bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal LncRNA LBX1-AS1 Derived From RBPJ Overexpressed-Macrophages Inhibits Oral Squamous Cell Carcinoma Progress via miR-182-5p/FOXO3
Authors: Ai Yilong , Wei Haigang , Wu Siyuan , Tang Zhe , Li Xia , Zou Chen 
Published: March 2021

ObjectivesMacrophage-derived exosomes (Mφ-Exos) are involved in tumor onset, progression, and metastasis, but their regulation in oral squamous cell carcinoma (OSCC) is not fully understood. RBPJ is implicated in macrophage activation and plasticity. In this study, we assessed the role of Mφ-Exos with RBPJ overexpression (RBPJ-OE Mφ-Exos) in OSCC.Materials and MethodsThe long non-coding RNA (lncRNA) profiles in RBPJ-OE Mφ-Exos and THP-1-like macrophages (WT Mφ)-Exos were evaluated using lncRNA microarray. Then the functions of Mφ-Exo-lncRNA in OSCC cells were assessed via CCK-8, EdU, and Transwell invasion assays. Besides, luciferase reporter assay, RNA immunoprecipitation, and Pearson’s correlation analysis were adopted to confirm interactions. Ultimately, a nude mouse model of xenografts was used to further analyze the function of Mφ-Exo-lncRNAs in vivo.ResultsIt was uncovered that lncRNA LBX1-AS1 was upregulated in RBPJ-OE Mφ-Exos relative to that in WT Mφ-Exos. RBPJ-OE Mφ-Exos and LBX1-AS1 overexpression inhibited OSCC cells to proliferate and invade. Meanwhile, LBX1-AS1 knockdown boosted the tumor to grow in vivo. The effects of RBPJ-OE Mφ-Exos on OSCC cells can be reversed by the LBX1-AS1 knockdown. Additionally, mechanistic investigations revealed that LBX1-AS1 acted as a competing endogenous RNA of miR-182-5p to regulate the expression of FOXO3.ConclusionExo-LBX1-AS1 secreted from RBPJ-OE Mφ inhibits tumor progression through the LBX1-AS1/miR-182-5p/FOXO3 pathway, and LBX1-AS1 is probably a diagnostic biomarker and potential target for OSCC therapy.
Presacral Tumor: Insights From a Decade’s Experience of This Rare and Diverse Disease
Authors: Li Zeyu , Lu Min 
Published: March 2021

BackgroundPresacral tumors are a group of rare and heterogeneous tumors that arise from the potential presacral space between the rectum and sacrum. The low occurrence and diverse origins make the diagnosis and treatment of these tumors a challenge. The aim of the study was to retrospectively review patient demographics and to identify advantages and disadvantages in the diagnosis and treatment of these tumors.MethodsRetrospectively collected and reviewed data from patients who received treatment of presacral tumors at the First Affiliated Hospital of China Medical University between August 2009 and June 2019.ResultsThe data from forty-four patients (33 females) with a median age of 50 years who were diagnosed with a presacral/retrorectal tumor were analyzed. The majority of tumors were congenital (61.4%) and benign tumors are more common (59.1%). The median age of patients with benign tumor was significantly higher than that of malignant tumor. The most common symptoms were sacrococcygeal/perianal pain (56.8%) and mass (36.4%), and 8 out of 9 patients having lower limb symptoms diagnosed with malignant tumor. The tumor detection rate of digital rectal examination was 75% and more than 90% of all patients underwent one or more radiology imaging exams for tumor diagnosis. Every patient had a biopsy result. The most common type of tumor was presacral cyst (40.9%) with overall tumor median size of 5.6 cm. Thirty-one (70.5%) patients underwent surgery, most often via the posterior route (83.9%). Posterior route surgery had significantly shorter operation time and tumors operated via posterior route were significantly smaller. The survival rate after surgery was 100%. The median course of disease was 6 months and median follow-up was 25 months.ConclusionsPresacral tumors have low occurrence and are more frequently observed in females in their 30s and 50s indicating a possible link between tumor occurrence and hormonal changes. Patients with lower limb symptoms were more likely to have a malignant presacral tumor. Posterior route was the most commonly utilized surgical approach. Supplementary iodine tincture treatment of cysts ruptured in operation could potentially be helpful in reducing the chance of recurrence.
Activation of the Cholinergic Anti-inflammatory Pathway Attenuated Angiotension II-Dependent Hypertension and Renal Injury
Authors: Wu Shu-jie , Shi Zhe-wei , Wang Xue , Ren Fang-fang , Xie Zuo-yi , Lei Li , Chen Peng 
Published: March 2021

