bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study
Authors: Vogel Frederick , Braun Leah , Rubinstein German , Zopp Stephanie , Oßwald Andrea , Schilbach Katharina , Schmidmaier Ralf , Bidlingmaier Martin , Reincke Martin 
Published: October 2021

ContextGlucocorticoid excess exhibits multiple detrimental effects by its catabolic properties. Metformin was recently suggested to protect from adverse metabolic side-effects of glucocorticoid treatment. Whether metformin is beneficial in patients with endogenous glucocorticoid excess has not been clarified.ObjectiveTo evaluate the phenotype in patients with endogenous Cushing’s syndrome (CS) treated with metformin at the time of diagnosis.Patients and MethodsAs part of the German Cushing’s Registry we selected from our prospective cohort of 96 patients all 10 patients who had been on pre-existing metformin treatment at time of diagnosis (CS-MET). These 10 patients were matched for age, sex and BMI with 16 patients without metformin treatment (CS-NOMET). All patients had florid CS at time of diagnosis. We analyzed body composition, metabolic parameters, bone mineral density and bone remodeling markers, muscle function and quality of life.ResultsAs expected, diabetes was more prevalent in the CS-MET group, and HbA1c was higher. In terms of comorbidities and the degree of hypercortisolism, the two groups were comparable. We did not observe differences in terms of muscle function or body composition. In contrast, bone mineral density in metformin-treated patients was superior to the CS-NOMET group at time of diagnosis (median T-Score -0.8 versus -1.4, p = 0.030). CS-MET patients showed decreased β-CTX levels at baseline (p = 0.041), suggesting reduced bone resorption under metformin treatment during glucocorticoid excess.ConclusionThis retrospective cohort study supports potential protective effects of metformin in patients with endogenous glucocorticoid excess, in particular on bone metabolism.
Baseline Quantitative Hepatitis B Core Antibody Titer Is a Predictor for Hepatitis B Virus Infection Recurrence After Orthotopic Liver Transplantation
Authors: Lou Bin , Ma Guanghua , LV Feifei , Yuan Quan , Xu Fanjie , Dong Yuejiao , Lin Sha , Tan Yajun , Zhang Jie , Chen Yu 
Published: October 2021

ObjectiveHepatitis B virus (HBV) reinfection is a serious complication that arise in patients who undergo hepatitis B virus related liver transplantation. We aimed to use biomarkers to evaluate the HBV reinfection in patients after orthotopic liver transplantation.MethodsSeventy-nine patients who underwent liver transplantation between 2009 and 2015 were enrolled, and levels of biomarkers were analyzed at different time points. Cox regression and receiver operating characteristic (ROC) curves of different markers at baseline were used to analyze sustained hepatitis B surface antigen (HBsAg) loss. The Kaplan-Meier method was used to compare the levels of the biomarkers.ResultsAmong the 79 patients, 42 sustained HBsAg loss with a median time of 65.2 months (12.0-114.5, IQR 19.5) after liver transplantation and 37 patients exhibited HBsAg recurrence with a median time of 8.8 (0.47-59.53, IQR 19.47) months. In the ROC curve analysis, at baseline, 4.25 log10 IU/mL qHBcAb and 2.82 log10 IU/mL qHBsAg showed the maximum Youden’s index values with area under the curves (AUCs) of 0.685and 0.651, respectively. The Kaplan-Meier method indicated that qHBsAg and quantitative antibody against hepatitis B core antigen (qHBcAb) levels in the two groups were significantly different (p = 0.031 and 0.006, respectively). Furthermore, the Cox regression model confirmed the predictive ability of qHBcAb at baseline (AUC = 0.685).ConclusionLower pretransplantation qHBcAb is associated with HBV infection. The baseline concentration of qHBcAb is a promising predictor for the recurrence of HBV in patients undergoing liver transplantation and can be used to guide antiviral treatment for HBV infection.
Clinical Characteristics of Pediatric Coats' Disease With Retinal Cyst Using Wide-Angle Fluorescein Angiography
Authors: Liu Jing-Hua , Deng Guangda , Ma Jing , Li Liang , Fang Yuxin , Li Songfeng , Lu Hai 
Published: October 2021

