bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrichment of fetal and maternal long cell‐free DNA fragments from maternal plasma following DNA repair
Authors: Vong Joaquim S.L. , Jiang Peiyong , Cheng Suk‐Hang , Lee Wing‐Shan , Tsang Jason C.H. , Leung Tak‐Yeung , Chan K.C. Allen , Chiu Rossa W.K. , Lo Y.M. Dennis 
Published: December 2018

AbstractObjectiveCell‐free DNA (cfDNA) fragments in maternal plasma contain DNA damage and may negatively impact the sensitivity of noninvasive prenatal testing (NIPT). However, some of these DNA damages are potentially reparable. We aimed to recover these damaged cfDNA molecules using PreCR DNA repair mix.MethodscfDNA was extracted from 20 maternal plasma samples and was repaired and sequenced by the Illumina platform. Size profiles and fetal DNA fraction changes of repaired samples were characterized. Targeted sequencing of chromosome Y sequences was used to enrich fetal cfDNA molecules following repair. Single‐molecule real‐time (SMRT) sequencing platform was employed to characterize long (>250 bp) cfDNA molecules. NIPT of five trisomy 21 samples was performed.ResultsSize profiles of repaired libraries were altered, with significantly increased long (>250 bp) cfDNA molecules. Single nucleotide polymorphism (SNP)‐based analyses showed that both fetal‐ and maternal‐derived cfDNA molecules were enriched by the repair. Fetal DNA fractions in maternal plasma showed a small but consistent (4.8%) increase, which were contributed by a higher increment of long fetal cfDNA molecules. z‐score values were improved in NIPT of all trisomy 21 samples.ConclusionPlasma DNA repair recovers and enriches long cfDNA molecules of both fetal and maternal origins in maternal plasma.
Involvement of the serotonergic system and neuroplasticity in the antidepressant effect of curcumin in ovariectomized rats: Comparison with oestradiol and fluoxetine
Authors: Abd‐Rabo Marwa M. , Georgy Gehan S. , Saied Nashwa M. , Hassan Wafaa A. 
Published: December 2018

Antidepressant drugs are associated with many challenges due to their adverse impacts. Seeking alternatives through medicinal plants could have a great merit in overcoming these deleterious effects. This study was designed to investigate the potential mechanism of curcumin (CUR) in modifying the depression‐like behaviour in ovariectomised (OVX) rats, inference with fluoxetine (FLX) and oestradiol (E2). The treatments of OVX rats started after 1 month post ovariectomy and proceeded for 1 month. The experimental animals were divided into five groups: sham‐operated, OVX‐, OVX‐FLX (20 mg kg−1, i.p., daily), OVX‐E2 (100 μg kg−1, i.m., every other day), and OVX‐CUR‐ (100 mg kg−1, p.o., daily) treated groups. The results showed that CUR modulated the depression‐like behaviour using forced swimming test. It improved the serotonin content in many brain regions by upregulating tryptophan hydroxylase‐2 and 5‐hydroxytryptamine1A,2A receptor messenger RNA (mRNA) and downregulating monoamine oxidase A mRNA in the limbic system. Furthermore, it upregulated aromatase, brain‐derived neurotropic factor mRNA, and extracellular‐regulated kinase 1/2 protein in the limbic system, relative to FLX and E2, compared with OVX group. In conclusion, CUR appears to be safe and efficient agent as serotonin modulator similar to FLX and neurotrophic agent like E2, in improving the depression‐like behaviour in OVX rats.
Development of an active polylactic acid (PLA) packaging film by adding bleached bagasse carboxymethyl cellulose (CMCB) for mango storage life extension
Authors: Kamthai Suthaphat , Magaraphan Rathanawan 
Published: December 2018

