bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota and radiculopathy: a bidirectional two-sample Mendelian randomization study
Authors: Wang Jinyv , Yan Chen , Han Linhui , Lu YiJuan , Sun JingChuan , Shi Jiangang , Sun Kaiqiang 
Published: January 2024

Abstract
BackgroundPrevious studies have suggested a potential link between the gut microbiome and radiculopathy, but the causal relationship remains unclear. Therefore, the aim of this study was to determine the causal effect of gut microbiome on radiculopathy using Mendelian randomization (MR) approach and single nucleotide polymorphisms (SNPs) associated with gut microbiome as instrumental variables
Methods Summary data from genome-wide association studies of gut microbiota (the MiBioGen) and radiculopathy (the FinnGen biobank) were acquired. The inverse variance weighting (IVW) was chosen as the main MR Analysis method. The weighted median, MR-Egger regression, weighted model, and simple model were provided as additional supplements. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to evaluate the horizontal pleiotropy and to eliminate outlier single-nucleotide polymorphisms (SNPs). Cochran’s Q-test was applied for heterogeneity detection.
Results We identified eight gut microbial taxa that were causally associated with radiculopathy (P<0.05). The Cochrane Q test produced results that did not indicate heterogeneity (P>0.05), indicating a lack of statistical significance. Furthermore, both the MR-Egger intercept test and the MR-PRESSO global test indicated that our findings were not influenced by horizontal pleiotropy (P>0.05), further supporting the reliability of our results. In the reverse analysis, no evidence was found to suggest that radiculopathy has an impact on the gut microbiota.
ConclusionWe identified four gut microbiota that were protective against radiculopathy and four that may elevate the risk of the condition. Our findings confirmed a potential causal link between gut microbiota and radiculopathy, thereby providing a theoretical foundation for the development of targeted prevention strategies.
Keywords
Estrogen receptor (ER)-, progesterone receptor (PR)- and HER2-dependent expression of largely understudied genes with large number of copy number gain events in breast cancer
Authors: Berkel Caglar 
Published: January 2024

Abstract
Breast cancer can be classified into several molecular subtypes based on the status of hormone receptors including estrogen receptor (ER) and the progesterone receptor (PR), and of human epidermal growth factor receptor 2 (HER2; ERBB2). Copy number variants (CNVs) cover 5-10% of the human genome, and are responsible for the majority of variability among different individuals’ genomes based on nucleotide coverage. In the present study, I identified largely understudied genes for which copy number gain events (CNV gains) are observed in more than half of breast cancer patients, and whose expression is upregulated in breast tumors compared to non-malignant breast tissue. I found 6 genes meeting these criteria: SLC45A3, RGS7, FCRL4, CSMD4, FAM135B and TRAF7. I then studied these 6 genes in terms of ER, PR and HER2 status in breast cancer patients. I found that SLC45A3 expression is lower in breast cancer patients with ER-positive or PR-positive status. RGS7 mRNA levels are higher in breast cancer patients with ER-positive or PR-positive status but lower in those with HER2-positive status. FCRL4 expression is lower in breast tumors with ER-positive or PR-positive status. CSMD3 transcript levels are lower in breast tumors with HER2-positive status. FAM135B expression is higher in breast cancer patients with ER-positive or PR-positive status but lower in those with HER2-positive status. Combined, our study points that most of the studied genes exhibit receptor status-dependent changes in the expression, and that further mechanistic studies are needed for these genes with large number of copy number gain events in breast cancer.
Specific knockdown of the NDUFS4 gene reveals important roles of Ferroptosis in UVB-induced photoaging
Authors: Yan Teng , Cui Hong , Xu Danfeng , Tang Hui , Tang Yi , Tao Xiaohua , Huang Youming , Fan Yibin 
Published: January 2024

Abstract
Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS levels, and increased glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Fer-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging.
The association of preoperative serum free fatty acid with the survival in breast cancer patients
Authors: Li Liuran , Jin Liang , You Lili , Liu Qiang , Yan Li 
Published: January 2024

