bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MYBL2–CCL2 axis promotes tumor progression and resistance to anti-PD-1 therapy in ovarian cancer by inducing immunosuppressive macrophages
Authors: Pan Baoyue , Wan Ting , Zhou Yun , Huang Shuting , Yuan Linjing , Jiang Yinan , Zheng Xiaojing , Liu Pingping , Xiang Huiling , Ju Mingxiu , Luo Rongzhen , Jia Weihua , Lan ChunYan , Li Jundong , Zheng Min 
Published: October 2023

Abstract
Background
An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored.

Methods
A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies—namely RNA-sequencing, western blotting, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay—were used to reveal the mechanisms of MYBL2 in the OVC microenvironment.

Results
We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance.

Conclusions
The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy.
Association between total cholesterol and lumbar bone density in Chinese: a study of physical examination data from 2018 to 2023
Authors: Sun Yongbing , Qi Xin , Lin Xinbei , Zhou Yang , Lv Xue , Zhou Jing , Li Zhonglin , Wu Xiaoling , Zou Zhi , Li Yongli , Li Hao 
Published: October 2023

Abstract
Background
The impact of total cholesterol (TC) on lumbar bone mineral density (BMD) is a topic of interest. However, empirical evidence on this association from demographic surveys conducted in China is lacking. Therefore, this study aimed to examine the relationship between serum TC and lumbar BMD in a sample of 20,544 Chinese adults between the ages of 20 and 80 years over a period of 5 years, from February 2018 to February 2023. Thus, we investigated the effect of serum TC level on lumbar BMD and its relationship with bone reduction in a Chinese adult population.

Methods
This cross-sectional study used data obtained from the Department of Health Management at Henan Provincial People’s Hospital between February 2018 and February 2023. The aim of this study was to examine the correlation between serum TC and lumbar BMD in individuals of different sexes. The research methodology encompassed population description, analysis of stratification, single-factor and multiple-equation regression analyses, smooth curve fitting, and analysis of threshold and saturation effects. The R and EmpowerStats software packages were used for statistical analysis.

Results
After adjusting for confounding variables, a multiple linear regression model revealed a significant correlation between TC and lumbar BMD in men. In subgroup analysis, serum TC was found to have a positive association with lumbar BMD in men, specifically those aged 45 years or older, with a body mass index (BMI) ranging from 24 to 28 kg/m2. A U-shaped correlation arose between serum TC and lumbar BMD was detected in women of different ages and BMI, the inflection point was 4.27 mmol/L for women aged ≥ 45 years and 4.35 mmol/L for women with a BMI of ≥ 28 kg/m2.

Conclusion
In this study, Chinese adults aged 20–80 years displayed different effects of serum TC on lumbar BMD in sex-specific populations. Therefore, monitoring BMI and serum TC levels in women of different ages could prevent osteoporosis and osteopenia.

Trial registration
The research protocol was approved by the Ethics Committee of Beijing Jishuitan Hospital, in accordance with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are part of the China Health Quantitative CT Big Data Research team, which has been registered at clinicaltrials.gov (code: NCT03699228).
Re-stratification of patients with copy-number low endometrial cancer by clinicopathological characteristics
Authors: Liwei Li , He Li , Yibo Dai , Luyang Zhao , Zhihui Shen , Nan Kang , Danhua Shen , Junzhu Wang , Zhiqi Wang , Jianliu Wang 
Published: October 2023

Abstract
Objective
To stratify patients with copy-number low (CNL) endometrial cancer (EC) by clinicopathological characteristics.

Methods
EC patients who underwent surgery between June 2018 and June 2022 at Peking University People’s Hospital were included and further classified according to TCGA molecular subtyping: POLE ultramutated, microsatellite instability high (MSI-H), CNL, and copy-number high (CNH). Clinicopathological characteristics and prognosis of CNL patients were retrospectively reviewed. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis, and independent risk factors were identified. Differentially expressed genes (DEGs) according to overall survival (OS) were screened based on the transcriptome of CNL cases from the TCGA program. Finally, a nomogram was established, with an accuracy analysis performed.

Results
(1) A total of 279 EC patients were included, of whom 168 (60.2%) were in the CNL group. A total of 21 patients had recurrence and 6 patients deceased, and no significant difference in recurrence-free survival (RFS) was exhibited among the four molecular subtypes (P = 0.104), but that in overall survival (OS) was statistically significant (P = 0.036). (2) CNL patients were divided into recurrence and non-recurrence groups, and significant differences (P < 0.05) were found between the two groups in terms of pathological subtype, FIGO stage, ER, PR, glycated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL-C). All the above factors were included in univariate and multivariate Cox regression models, among which pathological subtype, PR, and HDL-C were statistically different (P < 0.05), resulting in three independent risk factors for the prognosis of patients in the CNL group. (3) By comparing the transcriptome of tumor tissues between living and deceased CNL patients from the TCGA database, 903 (4.4%) DEGs were screened, with four lipid metabolism pathways significantly enriched. Finally, a nomogram was established, and internal cross-validation was performed, showing good discrimination accuracy with an AUC of 0.831 and a C-index of 0.748 (95% CI 0.444–1.052). (4) According to the established nomogram and the median total score (85.89), patients were divided into the high score group (n = 85) and low score group (n = 83), and the 8 patients with recurrence were all in the high score group. Survival analysis was performed between the two groups, and the difference in RFS was statistically significant (P = 0.010).