This study aimed to determine the properties of a new active packaging film in order to extend the storage life of fresh mangoes by packing “Nam Dok Mai” mangoes (Mangifera indica Linn) with an active packaging film composed of biodegradable polymer and cellulose derivatives. A new packaging bag was produced primarily by blending polylactic acid (PLA) with spray‐dried carboxymethyl cellulose (CMC) from bleached bagasse (CMCB) at various concentrations (0%, 1%, 2%, and 4% w/w). The film thickness of the PLA and PLA/CMCB bags was 75 μm. Unpacked mangoes were used as control before the packaged ones were stored at export conditions (13 ± 1°C and 90 ± 5% relative humidity [RH]) to evaluate the efficiency of the PLA/CMCB film. Mango respiration and ethylene production rate were measured periodically in a packaging atmosphere as an indicator of ripeness. Changing fruit physio‐chemistry parameters were also studied, including weight loss, peel and flesh colour, firmness, total soluble solid (TSS), and total acidity (TA). The capacity of PLA/CMCB packaging to absorb water vapour and prolong mango shelf life was demonstrated, and active packaging function by control of RH was also demonstrated. The absorption of PLA/CMCB packaging was increased dramatically at 4% (w/w) CMCB mixed with PLA. At this CMCB concentration, the packaging film could extend the shelf life of mangoes for 42 days in export condition as well as decrease the physio‐chemistry parameters and respiratory rate, which were significantly enhanced when compared with those of control mangoes or unpacked mangoes (P ≤ 0.05), which had a shelf life of approximately 3 weeks.
The isocloso capped pentagonal bipyramid versus the closo bisdisphenoid in hypoelectronic eight‐vertex metallaboranes having 16 skeletal electrons
Authors: Şeptelean Raluca Anamaria , Attia Amr A. A. , Lupan Alexandru , King R. Bruce 
Published: December 2018

AbstractThe lowest energy structures for all of the eight‐vertex [M]CB6H7 {[M] = CpFe, CpRu. Co(CO)2, Rh(CO)2, (Me3P)2Fe(H), (Me3P)2Ru(H)}, [M]C2B5H7 {[M] = CpMn, CpRe, Cr(CO)3, Mo(CO)3}, and [M]2C2B4H6 ([M] = CpFe, CpRu) systems having 16 skeletal electrons were found by density functional theory to be capped pentagonal bipyramids providing a degree 6 vertex for a metal atom. Thus the capped pentagonal bipyramid plays a similar role for eight‐vertex metallaboranes with 16 skeletal electrons as the isocloso deltahedra play in 9‐ and 10‐vertex metallaboranes with 18 and 20 skeletal electrons, respectively. Furthermore, in all of these metallaborane systems the closo bisdisphenoidal structures were always found to be higher energy structures than their capped pentagonal bipyramidal isomers. For the bimetallic systems Cp2M2C2B4H6 (M = Fe, Ru) even higher energy hexagonal bipyramid structures with degree 6 vertices for both metal atoms were also found.
A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties
Authors: Odame Felix , Betz Richard , Hosten Eric C. , Krause Jason , Isaacs Michelle , Hoppe Heinrich C. , Khanye Setshaba D. , Sayed Yasien , Frost Prof Carminita , Lobb Kevin A. , Tshentu Zenixole R. 
Published: December 2018

AbstractA new method for the synthesis of tetraazatricyclic compounds by a reaction of benzoyl isothiocyanates with 2‐aminobenzimidazole is presented and a possible mechanism proposed. The new base‐catalyzed degradation of the tetraazatricyclic ring has been carried out. A reaction of benzoyl isothiocyanate with 2‐aminobenzoxazole, however, resulted in the formation of 3‐benzoyl‐1‐(2‐hydroxyphenyl)urea while a reaction with 2‐aminobenzothiazole gave 3‐(1,3‐benzothiazol‐2‐yl)‐1‐(benzoyl)thiourea. Density functional theory computed reaction mechanism for the formation of tetraazaatricyclic compounds is discussed. Biological screening of the compounds against Plasmodium falciparium and HIV‐1 protease showed very little activity but they were moderately active against Trypanosoma brucei with an IC50 of 19.71 μM for 11‐(3‐methoxyphenyl)‐1,8,0,12‐tetraazatricyclo [7.4.0.02,7]trideca‐2(7),3,5,9,11‐pentaene‐13‐thione (4).
Inhibition of Mycobacterium tuberculosis L,D‐Transpeptidase 5 by Carbapenems: MD and QM/MM Mechanistic Studies
Authors: Tolufashe Gideon F. , Halder Amit K. , Ibeji Collins U. , Lawal Monsurat M. , Ntombela Thandokuhle , Govender Thavendran , Maguire Glenn E. M. , Lamichhane Gyanu , Kruger Hendrik G. , Honarparvar Bahareh 
Published: December 2018

