bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between complete blood cell count-derived inflammatory biomarkers and gallstones prevalence in American adults under 60 years of age
Authors: Fu Chang , Chen Junhong , Wang Yongxin , Yang Yibo , Li Xiaocong , Liu Kai 
Published: January 2025

BackgroundThe trend of gallstones occurring in younger populations has become a noteworthy public health issue. This study aims to investigate the association between complete blood cell count (CBC)-derived inflammatory indicators and gallstones in adults under 60 years of age in the United States.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Associations between CBC-derived inflammatory biomarkers and gallstones were assessed using multivariable logistic regression models, with results presented as odds ratio (OR) and 95% confidence interval (CI). Restricted cubic splines (RCS) were employed to examine potential non-linear relationships. Subgroup analyses were also conducted to explore differences across population subgroups.ResultsThis study comprised 4,977 participants, among whom 398 were diagnosed with gallstones. After adjusting for confounding variables, the highest quartile of systemic inflammation response index (SIRI) [OR (95%CI): 1.65(1.12,2.43)], systemic immune-inflammation index (SII) [OR (95%CI): 1.53(1.05,2.25)], monocyte-to-lymphocyte ratio (MLR) [OR (95%CI): 1.66(1.16,2.37)], and pan immune inflammatory value (PIV) [OR (95%CI): 1.82(1.23,2.71)] were associated with a significantly increased risk of gallstones compared to the lowest quartiles. RCS plots indicated a nonlinear relationship between several inflammatory biomarkers and gallstones.ConclusionOur study found that SIRI, SII, MLR, and PIV can serve as clinical indicators for predicting the risk of gallstones in adults under 60 years of age in the United States.
Higher monomeric C-reactive protein levels are associated with premature coronary artery disease
Authors: Melnikov Ivan , Kozlov Sergey , Okhota Sergey , Saburova Olga , Avtaeva Yuliya , Kuznetsova Tatiana , Guria Konstantin , Prokofieva Lyudmila , Riazantseva Tatiana , Ji Shang-Rong , Wu Yi , Gabbasov Zufar 
Published: January 2025

IntroductionChronic inflammation is a major risk factor for coronary artery disease (CAD). Currently, the inflammatory cardiovascular risk is assessed via C-reactive protein (CRP) levels measured using a high-sensitivity assay (hsCRP). Monomeric CRP (mCRP) is a locally produced form of CRP that has emerged as a potential biomarker of inflammation.AimThis study investigated whether mCRP levels are associated with premature CAD.Materials and methodsThis study comprised 103 participants of both sexes, including 50 patients 56 ± 7 years old with premature CAD and 53 patients 51 ± 10 years old without CAD. CAD was verified using coronary angiography, hsCRP levels were measured using a standard assay, and mCRP levels were measured using fluorescent cytometric beads conjugated with an anti-mCRP antibody.ResultsThe levels of hsCRP were 0.99 (0.59; 3.10) mg/L vs. 0.63 (0.35; 1.85) mg/L (p = 0.067), and mCRP 6.84 (4.20; 13.78) µg/L vs. 2.57 (0.32; 5.66) µg/L (p &lt;0.001) in patients with CAD vs. patients without CAD, respectively. There was a weak positive correlation between the mCRP and hsCRP levels (ρ = 0.214; p = 0.030). hsCRP levels were below 2.0 mg/L (i.e., residual inflammatory cardiovascular risk should have been excluded) in 70% of patients with CAD and 79% of patients without CAD (p = 0.365). mCRP levels differed between the groups of patients with hsCRP levels below 2.0 mg/L: 5.14 (4.07; 10.68) µg/L vs. 2.77 (0.53; 5.00) µg/L in patients with or without CAD, respectively (p &lt;0.001). Logistic regression analysis demonstrated that mCRP levels were independently associated with premature CAD. The adjusted odds ratio was 1.18 (95% CI 1.06-1.33, p = 0.004) per each µg/L increase in mCRP levels.ConclusionHigher mCRP levels were associated with premature CAD, independent of hsCRP levels and traditional risk factors.
Massive endocytosis mechanisms are involved in uptake of HIV-1 particles by monocyte-derived dendritic cells
Authors: Laguía Fernando , Chojnacki Jakub , Erkizia Itziar , Geli María Isabel , Enrich Carlos , Martinez-Picado Javier , Resa-Infante Patricia 
Published: January 2025