Conclusion
In the CNL group of EC patients, pathological subtype, PR, and HDL-C were independent prognostic risk factors, the nomogram established based upon which had a good predictive ability for the recurrence risk of patients with CNL EC.
Analytical reference framework to analyze non-COVID-19 events
Authors: del Pilar Villamil María , Velasco Nubia , Barrera David , Segura-Tinoco Andrés , Bernal Oscar , Hernández José Tiberio 
Published: October 2023

Abstract
Background
The COVID-19 pandemic has disrupted the healthcare system, leading to delays in detection of other non-COVID-19 diseases. This paper presents ANE Framework (Analytics for Non-COVID-19 Events), a reliable and user-friendly analytical forecasting framework designed to predict the number of patients with non-COVID-19 diseases. Prior to 2020, there were analytical models focused on specific illnesses and contexts. Then, most models have focused on understanding COVID-19 behavior. There is a lack of analytical frameworks that enable disease forecasting for non-COVID-19 diseases.

Methods
The ANE Framework utilizes time series analysis to generate forecasting models. The framework leverages daily data from official government sources and employs SARIMA models to forecast the number of non-COVID-19 cases, such as tuberculosis and suicide attempts.

Results
The framework was tested on five different non-COVID-19 events. The framework performs well across all events, including tuberculosis and suicide attempts, with a Mean Absolute Percentage Error (MAPE) of up to 20% and the consistency remains independent of the behavior of each event. Moreover, a pairwise comparison of averages can lead to over or underestimation of the impact. The disruption caused by the pandemic resulted in a 17% gap (2383 cases) between expected and reported tuberculosis cases, and a 19% gap (2464 cases) for suicide attempts. These gaps varied between 20 and 64% across different cities and regions. The ANE Framework has proven to be reliable for analyzing several diseases and exhibits the flexibility to incorporate new data from various sources. Regular updates and the inclusion of new associated data enhance the framework's effectiveness.

Conclusions
Current pandemic shows the necessity of developing flexible models to be adapted to different illness data. The framework developed proved to be reliable for the different diseases analyzed, presenting enough flexibility to update with new data or even include new data from different databases. To keep updated on the result of the project allows the inclusion of new data associated with it. Similarly, the proposed strategy in the ANE framework allows for improving the quality of the obtained results with news events.
Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study
Authors: Linhart Aleš , Dostálová Gabriela , Nicholls Kathy , West Michael L. , Tøndel Camilla , Jovanovic Ana , Giraldo Pilar , Vujkovac Bojan , Geberhiwot Tarekegn , Brill-Almon Einat , Alon Sari , Chertkoff Raul , Rocco Rossana , Hughes Derralynn 
Published: October 2023

Abstract
Background
Pegunigalsidase alfa is a novel, PEGylated α-galactosidase-A enzyme-replacement therapy approved in the EU and US to treat patients with Fabry disease (FD).

Objective/methods
BRIDGE is a phase 3 open-label, switch-over study designed to assess safety and efficacy of 12 months of pegunigalsidase alfa (1 mg/kg every 2 weeks) treatment in adults with FD who had been previously treated with agalsidase alfa (0.2 mg/kg every 2 weeks) for ≥ 2 years.

Results
Twenty-seven patients were screened; 22 met eligibility criteria; and 20 (13 men, 7 women) completed the study. Pegunigalsidase alfa was well-tolerated, with 97% of treatment-emergent adverse events (TEAEs) being of mild or moderate severity. The incidence of treatment-related TEAEs was low, with 2 (9%) discontinuations due to TEAEs. Five patients (23%) reported infusion-related reactions. Overall mean (SD; n = 22) baseline estimated glomerular filtration rate (eGFR) was 82.5 (23.4) mL/min/1.73 m2 and plasma lyso-Gb3 level was 38.3 (41.2) nmol/L (men: 49.7 [45.8] nmol/L; women: 13.8 [6.1] nmol/L). Before switching to pegunigalsidase alfa, mean (standard error [SE]) annualized eGFR slope was − 5.90 (1.34) mL/min/1.73 m2/year; 12 months post-switch, the mean eGFR slope was − 1.19 (1.77) mL/min/1.73 m2/year; and mean plasma lyso-Gb3 reduced by 31%. Seven (35%) out of 20 patients were positive for pegunigalsidase alfa antidrug antibodies (ADAs) at ≥ 1 study timepoint, two of whom had pre-existing ADAs at baseline. Mean (SE) changes in eGFR slope for ADA-positive and ADA-negative patients were + 5.47 (3.03) and + 4.29 (3.15) mL/min/1.73 m2/year, respectively, suggesting no negative impact of anti-pegunigalsidase alfa ADAs on eGFR slope.

