bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced peroxisome proliferator-activated receptor-α and bile acid nuclear receptor NR1H4/FXR may affect the hepatic immune microenvironment of biliary atresia
Authors: Ma Yingxuan , Lu Li , Tan Kezhe , Li Zhi , Guo Ting , Wu Yibo , Wu Wei , Zheng Lulu , Fan Feilong , Mo Jiayu , Gong Zhenhua 
Published: August 2022

BackgroundBiliary atresia (BA) is a childhood liver disease characterized by fibrous obstruction and obstruction of the extrahepatic biliary system and is one of the most common and serious biliary disorders in infants. Significant inflammation and fibrosis of the liver and biliary tract are the most prominent features, regardless of the initial damage to the BA. Abnormalities in innate or adaptive immunity have been found in human patients and mouse models of BA. We previously reported that children with BA had abnormal lipid metabolism, including free serum carnitine.ObjectiveTo study gene and protein expression levels of the hepatic peroxisome proliferator-activated receptor-α (PPARα) signaling pathway and farnesoid X receptor (FXR) in BA and BA fibrosis, and assess their clinical values.MethodsLow expression of PPARα and NR1H4 (FXR) in BA were validated in the Gene Expression Omnibus database. Functional differences were determined by gene set enrichment analysis based on of PPARα and NR1H4 expression. BA patients from GSE46960 were divided into two clusters by using consensus clustering according to PPARα, NR1H4, and SMAD3 expression levels, and immunoinfiltration analysis was performed. Finally, 58 cases treated in our hospital were used for experimental verification. (IHC: 10 Biliary atresia, 10 choledochal cysts; PCR: 10 Biliary atresia, 14 choledochal cysts; WB: 10 Biliary atresia, 4 choledochal cysts).ResultsBioinformatics analysis showed that the expression of PPARα, CYP7A1 and NR1H4 (FXR) in the biliary atresia group was significantly lower than in the control group. More BA-specific pathways, including TGFβ signaling pathway, P53 signaling pathway, PI3K-AKT-mTOR signaling pathway, etc., are enriched in BA patients with low PPARα and NR1H4 expression. In addition, low NR1H4 expression is abundant in inflammatory responses, IL6/STAT3 signaling pathways, early estrogen responses, IL2 STAT5 signaling pathways, and TGFβ signaling pathways. The TGFβ signaling pathway was significant in both groups. According to the expression of PPARα, NR1H4 and SMAD3, a key node in TGFβ pathway, BA patients were divided into two clusters using consensus clustering. In cluster 2, SMAD3 expression was high, and PPARα and NR1H4 expression were low. In contrast to cluster 1, immune cell infiltration was higher in cluster 2, which was confirmed by immunohistochemistry. The mRNA and protein levels of PPARα and NR1H4 in BA patients were lower than in the control group by immunohistochemistry, Western blot analysis and real-time PCR.ConclusionsThe downregulation of PPARα and NR1H4 (FXR) signaling pathway may be closely related to biliary atresia.
Preoperative prediction of glypican-3 positive expression in solitary hepatocellular carcinoma on gadoxetate-disodium enhanced magnetic resonance imaging
Authors: Chen Yidi , Qin Yun , Wu Yuanan , Wei Hong , Wei Yi , Zhang Zhen , Duan Ting , Jiang Hanyu , Song Bin 
Published: August 2022

