bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycyrrhizin has a high likelihood to be a victim of drug–drug interactions mediated by hepatic organic anion‐transporting polypeptide 1B1/1B3
Authors: Dong Jiajia , Olaleye Olajide E , Jiang Rongrong , Li Jing , Lu Chuang , Du Feifei , Xu Fang , Yang Junling , Wang Fengqing , Jia Weiwei , Li Chuan 
Published: June 2018

Background and PurposeIntravenous glycyrrhizin, having anti‐inflammatory and hepatoprotective properties, is incorporated into the management of liver diseases in China. This investigation was designed to elucidate the molecular mechanism underlying hepatobiliary excretion of glycyrrhizin and to investigate its potential for drug–drug interactions on organic anion‐transporting polypeptide (OATP)1B.Experimental ApproachHuman transporters mediating hepatobiliary excretion of glycyrrhizin were characterized at the cellular and vesicular levels and compared with rat hepatic transporters. The role of Oatp1b2 in glycyrrhizin's elimination and pharmacokinetics was evaluated in rats using the inhibitor rifampin. A physiologically based pharmacokinetic (PBPK) model for glycyrrhizin, incorporating transporter‐mediated hepatobiliary excretion, was established and applied to predict potential drug–drug interactions related to glycyrrhizin in humans.Key ResultsHepatobiliary excretion of glycyrrhizin involved human OATP1B1/1B3 (Oatp1b2 in rats)‐mediated hepatic uptake from blood and human multidrug resistance‐associated protein (MRP)2/breast cancer resistance protein (ABCP)/bile salt export pump (BSEP)/multidrug resistance protein 1 (Mrp2/Abcp/Bsep in rats)‐mediated hepatic efflux into bile. In rats, rifampin impaired hepatic uptake of glycyrrhizin significantly increasing its systemic exposure. Glomerular‐filtration‐based renal excretion of glycyrrhizin was slow due to extensive protein binding in plasma. Quantitative analysis using the PBPK model demonstrated that OATP1B1/1B3 have critical roles in the pharmacokinetics of glycyrrhizin, which is highly likely to be a victim of drug–drug interactions when co‐administered with potent dual inhibitors of these transporters.Conclusions and ImplicationsTransporter‐mediated hepatobiliary excretion governs glycyrrhizin's elimination and pharmacokinetics. Understanding glycyrrhizin's potential drug–drug interactions on OATP1B1/1B3 should enhance the therapeutic outcome of glycyrrhizin‐containing drug combinations on liver diseases.
Adenosine 5'‐monophosphate‐activated protein kinase‐dependent mTOR pathway is involved in flavokawain B‐induced autophagy in thyroid cancer cells
Authors: He Qin , Liu Wenping , Sha Sha , Fan Shanshan , Yu Yajing , Chen Li , Dong Ming 
Published: June 2018

Flavokawain B (FKB), a natural kava chalcone, shows potent antitumor activity in various types of cancer, although the mechanism of action remains unclear. In this study, we report that FKB has profound effects on the metabolic state of human thyroid cancer (TCa) cells, leading to high autophagy flux through upregulation of AMP‐activated protein kinase, which in turn inhibits mTOR and activates Beclin‐1 in TCa cells. We further report that the autophagy induced by FKB plays a prosurvival role in TCa cells both in vitro and in vivo. In conclusion, our findings provide evidence that combination treatment with FKB and pharmacological autophagy inhibitors will be a potential therapeutic strategy for the treatment of TCa.
Diabetes associated with immune checkpoint inhibition: presentation and management challenges
Authors: Galligan A. , Xu W. , Fourlanos S. , Nankervis A. , Chiang C. , Mant A. M. , Parente P. , Rischin D. , Krishnamurthy B. , Sandhu S. , Colman P. G. 
Published: June 2018

AbstractBackgroundIn recent years, immune checkpoint blockade has become a standard therapy for a wide range of cancers. Adverse events, including endocrinopathies, result from the induction of autoimmunity.Case reportWe report a case series of nine individuals who presented with immunotherapy‐induced Type 1 diabetes between 2015 and 2017. Onset of diabetes occurred within 12 weeks of commencing therapy. Anti‐glutamic acid decarboxylase antibodies were present in six people. Retrospective testing of islet antibodies in pre‐treatment samples was possible in two people and this revealed anti‐glutamic acid decarboxylase seroconversion in the first and high anti‐glutamic acid decarboxylase titres pre‐ and post‐treatment in the second person. Six people had high risk human leukocyte antigen haplotypes. Clinical and genetic factors are described and compared with previously published cases.ConclusionThis rare form of iatrogenic diabetes is a result of an accelerated, fulminant islet autoimmunity induced by immune checkpoint inhibitors. High risk human leukocyte antigen haplotypes have been found in the majority of cases. The role of pre‐existing islet autoantibodies as a biomarker is not yet known.
Body mass index and the risk of mortality among Chinese adults with Type 2 diabetes
Authors: Xu H. , Zhang M. , Xu D. , Zhang F. , Yao B. , Yan Y. , Zhao N. , Xu W. , Qin G. 
Published: June 2018

