bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the Minimum Acceptable Diagnostic Accuracy of Noninvasive Fibrosis Testing in Cirrhosis: A Decision Analytic Modeling Study
Authors: Majumdar Avik , Campos Sara , Gurusamy Kurinchi , Pinzani Massimo , Tsochatzis Emmanuel A. 
Published: July 2019

No studies explore the clinical consequences of using noninvasive tests (NITs) compared to liver biopsy (LB) in diagnosing cirrhosis. Our aim was to combine two decision analytic models to determine the minimum diagnostic accuracy criteria for NITs to diagnose cirrhosis with equivalence to LB in terms of mortality. We further evaluated selected existing NITs used alone and sequentially. A decision tree was constructed with associated 2‐year mortality incorporating an LB or NIT strategy to diagnose cirrhosis in a hypothetical cohort of 1,000 asymptomatic patients. Cirrhosis prevalence was modeled at 5%, 20%, and 50%. Decision curve analyses were performed, expressing the net benefit of tests over a range of threshold probabilities (Pt). The NIT deriving from the two models that could diagnose cirrhosis with at least equal mortality to LB was termed “mNIT.” Existing NITs were then compared using both decision models. The combined mNIT minimum sensitivity and specificity to diagnose cirrhosis with equivalence to LB at 5%, 20% and 50% cirrhosis prevalence were; 89% and 88%, 94% and 85%, and 94% and 87%, respectively at Pt = 0.20. Sequential NITs performed better than single NITs at any prevalence. Combining both decision models, FibroTest plus vibration‐controlled transient elastography (VCTE) and VCTE alone were the only existing NITs that were better than or equal to LB at diagnosing cirrhosis at 5% prevalence. At 20% and 50% prevalence, only FibroTest high specificity cutoff plus VCTE was equivalent to or better than LB. Conclusion: Decision analytic models were used to determine the minimum acceptable diagnostic accuracy of NITs for diagnosing cirrhosis; we recommend that such models should be used as the standard in evaluating the diagnostic performance of NITs.
An experimental study on thermal management of concentrated photovoltaic cell using loop heat pipe and heat sink
Authors: S. Anand , M. Senthil Kumar , K. R. Balasubramanian , R. Ajith Krishnan , L. Maheswari 
Published: July 2019

AbstractOne of the most critical innovations in the solar energy conversion is the use of concentrators for generating power from a smaller area of the cell. The thermal management has an exceptional role in the concentrated photovoltaic (CPV) cell, without which the operating temperature will increase owing to the thermal degradation. In the present study, a prototype of low CPV with single‐cell configuration using a Fresnel lens and a manual tracker with geometrical concentration ratio of up to 25 Suns is made. The performance of the CPV with passive cooling arrangements, such as heat sink and loop heat pipes (LHPs), is analyzed under real‐time outdoor conditions. The results obtained infer that the LHP‐based cooling system has brought down the average temperature rise above ambient to 37.8°C from 54.16°C and 72.6°C in the heat sink and bare CPV systems, respectively. Also, the LHP managed to reject the heat to the surrounding with an average thermal resistance of 1.005°C/W, which is the least when compared with the heat sink. Apart from the instabilities caused by the interference of clouds, the CPV with the LHP cooling system could generate 10% more power output than the one with a heat sink.
Activation of GPR30 promotes osteogenic differentiation of MC3T3‐E1 cells: An implication in osteoporosis
Authors: Lin Xiaozong , Li Li , Wu Shuliang , Tian Jun , Zheng Weizhuo 
Published: July 2019

AbstractOsteoporosis is an age‐related disease characterized by reduced bone volume and disturbed bone metabolism. Novel therapies to rescue or prevent reduced bone mass by guiding the differentiation of pluripotent bone marrow stromal cells away from adipocyte differentiation and toward osteoblastic differentiation may serve as a valuable treatment option against osteoporosis. Estrogen has long been recognized as a key effector of bone formation and mineralization, but the exact mechanisms involved remain poorly understood. In the present study, we investigated the role of the estrogen‐specific G protein‐coupled receptor 30 (GPR30/GPER) using its specific agonist G1 in MC3T3‐E1 preosteoblast cells. Our findings demonstrate that expression of GPR30 is upregulated during osteoblast differentiation and that agonism of GPR30 significantly increases some key markers of mineralization including alkaline phosphatase, osteocalcin, osterix, and type I collagen. We also demonstrate that GPR30 agonism upregulates expression of Runx2, which is recognized as an essential transcription factor involved in bone formation. Additionally, through a series of adenosine monophosphate‐activated protein kinase (AMPK)‐inhibition experiments using compound C, we show that the positive effects of GPR30 on mineralization and differentiation of preosteoblasts are mediated through the AMPK/anti‐acetyl‐CoA carboxylase (ACC) pathway. Taken together, the findings of the present study demonstrate the potential of GPR30 as a novel target for the treatment and prevention of osteoporosis.
Mass spectrometry‐based proteomic analysis of FSCN1‐interacting proteins in laryngeal squamous cell carcinoma cells
Authors: Liu Hongliang , Cui Jiajia , Zhang Yuliang , Niu Min , Xue Xuting , Yin Hongyu , Tang Yemei , Dai Li , Dai Fengsheng , Guo Yujia , Wu Yongyan , Gao Wei 
Published: July 2019