AbstractMycobacterium tuberculosis (Mtb) is the bacteria that currently claims the most number of human lives each year. The final step of peptidoglycan synthesis involves the generation of 4→3 and 3→3 transpeptide crosslinks catalyzed by D,D‐transpeptidase and L,D‐transpeptidase (Ldt) enzymes, respectively. Unlike in most other bacteria, for Mtb, the majority of the cross‐links are generated by L,D‐transpeptidases. LdtMt5 knock‐out strains of Mtb displayed aberrant growth, and are susceptibility to crystal violet, osmotic shock, and selected carbapenem antibiotics. Here, we used molecular dynamics (MD) and Quantum Mechanical (QM) simulations to probe the molecular interactions of LdtMt5 with carbapenems. LdtMt5 complexes with three carbapenems, ertapenem (ERT), imipenem (IMI) and meropenem (MERO) were simulated. The binding free energies of these complexes were calculated from the MD trajectories using the MM/GBSA approach, the theoretical results revealed higher ▵Gbind for ERT—LdtMt5 and IMI—LdtMt5 than MERO—LdtMt5. To further understand the catalytic reaction mechanism of LdtMt5 with the selected carbapenems, the possible reaction pathway was investigated. The high free energies of activation (▵G) for imipenem and meropenem, explain the reason behind inefficient binding of these carbapenems to LdtMt5. These results provide a better understanding of how the antibacterial agents function and will potentially contribute to the discovery of more potent LdtMt5 inhibitors.
Data Sources
Authors: Kubben Pieter 
Published: December 2018

AbstractThere are many sources that relevant data for clinical data science can originate from. The brief overview in this chapter highlights the most frequent sources, but is definitely not exhaustive. The goal of this chapter is to provide an introduction to the most common data sources and to familiarize the reader with basic terminology in this context, in order to more easily understand discussions in next chapters and in literature in general.
Reporting Standards and Critical Appraisal of Prediction Models
Authors: Wee Leonard , van Kuijk Sander M. J. , Dankers Frank J. W. M. , Traverso Alberto , Welch Mattea , Dekker Andre 
Published: December 2018

AbstractPrediction models have the potential to positively influence clinical decision-making and thus the overall quality of healthcare. The translational gap needs to be bridged between development of complex statistical models requiring multiple predictors and widespread usage in clinical consultation. A recent review found that inadequate quality of reporting of prediction modelling studies could be a contributing factor in slow transition to the clinic. This chapter emphasises the importance of high-quality reporting of modelling studies and the need for critical appraisal to understand the potential issues limiting generalizability of published models. Evidence synthesis (such as systematic reviews and pooled analysis of disparate models) are relatively under-represented in literature, though methodological studies and guidelines are now starting to appear.
Optimizing Care Processes with Operational Excellence & Process Mining
Authors: Boersma Henri J. , Leung Tiffany I. , Vanwersch Rob , Heeren Elske , van Merode G. G. 
Published: December 2018

AbstractHealthcare transformation is necessary to address rising costs of care. Operational Excellence can optimize care processes and create more value for each patient with the same resources. Operational Excellence uses different optimization tools in a continuous improvement (DMAIC-)cycle to optimize processes. In this regard, process mining can play an important role in discovering, analyzing and controlling care processes by making use of available data. Additionally, understanding the type of care process and care organization is important in order to choose the right Operational Excellence approach. Operational Excellence also includes a combination of leadership and work design (sociotechnical systems) which improves the success of process optimizations.
Value-Based Health Care Supported by Data Science
Authors: Leung Tiffany I. , van Merode G. G. 
Published: December 2018

AbstractThevalue agendainvolves measuring outcomes that matter and costs of care to optimize patient outcomes per dollar spent. Outcome and cost measurement in the value-based health care framework, centered around a patient condition or segment of the population, depends on data in every step towards healthcare system redesign. Technological and service delivery innovations are key components of driving transformation towards high-value health care. The learning health system and network-based thinking are complementary frameworks to the value agenda. Health care and medicine exist in a data-rich environment, and learning about how data can be used to measure and improve value of care for patients is and increasingly essential skill for current and future clinicians.
Standards in Healthcare Data
Authors: Schulz Stefan , Stegwee Robert , Chronaki Catherine 
Published: December 2018

