bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically based pharmacokinetic modelling of oxycodone drug–drug interactions
Authors: Rytkönen Jaana , Ranta Veli‐Pekka , Kokki Merja , Kokki Hannu , Hautajärvi Heidi , Rinne Valtteri , Heikkinen Aki T. 
Published: January 2020

AbstractOxycodone is an opioid analgesic with several pharmacologically active metabolites and relatively narrow therapeutic index. Cytochrome P450 (CYP) 3A4 and CYP2D6 play major roles in the metabolism of oxycodone and its metabolites. Thus, inhibition and induction of these enzymes may result in substantial changes in the exposure of both oxycodone and its metabolites. In this study, a physiologically based pharmacokinetic (PBPK) model was built using GastroPlus™ software for oxycodone, two primary metabolites (noroxycodone, oxymorphone) and one secondary metabolite (noroxymorphone). The model was built based on literature and in house in vitro and in silico data. The model was refined and verified against literature clinical data after oxycodone administration in the absence of drug–drug interactions (DDI). The model was further challenged with simulations of oxycodone DDI with CYP3A4 inhibitors ketoconazole and itraconazole, CYP3A4 inducer rifampicin and CYP2D6 inhibitor quinidine. The magnitude of DDI (AUC ratio) was predicted within 1.5‐fold error for oxycodone, within 1.8‐fold and 1.3–4.5‐fold error for the primary metabolites noroxycodone and oxymorphone, respectively, and within 1.4–4.5‐fold error for the secondary metabolite noroxymorphone, when compared to the mean observed AUC ratios. This work demonstrated the capability of PBPK model to simulate DDI of the administered compounds and the formed metabolites of both DDI victim and perpetrator. However, the predictions for the formed metabolites tend to be associated with higher uncertainty than the predictions for the administered compound. The oxycodone model provides a tool for forecasting oxycodone DDI with other CYP3A4 and CYP2D6 DDI perpetrators that may be co‐administered with oxycodone.
5‐year experience of a tertiary center in major congenital abnormalities in singleton pregnancies
Authors: Beksac M. Sinan , Fadiloglu Erdem , Unal Canan , Cetiner Sibel , Tanacan Atakan 
Published: January 2020

AbstractObjectiveTo demonstrate major congenital abnormalities delivered or terminated at our institution between 2014 and 2018.Materials and MethodsNecessary information was retrieved from the registries of the delivery room and electronic database of Hacettepe University Hospital, Ankara.ResultsThis study was consisted of 307 major congenital anomalies. The incidence of major congenital anomalies was 2.9 per 1,000 live births, while the majority of the cases were related to cardiovascular, central nervous system, and diaphragmatic hernia with 97, 87, and 25 cases at each group, respectively. Rate of termination of pregnancy (TOP) and live birth were 35.1 and 59.2%, respectively. The overall infant mortality rate was 28.9% in cases with live birth, while this rate was highest in cardiovascular system abnormalities and diaphragmatic hernia. Out of 182 newborns, 92.8% admitted to the neonatal intensive care unit after the delivery. Median gestational week at TOP was 21(20).ConclusionWe have shown that TOP and infant mortality rates were 35.1 and 28.9%, respectively in pregnancies with fetal malformations. Detailed multidisciplinary counseling must be provided for parents in pregnancies with major congenital abnormalities.
Population-based analysis of outcomes with early-age colorectal cancer
Authors: Saraste D , Järås J , Martling A 
Published: January 2020

Abstract

Background
The aim was to evaluate differences in stage, treatment and prognosis in patients aged less than 50 years with colorectal cancer compared with older age groups.

Methods
This population-based study included all patients diagnosed with colorectal cancer in Sweden, 2010–2015. Disease stage, treatment, 5-year disease-free survival (DFS) and relative survival were analysed in relation to age groups: less than 50, 50–74 and at least 75 years.

