bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing access to fertility preservation for women with breast cancer: protocol for a stepped-wedge cluster randomized trial in France
Authors: Addamiano Maria Claudia , Joannes Camille , Fonquerne Leslie , Morel Charlotte , Lauzeille Delphine , Belkadi Lorène , Empereur Fabienne , Grosclaude Pascale , Bauvin Eric , Delpierre Cyrille , Lamy Sébastien , Durand Marie-Anne 
Published: January 2024

Abstract
Background
With the increase in the number of long-term survivors, interest is shifting from cancer survival to life and quality of life after cancer. These include consequences of long-term side effects of treatment, such as gonadotoxicity. Fertility preservation is becoming increasingly important in cancer management. International recommendations agree on the need to inform patients prior to treatments about the risk of fertility impairment and refer them to specialized centers to discuss fertility preservation. However, the literature reveals suboptimal access to fertility preservation on an international scale, and particularly in France, making information for patients and oncologists a potential lever for action. Our overall goal is to improve access to fertility preservation consultations for women with breast cancer through the development and evaluation of a combined intervention targeting the access and diffusion of information for these patients and brief training for oncologists.

Methods
Firstly, we will improve existing information tools and create brief training content for oncologists using a qualitative, iterative, user-centred and participatory approach (objective 1). We will then use these tools in a combined intervention to conduct a stepped-wedge cluster randomized trial (objective 2) including 750 women aged 18 to 40 newly treated with chemotherapy for breast cancer at one of the 6 participating centers. As the primary outcome of the trial will be the access to fertility preservation counselling before and after using the combined intervention (brochures and brief training for oncologists), we will compare the rate of fertility preservation consultations between the usual care and intervention phases using linear regression models. Finally, we will analyse our approach using a context-sensitive implementation analysis and provide key elements for transferability to other contexts in France (objective 3).

Discussion
We expect to observe an increase in access to fertility preservation consultations as a result of the combined intervention. Particular attention will be paid to the effect of this intervention on socially disadvantaged women, who are known to be at greater risk of inappropriate treatment. The user-centred design principles and participatory approaches used to optimize the acceptability, usability and feasibility of the combined intervention will likely enhance its impact, diffusion and sustainability.

Trial registration
Registry: ClinicalTrials.gov. Trial registration number: NCT05989776. Date of registration: 7th September 2023. URL: https://classic.clinicaltrials.gov/ct2/show/NCT05989776.

Protocol version
Manuscript based on study protocol version 2.0, 21st may 2023.
The causal relationship of female infertility and psychiatric disorders in the European population: a bidirectional two-sample Mendelian randomization study
Authors: Zeng Pengfei , Zhang Hanxiao , Lu Liyue , Li Yanting , Yu Tong , Zhang Jun , Zhou Hang 
Published: January 2024

Abstract
Background
Infertility affects many couples globally, causing physical, emotional, and financial burdens. While observational studies suggest a link between psychiatric disorders and female infertility, causal relationships remain uncertain. Mendelian randomization analysis, using genome-wide association studies data, minimizes confounding factors and reverse causation, providing valuable insights into causal associations.

Methods
We conducted Mendelian randomization analysis to explore the potential causal relationship between female infertility and psychiatric disorders. Genome-wide association studies summary data for female infertility (112,105 individuals of European ancestry, comprising 11,442 cases and 100,663 controls), depression (807,553 individuals of European ancestry, comprising 246,363 cases and 561,190 controls), anxiety (21,763 individuals of European ancestry, comprising 7,016 cases and 14,745 controls), bipolar disorder (51,710 individuals of European ancestry, comprising 20,352 cases and 31,358 controls), and eating disorders (72,517 individuals of European ancestry, comprising 16,992 cases and 55,525 controls) were utilized. Instrumental variables were selected based on significant single nucleotide polymorphisms associated with each phenotype. We assessed instrumental variable strength, examined confounding factors, and employed inverse variance weighting, weighted median, and MR-Egger approaches for analysis.

