bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra‐ and interreader reproducibility of PI‐RADSv2: A multireader study
Authors: Smith Clayton P. , Harmon Stephanie A. , Barrett Tristan , Bittencourt Leonardo K. , Law Yan Mee , Shebel Haytham , An Julie Y. , Czarniecki Marcin , Mehralivand Sherif , Coskun Mehmet , Wood Bradford J. , Pinto Peter A. , Shih Joanna H. , Choyke Peter L. , Turkbey Baris
Published: December 2018

Background

The Prostate Imaging Reporting and Data System version 2 (PI‐RADSv2) has been in use since 2015; while interreader reproducibility has been studied, there has been a paucity of studies investigating the intrareader reproducibility of PI‐RADSv2.

Purpose

To evaluate both intra‐ and interreader reproducibility of PI‐RADSv2 in the assessment of intraprostatic lesions using multiparametric magnetic resonance imaging (mpMRI).

Study Type

Retrospective.

Population/Subjects

In all, 102 consecutive biopsy‐naïve patients who underwent prostate MRI and subsequent MR/transrectal ultrasonography (MR/TRUS)‐guided biopsy.

Field Strength/Sequences

Prostate mpMRI at 3T using endorectal with phased array surface coils (TW MRI, DW MRI with ADC maps and b2000 DW MRI, DCE MRI).

Assessment

Previously detected and biopsied lesions were scored by four readers from four different institutions using PI‐RADSv2. Readers scored lesions during two readout rounds with a 4‐week washout period.

Statistical Tests

Kappa (κ) statistics and specific agreement (Po) were calculated to quantify intra‐ and interreader reproducibility of PI‐RADSv2 scoring. Lesion measurement agreement was calculated using the intraclass correlation coefficient (ICC).

Results

Overall intrareader reproducibility was moderate to substantial (κ = 0.43–0.67, Po = 0.60–0.77), while overall interreader reproducibility was poor to moderate (κ = 0.24, Po = 46). Readers with more experience showed greater interreader reproducibility than readers with intermediate experience in the whole prostate (P = 0.026) and peripheral zone (P = 0.002). Sequence‐specific interreader agreement for all readers was similar to the overall PI‐RADSv2 score, with κ = 0.24, 0.24, and 0.23 and Po = 0.47, 0.44, and 0.54 in T2‐weighted, diffusion‐weighted imaging (DWI), and dynamic contrast‐enhanced (DCE), respectively. Overall intrareader and interreader ICC for lesion measurement was 0.82 and 0.71, respectively.

Data Conclusion

PI‐RADSv2 provides moderate intrareader reproducibility, poor interreader reproducibility, and moderate interreader lesion measurement reproducibility. These findings suggest a need for more standardized reader training in prostate MRI.

Level of Evidence: 2

Technical Efficacy: Stage 2
The interaction of circRNAs and RNA binding proteins: An important part of circRNA maintenance and function
Authors: Zang Jiankun , Lu Dan , Xu Anding
Published: December 2018

The widespread expression of circular RNAs (circRNAs) is regarded as a feature of gene expression in highly diverged eukaryotes. Recent studies have shown that circRNAs can act as a miRNA sponge to repress miRNA function, participate in splicing of target genes, translate genes into protein and interact with RNA binding proteins (RBPs). RBPs are a broad class of proteins involved in gene transcription and translation, and interaction with RBPs is considered an important part of circRNA function, which can serve as an essential element underlying the functions of circRNAs, including genesis, translation, transcriptional regulation of target genes, and extracellular transport. In this mini‐review, we attempt to explore in detail the relationship between circRNAs and RBPs, and the interactions between the two factors. The goal of this review is to investigate the emerging studies of RBPs and circRNAs to better understand how their interaction alters cellular function.
What are the lessons from nature for doing well and doing good in different environments? A hybrid perspective of microfinance and slow money
Authors: Jayashankar Priyanka , Ashta Arvind , Rasmussen Mark
Published: December 2018