PurposeAs a coreceptor in Wnt and HGF signaling, glypican-3 (GPC-3) promotes the progression of tumor and is associated with a poor prognosis in hepatocellular carcinoma (HCC). GPC-3 has evolved as a target molecule in various immunotherapies, including chimeric antigen receptor T cell. However, its evaluation still relies on invasive histopathologic examination. Therefore, we aimed to develop an easy-to-use and noninvasive risk score integrating preoperative gadoxetic acid–enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators to predict positive GPC-3 expression in HCC.Methods and materialsConsecutive patients with surgically-confirmed solitary HCC who underwent preoperative EOB-MRI between January 2016 and November 2021 were retrospectively included. EOB-MRI features were independently evaluated by two masked abdominal radiologists and the expression of GPC-3 was determined by two liver pathologists. On the training dataset, a predictive scoring system for GPC-3 was developed against pathology via logistical regression analysis. Model performances were characterized by computing areas under the receiver operating characteristic curve (AUCs).ResultsA total of 278 patients (training set, n=156; internal validation set, n=39; external validation set, n=83) with solitary HCC (208 [75%] with positive GPC-3 expression) were included. Serum alpha-fetoprotein &gt;10 ng/ml (AFP, odds ratio [OR]=2.3, four points) and five EOB-MR imaging features, including tumor size &gt;3.0cm (OR=0.5, -3 points), nonperipheral “washout” (OR=3.0, five points), infiltrative appearance (OR=9.3, 10 points), marked diffusion restriction (OR=3.3, five points), and iron sparing in solid mass (OR=0.2, -7 points) were significantly associated with positive GPC-3 expression. The optimal threshold of scoring system for predicting GPC-3 positive expression was 5.5 points, with AUC 0.726 and 0.681 on the internal and external validation sets, respectively.ConclusionBased on serum AFP and five EOB-MRI features, we developed an easy-to-use and noninvasive risk score which could accurately predict positive GPC-3 HCC, which may help identify potential responders for GPC-3-targeted immunotherapy.
Cost-effectiveness of using protons for breast irradiation aiming at minimizing cardiotoxicity: A risk-stratification analysis
Authors: Li Guo , Xia Yun-Fei , Huang Yi-Xiang , Okat Deniz , Qiu Bo , Doyen Jerome , Bondiau Pierre-Yves , Benezery Karen , Gao Jin , Qian Chao-Nan 
Published: August 2022

BackgroundIncidental exposure of the heart to ionizing irradiation is associated with an increased risk of ischemic heart disease and subsequent fatality in patients with breast cancer after radiotherapy. Proton beam therapy can limit the heart dose in breast irradiation to a negligible level. However, compared with conventional photon modality, proton breast irradiation is more expensive. In this study, we performed cost-effectiveness analyses to identify the type of patients who would be more suitable for protons.MethodsA Markov decision model was designed to evaluate the cost-effectiveness of protons vs. photons in reducing the risk of irradiation-related ischemic heart disease. A baseline evaluation was performed on a 50-year-old woman patient without the preexisting cardiac risk factor. Furthermore, risk-stratification analyses for photon mean heart dose and preexisting cardiac risk were conducted on 40-, 50-, and 60-year-old women patients under different proton cost and willingness-to-pay (WTP) settings.ResultsUsing the baseline settings, the incremental effectiveness (protons vs. photons) increased from 0.043 quality-adjusted life-year (QALY) to 0.964 QALY when preexisting cardiac risk increased to 10 times its baseline level. At a proton cost of 50,000 US dollars ($), protons could be cost-effective for ≤ 60-year-old patients with diabetes and ≤50-year-old patients with grade II–III hypertension at the WTP of China ($37,653/QALY); for ≤ 60-year-old patients with diabetes and ≤ 50-year-old patients with grade II–III hypertension or ≥ 2 major cardiac risk factors at a WTP of $50,000/QALY; and for ≤ 60-year-old patients with diabetes, grade II–III hypertension or ≥ 2 major cardiac risk factors and ≤ 50-year-old patients with total cholesterol ≥ 240 mg/dL at a WTP of $100,000/QALY.ConclusionPatients' preexisting cardiac risk status was a key factor affecting the cardiac benefits gained from protons and should therefore be a major consideration for the clinical decision of using protons; cost-effective scenarios of protons exist in those patients with high risk of developing cardiac diseases.
The correlation between neutrophil-to-lymphocyte ratio, carcinoembryonic antigen, and carbohydrate antigen 153 levels with chemotherapy-related cognitive impairment in early-stage breast cancer patients
Authors: Yu Sheng , Zhao Jingjing , Wang Menglian , Cheng Guo , Li Wen , Tang Lingxue , Yao Senbang , Pang Lulian , Yin Xiangxiang , Jing Yanyan , Cheng Huaidong 
Published: August 2022

