bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability, repeatability, and accordance between three different corneal diagnostic imaging devices for evaluating the ocular surface
Authors: Garcia-Terraza Abril L. , Jimenez-Collado David , Sanchez-Sanoja Francisco , Arteaga-Rivera José Y. , Morales Flores Norma , Pérez-Solórzano Sofía , Garfias Yonathan , Graue-Hernández Enrique O. , Navas Alejandro 
Published: July 2022

PurposeTo evaluate repeatability, reproducibility, and accordance between ocular surface measurements within three different imaging devices.MethodsWe performed an observational study on 66 healthy eyes. Tear meniscus height, non-invasive tear break-up time (NITBUT) and meibography were measured using three corneal imaging devices: Keratograph 5M (Oculus, Wetzlar, Germany), Antares (Lumenis, Sidney, Australia), and LacryDiag (Quantel Medical, Cournon d’Auvergne, France). One-way ANOVAs with post hoc analyses were used to calculate accordance between the tear meniscus and NITBUT. Reproducibility was assessed through coefficients of variation and repeatability with intraclass correlation coefficients (ICC). Reliability of meibography classification was analyzed by calculating Fleiss’ Kappa Index and presented in Venn diagrams.ResultsCoefficients of variation were high and differed greatly depending on the device and measurement. ICCs showed moderate reliability of NITBUT and tear meniscus height measurements. We observed discordance between measurements of tear meniscus height between the three devices, F2, 195 = 15.24, p &lt; 0.01. Measurements performed with Antares were higher; 0.365 ± 0.0851, than those with Keratograph 5M and LacryDiag; 0.293 ± 0.0790 and 0.306 ± 0.0731. NITBUT also showed discordance between devices, F2, 111 = 13.152, p &lt; 0.01. Measurements performed with LacryDiag were lower (10.4 ± 1.82) compared to those of Keratograph 5M (12.6 ± 4.01) and Antares (12.6 ± 4.21). Fleiss’ Kappa showed a value of -0.00487 for upper lid and 0.128 for inferior lid Meibography classification, suggesting discrete to poor agreement between measurements.ConclusionDepending on the device used and parameter analyzed, measurements varied between each other, showing a difference in image processing.
Identification of diagnostic signatures associated with immune infiltration in Alzheimer’s disease by integrating bioinformatic analysis and machine-learning strategies
Authors: Tian Yu , Lu Yaoheng , Cao Yuze , Dang Chun , Wang Na , Tian Kuo , Luo Qiqi , Guo Erliang , Luo Shanshun , Wang Lihua , Li Qian 
Published: July 2022

ObjectiveAs a chronic neurodegenerative disorder, Alzheimer’s disease (AD) is the most common form of progressive dementia. The purpose of this study was to identify diagnostic signatures of AD and the effect of immune cell infiltration in this pathology.MethodsThe expression profiles of GSE109887, GSE122063, GSE28146, and GSE1297 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between AD and control brain samples. Functional enrichment analysis was performed to reveal AD-associated biological functions and key pathways. Besides, we applied the Least Absolute Shrinkage Selection Operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analysis to screen potential diagnostic feature genes in AD, which were further tested in AD brains of the validation cohort (GSE5281). The discriminatory ability was then assessed by the area under the receiver operating characteristic curves (AUC). Finally, the CIBERSORT algorithm and immune cell infiltration analysis were employed to assess the inflammatory state of AD.ResultsA total of 49 DEGs were identified. The functional enrichment analysis revealed that leukocyte transendothelial migration, cytokine receptor interaction, and JAK-STAT signaling pathway were enriched in the AD group. MAF basic leucine zipper transcription factor F (MAFF), ADCYAP1, and ZFP36L1 were identified as the diagnostic biomarkers of AD with high discriminatory ability (AUC = 0.850) and validated in AD brains (AUC = 0.935). As indicated from the immune cell infiltration analysis, naive B cells, plasma cells, activated/resting NK cells, M0 macrophages, M1 macrophages, resting CD4+ T memory cells, resting mast cells, memory B cells, and resting/activated dendritic cells may participate in the development of AD. Additionally, all diagnostic signatures presented different degrees of correlation with different infiltrating immune cells.ConclusionMAFF, ADCYAP1, and ZFP36L1 may become new candidate biomarkers of AD, which were closely related to the pathogenesis of AD. Moreover, the immune cells mentioned above may play crucial roles in disease occurrence and progression.
Constructing prediction models for excessive daytime sleepiness by nomogram and machine learning: A large Chinese multicenter cohort study
Authors: Deng Penghui , Xu Kun , Zhou Xiaoxia , Xiang Yaqin , Xu Qian , Sun Qiying , Li Yan , Yu Haiqing , Wu Xinyin , Yan Xinxiang , Guo Jifeng , Tang Beisha , Liu Zhenhua 
Published: July 2022