Ten criteria derived from the evolutionary theory allow the comparison of the characteristics of hybrid organizations in India and the United States. The resulting taxonomy enables us to extrapolate management lessons based on our theory building initiative. We contribute to hybrid theory by discussing how hybrid organizations mirror nature. We extend our theoretical framework to social enterprise theory and naturological theory. Finally, we recommend strategies for hybrid organizations to enhance their resilience and balance different priorities.
The inclusive business model revisited: An “extended resource‐based theory” (re)definition built on the investigation of three diversified inclusive enterprises in France
Authors: Ranjatoelina Jérémy Tantely
Published: December 2018

The inclusive business model concerns organizations whose strategic intent is to include in their value creation predominantly people who are being wasted by the dominant practices of actors on the market due to a presumption of negative performance. Inclusive business models have been initially defined by the United Nations Development Programme (UNDP). The “extended resource‐based theory” proposes a new typology of resources, which includes the “wasted” resource notion. The strategic intent is being seen as a main component of the business model and plays an interface role. Inclusive enterprises predominantly employ people who are excluded from the workplace. The suggested definition of the inclusive business model is extended to any form of organization fighting against social exclusion and it specifies that the included vulnerable people must be the majority among the human resources. Through the “extended resource‐based theory” prism, inclusive organizations have both alternative perception and intention toward wasted human resources and inclusive business models realize this alternative intent. This renewed view of the inclusive business model could facilitate its appropriation and application by both practitioners and researchers, and both in developed and in developing countries.
Hepatocellular carcinoma: resection with adjuvant hepatic artery infusion therapy vs resection alone. A systematic review and meta‐analysis
Authors: Moran Alexandra , Ramos Lorena Flor , Picado Omar , Pendola Fiorella , Sleeman Danny , Dudeja Vikas , Merchant Nipun , Yakoub Danny
Published: December 2018

Hepatocellular carcinoma (HCC) has a recurrence rate of up to 70% in 5 years after resection, detrimentally lowering survival. The role of adjuvant therapy remains controversial; therefore, the aim of this study was to evaluate the disease‐free and overall survival of patients with HCC, not candidates for transplantation, undergoing resection and adjuvant hepatic artery infusion therapy vs resection alone. Our meta‐analysis showed that adjuvant HAIC improves overall and disease‐free survival after resection, especially in tumors ≥7 cm.
Clinical implications of the eighth edition of the American Joint Committee on Cancer melanoma staging
Authors: Crompton Joseph G. , Gilbert Elizabeth , Brady Mary S.
Published: December 2018

The new edition of the American Joint Committee on Cancer staging system for melanoma builds on the foundation of prior editions but has several important improvements. The availability of regional nodal staging using sentinel lymph node biopsy (with subsequent follow‐up) has resulted in more accurate prognostication for patients and clinicians. This facilitates identification of those at higher risk for recurrence, and allows for the appropriate selection of patients for new adjuvant therapy and clinical trials. Although more complex than previous editions, the eighth edition will provide granularity to outcome analysis based on more precise risk stratification.
Discrimination of cancerous and healthy colon tissues: A new laser‐based method
Authors: Gündoğdu Yasemin , Alptekin Hüsnü , Karabağlı Pınar , Şahin Mustafa , Kilic Hamdi Ş.
Published: December 2018

Background

Femtosecond (fs) Laser Ionisation Mass Spectrometry (fs‐LIMS) on colon tissues are described and investigated using ionization/fragmentation processes in details to present a new application in this study. Linear Time of Flight (L‐TOF) mass analyzer was utilized to investigate paraffin‐embedded human tissue in this study. The effect of fs laser intensity on the spectral characteristics was investigated and interpreted due to mass spectra obtained using 800 nm wavelength with 90 fs pulses at 1 kHz repetition rate.