AbstractClinical data interoperability requires shared specifications of meaning. This is the rationale for clinical data standards. Up until now, the adoption of such standards has been varied, although they are increasingly advocated in an area where proprietary specifications prevail, and semantic resources are geared to specific purposes and limited by boundaries of languages and jurisdictions. This chapter highlights the need of data standards in the context of the difficult and heterogeneous field of clinical data and the way how they are addressed by terminologies, ontologies and information models. It provides an overview of existing standards and discusses quality and implementation issues. Emphasis is also put on the eStandards methodology, which investigates needs for health data standards, supports the creation of standardised artefacts and defines actions for the implementation of standards.
Preparing Data for Predictive Modelling
Authors: van Kuijk Sander M. J. , Dankers Frank J. W. M. , Traverso Alberto , Wee Leonard 
Published: December 2018

AbstractThis is the first chapter of five that cover an introduction to developing and validating models for predicting outcomes for the individual patient. Such prediction models can be used for predicting the occurrence or recurrence of an event, or of the most likely value on a continuous outcome. We will mainly focus on the prediction of binary outcomes, such as the occurrence of a complication, recurrence of disease, the presence of metastases, remission, survival, etc. This chapter deals with the selection of an appropriate study design for a study on prediction, and on methods to manipulate the data before the statistical modelling can begin.
Effect of supplemental whey protein timing on postprandial glycaemia in centrally obese males
Authors: Allerton Dean M. , Rumbold Penny L. S. , West Daniel J. , Stevenson Emma J. 
Published: December 2018

AbstractConsuming whey protein before a meal may reduce postprandial glucose excursions, however, optimising timing of supplementation is important to improve its clinical utility. A total of thirteen centrally obese, insulin-resistant males (waist circumference: 121 (sem 3) cm; homeostasis model assessment for insulin resistance (HOMA-IR): 6·4 (sem 1·2)) completed four experimental conditions in a single-blind, crossover design. Participants consumed mixed-macronutrient breakfast and lunch meals on all occasions, with 20 g whey protein consumed 15 min before (PRE), alongside (DUR) or 15 min post-breakfast (POST) or omitted (CON). Capillary glucose and plasma concentrations of insulin, TAG and NEFA, in addition to subjective appetite ratings, were collected for 180 min after each meal. PRE and DUR reduced post-breakfast glucose peak by 17·0 (sem 1·9) % (P<0·001) and 9·2 (sem 2·9) % (P=0·046), respectively, compared with CON. Post-breakfast glucose AUC was lower following PRE compared with POST and CON (PRE: 982 (sem 30) v. POST: 1031 (sem 36) and CON: 1065 (sem 37) mmol/l×180 min; P≤0·042) but similar to DUR (1013 (sem 32) mmol/l×180 min; P=0·77). Insulin was lower during PRE, when compared with POST and DUR (both P≤0·042) but similar to CON. There were no between-condition differences in measures of postprandial lipaemia or appetite, and no effect of condition post-lunch. Consumption of whey protein as a preload or alongside a mixed-macronutrient breakfast reduces postprandial glucose excursions in centrally obese, insulin-resistant males. Whey consumed as a preload has superior glycaemic-lowering effects. Supplementation at breakfast does not alter glycaemic responses to subsequent meals.
Music as Organised Time: A strategy for transmedial composition and a questioning of the relation between music and sound
Authors: Blom Christian 
Published: December 2018

As a consequence of the universal alphabet of binary code, music is expanding to include transmedia practices. This text suggests that the seemingly exclusive bond between the art form of music and its primary medium, sound, might be opened up to include other media. If the practices of composers who also appear as sound- and kinetic artists are not recognised as music, possible contemporary perspectives on past music is lost and the future development of music is inhibited.The author presents an artistic perspective on transmediality, where two questions are addressed. The first is whether or not a transmedial structure can be made with light, movement and sound – and if so, how is this done? A strategy for transmedial composition with light, sound and movement is proposed, and exemplified with hand drawings. The second question raised in this article concerns whether or not transmedial compositions result in music. An idea of music as organised time is developed, and includes a discussion on the exclusive relation between art form and medium, especially between sound and music.
Sensing Heavy Precipitation With GNSS Polarimetric Radio Occultations
Authors: Cardellach E. , Oliveras S. , Rius A. , Tomás S. , Ao C. O. , Franklin G. W. , Iijima B. A. , Kuang D. , Meehan T. K. , Padullés R. , de la Torre Juárez M. , Turk F. J. , Hunt D. C. , Schreiner W. S. , Sokolovskiy S. V. , Van Hove T. , Weiss J. P. , Yoon Y. , Zeng Z. , Clapp J. , Xia‐Serafino W. , Cerezo F. 
Published: December 2018