Purpose: To assess the demographic and treatment features of pediatric patients of Coats' disease with retinal cyst using wide-angle FA.Design: A retrospective, hospital based, cross-sectional study.Participants: Pediatric patients of Coats' disease underwent wide-angle FA.Methods: A retrospective review of pediatric patients of Coats' disease who underwent wide-angle FA at a single center from January 2015 to July 2020. Demographic and treatment features were compared between patients with or without retinal cyst.Main Outcome Measures: Demographic and treatment outcomes.Results: There were 123 pediatric Coats' patients in our study, and 18.70% (23/123) of the patients developed complications with retinal cyst, 73.9% (17/23) of the retinal cysts were located in the inferior-temporal quadrant and 82.6% (19/23) of the retinal cysts were located in the peripheral retina anterior to the vortex veins. Compared with patients without retinal cyst, patients with retinal cyst had more clock-hours of telangiectasia on FA (7.32 vs. 5.41, p = 0.031), and may need more total treatments (7.47 vs. 3.53, p = 0.023) including laser photocoagulation (4.08 vs. 2.31, p = 0.019) or intravitreal anti-VEGF (3.13 vs. 2.23, p = 0.039), and also required a longer time for telangiectasia resolution (22.33 vs. 18.53 months, p = 0.043).Conclusion: Pediatric patients with Coats' disease complicated by retinal cyst presented with more clock-hours of telangiectasia on FA and needed more total treatments and longer time for telangiectasia resolution.
Lipidomics Analysis of the Tears in the Patients Receiving LASIK, FS-LASIK, or SBK Surgery
Authors: Gao Yan , Qi Yuanyuan , Huang Yue , Li Xiaorong , Zhou Lei , Zhao Shaozhen 
Published: October 2021

Purpose: Tear film lipid layer (TFLL) plays a vital role in maintaining the tear film stability and, thus, the lipid composition of the tears could greatly affect the physiological function and biophysical integrity of the tear film. The objective of this study is to assess the tear lipid composition of the patients receiving laser-assisted in situ keratomileusis (LASIK), femtosecond LASIK (FS-LASIK), or sub-Bowman's keratomileusis (SBK) surgery preoperatively and postoperatively.Methods: Tear samples were collected from the left eye of the patient who receiving LASIK (n = 10), FS-LASIK (n = 10), or SBK (n = 10) surgery in week 0, week 1, week 4, and week 52. A rapid direct injection shotgun lipidomics workflow, MS/MSALL (&lt;2 min/sample), was applied to examine the tear lipidome.Results: In week 52, the SBK group demonstrated a similar lipidome profile compared to week 0, while the FS-LASIK and LASIK groups shifted away from week 0. Two lipids, ganglioside (GD3) 27:4 and triacylglycerol (TAG) 59:3, were found to be associated with the lipidome changes preoperatively and postoperatively. No statistical significance was found in the overall lipid classes from the FS-LASIK group. The LASIK group showed significant alteration in the phospholipid and sphingolipid over time, while the SBK group demonstrated a significant difference in the (O-acyl)-ω-hydroxy fatty acid (OAHFA) and phospholipid.Conclusion: LASIK showed the greatest impact on the tear lipidome changes over time, while SBK demonstrated minimal impact among the three types of refractive surgeries after 1 year.
Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis
Authors: An Yang , Xu Shixue , Liu Yiting , Xu Xiangbo , Philips Cyriac Abby , Chen Jiang , Méndez-Sánchez Nahum , Guo Xiaozhong , Qi Xingshun 
Published: October 2021

Background: Galectins, a family of β-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear.Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model.Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61–2.34, p &lt; 0.001; galectin-3: HR = 3.29, 95% CI = 1.62–6.68, p &lt; 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18–2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58–5.60, p = 0.001); but, high expression of galectin-4 and −9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36–0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44–0.71, p &lt; 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19–0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37–0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79–4.32, p &lt; 0.001), liver failure (MD = 0.44, 95% CI = 0.23–0.66, p &lt; 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15–2.51, p &lt; 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91–27.00, p &lt; 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57–4.91, p &lt; 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61–9.99, p &lt; 0.001).Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.
Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein
Authors: Wang Yingchen , Zhang Zhe , Shang Lei , Gao Hong , Du Xiqiao , Li Falong , Gao Ya , Qi Guiyun , Guo Weiyuan , Qu Zhangyi , Dong Tuo 
Published: October 2021

Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations.Methods: The sequences of 74 adenovirus-type strains were used to predict the ancestral sequence of human adenovirus hexon protein using FastML and MEGA software. The three-dimensional structure model was built using homology modeling methods. The immunological features of ancestral loop 1 and loop 2 regions of sequences were tested using protein segments expressed in a prokaryotic expression system and polypeptides synthesized with human serum samples.Results: The tower region of the hexon protein had the highest sequence variability, while the neck and base regions remained constant among different types. The modern strains successfully predicted the common ancestral sequence of the human adenovirus hexon. The positive sera against neutralizing epitopes on the common ancestor of adenoviral hexon were relatively rare among healthy adults.Conclusion: The existing strains inferred the common ancestor of human adenoviruses, with epitopes never observed in the current human strains. The predicted common ancestor hexon is a good prospect in the improvement of adenovirus vectors.
Clinical Associations of Preoperative and Postoperative Serum CEA and Lung Cancer Outcome
Authors: Jiao Zonglin , Cao Shoubo , Li Jianhua , Hu Nan , Gong Yinghui , Wang Linduo , Jin Shi 
Published: October 2021

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis.Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression.Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p &lt; 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p &lt; 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p &lt; 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5–2.7, p &lt; 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9–1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4–2.7, p &lt; 0.001).Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.
Cerebellar Intermittent Theta-Burst Stimulation Reduces Upper Limb Spasticity After Subacute Stroke: A Randomized Controlled Trial
Authors: Chen Yi , Wei Qing-Chuan , Zhang Ming-Zhi , Xie Yun-Juan , Liao Ling-Yi , Tan Hui-Xin , Guo Qi-Fan , Gao Qiang 
Published: October 2021

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients.Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (Hmax/Mmax ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention.Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in Hmax/Mmax ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group.Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).
Monitoring and Evaluation of Emotion Regulation by Aerobic Exercise and Motor Imagery Based on Functional Near-Infrared Spectroscopy
Authors: Ding Peng , Wang Fawang , Li Siyu , Zhang Wei , Li Hongquan , Chen Zhuangfei , Zhao Lei , Gong Anmin , Fu Yunfa 
Published: October 2021

Objective: We sought to effectively alleviate the emotion of individuals with anxiety and depression, and explore the effects of aerobic exercise on their emotion regulation. Functional near-infrared spectroscopy (fNIRS) brain imaging technology is used to monitor and evaluate the process of aerobic exercise and imagination that regulates emotion.Approach:Thirty participants were scored by the state-trait anxiety inventory (STAI) and profile of mood states (POMS), and fNIRS images were collected before, after, and during aerobic exercise and motor imagery. Then, the oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (HbT) concentrations and their average value were calculated, and the ratio of HbO concentration in the left and right frontal lobes was determined. Spearman's correlation coefficient was used to calculate the correlation between variations in the average scores of the two scales and in blood oxygen concentrations.Results: In comparison with motor imagery, STAI, and POMS scores decreased after 20 min of aerobic exercise. The prefrontal cortex had asymmetry and laterality (with the left side being dominant in emotion regulation). The increase in hemoglobin concentration recorded by fNIRS was negatively correlated with STAI and POMS scores. Aerobic exercise has a good effect on emotion regulation.Significance:The study showed that portable fNIRS could be effectively used for monitoring and evaluating emotion regulation by aerobic exercise. This study is expected to provide ideas for constructing fNIRS-based online real-time monitoring and evaluation of emotion regulation by aerobic exercise.
Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Executive Function and Its Neural Mechanism: An Event-Related Potential Study
Authors: Liu Sishi , Wang Xianglong , Ma Junqin , Wang Kangling , Wang Zhengtao , Li Jie , Chen Jiali , Zhan Hongrui , Wu Wen 
Published: October 2021