Objectives

Mass spectra of tissues were recorded from L‐TOF system and then analyzed by performing a statistical approach called Principal Component Analysis (PCA). The fs‐LIMS method applied is proposed as a new and pioneering technology to analyze tissues using L‐TOF system, as a human free fast and reliable intra‐operative cancer diagnosis method for guiding surgeon to clean the edges of cancerous tissues to be applied during the surgical operation, for pathological examinations. Fs‐LIMS provides some unique diagnosis opportunities to investigate biochemical characteristics of cancerous tissues leading to obtain sensitive, fast, and reliable results. The analysis of tissue is based on distribution of molecular ion (m/z) peaks in low mass region (<m/z 100) in mass spectra. Fs‐LIMS provides a great data for identification of tissues (healthy and cancerous) in details. The effect of laser pulse was investigated in this study and also different types of lasers are utilized for various investigations from surgery to spectroscopy.

Methods

The experimental setup mainly consists of an ultrafast (90 fs) laser system, a mass spectrometer, laser‐tissue interaction/ablation chamber, data collection, and analysis system with windows based fast digital‐storage oscilloscope, statistical application codes which have been developed by our group for analyses running under MATLAB software.

Results

Paraffin embedded colon tissues have been distinguished from each other with statistical approaches using fs‐LIMS based data as an alternative to histological and pathological examinations.

Conclusion

The fs‐LIMS method provides a powerful novel approach to identify and analyze tissues. This promising method provides a fast and reliable (free of human mistakes) diagnosis and guidance for pathologists, surgeons, and patients during surgical operations, as well as increase the significance of mass spectrometric tissue analysis methods, especially with those capability of molecular identification of tissues. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.
Stress corrosion cracking behavior of 310S stainless steel in supercritical water at different temperature
Authors: Liu Jinhua , Tan Yueming , Jiang Er , Gong Bin , Zhao Yongfu , Wang Yuan , Lu Yuanyuan
Published: December 2018

The stress corrosion cracking (SCC) behavior and tensile properties of 310S stainless steel were studied by slow strain rate tensile (SSRT) tests, which were carried out in oxygenated supercritical water at the temperature of 400, 550, and 620 °C, respectively. The distribution of chemical composition of oxide, tensile properties, fracture morphology of the materials were analyzed for evaluating the SCC susceptibility of 310S stainless steel, respectively. The results show that both the elongation and tensile strength decreased significantly with the increase of the temperature, implying that a higher temperature may lead to a higher SCC susceptibility. The remarkable changes of the morphology of the fracture surface and gauge surface of 310S stainless steel were observed at different temperatures, that is, from an entire ductile fracture at lower temperature to a brittle fracture at higher temperature. The temperature has significant effects on morphologies and thickness. Oxides with double layer were observed. TEM analysis revealed that the inner oxide layer is composed of Cr and O, and Ni‐enrichment can be observed to segregate at the metal‐oxide interface.
APOBEC3B promotes hepatocarcinogenesis and metastasis through novel deaminase‐independent activity
Authors: Ma Wei , Ho Daniel W‐H. , Sze Karen M‐F. , Tsui Yu‐Man , Chan Lo‐Kong , Lee Joyce M‐F. , Ng Irene O‐L.
Published: December 2018

Cytidine deaminase APOBEC3B (A3B) is known to play important roles in creating de novo genomic C‐to‐T mutations in cancers and contribute to induction of genomic instability. Our study evaluated the roles of A3B in the progression and metastasis of human hepatocellular carcinoma (HCC). Using whole‐transcriptome and whole‐exome sequencing, and quantitative PCR, we found that A3B was overexpressed in human HCCs and A3B expression was significantly correlated with the proportion of genomic C‐to‐A and G‐to‐T mutations. Upon clinicopathological correlation, higher A3B expression was associated with more aggressive tumor behavior. Wild‐type A3B (wt‐A3B) overexpression in HCC cells promoted cell proliferation, and cell migratory and invasive abilities in vitro, and tumorigenicity and metastasis in vivo. On the other hand, knockdown of A3B suppressed cell proliferation, migratory, and invasive abilities of HCC cells with high endogenous A3B level. However, to our surprise, overexpression of A3B deaminase‐dead double mutant (E68A/E255Q) led to similar results as wt‐A3B in HCC. Furthermore, overexpression of wt‐A3B and mutant A3B both enhanced cell cycle progression in HCC cells. Altogether, our data demonstrated a novel deaminase‐independent role of A3B in contributing to HCC tumorigenesis and metastasis.
Who's boss? Physiological measures during performance assessment
Authors: Balconi Michela , Venturella Irene , Fronda Giulia , Vanutelli Maria Elide
Published: December 2018