Results
Of 34 434 patients included, 24·1, 19·7 and 14·0 per cent of patients aged less than 50, 50–74 and at least 75 years respectively were diagnosed with stage IV disease (P &lt; 0·001). Adverse histopathological features were more common in young patients. Among patients aged less than 50 years, adjuvant chemotherapy was given to 18·9, 42·0 and 93·9 per cent of those with stage I, III and III disease respectively, compared with 0·7, 4·4 and 29·6 per cent of those aged 75 years or older (P &lt; 0·001). Stage-adjusted DFS at 5 years for patients under 50 years old was 0·96, 0·90 and 0·77 in stage I, II and III respectively. Corresponding proportions were 0·88, 0·82 and 0·68 among patients aged 50–74 years, and 0·69, 0·62 and 0·49 for those aged 75 years or older. Relative survival was better for young patients only among those with stage III disease.

Conclusion
Patients younger than 50 years with colorectal cancer had a poorer stage at diagnosis and received more intensive oncological treatment. DFS was better than that among older patients in early-stage disease.
Establishment and validation of two nomograms to predict the benefit of concurrent chemotherapy in stage II‐IVa nasopharyngeal carcinoma patients with different risk factors: Analysis based on a large cohort
Authors: Sun Xue‐Song , Xiao Bei‐Bei , Lin Chao , Liu Sai‐Lan , Chen Qiu‐Yan , Tang Lin‐Quan , Mai Hai‐Qiang 
Published: January 2020

AbstractObjectiveWe aimed to establish and validate two nomograms that predict progression‐free survival (PFS) and overall survival (OS) in patients with stage II–IVa nasopharyngeal carcinoma (NPC) while evaluating the benefit of concurrent chemotherapy.Patients and MethodsWe randomly divided 3412 patients newly diagnosed with stage II‐IVa NPC between 2008 and 2013 into training and validation ‘A’ cohorts (n = 1706 each). Another set of patients diagnosed between 2014 and 2016 served as validation cohort ‘B’ (n = 1503). A Cox multivariate model using the backward stepwise approach was applied to develop the nomograms, which were assessed for accuracy (Harrel C index) and calibration.ResultsThe 3‐ and 5‐year PFS rates in the training cohort were 86.8% (95% confidence interval [CI] 85.0%‐88.6%) and 82.3% (95% CI 80.1%‐84.5%), respectively. For the PFS nomogram, 5 variables were selected based on a backward procedure in the multivariate Cox model (gender, T stage, N stage, Epstein‐Barr virus DNA, and treatment method). The same variables plus patient age and diabetes mellitus were used for the OS nomogram. The Harrell C indices of the training, validation A, and validation B cohorts were 0.711, 0.700, and 0.703, respectively, for PFS, and 0.775, 0.743, and 0.727, respectively, for OS. Both nomograms performed well in terms of calibration in the training and validation cohorts.ConclusionsOur nomograms are reliable prognostic predictors of PFS and OS in patients with stage II‐IVa NPC. These nomograms could robustly estimate an individual's benefit from concurrent chemotherapy, which assists in treatment decision‐making.
Postlaryngectomy sinonasal squamous cell carcinoma: Case report and review of the literature
Authors: Mantsopoulos Konstantinos , Taha Lava , Agaimy Abbas , Iro Heinrich 
Published: January 2020

AbstractPostlaryngectomy sinonasal squamous cell carcinoma, being theoretically associated with exposure to the same risk factors or development of precancerous lesions due to altered nasal physiology, should warrant a thorough head and neck examination.
Development and validation of a chiral LC‐MS method for the enantiomeric resolution of (+) and (−)‐medetomidine in equine plasma by using polysaccharide‐based chiral stationary phases
Authors: Karakka Kal Abdul Khader , Nalakath Jahfar , Kunhamu Karatt Tajudheen , Perwad Zubair , Mathew Binoy , Subhahar Michael 
Published: January 2020