AbstractFascin actin‐bundling protein 1 (FSCN1) is an evolutionarily conserved actin‐bundling protein that plays a critical role in cell migration, motility, adhesion, and cellular interactions. Although multiple clinical studies have implicated the expression of FSCN1 in laryngeal squamous cell carcinoma (LSCC) progression, the precise mechanism of FSCN1 in the process has not been clearly elucidated. To define FSCN1 function, we characterized FSCN1‐interacting proteins in LSCC cells by immunoprecipitation followed by mass spectrometry (MS). After data filtering, 119 proteins with expression in both the Hep‐2 and TU‐177 cell samples were identified as FSCN1‐interacting partners. With in‐depth bioinformatics analysis, we linked FSCN1 to critical cellular processes including cell adhesion, glycolysis/gluconeogenesis, regulation of protein ubiquitination, ribosomal RNA processing, and small molecule metabolism. We discuss the interactions between FSCN1 and some of the newly validated partners. The identification of these potential partners of FSCN1 expands our knowledge of the FSCN1 interactome and provides a valuable resource for understanding the functions of this protein in LSCC progression.
Novel multicomponent organic–inorganic WPI/gelatin/CaP hydrogel composites for bone tissue engineering
Authors: Dziadek Michal , Kudlackova Radmila , Zima Aneta , Slosarczyk Anna , Ziabka Magdalena , Jelen Piotr , Shkarina Svetlana , Cecilia Angelica , Zuber Marcus , Baumbach Tilo , Surmeneva Maria A. , Surmenev Roman A. , Bacakova Lucie , Cholewa‐Kowalska Katarzyna , Douglas Timothy E. L. 
Published: July 2019

AbstractThe present work focuses on the development of novel multicomponent organic–inorganic hydrogel composites for bone tissue engineering. For the first time, combination of the organic components commonly used in food industry, namely whey protein isolate (WPI) and gelatin from bovine skin, as well as inorganic material commonly used as a major component of hydraulic bone cements, namely α‐TCP in various concentrations (0–70 wt%) was proposed. The results showed that α‐TCP underwent incomplete transformation to calcium‐deficient hydroxyapatite (CDHA) during preparation process of the hydrogels. Microcomputer tomography showed inhomogeneous distribution of the calcium phosphate (CaP) phase in the resulting composites. Nevertheless, hydrogels containing 30–70 wt% α‐TCP showed significantly improved mechanical properties. The values of Young's modulus and the stresses corresponding to compression of a sample by 50% increased almost linearly with increasing concentration of ceramic phase. Incomplete transformation of α‐TCP to CDHA during preparation process of composites provides them high reactivity in simulated body fluid during 14‐day incubation. Preliminary in vitro studies revealed that the WPI/gelatin/CaP composite hydrogels support the adhesion, spreading, and proliferation of human osteoblast‐like MG‐63 cells. The WPI/gelatin/CaP composite hydrogels obtained in this work showed great potential for the use in bone tissue engineering and regenerative medicine applications.
The androgen receptor antagonist enzalutamide induces apoptosis, dysregulates the heat shock protein system, and diminishes the androgen receptor and estrogen receptor β1 expression in prostate cancer cells
Authors: Abazid Alexander , Martin Benedikt , Choinowski Anja , McNeill Rhiannon V. , Brandenburg Lars‐Ove , Ziegler Patrick , Zimmermann Uwe , Burchardt Martin , Erb Holger , Stope Matthias B. 
Published: July 2019

