bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between miRNA‐146a rs2910164 (G/C) polymorphism with the susceptibility to chronic HBV infection and spontaneous viral clearance in an Iranian population
Authors: Khanizadeh Sayyad , Hasanvand Banafsheh , Nikoo Hadi Razavi , Anbari Khatereh , Adhikary Hemanta , Shirkhani Somayeh , Lashgarian Hamed Esmaeili 
Published: January 2019

Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA‐146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma. The present study investigated the association between miRNA‐146a rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population.The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control adjusted for sex and age. The genotyping of the miRNA‐146a rs2910164 polymorphism was performed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method.Our data revealed that GG genotype and G allele of miRNA‐146a rs2910164 SNP is dominated (P < 0.001) in patients with chronic HBV infection (Odds ratio [OR] = 3.92; 95% confidence interval [CI] = 2.1‐7.32). miRNA‐146a rs2910164 polymorphism showed a statistically significant association (P < 0.001) between CC genotype and allele C with SVC (OR = 2.92; 95% CI = 1.56‐546).Our findings suggest miRNA‐146a SNP (C/G) in our population may be associated with the susceptibility to HBV infection and CC genotype is associated with SVC. Also, the GG genotype and G allele at miRNA‐146a rs2910164 is associated with chronic HBV infection in our population.
Establishing the chromatographic fingerprint of traditional Chinese medicine standard decoction based on quality by design approach: A case study of Licorice
Authors: Zhang Hui , Wang Jianan , Chen Yan , Shen Xiaowei , Jiang Huijie , Gong Xingchu , Yan Jizhong 
Published: January 2019

AbstractA novel analytical quality by design approach for developing a chromatographic fingerprint was established for analyzing complex traditional Chinese medicine, using a licorice standard decoction as an example. Considering the characteristics of integrity and ambiguity, the resolution of eight common peaks, total peak number, capacity factor distributions, and peak purity were selected as potential critical method attributes for assessing the quality of the chromatographic fingerprint. A central composite design was used to evaluate the relationship between critical method attributes and critical method parameters, including column temperature, wavelength, flow rate, formic‐acid concentration, and gradient parameters. A standard probability method was employed to calculate the design space of the fingerprint analysis parameters and evaluate the robustness of the methodology. The optimized high‐performance liquid chromatography fingerprint conditions were acetonitrile and 0.1% formic acid water gradient elution (0‐5 min, 5–19% A; 5–10 min, 19% A; 10–50 min, 19–42% A; 50–54 min, 42–100% A; 54–60 min, 100% A), column temperature 25±5°C, detection wavelength 265 nm. The design space of fingerprint analytical method based on the analytical quality by design approach not only met the requirements of the fingerprint analysis, but also improved the robustness and applicability of the fingerprint method.
Analysis of thermolabile residual solvents in a spray dried dispersion using static headspace gas chromatography
Authors: Oliveira Antonio , Bambrick Stephen T. , Pfund Laura Y. , Diamandopoulos Panos , Gong Xiaoyi , Liang Xihui , Mowery Mark D. , Zheng Jinjian 
Published: January 2019

AbstractIn this study, we discuss the development of a static headspace gas chromatography method for the analysis of residual acetone as well as its enriched impurities including mesityl oxide and diacetone alcohol, in a spray dried dispersion. The major challenges include the instability of mesityl oxide and diacetone alcohol at high temperature and peak tailing of diacetone alcohol. It was found that the headspace oven temperature has to be controlled to 150°C or below to prevent degradation beyond an acceptable level (< 1%). The peak tailing of diacetone alcohol was attributed to the “Phase Soaking” effect due to excessive diluent, which may condense and temporarily modify the stationary phase. The peak shape of diacetone alcohol is dependent on the column loading capacity and the peak area of N‐methyl pyrrolidone, the solvent that elutes after diacetone alcohol. The headspace oven temperature was set at 140°C, where the highest response ratio of diacetone alcohol/N‐methyl pyrrolidone at 1.46 and thus the best sensitivity was obtained. The calculated quantitation limits were 1 ppm for acetone, 3 ppm for mesityl oxide and 31 ppm for diacetone alcohol. The method successfully passed validation criteria for specificity, linearity, accuracy, and precision.
Antifibrotic effect of mitomycin‐C on human vocal cord fibroblasts
Authors: Szabó Diána , Kovács Dávid , Endrész Valéria , Igaz Nóra , Jenovai Kitti , Spengler Gabriella , Tiszlavicz László , Molnár József , Burián Katalin , Kiricsi Mónika , Rovó László 
Published: January 2019

