bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Biomarkers of a Recombinant Human Erythropoietin Administration to Thoroughbred Geldings by Label‐Free Proteomics
Authors: Cheung Hiu Wing , Wong Kin‐Sing , Tam Jimmy C. L. , Farrington Adrian F. , Bond Amanda J. , Wan Terence S. M. , Ho Emmie N. M. 
Published: September 2024

ABSTRACTErythropoiesis‐stimulating agents (ESAs) continue to be a significant threat to the integrity of human and equine sports. Besides conventional direct testing, monitoring the biomarkers associated with the effects of ESAs may provide a complementary approach via indirect detection to enhance doping control. In this study, we applied label‐free proteomics to discover plasma protein biomarkers in Thoroughbred geldings after administration with a long‐acting form of recombinant human erythropoietin (rhEPO), methoxy polyethylene glycol epoetin beta, Mircera. Increased haematocrit, haemoglobin and red blood cell (RBC) levels were evidenced as early as 4 days post‐administration in all three horses to varying extents. Tryptic peptides were obtained from plasma samples and analysed by nanoflow ultra‐high‐performance liquid chromatography–high‐resolution tandem mass spectrometry (nano‐UHPLC‐HRMSMS) using data‐independent acquisition. Differential protein abundance analysis has shortlisted seven protein biomarker candidates that showed significant changes specifically after Mircera administration in the treated but not in the control geldings, which comprised downregulation of two proteins, haptoglobin (HP) and haemopexin (HPX), and upregulation of five proteins, transferrin receptor 1 (TFR1), phospholipid transfer protein (PLTP), tenascin C (TNC), vascular cell adhesion molecule 1 (VCAM1) and galectin 3 binding protein (LGALS3BP). Multivariate analysis of plasma proteome has allowed the classification of control and treated samples. This is the first report on the discovery of plasma protein biomarkers of rhEPO administration to geldings. The results lay a foundation for applications of protein biomarkers for controlling the misuse of ESAs.
Innate immunity champions: The diverse functions of macrophages
Authors: Biscu Francesca , Zouzaf Anissa , Cicia Donatella , Pridans Clare , Matteoli Gianluca 
Published: September 2024

AbstractMacrophages are instrumental in maintaining tissue homeostasis, modulating inflammation, and driving regeneration. The advent of omics techniques has led to the identification of numerous tissue‐specific macrophage subtypes, thereby introducing the concept of the “macrophage niche”. This paradigm underscores the ability of macrophages to adapt their functions based on environmental cues, such as tissue‐specific signals. This adaptability is closely linked to their metabolic states, which are crucial for their function and role in health and disease. Macrophage metabolism is central to their ability to switch between proinflammatory and anti‐inflammatory states. In this regard, environmental factors, including the extracellular matrix, cellular interactions, and microbial metabolites, profoundly influence macrophage behavior. Moreover, diet and gut microbiota significantly impact macrophage function, with nutrients and microbial metabolites influencing their activity and contributing to conditions like inflammatory bowel disease. Targeting specific macrophage functions and their metabolic processes is leading to the development of novel treatments for a range of chronic inflammatory conditions. The exploration of macrophage biology enriches our understanding of immune regulation and holds the promise of innovative approaches to managing diseases marked by inflammation and immune dysfunction, offering a frontier for scientific and clinical advancement.
Increased behavioural inhibition and decreased behavioural activation in whiplash‐associated disorders: Associations with health outcomes
Authors: Smith Ashley , Becker Susanne 
Published: September 2024