AbstractEnzalutamide's accepted mode of action is by targeting the androgen receptor's (AR) activity. In clinical practice, enzalutamide demonstrates a good benefit‐risk profile for the treatment of advanced prostate cancer (PC), even after poor response to standard antihormonal treatment. However, since both, well‐established antiandrogens and enzalutamide, target AR functionality, we hypothesized that additional unknown mechanisms might be responsible for enzalutamide's superior anticancer activity. In the current study, PC cells were incubated with enzalutamide and enzalutamide‐dependent modulation of apoptotic mechanisms were assessed via Western blot analysis, TDT‐mediated dUTP‐biotin nick end‐labeling assay, and nuclear morphology assay. Alterations of heat shock protein (HSP), AR, and estrogen receptor (ER) expression were examined by Western blot analysis. Enzalutamide attenuated the proliferation of PC cells in a time‐ and dose‐dependent manner. In the presence of enzalutamide, apoptosis occurred which was shown by increased BAX expression, decreased Bcl‐2 expression, nuclear pyknosis, and genomic DNA fragmentation. Moreover, enzalutamide inhibited the expression of HSPs primarily involved in steroid receptor stabilization and suppressed AR and ERβ1 expression. This study demonstrates for the first time that enzalutamide treatment of PC cells triggers varying molecular mechanisms resulting in antiproliferative effects of the drug. In addition to the well‐characterized antagonistic inhibition of AR functionality, we have shown that enzalutamide also affects the intracellular synthesis of steroid receptor‐associated HSPs, thereby diminishing the expression of AR and ERβ1 proteins and inducing apoptotic pathways. According to an indirect attenuation of HSP‐associated factors such as steroid receptors, endometrial carcinoma, uterine leiomyosarcoma, and mamma carcinoma cells also demonstrated inhibited cell growth in the presence of enzalutamide. Our data, therefore, suggest that enzalutamide's high efficacy is at least partially independent of AR and p53 protein expression, which are frequently lost in advanced PC.
SKP2, positively regulated by circ_ODC1/miR‐422a axis, promotes the proliferation of retinoblastoma
Authors: Du Shanshan , Wang Shuai , Zhang Fengyan , Lv Yong 
Published: July 2019

AbstractRetinoblastoma (RB) is the most common intraocular malignancy in infants and children. S‐phase kinase‐associated protein 2 (SKP2) has been unmasked as an oncogene in a great many of carcinomas. The biologic function and the detailed molecular mechanism of SKP2 in RB need to be better understood. In this study, real‐time quantitative polymerase chain reaction and Western blot showed the ectopic expression of SKP2 in RB tissues and cell lines. Loss of function assays showed the attenuated cell proliferation in RB as a result of SKP2 knockdown. In addition, bioinformatics analysis predicted the interaction between SKP2 and miR‐422a. Luciferase reporter assay and Pearson's correlation analysis validated the negative correlation between miR‐422a and SKP2. MiR‐422a overexpression led to a decline of SKP2 expression and cell growth in RB. The binding capacity between miR‐422a and circ_ODC1 was also predicted by bioinformatics analysis. Pearson's correlation analysis and luciferase reporter assay confirmed that circ_ODC1 is negatively correlated with miR‐422a. Silencing circ_ODC1 resulted in a rise in miR‐422a expression and RB cell growth. Moreover, reduced cell growth was restored by SKP2 overexpression. In a word, SKP2, induced by circ_ODC1 and miR‐422a, promotes RB proliferation. Our new findings in this research might expedite the discovery of novel prognostic markers and therapeutic targets of RB.
Upregulation of long noncoding TNFSF10 contributes to osteoarthritis progression through the miR‐376‐3p/FGFR1 axis
Authors: Huang Bingzhe , Yu Haichi , Li Yingzhi , Zhang Wei , Liu Xiaoning 
Published: July 2019