IntroductionHIV-1 exploits dendritic cells (DCs) to spread throughout the body via specific recognition of gangliosides present on the viral envelope by the CD169/Siglec-1 membrane receptor. This interaction triggers the internalization of HIV-1 within a structure known as the sac-like compartment. While the mechanism underlying sac-like compartment formation remains elusive, prior research indicates that the process is clathrin-independent and cell membrane cholesterol–dependent and involves transient disruption of cortical actin. Here, we investigate the potential involvement of massive endocytosis (MEND) in this process.MethodsWe used live cell confocal imaging to measure the dimensions and dynamics of the compartment. We assessed the role of actin and cholesterol in fixed and live cells using confocal microscopy and evaluated the effect of PI3K and protein palmytoilation inhibitors during viral uptake.ResultsOur data demonstrate extensive plasma membrane invagination based on sac-like compartment dimensions (2.9 μm in diameter and 20 μm3 in volume). We showed that the cholesterol concentration doubles within the regions of viral uptake, suggesting lipid-phase separation, and that development of the sac-like compartment is accompanied by transient depolarization of cortical actin. Moreover, we observed that protein palmitoylation and PI3K inhibition reduce the sac-like compartment formation rate from 70% to 20% and 40%, respectively.ConclusionsOur results indicate the involvement of MEND mechanisms during sac-like compartment formation.
Identification of hub genes and immune-related pathways in acute myeloid leukemia: insights from bioinformatics and experimental validation
Authors: Shan Mingliang , Xu Li , Yang Wenzhe , Liu Shiguo , Cui Zhaoqing 
Published: January 2025

BackgroundThis study aims to identify the hub genes and immune-related pathways in acute myeloid leukemia (AML) to provide new theories for immunotherapy.MethodsWe use bioinformatics methods to find and verify the hub gene. At the same time, we use the results of GSEA enrichment analysis to find immune-related mediators. Through Mendelian randomization(MR) analysis, on the one hand, we look for related immune cells, and on the other hand, we use it to determine the causal relationship among immune cells, immune mediators, and AML. Finally, in vitro experiments are conducted to further verify and improve the reliability and physiological functions of the hub gene and its immune-related pathways.ResultsComplement Factor D(CFD) gene is identified as the highly expressed hub gene and is positively correlated with IL-2. IL-2 is also positively correlated with CD27 on CD24+CD27+B cells, JAK/STAT, and PI3K/Akt. The latter three are positively correlated with the occurrence and development of AML.ConclusionWe conclude that CFD gene uses IL-2 as a mediator to promote the disease progression of AML by promoting the CD27 on CD24+CD27+B cells, JAK-STAT, and PI3K-Akt pathways.
A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis
Authors: Stafford Lauren Stewart , Plummer Caryn E. , Smith W. Clay , Gibson Daniel J. , Sharma Jatin , Vicuna Valeria , Diakite Sisse , Larkin Joseph 
Published: January 2025

IntroductionRecurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine and human RU share many similarities including spontaneous disease and aberrant cytokine signaling. Reduced levels of SOCS1, a critical regulator of cytokine signaling, is associated with several autoimmune diseases. Topical administration of SOCS1-KIR, a peptide mimic of SOCS1, was previously correlated to reduced ocular pathologies within ERU patients.MethodsTo further assess the translational potential of a SOCS1 mimetic to treat RU, we assessed peptide-mediated modulation of immune functions in vitro, using equine peripheral blood mononuclear cells (PBMC), and in vivo through topical administration of SOCS1-KIR into the eyes of experimental (non-uveitic) horses. Equine PBMCs from non-uveitic control and ERU horses were cultured with or without SOCS1-KIR pretreatment, followed by 72 hours of mitogen stimulation. Proliferation was assessed using MTT, and cytokine production within cell supernatants was assessed by Luminex. SOCS1-KIR or carrier eye-drops were topically applied to experimental horse eyes twice daily for 21 days, followed by enucleation and isolation of ocular aqueous and vitreous humor. Histology was used to assess peptide treatment safety and localization within treated equine eyes. Cytokine secretion within aqueous humor and vitreous, isolated from experimental equine eyes, was measured by Luminex.ResultsFollowing SOCS1-KIR pretreatment, cell proliferation significantly decreased in control, but not ERU-derived PBMCs. Despite differential regulation of cellular proliferation, SOCS1-KIR significantly reduced TNFα and IL-10 secretion in PHA-stimulated control and ERU equine PBMC. SOCS1-KIR increased PBMC secretion of IL-8. Topically administered SOCS1-KIR was well tolerated. Although SOCS1-KIR was undetectable within the eye, topically treated equine eyes had significant reductions in TNFα and IL-10. Interestingly, we found that while SOCS1-KIR treatment reduced TNFα and IL-10 production in healthy and ERU PBMC, SOCS1-KIR differentially modulated proliferation, IP-10 production, and RANTES within these two groups suggesting possible differences in cell types or activation status.DiscussionTopical administration of a SOCS1 peptide mimic is safe to the equine eye and reduces ERU associated cytokines IL-10 and TNFα serving as potential biomarkers of drug efficacy in a future clinical trial.
Switch from eculizumab to satralizumab in aquaporin 4 immunoglobulin G–seropositive neuromyelitis optica spectrum disorder: a case series report
Authors: Abboud Hesham , Subei Adnan , Sengul Buse , Shin Robert K. , Goulette Paige , Walch Rosemarie , Coté Jeanie , Pace Robert , Obeidat Ahmed Z. , Ferayorni Lisa , Gholizadeh Shervin 
Published: January 2025