Leadership in organizations consists of a complex process, which includes the interpersonal relationship with collaborators. By using a neuroscientific approach, we evaluated the effect of the presence of unidirectional versus reciprocal feedback (provided only by the leader or by both figures), as well as the assignment of a quantitative or just a qualitative assessment. Skin conductance level and response (SCL and SCR), as well as heart rate (HR), have been recorded during a role playing. Results revealed increased emotional engagement (SCL/SCR) during no rating and reciprocal condition, as well as a stressful response (increased HR) during rating and unidirectional condition.
Pridopidine, a clinic‐ready compound, reduces 3,4‐dihydroxyphenylalanine‐induced dyskinesia in Parkinsonian macaques
Authors: Johnston Tom H. , Geva Michal , Steiner Lilach , Orbach Aric , Papapetropoulos Spyros , Savola Juha‐Matti , Reynolds Ian J. , Ravenscroft Paula , Hill Michael , Fox Susan H. , Brotchie Jonathan M. , Laufer Ralph , Hayden Michael R.
Published: December 2018

Background

Pridopidine, in development for Huntington's disease, may modulate aberrantl‐dopa‐induced effects includingl‐dopa‐induced dyskinesia (LID).

Objective

This study investigated whether pridopidine could reduce LID in the MPTP macaque model of Parkinson's disease and characterized the observed behavioral effects in terms of receptor occupancy.

Methods

The pharmacokinetic profile and effects of pridopidine (15‐30 mg/kg) on parkinsonism, dyskinesia, and quality of on‐time, in combination withl‐dopa, were assessed in MPTP macaques with LID. Pridopidine receptor occupancy was estimated using known in vitro binding affinities to σ1and dopamine D2receptors, in vivo PET imaging, and pharmacokinetic profiling across different species.

Results

Pridopidine produced a dose‐dependent reduction in dyskinesia (up to 71%, 30 mg/kg) and decreased the duration of on‐time with disabling dyskinesia evoked byl‐dopa by 37% (20 mg/kg) and 60% (30 mg/kg). Pridopidine did not compromise the anti‐parkinsonian benefit ofl‐dopa. Plasma exposures following the ineffective dose (15 mg/kg) were associated with full σ1occupancy (>80%), suggesting that σ1engagement alone is unlikely to account for the antidyskinetic benefits of pridopidine. Exposures following effective doses (20‐30 mg/kg), while providing full σ1occupancy, provide only modest dopamine D2occupancy (<40%). However, effective pridopidine doses clearly engage a range of receptors (including adrenergic‐α2C, dopamine‐D3, and serotoninergic‐5‐HT1Asites) to a higher degree than D2and might contribute to the antidyskinetic actions.

Conclusions

In MPTP macaques, pridopidine produced a significant decrease in LID without compromising the antiparkinsonian benefit ofl‐dopa. Although the actions of pridopidine were associated with full σ1occupancy, effective exposures are more likely associated with occupancy of additional, non‐sigma receptors. This complex pharmacology may underlie the effectiveness of pridopidine against LID. © 2018 International Parkinson and Movement Disorder Society
Construction of a hierarchy of negative‐order integrable Burgers equations of higher orders
Authors: Wazwaz Abdul‐Majid
Published: December 2018

In this work, we employ the recursion operator, the Burgers equation and its inverse operator, for constructing a hierarchy of negative‐order integrable Burgers equations of higher orders. The complete integrability of each established equation emerges by virtue of the correlation between integrability and recursion operators. We use the simplified Hirota's method to obtain multiple kink solutions for some of the derived equations, and in particular, for the generalized negative‐order Burgers equation.
Abnormality in Maternal Dietary Calcium Intake During Pregnancy and Lactation Promotes Body Weight Gain by Affecting the Gut Microbiota in Mouse Offspring
Authors: Li Ping , Tang Tiantian , Chang Xuelian , Fan Xiuqin , Chen Xiaoyu , Wang Rui , Fan Chaonan , Qi Kemin
Published: December 2018

Scope

To investigate the effects of calcium status in early life on adult body weight and the underlying mechanisms involved in gut microbiota and related lipid metabolism.

