bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant changes in advanced lung cancer survival during the past decade in Hungary: impact of modern immunotherapy and the COVID-19 pandemic
Authors: Kiss Zoltán , Gálffy Gabriella , Müller Veronika , Moldvay Judit , Sárosi Veronika , Pápai-Székely Zsolt , Csada Edit , Kerpel-Fronius Anna , Király Zsolt , Szász Zoltán , Hódi Gábor , Polányi Zoltán , Kovács Krisztina , Karamousouli Eugenia , Knollmajer Kata , Szabó Tamás G. , Berta Andrea , Vokó Zoltán , Rokszin György , Abonyi-Tóth Zsolt , Barcza Zsófia , Tamási Lilla , Bogos Krisztina 
Published: October 2023

ObjectiveThe approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database.MethodsThis retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology.ResultsIn total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1–66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011–2012 (28.7% [95% CI: 26.4%–30.9%] vs. 14.45% [95% CI: 13.21%–15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%–25.2%) and 13.37% (95% CI: 11.8%–15.0%) in 2019 and 2011–2012, respectively, the change was statistically significant. Compared to 2011–2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015–2016, 2017–2018, and 2019, respectively (p&lt;0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p&lt;0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020–2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period.Conclusion3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic.
A prognostic mathematical model based on tumor microenvironment-related genes expression for breast cancer patients
Authors: Chen Hong , Wang Shan , Zhang Yuting , Gao Xue , Guan Yufu , Wu Nan , Wang Xinyi , Zhou Tianyang , Zhang Ying , Cui Di , Wang Mijia , Zhang Dianlong , Wang Jia 
Published: October 2023

BackgroundTumor microenvironment (TME) status is closely related to breast cancer (BC) prognosis and systemic therapeutic effects. However, to date studies have not considered the interactions of immune and stromal cells at the gene expression level in BC as a whole. Herein, we constructed a predictive model, for adjuvant decision-making, by mining TME molecular expression information related to BC patient prognosis and drug treatment sensitivity.MethodsClinical information and gene expression profiles were extracted from The Cancer Genome Atlas (TCGA), with patients divided into high- and low-score groups according to immune/stromal scores. TME-related prognostic genes were identified using Kaplan-Meier analysis, functional enrichment analysis, and protein-protein interaction (PPI) networks, and validated in the Gene Expression Omnibus (GEO) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to construct and verify a prognostic model based on TME-related genes. In addition, the patients’ response to chemotherapy and immunotherapy was assessed by survival outcome and immunohistochemistry (IPS). Immunohistochemistry (IHC) staining laid a solid foundation for exploring the value of novel therapeutic target genes.ResultsBy dividing patients into low- and high-risk groups, a significant distinction in overall survival was found (p &lt; 0.05). The risk model was independent of multiple clinicopathological parameters and accurately predicted prognosis in BC patients (p &lt; 0.05). The nomogram-integrated risk score had high prediction accuracy and applicability, when compared with simple clinicopathological features. As predicted by the risk model, regardless of the chemotherapy regimen, the survival advantage of the low-risk group was evident in those patients receiving chemotherapy (p &lt; 0.05). However, in patients receiving anthracycline (A) therapy, outcomes were not significantly different when compared with those receiving no-A therapy (p = 0.24), suggesting these patients may omit from A-containing adjuvant chemotherapy. Our risk model also effectively predicted tumor mutation burden (TMB) and immunotherapy efficacy in BC patients (p &lt; 0.05).ConclusionThe prognostic score model based on TME-related genes effectively predicted prognosis and chemotherapy effects in BC patients. The model provides a theoretical basis for novel driver-gene discover in BC and guides the decision-making for the adjuvant treatment of early breast cancer (eBC).
Comparison of lobectomy and sublobar resection for stage I non-small cell lung cancer: a meta-analysis based on randomized controlled trials
Authors: Lu Genlin , Xiang Zhiyi , Zhou Yan , Dai Senjie , Tong Fei , Jiang Renya , Dai Min , Zhang Qiufeng , Zhang Difeng 
Published: October 2023

