bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folic Acid Functionalized Zirconium‐Based Metal–Organic Frameworks as Drug Carriers for Active Tumor‐Targeted Drug Delivery
Authors: Dong Hong , Yang Gui‐Xin , Zhang Xin , Meng Xiang‐Bin , Sheng Jing‐Li , Sun Xiao‐Jun , Feng Yu‐Jie , Zhang Feng‐Ming 
Published: August 2018

AbstractNanoscale metal–organic frameworks (NMOFs) have proven to be a class of promising drug carriers as a result of their high porosity, crystalline nature with definite structure information, and potential for further functionality. However, MOF‐based drug carriers with active tumor‐targeting function have not been extensively researched until now. Here we show a strategy for constructing active tumor‐targeted NMOF drug carriers by anchoring functional folic acid (FA) molecules onto the metal clusters of NMOFs. Two zirconium‐based MOFs, MOF‐808 and NH2‐UiO‐66, were chosen as models to reduce to the nanoscale for application as drug carriers, and then the terminal carboxylates of FA molecules were coordinated to Zr6 clusters on the surfaces of the nanoparticles by substitution of the original formate or terminal ‐OH ligands. The successful modification with FA was confirmed by solid‐state 13C MAS NMR and UV/Vis spectroscopy and other characterization methods. Drug loading and controlled release behavior at different pH were determined by utilizing the anticancer drug 5‐fluorouracil (5‐FU) as the model drug. Confocal laser scanning microscopy measurements further demonstrated that 5‐FU‐loaded FA‐NMOFs have excellent targeting ability through the efficient cellular uptake of FA‐NMOFs. This work opens up a new avenue to the construction of active tumor‐targeted NMOF‐based drug carriers with potential for cancer therapies.
Implementing a biogeographic ancestry inference service for forensic casework
Authors: Jin Soulbee , Chase Maretta , Henry Margaret , Alderson Gerry , Morrow James M. , Malik Sobia , Ballard David , McGrory Joel , Fernandopulle Neil , Millman Jonathan , Laird Jack 
Published: August 2018

AbstractThe Centre of Forensic Sciences has validated the Precision ID Ancestry Panel on the Ion S5™ Massively Parallel Sequencing instrument for use in forensic casework. The focus of this paper is the development of reporting guidelines for implementation of the biogeographic ancestry inference service based on the Admixture Prediction results produced using the Torrent Suite™ Software (Thermo Fisher Scientific). The Admixture Prediction algorithm estimates the genetic ancestry of a sample using seven root populations (Europe, East Asia, Oceania, America, Africa, South Asia, and Southwest Asia). For individuals that declared a single ancestry, there was a high correlation between the declared ancestry and the ancestry predicted by the algorithm. However, some individuals with declared ancestries of Southern Europe, Southwest Asia, South Asia and Horn of Africa had Admixture Predictions that were composed of two or more root populations at 20% or greater. For individuals with known admixed ancestry, the major component of their declaration was included in their results in all but one case. Based on these results, reporting guidelines were developed and subsequently evaluated using the Admixture Predictions of additional samples. This paper discusses the development and evaluation of these reporting guidelines, along with an implementation plan for forensic casework.
Interaction of groundwater with Lake Urmia in Iran
Authors: Vaheddoost Babak , Aksoy Hafzullah 
Published: August 2018

AbstractBeing a large hyper‐saline water body, Lake Urmia in north‐western Iran deals with a gradual decline in its water level. Most of the studies on Lake Urmia have neglected the groundwater issue. In this study, as a direct approach, the interaction between the groundwater level and the lake water level is investigated both in time and space by analysing the groundwater data compiled from observation wells surrounding the lake. Baseflow separation is considered as an indirect approach to understand the groundwater contribution to the river network flowing into the lake. It is determined that about 70% of run‐off in the rivers draining into the lake is born in the form of baseflow. An interaction between the lake and the groundwater storage is clearly seen from the analysis to conclude that groundwater has a potential to recharge the lake. Thus, the shrinkage of water level in Lake Urmia could be expected to accelerate with the drastic use of groundwater, which will be a disaster with no return.
A conceptual model for groundwater discharge to a coastal brackish lagoon based on seepage measurements (Ringkøbing Fjord, Denmark)
Authors: Duque Carlos , Haider Kinza , Sebok Eva , Sonnenborg Torben O. , Engesgaard Peter 
Published: August 2018

