bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic perfusion as a new predictor of prognosis and mortality in critical care patients with acute-on-chronic liver failure
Authors: Vogg Johannes , Maier-Stocker Constantin , Munker Stefan , Mehrl Alexander , Schlosser Sophie , Tews Hauke Christian , Gülow Karsten , Müller Martina , Schmid Stephan 
Published: October 2022

Background and aimsLiver diseases are frequent causes of morbidity and mortality worldwide. Liver diseases can lead to cirrhosis, with the risk of acute-on-chronic liver failure (ACLF). For the detection of changes in hepatic hemodynamics, Doppler ultrasonography is a well-established method. We investigated hepatic hemodynamics via serial Doppler ultrasonography to determine the predictive value of changes in hepatic perfusion for the outcome in patients with severe liver diseases compared to established prognostic models such as the MELD (Model for End-Stage Liver Disease) or CLIF-C (Chronic Liver Failure-Consortium) ACLF score.MethodsIn this prospective cohort study, hepatic perfusion was quantified at baseline before the initiation of treatment and every third day by means of serial measurements of the hepatic artery resistance index (HARI) and the maximum portal vein velocity (PVv) using Doppler ultrasonography in 50 consecutive patients with severe liver diseases admitted to a medical intensive care unit (MICU). The recorded hemodynamic parameters were compared to the MELD score, and the CLIF-C ACLF score to analyze their utility for the prediction of the outcome of patients with severe liver diseases, liver cirrhosis, and ACLF.ResultsThe changes (delta) obtained by serial measurements of the MELD score, HARI, and PVv were analyzed through scatter plots. Bivariate correlation analysis yielded a new positive linear correlation between the delta-HARI and the delta-MELD score (r = 0.469; p &lt; 0.001). In addition, our data revealed a new negative linear correlation between delta-PVv and the delta-MELD score (r = −0.279, p = 0.001). The leading cause of MICU mortality was acute-on-chronic liver failure (ACLF). A subgroup analysis of patients with liver cirrhosis revealed a positive linear correlation between the delta-HARI and the delta-CLIF-C-ACLF score (r = 0.252, p = 0.005). Of clinical relevance, non-survivors of ACLF exhibited a significantly higher mean value for the delta-HARI (0.010 vs. −0.005; p = 0.015) and a lower mean value for the delta-PVv (−0.7 vs. 1.9 cm/s; p = 0.037) in comparison to survivors of ACLF.ConclusionThis study shows the prognostic value of the assessment of hepatic perfusion in critical care patients with severe liver diseases by bedside Doppler ultrasound examination and its utility as an accurate predictor of the outcome in patients with ACLF. Increasing HARI and a decreasing PVv are predictors of an adverse outcome. Delta-HARI and delta-PVv are new biomarkers of prognosis and ACLF-related mortality in patients with liver diseases. Delta-HARI and delta-PVv may be helpful in guiding clinical decision-making, especially in catecholamine and fluid management.
Clinical characteristics and risk factors for 90-day overall survival among 204 adult patients with secondary hemophagocytic lymphohistiocytosis: Experience from a single-center retrospective study
Authors: Wang Dongguang , Tong Xiang , Liu Sitong , Zhang Wentao , Wang Lian , Zhang Shijie , Zhang Tianli , Wang Qian , Fan Hong 
Published: October 2022