BackgroundThis meta-analysis aimed to compare the prognostic between lobectomy and sublobar resection in patients with stage I non-small cell lung cancer (NSCLC).MethodsWe conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) comparing the prognosis of lobectomy and sublobar resection for stage I NSCLC, with the primary outcomes being overall survival (OS) and disease-free survival (DFS).ResultsA total of 2222 patients were included in the 5 RCTs. The results showed no statistical difference in OS (HR=0.87, p=0.445) and DFS (HR=0.99, p=0.918) between patients who underwent lobectomy and sublobar resection during the total follow-up period. In terms of dichotomous variables, there were no statistical differences in OS (relative ratio [RR]=1.05, p=0.848) and DFS (RR=1.21, p=0.075) between the two groups during the total follow-up period, as well as 5-year OS (RR=0.96, p=0.409) and 5-year DFS (RR=0.95, p=0.270). In addition, subgroup analysis showed a better prognosis for non-adenocarcinoma patients with sublobar resection than lobectomy (HR=0.53, p=0.037), but also an increased cause of cancer death (not limited to lung cancer) (RR=1.56, p=0.004).ConclusionOur results showed that for stage I NSCLC, lobectomy is usually not a justified operation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407301, identifier CRD42023407301.
Association between family income to poverty ratio and HPV infection status among U.S. women aged 20 years and older: a study from NHANES 2003-2016
Authors: Zhao Yuan , Zhao Jing , Xie Ruijie , Zhang Yu , Xu Ya , Mao Jing , Yan Cheng , Sun Yi 
Published: October 2023

BackgroundHPV infection is closely related to the occurrence of cervical cancer and has an important adverse effect on human life and health. This study used data from the NHANES 2003–2016 to investigate the relationship between PIR and HPV infection status among Americans aged 20 and older.MethodsThe data for this cross-sectional investigation came from the 2003–2016 National Health and Nutrition Examination Survey (NHANES), which included 9580 women who were 20 years of age or older. The linear and nonlinear correlations between PIR and the presence of HPV infection were investigated using multiple linear regression and smooth curve fitting. The stability of the relationship across groups was examined using subgroup analysis and interaction tests.ResultsThere were 2232 impoverished homes and 2543 rich households among the 9580 adult participants aged 20 and above. PIR (ratio of income to poverty) was found to be significantly inversely related to the presence of HPV infection [0.91 (0.89, 0.94)] after adjusting for all other covariates, and the trend persisted even after categorizing PIR into high- and low-income groups (PIR&gt;4 and PIR&lt;1). In addition, significant negative relationships were discovered in subgroup analyses for women aged 25 to 59 [0.90 (0.88, 0.93)], non-Hispanic whites [0.80 (0.70, 0.92)], non-diabetics [0.91 (0.88, 0.94)], and those who had ever engaged in sex [0.91 (0.89, 0.94)].ConclusionsPIR was highly and negatively correlated with the presence of HPV infection in American women aged 20 and older. The results of this study are of great significance for preventing HPV infection and improving the accuracy of HPV screening.
Coadministration of bedaquiline and pyrifazimine reduce exposure to toxic metabolite N-desmethyl bedaquiline
Authors: Ding Yangming , Liu Haiting , Wang Furun , Fu Lei , Zhu Hui , Fu Shuang , Wang Ning , Zhuang Xiaomei , Lu Yu 
Published: October 2023

Background: A new, effective anti-tuberculosis (TB) regimen containing bedaquiline (BDQ) and pyrifazimine (TBI-166) has been recommended for a phase IIb clinical trial. Preclinical drug–drug interaction (DDI) studies of the combination of BDQ and TBI-166 have been designed to support future clinical trials. In this study, we investigated whether a DDI between BDQ and TBI-166 affects the pharmacokinetics of BDQ.Methods: We performed in vitro quantification of the fractional contributions of the fraction of drug metabolism by individual CYP enzymes (fm) of BDQ and the inhibition potency of key metabolic pathways of TBI-166. Furthermore, we conducted an in vivo steady-state pharmacokinetics study in a murine TB model and healthy BALB/c mice.Results: The in vitro fm value indicated that the CYP3A4 pathway contributed more than 75% to BDQ metabolism to N-desmethyl-bedaquiline (M2), and TBI-166 was a moderate (IC50 2.65 µM) potential CYP3A4 inhibitor. Coadministration of BDQ and TBI-166 greatly reduced exposure to metabolite M2 (AUC0-t 76310 vs 115704 h ng/mL, 66% of BDQ alone), whereas the exposure to BDQ and TBI-166 did not changed. The same trend was observed both in healthy and TB model mice. The plasma concentration of M2 decreased significantly after coadministration of BDQ and TBI-166 and decreased further during treatment in the TB model.Conclusions: In conclusion, our results showed that the combination of BDQ and TBI-166 significantly reduced exposure to the toxic metabolite M2 by inhibiting the activity of the CYP3A4 pathway. The potential safety and efficacy benefits demonstrated by the TB treatment highly suggest that coadministration of BDQ and TBI-166 should be studied further.
In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban
Authors: Wang Zhi , Li Ying , He Xueru , Fu Yuhao , Li Yajing , Zhou Xin , Dong Zhanjun 
Published: October 2023

Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment.Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR).Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.
Myocardial stretch-induced compliance is abrogated under ischemic conditions and restored by cGMP/PKG-related pathways
Authors: Leite-Moreira André M. , Almeida-Coelho João , Neves João S. , Castro-Ferreira Ricardo , Ladeiras-Lopes Ricardo , Leite-Moreira Adelino F. , Lourenço André P. 
Published: October 2023

Introduction: Management of acute myocardial infarction (MI) mandates careful optimization of volemia, which can be challenging due to the inherent risk of congestion. Increased myocardial compliance in response to stretching, known as stretch-induced compliance (SIC), has been recently characterized and partly ascribed to cGMP/cGMP-dependent protein kinase (PKG)-related pathways. We hypothesized that SIC would be impaired in MI but restored by activation of PKG, thereby enabling a better response to volume loading in MI.Methods: We conducted experiments in ex vivo rabbit right ventricular papillary muscles under ischemic and non-ischemic conditions as well as pressure–volume hemodynamic evaluations in experimental in vivo MI induced by left anterior descending artery ligation in rats.Results: Acutely stretching muscles ex vivo yielded increased compliance over the next 15 min, but not under ischemic conditions. PKG agonists, but not PKC agonists, were able to partially restore SIC in ischemic muscles. A similar effect was observed with phosphodiesterase-5 inhibitor (PDE5i) sildenafil, which was amplified by joint B-type natriuretic peptide or nitric oxide donor administration. In vivo translation revealed that volume loading after MI only increased cardiac output in rats infused with PDE5i. Contrarily to vehicle, sildenafil-treated rats showed a clear increase in myocardial compliance upon volume loading.Discussion: Our results suggest that ischemia impairs the adaptive myocardial response to acute stretching and that this may be partly prevented by pharmacological manipulation of the cGMP/PKG pathway, namely, with PDE5i. Further studies are warranted to further elucidate the potential of this intervention in the clinical setting of acute myocardial ischemia.
Metabolomic and transcriptomic analyses identify external conditions and key genes underlying high levels of toxic glycoalkaloids in tubers of stress-sensitive potato cultivars
Authors: Merino Irene , Guasca Alexandra Olarte , Krmela Ales , Arif Usman , Ali Ashfaq , Westerberg Erik , Jalmi Siddhi Kashinanth , Hajslova Jana , Schulzova Vera , Sitbon Folke 
Published: October 2023

IntroductionHigh levels of toxic steroidal glycoalkaloids (SGAs) in potato tubers constitute a recognized food quality problem. Tuber SGA levels vary between potato cultivars and can increase after post-harvest stresses such as wounding and light exposure. A few cultivars, e.g., ‘Magnum Bonum’ and ‘Lenape,’ have been withdrawn from commercial sales due to excessive SGA levels during some cultivation years. However, these sudden SGA increases are diffucult to predict, and their causes are not understood. To identify external and genetic factors that underlie sudden SGA increases in certain potato cultivars, we have here in a 2-year study investigated ‘Magnum Bonum’ and five additional table potato cultivars for their SGA levels after wounding and light exposure.Results and methodsResults showed that ‘Magnum Bonum’ has an unusual strong SGA response to light exposure, but not to wounding, whereas ‘Bintje’ displayed an opposite regulation. Levels of calystegine alkaloids were not significantly altered by treatments, implicating independent metabolic regulation of SGA and calystegine levels also under conditions of high SGA accumulation. Metabolomic and transcriptomic analyses identified a small number of key genes whose expression correlated with SGA differences between cultivars. Overexpression of two key genes in transgenic low-SGA potato cultivars increased their leaf SGA levels significantly.DiscussionThe results show that a strong response to light can underlie the SGA peaks that occasionally occur in certain potato cultivars and indicate that a between-cultivar variation in the expression of single SGA key genes can account for cultivar SGA differerences. We propose that current attempts to mitigate the SGA hazard will benefit from an increased consideration of cultivar-dependent SGA responses to post-harvest conditions, particularly light exposure. The identified key SGA genes can now be used as a molecular tool in this work.
Priming methods affected deterioration speed of primed rice seeds by regulating reactive oxygen species accumulation, seed respiration and starch degradation
Authors: Ren Muyao , Tan Biao , Xu Jiayi , Yang Zhengpeng , Zheng Huabin , Tang Qiyuan , Zhang Xiaoli , Wang Weiqin 
Published: October 2023

