bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel prognostic scoring model based on copper homeostasis and cuproptosis which indicates changes in tumor microenvironment and affects treatment response
Authors: Ma Yun-Long , Yang Ya-Fei , Wang Han-Chao , Yang Chun-Cheng , Yan Lun-Jie , Ding Zi-Niu , Tian Bao-Wen , Liu Hui , Xue Jun-Shuai , Han Cheng-Long , Tan Si-Yu , Hong Jian-Guo , Yan Yu-Chuan , Mao Xin-Cheng , Wang Dong-Xu , Li Tao 
Published: February 2023

Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive.Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells’ pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes’ expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation.Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-Ⅱ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines.Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time.
Maternal serum iron status, hepcidin and interleukin-6 levels in women with preeclampsia
Authors: Ahmed Yasir I. B. , Yagoub Hind S. , Hassan Mohamed A. , Adam I. , Hamdan Hamdan Z. 
Published: February 2023

Introduction:Preeclampsia can lead to a number of adverse maternal and perinatal effects. The association between iron status [serum iron, ferritin and total iron-binding capacity (TIBC)], unsaturated iron-binding capacity, hepcidin, interleukin-6 (IL-6) levels and preeclampsia is not fully understood.Objective:To assess the levels of iron status, hepcidin and interleukin-6 in women with preeclampsia compared with healthy pregnant women.Method:A case-control study (60 women were recruited in each group) was conducted at Saad Abuelela Maternity Hospital in Khartoum, Sudan. Sociodemographic and clinical data were gathered through a questionnaire. The levels of iron status, hepcidin and IL-6 were measured using applicable methods.Results:There was no significant difference in the median [interquartile range (IQR)] of age, parity or body mass index between the two groups. Moreover, the median (IQR) of the iron status, hepcidin and interleukin-6 did not differ between women with preeclampsia and healthy controls. There were no significant correlations between haemoglobin, hepcidin and IL-6. There were also no significant correlations between serum iron, serum ferritin, hepcidin and IL-6. However, there was a significant positive correlation between hepcidin and IL-6 (r = 0.393,p= 0.002).Conclusion:In this study, women with preeclampsia had levels of iron status, hepcidin and IL-6 similar to those observed in healthy pregnant women. There was no significant correlation between iron status, hepcidin and IL-6.
Transcriptome and metabolome analyses reveal molecular mechanisms of anthocyanin-related leaf color variation in poplar (Populus deltoides) cultivars
Authors: Peng Xu Qian , Ai Yu Jie , Pu Yu Ting , Wang Xiao Jing , Li Yu Hang , Wang Zhong , Zhuang Wei Bing , Yu Bing Jun , Zhu Zhi Qi 
Published: February 2023

IntroductionColored-leaf plants are increasingly popular for their aesthetic, ecological, and social value, which are important materials for research on the regulation of plant pigments. However, anthocyanin components and the molecular mechanisms of anthocyanin biosynthesis in colored-leaf poplar remain unclear. Consequently, an integrative analysis of transcriptome and metabolome is performed to identify the key metabolic pathways and key genes, which could contribute to the molecular mechanism of anthocyanin biosynthesis in the colored-leaf cultivars poplar.MethodsIn this study, integrated metabolite and transcriptome analysis was performed to explore the anthocyanin composition and the specific regulatory network of anthocyanin biosynthesis in the purple leaves of the cultivars ‘Quanhong’ (QHP) and ‘Zhongshanyuan’ (ZSY). Correlation analysis between RNA-seq data and metabolite profiles were also performed to explore the candidate genes associated with anthocyanin biosynthesis. R2R3-MYB and bHLH TFs with differential expression levels were used to perform a correlation analysis with differentially accumulated anthocyanins.Results and discussionA total of 39 anthocyanin compounds were detected by LC-MS/MS analysis. Twelve cyanidins, seven pelargonidins, five delphinidins, and five procyanidins were identified as the major anthocyanin compounds, which were differentially accumulated in purple leaves of QHP and ZSY. The major genes associated with anthocyanin biosynthesis, including structural genes and transcription factors, were differentially expressed in purple leaves of QHP and ZSY through RNA-sequencing (RNA-seq) data analysis, which was consistent with quantitative real-time PCR analysis results. Correlation analysis between RNA-seq data and metabolite profiles showed that the expression patterns of certain differentially expressed genes in the anthocyanin biosynthesis pathway were strongly correlated with the differential accumulation of anthocyanins. One R2R3-MYB subfamily member in the SG5 subgroup, Podel.04G021100, showed a similar expression pattern to some structural genes. This gene was strongly correlated with 16 anthocyanin compounds, indicating that Podel.04G021100 might be involved in the regulation of anthocyanin biosynthesis. These results contribute to a systematic and comprehensive understanding of anthocyanin accumulation and to the molecular mechanisms of anthocyanin biosynthesis in QHP and ZSY.
Impact of marathon performance on muscles stiffness in runners over 50 years old
Authors: Mackala Krzysztof , Mroczek Dariusz , Chmura Paweł , Konefał Marek , Pawlik Damian , Ochman Bartosz , Chmura Jan , Paleczny Bartłomiej , Seredyński Rafał , Wyciszkiewicz Małgorzata , Nowicka-Czudak Adrianna , Łopusiewicz Wojciech , Adamiec Dorota , Wiecha Szczepan , Ponikowski Piotr , Ponikowska Beata 
Published: February 2023