AbstractAimsTo examine the associations between BMI and the risks of all‐cause, cardiovascular disease (CVD)‐specific and cancer‐specific mortality among people with Type 2 diabetes, and thus provide recommendations for weight management in the population.MethodsThis retrospective cohort study was conducted among 52 763 people with newly diagnosed Type 2 diabetes between 1 January 2004 and 31 December 2014 in Shanghai, China. All cases of death were identified by linking to the Shanghai Vital Statistics. Some 52 488 people were included in the analysis. Survival curves for people with different BMI categories were plotted using the Kaplan–Meier method. Cox proportional hazard models within or without restricted cubic spline functions were applied to examine the potential non‐linear or linear relationship between BMI and the risk of mortalities respectively.ResultsA total of 4777 deaths were identified during an average of 6‐year follow‐up. An L‐shaped association was observed between BMI and all‐cause mortality in men (P for overall association < 0.001 and P for non‐linearity < 0.001) while a U‐shaped association was found in women (P for overall association < 0.001 and P for non‐linearity< 0.001). In men, no significant association was observed for BMI with cancer‐specific and CVD‐specific mortality. In women, an increased risk of cancer‐specific mortality was observed with increasing BMI, whereas decreasing BMI was associated with the increased CVD‐specific mortality rate.ConclusionThe increased all‐cause mortality in men with low BMI and in women with either low or high BMI indicate the importance of keeping BMI in a normal range for Chinese adults with Type 2 diabetes.
Extranodal NK/T‐cell lymphoma, nasal type: Clinical features, outcome, and prognostic factors in 101 cases
Authors: Su Yi‐Jiun , Wang Po‐Nan , Chang Hung , Shih Lee‐Yung , Lin Tung‐Liang , Kuo Ming‐Chung , Chuang Wen‐Yu , Wu Jin‐Hou , Tang Tzung‐Chih , Hung Yu‐Shin , Dunn Po , Kao Hsiao‐Wen 
Published: June 2018

AbstractObjectivesWe aimed to define the clinical features, outcome, and prognostic factors for extranodal NK/T‐cell lymphoma (ENKTL) patients in Taiwan.MethodsWe retrospectively reviewed 101 ENKTL patients diagnosed between February 1998 and October 2015.ResultsThe median age of 101 patients was 52 years old (range 22‐85); 76.2% of patients were Ann Arbor stage I/II disease. The 5‐year progression‐free survival (PFS) and overall survival (OS) were 49.9% and 54.8%, respectively. Patients with log[EBV‐DNA] ≥ 3.8 and bone marrow hemophagocytosis at diagnosis had inferior PFS and OS. Most stage I/II patients received combined chemoradiotherapy with anthracycline‐containing regimen, with overall response rate of 96.7%, complete response rate 86.9%, 5‐year PFS 65%, and OS 72%. The relapse rate was 29.3% with a short median disease‐free survival of 6.2 months. In advanced stage patients, overall response rate was only 13.6%, with median PFS 2.3 months, and OS 4.8 months. Age ≥ 60 (HR 3.773, 95% CI 1.733‐8.215, P = 0.001) and stage III/IV (HR 7.785, 95% CI 2.312‐26.213, P = 0.001) were unfavorable prognostic factors for PFS and OS by multivariate analyses.ConclusionsAge ≥ 60 and stage III/IV are independent poor prognostic factors for PFS and OS. Early‐stage ENKTL patients had good response to combined chemoradiotherapy with anthracycline‐containing regimen but with a high relapse rate and short disease‐free survival. Anthracycline‐containing regimen in advanced stage had poor response and dismal outcome.
Combined fractional carbon dioxide laser and long‐pulsed neodymium : yttrium‐aluminium‐garnet (1064 nm) laser in treatment of hidradenitis suppurativa; a prospective randomized intra‐individual controlled study
Authors: Abdel Azim Amira A. , Salem Rania T. , Abdelghani Rania 
Published: June 2018

