bluuebunny/crossref_metadata_2025_split huggingface dataset:
The NSCLC immunotherapy response predicted by tumor-infiltrating T cells via a non-invasive radiomic approach
Authors: Min Jie , Dong Fei , Chen Yongyuan , Li Wenshan , Wu Yimin , Tan Yanbin , Yang Fan , Wu Pin , Chai Ying 
Published: September 2024

IntroductionsIdentifying patients with non-small cell lung cancer (NSCLC) who are optimal candidates for immunotherapy is a cornerstone in clinical decision-making. The tumor immune microenvironment (TIME) is intricately linked with both the prognosis of the malignancy and the efficacy of immunotherapeutic interventions. CD8+ T cells, and more specifically, tissue-resident memory CD8+ T cells [CD8+ tissue-resident memory T (TRM) cells] are postulated to be pivotal in orchestrating the immune system's assault on tumor cells. Nevertheless, the accurate quantification of immune cell infiltration—and by extension, the prediction of immunotherapeutic efficacy—remains a significant scientific frontier.MethodsIn this study, we introduce a cutting-edge non-invasive radiomic model, grounded in TIME markers (CD3+ T, CD8+ T, and CD8+ TRM cells), to infer the levels of immune cell infiltration in NSCLC patients receiving immune checkpoint inhibitors and ultimately predict their response to immunotherapy. Data from patients who had surgical resections (cohort 1) were employed to construct a radiomic model capable of predicting the TIME. This model was then applied to forecast the TIME for patients under immunotherapy (cohort 2). Conclusively, the study delved into the association between the predicted TIME from the radiomic model and the immunotherapeutic outcomes of the patients.ResultFor the immune cell infiltration radiomic prediction models in cohort 1, the AUC values achieved 0.765, 0.763, and 0.675 in the test set of CD3+ T, CD8+ T, and CD8+ TRM, respectively. While the AUC values for the TIME-immunotherapy predictive value were 0.651, 0.763, and 0.829 in the CD3-immunotherapy response model, CD8-immunotherapy response model, and CD8+ TRM-immunotherapy response model in cohort 2, respectively. The CD8+ TRM-immunotherapy model exhibited the highest predictive value and was significantly better than the CD3-immunotherapy model in predicting the immunotherapy response. The progression-free survival (PFS) analysis based on the predicted levels of CD3+ T, CD8+ T, and CD8+ TRM immune cell infiltration showed that the CD8+ T cell infiltration level was an independent factor (P=0.014, HR=0.218) with an AUC value of 0.938.DiscussionOur empirical evidence reveals that patients with substantial CD8+ T cell infiltration experience a markedly improved PFS compared with those with minimal infiltration, asserting the status of the CD8+ T cell as an independent prognosticator of PFS in the context of immunotherapy. Although CD8+ TRM cells demonstrated the greatest predictive accuracy for immunotherapy response, their predictive strength for PFS was marginally surpassed by that of CD8+ T cells. These insights advocate for the application of the proposed non-invasive radiomic model, which utilizes TIME analysis, as a reliable predictor for immunotherapy outcomes and PFS in NSCLC patients.
Neutrophil extracellular traps and citrullinated fibrinogen contribute to injury in a porcine model of limb ischemia and reperfusion
Authors: Zollet Valentina , Arenas Hoyos Isabel , Hirsiger Stefanie , Brahim Bilal Ben , Petrucci Maria Francesca , Casoni Daniela , Wang Junhua , Spirig Rolf , Nettelbeck Kay , Garcia Luisana , Fuest Lena , Vögelin Esther , Constantinescu Mihai , Rieben Robert 
Published: September 2024