ObjectiveAlthough risk factors for excessive daytime sleepiness (EDS) have been reported, there are still few cohort-based predictive models for EDS in Parkinson’s disease (PD). This 1-year longitudinal study aimed to develop a predictive model of EDS in patients with PD using a nomogram and machine learning (ML).Materials and methodsA total of 995 patients with PD without EDS were included, and clinical data during the baseline period were recorded, which included basic information as well as motor and non-motor symptoms. One year later, the presence of EDS in this population was re-evaluated. First, the baseline characteristics of patients with PD with or without EDS were analyzed. Furthermore, a Cox proportional risk regression model and XGBoost ML were used to construct a prediction model of EDS in PD.ResultsAt the 1-year follow-up, EDS occurred in 260 of 995 patients with PD (26.13%). Baseline features analysis showed that EDS correlated significantly with age, age of onset (AOO), hypertension, freezing of gait (FOG). In the Cox proportional risk regression model, we included high body mass index (BMI), late AOO, low motor score on the 39-item Parkinson’s Disease Questionnaire (PDQ-39), low orientation score on the Mini-Mental State Examination (MMSE), and absence of FOG. Kaplan–Meier survival curves showed that the survival prognosis of patients with PD in the high-risk group was significantly worse than that in the low-risk group. XGBoost demonstrated that BMI, AOO, PDQ-39 motor score, MMSE orientation score, and FOG contributed to the model to different degrees, in decreasing order of importance, and the overall accuracy of the model was 71.86% after testing.ConclusionIn this study, we showed that risk factors for EDS in patients with PD include high BMI, late AOO, a low motor score of PDQ-39, low orientation score of MMSE, and lack of FOG, and their importance decreased in turn. Our model can predict EDS in PD with relative effectivity and accuracy.
The past, present, and future of research on neuroinflammation-induced mild cognitive impairment: A bibliometric analysis
Authors: Cai Ming , Zhang Yuanqi , Chen Si , Wu Zhan , Zhu Lei 
Published: July 2022

BackgroundMild cognitive impairment (MCI) is a precursor to dementia, and neuroinflammation in the brain is thought to be one of the main pathogenic mechanisms of MCI. However, the underlying neurobiological mechanisms have not been fully explored. The purpose of this study was to establish a visual model map of the articles in the field of neuroinflammation-induced MCI over the past 11 years to reveal the research hotspots and predict the future development trends in this field, which will help to promote the research and development for MCI.MethodsThe “neuroinflammation” and “mild cognitive impairment” were used as search terms, and literature about neuroinflammation-induced MCI published between 2011 and 2021 was collected from the Web of Science. CiteSpace and VOSviewer were used to create visual model maps, and assess collaboration among different authors, countries, and institutions. Finally, the current research hotspots and future research directions were analyzed by using high-frequency keywords analysis and co-cited reference burst analysis.ResultsA total of 226 articles were retrieved. The number of publications in neuroinflammation-induced MCI shows an upward trend. Since 2018, the number of papers published in this field has increased significantly, with an average of more than 100 published each year. The United States had the highest literature production and the number of cited journals in this research area, and the National Institute on Aging was the most productive research institution. Brooks D.J. and Heneka M.T. had the highest number of publications and had the highest frequency of co-citations. The co-cited references revealed the evolution of the research themes, and the current studies are mainly focused on the effects of various metabolites on the control of microglial activation. “Cerebrospinal fluid,” “mouse model,” “tau,” “microglial activation,” “astrocytes,” and “TREM2” were the current high-frequency and emerging keywords.ConclusionResearch on neuroinflammation-induced MCI is burgeoning, and the close collaboration with different nations and institutions need to be further strengthened. Current research hotspots are focused on the effects of various metabolites on microglia activation. Future studies should focus on how to regulate the phenotypes of microglia and astrocyte to reduce neuroinflammation and treat MCI.
The effect of hyperbaric oxygen therapy on cognition, performance, proteomics, and telomere length—The difference between zero and one: A case report
Authors: Maroon Joseph C. 
Published: July 2022