AbstractThis study presents, for the first time ever, occulting signals of the Global Navigation Satellite Systems (GNSSs) acquired at two polarizations from a Low Earth Orbiter, and it shows that they sense heavy precipitation. The data sets are obtained from early stages of the Radio Occultation and Heavy Precipitation experiment aboard the PAZ satellite, launched in February 2018 and activated in May 2018. Preliminary calibration algorithms are applied to remove other systematic effects, and the resulting vertical profiles of polarimetric phase shift observations are compared to precipitation information from other missions. The analysis of the data shows consistency between Radio Occultation and Heavy Precipitation experiment aboard the PAZ satellite polarimetric phase shift measurements and presence of hydrometeors, with strong signatures from heavy precipitation. The polarimetric measurements also capture vertical features consistent with the vertical structures of precipitation.
Constraining Spatiotemporal Characteristics of Magma Migration at Piton De La Fournaise Volcano From Pre‐eruptive Seismicity
Authors: Duputel Z. , Lengliné O. , Ferrazzini V. 
Published: December 2018

AbstractVolcano‐tectonic seismicity has been recorded for decades on various volcanoes and is linked with the magma transport and reservoir pressurization. Yet earthquakes often appear broadly distributed such that magma movement is difficult to infer from its analysis. We explore the seismicity that occurred before eruptions at Piton de la Fournaise in the last 5 years. Using template matching and relocation techniques, we produce a refined image of the summit seismicity, demonstrating that most earthquakes are located on a ring structure. However, only a portion of this structure is activated before each eruption, which provides an indication as to the direction of the future eruptive site. Furthermore, we show that the delay between the pre‐eruptive swarm and the eruption onset is proportional to the distance of the eruptive fissures relative to the summit cone. This reveals that the beginning of the intrusion already bears information regarding the future eruption location.
Validation of anti-glucocerebrosidase antibodies for western blot analysis on protein lysates of murine and human cells
Authors: Qi Wenduo , Davidson Brad A. , Nguyen Matthew , Lindstrom Taylor , Grey Richard J. , Burnett Robert , Aflaki Elma , Sidransky Ellen , Westbroek Wendy 
Published: December 2018

Abstract
Gaucher disease (GD) is a rare lysosomal storage disorder caused by mutations in the GBA1 gene, encoding the lysosome-resident glucocerebrosidase enzyme involved in the hydrolysis of glucosylceramide. The discovery of an association between mutations in GBA1 and the development of synucleinopathies, including Parkinson disease, has directed attention to glucocerebrosidase as a potential therapeutic target for different synucleinopathies. These findings initiated an exponential growth in research and publications regarding the glucocerebrosidase enzyme. The use of various commercial and custom-made glucocerebrosidase antibodies has been reported, but standardized in-depth validation is still not available for many of these antibodies. This work details the evaluation of several previously reported glucocerebrosidase antibodies for western blot analysis, tested on protein lysates of murine gba+/+ and gba−/− immortalized neurons and primary human wild-type and type 2 GD fibroblasts.
Assessing molecular interactions with biophysical methods using the validation cross
Authors: Gossert Alvar D. 
Published: December 2018

Abstract
There are numerous methods for studying molecular interactions. However, each method gives rise to false negative- or false positive binding results, stemming from artifacts of the scientific equipment or from shortcomings of the experimental format. To validate an initial positive binding result, additional methods need to be applied to cover the shortcomings of the primary experiment. The aim of such a validation procedure is to exclude as many artifacts as possible to confirm that there is a true molecular interaction that meets the standards for publishing or is worth investing considerable resources for follow-up activities in a drug discovery project. To simplify this validation process, a graphical scheme — the validation cross — can be used. This simple graphic is a powerful tool for identifying blind spots of a binding hypothesis, for selecting the most informative combination of methods to reveal artifacts and, in general, for understanding more thoroughly the nature of a validation process. The concept of the validation cross was originally introduced for the validation of protein–ligand interactions by NMR in drug discovery. Here, an attempt is made to expand the concept to further biophysical methods and to generalize it for binary molecular interactions.