Methods and results

Three to four‐week‐old C57BL/6J female mice were fed diets with normal, insufficient, and excessive calcium respectively throughout pregnancy and lactation. The weaning male pups were fed with a high‐fat diet for 16 weeks, with a normal‐fat diet to the normal calcium group as control. The offspring fecal microbiota was analyzed by 16S rRNA high‐throughput sequencing, and mRNA expressions of genes were determined by the real‐time RT‐PCR. Maternal insufficient or excessive calcium intake exacerbated offspring obesity, with expressional changes in the Fasn, Acc1, LPL, Fiaf, and PPAR‐α genes in the liver or fat. The dysbiosis in gut microbiota in obese offspring was exacerbated by maternal imbalanced calcium intake, with increased Firmicutes and decreased Bacteroidetes in calcium insufficiency, and decreased Verrucomicrobia in calcium excess. Several genera, including Bacteroides, were reduced, and Lachnospiraceae and Lactobacillus were increased by maternal insufficient or excessive calcium intake.

Conclusion

Imbalance in maternal calcium intake promotes body weight gain in offspring, which may be mediated by calcium's modulation on the gut microbiota and lipid metabolism.
A compact and high gain substrate integrated horn array antenna system
Authors: Ramadurgakar Ameya , Song Heather H.
Published: December 2018

In this paper, a novel compact, lightweight and high gain array antennae system is demonstrated which is based on substrate integrated dielectric filled waveguide concepts. It is a planar design which can be easily fabricated with a common two‐layer substrate. The overall goal was to have a high gain so that this array antenna could be potentially used in autonomous unmanned aerial vehicle systems for collision avoidance. An initial model was designed, simulated and fabricated and, upon evaluation, was further modified to achieve a higher performance specification. Additionally, the design can be easily and inexpensively fabricated using standard substrates with a rapid prototyping platform. A two element array resulted in a simulated gain of 9.6 dB with a radiation pattern which had a maximum lobe between a broadside and an end‐fire. This was with a low loss substrate such as Rogers RT duroid 5880. For the design, a low dissipation factor material is preferable as it minimizes losses and also increases compactness of the entire antenna array.
Size‐adaptable “Trellis” structure for tailored MRI coil arrays
Authors: Zhang Bei , Brown Ryan , Cloos Martijn , Lattanzi Riccardo , Sodickson Daniel , Wiggins Graham
Published: December 2018

Purpose

We present a novel, geometrically adjustable, receive coil array whose diameter can be tailored to the subject in order to maximize sensitivity for a range of body sizes.

Theory and Methods

A key mechanical feature of the size‐adaptable receive array is its trellis structure that was motivated by similar structures found in gardening and fencing. Our implementation is a cylindrical trellis that features encircling, diagonally interleaved slats, which are linked together at intersecting points. The ensemble allows expansion or contraction to be controlled with the angle between the slats. This mechanical frame provides a base for radiofrequency coils wherein approximately constant overlap, and therefore coupling between adjacent elements, is maintained when the trellis is expanded or contracted. We demonstrate 2 trellis coil concepts for imaging lower extremity at 3T: a single‐row 8‐channel array built on a trellis support structure and a multirow 24‐channel array in which the coil elements themselves form the trellis structure.

Results

We show that the adjustable trellis array can accommodate a range of subject sizes with robust signal‐to‐noise ratio, loading, and coupling.