AbstractBackgroundMultiple treatment modalities were introduced for treatment of hidradenitis suppurativa (HS) but mostly with unsatisfactory results.ObjectiveIn this prospective randomized right‐left intra‐individual controlled study, we studied the safety and efficacy of combined treatment with fractional CO2 laser and long pulsed Nd : YAG (1064 nm) laser in treatment of HS.MethodsTwenty adult patients with HS were randomized into this study. The patients were randomly allocated to receive four laser sessions with 2 weeks interval. Control side received long pulsed Nd : YAG laser (1064 nm) only, and the other side (combined treatment side) received combined fractional CO2 laser and long pulsed Nd : YAG (1064 nm) laser. Patients were clinically and histopathologically evaluated 2 weeks post treatment. Recurrence was evaluated 3 months post treatment. Outcome was clinically evaluated by physician global assessment (PGA), 10‐point visual analog scale for patient's satisfaction, and side effects.ResultsStatistically significant higher improvement and patient's satisfaction was observed in combined treatment side compared with control side (P = 0.011, 0.048 respectively). Absence of recurrence was achieved by 55% of sides receiving combined treatment and 35% of control sides.ConclusionsCombination of fractional CO2 laser and long pulsed Nd : YAG (1064 nm) laser in treatment of HS had higher improvement and patient's satisfaction together with lower recurrence compared with long pulsed Nd : YAG (1064 nm) laser alone. Better results could be achieved with low PGA, non‐obese populations, and absence of surgeries for the lesions.
Evaluation of intralesional injection of bleomycin in the treatment of plantar warts: clinical and dermoscopic evaluation
Authors: Barkat Manal T. , Abdel‐Aziz Rasha T. A. , Mohamed Mervat S. 
Published: June 2018

AbstractBackgroundTreatment of plantar warts is difficult and requires multiple treatments, and they are more refractory to treatment than common warts. Intralesional bleomycin has been used in the treatment of warts with varying degrees of success.AimThe aim of the present work is to evaluate the efficacy of intralesional injection of bleomycin in the treatment of plantar warts based on clinical and dermoscopic observations.Patients and methodsBleomycin (1 mg/ml) was injected intralesionally into the pared plantar wart every 2 weeks for a maximum of four sessions. Patients were followed both clinically and by the use of dermoscope.ResultsThe cure rate of plantar warts treated with bleomycin was 69.3% with minimal and tolerable side effects.ConclusionIntralesional injection of bleomycin is an effective and safe treatment of plantar warts. Dermoscope is recommended in the evaluation of treatment success, as it can accurately tell if the wart needs further treatment, preventing premature stoppage of the treatment, thus decreasing the possibility of recurrences.
Peace, Self‐Determination and Reckoning with the Past: A Reply to Butt, Lippert‐Rasmussen, Pasternak, Wellman and Stemplowska
Authors: Fabre Cécile 
Published: June 2018

AbstractIn this article, I offer responses to five commentaries on my recently published book, Cosmopolitan Peace. Those articles address my conception of individual and collective agency, my account of self‐determination (and its implication for the problem of annexation during and after the war), and my accounts of, respectively, reparations and remembrance after war. I revise or provide further defences of those accounts in the light of my commentators’ probing remarks.
Life‐history trade‐offs promote the evolution of dioecy
Authors: Dorken Marcel E. , Van Drunen Wendy E. 
Published: June 2018

AbstractMost dioecious plants are perennial and subject to trade‐offs between sexual reproduction and vegetative performance. However, these broader life‐history trade‐offs have not usually been incorporated into theoretical analyses of the evolution of separate sexes. One such analysis has indicated that hermaphroditism is favoured over unisexuality when female and male sex functions involve the allocation of nonoverlapping types of resources to each sex function (e.g. allocations of carbon to female function vs. allocations of nitrogen to male function). However, some dioecious plants appear to conform to this pattern of resource allocation, with different resource types allocated to female vs. male sex functions. Using an evolutionarily stable strategy approach, we show that life‐history trade‐offs between sexual reproduction and vegetative performance enable the evolution of unisexual phenotypes even when there are no direct resource‐based trade‐offs between female and male sex functions. This result might help explain the preponderance of perennial life histories among dioecious plants and why many dioecious plants with annual life histories have indeterminate growth with ongoing trade‐offs between sexual reproduction and vegetative growth.
The efficacy of curcumin in managing acute inflammation pain on the post‐surgical removal of impacted third molars patients: A randomised controlled trial
Authors: Maulina T. , Diana H. , Cahyanto A. , Amaliya A. 
Published: June 2018