Abstract
Background
Several studies have analyzed the association between serum free fatty acid (FFA) and several types of cancer. However, the role of preoperative serum FFA and breast cancer (BC) prognosis remains largely unclear. This study aimed to elucidate the specific relationship between FFA and BC outcomes.
Methods
A retrospective review was conducted on 4133 breast cancer patients admitted to Sun Yat-sen Memorial Hospital from January 2015 to October 2021. Restricted cubic splines and multivariate Cox regression analyses were used to assess the relationship between preoperative serum FFA and overall survival (OS) in BC patients. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.
Results
Restricted cubic spline analysis revealed a U-shaped relationship between preoperative serum FFA levels and OS after adjusting for other variables. According to the cutoff points of FFA, multivariate Cox regression analyses showed that patients with low FFA levels (≤ 250µmol/L) had higher rates of all-cause mortality and cancer-specific mortality compared to patients with high FFA levels (250–715µmol/L) in total population and those with a BMI of 18.5 to 24.0 kg/m2.
Conclusion
A nonlinear U-shaped association was identified between preoperative serum FFA levels and the survival in BC patients, with lower FFA levels associated with worse OS.
Research on Vehicle Lane Keeping Capability in Low-Speed Scenarios Based on Autonomous Driving Technology
Authors: Duan Mengmeng , Wu Hao , Li Penghui , Feng Pengfei , Jin Huiqing , He Xinlei , Gu Junwen 
Published: January 2024

Abstract
Absrtact: In order to ensure the safety, stability and driving comfort of vehicle lane keeping in low-speed scenarios, this paper proposes an evaluation method of lane keeping behavior capability based on automatic driving technology. Taking low-speed scene as the research object, based on automatic driving technology, IDM intelligent driving model is applied to describe ACC car following model, and MATLAB/Simulink and Carsim are used to build a low-speed scene lane keeping simulation platform The three aspects of comfort are used to evaluate the vehicle lane keeping ability in low-speed scenarios. The structure shows that when the distance between the target vehicle behind and the vehicle in front reaches a stable safety distance, the average speed of the vehicle is 21.6 (km · h -1 ), and the floating size is not more than 1. The difference between floating up and floating down is 0.0002, which is conducive to the stability of the lane during driving. In addition, based on the IDM intelligent driving model, this paper obtains data through vehicle to vehicle communication in the urban low-speed scenario, that is, when the vehicle is driving in the lane, its acceleration changes slightly. When it approaches zero, it can reduce unnecessary deceleration, so as to improve the driver's riding comfort. Based on ACC simulation, the difference between the actual following distance between the target vehicle and the vehicle in front during lane keeping and the target following distance fluctuates between -0.06 and 0.05m, and most of the differences are greater than the average difference, which can well meet the actual requirements and make car following safer. It can be seen that it is effective to study the lane keeping ability of vehicles in low-speed scenarios based on automatic driving technology in this paper.
Codon optimization of voraxin α sequence enhances the immunogenicity of a recombinant vaccine against Hyalomma anatolicum infestation in rabbits
Authors: Nazari Mahmood , Monjezi  , Rooshanfekr Hedaiat allah , Salabi Fatemeh , Tabandeh Mohammad Reza 
Published: January 2024

Abstract

Research has shown that voraxin α derived from male ticks stimulates blood feeding to engorge in female ticks. Whereas, the oviposition rate, egg weight, and body weight of female ticks were reduced in animals vaccinated with recombinant (r-) voraxin α. These data suggest a potential role of r-voraxin α as a functional anti-tick antigen in Rhipicephalus appendiculatus and Amblyomma hebraeum tick infestation. This study investigated the immunogenicity of r-voraxin α protein from Hyalomma anatolicum (H. anatolicum) tick as an anti-tick vaccine in rabbits. The H. anatolicum voraxin α sequence was optimized according to the codon usage in E. coli before being sub-cloned into pQE30. The gene sequence of the voraxin α was synthesized, verified by DNA sequencing, cloned in a pQE30 vector, and transformed into E. coli. Then, the expression of the r-voraxin α protein was confirmed by SDS-PAGE and Western blot analysis. Subsequently, three rabbits were immunized with the r-voraxin α as the vaccinated group, whereas three rabbits without injection were considered the control group. The result indicated the success of cloning of codon-optimized H. anatolicum voraxin α gene. Moreover, the expression of the r-voraxin α protein (approximately 18 kDa) in the bacterial expression system was confirmed by SDS-PAGE and Western blot analysis. The results of this study showed that the mortality rate in vaccine recipients increased compared to the control group (P < 0.01). Also, the egg weight, oviposition rate, and engorgement weight of female ticks fed from vaccinated animals were significantly reduced compared to the control group (P < 0.01). The results confirmed that the codon-optimized H. anatolicumvoraxin α gene expressed in the bacterial expression system could be a suitable anti-tick vaccine against H. anatolicum tick infestation.
Exploring Healthcare Research Patterns in Developed and Developing Countries: ATopic Modeling Perspectives
Authors: Mahmoudi Laya , Sharifi Mohammad Hossein , Bagheri Ruhollah , berahmand kamal 
Published: January 2024