ObjectivesTo describe the clinical characteristics of secondary hemophagocytic lymphohistiocytosis (HLH) among adult patients, investigate its risk factors for 90-day overall survival (OS) from diagnosis, and establish a new prognostic model applicable to adult patients with secondary HLH.MethodsWe conducted a retrospective cohort study of 204 adult patients with secondary HLH, between January 2010 and December 2020. All patients met at least five HLH-2004 criteria. Clinical features, laboratory results, treatments, and clinical outcomes of the patients were reviewed. Prognostic factors associated with 90-day overall survival from diagnosis were screened using Cox proportional hazard models.ResultsThe most common trigger was malignancy (61.3%). Multivariate analysis showed that age, coagulopathy, levels of hemoglobin, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatinine, ferritin, and prothrombin time (PT) were independent prognostic factors for 90-day OS from the diagnosis of HLH. Based on the above risk factors, the patients were further divided into two groups: low-risk (≤4 risk factors) and high-risk (&gt;4 risk factors), with overall 90-day survival rates of 82.7 and 28.1%, respectively (P &lt; 0.001).ConclusionPatients with older age, coagulopathy, lower hemoglobin, and AST levels, elevated LDH, creatinine and ferritin levels, and prolonged PT tended to have a worse prognosis. Moreover, our prognostic model provides the possibility of forecasting the clinical outcome of adult secondary HLH patients, although a larger sample, multicenter, randomized controlled clinical study is needed to verify the accuracy of the prognostic model.
Current and investigational drugs in early clinical development for portal hypertension
Authors: Sakiani Sasan , Heller Theo , Koh Christopher 
Published: October 2022

IntroductionThe development of portal hypertension leads to a majority of complications associated with chronic liver disease. Therefore, adequate treatment of portal hypertension is crucial in the management of such patients. Current treatment options are limited and consist mainly of medications that decrease the hyperdynamic circulation, such as non-selective beta blockers, and treatment of hypervolemia with diuretics. Despite these options, mortality rates have not improved over the last two decades. Newer, more effective treatment options are necessary to help improve survival and quality of life in these patients.Areas coveredMultiple preclinical models and clinical studies have demonstrated potential efficacy of a variety of new treatment modalities. We introduce treatment options including the use of vasodilation promotors, vasoconstriction inhibitors, anticoagulants, antiangiogenics, and anti-inflammatory drugs. We examine the most recent studies for treatment options within these drug classes and offer insights as to which show the most promise in this field.MethodologyPublished studies that identified novel medical treatment options of portal hypertension were searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/). Clinical trials listed in Clinicaltrials.gov were also searched with a focus on more recent and ongoing studies, including those with completed recruitment. Searching with key terms including “portal hypertension” as well as individually searching specific treatment medications that were listed in other publications was carried out. Finally, current societal guidelines and recent review articles relevant to the management of portal hypertension were evaluated, and listed references of interest were included.ConclusionMany ongoing early phase studies demonstrate promising results and may shape the field of portal hypertension management in future. As concrete results become available, larger RCTs will be required before making definitive conclusions regarding safety and efficacy and whether or not they can be incorporated into routine clinical practice. Statins, anticoagulants, and PDE inhibitors have been among the most studied and appear to be most promising.
Potential biomarkers of Alzheimer’s disease and cerebral small vessel disease
Authors: Zou Chun , Huang Xiaohua , Zhang Yilong , Pan Mika , Xie Jieqiong , Chen Liechun , Meng Youshi , Zou Donghua , Luo Jiefeng 
Published: October 2022

BackgroundCerebral small vessel disease (CSVD) is associated with the pathogenesis of Alzheimer’s disease (AD). Effective treatments to alleviate AD are still not currently available. Hence, we explored markers and underlying molecular mechanisms associated with AD by utilizing gene expression profiles of AD and CSVD patients from public databases, providing more options for early diagnosis and its treatment.MethodsGene expression profiles were collected from GSE63060 (for AD) and GSE162790 (for CSVD). Differential analysis was performed between AD and mild cognitive impairment (MCI) or CSVD progression and CSVD no-progression. In both datasets, differentially expressed genes (DEGs) with the same expression direction were identified as common DEGs. Then protein-protein interaction (PPI) network was constructed for common DEGs. Differential immune cells and checkpoints were calculated between AD and MCI.ResultsA total of 146 common DEGs were identified. Common DEGs were mainly enriched in endocytosis and oxytocin signaling pathways. Interestingly, endocytosis and metabolic pathways were shown both from MCI to AD and from CSVD no-progression to CSVD progression. Moreover, SIRT1 was identified as a key gene by ranking degree of connectivity in the PPI network. SIRT1 was associated with obesity-related genes and metabolic disorders. Additionally, SIRT1 showed correlations with CD8 T cells, NK CD56 bright cells, and checkpoints in AD.ConclusionThe study revealed that the progression of AD is associated with abnormalities in gene expression and metabolism and that the SIRT1 gene may serve as a promising therapeutic target for the treatment of AD.
Association of low birthweight and small for gestational age with maternal ferritin levels: A retrospective cohort study in China
Authors: Tao Yun , Kang Jiawei , Liu Juan , Duan Jie , Wang Fang , Shi Yue , Li Yujuan , Wang Cheng , Xu Dan , Qu Xinlan , Guo Juanjuan , Ma Jianhong , Zhang Yuanzhen 
Published: October 2022

BackgroundBirthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial.ObjectiveThis retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA).MethodsNewborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose–response manners of ferritin level and birthweight outcomes.ResultsA total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37–2.32) for LBW and 1.87 (95% CI 1.38–2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03–4.47) for Quartile 2, 3.13 (95% CI 1.47–6.69) for Quartile 3, and 3.63 (95% CI 1.52–8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively.ConclusionsOur findings found a linear dose–response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.
The association between caffeine intake and risk of kidney stones: A population-based study
Authors: Geng Jiwen , Qiu Yuxuan , Kang Zhefeng , Li Yupei , Li Jiameng , Liao Ruoxi , Qin Zheng , Yang Qinbo , Su Baihai 
Published: October 2022

BackgroundAlthough many studies have proven the beneficial effects of caffeine on human health, the association between caffeine intake and the risk of kidney stones is limited in large epidemiologic studies.ObjectivesWe aimed to investigate the association between caffeine intake and the risk of kidney stones.MethodsA total of 30,716 participants (with weight numbers of 204, 189, and 886) with a history of kidney stone were included in this analysis. All data were survey-weighted, and corresponding logistic regression models were performed to examine the associations between caffeine intake and the risk of kidney stones.ResultsIn a fully adjusted model, a per-quartile increase in caffeine intake was associated with a 5.32% decreased risk of kidney stones. In the subgroup analysis, the multivariate-adjusted odds ratios (95% confidence intervals) of the risk of kidney stones for per-quartile increments in caffeine intake were 0.9650 (0.9643, 0.9656) for men, 0.9320 (0.9313, 0.9327) for women, 0.9384 (0.9378, 0.9389) for white race individuals, 1.0281 (1.0270, 1.0292) for nonwhite race individuals, 0.9460 (0.9455, 0.9465) for overweight/obese individuals, and 0.9314 (0.9303, 0.9324) for non-overweight individuals, 0.9100 (0.9094, 0.9105) for caffeine from coffee, and 1.0021 (1.0013, 1.0029) for caffeine from non-coffee sources.ConclusionCaffeine intake was negatively associated with the risk of kidney stones. In subgroup analyses, the negative association of caffeine with kidney stone risk was only found in white individuals. In addition, the decreased risk was found higher in women and non-overweight individuals. Especially for women, white individuals and non-overweight individuals. The protective effect of caffeine intake from coffee on stone formation was more significant than that of caffeine from non-coffee sources.
Addictive behavior and incident gallstone disease: A dose–response meta-analysis and Mendelian randomization study
Authors: Bai Ye , Zhang Min , Cui Huijie , Shan Xuefeng , Gu Dongqing , Wang Yutong , Tang Mingshuang , Wang Xin , Jiang Xia , Zhang Ben 
Published: October 2022

