bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-dependent effect of sublethal copper concentrations on de novo cholesterol synthesis in astrocytes and their possible links to variations in cholesterol and amyloid precursor protein levels in neuronal membranes
Authors: Zubillaga Marlene , Tau Julia , Rosa Diana , Bellini M. José , Arnal Nathalie 
Published: January 2024

Abstract
Background
Cholesterol (Cho) is an essential lipophilic molecule in cells; however, both its decrease and its increase may favor the development of neurological diseases such as Alzheimer’s disease (AD). Although copper (Cu) is an essential trace metal for cells, the increased plasma concentration of its free form has been linked with AD development and severity. AD affects aged people, but its prevalence and severity are higher in women than in men. We have previously shown that Cu promotes Cho de novo synthesis in immature neurons as well as increased Cho in membrane rafts and Aβ levels in culture medium, but there are no results yet regarding sex differences in the effects of sublethal Cu exposure on Cho de novo synthesis.

Methods
We examined the potential sex-specific impact of sublethal Cu concentrations on de novo Cho synthesis in primary cultures of male and female astrocytes. We also explored whether this had any correlation with variations in Cho and APP levels within neuronal membrane rafts.

Results
Flow cytometry analysis demonstrated that Cu treatment leads to a greater increase in ROS levels in female astrocytes than in males. Furthermore, through RT-PCR analysis, we observed an upregulation of SREBP-2 and HMGCR. Consistently, we observed an increase in de novo Cho synthesis. Finally, western blot analysis indicated that the levels of ABCA1 increase after Cu treatment, accompanied by a higher release of radiolabeled Cho and an elevation in Cho and APP levels in neuronal membrane rafts. Importantly, all these results were significantly more pronounced in female astrocytes than in males.

Conclusions
Our findings confirm that Cu stimulates Cho synthesis in astrocytes, both in a ROS-dependent and -independent manner. Moreover, female astrocytes displayed elevated levels of HMGCR, and de novo Cho synthesis compared to males following TBH and Cu treatments. This corresponds with higher levels of Cho released into the culture medium and a more significant Cho and APP rise within neuronal rafts. We consider that the increased risk of AD in females partly arises from sex-specific responses to metals and/or exogenous substances, impacting key enzyme regulation in various biochemical pathways, including HMGCR.
ImmunoPET provides a novel way to visualize the CD103+ tissue-resident memory T cell to predict the response of immune checkpoint inhibitors
Authors: Fan Xiaoyu , Nijman Hans W. , de Bruyn Marco , Elsinga Philip H. 
Published: January 2024

Abstract
Background
Immune checkpoint inhibitors (ICIs) have made significant progress in oncotherapy improving survival of patients. However, the benefits are limited to only a small subgroup of patients who could achieve durable responses. Early prediction of response may enable treatment optimization and patient stratification. Therefore, developing appropriate biomarkers is critical to monitoring efficacy and assessing patient response to ICIs.

Main body
Herein, we first introduce a new potential biomarker, CD103, expressed on tissue-resident memory T cells, and discuss the potential application of CD103 PET imaging in predicting immune checkpoint inhibitor treatment. In addition, we describe the current targets of ImmunoPET and compare these targets with CD103. To assess the benefit of PET imaging, a comparative analysis between ImmunoPET and other imaging techniques commonly employed for tumor diagnosis was performed. Additionally, we compare ImmunoPET and immunohistochemistry (IHC), a widely utilized clinical method for biomarker identification with respect to visualizing the immune targets.

Conclusion
CD103 ImmunoPET is a promising method for determining tumor-infiltrating lymphocytes (TILs) load and response to ICIs, thereby addressing the lack of reliable biomarkers in cancer immunotherapy. Compared to general T cell markers, CD103 is a specific marker for tissue-resident memory T cells, which number increases during successful ICI therapy. ImmunoPET offers noninvasive, dynamic imaging of specific markers, complemented by detailed molecular information from immunohistochemistry (IHC). Radiomics can extract quantitative features from traditional imaging methods, while near-infrared fluorescence (NIRF) imaging aids tumor detection during surgery. In the era of precision medicine, combining such methods will offer a more comprehensive approach to cancer diagnosis and treatment.
An efficient hybrid optimization of ETL process in data warehouse of cloud architecture
Authors: Dinesh Lina , Devi K. Gayathri 
Published: January 2024