ObjectivesThis case series describes adults with aquaporin 4 immunoglobulin G–seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) who switched treatment from eculizumab to satralizumab.MethodsCase information for patients with AQP4-IgG+ NMOSD who received satralizumab for ≥6 months was obtained from US healthcare providers from April 2022 to January 2024. Patient characteristics, examination findings, diagnostic test results, treatment response, and adverse events were recorded.ResultsAmong the 5 patients (4 women and 1 man) included, ages ranged from 32 to 81 years and 4 patients self-identified as Black/African American and 1 as White. Time since confirmed NMOSD diagnosis ranged from 1 to 14 years. The reasons for initiating satralizumab were route of administration/patient preference (n=3) and inadequate disease control with eculizumab (n=2). The duration of satralizumab treatment was 10 to 31 months. All 5 patients were relapse-free with satralizumab, and adverse events they experienced were primarily asymptomatic laboratory abnormalities.DiscussionIn this retrospective case series, satralizumab was effective and well tolerated in patients with NMOSD who switched from eculizumab due to route of administration/patient preference or inadequate disease control. These outcomes align with the long-term efficacy and safety outcomes with satralizumab in the phase 3 SAkura clinical trials.
Interaction with IGF1 overrides ANXA2-mediated anti-inflammatory functions of IGFBP5 in vivo
Authors: Fan Yan , Wu Yi-Jin , Guo Kai , Zhou Xia-Qing , Abulaiti Abulizi , Olatunji Opeyemi Joshua , Ji Cong-Lan , Zuo Jian 
Published: January 2025

BackgroundIGFBP5 is a differentially expressed gene (DEG) between M1 and M2 macrophages. This study explained why it causes opposite effects in different circumstances.MethodsGene expression profiles of various cell subsets were compared by mining a public database. THP-1 cells were treated by siRNAs, recombinant IGFBP5, lipopolysaccharide (LPS), picropodophyllin, IGF1 or the combinations. Clinical implication of IGFBP5 changes was investigated using rheumatoid arthritis (RA) and acute lung injury (ALI) models. IGFBP5-bound and differential proteins were identified by Liquid Chromatography Mass Spectrometry method.ResultsIGFBP5 situated in the center of a network constructed by the DEGs of M0 and M1/2 macrophages. Its expression negatively correlated to inflammation in vitro. When IGFBP5 was silenced, monocytes released more IL-1β and IL-6. NF-κB downstream proteins were overexpressed. IGFBP5 interacted with ANXA2 directly. In ANXA2-silenced cells, it showed no anti-inflammatory effect. Monocytes of adjuvant-induced arthritis rats and RA patients expressed less IGFBP5 than normal controls, but its blood levels increased significantly. Adipocytes secreted large amounts of IGFBP5. This secretion was reinforced by the above sera. IGFBP5 decreased in ALI mice’s blood, while its supplement exacerbated inflammation. By binding to IGF1, IGFBP5 prevented its interaction with IGF1R. An IGF1R inhibitor picropodophyllin antagonized functions of IGF1/IGF1R too, but didn’t reinforce the effects of IGFBP5.ConclusionIGFBP5 eases inflammation by interacting with ANXA2, an activator of NF-κB; as an antagonist of IGF1/IGF1R, IGFBP5 may disrupt immune homeostasis in vivo, due to impairment of the latter’s anti-inflammatory functions; excessive IGFBP from adipocytes would be a pathogenic factor in certain diseases.
The efficacy of sequentially comprehensive treatment based on surgery in the treatment of keloids: a retrospective study
Authors: Yang Kun , Shi Mengdong , Li Shubo , Sun Jianning , Huo Ran , Fu Cong 
Published: January 2025