AbstractGroundwater discharge to a brackish lagoon (Ringkøbing Fjord) was quantified with seepage meters along four transects perpendicular to the shore during four seasons in 1 year. The objectives were to develop a conceptual model of the spatiotemporal variability of seepage and how landscape characteristics and saltwater intrusion affect seepage fluxes. The electrical conductivity of the groundwater was measured in vertical sediment profiles up to 3 m below the lagoon bed to assess the effects of the freshwater–saltwater interface location on flux distribution. The main differences compared with existing theoretical models are a lower discharge near the shore line (0–5 m) and two discharge peaks more offshore (15–20 and >25 m), which allowed the development of a conceptual model that is different from the classical concepts introduced for marine or lake environments and which can be representative of other similar areas. These differences are explained by the vegetation and organic material deposition in the near‐shore environment reducing discharge, the presence of the saline wedge leading to upward flow, and the increase of recirculation of brackish water due to wave pumping in areas offshore most exposed to the wind. The seasonal variability in discharge is smaller than the spatial variability between and within transects along the shoreline. Based on the conceptual model, fresh water discharge in a 20‐m‐wide fringe was calculated to be between 66 and 388 L·day−1·m−1 shore line, corresponding to a difference of a factor of six due to the variations in coast morphology and local characteristics of the area. The seasonal changes were responsible for changes of only 8% to 75% depending on the location.
Performance analysis of meningioma brain tumor classifications based on gradient boosting classifier
Authors: Selvapandian A. , Manivannan K. 
Published: August 2018

AbstractDetection of abnormal regions in brain image is complex process due to its similarity between normal and abnormal regions. This article proposes an automated technique for the detection of meningioma tumor using Gradient Boosting Machine Learning (GBML) classification method. This proposed system consists of preprocessing, feature extraction and classification stages. In this article, Grey Level Co occurrence Matrix (GLCM) features, intensity features, and Gray Level Run Length Matrix features are derived from the test brain MRI image. These derived feature set are classified using GBML classification approach. Morphological functions are used to segment the tumor region in classified abnormal brain image. The performance of the proposed system is evaluated on brain MRI images which are obtained from open access data set. The proposed methodology stated in this article achieves 93.46% of sensitivity, 96.54% of specificity, and 97.75% of accuracy with respect to ground truth images.
“I'd Still Prefer to Read the Hard Copy”: Adolescents’ Print and Digital Reading Habits
Authors: Loh Chin Ee , Sun Baoqi 
Published: August 2018

AbstractDoes print still matter in this digital age? What is the role of technology in reading? Do adolescents who enjoy reading view the reading of print and digital material differently from those who do not enjoy reading? Drawing on survey data from 6,005 students and focus group data with 96 students across six secondary schools, the authors conducted a mixed‐methods study to examine adolescents’ print and digital reading habits in Singapore. Findings show that adolescents prefer print but move toward more online reading as they get older. Adolescents’ online reading habits are reflective of their print preferences and behavior with physical books. The authors explain how both print and technology matter to motivate adolescent reading.
Forkhead box p3 controls progression of oral lichen planus by regulating microRNA‐146a
Authors: Wang Jing , Yang Lijie , Wang Luyao , Yang Yanjie , Wang Yannan 
Published: August 2018