BackgroundIschemia/reperfusion injury (IRI) is a complex pathological process, triggered by the restoration of blood flow following an interrupted blood supply. While restoring the blood flow is the only option to salvage the ischemic tissue, reperfusion after a prolonged period of ischemia initiates IRI, triggering a cascade of inflammatory responses ultimately leading to neutrophil recruitment to the inflamed tissue, where they release neutrophil extracellular traps (NETs). NETs are web-like structures of decondensed chromatin and neutrophilic proteins, including peptidyl-arginine deiminase 2 and 4 (PAD2, PAD4), that, once outside, can citrullinate plasma proteins, irreversibly changing their conformation and potentially their function. While the involvement of NETs in IRI is known mainly from rodent models, we aimed to determine the effect of NET formation and especially PADs-mediated extracellular protein citrullination in a porcine model of limb IRI.MethodsWe conducted our study on amputated pig forelimbs exposed to 1 h or 9 h of ischemia and then reperfused in vivo for 12 h. Limb weight, edema formation, compartmental pressure were measured, and skeletal muscle was analyzed by immunofluorescence (TUNEL assay and dystrophin staining) to evaluate tissue damage. Fibrin tissue deposition, complement deposition and NETs were investigated by immunofluorescence. Citrullinated plasma proteins were immunoprecipitated and citrullinated fibrinogen was identified in the plasma by Western blot and in the tissue by immunofluorescence and Western blot.ResultsOur data consolidate the involvement of NETs in a porcine model of limb IRI, correlating their contribution to damage extension with the duration of the ischemic time. We found a massive infiltration of NETs in the group subjected to 9 h ischemia compared to the 1 h and citrullinated fibrinogen levels, in plasma and tissue, were higher in 9 h ischemia group. We propose fibrinogen citrullination as one of the mechanisms contributing to the worsening of IRI. NETs and protein citrullination represent a potential therapeutic target, but approaches are still a matter of debate. Here we introduce the idea of therapeutic approaches against citrullination to specifically inhibit PADs extracellularly, avoiding the downstream effects of hypercitrullination and keeping PADs’ and NETs’ intracellular regulatory functions.
Causal associations between gut microbiota, circulating inflammatory proteins, and epilepsy: a multivariable Mendelian randomization study
Authors: Yang Han , Liu Wei , Gao Tiantian , Liu Qifan , Zhang Mengyuan , Liu Yixin , Ma Xiaodong , Zhang Nan , Shi Kaili , Duan Minyu , Ma Shuyin , Zhang Xiaodong , Cheng Yuxuan , Qu Huiyang , Chen Mengying , Zhan Shuqin 
Published: September 2024

BackgroundPrevious studies have suggested that gut microbiota (GM) may be involved in the pathogenesis of epilepsy through the microbiota-gut-brain axis (MGBA). However, the causal relationship between GM and different epilepsy subtypes and whether circulating inflammatory proteins act as mediators to participate in epileptogenesis through the MGBA remain unclear. Therefore, it is necessary to identify specific GM associated with epilepsy and its subtypes and explore their underlying inflammatory mechanisms for risk prediction, personalized treatment, and prognostic monitoring of epilepsy.MethodsWe hypothesized the existence of a pathway GM-inflammatory proteins-epilepsy. We found genetic variants strongly associated with GM, circulating inflammatory proteins, epilepsy and its subtypes, including generalized and partial seizures, from large-scale genome-wide association studies (GWAS) summary data and used Multivariate Mendelian Randomization to explore the causal relationship between the three and whether circulating inflammatory proteins play a mediating role in the pathway from GM to epilepsy, with inverse variance weighted (IVW) method as the primary statistical method, supplemented by four methods: MR-Egger, weighted median estimator (WME), Weighted mode and Simple mode.Results16 positive and three negative causal associations were found between the genetic liability of GM and epilepsy and its subtypes. There were nine positive and nine negative causal associations between inflammatory proteins and epilepsy and its subtypes. Furthermore, we found that C-X-C motif chemokine 11 (CXCL11) levels mediated the causal association between Genus Family XIII AD3011 group and epilepsy.ConclusionOur study highlights the possible causal role of specific GM and specific inflammatory proteins in the development of epilepsy and suggests that circulating inflammatory proteins may mediate epileptogenesis through the MGBA.
Causal effects of systemic inflammatory proteins on Guillain-Barre Syndrome: insights from genome-wide Mendelian randomization, single-cell RNA sequencing analysis, and network pharmacology
Authors: Liu Jingwen , Pan Renbing 
Published: September 2024