Conclusion
Pegunigalsidase alfa may offer a safe and effective treatment option for patients with FD, including those previously treated with agalsidase alfa.
TRN: NCT03018730. Date of registration: January 2017.
Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)
Authors: Genta Sofia , Lajkosz Katherine , Yee Noelle R. , Spiliopoulou Pavlina , Heirali Alya , Hansen Aaron R. , Siu Lillian L. , Saibil Sam , Stayner Lee-Anne , Yanekina Maryia , Sauder Maxwell B. , Keshavarzi Sareh , Salawu Abdulazeez , Vornicova Olga , Butler Marcus O. , Bedard Philippe L. , Razak Albiruni R. Abdul , Rottapel Robert , Chruscinski Andrzej , Coburn Bryan , Spreafico Anna 
Published: October 2023

Abstract
Background
Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb).

Methods
We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal–Wallis test. MFI 500 was used as threshold to define autoAb reactivity.

Results
A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009).

Conclusions
Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).
Development of super-specific epigenome editing by targeted allele-specific DNA methylation
Authors: Rajaram Nivethika , Kouroukli Alexandra G. , Bens Susanne , Bashtrykov Pavel , Jeltsch Albert 
Published: October 2023

Abstract
Background
Epigenome editing refers to the targeted reprogramming of genomic loci using an EpiEditor which may consist of an sgRNA/dCas9 complex that recruits DNMT3A/3L to the target locus. Methylation of the locus can lead to a modulation of gene expression. Allele-specific DNA methylation (ASM) refers to the targeted methylation delivery only to one allele of a locus. In the context of diseases caused by a dominant mutation, the selective DNA methylation of the mutant allele could be used to repress its expression but retain the functionality of the normal gene.

Results
To set up allele-specific targeted DNA methylation, target regions were selected from hypomethylated CGIs bearing a heterozygous SNP in their promoters in the HEK293 cell line. We aimed at delivering maximum DNA methylation with highest allelic specificity in the targeted regions. Placing SNPs in the PAM or seed regions of the sgRNA, we designed 24 different sgRNAs targeting single alleles in 14 different gene loci. We achieved efficient ASM in multiple cases, such as ISG15, MSH6, GPD1L, MRPL52, PDE8A, NARF, DAP3, and GSPT1, which in best cases led to five to tenfold stronger average DNA methylation at the on-target allele and absolute differences in the DNA methylation gain at on- and off-target alleles of > 50%. In general, loci with the allele discriminatory SNP positioned in the PAM region showed higher success rate of ASM and better specificity. Highest DNA methylation was observed on day 3 after transfection followed by a gradual decline. In selected cases, ASM was stable up to 11 days in HEK293 cells and it led up to a 3.6-fold change in allelic expression ratios.

Conclusions
We successfully delivered ASM at multiple genomic loci with high specificity, efficiency and stability. This form of super-specific epigenome editing could find applications in the treatment of diseases caused by dominant mutations, because it allows silencing of the mutant allele without repression of the expression of the normal allele thereby minimizing potential side-effects of the treatment.
Remimazolam tosylate's long-term sedative properties in ICU patients on mechanical ventilation: effectiveness and safety
Authors: Yao Zhiyuan , Liao Zhaomin , Li Guang , Wang Lu , Zhan Liying , Xia Wenfang 
Published: October 2023

Abstract
Objective
This study compared remimazolam tosylate with propofol or midazolam to assess its safety and effectiveness for long-term sedation of intensive care unit (ICU) patients requiring mechanical ventilation.

Methods
Adult patients in the ICU receiving sedation and mechanical ventilation for longer than 24 h were included in this single-center, prospective, observational study. Depending on the sedatives they were given, they were split into two groups (midazolam or propofol group; remimazolam group). ICU mortality was the main result. Laboratory tests, adverse events, and the length of ICU stay were considered secondary outcomes.