IntroductionThe research examines the relationship between marathon performance and muscle stiffness changes from pre to marathon in recreational runners aged 50+ years.MethodsThirty-one male long-distance runners aged 50–73 years participated in the experiment. The muscle stiffness of quadriceps and calves was measured in two independent sessions: the day before the marathon and 30 min after the completed marathon run using a Myoton device.Results and DiscussionThe 42.195-km run was completed in 4.30,05 h ± 35.12 min, which indicates an intensity of 79.3% ± 7.1% of HRmax. The long-term, low-intensity running exercise (marathon) in older recreational runners and the low level of HRmax and VO2max showed no statistically significant changes in muscle stiffness (quadriceps and calves). There was reduced muscle stiffness (p= 0.016), but only in the triceps of the calf in the dominant (left) leg. Moreover, to optimally evaluate the marathon and adequately prepare for the performance training program, we need to consider the direct and indirect analyses of the running economy, running technique, and HRmax and VO2max variables. These variables significantly affect marathon exercise.
A cross-linguistic, sound symbolic relationship between labial consonants, voiced plosives, and Pokémon friendship
Authors: Kilpatrick Alexander , Ćwiek Aleksandra , Lewis Eleanor , Kawahara Shigeto 
Published: February 2023

IntroductionThis paper presents a cross-linguistic study of sound symbolism, analysing a six-language corpus of all Pokémon names available as of January 2022. It tests the effects of labial consonants and voiced plosives on a Pokémon attribute known asfriendship. Friendship is a mechanic in the core series of Pokémon video games that arguably reflects how friendly each Pokémon is.MethodPoisson regression is used to examine the relationship between the friendship mechanic and the number of times /p/, /b/, /d/, /m/, /g/, and /w/ occur in the names of English, Japanese, Korean, Chinese, German, and French Pokémon.ResultsBilabial plosives, /p/ and /b/, typically represent high friendship values in Pokémon names while /m/, /d/, and /g/ typically represent low friendship values. No association is found for /w/ in any language.DiscussionMany of the previously known cases of cross-linguistic sound symbolic patterns can be explained by the relationship between how sounds in words are articulated and the physical qualities of the referents. This study, however, builds upon the underexplored relationship between sound symbolism and abstract qualities.
Long-term postoperative quality of life in childhood survivors with cerebellar mutism syndrome
Authors: Zhu Kaiyi , Yang Wei , Ying Zesheng , Cai Yingjie , Peng XiaoJiao , Zhang Nijia , Sun Hailang , Ji Yuanqi , Ge Ming 
Published: February 2023

BackgroundTo investigate the long-term quality of life (QoL) of children with cerebellar mutism syndrome (CMS) and explore the risk factors for a low QoL.ProcedureThis cross-sectional study investigated children who underwent posterior fossa surgery using an online Pediatric Quality of Life Inventory questionnaire. CMS and non-CMS patients were included to identify QoL predictors.ResultsSixty-nine patients were included (male, 62.3%), 22 of whom had CMS. The mean follow-up time was 45.2 months. Children with CMS had a significantly lower mean QoL score (65.3 vs. 83.7, p &lt; 0.001) and subdomain mean scores (physical; 57.8 vs. 85.3, p &lt; 0.001; social: 69.5 vs. 85.1, p = 0.001; academic: p = 0.001) than those without CMS, except for the emotional domain (78.0 vs. 83.7, p = 0.062). Multivariable analysis revealed that CMS (coefficient = −14.748.61, p = 0.043), chemotherapy (coefficient = −7.629.82, p = 0.013), ventriculoperitoneal (VP) shunt placement (coefficient = −10.14, p = 0.024), and older age at surgery (coefficient = −1.1830, p = 0.007) were independent predictors of low total QoL scores. Physical scores were independently associated with CMS (coefficient = −27.4815.31, p = 0.005), VP shunt placement (coefficient = −12.86, p = 0.025), and radiotherapy (coefficient = −13.62, p = 0.007). Emotional score was negatively associated with age at surgery (coefficient = −1.92, p = 0.0337) and chemotherapy (coefficient = −9.11, p = 0.003). Social scores were negatively associated with male sex (coefficient = −13.68, p = 0.001) and VP shunt placement (coefficient = −1.36, p = 0.005), whereas academic scores were negatively correlated with chemotherapy (coefficient = −17.45, p &lt; 0.001) and age at surgery (coefficient = −1.92, p = 0.002). Extent of resection (coefficient = 13.16, p = 0.021) was a good predictor of higher academic scores.ConclusionCMS results in long-term neurological and neuropsychological deficits, negatively affecting QoL, and warranting early rehabilitation.
Amygdala's T1-weighted image radiomics outperforms volume for differentiation of anxiety disorder and its subtype
Authors: Li Qingfeng , Wang Wenzheng , Hu Zhishan 
Published: February 2023