SummaryCurcumin is a turmeric‐contained active ingredient that has been proven to be effective in treating pain and inflammation due to its analgesic as well as anti‐inflammation potential. Odontectomy, on the other hand, has been well known for its post‐procedure acute inflammation pain. The aim of the current study was to evaluate the efficacy of curcuminoid in treating acute inflammation post‐operative pain in the post‐surgical removal of impacted third molars patients. Ninety (44 males; 46 females) participants were recruited in this randomised controlled trial and randomly assigned to the control group (those who consumed mefenamic acid) or the experimental group (those who consumed curcumin).Numeric rating scale(NRS) was used as an evaluation tool to evaluate the intensity of the pain experienced by the participants. Pain evaluation was performed immediately after anaesthesia effect disappeared (T0) and an hour after participant took their first (T1), second (T2) and third (T3) course of drugs. All data were collected and analysed using Wilcoxon‐Mann‐Whitney test. The current study showed that participants in both groups experienced significantly (P < .01) less pain compared to their initial pain level. In addition, when the two groups were compared, it was revealed that those in the treatment group experienced even significantly (P < .01) less pain compared to those in the control group. It can be concluded that curcumin is effective in treating acute inflammation pain in the post‐surgical removal of impacted third molars patients.
Imaging sublingual microcirculatory perfusion in pediatric patients receiving procedural sedation with propofol: A pilot study
Authors: Riedijk Maaike A. , Milstein Dan M. J. 
Published: June 2018

AbstractObjectiveProcedural sedation with propofol is widely used in the pediatric population. A well‐known side effect of propofol is a decrease in peripheral vascular resistance resulting in hypotension, but little is known about the effects on microcirculation in humans. We aimed to evaluate the effects of propofol on the sublingual microcirculatory perfusion by continuous video imaging in pediatric patients undergoing procedural sedation.MethodsPatients admitted to the Pediatric Intensive Care Unit for procedural sedation were recruited. Oral microcirculation was measured employing a continuous monitoring strategy with incident dark‐field illumination imaging. Measurements were obtained before and 3 minutes after propofol induction. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, blood vessel diameter (Øbv), and systemic hemodynamics were analyzed.ResultsContinuous measurements were achieved in seven patients. Three minutes after propofol induction mean arterial pressure decreased (P = 0.028) and total and perfused vessel densities increased by 12% (P = 0.018) and 16% (P = 0.018), respectively. MFI was unaltered and mean Øbv increased but not significantly.ConclusionsPropofol induction induces a reduction in mean arterial pressure and a rise in sublingual microvascular perfusion. The observed effects of propofol on the sublingual microcirculation may be due to a decrease in microvascular resistance.
IL‐6, TNF–α levels and periodontal status changes during the menstrual cycle
Authors: Sahin Aydınyurt Hacer , Yuncu Yusuf Ziya , Tekin Yasin , Ertugrul Abdullah Seckin 
Published: June 2018

AbstractObjectivesSex steroid hormones are thought to affect periodontal tissues. A clear understanding of the effect of the menstrual cycle on oral tissues would be an important milestone in the timing of dental interventions in the future. The aim of this longitudinal, prospective study was to evaluate clinical periodontal parameters and levels of interleukin‐6 IL‐6 and tumour necrosis factor alpha (TNF‐α) in gingival crevicular fluid (GCF) during the menstrual cycle.MethodsForty‐five patients were included in this study. Clinical periodontal parameters and levels of IL‐6 and TNF‐α were evaluated at three points of the menstrual cycle: menstruation day MD, ovulation day (OD) and premenstruation day (PmD). Levels of IL‐6 and TNF‐α were determined by enzyme‐linked immunosorbent assay.ResultsThere were no statistically significant changes in plaque indexes or probing depths during the menstrual cycle (p > 0.006) The differences between OD and PmD for gingival index and bleeding on probing were significant (OD>MD) (p < 0.006). Statistically significant differences in TNF‐α and IL‐6 levels in the GCF were observed during the menstrual cycle (PmD>OD>MD) (p < 0.006).ConclusionsPeriodontal tissues did not exhibit evident changes, but this study demonstrated that the menstrual cycle affected the periodontium and induced inflammatory situations during the menstrual cycle.
Abscisic acid catabolism enhances dormancy release of grapevine buds
Authors: Zheng Chuanlin , Acheampong Atiako Kwame , Shi Zhaowan , Mugzech Amichay , Halaly‐Basha Tamar , Shaya Felix , Sun Yufei , Colova Violeta , Mosquna Assaf , Ophir Ron , Galbraith David W. , Or Etti 
Published: June 2018