IntroductionHyperbaric oxygen (HBO2) therapy has recently been suggested for the treatment of different brain injuries as well as for physical and cognitive enhancement. The author recently carried out a self-experiment to obtain objective information on the effects of HBO2 therapy on neurocognition, cardiopulmonary function, neuroimaging and its effect on novel biomarkers such as telomere length and proteomics. In the following case report, the author will present and discuss the results and the differences between zero and one.MethodsThis is a personal case report on a single subject, myself, who underwent a protocol of 60 daily HBO2 therapy sessions within 3 months. Pre- and post-therapy objective evaluation measured included computerized cognitive assessment, brain imaging, cardiopulmonary exercise test, physical assessments and blood tests including telomere length and proteomics.ResultsNeurocognitive results showed a 3.1–3.8% improvements in global cognitive function as well as all other cognitive function domains. In the perfusion MRI, there was a relative increase ranging from 43.3 to 52.3% in cerebral perfusion in various areas subserving memory, coordination, and visual motor cortex function. Similar improvements in cerebral perfusion were seen in the SPECT scans, which ranged from 8.79 to 16.12% increased perfusion in the temporal pole and entorhinal cortex subserving memory, as well as in the subcallosal area and lingual gyrus. MRI-DTI showed prominent increases in fractional anisotropy in several white matter areas including 9% in the body of the corpus callosum, 16.85% in for the fornix and 22.06% in the tapetum. In the physical domains, there were improvements in both anaerobic threshold, exercise endurance, muscle strength, gait speed and grip strength in the 7–15% range. The telomeres length was doubled and clusters of inflammatory proteins dropped around the 40th session and remained low at the 60th session.ConclusionThe difference between zero and one in this single case study of HBO2 therapy confirmed improvement in objective biomarkers which measured cognition, memory, brain processing speed, athletic performance and neuroimaging modalities measuring cerebral perfusion, blood flow and tractography. Additional studies with larger sample size and randomized clinical trials using similar biomarkers are needed to confirm the results and to delineate the longevity of these improvements.
Early changes in peripheral blood cytokine levels after the treatment of metastatic hepatic carcinoma with CalliSpheres microspheres drug-eluting beads transcatheter arterial chemoembolization
Authors: Liu Ying , Liu Song , Zhao Guang Sheng , Li Xiang , Gao Fei , Ren Zhi Zhong , Bian Jie , Wu Jian Lin , Zhang Yue Wei 
Published: July 2022

ObjectiveTo observe the early changes in peripheral blood cytokine levels after treatment of metastatic hepatic carcinoma (MHC) with CalliSpheres microspheres drug-eluting beads (DEB) transcatheter arterial chemoembolization (CSM-TACE).MethodsTwenty-eight patients with refractory MHC who underwent CSM-TACE were selected prospectively, and 5mL of peripheral blood was collected before CSM-TACE and on the 2nd and 5th day after CSM-TACE. Flow cytometry was used to detect immunological indicators. The early changes in levels of peripheral blood cell inflammatory factors Th1 (interleukin 2 (IL-2), tumor necrosis factor-α (TNF-a), interferon (IFN-r)), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were observed after CSM-TACE, as well as the ratio of CD4+/CD8+.ResultsAll the 28 patients underwent CSM-TACE successfully. CT at 4 days after CSM-TACE showed clear outline low-density changes in liver tumors, and honeycomb necrosis was observed in the tumors in some cases. After CSM-TACE, the IL-6 and IL-10 levels were increased and then decreased again. After CSM-TACE, IL-2 showed a trend of transient increase and then decreased again, and the TNF-a level decreased temporarily, and then decreased. After CSM-TACE, the IFN-r level showed a continuous and slowly increasing trend. The IL-17 level showed a continuous downward trend, and the CD4+/CD8+ ratio showed a gradual and continuous upward trend, and there was a negative correlation between them.ConclusionsThere are complex dynamic changes in TH1/Th2 in the early stage of CSM-TACE, and the acute inflammatory response and the enhancement of the body’s immune anti-tumor response coexist.
Whole-genome/exome analysis of circulating tumor DNA and comparison to tumor genomics from patients with heavily pre-treated ovarian cancer: subset analysis of the PERMED-01 trial
Authors: Sabatier Renaud , Garnier Séverine , Guille Arnaud , Carbuccia Nadine , Pakradouni Jihane , Adelaide José , Provansal Magali , Cappiello Maria , Rousseau Frédérique , Chaffanet Max , Birnbaum Daniel , Mamessier Emilie , Gonçalves Anthony , Bertucci François 
Published: July 2022

