bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood-based molecular and cellular biomarkers of early response to neoadjuvant PD-1 blockade in patients with non-small cell lung cancer
Authors: Zhang Xi , Chen Rui , Huo Zirong , Li Wenqing , Jiang Mengju , Su Guodong , Liu Yuru , Cai Yu , Huang Wuhao , Xiong Yuyan , Wang Shengguang 
Published: July 2024

Abstract
Background
Despite the improved survival observed in PD-1/PD-L1 blockade therapy, a substantial proportion of cancer patients, including those with non-small cell lung cancer (NSCLC), still lack a response.

Methods
Transcriptomic profiling was conducted on a discovery cohort comprising 100 whole blood samples, as collected multiple times from 48 healthy controls (including 43 published data) and 31 NSCLC patients that under treatment with a combination of anti-PD-1 Tislelizumab and chemotherapy. Differentially expressed genes (DEGs), simulated immune cell subsets, and germline DNA mutational markers were identified from patients achieved a pathological complete response during the early treatment cycles. The predictive values of mutational markers were further validated in an independent immunotherapy cohort of 1661 subjects, and then confirmed in genetically matched lung cancer cell lines by a co-culturing model.

Results
The gene expression of hundreds of DEGs (FDR p < 0.05, fold change < -2 or > 2) distinguished responders from healthy controls, indicating the potential to stratify patients utilizing early on-treatment features from blood. PD-1-mediated cell abundance changes in memory CD4 + and regulatory T cell subset were more significant or exclusively observed in responders. A panel of top-ranked genetic alterations showed significant associations with improved survival (p < 0.05) and heightened responsiveness to anti-PD-1 treatment in patient cohort and co-cultured cell lines.

Conclusion
This study discovered and validated peripheral blood-based biomarkers with evident predictive efficacy for early therapy response and patient stratification before treatment for neoadjuvant PD-1 blockade in NSCLC patients.
Metagenomic and metabolomic analysis showing the adverse risk–benefit trade-off of the ketogenic diet
Authors: Qiu Hongyan , Kan Chengxia , Han Fang , Luo Youhong , Qu Na , Zhang Kexin , Ma Yanhui , Hou Ningning , Wu Di , Sun Xiaodong , Shi Junfeng 
Published: July 2024

Abstract
Background
Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity.

Methods
Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents.

Results
Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity.

Conclusions
The study suggest that the ketogenic diet had an unfavorable risk–benefit trade-off and may compromise metabolic homeostasis in obese mice.
The EQ-5D-5L valuation study for Trinidad and Tobago
Authors: Bailey Henry , Jonker Marcel F. , Pullenayegum Eleanor , Rencz Fanni , Roudijk Bram 
Published: July 2024

AbstractPurposeThe 2016 EQ-5D-3L value set for Trinidad and Tobago (T&T) allows for the calculation of EQ-5D-5L values via the crosswalk algorithm. The 2016 value set was based on methods predating the EQ-VT protocol, now considered the gold standard for developing EQ-5D value sets. Furthermore, direct elicitation of EQ-5D-5L is preferred over crosswalked values. This study aimed to produce an EQ-5D-5L value set for T&T.MethodsA representative sample (age, sex, geography) of adults each completed 10 composite Time Trade-Off (cTTO) tasks and 12 Discrete Choice Experiment (DCE) tasks in face-to-face interviews. The cTTO data were analyzed using a Tobit model that corrects for heteroskedasticity. DCE data were analyzed using a mixed logit model. The cTTO and DCE data were combined in hybrid models.ResultsOne thousand and seventy-nine adults completed the valuation interviews. Among the modelling approaches that were explored, the hybrid heteroskedastic Tobit model produced all internally consistent, statistically significant coefficients, and performed best in terms of out-of-sample predictivity for single states. Compared to the existing EQ-5D-5L crosswalk set, the new value set had a higher number of negative values (236 or 7.6% versus 21 or 0.7%). The mean absolute difference was 0.157 and the correlation coefficient between the two sets was 0.879.ConclusionThis study provides a value set for the EQ-5D-5L for T&T using the EQ-VT protocol. We recommend this value set for QALY computations relating to T&T.
Relationships between apolipoprotein E and insulin resistance in patients with obstructive sleep apnoea: a large-scale cross-sectional study
Authors: Wei ZhiCheng , Tian Ling , Xu Huajun , Li Chenyang , Wu Kejia , Zhu Huaming , Guan Jian , Yu Yafeng , Qian Di , Li Xinyi 
Published: July 2024

Abstract
Background
Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA.

Methods
A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA.

Results
Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (β = 0.107, β = 0.102, β = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425–2.017; OR = 2.371, 95% confidence interval (CI): 2.009–2.816; OR = 3.392, 95% CI: 2.853–4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women.