AbstractOsteoarthritis (OA) is a common joint disease with high morbidity, but there is still no definitive treatment for it. Long noncoding RNAs (lncRNAs) have been confirmed to play key roles in OA progression. This work was done to investigate the roles and action mechanism of lncRNA TNFSF10 in OA. The messenger RNA levels of TNFSF10 in articular cartilage samples from patients or chondrocytes were detected by Quantitative real‐time PCR assay (qRT‐PCR). The effects of TNFSF10 on chondrocytes were evaluated on the basis of cell growth, apoptosis, and inflammation. Then, the interaction between TNFSF10 and miR‐376‐3p was explored by dual‐luciferase reporter test, RNA‐binding protein immunoprecipitation, and RNA pull‐down assay. Finally, various cell experiments, Western blot analysis, and qRT‐PCR were performed to study the interaction among TNFSF10, miR‐376‐3p, and fibroblast growth factor receptor 1 (FGFR1). It was found that TNFSF10 was upregulated in OA cartilages and stimulated cell proliferation, antiapoptosis, and inflammation for chondrocytes. In addition, TNFSF10 acted as a competing endogenous RNA to downregulate miR‐376‐3p, and the influence of TNFSF10 on chondrocytes was partly reversed by miR‐376‐3p. Moreover, FGFR1, as a target of miR‐376‐3p, had reversal functions on the outcomes mediated by miR‐376‐3p. The further analysis displayed that there was a negative relationship between TNFSF10 and miR‐376‐3p as well as miR‐376‐3p and FGFR1, while FGFR1 was positively related with TNFSF10. Altogether, TNFSF10 overexpression probably stimulated proliferation and inflammation, and inhibited apoptosis by regulating the miR‐376‐3p/FGFR1 axis, implying that its increase contributed to OA progression. Our study provided a new potential biomarker or therapeutic target‐TNFSF10, which was helpful to develop an efficient approach to cure OA.
Differentiation of human olfactory system‐derived stem cells into dopaminergic neuron‐like cells: A comparison between olfactory bulb and mucosa as two sources of stem cells
Authors: Alizadeh Rafieh , Ramezanpour Farnaz , Mohammadi Amirhossein , Eftekharzadeh Mina , Simorgh Sara , Kazemiha Milad , Moradi Fatemeh 
Published: July 2019

AbstractCell transplantation has become a possible therapeutic approach in the treatment of neurodegenerative diseases of the nervous system by replacing lost cells. The current study aimed to make a comparison between the differentiation capacity of the olfactory bulb neural stem cells (OB‐NSCs) and olfactory ectomesenchymal stem cells (OE‐MSCs) into dopaminergic‐like neurons under the inductive effect of transforming growth factor β (TGF‐β). After culturing and treating with TGF‐β, the differentiation capacities of both types of stem cells into dopaminergic neuron‐like cells were evaluated. Quantitative real‐time polymerase chain reaction analysis 3 weeks after induction demonstrated that the mRNA expression of the dopaminergic activity markers tyrosine hydroxylase (TH), dopamine transporter (DAT), paired box gene 2 (PAX2), and PAX5 in the neuron‐like cells derived from OB‐NSCs was significantly higher than those derived from OE‐MSCs. These findings were further supported by the immunocytochemistry staining showing that the expression of the tyrosine hydroxylase, DAT, PAX2, and paired like homeodomain 3 seemed to be slightly higher in OB‐NSCs compared with OE‐MSCs. Despite the lower differentiation capacity of OE‐MSCs, other considerations such as a noninvasive and easier harvesting process, faster proliferation attributes, longer life span, autologous transplantability, and also the easier and inexpensive cultural process of the OE‐MSCs, cumulatively make these cells the more appropriate alternative in the case of autologous transplantation during the treatment process of neurodegenerative disorders like Parkinson's disease.
Subcellular distribution of human tyrosine hydroxylase isoforms 1 and 4 in SH‐SY5Y cells
Authors: Kunzler Alice , Garcia Sobrinho Pedro , Smith Tenele , Gelain Daniel Pens , Moreira José Cláudio Fonseca , Dunkley Peter Robert , Dickson Phillip Wesley 
Published: July 2019

AbstractTyrosine hydroxylase (TH) is the key enzyme that controls the rate of synthesis of the catecholamines. SH‐SY5Y cells with stable transfections of either human tyrosine hydroxylase isoform 1 (hTH1) or human tyrosine hydroxylase isoform 4 (hTH4) were used to determined the subcellular distribution of TH protein and phosphorylated TH, under basal conditions and after muscarine stimulation. Muscarine was previously shown to increase the phosphorylation of only serine 19 and serine 40 in hTH1 cells. Under basal conditions, the hTH1 and hTH4 proteins, their serine 19 phosphorylated forms and hTH1 phosphorylated at serine 40 were all similarly distributed; with ~80% in the cytosolic fraction, ~20% in the membrane fraction, and less than 1%, or not detectable, in the nuclear fraction. However, hTH4 phosphorylated at serine 71 had a significantly different distribution with ~65% cytosolic and ~35% membrane associated. Muscarine stimulation led to hTH1 being redistributed from the cytosol and nuclear fractions to the membrane fraction and hTH4 being redistributed from the cytosol to the nuclear fraction. These muscarine stimulated redistributions were not due to TH phosphorylation at serine 19, serine 40, or serine 71 and were most likely due to TH binding to proteins whose phosphorylation was increased by muscarine. This is the first study to show a difference in subcellular distribution between two human TH isoforms under basal and stimulated conditions.
A pilot study to evaluate the practice of transvaginal gynecological sonography in a general gynecology clinic
Authors: Ooi Rucira , Griffiths Anthony , Wilson David 
Published: July 2019