Abstract

Healthcare research has become an integral part of shaping medical improvements due to its importance in discovering health challenges, examining public health concerns, and providing evidence-based practices. Regarding the differences that exist among nations concerning their culture, infrastructure, and politics, the study of healthcare research specific to each country provides valuable lessons for policymaking and reforms based on the needs of that nation. Moreover, if there are common concerns between different countries, it can facilitate scientific cooperation. Accordingly, the purpose of this current study is to provide a cross-country overview of research themes and sub-themes on healthcare in four countries: China, England, and Iran. A total of 5122 Scopus-indexed publications related to healthcare from 2010 to 2023 are analyzed using state-of-the-art topic modeling techniques: Latent Dirichlet allocation (LDA), Non-negative matrix factorization (NMF), and BERTopic. Comparing the topic models based on evaluation metrics, BERTopic was outperformed and selected for further analysis. The results give insights into the most prevalent themes and sub-themes on healthcare in each country. Additionally, the study shows the evolution trends of the predominant topics identified for each country, showing their rise, fall, and fluctuation patterns within the literature. The findings of this study can provide helpful insight for both academics and policymakers to develop their efforts and make better decisions in this field.
Conditioned pain modulation (CPM) as a biomarker of fibromyalgia and pain severity: effect of the CPM paradigm used
Authors: Gil-Ugidos Antonio , Vázquez-Millán A. , Samartin-Veiga N. , Carrillo-de-la-Peña M. T. 
Published: January 2024

Abstract
Fibromyalgia (FM) is a widespread chronic pain syndrome, possibly associated with the presence of central dysfunction in descending pain inhibition pathways. Conditioned Pain Modulation (CPM) has been proposed as a biomarker of FM. Nonetheless, the wide variety of methods used to measure CPM has hampered robust conclusions being reached. To clarify the validity of CPM as a biomarker of FM, we tested two CPM paradigms (parallel and sequential) in a sample of 23 female patients and 23 healthy women by applying test (mechanical) stimuli and conditioning (pressure cuff) stimuli. We evaluated whether CPM indices could correctly classify patients and controls, and we also determined the correlations between the indices and clinical variables such as symptomatology, impact, depression, quality of life, pain intensity, pain interference, fatigue and numbness. In addition, we compared the clinical status of CPM responders (efficient pain inhibitory mechanism) and non-responders. We observed that only parallel CPM testing correctly classified about 70% of patients with FM. In addition, more than 80% of healthy participants were found to be responders, while the rate was about 50% in the FM patients. The sequential CPM test was not as sensitive, with a decrease of up to 40% in the response rate for both groups. On the other hand, although we did not observe any correlation between CPM measures and clinical symptoms, we found that patients with impaired CPM response displayed more severe symptoms, though less generalized pain. In summary, our findings demonstrate the influence of the CPM paradigm used and confirm that CPM may be a useful marker to complement FM diagnosis. However, the findings also cast doubts on the sensitivity of CPM as a marker of pain severity in FM.
Spatial Time Series Analysis of Warming Patterns in the Kumaun Himalayas: A Future Perspective
Authors: Khan Zainab , Ahmad Ateeque , Shamim Syed Kausar 
Published: January 2024

Abstract
In this groundbreaking study, we introduce a novel approach to forecasting Land Surface Temperature (LST) in the Kumaun Himalayas, an area critical for understanding regional impacts of global warming. The novelty of our research lies in the utilization of spatial time series analysis, a method not previously applied for future LST prediction. Combined adoption of remote sensing and advanced statistical techniques such as the Simple Moving Average (SMA), Sen’s Slope, and z-statistics with excellent statistical power, our study analyses LST trends from 1990 to 2030 using comprehensive Landsat data. Notably, the application of z-statistics provides a robust framework for assessing temperature changes, with significant findings such as a z-statistics value of -15.04 for spring, indicating a marked shift in temperature patterns. Similarly, for autumn, the z-statistics value of -21.41 underscores a drastic deviation from historical norms i.e., from 1990 to 2020. These values highlight a future that is significantly warmer than the present, bringing into sharp focus the urgency of climate change mitigation and adaptation strategies in this ecologically sensitive region. The study also suggests differential rate of seasonal warming. The study is not only pivotal for local climate policy but also contribute significantly to the broader understanding of climate dynamics in mountainous terrains is seasonal variation in warming rates. Despite challenges like rugged terrain and variable cloud cover affecting data accuracy, our approach offers a scalable model for similar climatic studies in other regions, marking a significant advancement in the field of climate change.
Osimertinib-related Pulmonary Fibrosis, A case report and review of literature
Authors: Rasool Muhammad Haseeb ul , Ferman Yisrael , Ozeir Brandon , Mulkurti Ornela 
Published: January 2024