BackgroundEvidence from observational studies indicates that inflammatory proteins play a vital role in Guillain-Barre Syndrome (GBS). Nevertheless, it is unclear how circulating inflammatory proteins are causally associated with GBS. Herein, we conducted a two-sample Mendelian randomization (MR) analysis to systematically explore the causal links of genetically determined systemic inflammatory proteins on GBS.MethodsA total of 8,293 participants of European ancestry were included in a genome-wide association study of 41 inflammatory proteins as instrumental variables. Five MR approaches, encompassing inverse-variance weighted, weighted median, MR-Egger, simple model, and weighted model were employed to explore the causal links between inflammatory proteins and GBS. MR-Egger regression was utilized to explore the pleiotropy. Cochran’s Q statistic was implemented to quantify the heterogeneity. Furthermore, we performed single-cell RNA sequencing analysis and predicted potential drug targets through molecular docking technology.ResultsBy applying MR analysis, four inflammatory proteins causally associated with GBS were identified, encompassing IFN-γ (OR:1.96, 95%CI: 1.02-3.78, PIVW=0.045), IL-7 (OR:1.86, 95%CI: 1.07-3.23, PIVW=0.029), SCGF-β (OR:1.56, 95%CI: 1.11-2.19, PIVW=0.011), and Eotaxin (OR:1.99, 95%CI: 1.01-3.90, PIVW=0.046). The sensitivity analysis revealed no evidence of pleiotropy or heterogeneity. Additionally, significant genes were found through single-cell RNA sequencing analysis and several anti-inflammatory or neuroprotective small molecular compounds were identified by utilizing molecular docking technology.ConclusionsOur MR analysis suggested that IFN-γ, IL-7, SCGF-β, and Eotaxin were causally linked to the occurrence and development of GBS. These findings elucidated potential causal associations and highlighted the significance of these inflammatory proteins in the pathogenesis and prospective therapeutic targets for GBS.
The diagnostic performance of the one-step nucleic acid amplification assay for the detection of sentinel lymph node metastases in cytokeratin 19-positive breast cancer: a PRISMA-compliant meta-analysis
Authors: Liu Meirong , Wang Weihua , Wang Yufang 
Published: September 2024

BackgroundThe status of the sentinel lymph nodes (SLNs) is an important prognostic factor for many different types of cancer. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid intraoperative molecular diagnostic tool for LN metastasis detection. We aimed to evaluate and summarize the value of the OSNA assay for the diagnosis of SLN metastasis in cytokeratin 19 (CK19)-positive breast cancer.MethodsTo evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. The threshold effect, followed by subgroup analysis, was performed to explore the source of heterogeneity. A sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance.ResultsA total of 29 eligible studies, which consisted of 5,331 patients with 10,343 SLNs, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.86 (95% CI: 0.85–0.88), 0.94 (95% CI, 0.94–0.95), 18.00 (95% CI, 13.54–23.92), 0.13 (95% CI, 0.10–0.17), and 138.99 (95% CI, 86.66–222.92), respectively. The AUC was 0.97 (95% CI, 0.95–0.98). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability was 50%, the post-probability positive was 95%, and the post-probability negative was 11%.DiscussionOur results suggested that OSNA can predict the occurrence of SLN metastasis in CK19-positive breast cancer. However, more well-designed and multicenter diagnostic tests are needed to validate our results.
The impact of kaolin mining activities on bacterial diversity and community structure in the rhizosphere soil of three local plants
Authors: Gao Wei , Chen Xiaodie , He Jing , Sha Ajia , Ren Yuanhang , Wu Peng , Li Qiang 
Published: September 2024

IntroductionThus far, the impact of kaolin mining activities on the surrounding native plants and rhizosphere microecology has not been fully understood.MethodsIn this study, we used 16S rRNA high-throughput sequencing to examine the impact of kaolin mining on the rhizosphere bacterial communities and functions of three local plant species: Conyza bonariensis, Artemisia annua, and Dodonaea viscosa.ResultsThe results showed that kaolin mining significantly reduced the diversity of rhizosphere bacteria in these plants, as indicated by the Shannon, Simpson, Chao1, and observed species indices (p &lt; 0.05). Kaolin mining had an impact on the recruitment of three rhizosphere bacteria native to the area: Actinoplanes, RB41, and Mycobacterium. These bacteria were found to be more abundant in the rhizosphere soil of three local plants than in bulk soil, yet the mining of kaolin caused a decrease in their abundance (p &lt; 0.05). Interestingly, Ralstonia was enriched in the rhizosphere of these plants found in kaolin mining areas, suggesting its resilience to environmental stress. Furthermore, the three plants had different dominant rhizosphere bacterial populations in kaolin mining areas, such as Nocardioides, Pseudarthrobacter, and Sphingomonas, likely due to the unique microecology of the plant rhizosphere. Kaolin mining activities also caused a shift in the functional diversity of rhizosphere bacteria in the three local plants, with each plant displaying different functions to cope with kaolin mining-induced stress, such as increased abundance of the GlpM family and glucan-binding domain.DiscussionThis study is the first to investigate the effects of kaolin mining on the rhizosphere microecology of local plants, thus contributing to the establishment of soil microecological health monitoring indicators to better control soil pollution in kaolin mining areas.
Predicting superagers: a machine learning approach utilizing gut microbiome features
Authors: Kim Ha Eun , Kim Bori R. , Hong Sang Hi , Song Seung Yeon , Jeong Jee Hyang , Kim Geon Ha 
Published: September 2024