AbstractIn big data, analysis data is collected from different sources in various formats, transforming into the aspect of cleansing the data, customization, and loading it into a Data Warehouse. Extracting data in other formats and transforming it to the required format requires transformation algorithms. This transformation stage has redundancy issues and is stored across any location in the data warehouse, which increases computation costs. The main issues in big data ETL are handling high-dimensional data and maintaining similar data for effective data warehouse usage. Therefore, Extract, Transform, Load (ETL) plays a vital role in extracting meaningful information from the data warehouse and trying to retain the users. This paper proposes hybrid optimization of Swarm Intelligence with a tabu search algorithm for handling big data in a cloud-based architecture-based ETL process. This proposed work overcomes many issues related to complex data storage and retrieval in the data warehouse. Swarm Intelligence algorithms can overcome problems like high dimensional data, dynamical change of huge data and cost optimization in the transformation stage. In this work for the swarm intelligence algorithm, a Grey-Wolf Optimizer (GWO) is implemented to reduce the high dimensionality of data. Tabu Search (TS) is used for clustering the relevant data as a group. Clustering means the segregation of relevant data accurately from the data warehouse. The cluster size in the ETL process can be optimized by the proposed work of (GWO-TS). Therefore, the huge data in the warehouse can be processed within an expected latency.
Municipal heat provision experiences and expectations in Germany
Authors: Krikser Thomas , Ehlers Melf-Hinrich , Profeta Adriano 
Published: January 2024

Abstract
Background
Compared to other sectors, the building sector is seriously lagging in efforts to mitigate climate change. In particular, heat provision needs to move to low-carbon options at greater speed. Municipalities are essential players in the transition to low-carbon heating. However, little is known about their experiences in developing heat provision infrastructure and their expectations of low-carbon options, such as district heating based on renewable energy. To explore how the experiences and expectations of municipalities concerning low-carbon heating are related, we conducted a survey of officers responsible for heating technology in municipal authorities across Germany. The questionnaires were analysed using multiple quantitative data analysis techniques.

Results
Our findings suggest that officers in larger municipalities have more positive expectations of low-carbon heating technologies than those in smaller and medium-sized municipalities. They also have more experience with these technologies. We identified four different clusters of municipalities based on their attitudes towards heating systems. The findings suggest that attitudes and experiences have a significant influence on the desirability and expected feasibility of the expansion of district heating. Furthermore, there are differences between south, north, and east Germany.

Conclusions
Exchange of experiences and expectations between larger and smaller municipalities could facilitate the transition to low-carbon heating. Public policy could strategically provide spaces for the required exchange, but it also needs to engage with more complex questions of finance and regulation.
Exploring factors for antibiotic over-prescription in children with acute upper respiratory tract infections in Assiut, Egypt: a qualitative study
Authors: AbdEl-Aty Mahmoud Attia , Amin Mariam Taher , Ahmed Sabra Mohamed , Elsedfy Ghada Omar , El-Gazzar Amira Fathy 
Published: January 2024

Abstract
Background
Over-prescription of antibiotics contributes to antibiotic resistance, which is a global health threat. Egypt has alarmingly high rates of antibiotic over-prescription for acute upper respiratory tract infections (URIs) in children. To effectively address this issue, it is important to understand the various factors that influence prescription behaviors. The Teixeira antibiotic prescription behavioral model (TAPBM) offers a comprehensive framework through which these factors can be explored. This qualitative study sought to investigate the perspectives of key stakeholders involved in pediatric healthcare in Egypt, with the primary goal of identifying the underlying determinants that contributed to this problem.

Methods
This qualitative study was conducted in Assiut City, Egypt, between January and March 2023. Purposive sampling was used to select participants, including consultant pediatricians, supervisors of pediatric training programs, and specialists in infection prevention and control. Thirteen semi-structured in-depth interviews (IDIs) were conducted, audio-recorded, and transcribed. Thematic analysis was performed using MAXQDA 2020 software.

Results
Two main themes emerged from the analysis: intrinsic factors related to physicians, extrinsic factors related to patients, and nonphysician factors. Intrinsic factors encompass personal characteristics and attitudes. Prescribing decisions were influenced by factors such as fear of complications, limited follow-up visits, and competition. Knowledge and education also played a significant role. Moreover, diagnostic uncertainty in distinguishing between bacterial and viral infections posed a challenge. Extrinsic factors included patient and caregiver factors, such as parental expectations and demands for antibiotics, driven by the belief that they produced rapid results. Moreover, patients’ demographic factors, including socioeconomic status and living conditions, affected their prescribing behavior. Health system-related factors, such as the type of healthcare institution and the absence of formal national guidelines, were identified as influential factors. Additionally, this study highlighted the influence of the pharmaceutical industry. The potential impact of the COVID-19 pandemic on antibiotic prescriptions was addressed.

Conclusions
The study highlights the intricate interplay between intrinsic and extrinsic factors that shape antibiotic prescription decisions, underscoring the significance of addressing these factors in mitigating overprescribing.
Assessing causality between inflammatory bowel diseases with frailty index and sarcopenia: a bidirectional Mendelian randomization study
Authors: Wang Peng , Tao Wei , Zhang Zhiqiang , Xu Cong , Qiu Yuan , Xiao Weidong 
Published: January 2024

Abstract
Background
Previous studies have found that frailty and sarcopenia are commonly diagnosed in inflammatory bowel disease (IBD) patients, indicating an association between these conditions. Nonetheless, the cause‒effect connection between IBD, frailty, and sarcopenia remains unclear.

