bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of 21q11.2‐q22.11 deletions in a fetus by NIPT
Authors: Zheng Yunyun , Chen Biliang , Wan Shanning , Xu Hui , Dang Yinghui , Song Tingting , Li Yu , Zhang Jianfang
Published: January 2019

Background

Non‐invasive prenatal testing (NIPT) is extensively used in the detection of fetal trisomies 21, 18, and 13, which is promptly becoming a common clinical practice. Concerned about the clinical application of non‐invasive detection of the fetal autosomal duplications or deletion.

Case Presentation

A 34‐year‐old, healthy pregnant woman was referred to the First Affiliated Hospital of the Air Force Medical University. The ultrasound examination indicates that low‐lying placenta, the fetus has a left ventricular bright spot and small amount of pericardial effusion. NIPT was chosen to further screen for fetal chromosomal abnormalities. NIPT results indicated an approximately 18 Mb deletion, which was verified by prenatal diagnosis. The chromosome microarray analysis (CMA) result showed about 19.2 Mb deletions in 21q11.2‐q22.11. The karyotype analysis result showed 46,XN,del(21)(q11.2q22.1). Prenatal diagnosis was consistent with NIPT results, and the paternal karyotype revealed no obvious abnormalities.

Conclusion

In this study, we successfully detected and diagnosed deletions of large fragments in chromosome 21 in a fetus using NIPT. This indicates that NIPT can provide effective genetic information for detecting fetal subchromosomal deletions/duplications.
Association of pro‐ and anti‐inflammatory cytokines in preeclampsia
Authors: Aggarwal Ruby , Jain Arun Kumar , Mittal Pratima , Kohli Mangala , Jawanjal Poonam , Rath Gayatri
Published: January 2019

Introduction

The pro‐ and anti‐inflammatory cytokines play crucial role in the development and functions of placenta. Any changes in these cytokines may be associated with many pregnancy‐related disorders like preeclampsia. Therefore, the present study is aimed to study the expression of pro‐inflammatory (TNF‐α, IL‐6) and anti‐inflammatory (IL‐4, IL‐10) cytokines in placenta and serum of preeclamptic pregnant women.

Material and Methods

For this study, a total of 194 cases of preeclamptic and control cases were enrolled in two Groups as per the gestational age that is, Group I (28‐36 weeks) and II (37 weeks onwards). The number of samples was 55 in Group I and 139 in Group II. The immunohistochemistry (IHC) and enzyme‐linked immunosorbent assay (ELISA) were conducted on placenta and serum of both preeclamptic and normal samples, respectively. IHC results were revalidated by reverse transcriptase PCR (RT‐PCR).

Results

Both Groups (I, II) of preeclampsia showed amended levels of pro‐ and anti‐inflammatory cytokines in placental tissues and serum samples. The levels of TNF‐α and IL‐6 were significantly increased in preeclamptic cases (P = 0.0001, P = 0.0001) while the IL‐4 and IL‐10 were downregulated (P = 0.0001, P = 0.0001) in comparison to control. In addition, a negative correlation was also observed between the two in preeclampsia (P = 0.0001).

Conclusion

The balanced ratio of pro‐ and anti‐inflammatory cytokines is essential to regulate the maternal inflammation system throughout pregnancy. Therefore, the gradual cytokine profiling of the pregnant women may be useful for the management of preeclampsia.
Synthesis, Characterization, and Theoretical Calculation of New Azo Dyes Derived from [1,5‐a]Pyrimidine‐5‐one Having Solvatochromic Properties
Authors: Şener Nesrin , Gür Mahmut , Çavuş M. Serdar , Zurnaci Merve , Şener İzzet
Published: January 2019