BackgroundPrevious studies have suggested associations between addictive behavior and gallstone disease (GSD) risk, yet conflicting results exist. It also remains unclear whether this association is causal or due to confounding or reverse associations. The present study aims to systematically analyze the epidemiological evidence for these associations, as well as estimate the potential causal relationships using Mendelian randomization (MR).MethodsWe analyzed four common addictive behaviors, including cigarette smoking, alcohol intake, coffee, and tea consumption (N = 126,906–4,584,729 participants) in this meta-analysis based on longitudinal studies. The two-sample MR was conducted using summary data from genome-wide associations with European ancestry (up to 1.2 million individuals).ResultsAn observational association of GSD risk was identified for smoking [RR: 1.17 (95% CI: 1.06–1.29)], drinking alcohol [0.84 (0.78–0.91)], consuming coffee [0.86 (0.79–0.93)], and tea [1.08 (1.04–1.12)]. Also, there was a linear relationship between smoking (pack-years), alcohol drinking (days per week), coffee consumption (cups per day), and GSD risk. Our MRs supported a causality of GSD incidence with lifetime smoking [1.008 (1.003–1.013), P = 0.001], current smoking [1.007 (1.002–1.011), P = 0.004], problematic alcohol use (PAU) [1.014 (1.001–1.026), P = 0.029], decaffeinated coffee intake (1.127 [1.043–1.217], P = 0.002), as well as caffeine-metabolism [0.997 (0.995–0.999), P = 0.013], and tea consumption [0.990 (0.982–0.997), P = 0.008], respectively.ConclusionOur study suggests cigarette smoking, alcohol abuse, and decaffeinated coffee are causal risk factors for GSD, whereas tea consumption can decrease the risk of gallstones due to the effect of caffeine metabolism or polyphenol intake.
Prognostic value of lncRNAs related to fatty acid metabolism in lung adenocarcinoma and their correlation with tumor microenvironment based on bioinformatics analysis
Authors: Pan Ya-Qiang , Xiao Ying , Long Tao , Liu Chao , Gao Wen-Hui , Sun Yang-Yong , Liu Chang , Shi Yi-Jun , Li Shuang , Shao Ai-Zhong 
Published: October 2022

BackgroundAs a key regulator of metabolic pathways, long non-coding RNA (lncRNA) has received much attention for its relationship with reprogrammed fatty acid metabolism (FAM). This study aimed to investigate the role of the FAM-related lncRNAs in the prognostic management of patients with lung adenocarcinoma (LUAD) using bioinformatics analysis techniques.MethodsWe obtained LUAD-related transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) database. The lncRNA risk models associated with FMA were constructed by single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network (WGCNA), differential expression analysis, overlap analysis, and Cox regression analysis. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were utilized to assess the predictive validity of the risk model. Gene set variation analysis (GSVA) revealed molecular mechanisms associated with the risk model. ssGSEA and microenvironment cell populations-counter (MCP-counter) demonstrated the immune landscape of LUAD patients. The relationships between lncRNAs, miRNAs, and mRNAs were predicted by using LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using DAVID v6.8. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of the prognostic lncRNAs.ResultsWe identified 249 differentially expressed FMA-related lncRNAs in TCGA-LUAD, six of which were used to construct a risk model with appreciable predictive power. GSVA results suggested that the risk model may be involved in regulating fatty acid synthesis/metabolism, gene repair, and immune/inflammatory responses in the LUAD process. Immune landscape analysis demonstrated a lower abundance of immune cells in the high-risk group of patients associated with poor prognosis. Moreover, we predicted 279 competing endogenous RNA (ceRNA) mechanisms for 6 prognostic lncRNAs with 39 miRNAs and 201 mRNAs. Functional enrichment analysis indicated that the ceRNA network may be involved in the process of LUAD by participating in genomic transcription, influencing the cell cycle, and regulating tissue and organogenesis. In vitro experiments showed that prognostic lncRNA CTA-384D8.35, lncRNA RP5-1059L7.1, and lncRNA Z83851.4 were significantly upregulated in LUAD primary tumor tissues, while lncRNA RP11-401P9.4, lncRNA CTA-384D8.35, and lncRNA RP11-259K15.2 were expressed at higher levels in paraneoplastic tissues.ConclusionIn summary, the prognostic factors identified in this study can be used as potential biomarkers for clinical applications. ceRNA network construction provides a new vision for the study of LUAD pathogenesis.
Case report: NAFLD and maple syrup urine disease: Is there an interplay between branched-chain amino acids and fructose consumption?
Authors: Moreira-Silva Helena , Ferreira Sandra , Almeida Manuela , Gonçalves Isabel , Cipriano Maria Augusta , Vizcaíno J. R. , Santos-Silva Ermelinda , Gomes-Martins Esmeralda 
Published: October 2022