IntroductionThe poor prognosis of ovarian carcinoma (OvC) is due to the advanced stage at diagnosis, a high risk of relapse after first-line therapies, and the lack of efficient treatments in the recurrence setting. Circulating tumor DNA (ctDNA) analysis is a promising tool to assess treatment-resistant OvC and may avoid iterative tissue biopsies. We aimed to evaluate the genomic profile of recurrent heavily pre-treated OvC.MethodsWe performed tumor panel-based sequencing as well as low-coverage whole-genome sequencing (LC-WGS) of tumor and plasma collected in patients with ovarian cancer included in the PERMED-01 trial. Whole-exome sequencing (WES) data of plasma samples were also analyzed and compared to mutation and copy number alteration (CNA) tumor profiles. The prognostic value [progression-free survival (PFS)] of these alterations was assessed in an exploratory analysis.ResultsTumor and plasma genomic analyses were done for 24 patients with heavily pretreated OvC [67% high-grade serous carcinoma (HGSC)]. Tumor mutation burden was low (median 2.04 mutations/Mb) and the most frequent mutated gene was TP53 (94% of HGSC). Tumor CNAs were frequent with a median of 50% of genome altered fraction. Plasma LC-WGS and WES detected ctDNA in 21/24 cases (88%) with a median tumor fraction of 12.7%. We observed a low correlation between plasma and tumor CNA profiles. However, this correlation was significant in cases with the highest circulating tumor fraction. Plasma genome altered fraction and plasma mutation burden (p = 0.011 and p = 0.041, respectively, log-rank tests) were associated with PFS.ConclusionsCombination of LC-WGS and WES can detect ctDNA in most pre-treated OvCs. Some ctDNA characteristics, such as genome altered fraction and plasma mutation burden, showed prognostic value. ctDNA assessment with LC-WGS may be a promising and non-expansive tool to evaluate disease evolution in this disease with high genomic instability.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02342158, identifier NCT02342158.
Serum levels of IL-6 and CRP can predict the efficacy of mFOLFIRINOX in patients with advanced pancreatic cancer
Authors: Shen Feifei , Liu Chuan , Zhang Weiguo , He Sijia , Wang Fan , Wang Jingjue , Li Qi , Zhou Fei 
Published: July 2022

ObjectivesThere is an urgent need for biomarkers that predict the survival outcome of patients diagnosed with metastatic pancreatic cancer, undergoing systemic chemotherapy. This study aimed to identify biomarkers associated with the survival of mPC patients treated with modified FOLFIRINOX (mFOLFIRINOX) as first-line chemotherapy.MethodsThis was a retrospective study of 30 patients with mPC who received mFOLFIRINOX between October 2018 and March 2021. Data on carcinoembryonic antigen (CEA), cancer antigen (CA)199, interleukin (IL)-6, C-reactive protein (CRP), neutrophils, platelets, lymphocytes, and albumin were collected and dichotomized using the upper or lower limit, as appropriate. These markers were examined for their association with progression-free survival (PFS). A receiver operating characteristic (ROC) curve analysis was used to explore a suitable model to predict mFOLFIRINOX effectiveness.ResultsIL-6 and CRP levels were associated with poor progression (P = 0.004 and P = &lt;0.001, respectively) of mPC. The high IL-6 level was an independent poor prognostic factor for PFS (HR=4.66, 95%CI: 1.32-16.37, P=0.016) in the multivariable analysis. Patients with high IL-6 levels had a shorter PFS than those with low IL-6 levels (median PFS: 257 vs. 150 days, P=0.020). An increase in IL-6 and CRP levels during chemotherapy positively correlated with disease progression (P = &lt;0.001 for both). The model combining IL-6 with CRP levels helped predict the outcomes of mPC patients treated with mFOLFIRINOX (AUC: 0.811, 95%CI: 0.639-0.983, P=0.003).ConclusionsThe serum levels of IL-6 and CRP might be considered as valuable biomarkers in predicting the outcomes of patients with mPC who received the mFOLFIRINOX regimen.
Association of preoperative albumin–bilirubin with surgical textbook outcomes following laparoscopic hepatectomy for hepatocellular carcinoma
Authors: Xu Fei-Qi , Ye Tai-Wei , Wang Dong-Dong , Xie Ya-Ming , Zhang Kang-Jun , Cheng Jian , Xiao Zun-Qiang , Liu Si-Yu , Jiang Kai , Yao Wei-Feng , Shen Guo-Liang , Liu Jun-Wei , Zhang Cheng-Wu , Huang Dong-Sheng , Liang Lei 
Published: July 2022