AbstractBackgroundMotivation can be investigated with the BIS (Behavioural Inhibition System)/BAS (Behavioural Activation System) scale. BAS regulates the motivation to approach goal‐oriented outcomes, particularly rewarding stimuli and situations, while BIS regulates escape and avoidance of unpleasant outcomes. Chronic whiplash‐associated disorders (WAD) is a heterogenous pain condition with known alterations in motivated behaviour. The study aimed (1) to investigate the relationship between BIS/BAS, and pain and disability with quality of life and psychological measures in chronic WAD; (2) to determine if BIS and/or BAS mediate the relationships between pain, disability, and psychological symptoms and quality of life.Methods254 chronic WAD patients participated in the study. Outcome measures were assessed using self‐report questionnaires. BIS/BAS scores were compared to published normative data. Differences in health outcomes for participants within/outside normative 95% confidence intervals were compared and correlations with health measures tested. Mediation models explored bi‐directional associations between stress, anxiety, depression, post‐traumatic stress severity, pain catastrophizing, and quality of life with pain and disability.ResultsParticipants who exceeded normative 95% confidence intervals for BIS demonstrated higher scores for pain interference, disability and all mental health measures. No mediating role of BIS/BAS on the relation between pain and disability with quality of life and health outcomes could be confirmed.ConclusionsA comparatively large proportion of the sample exceeded the 95% confidence interval for BIS and BAS scores with associations of these scores with health outcomes, but altered motivation to approach goal‐oriented outcomes appears to play only a subordinate role in chronic WAD.Significance statementIn line with current theories, we found a large proportion (30%–50%) of patients with whiplash‐associated disorders (WAD) showing signs of altered function in the Behavioural Inhibition System (BIS) and Behavioural Activation System (BAS) suggesting altered reward processing and motivation in these patients. While such altered functions showed associations with pain interference, disability and all mental health measures, reward processing could no be demonstrated as a pathogenetically relevant factor in chronic WAD patients.
Are we there yet? Exploring astrocyte heterogeneity one cell at a time
Authors: O'Dea Michael R. , Hasel Philip 
Published: September 2024

AbstractAstrocytes are a highly abundant cell type in the brain and spinal cord. Like neurons, astrocytes can be molecularly and functionally distinct to fulfill specialized roles. Recent technical advances in sequencing‐based single cell assays have driven an explosion of omics data characterizing astrocytes in the healthy, aged, injured, and diseased central nervous system. In this review, we will discuss recent studies which have furthered our understanding of astrocyte biology and heterogeneity, as well as discuss the limitations and challenges of sequencing‐based single cell and spatial genomics methods and their potential future utility.
Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real‐world cohort of patients with lower‐risk MDS
Authors: Mazzeo Paolo , Ganster Christina , Wiedenhöft John , Shirneshan Katayoon , Rittscher Katharina , Brzuszkiewicz Elzbieta B. , Steinemann Doris , Schieck Maximilian , Müller‐Thomas Catharina , Treiber Hannes , Braulke Friederike , Germing Ulrich , Sockel Katja , Balaian Ekaterina , Schanz Julie , Platzbecker Uwe , Götze Katharina S. , Haase Detlef 
Published: September 2024

AbstractThe acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high‐risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower‐risk MDS (LR‐MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real‐world cohort of LR‐MDS patients. We screened 68 patients with a median follow‐up of 40.5 months and a median of 7.5 (range: 2–22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease‐modifying therapy.
The prevalence of hepatitis C virus genotypes and factors associated with cirrhosis, fatty liver, and viral load: A registry‐based cross‐sectional cohort study in Western Iran during 1999–2023
Authors: Sayad Babak , Bozorgomid Arezoo , Sayad Nazanin , Azhdari Marya , Bahadori Maryam , Rezaeian Shahab , Gholizadeh Maryam 
Published: September 2024

AbstractBackground and AimsHepatitis C virus (HCV) is an important infectious disease that imposes a significant burden on healthcare systems. Determining the prevalence of HCV genotypes in a area is essential for the successful implementation of HCV elimination programs and allocation of financial resources to direct‐acting antiviral direct‐acting antivirals (DAA) treatments against prevalent HCV genotypes. Accordingly, we conducted a registry‐based cross‐sectional cohort study to investigate the prevalence of HCV genotypes and factors associated with cirrhosis, fatty liver, and viral load in Kermanshah Province, Western Iran.MethodsPatients presenting to the Hepatitis Clinic of the Research Center for Infectious Diseases affiliated with Kermanshah University of Medical Sciences between 1999 and 2023 were enrolled in this study. Serum samples were collected to assess HCV genotypes and viral load. Additionally, demographic data and the status of cirrhosis and fatty liver were extracted from the registry system records throughout the study period.ResultsRecords of 828 patients with an average age of 40.38 ± 11.72 years (range: 11–80 years) were included in the study that 721 individuals were male, and 107 were female. The prevalence of fatty liver and cirrhosis was 30.3% and 12.9%, respectively. Four genotypes (1, 2, 3, and 4) and four subtypes (1a, 1b, 3a, and 3b) were identified, with subtype 3a (55.7%) being the most prevalent, followed by subtype 1a (34.3%). None of the variables including age, gender, viral load level, and genotypes 1 and 3 were associated with fatty liver or cirrhosis. However, age, gender, and genotype were correlated with the viral load (p ≤ 0.05).ConclusionThe most common HCV subtypes in Kermanshah were 3a and 1a. Genotypes 2 and 4 were identified in one case each. Further studies on identifying HCV subtypes in different regions of the country are recommended to manage HCV infection and predict the prognosis.
A Dual Cascaded Deep Theoretic Learning Approach for the Segmentation of the Brain Tumors in MRI Scans
Authors: Sreedhar Jinka , Dara Suresh , Srinivasulu C. H. , Katari Butchi Raju , Alkhayyat Ahmed , Vidyarthi Ankit , Alsulami Mashael M. 
Published: September 2024