7‐Amino‐3‐phenylazo‐2‐methyl‐4H‐pyrazolo[1,5‐a]pyrimidine‐5‐one (3) was synthesized by the reaction of 5‐amino‐3‐methyl‐4‐phenylazo‐1H‐pyrazole and 2‐aminobenzothiazole with ethyl cyanoacetate in acetic acid at 150°C. Four novel heterocyclic azo disperse dyes were obtained by the coupling of heterocyclic amines‐based diazonium chloride with compound 3. They were purified and characterized by elemental analysis, FTIR, and 1H NMR. Furthermore, solvatochromic behaviors of related dyes were studied in detail by using ultraviolet–visible absorption spectrometer. The experimental data were supported by density functional theory using b3lyp/cc‐pvtz level calculations, and a detailed analysis of predicted tautomeric structures was made.
Classifying cognitive impairment based on the spatial heterogeneity of cerebral blood flow images
Authors: Shirzadi Zahra , Stefanovic Bojana , Mutsaerts Henri J.M.M. , Masellis Mario , MacIntosh Bradley J. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: January 2019

Background

The spatial coefficient of variation (sCoV) of arterial spin‐labeled (ASL) MRI can index cerebral blood flow spatial heterogeneity. This metric reflects delayed blood delivery—seen as a hyperintense ASL signal juxtaposed by hypointense regions.

Purpose

To investigate the use of ASL‐sCoV in the classification of cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's disease (AD) cohorts.

Study Type

Prospective/cohort.

Population

Baseline ASL images from AD neuroimaging initiative dataset in three groups of CU, MCI, and AD (N = 258).

Field Strength/Sequence

Pulsed ASL (PICORE QT2) images were acquired on 3 T Siemens systems (TE/TR = 12/3400 msec, TI1/2 = 700/1900 msec).

Assessment

ASL‐sCoV was calculated in temporal, parietal, occipital, and frontal lobes as well as whole gray matter.

Statistical Tests

The primary analysis used an analysis of covariance to investigate sCoV and cognitive group (CU, MCI, AD) associations. We also evaluated the repeatability of sCoV by calculating within‐subject agreement in a subgroup of CU participants with a repeat ASL. The secondary analyses assessed ventricular volume, amyloid burden, glucose uptake, ASL‐sCoV, and regional CBF as cognitive group classifiers using logistic regression models and receiver operating characteristic analyses.

Results

We found that global and temporal lobe sCoV differed between cognitive groups (P = 0.006). Post‐hoc tests showed that temporal lobe sCoV was lower in CU than in MCI (Cohen's d = –0.36) or AD (Cohen's d = –1.36). We found that sCoV was moderately repeatable in CU (intersession intraclass correlation = 0.50; intrasession intraclass correlation = 0.88). Subsequent logistic regression analyses revealed that temporal lobe sCoV and amyloid uptake classified CU vs. MCI (P < 0.01; accuracy = 78%). Temporal lobe sCoV, amyloid, and glucose uptake classified CU vs. AD (P < 0.01; accuracy = 97%); glucose uptake significantly classified MCI vs. AD (P < 0.01; accuracy = 85%).

Data Conclusion

We showed that ASL spatial heterogeneity can be used alongside AD neuroimaging markers to distinguish cognitive groups, in particular, cognitively unimpaired from cognitively impaired individuals.

Level of Evidence: 2

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2019;50:858–867.
Clinical Value of Shear Wave Elastography Added to Targeted Ultrasound (Second‐Look Ultrasound) in the Evaluation of Breast Lesions Suspicious of Malignancy Detected on Magnetic Resonance Imaging
Authors: Au Frederick Wing‐Fai , Ghai Sandeep , Lu Fang‐I , Lu Hua
Published: January 2019

Objectives

To determine the value of shear wave elastography (SWE) added to targeted ultrasound (US) after breast magnetic resonance imaging (MRI).

Methods

From July 2015 to October 2017, 40 patients who underwent targeted US evaluations of suspicious MRI‐detected American College of Radiology Breast Imaging Reporting and Data System category 4 lesions (mass or nonmass enhancement) were enrolled in this prospective study. B‐mode US and SWE examinations were performed to detect US correlates to MRI‐detected lesions; their Breast Imaging Reporting and Data System categories were recorded; lesions that were dark blue on a 6‐point color scale or had maximum elasticity of 30 kPa or less were categorized as soft. Biopsy was performed with US or MRI guidance, with the pathologic findings correlated with MRI, US, and SWE findings. The value of SWE for lesion detection and identification of benign lesions was determined.