ObjectiveCognitive decline is often considered an inevitable aspect of aging; however, recent research has identified a subset of older adults known as “superagers” who maintain cognitive abilities comparable to those of younger individuals. Investigating the neurobiological characteristics associated with superior cognitive function in superagers is essential for understanding “successful aging.” Evidence suggests that the gut microbiome plays a key role in brain function, forming a bidirectional communication network known as the microbiome-gut-brain axis. Alterations in the gut microbiome have been linked to cognitive aging markers such as oxidative stress and inflammation. This study aims to investigate the unique patterns of the gut microbiome in superagers and to develop machine learning-based predictive models to differentiate superagers from typical agers.MethodsWe recruited 161 cognitively unimpaired, community-dwelling volunteers aged 60 years or from dementia prevention centers in Seoul, South Korea. After applying inclusion and exclusion criteria, 115 participants were included in the study. Following the removal of microbiome data outliers, 102 participants, comprising 57 superagers and 45 typical agers, were finally analyzed. Superagers were defined based on memory performance at or above average normative values of middle-aged adults. Gut microbiome data were collected from stool samples, and microbial DNA was extracted and sequenced. Relative abundances of bacterial genera were used as features for model development. We employed the LightGBM algorithm to build predictive models and utilized SHAP analysis for feature importance and interpretability.ResultsThe predictive model achieved an AUC of 0.832 and accuracy of 0.764 in the training dataset, and an AUC of 0.861 and accuracy of 0.762 in the test dataset. Significant microbiome features for distinguishing superagers included Alistipes, PAC001137_g, PAC001138_g, Leuconostoc, and PAC001115_g. SHAP analysis revealed that higher abundances of certain genera, such as PAC001138_g and PAC001115_g, positively influenced the likelihood of being classified as superagers.ConclusionOur findings demonstrate the machine learning-based predictive models using gut-microbiome features can differentiate superagers from typical agers with a reasonable performance.
Association between composite dietary antioxidant index and migraine in American young women: insights from NHANES 1999–2004 cross-sectional data
Authors: Li Zeyan , Zhang Xinyu , Kong Simin , Fu Chuan-Chuan , Lv Tian-Qi , Xiao Bin 
Published: September 2024

BackgroundExcessive oxidative stress is one of the key pathophysiological mechanisms underlying migraine, and increasing antioxidant intake has proven to be an effective strategy for the prevention and improvement of migraine symptoms. To explore the relationship between the composite dietary antioxidant index (CDAI) and the occurrence of migraine attacks.MethodsCross-sectional data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999–2004 were utilized. Logistic regression, stratified analysis, and restricted cubic spline (RCS) models were employed to investigate the association between CDAI and migraine attacks.ResultsA total of 8,137 adults aged ≥20 were enrolled, comprising 1,610 patients with migraine and 6,527 non-migraine individuals. After adjusting for all covariates, CDAI was negatively correlated with migraine. In the overall participants, compared with the CDAI Q1 (−5.83 to −2.14) group, the adjusted odds ratio (OR) for migraine in Q3 (−0.59 to 1.53) and Q4 (1.53–44.63) groups were 0.71 [95% confidence interval (95% CI): 0.54–0.92, p = 0.011] and 0.64 (95% CI: 0.47–0.87, p = 0.005), respectively. After stratifying by age and gender, the protective effect was more pronounced in females aged 20–50, with adjusted OR for Q3 (−0.59 to 1.53) and Q4 (1.53–44.63) groups of 0.60 (95% CI: 0.40–0.90, p = 0.013) and 0.48 (95% CI: 0.30–0.78, p = 0.003), respectively. The RCS curve indicated a nonlinear relationship between CDAI and migraine in females aged 20–50, with a threshold of 0.006.ConclusionCDAI is negatively correlated with migraine attacks, and a higher CDAI may be an effective protective factor in preventing migraine attacks, especially in women aged 20–50.
Observations on the efficacy of edaravone dexborneol in preventing post-stroke depression and its inflammatory mechanism: a prospective, randomized, control trial
Authors: Xu Mingyuan , Li Lan , Xu Bu , Yuan Shanfang , Zheng Qin , Sun Wenjun 
Published: September 2024