ABSTRACTAccurate segmentation of brain tumors from magnetic resonance imaging (MRI) is crucial for diagnosis, treatment planning, and monitoring of patients with neurological disorders. This paper proposes an approach for brain tumor segmentation employing a cascaded architecture integrating L‐Net and W‐Net deep learning models. The proposed cascaded model leverages the strengths of U‐Net as a baseline model to enhance the precision and robustness of the segmentation process. In the proposed framework, the L‐Net excels in capturing the mask, while the W‐Net focuses on fine‐grained features and spatial information to discern complex tumor boundaries. The cascaded configuration allows for a seamless integration of these complementary models, enhancing the overall segmentation performance. To evaluate the proposed approach, extensive experiments were conducted on the datasets of BraTs and SMS Medical College comprising multi‐modal MRI images. The experimental results demonstrate that the cascaded L‐Net and W‐Net model consistently outperforms individual models and other state‐of‐the‐art segmentation methods. The performance metrics such as the Dice Similarity Coefficient value achieved indicate high segmentation accuracy, while Sensitivity and Specificity metrics showcase the model's ability to correctly identify tumor regions and exclude healthy tissues. Moreover, the low Hausdorff Distance values confirm the model's capability to accurately delineate tumor boundaries. In comparison with the existing methods, the proposed cascaded scheme leverages the strengths of each network, leading to superior performance compared to existing works of literature.
Glycerol‐plasticized silk fibroin vascular grafts mimic key mechanical properties of native blood vessels
Authors: Alkazemi Hazem , Chai Jaydon , Allardyce Benjamin J. , Lokmic‐Tomkins Zerina , O'Connor Andrea J. , Heath Daniel E. 
Published: September 2024

AbstractCardiovascular diseases are a major global health challenge. Blood vessel disease and dysfunction are major contributors to this healthcare burden, and the development of tissue‐engineered vascular grafts (TEVGs) is required, particularly for the replacement of small‐diameter vessels. Silk fibroin (SF) is a widely used biomaterial for TEVG fabrication due to its high strength and biocompatibility. However, the stiffness of SF is much higher than that of native blood vessels (NBVs), which limits its application for vascular tissue engineering. In this study, SF was plasticized with glycerol to produce TEVGs exhibiting similar stiffness and ultimate tensile strength to those of NBVs. The electrospun SF/glycerol TEVGs exhibited mechanical properties comparable to NBVs and supported the in vitro proliferation of essential vascular cells—endothelial and smooth muscle cells. After 5 days of culture, the TEVGs exhibited an endothelial monolayer in the lumen, demonstrating their potential for functional vascular tissue regeneration. Our study demonstrates the feasibility of producing TEVGs from SF with tailored mechanical properties, paving the way for more functional and durable TEVGs for future clinical applications.
Trim21 mediates metabolic reprogramming in renal tubular cells via PFKP ubiquitination to alleviate renal fibrosis
Authors: Wen Yang , Tian Maoqing , Jiang Xushun , Gong Ying , Gan Hua 
Published: September 2024