PurposeThe objective of this study is to investigate the clinical efficacy of sequentially comprehensive treatment based on surgery and to furnish clinical evidence for the management of keloids.Patients and methodsThe patients with keloids were retrospectively analyzed who underwent surgery-based sequentially comprehensive treatment at the Plastic Surgery Department of Shandong Provincial Hospital from January 2018 to August 2021. The recurrence rate and incidence of adverse reactions were explored for all the included patients. For patients who were followed up for more than 1 year, the clinical response rate was calculated, and the chi-square test was used to analyze which factors could influence clinical effectiveness. Binary logistic analysis was performed on the factors with statistical differences. For patients with a follow-up time of less than 1-year, paired t-test was used to evaluate their Vancouver Scar Scale (VSS) before and after treatment.ResultsA total of 67 patients with 80 keloids were included. The clinical response rate was 81.5% (44/54), the recurrence rate was 15.0% (12/80) and the adverse reaction rate was 4.5% (3/67). The clinical response rate of tumor-type keloids (95.8%) was higher than that of inflammatory-type (70.0%) with a significant difference (P = 0.040). After treatment, the color, blood vessel distribution, softness, thickness, and VSS score were all decreased, and the difference was statistically significant (P &lt; 0.001).ConclusionThe sequentially comprehensive treatment based on surgery has a significant curative effect, as well as a low recurrence rate and a low adverse effect rate. The type of keloid has a statistically significant effect on clinical efficacy, and tumor-type keloids are more suitable for sequentially comprehensive treatment based on surgery.
Perceptions of final-year medical students and interns toward pursuing a career in critical care medicine
Authors: Ageel Mohammed 
Published: January 2025

BackgroundCritical care medicine (CCM) faces challenges in attracting new physicians due to its demanding nature. Understanding medical students’ and interns’ perceptions of CCM is essential to address physician shortages and improve medical training.ObjectiveTo evaluate the factors influencing specialty selection and explore perceptions of final-year medical students and interns toward CCM at Jazan University.MethodsA cross-sectional survey using convenience sampling was conducted. Participants completed questionnaire assessing factors influencing career choice and perceptions of CCM. Chi-squared tests analyzed the associations between demographic variables and perceptions.ResultsThe study included 165 medical students (80% interns, 20% final-year students), primarily male (56.36%) and single (90.91%), with a mean age of 24.56 ± 1.46 years. The most influential career factors were job security (11.65%), enthusiasm/commitment (10.36%), and acceptable working hours (10.36%). Most students (81.82%) found CCM intellectually challenging, while 76.36% recognized its financial benefits. However, only 29.09% were considering a career in CCM, with concerns about work-life balance (34.54%) and family time (32.73%). Interns were more likely than final-year students to view limited working hours positively (p = 0.046), perceive greater colleague prestige (p = 0.035), expect private practice opportunities (p = 0.004), anticipate higher salaries (p &lt; 0.001), and acknowledge the shortage of staff in CCM (p = 0.009).ConclusionThere is a tension between the intellectual and financial benefits of CCM and its lifestyle demands. While students recognize its rewards, concerns about work-life balance and staffing challenges discourage many from pursuing the specialty. Tailored career counseling, mentorship, and addressing lifestyle concerns in medical curricula may improve interest in CCM.
Effect of an individualized bismuth quadruple regimen guided by 10-day or 14-day antibiotic susceptibility testing for first-line eradication treatment of Helicobacter pylori in Ningxia, China
Authors: Su Xiaoming , Deng Yanhong , Chen Xianmei , Li Yanling , Hao Qian , Tang Yuanyuan , Mu Rui , Wu Yuting , Zhou Yan , Hu Shengjuan 
Published: January 2025

IntroductionHelicobacter pylori (H. pylori) is becoming more resistant to antibiotics, and the implementation of individualized therapy is highly valuable for its eradication. This study aimed to investigate the efficacy and safety of individualized treatment guided by antibiotic susceptibility testing (AST) with a 10-day or 14-day course for the eradication of H. pylori.MethodsThis was a prospective, open-label, single-center, quasi-randomized trial in which 220 participants were randomized into groups based on AST results as AST-10-day (n = 98) and AST-14-day (n = 112) treatment groups. All participants were retested for a 14-carbon urease breath test at weeks 4–8 after the end of the treatment.ResultsThe primary resistance rates of H. pylori to metronidazole, levofloxacin, clarithromycin, and amoxicillin were 94.1% (207/220), 42.7% (95/220), 41.4% (91/220), and 0.9% (2/220), respectively; however, no resistance to furazolidone and tetracycline was observed. In the AST-10-day and AST-14-day groups, the intention-to-treat (ITT) eradication rates were 89.8% (88/98) and 90.2% (110/122), respectively, with no statistically significant difference (p = 0.928). The per-protocol (PP) eradication rates were 92.6% (88/95) and 98.2% (110/112), respectively, with a statistically significant difference (p = 0.049). The incidence rates of adverse events (AEs) in the AST-10-day and AST-14-day groups were 6.3% (6/95) and 7.2% (8/112), respectively, with no statistically significant difference (p = 0.813). No statistically significant difference was observed in compliance between the two groups (p = 0.467).ConclusionBoth 10-day and 14-day AST guided individualized therapy can achieve satisfactory eradication effect. Compared with the 14-day regimen, the 10-day regimen has similar eradication rate and incidence of adverse events and compliance but shorter duration and lower cost.
Artificial intelligence-powered innovations in periodontal diagnosis: a new era in dental healthcare
Authors: Jundaeng Jarupat , Chamchong Rapeeporn , Nithikathkul Choosak 
Published: January 2025