Results
A total of 106 patients were involved (46 received propofol or midazolam versus 60 received remimazolam). Age (P = 0.182), gender (P = 0.325), and the amount of time between being admitted to the ICU and receiving medication infusion (P = 0.770) did not substantially differ between the two groups. Multivariate analysis revealed no statistically significant difference in ICU mortality between the two groups. The remimazolam group showed less variability in heart rate (P = 0.0021), pH (P = 0.048), bicarbonate (P = 0.0133), lactate (P = 0.0002), arterial blood gas analyses, liver, and kidney function. The Richmond Agitation and Sedation Scale scores, length of ICU stay, and occurrence of adverse events did not exhibit significant differences between the two groups.

Conclusion
Remimazolam tosylate did not increase the total inpatient cost, the incidence of adverse events, and ICU mortality in patients with mechanical ventilation. These findings suggest that remimazolam may represent a promising alternative for sedation in the ICU setting.
Fashion consumption behaviors of sustainability consumers: Fast fashion or slow fashion?
Authors: Güven Hüseyin , Yakın Volkan 
Published: October 2023

Sustainability is a critical issue shaping our future, and consumer behavior is a major force in this area. Conscious choices of consumers have a critical impact on businesses achieving their sustainability goals. In order to protect the quality of life of future generations and protect our planet, it is of great importance that the interaction between consumers and businesses is shaped on the basis of sustainability. Sustainability is influential in different sectors and fields such as health, transportation, fashion and clothing, tourism and travel. Especially the clothing and fashion industry has a great potential in terms of sustainability. The fashion industry is a huge industry serving people around the world to foster creativity, trends and personal expression. Since the fashion sector has a great role in the destruction of nature, researchers and marketers have drawn attention to the importance of slow fashion and sustainability in order to raise awareness of the producer and the consumer. Therefore, sustainability is becoming an increasingly important issue in the fashion industry. Within the scope of this study, the effect of consumers' knowledge of sustainability on their attitudes and perceptions towards advertising messages and their fast/slow fashion preferences are examined.
(Extended English summary is at the end of this document)
Özet

Sürdürülebilirlik, geleceğimizi şekillendiren kritik bir konudur ve tüketici davranışları bu alanda büyük bir güç oluşturur. Tüketicilerin bilinçli tercihleri, işletmelerin sürdürülebilirlik hedeflerine ulaşmasında kritik bir etkiye sahiptir. Gelecek nesillerin yaşam kalitesini ve gezegenimizi korumak için, tüketiciler ve işletmeler arasındaki etkileşimin sürdürülebilirlik temelinde şekillenmesi büyük önem taşımaktadır. Sürdürülebilirlik sağlık, ulaşım, moda ve giyim, turizm ve seyahat gibi farklı sektörlerde ve alanlarda etkilidir. Özellikle giyim ve moda sektörü, sürdürülebilirlik açısından büyük bir potansiyele sahiptir. Moda endüstrisi, yaratıcılığı, trendleri ve kişisel ifadeyi teşvik etmek için dünyanın dört bir yanındaki insanlara hizmet veren devasa bir sektördür. Doğanın tahrip edilmesinde moda sektörünün rolü büyük olduğundan dolayı üreticinin ve tüketicinin bilinçlenmesi için araştırmacılar ve pazarlamacılar yavaş moda ve sürdürülebilirliğin önemine dikkat çekmişlerdir. Bu nedenle, sürdürülebilirlik moda sektöründe giderek daha önemli bir konu haline gelmektedir. Bu çalışma kapsamında tüketicilerin sürdürülebilirlik konusunda bilinç düzeylerinin reklam mesajlarına yönelik tutum ve algıları ile hızlı/yavaş moda tercihleri üzerindeki etkisi incelenmektedir.
Cultural and Linguistic Capital of Second-Generation Migrants in Cyprus and Sweden
Authors: Karpava Sviatlana , Ringblom Natasha 
Published: October 2023

Abstract
The linguistic and cultural values of migrants, as well as their attitudes and behaviour, differ from those of the host society. All resources and values can be characterised as linguistic and cultural capital, which can provide migrants with certain advantages in their new country of settlement. A heritage language (HL) and knowledge about another culture are important components of this linguistic cultural capital. It is crucial for multi-generational families to maintain their HL and transmit the culture of their heritage to help individuals gain a better understanding of their own identity. This study aims to investigate the views, attitudes, and beliefs of second-generation migrants in Cyprus and Sweden in relation to their HL, linguistic and cultural capital, factors affecting HL use, maintenance, and development, as well as their future plans and aspirations regarding HL transmission. Narrative analysis of the semi-structured interviews revealed certain differences and similarities between the countries under investigation regarding the personal reflections of the participants and their perceptions regarding the role of family language policies, home literacy environments, child and parental agency, socio-emotional well-being, local context, and other internal and external factors influencing HL use, maintenance, and transmission. Storytelling proved to be an effective method of narrative inquiry, providing a deeper insight into the complex process of HL development and support. In addition, it offered participants an opportunity to reflect on their personality, language, and culture.