IntroductionAnxiety disorder is the most common psychiatric disorder among adolescents, with generalized anxiety disorder (GAD) being a common subtype of anxiety disorder. Current studies have revealed abnormal amygdala function in patients with anxiety compared with healthy people. However, the diagnosis of anxiety disorder and its subtypes still lack specific features of amygdala from T1-weighted structural magnetic resonance (MR) imaging. The purpose of our study was to investigate the feasibility of using radiomics approach to distinguish anxiety disorder and its subtype from healthy controls on T1-weighted images of the amygdala, and provide a basis for the clinical diagnosis of anxiety disorder.MethodsT1-weighted MR images of 200 patients with anxiety disorder (including 103 GAD patients) as well as 138 healthy controls were obtained in the Healthy Brain Network (HBN) dataset. We extracted 107 radiomics features for the left and right amygdala, respectively, and then performed feature selection using the 10-fold LASSO regression algorithm. For the selected features, we performed group-wise comparisons, and use different machine learning algorithms, including linear kernel support vector machine (SVM), to achieve the classification between the patients and healthy controls.ResultsFor the classification task of anxiety patients vs. healthy controls, 2 and 4 radiomics features were selected from left and right amygdala, respectively, and the area under receiver operating characteristic curve (AUC) of linear kernel SVM in cross-validation experiments was 0.6739±0.0708 for the left amygdala features and 0.6403±0.0519 for the right amygdala features; for classification task for GAD patients vs. healthy controls, 7 and 3 features were selected from left and right amygdala, respectively, and the cross-validation AUCs were 0.6755±0.0615 for the left amygdala features and 0.6966±0.0854 for the right amygdala features. In both classification tasks, the selected amygdala radiomics features had higher discriminatory significance and effect sizes compared with the amygdala volume.DiscussionOur study suggest that radiomics features of bilateral amygdala potentially could serve as a basis for the clinical diagnosis of anxiety disorder.
Online HIV prophylaxis delivery: Protocol for the ePrEP Kenya pilot study
Authors: Kiptinness Catherine , Naik Paulami , Thuo Nicholas , Malen Rachel C. , Dettinger Julia C. , Pintye Jillian , Rafferty Maeve , Jomo Edwin , Nyamasyo Nicky , Wood Tony , Isabelli Paul , Morris Sarah , Hattery David , Stergachis Andy , Were Daniel , Sharma Monisha , Ngure Kenneth , Mugambi Melissa Latigo , Ortblad Katrina F. 
Published: February 2023

BackgroundOnline pharmacies in Kenya provide sexual and reproductive health products (e.g., HIV self-testing, contraception) and could be leveraged to increase the reach of HIV pre-exposure and post-exposure prophylaxis (PrEP/PEP) to populations who do not frequently attend health facilities. To date, evidence is limited for operationalizing online PrEP/PEP delivery and the type of populations reached with this differential service delivery model.MethodsThe ePrEP Kenya Pilot will deliver daily oral PrEP and PEPviaMYDAWA, a private online pharmacy retailer, to clients in Nairobi for 18 months. Potential clients will obtain information about PrEP/PEP on MYDAWA's sexual wellness page and self-screen for HIV risk. Individuals ≥18 years, identified as at HIV risk, and willing to pay for a blood-based HIV self-test and PrEP/PEP delivery will be eligible for enrollment. To continue with online PrEP/PEP initiation, eligible clients will purchase a blood-based HIV self-test for 250 KES (~USD 2) [delivered to their setting of choice for 99 KES (~USD 1)], upload an image of their self-test result, and attend a telemedicine visit with a MYDAWA provider. During the telemedicine visit, providers will screen clients for PrEP/PEP eligibility, including clinical concerns (e.g., kidney disease), discuss self-test results, and complete counseling on PrEP/PEP use and safety. Providers will refer clients who self-test HIV positive or report any existing medical conditions to the appropriate services at healthcare facilities that meet their preferences. Eligible clients will be prescribed PrEP (30-day PrEP supply at initiation; 90-day PrEP supply at follow-up visits) or PEP (28-day supply) for free and have it delivered for 99 KES (~USD 1). We will measure PrEP and PEP initiation among eligible clients, PEP-to-PrEP transition, PrEP continuation, and implementation outcomes (e.g., feasibility, acceptability, and costs).DiscussionEstablishing pathways to increase PrEP and PEP access is crucial to help curb new HIV infections in settings with high HIV prevalence. The findings from this study will provide evidence on the implementation of online pharmacy PrEP and PEP service delivery that can help inform guidelines in Kenya and similar settings.
A cost-effectiveness analysis of risk-based intervention for prevention of cardiovascular diseases in IraPEN program: A modeling study
Authors: Jamshidi Amirparviz , Daroudi Rajabali , Aas Eline , Khalili Davood 
Published: February 2023