BackgroundThe aging population is increasingly affected by periodontal disease, a condition often overlooked due to its asymptomatic nature. Despite its silent onset, periodontitis is linked to various systemic conditions, contributing to severe complications and a reduced quality of life. With over a billion people globally affected, periodontal diseases present a significant public health challenge. Current diagnostic methods, including clinical exams and radiographs, have limitations, emphasizing the need for more accurate detection methods. This study aims to develop AI-driven models to enhance diagnostic precision and consistency in detecting periodontal disease.MethodsWe analyzed 2,000 panoramic radiographs using image processing techniques. The YOLOv8 model segmented teeth, identified the cemento-enamel junction (CEJ), and quantified alveolar bone loss to assess stages of periodontitis.ResultsThe teeth segmentation model achieved an accuracy of 97%, while the CEJ and alveolar bone segmentation models reached 98%. The AI system demonstrated outstanding performance, with 94.4% accuracy and perfect sensitivity (100%), surpassing periodontists who achieved 91.1% accuracy and 90.6% sensitivity. General practitioners (GPs) benefitted from AI assistance, reaching 86.7% accuracy and 85.9% sensitivity, further improving diagnostic outcomes.ConclusionsThis study highlights that AI models can effectively detect periodontal bone loss from panoramic radiographs, outperforming current diagnostic methods. The integration of AI into periodontal care offers faster, more accurate, and comprehensive treatment, ultimately improving patient outcomes and alleviating healthcare burdens.
Retinal biomarkers for the risk of Alzheimer’s disease and frontotemporal dementia
Authors: Wang Ruihan , Cai Jiajie , Gao Yuzhu , Tang Yingying , Gao Hui , Qin Linyuan , Cai Hanlin , Yang Feng , Ren Yimeng , Luo Caimei , Feng Shiyu , Yin Hongbo , Zhang Ming , Luo Chunyan , Gong Qiyong , Xiao Xiong , Chen Qin 
Published: January 2025

PurposeDifferentiating between Alzheimer’s disease (AD) and frontotemporal dementia (FTD) can be challenging due to overlapping cognitive and behavioral manifestations. Evidence regarding non-invasive and early-stage biomarkers remains limited. Our aim was to identify retinal biomarkers for the risk of AD and FTD in populations without dementia and explore underlying brain structural mechanisms.MethodsWe included a total of 3,0573 UK Biobank participants without dementia, ocular disorders, and diabetes who underwent baseline retinal optical coherence tomography (OCT) imaging. Cox proportional hazards models were used to estimate the associations between macular OCT parameters and the risk of AD and FTD. Mediation analysis was used to explore the underlying mechanisms affected by brain structures.ResultsThe mean age at recruitment was 55.27, and 46.10% of the participants were male. During a mean follow-up of 9.15 ± 2.59 years, 148 patients with AD and eight patients with FTD were identified. Reduced thickness of the ganglion cell-inner plexiform layer (GC-IPL) at baseline was associated with an increased risk of AD (HR, 1.033; 95% CI, 1.001–1.066; P = 0.044), while thinner retinal pigment epithelial in the inner superior subfield at baseline was associated with an elevated risk of FTD (HR, 1.409; 95% CI, 1.060–1.871; P = 0.018). Structurally abnormal visual pathways, including cortical and subcortical gray matter volumes, as well as white matter integrity, mediated the association between the GC-IPL thickness and AD risk.ConclusionOur findings provide preliminary empirical support for a relationship between prodromal changes in retinal layers and a higher risk of AD or FTD, suggesting that macular OCT may serve as a non-invasive, sensitive biomarker of high-risk years before the onset of dementia.