IntroductionSeed priming is a pre-sowing seed treatment that is beneficial for rice seed germination and seedling growth, but the reduced seed longevity after seed priming greatly limited its adoption. The deterioration of primed seeds showed large differences among different studies, and the priming method might play an important role in regulating the deterioration speed of primed seeds. However, whether and how the priming method affected the deterioration of primed rice seeds during storage remains unknown. MethodsIn this study, two typical seed priming methods, namely hydropriming (HP) and osmopriming (PEG) were compared under artificially accelerated aging conditions, the changes in germination performance, starch metabolism, seed respiration and reactive oxygen species accumulation before and after accelerated aging were determined.Results and discussionHydroprimed rice seeds exhibited significantly faster deterioration speed than that of PEG-primed seeds in terms of germination speed and percentage. Meanwhile, α-amylase activity and total soluble sugar content in hydroprimed seeds were reduced by 19.3% and 10.0% respectively after aging, as compared with PEG-primed seeds. Such effects were strongly associated with the increased reactive oxygen generation and lipid peroxidation, as the content of superoxide anion, hydrogen peroxide and malondialdehyde in hydroprimed seeds were 4.4%, 12.3% and 13.7% higher than those in PEG-primed seeds after aging, such effect could be attributed to the increased respiratory metabolism in hydroprimed seeds. In addition, the simultaneous use of N-acetylcysteine with HP and PEG priming greatly inhibited the deterioration of primed rice seeds, suggesting that the ability to scavenge reactive oxygen species may be the key factor affecting the speed of deterioration in primed rice seeds during storage.
Energizing compassion: using music and community focus to stimulate compassion drive and sense of connectedness
Authors: Gilbert Paul , Basran Jaskaran Kaur , Plowright Ptarmigan , Gilbert Hannah 
Published: October 2023

ObjectivesThe last 20 years have seen considerable research on the nature and biopsychosocial impacts of compassion training on self and others. This training is usually focused on calming and slowing the mind and body and on individual imagery practices and mantras. This study explored the effects of three variations: 1. The impact of using energizing music to generate activation and “drive” for compassion; 2. To focus on imagining “breathing in and breathing out a white light or mist of compassion” to bring compassion to the world; and 3. While listening to energizing music, participants were guided to imagining connecting to the compassion (Sangha) community, imagining oneself as linking with others as part of communities seeking to help the world.MethodsFrom approximately 1,600 members of the Compassionate Mind discussion list, participants were invited to take part in a new energizing focused self-practice study. The study involved listening to recorded guidance on the evolutionary model of compassion and the need to address the potentially harmful side of our nature. This was followed by a 4 1/2-min tonglen-informed guided practice of breathing in and breathing out compassion accompanied by energizing music. Forty-three participants completed several self-report scales measuring compassion orientation, wellbeing, social safeness, and positive affect before and following 2 weeks of practice. Participant experiences were recorded from 6 open explorative questions.ResultsSelf-report measures taken before and following 2 weeks of practice revealed significant increases in self-compassion, compassion to others, openness to compassion from others, activated positive affect, safe positive affect, social safeness, and wellbeing, with the largest effect size relating to compassion for the self (d = −0.76). In addition, qualitative data revealed that the participants had experienced the practice as energizing, inspiring, and felt socially connected and that it had significant impacts on other aspects of their lives. Some participants noted that engaging with suffering also stimulated sadness.ConclusionThis study found that pairing energizing music with breathing practices and specific compassion visualizations, focusing on the desire to bring compassion to the world and be part of a compassionate community, was well-accepted and had a range of significant positive impacts. This study indicates the potential value of exploring energizing in comparison to the more standard soothing and settling practices as ways of stimulating the biopsychosocial processes of compassion.