Results
Our analysis included 85 single nucleotide polymorphisms for female infertility and 62 single nucleotide polymorphisms for psychiatric disorders. Results suggest a potential causal relationship between depression and female infertility, with both inverse variance weighting and weighted median methods showing increased infertility risk in depressed patients. Evidence is weak regarding bipolar disorder not increasing female infertility risk. We found no evidence supporting causal links between anxiety, eating disorders, and female infertility. Similarly, no causal relationship was found between female infertility and psychiatric disorders in the opposite direction. Sensitivity analyses and tests for heterogeneity and polymorphism supported result robustness.

Conclusions
This analysis provides evidence for a potential causal relationship between depression and female infertility. Addressing depression in infertile women may improve fertility outcomes. Further research is needed to explore underlying mechanisms and potential interventions for improving fertility outcomes in women with psychiatric disorders.
Based on whole-exome sequencing to explore the rule of Herceptin and TKI resistance in breast cancer patients
Authors: Guo Liantao , Cheng Hong , Liu Jianhua , Shao Weikang , Luo Lan , Zheng Weijie , Sun Shengrong , Kong Deguang , Chen Chuang 
Published: January 2024

Abstract
Background
Breast cancer is the second leading cause of cancer-related death in women, and drug resistance during treatment is a major challenge. However, the mechanisms underlying drug resistance are not fully understood. Here we applied whole-exome sequencing (WES) to clarify resistant rules to Herceptin and tyrosine kinase inhibitors (TKIs).

Methods
There are 12 HER2+ breast cancer patients who were done WES. Samples from tumor and surrounding tissues underwent DNA sequencing and analysis. Various experimental and bioinformatics techniques were employed, including genomic capture, mutation analysis (Genome Analysis Toolkit (GATK), etc.), bioinformatics assessments, and drug-gene interaction investigations. Ultimately, the study explored the association of APOB gene expression with breast cancer recurrence rates, immune cell infiltration, and drug response.

Results
The C > T mutation frequency was highest in the Herceptin-insensitive (HI) and verification groups, codenamed YI, contrasting with the Herceptin-sensitive (HE) group. No microsatellite instability (MSI)-H patients were in the HE group, but both HI and YI groups had 1 each. Significant differences in transition-transversion (TiTv) were observed in the HI and YI groups rather than the HE group. In the TKI- insensitive (TI) group, C > T mutations were highest, differing from the TKI-sensitive (TE) group. TE group included 2 MSI-H patients. Significant differences in TiTv were found in the TI group rather than the TE group. Mutated APOB may resist Herceptin and TKI, increasing immune infiltration. We identified potential drugs targeting it.

Conclusions
Our study suggested that a higher percentage of C > T mutations, significant differences in TiTv, and MSI-H status may indicate Herceptin resistance, while a higher percentage of C > T mutations, significant differences in TiTv, and the absence of MSI-H may indicate TKI resistance in breast cancer patients. For patients resistant to both Herceptin and TKI, mutated APOB may play a crucial role in resistance.
What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study
Authors: de Diego Cristina , Lasierra Ana Belén , López-Vergara Lucía , Torralba Laura , Ruiz de Gopegui Pablo , Lahoz Raquel , Abadía Claudia , Godino Javier , Cebollada Alberto , Jimeno Beatriz , Bello Carlota , Tejada Antonio , Bello Salvador 
Published: January 2024

Abstract
Background
Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, and there are scarce data on their evolution during the disease. We studied circulating NET markers in patients with COVID-19 throughout their hospitalization.

Methods
We prospectively included 93 patients (201 blood samples), evaluating the disease severity in 3 evolutionary phases (viral, early, and late inflammation). Of these, 72 had 180 samples in various phases. We also evaluated 55 controls with similar age, sex and comorbidities. We measured 4 NET markers in serum: cfDNA, CitH3, and MPO-DNA and NE-DNA complexes; as well as neutrophil-related cytokines IL-8 and G-CSF.

Results
The COVID-19 group had higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), and cfDNA, MPO-DNA, and NE-DNA (7.87 vs 2.56 ng/mL; 0.80 vs 0.52 and 1.04 vs 0.72, respectively, p < 0.001 for all) than the controls throughout hospitalisation. cfDNA was the only NET marker clearly related to severity, and it remained higher in non-survivors during the 3 phases. Only cfDNA was an independent risk factor for mortality and need for intensive care. Neutrophil count, IL-8, and G-CSF were significantly related to severity. MPO-DNA and NE-DNA showed significant correlations (r: 0.483, p < 0.001), including all 3 phases and across all severity grades, and they only remained significantly higher on days 10–16 of evolution in those who died. Correlations among the other NET markers were lower than expected.