AbstractPurposeUltrasound is the imaging method of choice in gynecology. The quality and diagnostic accuracy of ultrasound depends on the skills of the individual performing the scan. Evaluation of ultrasound practice has received limited attention.MethodsA video recording device was connected to an ultrasound machine in gynecology clinics in a teaching hospital. To minimize the observer effect, all staff were notified through email in advance. Data were collected over a 3‐week period. Anonymous recordings of both patients and user were compared with current guidelines, and practice was categorized as: compliant, partially compliant, or non‐compliant.ResultsObservations (n = 43) were categorized and the results described as percentage frequencies (%). Image optimization was compliant in 23.3% of recorded observations, 11.6% was partially compliant, and 65.1% was noncompliant. The study also found that global examination on gynecology was 20.9% compliant, 18.6% partially compliant, and 60.47% noncompliant. Images were annotated in appropriately 41.9% of instances, and 25.6% of end‐users examined bladder, vagina, and cervix when indicated.ConclusionThe pilot evaluation showed that ultrasound practice among end‐users did not reflect current guidelines, suggesting a need for improvement. Accuracy and performance of ultrasound examination remains highly operator‐dependent although video evaluation can be an effective tool for assessing such skills.
Drug‐drug interactions between feminizing hormone therapy and pre‐exposure prophylaxis among transgender women: the iFACT study
Authors: Hiransuthikul Akarin , Janamnuaysook Rena , Himmad Kanittha , Kerr Stephen J , Thammajaruk Narukjaporn , Pankam Tippawan , Phanjaroen Kannapat , Mills Stephen , Vannakit Ravipa , Phanuphak Praphan , Phanuphak Nittaya ,   the iFACT Study Team
Published: July 2019

AbstractIntroductionConcerns over potential drug‐drug interactions (DDI) between feminizing hormone therapy (FHT) and pre‐exposure prophylaxis (PrEP) have hampered uptake and adherence of PrEP among transgender women (TGW). To determine DDI between FHT and PrEP, we measured the pharmacokinetic (PK) parameters of blood plasma estradiol (E2) and tenofovir (TFV) in Thai TGW.MethodsTwenty TGW who never underwent orchiectomy and had not received injectable FHT within six months were enrolled between January and March 2018. FHT (E2 valerate and cyproterone acetate) were prescribed to participants at baseline until week 5, and then from week 8 until the end of study. Daily PrEP (tenofovir disoproxil fumarate/emtricitabine) was initiated at week 3 and continued without interruption. Intensive E2 PK parameters and testosterone concentration at 24 hours (C24) were measured at weeks 3 (without PrEP) and 5 (with PrEP), and intensive TFV PK parameters were measured at weeks 5 (with FHT) and 8 (without FHT).ResultsMedian (interquartile range) age, body mass index, and creatinine clearance were 21.5 (21–26) years, 20.6 (19.0‐22.4) kg/m2, and 116 (101‐126.5) mL/min, respectively. The geometric mean (%CV) of area under curve from time zero to 24 hours (AUC0‐24), maximum concentration (Cmax), and C24 of E2 at weeks 3 and 5 were 775.13 (26.2) pg h/mL, 51.47 (26.9) pg/mL, and 15.15 (42.0) pg/mL; and 782.84 (39.6), 55.76 (32.9), and 14.32 (67.4), respectively. The geometric mean (%CV) of TFV AUC0‐24, Cmax, and C24 at weeks 5 and 8 were 2242.1 (26.5) ng h/mL, 353.9 (34.0) ng/mL, and 40.9 (31.4) ng/mL; and 2530.2 (31.3), 311.4 (30.0), and 49.8 (29.6), respectively. The geometric mean of TFV AUC0‐24 and C24 at week 5 were significantly less than that at week 8 by 12% (p = 0.03) and 18% (p < 0.001), respectively. There were no significant changes in E2 PK parameters and median C24 of bioavailable testosterone between week 3 and week 5.ConclusionsOur study demonstrated lower blood plasma TFV exposure in the presence of FHT, suggesting that FHT may potentially affect PrEP efficacy among TGW; but E2 exposure was not affected by PrEP. Further studies are warranted to determine whether these reductions in TFV are clinically significant.Clinical Trial Number: NCT03620734.