BackgroundThe changes in inflammation and tumor biomarkers are associated with the anti-tumor immunological processes. Early detection and intervention are of great significance to the clinical management of cancer-related diseases. Peripheral blood biomarkers [e.g., neutrophil-to-lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), and carbohydrate antigen 153 (CA153)] are obtained in real-timely, conveniently, and less invasively, and proved to availably predicted the disease states and prognosis of various cancers, including breast cancer (BC). Inflammation and poor disease management promote cognitive impairment. Chemotherapy-related cognitive impairment (CRCI) hazard long-term survival and quality of life (QOL) of BC patients, but its correlation with NLR, CEA, and CA153 is not clear.PurposeThis study aimed to investigate changes in NLR, CEA, and CA153 levels before and after chemotherapy and their correlation with CRCI in patients with early-stage BC.Materials and methodsThe 187 patients with BC who were measured for NLR, CEA, and CA153 values within the first 24 hours of admission, were assigned into two groups: the before/after chemotherapy group (BCG/ACG). The ACG was assigned into two subgroups based on the cognitive assessment results: the cognitive normal/impaired group (CNG/CIG). Patients’ self-perceived cognitive impairments were evaluated using a mini-mental state examination (MMSE), prospective and retrospective memory (PM and RM) questionnaire (PRMQ), and functional assessment of cancer therapy-cognitive function version 3 (FACT-Cog, version 3, including CogPCI, CogOth, CogPCA, and CogQOL). Their QOL was also evaluated.ResultsThe NLR and CA153 levels were elevated after chemotherapy (BCG vs ACG: Z = −1.996 and −1.615, P = 0.046 and 0.106, respectively), and significantly elevated in patients with CRCI (BCG vs CIG: Z = −2.444 and -2.293, P = 0.015 and 0.022; respectively). However, there was not reach significant difference in CEA levels between the four groups. In addition, there was a weak to moderate correlation between peripheral blood biomarkers (NLR, CEA, and CA153) levels and CRCI (r = −0.404, −0.205, −0.322; respectively; P &lt; 0.001). Cognitive impairment scores (MMSE, PM, RM, and FACT-Cog) had a strong correlation with QOL in patients with early-stage BC (r = −0.786, 0.851, 0.849, and 0.938; respectively; P &lt; 0.001).ConclusionNLR and CA153 m be valuable diagnostic adjuncts of CRCI, and CRCI has a strong correlation with QOL in patients with early-stage BC.
LNG-IUS vs. medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis
Authors: Chen Sijing , Liu Jianhong , Peng Shiyi , Zheng Ying 
Published: August 2022

IntroductionTo compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with medical treatments for women with heavy menstrual bleeding.Materials and methodsWe searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant randomized controlled trials (RCTs) in November 2021. All meta-analyses were performed using the random-effects model. PROSPERO registration number: CRD42021295379.ResultsA total of trials (with 14 references) reporting on 1,677 women were included in this systematic review. The majority of the included RCTs were rated with low-to-unclear risk of bias in selection, detection, attrition, reporting, and other bias. All RCTs were rated as high risk in performance bias because blinding was difficult to ensure in the compared groups. Results of meta-analyses revealed that the number of clinical responders was greater in the LNG-IUS group than that in the medical treatments group at both 6-month (steroidal: five RCTs; n = 490; risk ratio [RR]: 1.72 [1.13, 2.62]; I2 = 92%; nonsteroidal: one RCT; n = 42; RR: 2.34 [1.31, 4.19]) and 12-month (steroidal: three RCTs; n = 261; RR: 1.31 [1.01, 1.71]; I2 = 74%) endpoints, with no clear differences on number of dropouts, and the incidence of adverse events.ConclusionEvidence indicates that LNG-IUS is superior to the medical treatments in short-term and medium-term clinical responses, blood loss control, compliance, and satisfaction. Meanwhile, frequency of adverse events related to LNG-IUS is acceptable.Systematic review registrationPROSPERO, identifier CRD42021259335, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021295379.
Relationships Among Temporal Fine Structure Sensitivity, Transient Storage Capacity, and Ultra-High Frequency Hearing Thresholds in Tinnitus Patients and Normal Adults of Different Ages
Authors: Ding Yu , Liang Yibo , Cao Chunmei , Zhang Yueqi , Hu Ming 
Published: August 2022