AbstractOral lichen planus (OLP) is a severe T cell–mediated disorder of the mucosa, which causes chronic inflammation. Forkhead box P3 (Foxp3) regulates the immune response and plays an important role in immunological diseases. The current study aimed to determine the role of Foxp3 and microRNA (miR)‐146a in OLP. Western blot analysis and a quantitative real‐time polymerase chain reaction assay showed that the expression of Foxp3 and miR‐146a was upregulated in OLP tissues and in lipopolysaccharide (LPS)‐incubated HaCaT cells, compared with controls. Foxp3 inhibition significantly decreased miR‐146a expression, ameliorated LPS stimulation by decreased cell proliferation, and apoptosis in LPS‐incubated HaCaT cells as compared with the LPS group. Cotransfection of Foxp3 small interfering RNA and miR‐146a mimics elevated cell proliferation and apoptosis compared with the Foxp3 small interfering RNA group. In addition, miR‐146a overexpression upregulated, whereas miR‐146a inhibition downregulated, the proliferation and apoptosis of LPS‐incubated HaCaT cells. The target gene of miR‐–146a, tumor necrosis factor receptor–associated factor 6 (TRAF6), was predicted by bioinformatics software and identified by the luciferase reporter assay. Furthermore, Foxp3/miR‐146a elevated T regulatory cells and regulated TRAF6 expression in CD4+ T cells that were isolated from peripheral blood of patients with OLP. In conclusion, our study suggests that Foxp3 and miR‐146a regulate the progression of OLP by negatively regulating TRAF6, which may provide a promising therapeutic target for OLP treatment.
Molecular docking and simulation study for synthesis of alternative dapsone derivative as a newer antileprosy drug in multidrug therapy
Authors: Swain Shasank S. , Paidesetty Sudhir K. , Dehury Budheswar , Sahoo Jyotirmaya , Vedithi Sundeep Chaitanya , Mahapatra Namita , Hussain Tahziba , Padhy Rabindra N. 
Published: August 2018

AbstractLeprosy (causative, Mycobacterium leprae) continues to be the persisting public health problem with stable incidence rates, owing to the emergence of dapsone resistance that being the principal drug in the ongoing multidrug therapy. Hence, to overcome the drug resistance, structural modification through medicinal chemistry was used to design newer dapsone derivative(s) (DDs), against folic acid biosynthesis pathway. The approach included theoretical modeling, molecular docking, and molecular dynamic (MD) simulation as well as binding free energy estimation for validation of newly designed seven DDs, before synthesis. Theoretical modeling, docking, and MD simulation studies were used to understand the mode of binding and efficacy of DDs against the wild‐type and mutant dihydropteroate synthases (DHPS). Principal component analysis was performed to understand the conformational dynamics of DHPS‐DD complexes. Furthermore, the overall stability and negative‐binding free energy of DHPS‐DD complexes were deciphered using Molecular Mechanics/Poisson‐Boltzmann Surface Area technique. Molecular mechanics study revealed that DD3 possesses higher binding free energy than dapsone against mutant DHPS. Energetic contribution analysis portrayed that van der Waals and electrostatic energy contributes profoundly to the overall negative free energy, whereas polar solvation energy opposes the binding. Finally, DD3 was synthesized and characterized using Fourier‐transform infrared spectroscopy, UV, liquid chromatography‐mass spectrometry, and proton nuclear magnetic resonance techniques. This study suggested that DD3 could be further promoted as newer antileprosy agent. The principles of medicinal chemistry and bioinformatics tools help to locate effective therapeutics to minimize resources and time in current drug development modules.
Mechanism of imipenem resistance in metallo‐β‐lactamases expressing pathogenic bacterial spp. and identification of potential inhibitors: An in silico approach
Authors: Malathi Kullappan , Ramaiah Sudha 
Published: August 2018

AbstractThe World Health Organization reports that millions of people around the world are infected with antibiotic‐resistant bacteria. Such resistance is more common in Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae strains because of the expression of the metallo‐β‐lactamases (MBLs) namely Imipenemase (IMP)‐1, IMP‐2, New Delhi metallo‐β‐lactamases‐, Verona imipenemase (VIM)‐4, VIM‐5, and VIM‐7. We did an in silico analysis to understand the resistance mechanism of imipenem at the structural level. Our modeling studies reveal that the VIM‐4‐imipenem complex has highest binding energy and forms a stable complex as indicated by a consensus score (C‐score) value of 5.44. The intense interaction between the substrate and the β‐lactamases leads to the increased hydrolysis of the substrate resulting in rapid hydrolysis of the antibiotic imipenem by VIM‐4. Virtual screening of compounds from the ZINC database targeting VIM‐4 was done, and we found compound ZINC44608383 as the high binding energy compound with the C‐score value of 5.58. This compound could be exploited for inhibitor design and development. The current study helps us to understand the resistance mechanism of imipenem in MBL‐expressing strains. Also, we have identified a probable inhibitor for VIM‐4. We believe that our results will be useful for researchers in designing potent inhibitors for VIM‐4.
The equivalence of the Calcium‐Acetate‐Lactate and Double‐Lactate extraction methods to assess soil phosphorus fertility
Authors: van Laak Michael , Klingenberg Uwe , Peiter Edgar , Reitz Thomas , Zimmer Dana , Buczko Uwe 
Published: August 2018

