bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine modification of glycolytic enzymes impairs glycolysis: possible implications for Parkinson’s disease
Authors: Chen Bing , Zhang Qian , Zhong Xiaoru , Zhang Xinwei , Liu Xin , Wang Hongyang , Yang Fan , Zhang Jingjing , Huang Jingnan , Wong Yin-Kwan , Luo Piao , Wang Jigang , Sun Jichao 
Published: January 2024

Abstract
Background
Parkinson’s disease (PD), a chronic and severe neurodegenerative disease, is pathologically characterized by the selective loss of nigrostriatal dopaminergic neurons. Dopamine (DA), the neurotransmitter produced by dopaminergic neurons, and its metabolites can covalently modify proteins, and dysregulation of this process has been implicated in neuronal loss in PD. However, much remains unknown about the protein targets.

Methods
In the present work, we designed and synthesized a dopamine probe (DA-P) to screen and identify the potential protein targets of DA using activity-based protein profiling (ABPP) technology in combination with liquid chromatography-tandem mass spectrometry (LC–MS/MS). In situ pull-down assays, cellular thermal shift assays (CETSAs) and immunofluorescence were performed to confirm the DA modifications on these hits. To investigate the effects of DA modifications, we measured the enzymatic activities of these target proteins, evaluated glycolytic stress and mitochondrial respiration by Seahorse tests, and systematically analyzed the changes in metabolites with unbiased LC–MS/MS-based non-targeted metabolomics profiling.

Results
We successfully identified three glycolytic proteins, aldolase A, α-enolase and pyruvate kinase M2 (PKM2), as the binding partners of DA. DA bound to Glu166 of α-enolase, Cys49 and Cys424 of PKM2, and Lys230 of aldolase A, inhibiting the enzymatic activities of α-enolase and PKM2 and thereby impairing ATP synthesis, resulting in mitochondrial dysfunction.

Conclusions
Recent research has revealed that enhancing glycolysis can offer protection against PD. The present study identified that the glycolytic pathway is vulnerable to disruption by DA, suggesting a promising avenue for potential therapeutic interventions. Safeguarding glycolysis against DA-related disruption could be a potential therapeutic intervention for PD.
Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis
Authors: Chen Chuwen , Cai Haozheng , Shen Junyi , Zhang Xiaoyun , Peng Wei , Li Chuan , Lv Haopeng , Wen Tianfu 
Published: January 2024

Abstract
Background
Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis.

Method
Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data.

Results
Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study.

Conclusion
The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.
m6A methylation-mediated regulation of LncRNA MEG3 suppresses ovarian cancer progression through miR-885-5p and the VASH1 pathway
Authors: Li Yan , Lou Shenghan , Zhang Jian , Zhao Shilu , Lou Ge 
Published: January 2024

Abstract
Background
Ovarian cancer poses a serious threat to women's health. Due to the difficulty of early detection, most patients are diagnosed with advanced-stage disease or peritoneal metastasis. We found that LncRNA MEG3 is a novel tumor suppressor, but its role in tumor occurrence and development is still unclear.

Methods
We investigated the expression level of MEG3 in pan-cancer through bioinformatics analysis, especially in gynecological tumors. Function assays were used to detect the effect of MEG3 on the malignant phenotype of ovarian cancer. RIP, RNA pull-down, MeRIP-qPCR, actinomycin D test were carried out to explore the m6A methylation-mediated regulation on MEG3. Luciferase reporter gene assay, PCR and Western blot were implemented to reveal the potential mechanism of MEG3. We further confirmed the influence of MEG3 on tumor growth in vivo by orthotopic xenograft models and IHC assay.

Results
In this study, we discovered that MEG3 was downregulated in various cancers, with the most apparent downregulation in ovarian cancer. MEG3 inhibited the proliferation, migration, and invasion of ovarian cancer cells. Overexpression of MEG3 suppressed the degradation of VASH1 by negatively regulating miR-885-5p, inhibiting the ovarian cancer malignant phenotype. Furthermore, we demonstrated that MEG3 was regulated at the posttranscriptional level. YTHDF2 facilitated MEG3 decay by recognizing METTL3‑mediated m6A modification. Compared with those injected with vector control cells, mice injected with MEG3 knockdown cells showed larger tumor volumes and faster growth rates.