BackgroundIraPEN, a program developed in Iran based on the World Health Organization (WHO) package of essential noncommunicable (PEN) disease interventions for primary healthcare, was launched in 2015. Preventive interventions for cardiovascular diseases (CVDs) are based on the level of risk calculated using the WHO CVD risk chart.ObjectiveThe main objective of this study was to measure the potential cost-effectiveness (CE) of IraPEN preventive actions for CVD in comparison with the status quo.MethodsA CE analysis from a healthcare perspective was conducted. Markov models were employed for individuals with and without diabetes separately. Based on the WHO CVD risk chart, four index cohorts were constructed as low (&lt;10%), moderate (10%−19%), high (20%−29%), and very high risk (≥30%). Life years (LY) gained and quality-adjusted life years (QALY) were used as the outcome measures.ResultsThe intervention yields an incremental cost-effectiveness ratio (ICER) of $804, $551, and –$44 per QALY for moderate, high, and very high CVD risk in groups without diabetes, respectively. These groups gained 0.69, 0.96, and 1.45 LY, respectively, from the intervention. The results demonstrated an ICER of $711, $630, –$42, and –$71 for low, moderate, high, and very high-risk groups with diabetes, respectively, while they gained 0.46, 1.2, 2.04, and 2.29 years from the intervention.ConclusionThe IraPEN program was highly cost-effective for all CVD risk groups in the individuals without diabetes except the low-risk group. The intervention was cost-effective for all patients with diabetes regardless of their CVD risk. The results demonstrated that the IraPEN program can likely provide substantial health benefits to Iranian individuals and cost savings to the national healthcare provider.
The global, regional, and national burden of stomach cancer among adolescents and young adults in 204 countries and territories, 1990–2019: A population-based study
Authors: Zhang Ziqiang , Wang Jun , Song Ning , Shi Liubin , Du Jianjun 
Published: February 2023

BackgroundStomach cancer is a significant health problem in many countries. But healthcare needs of adolescents and young adults (AYAs) stomach cancer patients have been historically neglected. An accurate appraisal of the burden of AYA stomach cancer is crucial to formulating effective preventive strategies. In this study, we report the most recent estimates of AYA stomach cancer burden concerning socio-demographic index (SDI) in 204 countries and territories between 1990 and 2019.MethodsEstimates from the Global Burden of Disease study 2019 were used to analyze incidence, mortality, and disability-adjusted life years (DALYs) due to AYA stomach cancer at global, regional, and national levels. Association between AYA stomach cancer burden and SDI were investigated. All estimates are reported as absolute numbers and age-standardized rates, which were standardized to the GBD world population and reported per 100,000 population.ResultsIn 2019, there were 49,000 incident cases, 27,895 deaths, and 1.57 million DALYs due to AYA stomach cancer globally. The highest age-standardized incidence rate occurred in East Asia [2.42 (women) and 4.71 (men) per 100,000 person-years] and high-income Asia Pacific [3.16 (women) and 2.61 (men) per 100,000 person-years]. Age-standardized death [1.53 (women) and 2.65 (men) per 100,000 person-years] and DALY [150.96 (women) and 87.13 (men) per 100,000 person-years] rates were highest in Oceania. Compared with 1990, in 2019 more than 1,075 more incident cases of AYA stomach cancer were estimated with a decrease of 7,784 deaths. Despite the increase in absolute number of incident cases, the worldwide age-standardized rates of AYA stomach cancer (incidence, deaths, and DALYs) have declined since 1990. The drop in the disease burden was associated with an improved SDI. Globally, 24.41% of the age-standardized DALYs were attributable to a high-sodium diet in both sexes combined, and 0.57% of the age-standardized DALYs were attributable to smoking in men.ConclusionThe global burden of AYA stomach cancer is substantial, especially in developing regions. Capacity-building activities for AYA stomach cancer will benefit the younger generation and population health worldwide.