AbstractA large variety of extraction methods are used worldwide for the estimation of “plant‐available P” in soils. In Germany, the standard extractants are Calcium‐Acetate‐Lactate (CAL) and Double‐Lactate (DL). Until now there is no validated transformation procedure available and studies on the comparability of both methods have reported conflicting evidence. The uncertainty about the equivalence of CAL‐P and DL‐P hinders a direct comparison of the P fertility status and P fertilizer recommendations across Germany. Based on 136 datasets for soil samples from an interlaboratory comparison program and three P fertilization field trial sites, for which plant‐available P had been determined by both the CAL and DL method, we assessed the comparability of both extraction methods and derived simple and multiple regression equations to transform DL‐P into CAL‐P values. On average, DL extracted 30% more P than CAL. However, this strongly depended on soil pH and carbonate content. A simple linear regression model explained 70% of the variance. However, if simple linear regression models were fitted to pH‐specific samples (pH range 4.5 to 7.0) the R2 increased to 0.96. Based on an independent validation dataset (n = 48) we demonstrated that such pH‐specific models were more accurate than models that did not consider pH when transforming DL‐P to CAL‐P values. Multiple regression results showed that out of soil pH, Corg, Nt, and C : N ratio, only soil pH improved the model. The transformation equations in this study provide a step towards an improved comparability of P fertility status assessments of soils across Germany.
Degradation of triadimefon and residue levels of metabolite triadimenol: tracing rapeseed from harvesting and storage to household oil processing
Authors: Li Yinghong , Hu Jing , Qian Mingrong , Wang Qiang , Zhang Hu 
Published: August 2018

AbstractBACKGROUNDTriadimefon is a fungicide used in agriculture to control fungal diseases such as sclerotinia sclerotiorum.RESULTSIn field trials, rape plants were sprayed with triadimefon at three different dosages during the flowering period. The degradation of triadimefon and the residue levels of its metabolite, triadimenol, in rapeseed obtained from harvesting, storage, and household oil processing were traced and evaluated. The pesticides were determined by high‐performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS) at each processing step. Triadimefon degraded completely and only its metabolite, triadimenol, was detected in rapeseed after harvesting. The stability of triadimenol in rapeseed was studied at weekly storage intervals, from 0 to 7 weeks at ambient temperature (25 °C) and freezing temperature (−20 °C), respectively. Storage temperature had an important influence on the residue levels of triadimenol. The processing factor (PF) was defined as the ratio of pesticide residue levels in rapeseed to rapeseed oil levels during household oil processing. The average PF of triadimenol was about 0.96 for a hot pressing technique and 0.88 for a cold pressing technique.CONCLUSIONDifferent storage conditions and food processing could reduce the pesticide level to a greater or lesser extent. However, it is not easy to eliminate or significantly weaken triadimenol once triadimefon has degraded completely. © 2018 Society of Chemical Industry
Ethical considerations for modern molecular pathology
Authors: Vos Shoko , van Diest Paul J , Ausems Margreet GEM , van Dijk Marijke R , de Leng Wendy WJ , Bredenoord Annelien L 
Published: August 2018