Results

The mean age of the 40 patients was 51.1 years. There were 48 MRI‐detected lesions (20 cancers, 3 high‐risk lesions, and 25 benign lesions). Ultrasound correlates (8 category 3 and 25 category 4) were shown for 33 lesions (69%; P < .0001), with 16 cancers (80%; P < .0001) and 17 benign lesions. Shear wave elastography assisted detection of 3 (19%) cancers on US imaging. All 7 soft US category 3 lesions were benign (7 of 33 [21%]; P = .0014).

Conclusions

Shear wave elastography was useful with targeted US after breast MRI to increase cancer detection by US. A significant number of US correlates to MRI‐detected lesions could have been identified as benign (category 3 and soft) before biopsy, with the potential of short‐interval follow‐up of MRI‐detected lesions with benign US correlates instead of biopsy.
Deep Brain Stimulation as Management of Generalized Dystonia in the 18p Deletion Syndrome
Authors: Duma Stephen R. , Fois Alessandro F. , Morales‐Briceño Hugo , Fong Michael W.K. , Colebatch James G. , Colley Alison , McMaster Jacqueline , Mahant Neil
Published: January 2019

View Supplementary Video 1
Functional reconstruction of total upper eyelid defects with a composite radial forearm‐palmaris longus tenocutaneous free flap: A report of two cases
Authors: Iwanaga Hiroyuki , Nuri Takashi , Okada Masashi , Ueda Koichi
Published: January 2019

This report presents reconstruction of wide‐ and full‐thickness upper eyelid defects with a composite radial forearm–splitting palmaris longus tendon flap, which maintains eyelid opening and closing functions and supporting tissue in a Meibomian gland carcinoma in the right upper eyelid (case 1) and Merkel cell carcinoma in the right upper eyelid (case 2). After tumor resection with excisional margins, the defects involved the muscle, tarsal, and mucosa, with defect sizes of 60 × 40 mm and 85 × 40 mm, respectively. A radial forearm flap with the palmaris longus tendon was transferred. The tendon was split into two strips: the upper strip was fixed to the frontal muscles for the opening function and the lower strip to the medial palpebral ligament and orbicularis oculi muscle to maintain the closing function. Flap vessels were anastomosed to the superficial temporal artery and vein through the subdermal tunnel. Postoperative courses were uneventful. At the 5‐year (case 1) and 4‐year (case 2) follow‐up periods, there were no tumor recurrence and keratalgia, and the eyelid opening and closing functions were maintained. This approach may contribute to achievement of not only the opening function but also the closing function of the reconstructed eyelid.
Energy stable numerical scheme for the viscous Cahn–Hilliard–Navier–Stokes equations with moving contact line
Authors: Cherfils Laurence , Petcu Madalina
Published: January 2019

In the present article we study the numerics of the viscous Cahn–Hilliard–Navier–Stokes model, endowed with dynamic boundary conditions which allow us to take into account the interaction between the fluids interface and the moving walls of the physical domain. In what follows, we propose an energy stable temporal scheme for the problem and we prove the stability and the unconditional solvability of the discretization proposed. We also propose a fully discrete scheme for which we prove the stability and the unconditional solvability. Numerical simulations are presented to illustrate the theoretical results.
125I interstitial brachytherapy in management of pediatric skull base tumors
Authors: Chen Peng , Wu Wen‐Jie , Yi Zhi‐Qiang , Ma Xiao‐Li , Zhao Wei‐Hong , Zhang Jian‐Guo
Published: January 2019

Background

The purpose of this study was to present our preliminary assessment of the safety and efficacy of 125I interstitial brachytherapy (IBT) in the management of pediatric skull base tumors.

Methods

Thirty pediatric patients with skull base tumors treated with 125I IBT from April 2007 to May 2017 were included in this study. The probabilities of local control (LC) and overall survival (OS) were calculated by the Kaplan–Meier method.

Results

The one‐ and two‐year LC rates were 96.7% and 74.8%, respectively. The one‐ and two‐year OS rates were 93.3% and 72.2%, respectively. No severe acute toxicity was observed. Severe late toxicities were observed in one (3.33%) of 30 patients.