Background: Angiotensin II (AngII) induces renal fibrosis, characterized by fibroblast proliferation, inflammatory cell infiltration and excessive extracellular matrix deposition, all of which was relevant closely to hypertension. The vagus nerve-related cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses. The aim of present study was to determine the effect of CAP on renal inflammation and fibrosis.Methods and Results: AngII-induced hypertension was induced in vivo by 14-days low-dose AngII infusion from osmotic minipumps. We used GTS-21 dihydrochloride, a selective nicotinic acetylcholine receptor agonist. Daily intraperitoneal GTS-21 injection and/or vagotomy started after hypertension was confirmed and continued for 4 weeks. The elevated blood pressure caused by AngII was significantly attenuated by GTS-21. Improved baroreflex sensitivity was observed after GTS-21 administration. Masson stain and immunoblotting revealed that deposition of excessive fibrosis and overexpression of inflammatory cytokines induced by AngII was reduced by GTS-21. To determine the role of autonomic control in CAP, unilateral vagotomy was performed. Vagotomy weakened the effect of CAP on AngII-induced hypertension. In vitro, GTS-21 suppressed NF-κB activation, attenuated AngII-induced epithelial-mesenchymal transition and reduced inflammation and fibrosis in NRK-52E cells; α-bungarotoxin (α-Bgt, an α7-nAChR selective antagonist) partly inhibited these effects.Conclusion: CAP protected against AngII-induced hypertension via improvement in autonomic control, suppression of NF-κB activation, and reduction of renal fibrosis and inflammatory response.
The Efficacy of Tocilizumab in the Treatment of Patients with Refractory Immune-Mediated Necrotizing Myopathies: An Open-Label Pilot Study
Authors: Li Sizhao , Li Wenli , Jiang Wei , He Linrong , Peng Qinglin , Wang Guochun , Lu Xin 
Published: March 2021

Objective: To evaluate the efficacy of tocilizumab (TCZ) in adult patients with refractory immune-mediated necrotizing myopathies (IMNMs) and investigate possible predictive biomarkers of the response to treatment with TCZ.Methods: Patients with refractory IMNM were enrolled in this open-label pilot observational study and received intravenous TCZ treatment. The clinical response was assessed after 6 months of TCZ treatment according to the 2016 American College of Rheumatology–European League Against Rheumatism (ACR–EULAR) response criteria for adult dermatomyositis and polymyositis. Muscle biopsies were performed to investigate muscle fiber regeneration by immunohistochemical staining of CD56. Serum levels of interleukin (IL)-6 were measured using a multiplex bead-based flow fluorescent immunoassay. The levels of muscle IL-6 mRNA were detected by real-time polymerase chain reaction.Results: A total of 11 patients with refractory IMNM were enrolled in the study, including 3 anti-3-hydroxy-3-methylglutaryl-CoA reductase- and 8 anti-signal recognition particle-positive patients. Seven (63.6%) of these patients achieved clinically significant responses according to the 2016 ACR–EULAR myositis response criteria. Responders had higher baseline serum IL-6 and muscle IL-6 mRNA levels and percentage of CD56-positive muscle fibers than non-responders. Baseline serum IL-6 levels and the percentage of CD56-positive muscle fibers were positively correlated with total improvement score after 6 months of TCZ treatment. Furthermore, muscle fiber necrosis and muscle fiber size variation decreased in repeated muscle biopsies in five responders.Conclusion: Patients with refractory IMNM may respond to TCZ. Baseline serum IL-6 and muscle IL-6 mRNA levels and the percentage of CD56-positive muscle fibers may predict the response to TCZ treatment in these patients.
Influence of the Circadian Timing System on Tacrolimus Pharmacokinetics and Pharmacodynamics After Kidney Transplantation
Authors: Fontova Pere , Colom Helena , Rigo-Bonnin Raül , van Merendonk Lisanne N. , Vidal-Alabró Anna , Montero Nuria , Melilli Edoardo , Meneghini Maria , Manonelles Anna , Cruzado Josep M. , Torras Juan , Grinyó Josep Maria , Bestard Oriol , Lloberas Nuria 
Published: March 2021

