bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation regulator-mediated modification patterns and risk of intracranial aneurysm: a multi-omics and epigenome-wide association study integrating machine learning, Mendelian randomization, eQTL and mQTL data
Authors: Maimaiti Aierpati , Turhon Mirzat , Abulaiti Aimitaji , Dilixiati Yilidanna , Zhang Fujunhui , Axieer Aximujiang , Kadeer Kaheerman , Zhang Yisen , Maimaitili Aisha , Yang Xinjian 
Published: September 2023

Abstract
Background
Intracranial aneurysms (IAs) pose a significant and intricate challenge. Elucidating the interplay between DNA methylation and IA pathogenesis is paramount to identify potential biomarkers and therapeutic interventions.

Methods
We employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association studies (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). Our sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA.

Results
We identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition.

Conclusion
These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although our study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis.

Graphical Abstract
Multi-omics analysis reveals attenuation of cellular stress by empagliflozin in high glucose-treated human cardiomyocytes
Authors: Scisciola Lucia , Chianese Ugo , Caponigro Vicky , Basilicata Manuela Giovanna , Salviati Emanuela , Altucci Lucia , Campiglia Pietro , Paolisso Giuseppe , Barbieri Michelangela , Benedetti Rosaria , Sommella Eduardo 
Published: September 2023

Abstract
Background
Sodium–glucose cotransporter 2 (SGLT2) inhibitors constitute the gold standard treatment for type 2 diabetes mellitus (T2DM). Among them, empagliflozin (EMPA) has shown beneficial effects against heart failure. Because cardiovascular diseases (mainly diabetic cardiomyopathy) are the leading cause of death in diabetic patients, the use of EMPA could be, simultaneously, cardioprotective and antidiabetic, reducing the risk of death from cardiovascular causes and decreasing the risk of hospitalization for heart failure in T2DM patients. Interestingly, recent studies have shown that EMPA has positive benefits for people with and without diabetes. This finding broadens the scope of EMPA function beyond glucose regulation alone to include a more intricate metabolic process that is, in part, still unknown. Similarly, this significantly increases the number of people with heart diseases who may be eligible for EMPA treatment.

Methods
This study aimed to clarify the metabolic effect of EMPA on the human myocardial cell model by using orthogonal metabolomics, lipidomics, and proteomics approaches. The untargeted and multivariate analysis mimicked the fasting blood sugar level of T2DM patients (hyperglycemia: HG) and in the average blood sugar range (normal glucose: NG), with and without the addition of EMPA.

Results
Results highlighted that EMPA was able to modulate and partially restore the levels of multiple metabolites associated with cellular stress, which were dysregulated in the HG conditions, such as nicotinamide mononucleotide, glucose-6-phosphate, lactic acid, FA 22:6 as well as nucleotide sugars and purine/pyrimidines. Additionally, EMPA regulated the levels of several lipid sub-classes, in particular dihydroceramide and triacylglycerols, which tend to accumulate in HG conditions resulting in lipotoxicity. Finally, EMPA counteracted the dysregulation of endoplasmic reticulum-derived proteins involved in cellular stress management.

Conclusions
These results could suggest an effect of EMPA on different metabolic routes, tending to rescue cardiomyocyte metabolic status towards a healthy phenotype.

Graphical Abstract
Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets
Authors: Jin Zhuangzhuang , Zhang He , Bai Lunhao , Yue Lingyu , Zhang Weiming , Liang Jiajian , Chang Bohan , Yang Yue , Hu Zhehan , Chen Liang , Guo Chuanji 
Published: September 2023

Abstract
Background
The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients.

Methods
The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium.

Results
JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level.

Conclusions
The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis.
Does it matter that standard preparedness indices did not predict COVID-19 outcomes?
Authors: Stoto Michael A. , Nelson Christopher D. , Kraemer John D. 
Published: September 2023