Conclusion
We demonstrated that MEG3 is influenced by METTL3/YTHDF2 methylation and restrains ovarian cancer proliferation and metastasis by binding miR-885-5p to increase VASH1 expression. MEG3 is expected to become a therapeutic target for ovarian cancer.
Fall risk classification with posturographic parameters in community-dwelling older adults: a machine learning and explainable artificial intelligence approach
Authors: Liang Huey-Wen , Ameri Rasoul , Band Shahab , Chen Hsin-Shui , Ho Sung-Yu , Zaidan Bilal , Chang Kai-Chieh , Chang Arthur 
Published: January 2024

Abstract
Background
Computerized posturography obtained in standing conditions has been applied to classify fall risk for older adults or disease groups. Combining machine learning (ML) approaches is superior to traditional regression analysis for its ability to handle complex data regarding its characteristics of being high-dimensional, non-linear, and highly correlated. The study goal was to use ML algorithms to classify fall risks in community-dwelling older adults with the aid of an explainable artificial intelligence (XAI) approach to increase interpretability.

Methods
A total of 215 participants were included for analysis. The input information included personal metrics and posturographic parameters obtained from a tracker-based posturography of four standing postures. Two classification criteria were used: with a previous history of falls and the timed-up-and-go (TUG) test. We used three meta-heuristic methods for feature selection to handle the large numbers of parameters and improve efficacy, and the SHapley Additive exPlanations (SHAP) method was used to display the weights of the selected features on the model.

Results
The results showed that posturographic parameters could classify the participants with TUG scores higher or lower than 10 s but were less effective in classifying fall risk according to previous fall history. Feature selections improved the accuracy with the TUG as the classification label, and the Slime Mould Algorithm had the best performance (accuracy: 0.72 to 0.77, area under the curve: 0.80 to 0.90). In contrast, feature selection did not improve the model performance significantly with the previous fall history as a classification label. The SHAP values also helped to display the importance of different features in the model.

Conclusion
Posturographic parameters in standing can be used to classify fall risks with high accuracy based on the TUG scores in community-dwelling older adults. Using feature selection improves the model’s performance. The results highlight the potential utility of ML algorithms and XAI to provide guidance for developing more robust and accurate fall classification models.
Trial registration Not applicable
Gastric and cardiac inflammatory myofibroblastic tumor: an extremely rare case
Authors: Huang Yueqi , Zhang Mingqi , Li Qingchun , Huang Qiulin 
Published: January 2024

Abstract
Background
Inflammatory myofibroblastic tumor (IMT) is a unique, rarely metastatic tumor composed of myofibroblasts and fibrous spindle cells with inflammatory cell infiltration that can affect any organ in the human body. By reviewing the relevant literature on PubMed, we found that this is the first case report of IMT with both gastric and cardiac involvement.

Case presentation
A 57-year-old male patient was admitted to the hospital with complaints of malaise, poor appetite, and epigastric pain with black stools. We found a mass in the patient’s stomach and left atrium by contrast-enhanced computed tomography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and other tests. The patient underwent laparoscopic Billroth II subtotal gastrectomy and Braun’s gastrointestinal reconstruction under general anesthesia. On the 46th day following stomach surgery, the cardiac tumor was removed under general anesthesia. The patient has treated with doxorubicin 70 mg of D1 chemotherapy two months after cardiac surgery. Postoperative pathological immunohistochemistry of the mass confirmed the diagnosis of an IMT. His review three months after the cardiac surgery suggested the progression of the left atrial mass, but he declined further treatment and finally died one month after the review.