Conclusion

The trellis coil concept enables an array of surface coils to expand and contract with negligible effect on tuning, matching, and decoupling. This allows an encircling array to conform closely to anatomy of various sizes, which provides significant gains in signal‐to‐noise ratio.
The mechanics of urethral closure, incontinence and midurethral sling repair. Part 2 further experimental validation (1993‐2003)
Authors: Petros Peter , Abendstein Burghard
Published: December 2018

In

Part 1, The original 1990 science behind the MUS, the hypothesized closure mechanisms, and the prototype MUS itself were presented. The next phase of MUS development began in 1990 in collaboration with the late Ulf Ulmsten. It had two arms

Further development of the prototype MUS.

Further anatomical, imaging, urodynamic studies to validate the role of PUL in the closure mechanisms.

A second series of prototype MUS operations performed under LA/sedation resulted in a permanently implanted polypropylene sling and the MUS as is known today. The tape was elevated until no urine leaked on coughing. This demonstrated that the artificial PUL neoligament needed to be at a specific length to work. Anatomical, EMG and video ultrasound, and X‐ray studies confirmed three directional muscles contracted pubourethral (PUL) and uterosacral (USL) ligaments. The contribution of the horseshoe shaped rhabdosphincter (RS) to continence was directly tested with pressure measurements under live surgery conditions. It was concluded that the RS was responsible for pressure generation but not continence. Continence was a consequence of intraurethral resistance to flow created by the distal and proximal urethral closure mechanisms, both governed ultimately by the Law of Poiseuille.

Conclusions

The key element in curing USI is creation of a competent PUL using the collagenous neoligament surgical principle described in Part 1. This creates a firm insertion point for the three directional muscle forces, restoring their contractile strength and closure.
Quantifying cardiac‐induced brain tissue expansion using DENSE
Authors: Adams Ayodeji L. , Kuijf Hugo J. , Viergever Max A. , Luijten Peter R. , Zwanenburg Jaco J.M.
Published: December 2018

Brain tissue undergoes viscoelastic deformation and volumetric strain as it expands over the cardiac cycle due to blood volume changes within the underlying microvasculature. Volumetric strain measurements may therefore provide insights into small vessel function and tissue viscoelastic properties. Displacement encoding via stimulated echoes (DENSE) is an MRI technique that can quantify the submillimetre displacements associated with brain tissue motion. Despite previous studies reporting brain tissue displacements using DENSE and other MRI techniques, a complete picture of brain tissue volumetric strain over the cardiac cycle has not yet been obtained. To address this need we implemented 3D cine‐DENSE at 7 T and 3 T to investigate the feasibility of measuring cardiac‐induced volumetric strain as a marker for small vessel blood volume changes. Volumetric strain over the entire cardiac cycle was computed for the whole brain and for grey and white matter tissue separately in six healthy human subjects. Signal‐to‐noise ratio (SNR) measurements were used to determine the voxel‐wise volumetric strain noise. Mean peak whole brain volumetric strain at 7 T (mean ± SD) was (4.5 ± 1.0) × 10−4 (corresponding to a volume expansion of 0.48 ± 0.1 mL), which is in agreement with literature values for cerebrospinal fluid that is displaced into the spinal canal to maintain a stable intracranial pressure. The peak volumetric strain ratio of grey to white matter was 4.4 ± 2.8, reflecting blood volume and tissue stiffness differences between these tissue types. The mean peak volumetric strains of grey and white matter tissue were found to be significantly different (p < 0.001). The mean SNR at 7 T and 3 T of the DENSE measurements was 22.0 ± 7.3 and 7.0 ± 2.8 respectively, which currently limits a voxel‐wise strain analysis at both field strengths. We demonstrate that tissue specific quantification of volumetric strain is feasible with DENSE. This metric holds potential for studying blood volume pulsations in the ageing brain in healthy and diseased states.
A new algorithm for the shortest‐path problem
Authors: Elmasry Amr , Shokry Ahmed
Published: December 2018

In this article we propose a new single‐source shortest‐path algorithm that achieves the same O(n · m) time bound as the Bellman‐Ford‐Moore algorithm but outperforms it and other state‐of‐the‐art algorithms in many cases in practice. Our claims are supported by experimental evidence.
Second‐order cone programming formulation of discontinuous deformation analysis
Authors: Meng Jingjing , Cao Ping , Huang Jinsong , Lin Hang , Chen Yu , Cao Rihong
Published: December 2018