Conclusions
The circulating biomarkers of NETs were present in patients with COVID-19 throughout hospitalization. cfDNA was associated with severity and mortality, but the three other markers showed little or no association with these outcomes. Neutrophil activity and neutrophil count were also associated with severity. MPO-DNA and NE-DNA better reflected NET formation. cfDNA appeared to be more associated with overall tissue damage; previous widespread use of this marker could have overestimated the relationship between NETs and severity. Currently, there are limitations to accurate NET markers measurement that make it difficult to assess its true role in COVID-19 pathogenesis.
How do the carbon and nitrogen sources affect the synthesis of β-(1,3/1,6)-glucan, its structure and the susceptibility of Candida utilis yeast cells to immunolabelling with β-(1,3)-glucan monoclonal antibodies?
Authors: Bzducha-Wróbel Anna , Farkaš Pavol , Bieliková Sandra , Čížová Alžbeta , Sujkowska-Rybkowska Marzena 
Published: January 2024

Abstract
Background
The need to limit antibiotic therapy due to the spreading resistance of pathogenic microorganisms to these medicinal substances stimulates research on new therapeutic agents, including the treatment and prevention of animal diseases. This is one of the goals of the European Green Deal and the Farm-To-Fork strategy. Yeast biomass with an appropriate composition and exposure of cell wall polysaccharides could constitute a functional feed additive in precision animal nutrition, naturally stimulating the immune system to fight infections.

Results
The results of the research carried out in this study showed that the composition of Candida utilis ATCC 9950 yeast biomass differed depending on growth medium, considering especially the content of β-(1,3/1,6)-glucan, α-glucan, and trehalose. The highest β-(1,3/1,6)-glucan content was observed after cultivation in deproteinated potato juice water (DPJW) as a nitrogen source and glycerol as a carbon source. Isolation of the polysaccharide from yeast biomass confirmed the highest yield of β-(1,3/1,6)-glucan after cultivation in indicated medium. The differences in the susceptibility of β-(1,3)-glucan localized in cells to interaction with specific β-(1,3)-glucan antibody was noted depending on the culture conditions. The polymer in cells from the DPJW supplemented with glycerol and galactose were labelled with monoclonal antibodies with highest intensity, interestingly being less susceptible to such an interaction after cell multiplication in medium with glycerol as carbon source and yeast extract plus peptone as a nitrogen source.

Conclusions
Obtained results confirmed differences in the structure of the β-(1,3/1,6)-glucan polymers considering side-chain length and branching frequency, as well as in quantity of β-(1,3)- and β-(1,6)-chains, however, no visible relationship was observed between the structural characteristics of the isolated polymers and its susceptibility to immunolabeling in whole cells. Presumably, other outer surface components and molecules can mask, shield, protect, or hide epitopes from antibodies. β-(1,3)-Glucan was more intensely recognized by monoclonal antibody in cells with lower trehalose and glycogen content. This suggests the need to cultivate yeast biomass under appropriate conditions to fulfil possible therapeutic functions. However, our in vitro findings should be confirmed in further studies using tissue or animal models.
Tumor-derived small extracellular vesicles in cancer invasion and metastasis: molecular mechanisms, and clinical significance
Authors: Zhang Chi , Qin Chaoying , Dewanjee Saikat , Bhattacharya Hiranmoy , Chakraborty Pratik , Jha Niraj Kumar , Gangopadhyay Moumita , Jha Saurabh Kumar , Liu Qing 
Published: January 2024