Conclusions
As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.
Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study
Authors: Muccee Fatima , Ashraf Naeem Mahmood , Razak Suhail , Afsar Tayyaba , Hussain Nadia , Husain Fohad Mabood , Shafique Huma 
Published: January 2024

Abstract
Background
Polycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrogen receptor genes ESR1 and ESR2, involved in normal follicular development and ovulation, can contribute to development of the PCOS. The present study focuses on investigating the potential correlation between single nucleotide polymorphisms (SNPs) of ESR1 and ESR2 genes and the incidence of this syndrome.

Methods
For this study, SNPs in ESR1 and ESR2 genes were retrieved from the ENSEMBL database and analyzed for their effect on mutated proteins using different bioinformatics tools including SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL and HDDOCK.

Results
All the SNPs documented in the present study were deleterious. All the SNPs except rs1583384537, rs1450198518, and rs78255744 decreased protein stability. Two variants rs1463893698 and rs766843910 in the ESR2 gene altered the localization of mutated proteins i.e. in addition to the nucleus, proteins were also found in mitochondria and extracellular, respectively. SNPs rs104893956 in ESR1 and rs140630557, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene significantly changed the secondary structure of proteins (2D). SNPs that markedly changed 3D configuration included rs1554259481, rs188957694 and rs755667747 in ESR1 gene and rs1463893698, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene. Variants rs1467954450 (ESR1) and rs140630557 (ESR2) were identified to reduce the binding tendency of ESRα and β receptors with estradiol as reflected by the docking scores i.e. -164.97 and -173.23, respectively.

Conclusion
Due to the significant impact on the encoded proteins, these variants might be proposed as biomarkers to predict the likelihood of developing PCOS in the future and for diagnostic purposes.
ADAMTS18 deficiency associates extracellular matrix dysfunction with a higher risk of HER2-positive mammary tumorigenesis and metastasis
Authors: Nie Jiahui , Dang Suying , Zhu Rui , Lu Tiantian , Zhang Wei 
Published: January 2024

Abstract
Background
Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for about 20% of all breast cancer cases and is correlated with a high relapse rate and poor prognosis. ADAMTS18 is proposed as an important functional tumor suppressor gene involved in multiple malignancies, including breast cancer. It functions as an extracellular matrix (ECM) modifier. However, it remains unclear whether ADAMTS18 affects mammary tumorigenesis and malignant progression through its essential ECM regulatory function.

Methods
To elucidate the role of ADAMTS18 in HER2-positive mammary tumorigenesis and metastasis in vivo, we compared the incidence of mammary tumor and metastasis between Adamts18-knockout (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18−/−) and Adamts18-wildtype (MMTV)-Her2/ErbB2/Neu+ transgenic mice (i.e., Her2t/w/Adamts18+/+). The underlying mechanisms by which ADAMTS18 regulates HER2-positive tumorigenesis and metastasis were investigated by pathology, cell culture, Western blot and immunochemistry.

Results
Adamts18 mRNA is mainly expressed in myoepithelial cells of the mammary duct. ADAMTS18 deficiency leads to a significantly increased incidence of mammary tumors and metastasis, as well as mammary hyperplasia in mice, over 30 months of observation. The proliferation, migration and invasion capacities of primary Her2t/w/Adamts18−/− mammary tumor cells are significantly higher than those of primary Her2t/w/Adamts18+/+ mammary tumor cells in vitro. At 30 months of age, the expression levels of laminin (LNα5), fibronectin (FN) and type I collagen (ColI) in the mammary glands of Her2t/w/Adamts18−/− mice are significantly increased, and the activities of integrin-mediated PI3K/AKT, ERK and JNK signaling pathways are enhanced.

Conclusions
ADAMTS18 deficiency leads to alterations in mammary ECM components (e.g., LNα5, FN, ColI), which are associated with a higher risk of HER2-positive mammary tumorigenesis and metastasis.
Mosaic loss of Y chromosome is associated with aging and epithelial injury in chronic kidney disease
Authors: Wilson Parker C. , Verma Amit , Yoshimura Yasuhiro , Muto Yoshiharu , Li Haikuo , Malvin Nicole P. , Dixon Eryn E. , Humphreys Benjamin D. 
Published: January 2024

Abstract
Background
Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease.