ObjectiveAcquired laryngotracheal stenosis is a potentially life‐threatening situation and a very difficult and challenging problem in laryngology. Therefore, new trends and innovative approaches based on antifibrotic drugs and minimally invasive regimens are being developed to attenuate laryngotracheal fibrosis and scarring. The purpose of this study was to examine the efficacy of mitomycin‐C (MMC) to reverse the transforming growth factor (TGF)‐β‐induced differentiation of MRC‐5 fibroblast and human primary vocal cord fibroblasts to reveal the possible applicability of MMC to laryngotracheal fibrotic conditions.MethodsHuman primary fibroblast cells were isolated from vocal cord specimens of patients undergoing total laryngectomy. The established primary vocal cord fibroblast cell cultures as well as the MRC‐5 human fibroblast cells were treated with 5 ng/mL TGF‐β alone and then with 0.5 µg/mL MMC for 24 hours. Differentiation of fibroblasts was characterized by α‐smooth muscle actin (α‐SMA) immunhistochemistry, Western blot analysis, and real‐time polymerase chain reaction. Cell motility was assessed by wound‐healing assay.ResultsElevated α‐SMA mRNA and protein expression as well as increased cell motility were observed upon TGF‐β exposures. However, after MMC treatments the TGF‐β‐induced fibroblasts exhibited a significant decrease in α‐SMA expression and wound‐healing activity. Therefore, TGF‐β‐stimulated fibroblast‐myofibroblast transformation was reversed at least in part by MMC treatment. Histopathological examinations of tissue specimens of a laryngotracheal stenosis patient supported these findings.ConclusionAntifibrotic effects of MMC were demonstrated on the human MRC‐5 cell line and on primary vocal cord fibroblast cultures. These results verify that MMC can be used with success to reverse upper airway stenosis by reverting the myofibroblast phenotype.Level of EvidenceNALaryngoscope, 129:E255–E262, 2019
Laryngeal fracture presentation and management in United States emergency rooms
Authors: Sethi Rosh K. V. , Khatib Dara , Kligerman Maxwell , Kozin Elliott D. , Gray Stacey T. , Naunheim Matthew R. 
Published: January 2019

Objectives/HypothesisThere are limited data on laryngeal fracture presentation and management in US emergency departments (EDs). We aimed to characterize patients who are diagnosed with laryngeal fractures in the ED and identify management patterns.Study DesignRetrospective review of the Nationwide Emergency Department Sample (NEDS) from 2009 to 2011.MethodsThe NEDS was queried for patient visits with a primary diagnosis of open or closed laryngeal fracture (International Classification of Diseases, Ninth Revision codes 807.5 and 807.6). Patient demographics, comorbidities, ED management, and hospital characteristics were extracted.ResultsThere were 3,102 ED visits with a diagnosis of laryngeal fracture during the study period. Mean patient age was 40.9 years (range, 3–93 years). The majority of patients were male (85.5%) and sustained a closed (vs. open) fracture (91.4%), with an overall mortality rate of 3.8%. The majority of patients were treated for more than one injury during the same visit (76.2%). Most patients were evaluated at a trauma hospital (53.9%), and most patients were admitted to the hospital (71.9%). Emergent intubation or tracheostomy was rarely reported (2.6% and 0.1% of all cases), and a minority of patients underwent fiberoptic flexible laryngoscopy in the ED (1.9%). Laryngeal fractures occurred more frequently during summer months (28.2%). Mean charge for the entirety of the ED stay was $4,957.34.ConclusionsLaryngeal fracture is rare and frequently associated with other injuries. The frequency of emergent airway procedure, imaging, and flexible fiberoptic laryngoscopy is lower than expected, raising concerns about appropriate workup and management or recognition of injury in the ED setting.Level of EvidenceNALaryngoscope, 129:2341–2346, 2019
Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia
Authors: Alfedi Giulia , Luffarelli Riccardo , Condò Ivano , Pedini Giorgia , Mannucci Liliana , Massaro Damiano S. , Benini Monica , Toschi Nicola , Alaimo Giorgia , Panarello Luca , Pacini Laura , Fortuni Silvia , Serio Dario , Malisan Florence , Testi Roberto , Rufini Alessandra 
Published: January 2019