AbstractA number of scientific publications and commentaries have suggested that standard preparedness indices such as the Global Health Security Index (GHSI) and Joint External Evaluation (JEE) scores did not predict COVID-19 outcomes. To some, the failure of these metrics to be predictive demonstrates the need for a fundamental reassessment which better aligns preparedness measurement with operational capacities in real-world stress situations, including the points at which coordination structures and decision-making may fail. There are, however, several reasons why these instruments should not be so easily rejected as preparedness measures.From a methodological point of view, these studies use relatively simple outcome measures, mostly based on cumulative numbers of cases and deaths at a fixed point of time. A country’s “success” in dealing with the pandemic is highly multidimensional – both in the health outcomes and type and timing of interventions and policies – is too complex to represent with a single number. In addition, the comparability of mortality data over time and among jurisdictions is questionable due to highly variable completeness and representativeness. Furthermore, the analyses use a cross-sectional design, which is poorly suited for evaluating the impact of interventions, especially for COVID-19.Conceptually, a major reason that current preparedness measures fail to predict pandemic outcomes is that they do not adequately capture variations in the presence of effective political leadership needed to activate and implement existing system, instill confidence in the government’s response; or background levels of interpersonal trust and trust in government institutions and country ability needed to mount fast and adaptable responses. These factors are crucial; capacity alone is insufficient if that capacity is not effectively leveraged. However, preparedness metrics are intended to identify gaps that countries must fill. As important as effective political leadership and trust in institutions, countries cannot be held accountable to one another for having good political leadership or trust in institutions. Therefore, JEE scores, the GHSI, and similar metrics can be useful tools for identifying critical gaps in capacities and capabilities that are necessary but not sufficient for an effective pandemic response.
Highly efficient Agrobacterium rhizogenes-mediated transformation for functional analysis in woodland strawberry
Authors: Yan Huiqing , Ma Dandan , Yi Peipei , Sun Guilian , Chen Xingyan , Yi Yin , Huang Xiaolong 
Published: September 2023

Abstract
Background
The diploid woodland strawberry (Fragaria vesca) is an excellent model plant for investigating economically significant traits and several genetic resources within the Rosaceae family. Agrobacterium rhizogenes-mediated hairy root transformation is an alternative for exploring gene functions, especially the genes specifically expressed in roots. However, the hairy root transformation has not been established in strawberry.

Results
Here, we described an efficient and rapid hairy root transgenic system for strawberry using A. rhizogenes. Strain of A. rhizogenes MSU440 or C58C1 was the most suitable for hairy root transformation. The transformation efficiency was highest when tissues contained hypocotyls as explants. The optimal procedure involves A. rhizogenes at an optical density (OD600) of 0.7 for 10 min and co-cultivation duration for four days, achieving a transgenic efficiency of up to 71.43%. An auxin responsive promoter DR5ver2 carrying an enhanced green fluorescent protein (eGFP) marker was transformed by A. rhizogenes MSU440, thereby generating transgenic hairy roots capable of high eGFP expression in root tip and meristem of strawberry where auxin accumulated. Finally, this system was applied for functional analysis using jGCaMP7c, which could sense calcium signals. A significant upsurge in eGFP expression in the transgenic hairy roots was displayed after adding calcium chloride. The results suggested that this approach was feasible for studying specific promoters and could be a tool to analyze gene functions in the roots of strawberries.

Conclusion
We established a rapid and efficient hairy root transformation in strawberry by optimizing parameters, which was adequate for promoter analysis and functional characterization of candidate genes in strawberry and other rosaceous plants.
Comparison of different surgical treatments for stage II progressive collapsing foot deformity: a finite element analysis
Authors: Chen Fanglin , Yuan Chengjie , Liang Mian , Le Guoping , Xu Jian 
Published: September 2023

Abstract
Background
This study analyzed the advantages and disadvantages of different procedures for stage IIA progressive collapsing foot deformity (PCFD) through three-dimensional finite element models.

Methods
A previous validated stage IIA PCFD FEA model was established consisting of 16 bones, 56 ligaments, 5 muscles and soft tissues. The ligament properties of the spring, deltoid, short plantar and long plantar ligaments, and plantar fascia were attenuated according to a previous publication. Medial column fusion (MCF), medializing calcaneal osteotomy (MCO), lateral column lengthening (LCL), and subtalar joint arthroereisis (SJA) operations were simulated in this model. The indexes of plantar stress distribution, maximum von Mises of the medial and lateral columns, strain of the medial ligaments and plantar fascia that supported the medial longitudinal arch, arch height, talo-first metatarsal angle, calcaneus pitch angle, and talonavicular coverage angle were all compared before and after simulated single-foot weight loading.

