplinary pharmaceutical care context of long-term healthcare for older people. Design: A systematic review utilizing an integrative approach was performed. Methods: Multiple databases were searched, including PubMed (covering MEDLINE), Scopus, CINAHL, ProQuest and Embase, focusing on studies published in English from 2014 to 2024. The preliminary search yielded 4872 studies, which were then refined to 32 qualitative and quantitative studies chosen for data analysis and narrative synthesis. Thematic comparisons and analysis led to the creation of meaningful categories integrating the studies’ findings to meet the review’s objective. Results: The review findings were classified into categories: ‘necessity and benefits of deprescribing’, ‘multidisciplinary collaboration for deprescribing’, ‘nurse role in deprescribing’, ‘identified challenges to deprescribing’, ‘involvement of older people and families in deprescribing’. They illustrated and exemplified various aspects of nurses’ roles and contributions in deprescription initiatives within the multidisciplinary pharmaceutical care team, such as support for reducing doses, discontinuing medications or transitioning to safer alternatives, as well as factors influencing this process. Conclusion: The main dimensions of nurses’ roles and contributions in deprescription initiatives encompass monitoring, communicating and educating. Challenges to nurses’ active participation in deprescribing, such as the need for increased knowledge, confidence and inclusion in team discussions, should be addressed through education, training and changing attitudes. These steps are essential for improving the safety of medication deprescribing in long-term care settings. Trial registration: The review was registered under PROSPERO ID: CRD42023486484, and can be accessed at crd.york.ac.uk/PROSPERO/display_record.php?RecordID=486484
In silico prediction of some pharmacokinetic, safety, biological activity and molecular docking studies of 1-piperazine indole hybrid with nicotinic amide and nicotinic acid and their analogues
Authors: Mitku Melese Legesse , Dagnaw Abera Dessie , Geremew Derso Teju , Anagaw Yeniewa Kerie , Worku Minichil Chanie , Limenh Liknaw Workie , Tadesse Yabibal Berie , Ergena Asrat Elias 
Published: October 2024

Background: In silico predictions are now being utilized in drug discovery and design to assess the physicochemical, pharmacokinetics, and safety properties of compounds at the beginning of the drug discovery process. This early evaluation of the physicochemical, pharmacokinetics, and safety properties of compounds helps the researchers to invest their time and resources only in the best prospective lead compounds by eliminating compounds with a low chance of success. Objective: The purpose of this study was to explore a promising lead compound designed from 1-piperazine indole hybrid with nicotinic amide and nicotinic acid analogs targeted on Trypanosoma brucei phosphofructokinase for Trypanosomiasis activity by using in silico predictions strategy. Results: The physicochemical, safety, pharmacokinetic, and biological activity properties of those molecules were predicted by using ADMETlab 2.0, ACD labs Chem Sketch software version 14.0, Molinspiration software, and MolPredictX online tool. Our results indicate that several promising candidates exhibit favorable characteristics. Based on Molinspiration software both nicotinic acid and nicotinic amide derivatives showed higher kinase inhibitor activity and all nicotinic acid derivatives revealed enzyme inhibitors and GPCR ligand activity. According to the MolPredictX online tool, the most biologically active derivatives were NA-4, NA-11, and NAD-11. Conclusion: Overall, our findings offer valuable insights into the potential efficacy and safety of these compounds. It appears that almost all of the compounds have successfully passed the pharmacokinetic evaluations and integration of nicotinic acid into indole appears to be more beneficial than nicotinic amide regarding certain biological activities.
Longitudinal Links Between Identity Development and the Vision of One’s Adult Life in Emerging Adulthood
Authors: Janowicz Kamil , Piotrowski Konrad , Bakiera Lucyna 
Published: October 2024

Our longitudinal study aimed to investigate relationships between identity development and the vision of one’s adult life (VOAL) in emerging adults. In the first measurement, 299 emerging adults aged 17 to 27 participated, and 177 participated in the second measurement (9-10 months later). Participants were asked to complete the Dimensions of Identity. Development Scale and write about their envisioned future adult life. Written answers about the VOAL were coded by trained judges to allow for quantitative analyses. The results indicated that both identity exploration and commitment were related to the structure of the emerging adults’ VOAL and their subjective attitudes toward the possessed VOAL but in different ways. We also observed that changes in identity processes over time turned out to be related to changes in the VOAL. Our results suggest the presence of a reciprocal relationship between identity development and thinking about the future in emerging adults.
“Huanglianjiedu Decoction” Against Pancreatic Adenocarcinoma Proliferation of by Downregulating the PI3K/AKT/mTOR and MAPK/ERK1/2 Signaling Pathways
Authors: Dong, MD Shu , Xu, MD Panling , Yang, MD Peiwen , Jiao, MD Juying , Cheng, MD, PhD Chien-shan , Chen, MD, PhD Lianyu 
Published: October 2024

Background Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear. Aims This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways. Methods A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays. Results HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2. Conclusion HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.
Cross-cultural adaptation and psychometric evaluation of the Emergency Medical Services Safety Attitudes Questionnaire in the Brazilian context
Authors: Camargo Fernanda Silva Oliveira , Massago Miyoko , Bonfim Samile , Dutra Amanda de Carvalho , Oliveira Araújo Edilaine Aparecida de , Oliveira Márcia Rosângela Neves de , Pujals Constanza , Gurgel Sanderland José Tavares , Radovanovic Cremilde Aparecida Trindade , Vissoci João Ricardo Nickenig , de Andrade Luciano 
Published: October 2024

Background Ensuring patient safety is essential to prevent and minimize adverse events, and pre-hospital services play a vital role in the healthcare network, serving as the starting point for quality care. This study aimed to adapt the Emergency Medical Services Safety Attitudes Questionnaire to the Brazilian context and evaluate its psychometric properties. Methods Beaton and colleagues’ guidelines were used as a reference. Construct validity was evaluated by confirmatory factor analysis (CFA) based on the responses of 93 participants. Questions with reverse scoring were excluded in a further CFA. Results The content validity index was 0.99, and Cronbach's alpha was 0.90. The initial CFA resulted in a Tucker–Lewis index (TLI) of 0.95 and a comparative fit index (CFI) of 0.951. After the exclusion of reverse-coded questions (Q4 and Q9), TLI increased to 0.96 and CFI to 0.97. Conclusions The adapted instrument demonstrated good content, face, and construct validity, confirming its suitability for evaluating patient safety in prehospital services in Brazil. It can guide adjustments in care protocols, contributing to the safety and effectiveness of prehospital care while aligning with patient-centered best practices.