Introduction: Tacrolimus is the backbone immunosuppressant after solid organ transplantation. Tacrolimus has a narrow therapeutic window with large intra- and inter-patient pharmacokinetic variability leading to frequent over- and under-immunosuppression. While routine therapeutic drug monitoring (TDM) remains the standard of care, tacrolimus pharmacokinetic variability may be influenced by circadian rhythms. Our aim was to analyze tacrolimus pharmacokinetic/pharmacodynamic profiles on circadian rhythms comparing morning and night doses of a twice-daily tacrolimus formulation.Methods: This is a post-hoc analysis from a clinical trial to study the area under curve (AUC) and the area under effect (AUE) profiles of calcineurin inhibition after tacrolimus administration in twenty-five renal transplant patients. Over a period of 24 h, an intensive sampling (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 15, 20, and 24 h) was carried out. Whole blood and intracellular tacrolimus concentrations and calcineurin activity were measured by UHPLC-MS/MS.Results: Whole blood and intracellular AUC12–24 h and Cmax achieved after tacrolimus night dose was significantly lower than after morning dose administration (AUC0–12 h) (p &lt; 0.001 for both compartments). AUE0–12 h and AUE12–24 h were not statistically different after morning and night doses. Total tacrolimus daily exposure (AUC0–24 h), in whole blood and intracellular compartments, was over-estimated when assessed by doubling the morning AUC0–12 h data.Conclusion: The lower whole blood and intracellular tacrolimus concentrations after night dose might be influenced by a distinct circadian clock. This significantly lower tacrolimus exposure after night dose was not translated into a significant reduction of the pharmacodynamic effect. Our study may provide conceptual bases for better understanding the TDM of twice-daily tacrolimus formulation.
Application of a Physiologically Based Pharmacokinetic Model to Characterize Time-dependent Metabolism of Voriconazole in Children and Support Dose Optimization
Authors: Zhang Yahui , Zhao Sixuan , Wang Chuhui , Zhou Pengxiang , Zhai Suodi 
Published: March 2021

Background: Voriconazole is a potent antifungal drug with complex pharmacokinetics caused by time-dependent inhibition and polymorphisms of metabolizing enzymes. It also exhibits different pharmacokinetic characteristics between adults and children. An understanding of these alterations in pharmacokinetics is essential for pediatric dose optimization.Objective: To determine voriconazole plasma exposure in the pediatric population and further investigate optimal dosage regimens.Methods: An adult and pediatric physiologically based pharmacokinetic (PBPK) model of voriconazole, integrating auto-inhibition of cytochrome P450 3A4 (CYP3A4) and CYP2C19 gene polymorphisms, was developed. The model was evaluated with visual predictive checks and quantitative measures of the predicted/observed ratio of the area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax). The validated pediatric PBPK model was used in simulations to optimize pediatric dosage regimens. The probability of reaching a ratio of free drug (unbound drug concentration) AUC during a 24-h period to minimum inhibitory concentration greater than or equal to 25 (fAUC24h/MIC ≥ 25) was assessed as the pharmacokinetic/pharmacodynamic index.Results: The developed PBPK model well represented voriconazole's pharmacokinetic characteristics in adults; 78% of predicted/observed AUC ratios and 85% of Cmax ratios were within the 1.25-fold range. The model maintained satisfactory prediction performance for intravenous administration in pediatric populations after incorporating developmental changes in anatomy/physiology and metabolic enzymes, with all predicted AUC values within 2-fold and 73% of the predicted Cmax within 1.25-fold of the observed values. The simulation results of the PBPK model suggested that different dosage regimens should be administered to children according to their age, CYP2C19 genotype, and infectious fungal genera.Conclusion: The PBPK model integrating CYP3A4 auto-inhibition and CYP2C19 gene polymorphisms successfully predicted voriconazole pharmacokinetics during intravenous administration in children and could further be used to optimize dose strategies. The infectious fungal genera should be considered in clinical settings, and further research with large sample sizes is required to confirm the current findings.
A High Percentage of Patients Recovered From COVID-19 but Discharged With Abnormal Liver Function Tests
Authors: Gan Qinyi , Gong Beilei , Sun Manli , Cao Zhujun , Zheng Yuyan , Zhang Yajie , Wen Pengfei , Shen Yuanbing , Hong Lei , Hou Tingting , Jia Yuqin , Li Wei , Li Hecheng , Xie Qing 
Published: March 2021