Methods
We sourced the genetic variants for the exposures and outcomes from publicly accessible, extensive genome-wide association studies (GWAS). Specifically, we obtained IBD data from the International IBD Genetics Consortium, frailty index (FI) data from the United Kingdom Biobank and Swedish TwinGene, and sarcopenia data from a recent GWAS meta-analysis. Five methods, including inverse variance weighted (IVW), simple mode, MR-Egger, weighted mode, and the weighted median, were used to proceed with MR estimates. We also performed heterogeneity and horizontal pleiotropy tests.

Results
Our results indicated a positive causal relationship between ulcerative colitis (UC) (IVW: β = 0.014, 95% CI, 0.006 to 0.021, p = 0.001) and Crohn's disease (CD) (IVW: β = 0.012; 95% CI, 0.006 to 0.018, p = 2e−04) with the FI. However, we uncovered no proof of a cause-and-effect relationship between UC (IVW: β = 0.001, 95% CI, −0.015 to 0.017, p = 0.344) or CD (IVW: β = 0.003, 95% CI, −0.009 to 0.015, p = 0.214) and sarcopenia. Additionally, in the inverse order, we also discovered no cause-and-effect connection between FI or sarcopenia on UC or CD in this study.

Conclusion
The MR analysis showed a positive causal association between IBD and FI, indicating that IBD patients may exhibit aging-related characteristics. Therefore, frailty assessments should be conducted as early as possible in IBD patients.
Prognostic, diagnostic and clinicopathological roles of tsRNAs: a meta-analysis in breast cancer
Authors: Gao Lu-Jue , Zhu Si-Xun , Wei Ying-Yi , Meng Hua-Wei , Gu Jing , Zhang Hao , Dai Li-Juan 
Published: January 2024

AbstractBreast cancer (BC) is one of the most common malignancies in women and the leading cause of cancer-related death in women. The newly emerged non-coding RNAs tsRNAs (tRNA-derived small RNAs) play an important role in the occurrence and development of BC. The purpose of this study was to comprehensively evaluate the prognostic, diagnostic and clinicopathological roles of tsRNAs in BC. Through literature screening, a total of 13 BC-related tsRNA studies were included in this meta-analysis, all of which passed quality assessment. Prognostic studies showed upregulated tsRNAs to be associated with poor survival outcomes (HR = 1.64, 95%CI 1.51–1.77) and downregulated tsRNAs to be associated with better outcomes (HR = 0.58, 95%CI 0.50–0.68). Results of diagnostic studies showed a combined sensitivity of 72% (95%CI 68–76%) and combined specificity of 64% (95%CI 61–67%); the AUC was 0.72 (95%CI 0.68–0.75) and the DOR 4.62 (95%CI 3.76–5.68). Finally, correlation analysis of clinicopathological features showed that downregulation of tsRNAs correlated significantly with age, TNM stage and lymphatic metastasis. Sensitivity analysis and publication bias showed no significant difference. In conclusion, BC-associated tsRNAs are closely related to the prognosis and clinicopathological features of patients with this disease and can be used to assist in early diagnosis of BC. Therefore, tsRNAs are potential targets for the diagnosis and treatment of BC.
Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease
Authors: Qi Xiu-Hong , Chen Peng , Wang Yue-Ju , Zhou Zhe-Ping , Liu Xue-Chun , Fang Hui , Wang Chen-Wei , Liu Ji , Liu Rong-Yu , Liu Han-Kui , Zhang Zhen-Xin , Zhou Jiang-Ning 
Published: January 2024

Abstract
Background
Microglia-mediated neuroinflammation in Alzheimer’s disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD.

Methods
Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining.

Results
A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD.

Conclusions
The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.
Individualized microbiotas dictate the impact of dietary fiber on colitis sensitivity
Authors: Bonazzi Erica , Bretin Alexis , Vigué Lucile , Hao Fuhua , Patterson Andrew D. , Gewirtz Andrew T. , Chassaing Benoit 
Published: January 2024

Abstract
Background
The observation that the intestinal microbiota is central in the development of IBD suggests that dietary fiber, the microbiota’s primary source of nourishment, could play a central role in these diseases. Accordingly, enriching diets with specific soluble fibers remodels microbiota and modulates colitis sensitivity. In humans, a recent study suggests that the microbiota of select IBD patients might influence the impacts they would experience upon fiber exposure. We sought here to define the extent to which individual microbiotas varied in their responsiveness to purified soluble fiber inulin and psyllium. Moreover, the extent to which such variance might impact proneness to colitis.