AbstractThe detection and separation of medetomidine enantiomers from the complex biological matrices poses a great analytical challenge, especially in the field of forensic toxicology and pharmacology. Couple of researchers reported resolution of medetomidine using protein‐based chiral columns, but the reported method is quiet challenging and tedious to be employed for routine analysis. This research paper reported a method that enables the enantio‐separation of medetomidine by using polysaccharide cellulose chiral column. The use of chiralcel OJ‐3R column was found to have the highest potential for successful chiral resolution. Ammonium hydrogen carbonate was the ideal buffer salt for chiral liquid chromatography (LC) with electrospray ionization (ESI)+ mass spectrometry (MS) detection for the successful separation and detection of racemic compound. The method was linear over the range of 0 to 20 ng/mL in equine plasma and the inter‐day precisions of levomedetomidine, dexmedetomidine were 1.36% and 1.89%, respectively. The accuracy of levomedetomidine was in the range of 99.25% to 101.57% and that for dexmedetomidine was 99.17% to 100.99%. The limits of quantification for both isomers were 0.2 ng/mL. Recovery and matrix effect on the analytes were also evaluated. Under the optimized conditions, the validated method can be adapted for the identification and resolution of the medetomidine enantiomers in different matrices used for drug testing and analysis.
The Role of Lone‐Pair Electrons in Pt–N Interactions for the Oxygen Reduction Reaction in Polymer Exchange Membrane Fuel Cells
Authors: Ham Kahyun , Shin Dongyoon , Lee Jaeyoung 
Published: January 2020

AbstractAn N‐doped carbon with various N concentrations was prepared by using a scalable ball‐milling method. The importance of the lone pair of electrons on the N species for the stability of Pt nanoparticles and their activity toward the oxygen reduction reaction was investigated. X‐ray spectroscopic analysis was used to investigate the interaction between Pt and the pyridinic N. The pyridinic N modified the Pt oxidation state and helped achieve size homogeneity and high catalytic activity by facilitating the rate‐determining step.
Role of noncanonical Wnt ligands and Ror‐family receptor tyrosine kinases in the development, regeneration, and diseases of the musculoskeletal system
Authors: Kamizaki Koki , Endo Mitsuharu , Minami Yasuhiro , Kobayashi Yasuhiro 
Published: January 2020

AbstractThe Ror‐family receptor tyrosine kinases (RTKs), consisting of Ror1 and Ror2, play crucial roles in morphogenesis and formation of various tissues/organs, including the bones and skeletal muscles, the so‐called musculoskeletal system, during embryonic development, by acting as receptors or coreceptors for a noncanonical Wnt protein Wnt5a. Furthermore, several lines of evidence have indicated that Ror1 and/or Ror2 play critical roles in the regeneration and maintenance of the musculoskeletal system in adults. Considering the anatomical and functional relationship between the skeleton and skeletal muscles, their structural and functional association might be tightly regulated during their embryonic development, development after birth, and their regeneration after injury in adults. Importantly, in addition to their congenital anomalies, much attention has been paid onto the age‐related disorders of the musculoskeletal system, including osteopenia and sarcopenia, which affect severely the quality of life. In this article, we overview recent advances in our understanding of the roles of Ror1‐ and/or Ror2‐mediated signaling in the embryonic development, regeneration in adults, and congenital and age‐related disorders of the musculoskeletal system and discuss possible therapeutic approaches to locomotive syndromes by modulating Ror1‐ and/or Ror2‐mediated signaling.
High‐severity wildfire leads to multi‐decadal impacts on soil biogeochemistry in mixed‐conifer forests
Authors: Dove Nicholas C. , Safford Hugh D. , Bohlman Gabrielle N. , Estes Becky L. , Hart Stephen C. 
Published: January 2020

AbstractDuring the past century, systematic wildfire suppression has decreased fire frequency and increased fire severity in the western United States of America. While this has resulted in large ecological changes aboveground such as altered tree species composition and increased forest density, little is known about the long‐term, belowground implications of altered, ecologically novel, fire regimes, especially on soil biological processes. To better understand the long‐term implications of ecologically novel, high‐severity fire, we used a 44‐yr high‐severity fire chronosequence in the Sierra Nevada where forests were historically adapted to frequent, low‐severity fire, but were fire suppressed for at least 70 yr. High‐severity fire in the Sierra Nevada resulted in a long‐term (44 +yr) decrease (>50%, P < 0.05) in soil extracellular enzyme activities, basal microbial respiration (56–72%, P < 0.05), and organic carbon (>50%, P < 0.05) in the upper 5 cm compared to sites that had not been burned for at least 115 yr. However, nitrogen (N) processes were only affected in the most recent fire site (4 yr post‐fire). Net nitrification increased by over 600% in the most recent fire site (P < 0.001), but returned to similar levels as the unburned control in the 13‐yr site. Contrary to previous studies, we did not find a consistent effect of plant cover type on soil biogeochemical processes in mid‐successional (10–50 yr) forest soils. Rather, the 44‐yr reduction in soil organic carbon (C) quantity correlated positively with dampened C cycling processes. Our results show the drastic and long‐term implication of ecologically novel, high‐severity fire on soil biogeochemistry and underscore the need for long‐term fire ecological experiments.
Background matching, disruptive coloration, and differential use of microhabitats in two neotropical grasshoppers with sexual dichromatism
Authors: Ramírez‐Delgado Víctor Hugo , Cueva del Castillo Raúl 
Published: January 2020