Conclusions
This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.
Genomic characteristics and evolution of Multicentric Esophageal and gastric Cardiac Cancer
Authors: Liu Xi , Cai Lijun , Ji Juan , Tian Dongping , Guo Yi , Chen Shaobin , Zhao Meng , Su Min 
Published: July 2024

Abstract
Background
Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear.

Materials and methods
In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics.

Result
The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes.

Conclusions
The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.
Facile synthesis of copper nitroprusside chitosan nanocomposite and its catalytic reduction of environmentally hazardous azodyes
Authors: El Mously Dina A. , Mahmoud Amr M. , Khallaf Moustafa Ali , Mandour Howida S. , Batakoushy Hany A. 
Published: July 2024

AbstractOne of the biggest issues affecting the entire world currently is water contamination caused by textile industries’ incapacity to properly dispose their wastewater. The presence of toxic textile dyes in the aquatic environment has attracted significant research interest due to their high environmental stability and their negative effects on human health and ecosystems. Therefore, it is crucial to convert the hazardous dyes such as methyl orange (MO) azo dye into environmentally safe products. In this context, we describe the use of Copper Nitroprusside Chitosan (Cu/SNP/Cts) nanocomposite as a nanocatalyst for the chemical reduction of azodyes by sodium borohydride (NaBH4). The Cu/SNP/Cts was readily obtained by chemical coprecipitation in a stoichiometric manner. The X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT-IR) spectroscopy were applied to investigate chemical, phase, composition, and molecular interactions. Additionally, Scanning electron microscope (SEM) was used to examine the nanomaterial's microstructure. UV–vis spectroscopy was utilized for studying the Cu Nitroprusside Chitosan's catalytic activity for the reduction of azodye. The Cu/SNP/Cts nanocomposite demonstrated outstanding performance with total reduction time 160 s and pseudo-first order constant of 0.0188 s−1. Additionally, the stability and reusability study demonstrated exceptional reusability up to 5 cycles with minimal activity loss. The developed Cu/SNP/Cts nanocomposite act as efficient nanocatalysts for the reduction of harmful Methyl orange azodye.
Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury
Authors: Chen Jiating , Zhang Chi , Yang Zihan , Wu Weiling , Zou Weihao , Xin Zixuan , Zheng Shuyu , Liu Runchun , Yang Lili , Peng Hongjuan 
Published: July 2024

Abstract
Background
Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage.

Methods
Vimentin gene knockout (vim−/−) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim−/− and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection.

Results
Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8+ T cells and the secretion of interferon-gamma.

Conclusion
Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.

Graphical Abstract
Mitochondrial genome of the fluke pond snail, Austropeplea cf. brazieri (Gastropoda: Lymnaeidae)
Authors: Sukee Tanapan , Koehler Anson V. , Webster Bonnie L. , Gauci Charles G. , Fogarty Conor E. , Ponder Winston F. , Gasser Robin B. , Young Neil D. 
Published: July 2024

Abstract
Background
Lymnaeid snails of the genus Austropeplea are an important vector of the liver fluke (Fasciola hepatica), contributing to livestock production losses in Australia and New Zealand. However, the species status within Austropeplea is ambiguous due to heavy reliance on morphological analysis and a relative lack of genetic data. This study aimed to characterise the mitochondrial genome of A. cf. brazieri, an intermediate host of liver fluke in eastern Victoria.

Methods
The mitochondrial genome was assembled and annotated from a combination of second- and third-generation sequencing data. For comparative purposes, we performed phylogenetic analyses of the concatenated nucleotide sequences of the mitochondrial protein-coding genes, cytochrome c oxidase subunit 1 and 16S genes.

Results
The assembled mt genome was 13,757 base pairs and comprised 37 genes, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The mt genome length, gene order and nucleotide compositions were similar to related species of lymnaeids. Phylogenetic analyses of the mt nucleotide sequences placed A. cf. brazieri within the same clade as Orientogalba ollula with strong statistical supports. Phylogenies of the cox1 and 16S mt sequences were constructed due to the wide availability of these sequences representing the lymnaeid taxa. As expected in both these phylogenies, A. cf. brazieri clustered with other Austropeplea sequences, but the nodal supports were low.

Conclusions
The representative mt genome of A. cf. brazieri should provide a useful resource for future molecular, epidemiology and parasitological studies of this socio-economically important lymnaeid species.