Results
We observed a high level of inter-individual variation in microbiota responsiveness to fiber inulin and psyllium: while microbiotas from select donors exhibited stark fiber-induced modulation in composition, pro-inflammatory potential, and metabolomic profile, others were only minimally impacted. Mice transplanted with fiber-sensitive microbiomes exhibited colitis highly modulated by soluble fiber consumption, while mice receiving fiber-resistant microbiotas displayed colitis severity irrespective of fiber exposure.

Conclusion
The extent to which select soluble fibers alter proneness to colitis is highly influenced by an individual's microbiota composition and further investigation of individual microbiota responsiveness toward specific dietary fiber could pave the way to personalized fiber-based intervention, both in IBD patients and healthy individuals.
In-depth metaproteomics analysis of tongue coating for gastric cancer: a multicenter diagnostic research study
Authors: Chen Jiahui , Sun Yingying , Li Jie , Lyu Mengge , Yuan Li , Sun Jiancheng , Chen Shangqi , Hu Can , Wei Qing , Xu Zhiyuan , Guo Tiannan , Cheng Xiangdong 
Published: January 2024

Abstract
Background
Our previous study revealed marked differences in tongue images between individuals with gastric cancer and those without gastric cancer. However, the biological mechanism of tongue images as a disease indicator remains unclear. Tongue coating, a major factor in tongue appearance, is the visible layer on the tongue dorsum that provides a vital environment for oral microorganisms. While oral microorganisms are associated with gastric and intestinal diseases, the comprehensive function profiles of oral microbiota remain incompletely understood. Metaproteomics has unique strength in revealing functional profiles of microbiota that aid in comprehending the mechanism behind specific tongue coating formation and its role as an indicator of gastric cancer.

Methods
We employed pressure cycling technology and data-independent acquisition (PCT-DIA) mass spectrometry to extract and identify tongue-coating proteins from 180 gastric cancer patients and 185 non-gastric cancer patients across 5 independent research centers in China. Additionally, we investigated the temporal stability of tongue-coating proteins based on a time-series cohort. Finally, we constructed a machine learning model using the stochastic gradient boosting algorithm to identify individuals at high risk of gastric cancer based on tongue-coating microbial proteins.

Results
We measured 1432 human-derived proteins and 13,780 microbial proteins from 345 tongue-coating samples. The abundance of tongue-coating proteins exhibited high temporal stability within an individual. Notably, we observed the downregulation of human keratins KRT2 and KRT9 on the tongue surface, as well as the downregulation of ABC transporter COG1136 in microbiota, in gastric cancer patients. This suggests a decline in the defense capacity of the lingual mucosa. Finally, we established a machine learning model that employs 50 microbial proteins of tongue coating to identify individuals at a high risk of gastric cancer, achieving an area under the curve (AUC) of 0.91 in the independent validation cohort.

Conclusions
We characterized the alterations in tongue-coating proteins among gastric cancer patients and constructed a gastric cancer screening model based on microbial-derived tongue-coating proteins. Tongue-coating proteins are shown as a promising indicator for identifying high-risk groups for gastric cancer.
A comparative effectiveness study of the Breaking the Cycle and Maxxine Wright intervention programs for substance-involved mothers and their children: study protocol
Authors: Racine Nicole , Barriault Sophie , Motz Mary , Leslie Margaret , Poole Nancy , Premji Shainur , Andrews Naomi C. Z. , Penaloza Denise , Pepler Debra 
Published: January 2024

Abstract
Background
Children of substance-involved mothers are at especially high risk for exposure to adverse childhood experiences (ACEs) and poor mental health and development. Early interventions that support mothers, children, and the mother-child relationship have the greatest potential to reduce exposure to early adversity and the mental health problems associated with these exposures. Currently, there is a lack of evidence from the real-world setting demonstrating effectiveness and return on investment for intervention programs that focus on the mother-child relationship in children of substance-involved mothers.

Methods
One hundred substance-involved pregnant and/or parenting women with children between the ages of 0–6 years old will be recruited through the Breaking the Cycle and Maxxine Wright intervention programs, in Toronto, Ontario, Canada and Surrey, British Columbia, Canada, respectively. Children’s socioemotional development and exposure to risk and protective factors, mothers’ mental health and history of ACEs, and mother-child relationship quality will be assessed in both intervention programs. Assessments will occur at three time points: pre-intervention, 12-, and 24-months after engagement in the intervention program.

Discussion
There is a pressing need to identify interventions that promote the mental health of infants and young children exposed to early adversity. Bringing together an inter-disciplinary research team and community partners, this study aligns with national strategies to establish strong evidence for infant mental health interventions that reduce child exposure to ACEs and support the mother-child relationship. This study was registered with clinicaltrials.gov (NCT05768815) on March 14, 2023.