AbstractCryptic coloration is an adaptative defensive mechanism against predators. Color patterns can become cryptic through background coloration‐matching and disruptive coloration. Disruptive coloration may evolve in visually heterogeneous microhabitats, whereas background matching could be favored in chromatically homogeneous microhabitats. In this work, we used digital photography to explore the potential use of disruptive coloration and background matching in males and females of two grasshopper species of the Sphenarium genus in different habitats. We found chromatic differences in the two grasshopper species that may be explained by local adaptation. We also found that the females and males of both species are dichromatic and seem to follow different color cryptic strategies, males are more disruptive than females, whereas females have a high background matching with less disruptive elements. The selective pressures of the predators in different microhabitats and the differences in mobility between sexes may explain the color pattern divergence between females and males. Nevertheless, more field experiments are needed in order to understand the relative importance of disruptive and background matching coloration in the evolution of sexual dichromatism in these grasshoppers.
Restoring apoptosis dysregulation using survivin inhibitor in nasopharyngeal cancer
Authors: Shi Junli , Tan Soo Yee , Lee Andrea Zhe Ern , Zhang Siting , Sasidharan Swarnalatha Lucky , Wong Benjamin , Tan Min Han , Lim Chwee Ming 
Published: January 2020

AbstractBackgroundRestoring apoptosis dysregulation via survivin inhibition has been investigated in several cancers. In Epstein‐Barr Virus (EBV)‐driven nasopharyngeal cancer (NPC), virally induced oncogenes can upregulate survivin. Therefore, we seek to investigate the therapeutic efficacy of YM‐155 (a survivin inhibitor) in NPC, both in vitro and in vivo models.MethodsCytotoxicity, apoptosis, and active‐caspase 3 expression assays were performed.ResultsBoth NPC tissue and cells expressed high levels of survivin which were inhibited by YM‐155 in a dose‐dependent manner. In addition, YM‐155 induced apoptosis of NPC cells with an IC50 of 100 nM and inhibited tumor growth in vivo (P < 0.05). YM‐155 in combination with cisplatin or radiation significantly increased overall cytotoxicity as compared to YM‐155 monotherapy. In the xenograft model, YM‐155 plus radiation additively achieved significantly higher percentage of active‐caspase 3‐positive tumor cells than radiation alone (P < 0.05).ConclusionsYM‐155 is a potential therapeutic agent for NPC through inhibiting survivin and restoring apoptosis dysregulation.
Hepatitis B Virus Particles Activate Toll‐Like Receptor 2 Signaling Initially Upon Infection of Primary Human Hepatocytes
Authors: Zhang Zhenhua , Trippler Martin , Real Catherine I. , Werner Melanie , Luo Xufeng , Schefczyk Stefan , Kemper Thekla , Anastasiou Olympia E. , Ladiges Yvonne , Treckmann Juergen , Paul Andreas , Baba Hideo A. , Allweiss Lena , Dandri Maura , Gerken Guido , Wedemeyer Heiner , Schlaak Joerg F. , Lu Mengji , Broering Ruth 
Published: January 2020

BACKGROUND AND AIMS
To date, conflicting data exist as to whether hepatitis B virus (HBV) has the ability to induce innate immune responses. Here, we investigated cellular changes after the first contact between HBV and primary human hepatocytes (PHH) in vitro and in vivo.