In classic discontinuous deformation analysis (DDA), artificial springs must be employed to enforce the contact condition through the open‐close iteration. However, improper stiffness parameters might cause numerical problems. The main goal of this paper is to propose a new framework of DDA using second‐order cone programming. The complementarity relationship at contacts can be formulated directly; thus, artificial springs are avoided. Stemming from the equations of momentum conservation of each block, the governing equations of DDA can be cast as convex optimization problems. The basic variables in the formulations can be either block displacements or contact forces. The derived optimization problems can be reformulated into a standard second‐order cone programming program, which can be solved using standard efficient optimization solvers. The proposed approach is validated by a series of numerical examples.
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

Objective

Cell‐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.

Methods

cfDNA 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.

Results

Size 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.

Conclusion

Plasma 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

The 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

A 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

Mycobacterium 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

There 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

Prediction 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.
Mobile Apps
Authors: Kubben Pieter
Published: December 2018

Mobile apps are an important source of data, but also an important tool for applying models. The goal of this chapter is to provide a short overview of relevant app development background including data collection tools, as well as provide a literature review on mobile clinical decision support systems. Regulatory issues will be touched upon to create awareness for this important topic.
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

Healthcare 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

Thevalue 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

Clinical 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

This 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.
Plastic pipe seals developed for aluminium structures
Authors: Atkinson Simon
Published: December 2018

Sweden's Roxtec Group – a provider of modular-based cable and pipe transits – has extended its range of plastic pipe seals to meet the demand for high-quality lightweight aluminium structures in the marine and offshore sector. The Roxtec Sleev-it™ penetration seals are available not only in steel, but also with an aluminium flange – for use in aluminium decks and bulkheads on board ships.
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

Consuming 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.
The Cake Walk Photo Girl and Other Footnotes in African American Musical Theatre
Authors: Klein Jeanne
Published: December 2018

On 22 August 1897, theAmerican Woman's Home Journalpublished seven photographs of “The Cake Walk as It Is Done by Genuine Negroes” in which “Williams and Walker Show How the Real Thing Is Done before the Journal Camera.” In this series, the African American stars Bert Williams, George Walker, Belle Davis, and Stella Wiley perform their popular cake walk act with situational humor in medias res before an unknown photographer in a nondescript space. Among the seven selected poses, one intriguing photograph in the lower right-hand corner depicts the encircled dancers gazing down upon an empty space in the center. The subject of their gaze becomes apparent when comparing the magazine images with the seven “Post Cards” Franz Huld published as part of his “Cake Walk/Negro Dance” series around 1901. Although the performers’ poses are the same, the postcard includes extra space between Wiley and Walker to feature a young girl of mixed racial heritage bending forward while hiking the back of her dress with her smiling face proudly held high (Fig. 1). If standing upright, she appears to be less than four feet tall and perhaps five to nine years of age. Given the obscure date and location of her photo shoot, her birth year could range anywhere from the mid-1880s to the early 1890s. Like Thomas F. DeFrantz, an African American dance theorist who gazes upon two 1920s photographs of other dancing girls, my gaze leads me to wonder about her identity, how she met and socialized with these four dancers, and whether she pursued a theatrical career.
From Totenmal to Trend: Wigman, Holm, and Theatricality in Modern Dance
Authors: Kattner Elizabeth
Published: December 2018

This article examines the development of theatricality in modern dance by comparing two dances: Mary Wigman's Totenmal (1930) and Hanya Holm's Trend (1937). By looking at the interplay between group and solo choreography, lighting design and themes, this paper will show how Holm combined the skills she learned codirecting Totenmal at the Dancers’ Congress in Munich to her work with American dance artists at the Bennington School of the Dance to create her first important work. It will examine why Trend was successful as a collaborative project, as well as show how it diverged ideologically from Wigman's work in the 1930s.