AbstractChronic kidney disease (CKD), stemming from varied nephric impairments, manifests a steadily escalating global incidence. As a progressive pathological condition, CKD is typified by an intensification in the gravity of renal interstitium fibrotic transformations. Nonetheless, the intrinsic mechanisms underpinning nephric fibrosis remain elusive. In this context, we elucidated a marked augmentation in aerobic glycolysis within proximal tubular epithelial cells (TECs) of CKD patients, alongside unilateral ureteral obstruction (UUO) and ischemia‐reperfusion injury (IRI) murine models, concomitant with deficiency of Trim21. Experimental investigations, both in vivo and in vitro, revealed that Trim21 deficiency aggravates the aberrantly heightened aerobic glycolysis, thereby exacerbating fibrotic reaction progression. Concomitantly, enhancive glycolytic flux paralleled an elevation in ATP genesis and reconstitution of cytoskeletal architecture. Mechanistically, we uncovered that Trim21 modulates aerobic glycolysis in TECs via ubiquitin‐facilitated degradation of phosphofructokinase platelet (PFKP), thus attenuating nephric fibrosis. Collectively, our insights posit Trim21 as a prospective therapeutic target in the amelioration of renal fibrosis.
Maslinic acid prevented lipopolysaccharide‐induced injury of IPEC‐J2 cells through regulating PTEN‐FAK signaling pathway
Authors: Wang Rui , Yu Hao , Li Aike , Wang Ting , Wang Qiyuan , Qi Huiyu , Wang Chuanqi , Zhang Jing 
Published: September 2024

AbstractIntestinal epithelial injury is one of the typical symptoms associated with intestinal inflammation and diarrhea, and the repair of the intestinal epithelium intricately linked to cell migration. Here, we test the hypothesis that maslinic acid (MA) regulates porcine intestinal epithelial cell migration by inhibiting focal adhesion kinase (FAK)/AKT signaling pathway. In this experiment, the optimal concentration of MA (0.5 μg/mL) on IPEC‐J2 cell viability was selected to investigate the effect under low‐dose lipopolysaccharide (LPS) (1 μg/mL) conditions. Transcriptome sequencing and polymerase chain reaction array results revealed that MA could alleviate LPS‐induced the gene expressions decreasing in focal adhesion signaling pathway. From the pathway map analysis and western blot analysis results, MA alleviated the LPS‐induced decrease in FAK protein expression mainly by promoting FAK protein phosphorylation, which in turn alleviated the decrease in cell migration and formation of cytoskeleton protein Vinculin and F‐actin, the above results were verified by FAK phosphorylation inhibitors Defactinib. The molecular docking and immunoprecipitation further verified that MA could bind to PTEN protein and significantly inhibit its interaction with FAK protein, blocking the function of PTEN to inhibit FAK phosphorylation finally shown to promote the level of FAK phosphorylation, meanwhile LPS inhibited FAK protein expression and its binding to PKC and PTEN proteins. Our study revealed the role of MA and LPS in FAK protein, and increased understanding of MA anti‐inflammatory mechanism.
Aziridine‐Functionalized 1,3,5‐Triazine Derivatives as Promising Anticancer Agents: Synthesis, DFT Study, DNA Binding Investigations and In Vitro Cytotoxic Activity
Authors: Protas Aleksandra V. , Mikolaichuk Olga V. , Popova Еlena А. , Timoshchuk Kirill V. , Kornyakov Ilya V. , Maistrenko Dmitrii N. , Molchanov Oleg E. , Sharoyko Vladimir V. , Semenov Konstantin N. 
Published: September 2024

AbstractHerein, we report a synthesis and characterization of aziridine‐functionalized 1,3,5‐triazine derivatives. Electronic structure and the most preferable geometry of substances were calculated by DFT method. DNA binding investigations were conducted as part of the biomedicinal research as well as the cytotoxic activity of these compounds was evaluated using in vitro assays toward Huh‐7 and A549 cancer cell lines and HEK‐293 normal cell line. The results demonstrate that some of the synthesized compounds exhibit potent cytotoxic activity ([5‐[[4,6‐bis(aziridin‐1‐yl)‐1,3,5‐triazin‐2‐yl]amino]‐2,2‐dimethyl‐1,3‐dioxan‐5‐yl]methanol (1) and 4,6‐di(aziridine‐1‐yl)‐N‐(2,2,5‐trimethyl‐1,3‐dioxane‐5‐yl)‐1,3,5‐triazine‐2‐amine (9)), making them potential candidates for further development as anticancer agents.
Bmi‐1 alleviates alveolar bone resorption through the regulation of autophagy
Authors: Chu Yiting , Liu Shuying , Yan Lixueer , Gong Aixiu 
Published: September 2024