Conclusion

125I IBT is effective and safe in the management of pediatric skull base tumors, with satisfactory cosmetic and functional outcomes.
Characterization and structure determination of prolyl‐tRNA synthetase from Pseudomonas aeruginosa and development as a screening platform
Authors: Pena Noah , Dranow David M. , Hu Yanmei , Escamilla Yaritza , Bullard James M.
Published: January 2019

Pseudomonas aeruginosa is an opportunistic multi‐drug resistant pathogen implicated as a causative agent in nosocomial and community acquired bacterial infections. The gene encoding prolyl‐tRNA synthetase (ProRS) from P. aeruginosa was overexpressed in Escherichia coli and the resulting protein was characterized. ProRS was kinetically evaluated and the KM values for interactions with ATP, proline, and tRNA were 154, 122, and 5.5 μM, respectively. The turn‐over numbers, kcatobs, for interactions with these substrates were calculated to be 5.5, 6.3, and 0.2 s−1, respectively. The crystal structure of the α2 form of P. aeruginosa ProRS was solved to 2.60 Å resolution. The amino acid sequence and X‐ray crystal structure of P. aeruginosa ProRS was analyzed and compared with homologs in which the crystal structures have been solved. The amino acids that interact with ATP and proline are well conserved in the active site region and overlay of the crystal structure with ProRS homologs conforms to a similar overall three‐dimensional structure. ProRS was developed into a screening platform using scintillation proximity assay (SPA) technology and used to screen 890 chemical compounds, resulting in the identification of two inhibitory compounds, BT06A02 and BT07H05. This work confirms the utility of a screening system based on the functionality of ProRS from P. aeruginosa.
Further Refining the de Sitter Swampland Conjecture
Authors: Andriot David , Roupec Christoph
Published: January 2019

We propose an alternative refined de Sitter conjecture. It is given by a natural condition on a combination of the first and second derivatives of the scalar potential. We derive our conjecture in the same weak coupling, semi‐classical regime where the previous refined de Sitter conjecture was derived, using the same tools together with a few more assumptions that we discuss. We further test and constrain free parameters in our conjecture using data points of a classical type IIA supergravity setup. Interestingly, our conjecture easily accommodates slow‐roll single field inflation with a concave potential, favored by observations. The standard quintessence potential is in tension with our new conjecture, and we thus propose a different type of quintessence model.
The stability and nonlinear evolution of quasi-geostrophic toroidal vortices
Authors: Reinaud Jean N. , Dritschel David G.
Published: January 2019

We investigate the linear stability and nonlinear evolution of a three-dimensional toroidal vortex of uniform potential vorticity under the quasi-geostrophic approximation. The torus can undergo a primary instability leading to the formation of a circular array of vortices, whose radius is approximately the same as the major radius of the torus. This occurs for azimuthal instability mode numbers $m\geqslant 3$, on sufficiently thin tori. The number of vortices corresponds to the azimuthal mode number of the most unstable mode growing on the torus. This value of $m$ depends on the ratio of the torus’ major radius to its minor radius, with thin tori favouring high mode $m$ values. The resulting array is stable when $m=4$ and $m=5$ and unstable when $m=3$ and $m\geqslant 6$. When $m=3$ the array has barely formed before it collapses towards its centre with the ejection of filamentary debris. When $m=6$ the vortices exhibit oscillatory staggering, and when $m\geqslant 7$ they exhibit irregular staggering followed by substantial vortex migration, e.g. of one vortex to the centre when $m=7$. We also investigate the effect of an additional vortex located at the centre of the torus. This vortex alters the stability properties of the torus as well as the stability properties of the circular vortex array formed from the primary toroidal instability. We show that a like-signed central vortex may stabilise a circular $m$-vortex array with $m\geqslant 6$.
Pesticide Use and Risk Aversion in the French Wine Sector
Authors: Aka Joël , Ugaglia Adeline Alonso , Lescot Jean-Marie
Published: January 2019