AbstractThe molecular mechanism regulating dormancy release in grapevine buds is as yet unclear. It was formerly proposed that dormancy is maintained by abscisic acid (ABA)‐mediated repression of bud–meristem activity and that removal of this repression triggers dormancy release. It was also proposed that such removal of repression may be achieved via natural or artificial up‐regulation of VvA8H‐CYP707A4, which encodes ABA 8′‐hydroxylase, and is the most highly expressed paralog in grapevine buds.The current study further examines these assumptions, and its experiments reveal that (a) hypoxia and ethylene, stimuli of bud dormancy release, enhance expression of VvA8H‐CYP707A4 within grape buds, (b) the VvA8H‐CYP707A4 protein accumulates during the natural transition to the dormancy release stage, and (c) transgenic vines overexpressing VvA8H‐CYP707A4 exhibit increased ABA catabolism and significant enhancement of bud break in controlled and natural environments and longer basal summer laterals.The results suggest that VvA8H‐CYP707A4 functions as an ABA degrading enzyme, and are consistent with a model in which the VvA8H‐CYP707A4 level in the bud is up‐regulated by natural and artificial bud break stimuli, which leads to increased ABA degradation capacity, removal of endogenous ABA‐mediated repression, and enhanced regrowth. Interestingly, it also hints at sharing of regulatory steps between latent and lateral bud outgrowth.
Pretransplant increases in left ventricular volume and mass are associated with QT prolongation during pediatric liver transplantation
Authors: Cho Hyun‐Seok , Kim Wook‐Jong , Lee Byungdoo Andrew , Cho Junki , Shin Won‐Jung , Hwang Gyu‐Sam 
Published: June 2018

AbstractStructural alterations in the cirrhotic heart may contribute to electromechanical abnormalities, represented by QT prolongation. The aim of this study was to investigate the changes in QTc according to the operative stage during pediatric LT and to identify which baseline echocardiographic parameters were associated with intraoperative QTc prolongation. Data were evaluated from 39 children undergoing LT for chronic liver disease (median age 9 months). In 19 patients (48.7%), baseline QTc was prolonged ≥440 ms (462 ± 19 ms). Through the period of post‐reperfusion, QTI, QTc, and JTI progressively increased, although values partially recovered toward the end of surgery. High LVMI (≥82.51 g/m2) was associated with baseline QTc ≥ 440 ms (OR = 1.034, P = .032). In the 5 minutes post‐reperfusion stage, marked QTc prolongation (defined as QTc ≥ 500 ms; n = 24, 61.5%) was significantly associated with high EDVI (OR = 1.060, P = .027) and SVI (OR = 1.075, P = .026). In children with chronic liver disease, increased ventricular volumes and mass may increase the risk of QTc prolongation during LT, suggesting that repolarization abnormalities might be contributed by structural changes characteristic of cirrhotic cardiomyopathy.
Potential of efficient and resistant plant growth‐promoting rhizobacteria in lead uptake and plant defence stimulation in Lathyrus sativus under lead stress
Authors: Abdelkrim S. , Jebara S. H. , Saadani O. , Jebara M. 
Published: June 2018

Abstract

The ability of plant growth‐promoting rhizobacteria (PGPR) to enhance Lathyrus sativus tolerance to lead (Pb) stress was investigated.

Ten consortia formed by mixing four efficient and Pb‐resistant PGPR strains were assessed for their beneficial effect in improving Pb (0.5 mM) uptake and in inducing the host defence system of L. sativus under hydroponic conditions based on various physiological and biochemical parameters.

Lead stress significantly decreased shoot (SDW) and root (RDW) dry weight, but PGPR inoculation improved both dry weights, with highest increases in SDW and RDW of plants inoculated with I5 (R. leguminosarum (M5) + P. fluorescens (K23) + Luteibacter sp. + Variovorax sp.) and I9 (R. leguminosarum (M5) + Variovorax sp. + Luteibacter sp. + S. meliloti) by 151% and 94%, respectively. Additionally, inoculation significantly enhanced both chlorophyll and soluble sugar content, mainly in I5 inoculated leaves by 238% and 71%, respectively, despite the fact that Pb decreased these parameters. We also found that PGPR inoculation helps to reduce oxidative damage and enhances antioxidant enzyme activity, phenolic compound biosynthesis, carotenoids and proline content. PGPR inoculation increased Pb uptake in L. sativus, with highest increase in shoots of plants inoculated with I5 and I7, and in roots and nodules of plants inoculated with I1. Moreover, PGPR inoculation enhanced mineral homeostasis for Ca, Cu and Zn under Pb stress, mainly in plants inoculated with I1, I5, I7 and I9.

Results of our study suggest the potential of efficient and Pb‐resistant PGPR in alleviating harmful effects of metal stress via activation of various defence mechanisms and enhancing Pb uptake that promotes tolerance of L. sativus to Pb stress.