Objective: Executive function refers to the conscious control of thinking and behavior in psychological process. Executive dysfunction widely exists in a variety of neuropsychiatric diseases, and is closely related to the decline of daily living ability and function. This study intends to explore the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on executive function and its neural mechanism by using event-related potential (ERP), so as to provide basis for further study on the relationship between cerebral cortex and executive function.Methods: Task switching paradigm was used to study the cognitive flexibility in executive function. Thirty-one healthy subjects were randomly assigned to receive rTMS stimulations (1 Hz rTMS or sham rTMS) to the left dorsolateral prefrontal cortex (DLPFC) twice. The switching task and the electroencephalography EEG recordings were performed before (pre-rTMS/pre-sham rTMS) and immediately after the end of the rTMS application (post-rTMS/post-sham rTMS).Results: The analysis of RTs showed that the main effects of switching and time were statistically significant. Further analysis revealed that the RT of rTMS stimulation was longer than sham rTMS at post-stimulation. ERP analysis showed that there was a significant switching effect in frontal and central scalp location, and the P2 amplitude in switch trials was greater than that in non-switch trials. At post-stimulation, the N2 amplitude of rTMS is more negative than that of sham rTMS at non-switch trials, whereas no such difference was found at switch trials. The P3 amplitude and LPC amplitude are significantly reduced by rTMS at post-stimulation.Conclusion: Low-frequency rTMS of the left DLPFC can cause decline of cognitive flexibility in executive function, resulting in the change of N2 amplitude and the decrease of P3 and LPC components during task switching, which is of positive significance for the evaluation and treatment of executive function.
Case Report: Disruption of Resting-State Networks and Cognitive Deficits After Whole Brain Irradiation for Singular Brain Metastasis
Authors: Kocher Martin , Jockwitz Christiane , Lerche Christoph , Sabel Michael , Lohmann Philipp , Stoffels Gabriele , Filss Christian , Mottaghy Felix M. , Ruge Maximilian I. , Fink Gereon R. , Shah Nadim J. , Galldiks Norbert , Caspers Svenja , Langen Karl-Josef 
Published: October 2021

Introduction: Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited. Therefore, we here report a rare case with a singular brain metastasis treated by resection and WBRT that survived for more than 10 years where we investigated the integrity of brain networks using resting-state functional MRI.Methods: A female patient with a left frontal non-small cell lung cancer (NSCLC) brain metastasis had resection and postoperative WBRT (30.0 in 3.0 Gy fractions) and stayed free from brain metastasis recurrence for a follow-up period of 11 years. Structural magnetic resonance imaging (MRI) and amino acid [O-(2-[18F]fluoroethyl)-L-tyrosine] positron emission tomography (FET PET) were repeatedly acquired. At the last follow up, neurocognitive functions and resting-state functional connectivity (RSFC) using resting-state fMRI were assessed. Within-network and inter-network connectivity of seven resting-state networks were computed from a connectivity matrix. All measures were compared to a matched group of 10 female healthy subjects.Results: At the 11-year follow-up, T2/FLAIR MR images of the patient showed extended regions of hyper-intensities covering mainly the white mater of the bilateral dorsal frontal and parietal lobes while sparing most of the temporal lobes. Compared to the healthy subjects, the patient performed significantly worse in all cognitive domains that included executive functions, attention and processing speed, while verbal working memory, verbal episodic memory, and visual working memory were left mostly unaffected. The connectivity matrix showed a heavily disturbed pattern with a widely distributed, scattered loss of RSFC. The within-network RSFC revealed a significant loss of connectivity within all seven networks where the dorsal attention and fronto-parietal control networks were affected most severely. The inter-network RSFC was significantly reduced for the visual, somato-motor, and dorsal and ventral attention networks.Conclusion: As demonstrated here in a patient with a metastatic NSCLC and long-term survival, WBRT may lead to extended white matter damage and cause severe disruption of the RSFC in multiple resting state networks. In consequence, executive functioning which is assumed to depend on the interaction of several networks may be severely impaired following WBRT apart from the well-recognized deficits in memory function.