AbstractBackgroundB‐cell‑specific Moloney MLV insertion site‐1(Bmi‐1)is a crucial osteopenic target molecule. The aim of this study is to explore the effects of Bmi‐1 on alveolar bone resorption and the underlying mechanisms in vitro and vivo.MethodsA Bmi‐1‐knockout (Bmi‐1−/−) mouse model was used to investigate the effect of Bmi‐1 on alveolar bone metabolism, with micro‐computed tomography imaging, histology, and immunohistochemistry staining. Furthermore, we utilized a ligature‐induced experimental periodontitis model to examine the impact of Bmi‐1‐knockdown (Bmi‐1±) on inflammatory alveolar bone resorption. Finally, we stimulated human periodontal ligament stem cells (hPDLSCs) with lipopolysaccharide (LPS) to explore the potential mechanism of Bmi‐1 overexpression in the process of osteogenesis.ResultsCompared with wild‐type mice, Bmi‐1−/− mice demonstrated more alveolar bone resorption by inhibiting osteogenesis, which was characterized by decreases in Runt‐related transcription factor 2 and type 1 collagen formation. In addition, Bmi‐1−/− mice had lower levels of autophagy markers such as Parkin and LC3, but higher levels of inflammation‐related factors such as interleukin (IL)‐6 and IL‐1β in periodontal tissues. In addition, Bmi‐1‐knockdown aggravated ligature‐induced alveolar bone loss. Under in vitro inflammatory conditions, Bmi‐1 overexpression stimulated osteoblast differentiation and inhibited the production of inflammatory factors, as well as the autophagy and apoptosis in hPDLSCs stimulated with LPS. When 3‐methyladenine (3‐MA), an autophagy inhibitor, was added, the osteogenic effect of Bmi‐1 was further enhanced.ConclusionsBmi‐1 alleviates alveolar bone resorption by regulating autophagy, indicating that it could be a potential target for periodontitis prevention and treatment.Plain Language SummaryPeriodontitis is a chronic inflammatory disease, which leads to progressive destruction of periodontal tissues, manifested as periodontal pocket formation, loss of periodontal attachment and alveolar bone resorption. Currently, there is a lack of effective treatments to regenerate damaged periodontal tissues. Therefore, it is of great clinical significance to explore new mechanisms of periodontitis and effective intervention targets. B‐cell‑specific Moloney MLV insertion site‐1 (Bmi‐1) is involved in the regulation of the cell cycle, DNA damage repair, autophagy, bone metabolism, tumor, and other physiopathological processes. Autophagy, as an important mechanism of intracellular self‐regulation, plays an indispensable role in the destruction and repair of periodontal tissues. The aim of this study was to investigate the role of Bmi‐1 on periodontal tissues and its intrinsic mechanism. The results revealed that Bmi‐1 regulates autophagy to protect periodontal tissues, suggesting that it may be a potential target for the prevention and treatment of periodontitis.
Successful treatment of pyoderma gangrenosum with guselkumab
Authors: Botvid Sofia , Zachariae Claus , Skov Lone , Schwensen Jakob Ferløv 
Published: September 2024

AbstractGuselkumab, a monoclonal antibody known for its effective inhibition of T‐cell‐immunoactivity through specific binding to interleukin‐23 (IL‐23)‐cytokines, may be used for off‐label treatment of pyoderma gangrenosum (PG). Herein, we report two successful cases of off‐label treatment for PG, using guselkumab, after unsuccessful treatments with standard regimens of corticosteroids, immunomodulating therapy and other biological agents. Case 1 involves a 39‐year‐old female with treatment‐resistant peristomal PG post‐colectomy and ileostomy. Case 2 features a 35‐year‐oldfemale with treatment‐resistant PG, presenting with deep necrotic lower extremity ulcers. In both cases, we observed remarkable healing within months to a year. These two cases support the potential use of systemic IL‐23‐targetedtherapy for treatment‐resistant PG.