BackgroundElderlies and tinnitus patients often find it challenging to process acoustic signals in noisy environments. The sensitivity to temporal fine structure (TFS), the transient storage capacity for TFS, and the ultra-high frequency (UHF) thresholds are all associated with aging-related damage, evidenced by speech-in-noise perception deficits. In the present study, we aimed to investigate the relationships among TFS sensitivity, transient storage capacity, and UHF thresholds in tinnitus patients and normal adults of different ages.MethodsIn the present study, 38 tinnitus patients (age ranging from 21 to 65) and 23 non-tinnitus adults (age ranging from 22 to 56) were enrolled, and some of their auditory indicators were examined, including the TFS-adaptive frequency (TFS-AF), break in interaural correlation (BIAC) delay threshold, and UHF thresholds.ResultsWe found no significant difference in TFS-AF thresholds and BIAC delay thresholds between the tinnitus group and normal group, while their relationships with age were more evident in the tinnitus group. Moreover, these two tests were only significantly correlated in the tinnitus group. UHF thresholds were significantly correlated with TFS-AF thresholds only in the tinnitus group, suggesting that the UHF hearing was positively associated with the TFS sensitivity.ConclusionThese findings indicated that the influencing factors, such as tinnitus and UHF thresholds, should be fully considered when examining age-related hearing decline, because the combination of tinnitus and poor UHF hearing might play a role in affecting hearing ability, such as TFS sensitivity.
Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients
Authors: Kular Lara , Klose Dennis , Urdánoz-Casado Amaya , Ewing Ewoud , Planell Nuria , Gomez-Cabrero David , Needhamsen Maria , Jagodic Maja 
Published: August 2022

BackgroundMultiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks.MethodsWe applied Horvath’s multi-tissue and Shireby’s brain-specific Cortical clock on bulk brain tissue (n = 46), sorted neuronal (n = 54), and glial nuclei (n = 66) from post-mortem brain tissue of progressive MS patients and controls.ResultsWe found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls (P = 0.0024) using the Cortical clock, which held after adjustment for covariates (Padj = 0.0263). The 4.8-year age acceleration found in MS neurons (P = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls.ConclusionWhile the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.
The impact of age and electrode position on amplitude-integrated EEGs in children from 1 month to 17 years of age
Authors: Greve Sandra , Löffelhardt Verena Tamara , Della Marina Adela , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Bruns Nora 
Published: August 2022

AimAmplitude-integrated electroencephalography (aEEG) is used to monitor electrocortical activity in critically ill children but age-specific reference values are lacking. We aimed to assess the impact of age and electrode position on aEEG amplitudes and derive normal values for pediatric aEEGs from neurologically healthy children.MethodsNormal EEGs from awake children aged 1 month to 17 years (213 female, 237 male) without neurological disease or neuroactive medication were retrospectively converted into aEEGs. Two observers manually measured the upper and lower amplitude borders of the C3 – P3, C4 – P4, C3 – C4, P3 – P4, and Fp1 – Fp2 channels of the 10–20 system. Percentiles (10th, 25th, 50th, 75th, 90th) were calculated for each age group (&lt;1 year, 1 year, 2–5 years, 6–9 years, 10–13 years, 14–17 years).ResultsAmplitude heights and curves differed between channels without sex-specific differences. During the first 2 years of life, upper and lower amplitudes of all but the Fp1–Fp2 channel increased and then declined until 17 years. The decline of the upper Fp1–Fp2 amplitude began at 4 years, while the lower amplitude declined from the 1st year of life.ConclusionsaEEG interpretation must account for age and electrode positions but not for sex in infants and children.
The Body Adiposity Index is not applicable to the Brazilian adult population
Authors: Ribeiro da Costa José Ronaldo , Costa Roberto Fernandes da , Goncalves Ciro Alexandre Mercês , de Oliveira Borges Michelle Vasconcelos , Almeida-Neto Paulo Francisco De , De Assis Gilmara Gomes , Cabral Breno Guilherme De Araujo Tinoco , Dantas Paulo Moreira Silva 
Published: August 2022