Graphical abstract
Overwintering West Nile virus in active Culex pipiens mosquito populations in Greece
Authors: Balatsos Georgios , Beleri Stavroula , Tegos Nikolaos , Bisia Marina , Karras Vasileios , Zavitsanou Evangelia , Papachristos Dimitrios P. , Papadopoulos Nikos T. , Michaelakis Antonios , Patsoula Eleni 
Published: July 2024

AbstractThe flavivirus West Nile Virus (WNV), which is transmitted by mosquitoes, poses a significant threat to both humans and animals, and its outbreaks often challenge public health in Europe and other continents. In recent years, there is an increasing trend of WNV incidence rates across several European countries. However, whether there is a year-round circulation or seasonal introduction has yet to be elucidated. Real-time polymerase chain reaction (PCR) identified WNV-positive Culex pipiens mosquitos in 6 out of 146 pools examined in winter 2022 that correspond to three out of the 24 study areas, located in two coastal regions units in Attica, Greece. Spatial dispersion of the six positive pools in the same region suggests a clustered circulation of WNV during the winter of 2022. This is the first study that documents the identification of WNV in Cx. pipiens populations, captured in adult traps during winter period. Our findings underscore the need to extend entomological surveillance programs to include the winter period, specifically in temperate climates and historically affected areas by WNV.
Graphical Abstract
Cognitive reappraisal and affective response to physical activity: associations with physical activity behavior
Authors: Gürdere Ceren , Sorgenfrei Julina , Pfeffer Ines 
Published: July 2024

Abstract
Objective
Cognitive reappraisal (CR), as an adaptive emotion regulation strategy, may play a role in transforming affect in a positive direction during or after exercise, thereby supporting physical activity (PA) adherence. The present study aimed to test the associations among PA, CR frequency, and affective response to PA, and further to examine the role of CR on PA behavior through affective response.

Methods
A cross-sectional study was conducted with a sample of 105 adults, 74 of whom were women, with a mean age of 25.91. Self-report scales were used to measure PA, CR, and affective response to PA. Along with scales, demographic questions on age, sex, and education level were included. Data was collected via an online questionnaire.

Results
The frequency of CR use was positively associated with affective response, and affective response with PA behavior. Mediation analysis revealed that affective response mediated the relationship between CR and PA.

Discussion
Results were in the expected direction demonstrating the mediating role of affective response between CR and PA which implies that PA adherence might be facilitated by CR engagement. PA intervention programs should consider implementing CR ability and use frequency improving techniques.
Autophagy modulation effect on homotypic transfer of intracellular components via tunneling nanotubes in mesenchymal stem cells
Authors: Sadeghsoltani Fatemeh , Avci Çığır Biray , Hassanpour Parisa , Haiaty Sanya , Rahmati Mohamad , Mota Ali , Rahbarghazi Reza , Nemati Maryam , Mahdipour Mahdi , Talebi Mehdi , Takanlou Leila Sabour , Takanlou Maryam Sabour , Mehdizadeh Amir 
Published: July 2024

Abstract
Background
Recent studies have proved the role of autophagy in mesenchymal stem cell (MSCs) function and regenerative properties. How and by which mechanism autophagy modulation can affect the juxtacrine interaction of MSCs should be addressed. Here, the role of autophagy was investigated in the formation of tunneling nanotubes (TNTs) and homotypic mitochondrial donation.

Methods
MSCs were incubated with 15 µM Metformin (Met) and/or 3 µM 3-methyladenine (3-MA) for 48 h. The formation of TNTs was assessed using bright-field and SEM images. The mitochondria density and ΔΨ values were monitored using flow cytometry analysis. Using RT-PCR and protein array, the close interaction and shared mediators between autophagy, apoptosis, and Wnt signaling pathways were also monitored. The total fatty acid profile was assessed using gas chromatography.

Result
Data indicated the increase of TNT length and number, along with other cell projections after the induction of autophagy while these features were blunted in 3-MA-treated MSCs (p < 0.05). Western blotting revealed the significant reduction of Rab8 and p-FAK in 3-MA-treated MSCs (p < 0.05), indicating the inhibition of TNT assembly and vesicle transport. Likewise, the stimulation of autophagy increased autophagic flux and mitochondrial membrane integrity compared to 3-MA-treated MSCs. Despite these findings, protein levels of mitochondrial membrane Miro1 and 2 were unchanged after autophagy inhibition/stimulation (p > 0.05). We found that the inhibition/stimulation of autophagy can affect the protein, and transcription levels of several mediators related to Wnt and apoptosis signaling pathways involved in different cell bioactivities. Data confirmed the profound increase of mono and polyunsaturated/saturated fatty acid ratio in MSCs exposed to autophagy stimulator.

Conclusions
In summary, autophagy modulation could affect TNT formation which is required for homotypic mitochondrial donation. Thus, the modulation of autophagy creates a promising perspective to increase the efficiency of cell-based therapies.
NOX4-mediated astrocyte ferroptosis in Alzheimer’s disease
Authors: Maimaiti Yasenjiang , Su Ting , Zhang Zhanying , Ma Lingling , Zhang Yuan , Xu Hong 
Published: July 2024

AbstractThis study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer’s Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4’s role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aβ and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.