BackgroundThe worldwide increase in pediatric overweight and obesity, in parallel with the global increase in the consumption of sucrose and fructose, is associated with non-alcoholic fatty liver disease (NAFLD). Elevated branched-chain amino acids (BCAAs) are a metabolic feature related to obesity and an early risk factor for insulin resistance and NAFLD. However, few studies have assessed metabolic risk factors and nutritional status in maple syrup urine disease (MSUD) patients under restricted BCAA and high carbohydrate diets.Methods and resultsHerein, we present a pilot report of a 17-year-old boy with classic MSUD with poor diet compliance and high fructose consumption, mainly during early adolescence. At that time, he was overweight and developed features of metabolic syndrome, including persistently elevated liver enzymes and hepatic steatosis. He underwent liver transplantation at the age of 13 years to prevent the risk of progressive cognitive impairment. Two months later, NAFLD relapsed in the graft, despite a better BCAA balance and weight loss. Nevertheless, 6 months after dietary restriction of fructose consumption, NAFLD had sustainably improved.ConclusionChildhood overweight and fructose overconsumption are wellestablished driving forces in the development of pediatric NAFLD. However, their role in the early onset and progression of NAFLD in the allograft remains to be established. Furthermore, it is not known whether the dysmetabolic state associated with elevated BCAAs may be contributory. Further studies are required with a cohort of MSUD subjects to validate our findings and to ascertain the possible interaction between a BCAA imbalance and dietary intake in the development of NAFLD.
Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study
Authors: Xu Xuefeng , Liu Xiaohui , Zheng Wenjie , Xiao Jihong , Li Xiaozhong , Wu Ling , Zou Lixia , Ouyang Qian , Shangguan Yaoyao , Lin Kezhao , Dai Xiaomei , Chen Yuanling , Xu Yiping , Wu Jianqiang , Lu Meiping 
Published: October 2022

BackgroundEtanercept biosimilar recombinant human TNF-α receptor II: IgG Fc fusion protein (rhTNFR-Fc) has showed its efficacy and safety in Chinese patients with rheumatoid arthritis. However, data on rhTNFR-Fc's application in juvenile idiopathic arthritis (JIA) is limited.MethodsA prospective, observational, multicenter study was performed at 6 institutes in China from July 2020 to December 2021. In a 24-week follow-up, patients with JIA including polyarticular JIA and enthesitis related arthritis received rhTNFR-Fc plus methotrexate (MTX) treatment. The primary outcome parameters were improvements of cJADAS-10 (clinical Juvenile Arthritis Disease Activity Score), and the secondary outcome parameter was an inactive disease.Results60 patients completed at least 12-week follow-up, and 57 completed 24-week follow-up. They had high C reactive protein values (11.6 mg/L) and cJADAS-10 (14.6) at baseline. Thirteen patients had morning stiffness. 33 patients showed synovial thickening, and 34 showed bone marrow edemas on MRI. Ultrasonography demonstrated significant joint effusions in 43 patients. The cJADAS-10 sharply decreased from 14.66 at the baseline to 2.4 at 24 weeks of rhTNFR-Fc therapy, respectively (P &lt; 0.01). About half of patients achieved inactive disease at 24 weeks of therapy. Compared with the baseline, the number of patients with morning stiffness, joint effusions, bone marrow edema and synovial thickening on MRI significantly decreased at 24 weeks. Adverse events were consistent with known side effects of biologic agents.ConclusionsThe present study indicated that the combination of rhTNFR-Fc and MTX significantly improve symptoms and disease activity of children with JIA. This study suggests etanercept biosimilar rhTNFR-Fc as an effective and safe therapy for children with JIA.