APPROACH AND RESULTS
The exposure of PHH to HBV particles resulted in nuclear translocation of NFκB, followed by the expression and secretion of inflammatory cytokines (IL [interleukin] 1B, IL6, and TNF [tumor necrosis factor]). Ultraviolet irradiation of viral particles suppressed HBV infectivity but not the induction of cytokines in PHH, suggesting that the inoculum contains the immune‐inducing agent. Purified HBV particles on the whole, which were prepared from HBV DNA‐positive and protein‐rich fractions after heparin column separation, still had immune‐inducing capacity in PHH. The HBV‐induced gene expression profile was similar to that induced by toll‐like receptor 2 (TLR2) ligand Pam3Cys, but different from those induced by the viral sensors TLR3 or TLR7‐9. Treatment of PHH with both HBV particles and Pam3Cys led to phosphorylation of ERK (extracellular signal–regulated kinase), JNK, and p38 mitogen‐activated protein kinases as well as NFκB (nuclear factor kappa B). Finally, HBV‐induced gene expression could be neutralized by TLR2‐specific antibodies. Of note, pretreatment with an HBV entry inhibitor attenuated the TLR2‐mediated response to HBV, suggesting a receptor binding‐related mechanism. In liver‐humanized uPA/severe combined immunodeficient (SCID)/beige mice challenged with HBV in vivo, immune induction could only marginally be seen.

CONCLUSIONS
PHHs are able to sense HBV particles through TLR2, leading to an activation of anti‐HBV immune responses in vitro. These findings challenge the previously described stealth properties of HBV.
Diosmin for the prevention of ovarian hyperstimulation syndrome
Authors: Li Tingting , Zhu Wanshan , Liu Guihua , Fang Cong , Quan Song 
Published: January 2020

AbstractObjectiveTo evaluate the effect of oral diosmin on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) and explore the value of diosmin in preventing and treating OHSS.MethodA retrospective study of women attending a reproductive center in Guangzhou, China, between September and December 2016. The inclusion criterion was previous cancellation of embryo transfer after oocyte retrieval during IVF owing to a high risk of OHSS. The women were divided into two groups depending on whether they received oral diosmin (1000 mg twice daily for 10 days) after oocyte retrieval (diosmin group) or not (control group). Apart from diosmin, both groups underwent the same treatment. Baseline information and data related to OHSS were compared.ResultsOverall, 146 women were included: 74 in the diosmin group and 72 in the control group. The incidence of moderate‐to‐severe OHSS in the diosmin and control groups was 5/74 (6.2%) and 14/72 (13.4%), respectively (P=0.027). The control group included four cases of paracentesis due to ascites; there were no cases of paracentesis or severe OHSS in the diosmin group.ConclusionOral administration of diosmin effectively reduced both the incidence of moderate‐to‐severe OHSS and the severity of OHSS among high‐risk women.
Coordination of Multi‐Underwater Drones: Towards an Integrated Object‐Oriented Methodology in an Open‐Source Environment
Authors: Pham Hoang Anh , Soriano Thierry , Van Ngo Hien 
Published: January 2020

ABSTRACTThis paper's goal is to present a framework for studying multi‐underwater drone coordination, specifically formation control, based on a real‐time object‐oriented paradigms in an open‐source environment (the Operating Robot System Environment). This framework will capture the system's whole development life cycle, from the requirements specification to testing out the simulation and realization models. Based on this specialized framework, we can easily and quickly develop and verify the control algorithms while meeting future input requirements or manageable changes.
Ultrasound assisted, synthesis of N‐(7‐(R)‐2‐oxa‐8‐azabicyclo[4.2.0]octan‐8‐yl)isonicotinamide derivatives and their biological evaluation
Authors: Chavan Pravin , Salve Amol , Jadhav Shivaji , Pansare Dattatraya , Rai Megha 
Published: January 2020

AbstractIn this study, new series of azetidine derivatives were synthesized (4a‐n) from isoniazide (1), Aromatic aldehydes (2a‐n), dihydropyran (3) using SnCl2 catalyst, via one pot multicomponent reaction/cycloaddition reaction. The synthesized azetidine derivatives were characterized by IR, 1H NMR and 13C NMR and have been screened for antimicrobial, antituberculosis and anti‐inflammatory activities. In relation to Staphylococcus aureus (ATCC 25923) promising antibacterial activity was shown, compounds 4e and 4k, followed by compounds 4h, 4n, 4f, 4g and 4l. The synthesized azetidine derivatives, 4a, 4e, 4j and 4m (with zone 12 mm) displayed antituberculosis activity. But its lower potential than, the standard streptomycin (with zone 18 mm). Further 4d compound alone displayed similar activity.