Results
The maximum plantar stress of PCFD decreased with MCO and SJA but increased with MCF and LCL. MCF and LCL failed to significantly reduce the stress on the medial column fragments, thereby increasing their stress. Both MCO and SJA relieved medial plantar stress. MCF had no significant effect on stress relief of the medial ligament. MCO, LCL, and SJA were all shown to reduce the pressure on the medial plantar ligament, with LCL having the most obvious effect. All four procedures corrected the arch deformity; however, MCF was not as effective as the other methods. SJA is the best method for restoring arch height and correcting arch deformities. For stage IIA PCFD, isolated MCF failed to reduce pressure on the medial column; however, isolated MCO significantly reduced the pressure on the medial plantar and ligamentous soft tissues while restoring the foot’s arch and correcting the hindfoot valgus.

Conclusion
SJA with type II sinus tarsi implant effectively transferred pressure from the medial plantar tract to the lateral side and restored the arch. Isolated LCL was not found suitable for stage IIA PCFD.
Validation of the Chinese version of the Brief Pain Inventory in patients with knee osteoarthritis
Authors: Wang Shunxing , Yao Shuxin , Shang Lei , Xu Chao , Ma Jianbing 
Published: September 2023

Abstract
Background
Knee osteoarthritis (KOA) primarily presents with symptoms of pain and compromised functionality. Pain is a subjective manifestation that necessitates the employment of reliable evaluation tools for practical assessment, thereby enabling the formulation of appropriate interventional strategies. The Brief Pain Inventory (BPI) is a widely utilized questionnaire for evaluating the status of chronic pain. The purpose of the present study is to translate the short form of BPI into Chinese version (BPI-CV) and conduct cross-cultural adaptation to evaluate the psychometric characteristics of BPI-CV in KOA patients.

Methods
BPI-CV was translated and cross-culturally adapted according to internationally recognized guidelines. A cohort comprising 150 patients diagnosed with KOA successfully completed the demographic questionnaire, BPI-CV, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the EuroQoL Group's five-dimension questionnaire (EQ-5D). Internal consistency and test–retest analysis were used to evaluate the reliability. The internal consistency of the scale items was evaluated by calculating the Cronbach's α value (> 0.7). We chose to employ two scales commonly used in the evaluation of KOA patients: the disease-specific WOMAC scale and the universal EQ-5D scale. Construct validity was determined through Pearson correlation analysis, comparing BPI scores with those obtained from the WOMAC and EQ-5D scales. Exploratory factor analysis was used to structural validity.

Results
The BPI-CV was well accepted with no ceiling or floor effect. Cronbach's α for assessing internal consistency was 0.894. Test–retest reliability was excellent with an ICC of 0.852 (95%CI 0.785–0.905). The BPI-CV showed moderate to strong correlations with the pain dimension (r = 0.496–0.860) and the functional interference dimension (r = 0.517–0.712) of the WOMAC and the EQ-5D (r = 0.527–0.743). Three factors resulted using exploratory factor analysis: pain severity, activity interference, and emotional interference, accounting for 79.0% of the total variance. Standard error of measurement was 0.539.

Conclusion
BPI-CV has good feasibility, reliability, and validity. It can be recommended for KOA patients in mainland China.
Long-term clinical outcomes of the Biomet M2a-38: a retrospective review of 335 total hip arthroplasty cases
Authors: Jones Caché S. , Gaillard-Campbell Dani , Gross Thomas P. 
Published: September 2023

Abstract
Background
At the turn of the century, over one-third of total hip arthroplasties comprised metal-on-metal bearings. As this patient population and their implants age, it is crucial to understand associated late failure modes and expected long-term functional outcomes. We report the long-term results of a large metal-on-metal uncemented total hip arthroplasty system with unique design characteristics compared to others that have been reported with high failure rates.

Methods
We retrospectively analyze our prospective clinical database to determine overall implant survivorship and functional outcomes. Further, we compare these results to the clinical outcomes reported in orthopedic registries and in other published studies with similar metal-on-metal total hip arthroplasty cohorts.