BackgroundObesity is a serious disease that burdens public health systems around the world. It is a risk factor for the development of several non-communicable chronic diseases that are related to the amount and distribution of body fat. Body composition assessment using simple and low-cost techniques can help in the early detection of excess fat, allowing for the prevention and treatment of both obesity and associated diseases. Thus, identifying and proposing valid anthropometric indices for this purpose can be a great ally of health programs.ObjectiveTo verify the validity of the Body Adiposity Index (BAI) in relation to Dual Energy X-Ray Absorptiometry (DXA) for estimating body fat percentage in Brazilian adults, as well as to propose a new mathematical model to estimate the fat-free mass of this population.MethodsIn a cross-sectional study, 424 subjects (of which 220 were women), aged between 20 and 59 years, were evaluated by BAI and DXA, then randomly divided into two groups stratified by sex: the development group (n = 283) and the cross-validation group (n = 141). Statistical analyses to test the validity of BAI as a predictor of fat mass, in addition to proposing a new mathematical model for estimating fat-free mass, using DXA as a reference method. The analysis included paired t-test, stepwise multiple regression, coefficient of concordance correlation, and Bland-Altman plots.ResultsThe BAI validity analysis showed a low correlation coefficient of agreement [CCC = 0.626; ρ (precision) = 0.795; Cb(accuracy) = 0.787]; in addition, the mean difference in the Bland-Altman plot was different from zero in the cross-validation group (p &lt; 0.01) and limits of agreement (LOA) ranged between−8.0 and 14.4 kg, indicating a poor agreement between the BAI and the reference method. The new mathematical model for estimating FFM showed a high correlation coefficient of agreement (CCC = 0.952; ρ = 0.953; Cb = 0.999), in addition to acceptable LOA in the Bland-Altman plot (-6.7 and 6.7).ConclusionIn the studied sample, the BAI showed low validity for estimating body fat, while the new proposed model was found to be a good option to assess the body composition of Brazilian adults.
Based on clinical Ki-67 expression and serum infiltrating lymphocytes related nomogram for predicting the diagnosis of glioma-grading
Authors: Zhang Zhi , Gu Weiguo , Hu Mingbin , Zhang Guohua , Yu Feng , Xu Jinbiao , Deng Jianxiong , Xu Linlin , Mei Jinhong , Wang Chunliang , Qiu Feng 
Published: August 2022

BackgroundCompelling evidence indicates that elevated peripheral serum lymphocytes are associated with a favorable prognosis in various cancers. However, the association between serum lymphocytes and glioma is contradictory. In this study, a nomogram was established to predict the diagnosis of glioma-grading through Ki-67 expression and serum lymphocytes.MethodsWe performed a retrospective analysis of 239 patients diagnosed with LGG and 178 patients with HGG. Immunohistochemistry was used to determine the Ki-67 expression. Following multivariate logistic regression analysis, a nomogram was established and used to identify the most related factors associated with HGG. The consistency index (C-index), decision curve analysis (DCA), and a calibration curve were used to validate the model.ResultsThe number of LGG patients with more IDH1/2 mutations and 1p19q co-deletion was greater than that of HGG patients. The multivariate logistic analysis identified Ki-67 expression, serum lymphocyte count, and serum albumin (ALU) as independent risk factors associated with HGG, and these factors were included in a nomogram in the training cohort. In the validation cohort, the nomogram demonstrated good calibration and high consistency (C-index = 0.794). The Spearman correlation analysis revealed a significant association between HGG and serum lymphocyte count (r = −0.238, P &lt;0.001), ALU (r = −0.232, P &lt;0.001), and Ki-67 expression (r = 0.457, P &lt;0.001). Furthermore, the Ki-67 expression was negatively correlated with the serum lymphocyte count (r = −0.244, P &lt;0.05). LGG patients had lower Ki-67 expression and higher serum lymphocytes compared with HGG patients, and a combination of these two variables was significantly higher in HGG patients.ConclusionThe constructed nomogram is capable of predicting the diagnosis of glioma-grade. A decrease in the level of serum lymphocyte count and increased Ki-67 expression in HGG patients indicate that their immunological function is diminished and the tumor is more aggressive.