AbstractThe production and release of tumor-derived small extracellular vesicles (TDSEVs) from cancerous cells play a pivotal role in the propagation of cancer, through genetic and biological communication with healthy cells. TDSEVs are known to orchestrate the invasion-metastasis cascade via diverse pathways. Regulation of early metastasis processes, pre-metastatic niche formation, immune system regulation, angiogenesis initiation, extracellular matrix (ECM) remodeling, immune modulation, and epithelial-mesenchymal transition (EMT) are among the pathways regulated by TDSEVs. MicroRNAs (miRs) carried within TDSEVs play a pivotal role as a double-edged sword and can either promote metastasis or inhibit cancer progression. TDSEVs can serve as excellent markers for early detection of tumors, and tumor metastases. From a therapeutic point of view, the risk of cancer metastasis may be reduced by limiting the production of TDSEVs from tumor cells. On the other hand, TDSEVs represent a promising approach for in vivo delivery of therapeutic cargo to tumor cells. The present review article discusses the recent developments and the current views of TDSEVs in the field of cancer research and clinical applications.
Cumulative residual cholesterol predicts the risk of cardiovascular disease in the general population aged 45 years and older
Authors: Zhao Mengjie , Xiao Mengli , Tan Qin , Ji Jinjin , Lu Fang 
Published: January 2024

Abstract
Background
Numerous studies have affirmed a robust correlation between residual cholesterol (RC) and the occurrence of cardiovascular disease (CVD). However, the current body of literature fails to adequately address the link between alterations in RC and the occurrence of CVD. Existing studies have focused mainly on individual RC values. Hence, the primary objective of this study is to elucidate the association between the cumulative RC (Cum-RC) and the morbidity of CVD.

Methods
The changes in RC were categorized into a high-level fast-growth group (Class 1) and a low-level slow-growth group (Class 2) by K-means cluster analysis. To investigate the relationship between combined exposure to multiple lipids and CVD risk, a weighted quantile sum (WQS) regression analysis was employed. This analysis involved the calculation of weights for total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which were used to effectively elucidate the RC.

Results
Among the cohort of 5,372 research participants, a considerable proportion of 45.94% consisted of males, with a median age of 58. In the three years of follow-up, 669 participants (12.45%) had CVD. Logistic regression analysis revealed that Class 2 individuals had a significantly reduced risk of developing CVD compared to Class 1. The probability of having CVD increased by 13% for every 1-unit increase in the Cum-RC according to the analysis of continuous variables. The restricted cubic spline (RCS) analysis showed that Cum-RC and CVD risk were linearly related (P for nonlinearity = 0.679). The WQS regression results showed a nonsignificant trend toward an association between the WQS index and CVD incidence but an overall positive trend, with the greatest contribution from TC (weight = 0.652), followed by LDL (weight = 0.348).

Conclusion
Cum-RC was positively and strongly related to CVD risk, suggesting that in addition to focusing on traditional lipid markers, early intervention in patients with increased RC may further reduce the incidence of CVD.
CircNUP50 is a novel therapeutic target that promotes cisplatin resistance in ovarian cancer by modulating p53 ubiquitination
Authors: Zhu Yunshu , Liang Leilei , Zhao Yuxi , Li Jian , Zeng Jia , Yuan Yihang , Li Ning , Wu Lingying 
Published: January 2024

Abstract
Background
Most patients with ovarian cancer (OC) treated with platinum-based chemotherapy have a dismal prognosis owing to drug resistance. However, the regulatory mechanisms of circular RNA (circRNA) and p53 ubiquitination are unknown in platinum-resistant OC. We aimed to identify circRNAs associated with platinum-resistant OC to develop a novel treatment strategy.

Methods
Platinum-resistant circRNAs were screened through circRNA sequencing and validated using quantitative reverse-transcription PCR in OC cells and tissues. The characteristics of circNUP50 were analysed using Sanger sequencing, oligo (dT) primers, ribonuclease R and fluorescence in situ hybridisation assays. Functional experimental studies were performed in vitro and in vivo. The mechanism underlying circNUP50-mediated P53 ubiquitination was investigated through circRNA pull-down analysis and mass spectrometry, luciferase reporters, RNA binding protein immunoprecipitation, immunofluorescence assays, cycloheximide chase assays, and ubiquitination experiments. Finally, a platinum and si-circNUP50 co-delivery nanosystem (Psc@DPP) was constructed to treat platinum-resistant OC in an orthotopic animal model.

Results
We found that circNUP50 contributes to platinum-resistant conditions in OC by promoting cell proliferation, affecting the cell cycle, and reducing apoptosis. The si-circNUP50 mRNA sequencing and circRNA pull-down analysis showed that circNUP50 mediates platinum resistance in OC by binding p53 and UBE2T, accelerating p53 ubiquitination. By contrast, miRNA sequencing and circRNA pull-down experiments indicated that circNUP50 could serve as a sponge for miR-197-3p, thereby upregulating G3BP1 to mediate p53 ubiquitination, promoting OC platinum resistance. Psc@DPP effectively overcame platinum resistance in an OC tumour model and provided a novel idea for treating platinum-resistant OC using si-circNUP50.