Results
The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of these cells acquires a pro-inflammatory transcription and chromatin accessibility profile associated with expression of HAVCR1, VCAM1, and PROM1. These injured epithelial cells have the greatest proportion of LOY and their presence predicts future kidney function decline. Moreover, proximal tubule cells with LOY are more likely to harbor additional large chromosomal gains and express pro-survival pathways. Spatial transcriptomics localizes injured proximal tubule cells to a pro-fibrotic microenvironment where they adopt a secretory phenotype and likely communicate with infiltrating immune cells.

Conclusions
We hypothesize that LOY is an indicator of increased DNA damage and potential marker of cellular senescence that can be applied to single-cell datasets in other tissues.
Impact of Menstrual cycle-based Periodized training on Aerobic performance, a Clinical Trial study protocol—the IMPACT study
Authors: Ekenros Linda , von Rosen Philip , Norrbom Jessica , Holmberg Hans-Christer , Sundberg Carl Johan , Fridén Cecilia , Hirschberg Angelica Lindén 
Published: January 2024

Abstract
Background
The menstrual cycle and its impact on training and performance are of growing interest. However, evidence is lacking whether periodized exercise based on the menstrual cycle is beneficial. The primary purpose of this proposed randomized, controlled trial, the IMPACT study, is to evaluate the effect of exercise periodization during different phases of the menstrual cycle, i.e., comparing follicular phase-based and luteal phase-based training with regular training during the menstrual cycle on physical performance in well-trained women.

Methods
Healthy, well-trained, eumenorrheic women between 18 and 35 years (n = 120) will be recruited and first assessed for physical performance during a run-in menstrual cycle at different cycle phases and then randomized to three different interventions: follicular phase-based training, luteal phase-based training, or regular training during three menstrual cycles. The training intervention will consist of high-intensity spinning classes followed by strength training. The menstrual cycle phases will be determined by serum hormone analysis throughout the intervention period. Assessment of aerobic performance (primary outcome) and muscle strength, body composition, and blood markers will be performed at baseline and at the end of the intervention.

Discussion
With a robust methodology, this study has the potential to provide evidence of the differential effects of exercise periodization during different phases of the menstrual cycle in female athletes.

Trial registration
ClinicalTrials.gov NCT05697263. Registered on 25 January 2023
Single-cell analysis of immune and stroma cell remodeling in clear cell renal cell carcinoma primary tumors and bone metastatic lesions
Authors: Mei Shenglin , Alchahin Adele M. , Tsea Ioanna , Kfoury Youmna , Hirz Taghreed , Jeffries Nathan Elias , Zhao Ting , Xu Yanxin , Zhang Hanyu , Sarkar Hirak , Wu Shulin , Subtelny Alexander O. , Johnsen John Inge , Zhang Yida , Salari Keyan , Wu Chin-Lee , Randolph Mark A. , Scadden David T. , Dahl Douglas M. , Shin John , Kharchenko Peter V. , Saylor Philip J. , Sykes David B. , Baryawno Ninib 
Published: January 2024

Abstract
Background
Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets.

Methods
We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis.

Results
The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption.

Conclusions
These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.
Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
Authors: Ricardo-da-Silva Fernanda Yamamoto , Armstrong-Jr Roberto , Ramos Mayara Munhoz de Assis , Vidal-dos-Santos Marina , Jesus Correia Cristiano , Ottens Petra J. , Moreira Luiz Felipe Pinho , Leuvenink Henri G. D. , Breithaupt-Faloppa Ana Cristina 
Published: January 2024

Abstract
Background
Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP.

Methods
Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart–lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1β levels. Leukocyte infiltration, myeloperoxidase presence, IL-1β gene expression, and long-term release in lung culture (explant) were evaluated.

Results
Brain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1β levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile.

Conclusion
In this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.