ObjectiveThis study aimed to observe the effect of edaravone dexborneol (EDB) on the incidence of early post-stroke depression (PSD) and explore its inflammatory mechanisms.MethodsA prospective, randomized controlled study was conducted from January 2022 to June 2023, involving patients with acute ischemic stroke (AIS) at the Neurology Department of the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine. The control group received routine treatment, while the experimental group received routine combined EDB treatment. The main outcome measures included PSD incidence, Patient Health Questionnaire (PHQ-9) and Hamilton Depression Scale (HAMD) scores on days 14 and 30, and inflammatory factor levels on day 14.ResultsA total of 93 patients were included in the study, 51 in the experimental group and 42 in the control group. On day 14, the PSD incidence was 13.7% in the experimental group, lower than 31.0% in the control group (95%CI 0.127–0.996; p = 0.044). Compared to the control group, the experimental group showed significantly lower concentrations of pro-inflammatory cytokines IL-1β (95%CI 3.353–5.184), IL-6 (95%CI 2.694–3.426), TNF-α (95%CI 4.985–12.196), IFN-γ (95%CI 0.163–0.451), MCP-1 (95%CI 0.335–0.787), IL-17A (95%CI 0.543–1.024), and IL-23p19 (95%CI 1.677–1.959) (all p &lt; 0.001), and higher levels of anti-inflammatory cytokines IL-4 (95%CI −1.087 to −0.941), IL-10 (95%CI −6.125 to −1.662), and IL-13 (95%CI −6.078 to −2.953) (all p ≤ 0.001). On day 30, the PSD incidence in the experimental group was 15.7%, lower than 40.5% in the control group (95%CI 0.103–0.725; p = 0.007). Compared with the control group, the experimental group had lower PHQ-9 scores on day 14 (95%CI 0.034–1.577; p = 0.041) and day 30 (95%CI 0.018–1.573; p = 0.045), and also had lower HAMD scores on day 14 (95% CI 0.281–2.856; p = 0.018) and day 30 (95% CI 0.647–3.482; p = 0.005).ConclusionEDB could reduce the incidence of early PSD, reduce pro-inflammatory cytokine levels, and elevate anti-inflammatory cytokine levels, which was possibly related to the anti-inflammatory mechanism of EDB.Clinical trial registrationhttp://www.chictr.org.cn/, identifier [ChiCTR2300067750].
The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and chronic obstructive pulmonary disease: the mediating role of dietary inflammatory index
Authors: Wu Ruying , Gong Hongyang 
Published: September 2024

BackgroundNumerous studies have indicated a potential correlation between COPD, lipid metabolism, and dietary inflammation. However, the exact mechanisms by which dietary inflammation regulates the pathological processes of COPD related to lipid metabolism remain unclear. NHHR is a novel composite index of atherosclerotic lipid profiles, while the Dietary Inflammatory Index (DII) measures diet-induced inflammation. This study explores the relationship between NHHR and COPD and evaluates whether DII mediates this association.MethodsWe employed multivariable logistic regression, smooth curve fitting, threshold effect analysis, and subgroup analysis to explore the relationship between NHHR and the incidence of COPD. Additionally, we conducted a mediation analysis to explore the potential relationship between dietary inflammatory index (DII) levels and the relationship between NHHR and COPD.ResultsThis analysis encompassed 13,452 participants, with 2,332 reporting incidents of COPD. Following adjustment for all covariates using multivariable logistic regression, each unit increase in NHHR level and DII level was associated with a 10% (OR = 1.10, 95% CI: 1.05, 1.16) and 8% (OR = 1.08, 95% CI: 1.04, 1.13) increase, respectively, in the incidence rate of COPD. Furthermore, compared to the lowest quartile, the highest quartile of NHHR level and DII level was associated with a 47% (p &lt; 0.001) and 50% (p &lt; 0.001) increase, respectively, in the incidence rate of COPD. Smooth curve fitting and threshold effect analysis revealed a nonlinear relationship between NHHR and the risk of COPD, with a breakpoint at 2.60. Mediation analysis indicated that DII mediated 7.24% of the association between NHHR and COPD (p = 0.004).ConclusionHigher NHHR levels are associated with an increased prevalence of COPD. Moreover, this association is mediated by DII, suggesting that an anti-inflammatory diet may be beneficial.