Abstract
Lung cancers are the leading cause of mortality worldwide. Pulmonary malignancies are grossly divided into small-cell lung carcinoma and non-small-cell lung carcinoma. Non-small cell lung carcinoma contributes to the majority of tumor burden. The treatment regimen and subsequent prognosis for lung cancer depend on the type of cancer, the grade, and the stage. With the advancement in modern immunology and genetics, targeted treatment therapies targeted against specific genetic mutations and immune markers resulted in improved survival. Though these treatment modalities are considered to have minimal to no effect on co-existing normal tissues, there have been reports of side effects among patients on these advanced treatments. Here we present a case of 72 years old female with advanced metastatic non-small cell lung carcinoma who presented with significant deterioration of respiratory status. Initially, due to elevated inflammatory markers and fever, was treated with antibiotics. However, with worsening respiratory status despite being on appropriate antibiotics, she was started on steroids for the imaging findings suggestive of pulmonary fibrosis. Initiation of steroids resulted in rapid recovery, with the improvement of imaging findings and oxygen requirements. The patient was eventually discharged home without oxygen to follow up with hematology regarding further treatment. Osimertinib has been shown to improve progression-free survival compared to the earlier generations of EGFR TKIs, however, there are adverse effects to Osimertinib, with the most common being rash, diarrhea, and dry skin. More severe and potentially fatal, side effects like QT interval prolongation, interstitial lung disease, and drug-related pneumonitis are documented potential adverse effects as well. In all the reported cases, the removal of medication results in the improvement of pulmonary fibrosis. However, a few cases have reported successful reintroduction of Osimertinib once the fibrosis improves with no recurrence. There is a need to run blinded trials to find the association of Osimertinib with co-existent factors that can contribute to pulmonary fibrosis.
Characterizing Age-related Changes in Intact Mitochondrial Proteoforms in Murine Hearts using Quantitative Top-Down Proteomics
Authors: Ramirez-Sagredo Andrea , Sunny Anju , Cupp-Sutton Kellye , Chowdhury Trishika , Zhao Zhitao , wu si , Chiao Ying Ann 
Published: January 2024

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and the prevalence of CVDs increases markedly with age. Due to the high energetic demand, the heart is highly sensitive to mitochondrial dysfunction. The complexity of the cardiac mitochondrial proteome hinders the development of effective strategies that target mitochondrial dysfunction in CVDs. Mammalian mitochondria are composed of over 1000 proteins, most of which can undergo post-translational protein modifications (PTMs). Top-down proteomics is a powerful technique for characterizing and quantifying all protein sequence variations and PTMs. However, there are still knowledge gaps in the study of age-related mitochondrial proteoform changes using this technique. In this study, we used top-down proteomics to identify intact mitochondrial proteoforms in young and old hearts and determined changes in protein abundance and PTMs in cardiac aging.
METHODS: Intact mitochondria were isolated from the hearts of young (4-month-old) and old (24-25-month-old) mice. The mitochondria were lysed, and mitochondrial lysates were subjected to denaturation, reduction, and alkylation. For quantitative top-down analysis, there were 12 runs in total arising from 3 biological replicates in two conditions, with technical duplicates for each sample. The collected top-down datasets were deconvoluted and quantified, and then the proteoforms were identified.
RESULTS: From a total of 12 LC-MS/MS runs, we identified 134 unique mitochondrial proteins in the different sub-mitochondrial compartments (OMM, IMS, IMM, matrix). 823 unique proteoforms in different mass ranges were identified. Compared to cardiac mitochondria of young mice, 7 proteoforms exhibited increased abundance and 13 proteoforms exhibited decreased abundance in cardiac mitochondria of old mice. Our analysis also detected PTMs of mitochondrial proteoforms, including N-terminal acetylation, lysine succinylation, lysine acetylation, oxidation, and phosphorylation.
CONCLUSION: By combining mitochondrial protein enrichment using mitochondrial fractionation with quantitative top-down analysis using ultrahigh-pressure liquid chromatography (UPLC)-MS and label-free quantitation, we successfully identified and quantified intact proteoforms in the complex mitochondrial proteome. Using this approach, we detected age-related changes in abundance and PTMs of mitochondrial proteoforms in the heart.