Background and aimsRecently, the effectiveness of “textbook outcomes (TO)” in the evaluation of surgical quality has been recognized by more and more scholars. This study tended to examine the association between preoperative albumin–bilirubin (ALBI) grades and the incidence of achieving or not achieving TO (non-TO) in patients with hepatocellular carcinoma (HCC) undergoing laparoscopic hepatectomy.MethodsThe patients were stratified into two groups: ALBI grade 1 (ALBI ≤ -2.60) and ALBI grade 2/3 (ALBI &gt; -2.60). The characteristics of patients and the incidence of non-TO were compared. Multivariate analyses were performed to determine whether ALBI grade was independently associated with TO.ResultsIn total, 378 patients were enrolled, including 194 patients (51.3%) in the ALBI grade 1 group and 184 patients (48.7%) in the ALBI grade 2/3 group. In the whole cohort, 198 patients (52.4%) did not achieve TO, and the incidence of non-TO in the ALBI grade 2/3 group was obviously higher than that in the ALBI grade 1 group (n = 112, 60.9% vs. n = 86, 44.3%, P = 0.001). The multivariate analyses showed that ALBI grade 2/3 was an independent risk factor for non-TO (OR: 1.95, 95%CI: 1.30–2.94, P = 0.023).ConclusionsMore than half (52.4%) of the patients with hepatocellular carcinoma did not achieve TO after laparoscopic hepatectomy, and preoperative ALBI grade 2/3 was significantly associated with non-TO. Improving the liver function reserve of patients before operation, thereby reducing the ALBI grade, may increase the probability for patients to reach TO and enable patients to benefit more from surgery.
Adjusting CA19-9 values with clinical stage and bilirubin to better predict survival of resectable pancreatic cancer patients: 5-year-follow-up of a single center
Authors: Wu Zuowei , Zhao Pengcheng , Wang Zihe , Huang Xing , Wu Chao , Li Mao , Wang Li , Tian Bole 
Published: July 2022

BackgroundPancreatic cancer mortality is growing every year, and radical resection is the most essential therapy strategy. It is critical to evaluate the long-term prognosis of individuals receiving radical surgery. CA19-9 is a biomarker for patient recurrence and survival, however obstructive jaundice has a significant impact on this index. Researchers have attempted to modify the index using various modification methods, but the results have been unsatisfactory. In this study, we adjusted CA19-9 values based on clinical stage and bilirubin and found that it provided better prediction than CA19-9 alone in assessing patients.MethodsWe analyzed over 5 years follow-up records of patients who underwent radical pancreatic cancer surgery between August 2009 and May 2017 in a single center. We investigated the association of risk factors with overall survival (OS) as well as disease-free survival (DFS) after surgery. Threshold values for high-risk features associated with poor prognosis in resectable pancreatic cancer were determined. The hazard ratios of the indicators were eventually examined under the stratification of patients’ clinical stages.ResultsA total of 202 patients were involved in the study. The optimum cut-off values for CA19-9 and CA19-9/TB for predicting overall survival were 219.4 (p = 0.0075) and 18.8 (p = 0.0353), respectively. CA19-9&gt;219.4 increased the risk of patient mortality by 1.70 times (95% CI 1.217-2.377, p = 0.002), and tumor poor differentiation raised the risk by 1.66 times (95% CI 1.083-2.553, P = 0.02). Based on clinical stage stratification, we found discrepancies in the predictive efficacy of CA19-9 and CA19-9/TB. CA19-9 was a better predictor in clinical stage 1 (HR = 2.056[CI 95%1.169-3.616], P = 0.012), whereas CA19-9/TB indications were better in stages 2 (HR = 1.650[CI 95%1.023-2.662], P = 0.040) and 3 (HR = 3.989[CI95%1.145-13.896], P = 0.030).ConclusionsCA19-9, CEA, and tumor differentiation are predictors for patients with resectable PDAC. CA19-9 values can be adjusted based on clinical stage and bilirubin levels to better predict overall survival in patients with resectable PDAC. CA19-9&gt;219.4 predicted poor survival in individuals in clinical stage 1, whereas CA19-9/TB&gt;18.8 predicted poor survival for individuals in stages 2 and 3.