ABSTRACTBackgroundFriedreich's ataxia is an autosomal‐recessive cerebellar ataxia caused by mutation of the frataxin gene, resulting in decreased frataxin expression, mitochondrial dysfunction, and oxidative stress. Currently, no treatment is available for Friedreich's ataxia patients. Given that levels of residual frataxin critically affect disease severity, the main goal of a specific therapy for Friedreich's ataxia is to increase frataxin levels.ObjectivesWith the aim to accelerate the development of a new therapy for Friedreich's ataxia, we took a drug repositioning approach to identify market‐available drugs able to increase frataxin levels.MethodsUsing a cell‐based reporter assay to monitor variation in frataxin amount, we performed a high‐throughput screening of a library containing 853 U.S. Food and Drug Administration–approved drugs.ResultsAmong the potentially interesting candidates isolated from the screening, we focused our attention on etravirine, an antiviral drug currently in use as an anti–human immunodeficiency virus therapy. Here, we show that etravirine can promote a significant increase in frataxin levels in cells derived from Friedreich's ataxia patients, by enhancing frataxin messenger RNA translation. Importantly, frataxin accumulation in treated patient cell lines is comparable to frataxin levels in unaffected carrier cells, suggesting that etravirine could be therapeutically relevant. Indeed, etravirine treatment restores the activity of the iron‐sulphur cluster containing enzyme aconitase and confers resistance to oxidative stress in cells derived from Friedreich's ataxia patients.ConclusionsConsidering its excellent safety profile along with its ability to increase frataxin levels and correct some of the disease‐related defects, etravirine represents a promising candidate as a therapeutic for Friedreich's ataxia. © 2019 International Parkinson and Movement Disorder Society
Response‐guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML‐01
Authors: De Moerloose Barbara , Reedijk Ardine , de Bock Geertruida H , Lammens Tim , de Haas Valerie , Denys Barbara , Dedeken Laurence , van den Heuvel‐Eibrink Marry M. , te Loo Maroeska , Uyttebroeck Anne , Van Damme An , Van der Werff‐ten Bosch Jutte , Zsiros Jozsef , Kaspers Gertjan , de Bont Eveline 
Published: January 2019

AbstractBackgroundChildren with acute myeloid leukemia (AML) have a 70% survival rate with treatment regimens containing high doses of cytarabine and anthracyclines and, in some, hematopoietic stem cell transplantation (allo‐HSCT).ProcedureIn this multicenter Dutch–Belgian protocol (DB AML‐01), 112 children with de novo AML were included. Treatment was stratified according to day 15 bone marrow response after the first induction course. Poor responders received a second course without delay while good responders awaited hematological recovery. Patients achieving CR after two induction courses continued with three consolidation courses without HSCT in CR1.ResultsThe overall remission rate was 93.5%. After a median follow‐up of 4.1 years, three‐year event‐free survival (EFS) was 52.6% (95% CI, 42.9%–61.3%), three‐year cumulative incidence of relapse 39.7% (95% CI, 30.1%–49.0%), and three‐year overall survival (OS) 74.0% (95% CI, 64.8%–81.2%). Significantly more events occurred in patients with high WBC at diagnosis or FLT3‐ITD/NPM1‐WT, whereas core binding factor (CBF) leukemia had a significantly better EFS. KMT2A rearrangements and age > 10 years negatively impacted OS.ConclusionsDB AML‐01 response‐guided therapy results in a favorable OS, particularly for children with CBF leukemia, children younger than 10 years or with initial WBC counts below 100 × 109/L. Outcome of patients with FLT3‐ITD/NPM1‐WT remains poor and warrants alternative treatment strategies.
Analysis of the short‐term curative effect of 356 cases of intraocular retinoblastoma in children
Authors: Jin Mei , Zhao Junyang , Zhang Dawei , Zhang Chengyue , Zhao Wen , Wang Xisi , Zhao Qian , Duan Chao , Su Yan , Hong Huimin , Ma Xiaoli 
Published: January 2019