Results
Implant survivorship at 10 years was 99.1% and continued to 97.6% survivorship at 20 years. Implant survivorship at 20 years did not vary significantly between sexes (Male: 98.3%, Female: 97.2%; log-rank p-value = 0.46). Mean whole blood cobalt levels were 2.6 µg/L in unilateral cases, 5.3 µg/L in bilateral patients, and 3.4 µg/L for the combined cohort. Average blood chromium levels were 1.4 µg/L in unilateral patients, 2.9 µg/L in bilateral patients, and 1.8 µg/L for group combined. We observed a 0.9% rate of failure due trunnion corrosion at a mean of 13.1 years postoperatively (10.6–15.6 years) but had no bearing wear failures.

Conclusions
Our 20-year implant survivorship of 97.6% with the M2a-38 bearing surpassed registry benchmarks for THA. This large-bearing (38 mm), full hemisphere coverage metal-on-metal system had no bearing wear failures, one failure of instability, one failure of fixation, and three trunnion failures, perhaps suggesting an optimum balance between stability of the joint and the trunnion.
Surgical removal of an unusual huge solitary fibrous tumor in the mediastinum: a case report
Authors: Mardani Parviz , Nekooeian Mohammad , Zangeneh Saba , Kamran Hooman , Shahriarirad Reza , Anbardar Mohammad Hossein , Amirian Armin , Vafabin Masoud 
Published: September 2023

Abstract
Background
Intrathoracic Solitary Fibrous Tumors (SFT) mainly arise from the pleura; however, these tumors may also originate from the mediastinum. We present a rare case of posterior SFT extending to several mediastinal sites and with an unusual large size, successfully treated with surgical resection.

Case presentation
A 66-year-old female presented with an initial manifestation of ambiguous pain in the chest and dysphagia and later developed pitting edema in both lower extremities and cachexia five months before admission. Chest imaging confirmed a mediastinal mass (17 × 15 × 8 cm) which was surgically removed. Immunohistochemistry confirmed the diagnosis of a solitary fibrous tumor with positive B-cell lymphoma 2, STAT6, and CD99, negative S100 and smooth muscle actin, and low levels of Ki67 (5–7%). The patient’s follow-up course was unremarkable.

Conclusion
Mediastinal SFTs may grow extremely huge, with the potential to invade multiple adjacent sites. Surgical removal of the tumor remains the mainstay of treatment in these cases.
Exploring the potential use of Chinese herbs in regulating the inflammatory microenvironment of tumours based on the concept of ‘state-target identification and treatment’: a scooping review
Authors: Lian Jing , Lin Dongxin , Huang Yuchan , Chen Xiaohui , Chen Lian , Zhang Fan , Tang Peiling , Xie Jinling , Hou Xiaotao , Du Zhengcai , Deng Jiagang , Hao Erwei , Liu Junhui 
Published: September 2023

AbstractTumours do not exist in isolation from the organism; their growth, proliferation, motility, and immunosuppressive response are intricately connected to the tumour’s microenvironment. As tumour cells and the microenvironment coevolve, an inflammatory microenvironment ensues, propelling the phenomenon of inflammation-cancer transformation—an idea proposed by modern medicine. This review aims to encapsulate the array of representative factors within the tumour’s inflammatory microenvironment, such as interleukins (IL-6, IL-10, IL-17, IL-1β), transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Moreover, drawing upon research in traditional Chinese medicine (TCM) and pharmacology, we explore the delicate interplay between these factors and tumour-associated inflammatory cells: tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs) and dendritic cells (DCs). By analyzing the tumour-promoting effects of these entities, we delve into the connotations of Academician Tong Xiao-lin’s novel model of “state-target differentiation” and its application in the diagnosis and treatment of tumours. Our aim is to enhance the precision and targeting of tumour treatment in clinical practice. Delving deeper into our understanding of tumour pathogenesis through the lens of modern medicine, we discern the key etiology and pathogenesis throughout the entire developmental stage of tumours, unveiling the evolutionary patterns of Chinese Medicine (CM) states: heat state → phlegm state → stagnation state → deficiency state. Building upon this foundation, we devised a state-regulating formula. Simultaneously, drawing on pharmacological research in traditional Chinese medicine (TCM), we meticulously identified a range of targeted drugs that effectively modulate the aforementioned tumour-related mediators. This comprehensive strategy—a harmonious integration of state identification, target recognition, and simultaneous regulation—aims to elevate clinical efficacy. The fusion of TCM with Western medicine in tumour treatment introduces novel dimensions to the precise and refined application of TCM in clinical practice.