BackgroundCoronavirus disease 2019 (COVID-19) pandemic has become the most severe global health issue. Abnormal liver functions are frequently reported in these patients. However, liver function abnormality was often overlooked during COVID-19 treatment, and data regarding liver functions after cure of COVID-19 is limited. This study aimed to reveal the changes of liver function tests (LFTs) during hospitalization, and its clinical significance in patients with COVID-19.MethodsIn this retrospective, bi-center study, a total of 158 hospitalized patients diagnosed with COVID-19 in China were included from January 22nd, 2020 to February 20th, 2020. Clinical features, laboratory parameters including LFTs, and treatment data were collected and analyzed. LFTs included alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin. Patients were considered with abnormal LFTs when any value of these tests was higher than upper limit of normal.ResultsOf 158 patients with COVID-19, 67 (42.41%) patients had abnormal LFTs on admission and another 50 (31.65%) patients developed abnormal LFTs during hospitalization. The incidence of LFTs abnormality in severe COVID-19 cases was significantly higher than non-severe cases. All LFTs in COVID-19 patients were correlated with oxygenation index. There was no statistical difference in treatment between the patients with or without liver test abnormalities. By the time of discharge, there were still 64 (40.50%) patients with abnormal LFTs. Logistic regression analysis identified younger age, hypertension and low lymphocyte counts as independent risk factors for persistent abnormal LFTs during hospitalization.ConclusionLiver function tests abnormality was common in COVID-19 patients and was more prevalent in severe cases than in non-severe cases. A substantial percentage of patients still had abnormal LFTs by the time of discharge.
Individual, Sociodemographic, and Environmental Factors Related to Physical Activity During the Spring 2020 COVID-19 Lockdown
Authors: Teran-Escobar Claudia , Forestier Cyril , Ginoux Clément , Isoard-Gautheur Sandrine , Sarrazin Philippe , Clavel Anna , Chalabaev Aïna 
Published: March 2021

Background: Research has shown important between-individual variations in physical activity (PA) during the COVID-19 lockdown.Objectives: The objectives of this is study are to examine the individual, sociodemographic, and environmental factors related to PA during the spring 2020 COVID-19 lockdown in France and to explore the mediating and moderating role of intention and self-efficacy toward PA in the relationships between sociodemographic/environmental variables and PA.Design: In this cross-sectional study, participants living in France (N = 386) completed an online survey between March 30 and April 10, 2020.Method: Minutes per week of moderate-to-vigorous PA during the lockdown; usual physical activity before the lockdown; and psychological (e.g., intention, self-efficacy, and autonomous and controlled motivation), sociodemographic (gender, age, and number of children), and environmental (habitat surface area and type of housing) factors were measured in the survey. Multiple linear regressions were used to investigate the role of these predictors on PA. Intention and self-efficacy were also examined as moderators and mediators of the association between sociodemographic/environmental factors and PA.Results: Usual physical activity before the COVID-19 lockdown, intention toward PA, habitat surface area, and controlled motivation significantly predicted PA during the lockdown. No mediating effects of intention or self-efficacy were found. Intention significantly moderated the association between gender and PA and the association between part-time work and PA.Conclusions: PA during the COVID-19 lockdown was mainly predicted by individual factors and notably usual PA. These results highlight the important role of habits in a highly changing context.
No Association Between Autonomic Functioning and Psychopathy and Aggression in Multi-Problem Young Adults
Authors: Zijlmans Josjan , Marhe Reshmi , van Duin Laura , Luijks Marie-Jolette A. , Bevaart Floor , Popma Arne 
Published: March 2021

BackgroundAberrant functioning of the autonomic nervous system (ANS) is an important factor in the occurrence of antisocial behavior. Baseline autonomic functioning and the responsivity of the ANS have been related to psychopathic traits and aggression. Here we investigated whether a naturalistic sample of male multi-problem young adults (age 18–27) present with similar autonomic deficits in relation to their psychopathy and aggression as previous studies observed in clinical samples.MethodsIn a sample of 112 multi-problem young adults, baseline autonomic functioning and autonomic responsivity to emotional stimuli were assessed through four physiological measures: heart rate, respiratory sinus arrhythmia, pre-ejection period, and skin conductance. 27 control participants were included primarily to assess whether the task worked appropriately. Participants watched a neutral 5 min video to assess baseline autonomic functioning and watched two sad clips to assess autonomic reactivity to sadness. We investigated the association between autonomic functioning and self-reported psychopathic traits and aggression within the multi-problem group.ResultsWe found no significant associations between autonomic functioning and psychopathy and aggression.ConclusionThese null-findings highlight the importance of research in naturalistic samples in addition to research in clinical and general populations samples and underscore the complexity of translating research findings into practical and clinical implications.
Naturalistic and Uncontrolled Pilot Study on the Efficacy of Vortioxetine in Binge Eating Disorder With Comorbid Depression
Authors: Segura-Garcia Cristina , Rania Marianna , Carbone Elvira Anna , de Filippis Renato , Aloi Matteo , Caroleo Mariarita , Grasso Gloria , Calabrò Giuseppina , Fazia Gilda , Staltari Filippo Antonio , Falvo Antonella , Pugliese Valentina , Gaetano Raffaele , Steardo Luca , De Fazio Pasquale 
Published: March 2021