AbstractMolecular pathology is becoming an increasingly important discipline in oncology as molecular tumor characteristics will increasingly determine targeted clinical cancer care. In recent years, many technological advances have taken place that contributed to the development of molecular pathology. However, attention to ethical aspects has been lagging behind as illustrated by the lack of publications or professional guidelines. Existing guidelines or publications on ethical aspects of DNA sequencing are mostly aimed at germline or tumor sequencing in clinical genetics or biomedical research settings. As a result, large differences have been demonstrated in the process of tumor sequencing analysis between laboratories. In this perspective we discuss the ethical issues to consider in molecular pathology by following the process of tumor DNA sequencing analysis from the preanalytical to postanalytical phase. For the successful and responsible use of DNA sequencing in clinical cancer care, several moral requirements must be met, for example, those related to the interpretation and returning of genetic results, informed consent, and the retrospective as well as future use of genetic data for biomedical research. Many ethical issues are new to pathology or more stringent than in current practice because DNA sequencing could yield sensitive and potentially relevant data, such as clinically significant unsolicited findings. The context of molecular pathology is unique and complex, but many issues are similar to those applicable to clinical genetics. As such, existing scholarship in this discipline may be translated to molecular pathology with some adaptations and could serve as a basis for guideline development. For responsible use and further development of clinical cancer care, we recommend that pathologists take responsibility for the adequate use of molecular analyses and be fully aware and capable of dealing with the diverse, complex, and challenging aspects of tumor DNA sequencing, including its ethical issues. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Alveolar soft‐part sarcoma: Primary metastatic disease and metastatic relapse occurring during long‐term follow‐up
Authors: Sparber‐Sauer Monika , Seitz Guido , von Kalle Thekla , Vokuhl Christian , Scheer Monika , Münter Marc , Bielack Stefan S. , Kazanowska Bernarda , Ladenstein Ruth , Niggli Felix , Klingebiel Thomas , Fuchs Joerg , Koscielniak Ewa ,   on behalf of the CWS Study Group
Published: August 2018

AbstractBackgroundPatients with metastatic alveolar soft‐part sarcoma (ASPS) are known to have a very poor prognosis. Little is known about best treatment of primary metastatic disease (MD) or relapsed metastatic disease (rMD).Patients and methodsPatients with localized disease (LD), primary MD, and metastatic recurrence after complete remission (CR) treated within the CWS‐86, −91, −96, −2002P trials and the recent registry SoTiSaR (1985–2016) were analyzed.ResultsFifteen of 61 patients had primary metastases at initial diagnosis at the age of 14.6 years (range, 7.8–19.7). Nine of 46 patients with initial LD suffered of rMD at a median age of 9.9 years (range, 3.5–30), 3.75 years (0.75–21) after CR of primary disease. Complete resection (microscopically or macroscopically) was possible in 2 of 15 patients with MD and in 5 of 9 with rMD. RT was administered in 4 of 15 MD and 1 of 9 rMD. Chemotherapy was administered to 11 of 15 MD and 3 of 9 rMD, targeted therapy to 3 of 15 MD and 1 of 9 rMD. Median time to progression of patients treated with targeted therapy (n = 4), CHT (n = 14), and resection only (n = 6) was 56, 17, and 23 months, respectively. The 5‐year event‐free survival and overall survival (OS) rates were 19.8% and 61%, respectively, for patients with MD compared with 79% and 98% for patients with LD. The 5‐year progression‐free survival and OS were 67% and 100% for patients with rMD.ConclusionsComplete tumor resection correlates with long‐term survival in patients with primary and relapsed MD.
Is the cancer survival improvement in European and American adolescent and young adults still lagging behind that in children?
Authors: Trama Annalisa , Bernasconi Alice , McCabe Martin G. , Guevara Marcela , Gatta Gemma , Botta Laura ,   the RARECAREnet Working Group, Ries Lynn , Bleyer Archie 
Published: August 2018

AbstractImprovements during 1978 to 2006 in the 5‐year survival rate of adolescents and young adults (AYAs, age 15–39) and children with cancers common to both age groups were evaluated for 1978 to 2006 in Europe and the USA. AYAs had absolute survival increases of 25% and 15% in Europe and the USA, respectively, but in both cases, AYA 5‐year survival was, as of 2006, 4% lower than those in children. Acute lymphoblastic leukemia (ALL) explained most of the survival difference between AYAs and children on both the continents. In the USA, 20‐ to 39‐year‐olds with ALL have had less survival improvement than those in Europe.