ABSTRACTImportanceRetinoblastoma (Rb) is the most common primary malignant intraocular cancer in children. Systemic chemotherapy combined with local therapy is safe and effective for intraocular Rb.ObjectiveTo summarize the short‐term outcomes of patients with Rb to provide evidence for optimizing treatment protocols and improving therapeutic safety and efficacy.MethodsThe clinical data of 356 patients (486 eyes) with intraocular Rb admitted to our center from December 2009 to April 2017 were retrospectively analyzed. The measures included drug toxicity, eye‐preservation rate, and survival rate, with an emphasis on safety and short‐term efficacy. The date of last follow‐up was 30 November, 2017.ResultsThe patients comprised 226 unilateral Rb and 130 bilateral Rb. Enucleation before chemotherapy was performed in 72 patients. Among the 174 patients with unilateral Rb, enucleation after chemotherapy was performed in 80 patients (46.0%), and the eye was not enucleated in 89 (51.1%); 68 eyes were preserved (68/114, 59.6%) in Group D and 20 eyes (20/59, 33.8%) in Group E. Among the 220 eyes in patients with bilateral Rb, enucleation after chemotherapy was performed for 35 eyes; the eye‐preservation rate was 91.7% in Group C, 79.1% in Group D, and 52.1% in Group E. All patients developed grade II to IV myelosuppression after chemotherapy, among whom 18 patients (5%) requiring transfusion. Fourteen patients (3.9%) died of intracranial metastasis following self‐elected discontinuation of treatment (n = 7). Patients were followed up for a median of 47 (range, 1–96) months. The expected 5‐year overall survival rate was 95.3% (96.7% for unilateral Rb and 92.9% for bilateral Rb, P = 0.074).InterpretationThe VEC (vincristine, etoposide, and carboplatin) regimen with local treatment was safe for intraocular Rb. Intracranial metastasis remains the most common cause of Rb‐related death.
Effects of Atypical Antipsychotic Treatment and Resistant Starch Supplementation on Gut Microbiome Composition in a Cohort of Patients with Bipolar Disorder or Schizophrenia
Authors: Flowers Stephanie A. , Baxter Nielson T. , Ward Kristen M. , Kraal A. Zarina , McInnis Melvin G. , Schmidt Thomas M. , Ellingrod Vicki L. 
Published: January 2019

Study ObjectivePrevious studies identified shifts in gut microbiota associated with atypical antipsychotic (AAP) treatment that may link AAPs to metabolic burden. Dietary prebiotics such as resistant starch may be beneficial in obesity and glucose regulation, but little is known mechanistically about their ability to modify gut microbiota in AAP‐treated individuals. This investigation was undertaken to delineate mechanistically the effects of AAP treatment and resistant starch supplementation on gut microbiota in a psychiatric population.DesignCross‐sectional cohort study.SettingThe study was performed in an outpatient setting.PatientsA total of 37 adults with a diagnosis of bipolar disorder or schizophrenia who were treated with an AAP (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone [21 patients]) or lithium and/or lamotrigine (16 patients) for at least 6 months.InterventionPatients in the AAP group received raw unmodified potato starch (resistant starch) daily for 14 days.Measurements and Main ResultsOf the 37 patients, the mean ± SD age was 52.2 ± 12.5 years, and 57% were male. The primary outcome was gut microbiome DNA composition. Microbiome DNA obtained from stool samples from all patients was subject to 16S ribosomal RNA (rRNA) gene sequencing before and during resistant starch supplementation. Inter‐ and intragroup microbial diversity measures were performed by permutational multivariate analysis of variance and the Inverse Simpson Diversity Index, respectively. Differentially abundant organisms were detected by using linear discriminant analysis effect size. Although no significant difference in overall microbiota composition was detected at baseline between AAP users and nonusers, non‐AAP users showed increased fractional representation of Alistipes. AAP‐treated women exhibited decreased diversity compared with non–AAP‐treated women. Although the microbiome of AAP‐treated patients varied with resistant starch administration, an increased abundance of the Actinobacteria phylum was observed.ConclusionThese data suggest that AAP treatment is associated with measurable differences in gut microbiota, particularly in female AAP‐treated patients in whom reduced species richness was observed. Additionally, variable microbiome responses to resistant starch supplementation were seen, with a significant increase in starch degraders.
Inspiratory muscle strength, diaphragmatic mobility, and body composition in chronic obstructive pulmonary disease
Authors: Souza Rosália M.P. , Cardim Adriane B. , Maia Tuíra O. , Rocha Lívia G. , Bezerra Shirley D. , Marinho Patrícia Érika M. 
Published: January 2019