Background:Binge eating disorder (BED) is clinically relevant by virtue of the global impairment, poor quality of life, and increased overall medical morbidity. The high comorbidity with psychiatric disorders, particularly depression, has received attention as a possible mediator of the poor outcome. Further, BED and depression share cognitive dysfunctions. This naturalistic and uncontrolled pilot study aimed at evaluating the efficacy of vortioxetine (VTX) on depressive symptoms in patients with BED, secondly the efficacy in improving a broad array of executive functions, and third to explore the effect on eating behavior and body weight.Methods:This pilot study involved 30 patients with BED and comorbid MDD, treated with VTX for 24 weeks. Assessments were run at baseline (t0), 4 (t1), 8 (t2), 12 (t3), and 24 (t4) weeks. Changes in depressive symptoms (HDRS and BDI), executive functions, eating behaviors (binge frequency and severity, night eating, food addiction), and body weight were estimated after treatment with VTX through GLM.Results:Significant improvements emerged after treatment with VTX in: depression (HDRSp&lt; 0.001; BDIp= 0.002) regardless the dose of VTX and first diagnosis (BED/MDD), working memory (RAVLT acquisitionp= 0.01, delay recallp&lt; 0.001, RCFT percentage of recallp= 0.01, and Attentional Matricesp= 0.05), binge days frequency (p&lt; 0.001), binge eating severity (BESp&lt; 0.001), night eating (p= 0.001), food addiction (YFAS 2.0p= 0.039), and body weight (p= 0.039). The improvement in depressive symptoms was associated with the concurrent improvement in night eating as assessed by the I-NEQ.Conclusions:VTX can be a valid therapeutic choice for patients with BED with comorbid depression in controlling the depressive symptoms, working memory, and eating behavior. Indeed, by acting on affective symptoms, neurocognitive functioning, and eating behaviors, it confirms the results already obtained with VTX in other disorders, expanding them to BED.
Voice Assessment in Patients With Obstructive Sleep Apnea Syndrome After Transoral Robotic Surgery
Authors: Huang Hsin-Hsin , Tsao Chien-Han , Wei James Cheng-Chung 
Published: March 2021

Objectives: Removal of part of the tongue base, in combination with uvulopharyngopalatoplasty via transoral robotic surgery (TORS), for treating obstructive sleep apnea syndrome (OSAS) results in enlargement of the oropharynx and hypopharynx and change in the size of the resonance chamber. These procedures may also alter the laryngeal-hyoid bone complex, which is linked to vocal fold tension. Thus, there is the potential for change in phonation and pitch after surgery.Study Design: Prospective, nonrandomized, institutional board-approved study.Methods: From January to August 2018, 15 patients with OSAS receiving TORS underwent voice and pitch sampling. The multi-dimensional voice program (MDVP) was applied to the evaluation of preoperative sound parameters. Highest pitch and lowest pitch were obtained with real-time pitch software, with pitch synchronized to electronic organ or tuner. Subjects also completed the Voice Handicap Index-10 scale (VHI-10), to assess their subjective perception and to detect factors affecting the VHI-10 score. The relevant parameters were analyzed again 3 months after the operation.Results: There was an increase in VHI-10 score 3 months after operation that did not reach statistical significance. There were also no significant differences in sound parameters. Increases in highest pitch (353.18 Hz shift to 387.99 Hz), highest semitone (F5# shift to F5#), lowest pitch (117.45 Hz shift to 131.42 Hz), and lowest semitone (C3 shift to C3) did not reach statistical significance. The increase in the lowest semitone was significantly related to change in VHI-10 score (r = −0.808, P = 0.028).Conclusion: Patients with OSA undergoing TORS showed a negative correlation coefficient over 0.8 with change in VHI-10 score. That is, increase in the lowest semitone after operation correlated with increase in VHI-10 score which may cause perceive changes in subjective pronunciation.