Conclusions
This study reveals a novel molecular mechanism by which circNUP50 mediates platinum resistance in OC by modulating p53 ubiquitination and provides new insights for developing effective therapeutic strategies for platinum resistance in OC.

Graphical Abstract
Cell-cell communication characteristics in breast cancer metastasis
Authors: Xu Jingtong , Gao Fangyan , Liu Weici , Guan Xiaoxiang 
Published: January 2024

AbstractBreast cancer, a highly fatal disease due to its tendency to metastasize, is the most prevalent form of malignant tumors among women worldwide. Numerous studies indicate that breast cancer exhibits a unique predilection for metastasis to specific organs including the bone, liver, lung, and brain. However, different types of, The understanding of the heterogeneity of metastatic breast cancer has notably improved with the recent advances in high-throughput sequencing techniques. Focusing on the modification in the microenvironment of the metastatic organs and the crosstalk between tumor cells and in situ cells, noteworthy research points include the identification of two distinct modes of tumor growth in bone metastases, the influence of type II pneumocyte on lung metastases, the paradoxical role of Kupffer cells in liver metastases, and the breakthrough of the blood-brain barrier (BBB) breach in brain metastases. Overall, this review provides a comprehensive overview of the characteristics of breast cancer metastases, shedding light on the pivotal roles of immune and resident cells in the development of distinct metastatic foci.
Graphical Abstract
Exploring the predictive power of jejunal microbiome composition in clinical and subclinical necrotic enteritis caused by Clostridium perfringens: insights from a broiler chicken model
Authors: Gautam Hemlata , Ayalew Lisanework E. , Shaik Noor Ahmad , Subhasinghe Iresha , Popowich Shelly , Chow-Lockerbie Betty , Dixon Alexa , Ahmed Khawaja Ashfaque , Tikoo Suresh K. , Gomis Susantha 
Published: January 2024

Abstract
Background
Necrotic enteritis (NE) is a severe intestinal infection that affects both humans and poultry. It is caused by the bacterium Clostridium perfringens (CP), but the precise mechanisms underlying the disease pathogenesis remain elusive. This study aims to develop an NE broiler chicken model, explore the impact of the microbiome on NE pathogenesis, and study the virulence of CP isolates with different toxin gene combinations.

Methods
This study established an animal disease model for NE in broiler chickens. The methodology encompassed inducing abrupt protein changes and immunosuppression in the first experiment, and in the second, challenging chickens with CP isolates containing various toxin genes. NE was evaluated through gross and histopathological scoring of the jejunum. Subsequently, jejunal contents were collected from these birds for microbiome analysis via 16S rRNA amplicon sequencing, followed by sequence analysis to investigate microbial diversity and abundance, employing different bioinformatic approaches.

Results
Our findings reveal that CP infection, combined with an abrupt increase in dietary protein concentration and/or infection with the immunosuppressive variant infectious bursal disease virus (vIBDV), predisposed birds to NE development. We observed a significant decrease (p < 0.0001) in the abundance of Lactobacillus and Romboutsia genera in the jejunum, accompanied by a notable increase (p < 0.0001) in Clostridium and Escherichia. Jejunal microbial dysbiosis and severe NE lesions were particularly evident in birds infected with CP isolates containing cpa, netB, tpeL, and cpb2 toxin genes, compared to CP isolates with other toxin gene combinations. Notably, birds that did not develop clinical or subclinical NE following CP infection exhibited a significantly higher (p < 0.0001) level of Romboutsia. These findings shed light on the complex interplay between CP infection, the gut microbiome, and NE pathogenesis in broiler chickens.

Conclusion
Our study establishes that dysbiosis within the jejunal microbiome serves as a reliable biomarker for detecting subclinical and clinical NE in broiler chicken models. Additionally, we identify the potential of the genera Romboutsia and Lactobacillus as promising candidates for probiotic development, offering effective alternatives to antibiotics in NE prevention and control.