AbstractBackground and purposeChronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease that can cause repercussions on respiratory muscles and body composition. The aim of the current study was to evaluate inspiratory muscle strength, diaphragmatic mobility, and body composition in COPD subjects and to correlate these variables.MethodsThis was a cross‐sectional study performed with 21 COPD patients. Inspiratory muscle strength (manovacuometry), pulmonary function test (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and FEV1/FVC ratio), diaphragmatic mobility (ultrasonography), and body composition (bioelectrical impedance analysis) were examined.ResultsCOPD individuals in Stages II (28.9%), III (52%), and IV (19%) according to Global Initiative for Chronic Obstructive Disease were recruited, 61.9% of which were men. Inspiratory muscle weakness was found in 47.6% of subjects, who presented a lower fat‐free mass percentage (p = 0.017) and smaller fat‐free mass index (p = 0.001) and greater fat mass percentage (p = 0.029) and less diaphragmatic mobility (p = 0.007) compared with the nonrespiratory weakness group. Maximal inspiratory pressure exhibited a moderately positive relationship to the fat‐free mass index (r = 0.767, p < 0.001) and a weak positive relationship to diaphragmatic mobility (r = 0.496, p = 0.022).ConclusionOur study showed a high prevalence of inspiratory muscle weakness based on the severity of airway obstruction and on the presence of muscular depletion. The evaluation of body composition detected important changes. It also demonstrated that not only muscular weakness was present in these patients but also this had repercussions on the mobility of the diaphragm muscle.
Inhibition on acid‐sensing ion channels and analgesic activities of flavonoids isolated from dragon's blood resin
Authors: Wan Ying , Yu Yi , Pan Xinxin , Mo Xiaoqiang , Gong Weifan , Liu Xiangming , Chen Su 
Published: January 2019

Acid‐sensing ion channel (ASIC) serves important roles in the transmission of nociceptive information. To confirm the analgesic mechanism of dragon's blood resin, patch–clamp technique, in vivo animal experiments, and immunohistochemical staining were used to observe the effects of the three flavonoids (loureirin B, cochinchinemin A, and cochinchinemin B) isolated from dragon's blood resin on ASIC. Results showed that the three flavonoids exerted various inhibitory effects on ASIC currents in rat dorsal root ganglion (DRG) neurons. The combination of the three flavonoids with total concentration of 6.5 μM could decrease (53.8 ± 4.3%) of the peak amplitude and (45.8 ± 4.5%) of the sustained portion of ASIC currents. The combination of the three flavonoids was fully efficacious on complete Freud's adjuvant (CFA)–induced inflammatory thermal hyperalgesia at a dose of 6.5 mM similar with amiloride at 10 mM. The analgesic effects of the combination could be weakened by an ASIC activator 2‐guanidine‐4‐methylquinazoline. CFA‐induced hyperalgesia was accompanied by c‐Fos up‐regulation in DRG neurons, and the combination rescued thermal hyperalgesia through down‐regulation of c‐Fos and ASIC3 expression in CFA‐induced inflammation. These collective results suggested that the flavonoids isolated from dragon's blood resin could be considered as the chemical compounds that exert analgesic effects on inflammatory thermal pain due to action on ASIC.