This paper studies the risk attitudes of winegrowers in France. In French viticulture, most of the production is done under an appellation regime that constrains maximum authorized yields. We consider a trans-log cost function under the constraint of this maximum yield and estimate winegrowers' attitudes to risk. Our estimates are based on the European Farm Accountancy Data Network database (2005–2014) and data from the French National Institute of Origin and Quality. We find that winegrowers are risk averse. For the majority of winegrowers, risk aversion is declining with expected profit. In the Champagne region, however, where expected profits are far higher than in the other regions, we observe the reverse relation: winegrowers become more risk averse as expected profits rise. (JEL Classifications: C13, C33, O33, Q16).
Mineralogy, geochemistry and40Ar–39Ar geochronology of the Barda and Alech complexes, Saurashtra, northwestern Deccan Traps: early silicic magmas derived by flood basalt fractionation
Authors: Cucciniello Ciro , Choudhary Ashwini Kumar , Pande Kanchan , Sheth Hetu
Published: January 2019

Most continental flood basalt (CFB) provinces of the world contain silicic (granitic and rhyolitic) rocks, which are of significant petrogenetic interest. These rocks can form by advanced fractional crystallization of basaltic magmas, crustal assimilation with fractional crystallization, partial melting of hydrothermally altered basaltic lava flows or intrusions, anatexis of old basement crust, or hybridization between basaltic and crustal melts. In the Deccan Traps CFB province of India, the Barda and Alech Hills, dominated by granophyre and rhyolite, respectively, form the largest silicic complexes. We present petrographic, mineral chemical, and whole-rock geochemical (major and trace element and Sr–Nd isotopic) data on rocks of both complexes, along with40Ar–39Ar ages of 69.5–68.5 Ma on three Barda granophyres. Whereas silicic magmatism in the Deccan Traps typically postdates flood basalt eruptions, the Barda granophyre intrusions (and the Deccan basalt flows they intrude) significantly pre-date (by 3–4 My) the intense 66–65 Ma flood basalt phase forming the bulk of the province. A tholeiitic dyke cutting the Barda granophyres contains quartzite xenoliths, the first being reported from Saurashtra and probably representing Precambrian basement crust. However, geochemical–isotopic data show little involvement of ancient basement crust in the genesis of the Barda–Alech silicic rocks. We conclude that these rocks formed by advanced (70–75 %), nearly-closed system fractional crystallization of basaltic magmas in crustal magma chambers. The sheer size of each complex (tens of kilometres in diameter) indicates a very large mafic magma chamber, and a wide, pronounced, circular-shaped gravity high and magnetic anomaly mapped over these complexes is arguably the geophysical signature of this solidified magma chamber. The Barda and Alech complexes are important for understanding CFB-associated silicic magmatism, and anorogenic, intraplate silicic magmatism in general.
Ship Heading Control with Speed Keeping via a Nonlinear Disturbance Observer
Authors: Liu Zhiquan , Lu Xiaoyang , Gao Diju
Published: January 2019

The control problem for a ship steering system with speed loss is discussed in this paper. Two methods are proposed to deal with the unknown bounded disturbance for a sliding mode controller applied to a nonlinear surface vessel heading control system. The system uncertainties caused by speed changes are taken as internal disturbances, while the wave moments are considered as external disturbances. A feedback linearization method is adopted to simplify the nonlinear system. An adaptive method and a Nonlinear Disturbance Observer (NDO) are proposed for course keeping manoeuvres and speed keeping in vessel steering and provide robust performance for time varying wave disturbance and actuator dynamics. Furthermore, the overall stability conditions of the proposed controllers are analysed by Lyapunov's direct method. Finally, simulation results using the characteristics of a naval vessel illustrate the effectiveness of the presented control algorithms.
Moderation of associations between maternal parenting styles and Australian pre-school children’s dietary intake by family structure and mother’s employment status
Authors: Burnett Alissa J , Worsley Anthony , Lacy Kathleen E , Lamb Karen E
Published: January 2019

Objective

To examine associations between maternal parenting style and pre-school children’s dietary intake and to test whether perceived maternal time pressures, parenting arrangements and employment status influence these relationships.

Design

This cross-sectional study examined mothers’ reports of their child’s frequency of consumption of eight food and drink groups, including sugar-sweetened beverages (SSB), unhealthy snacks, takeaway foods, fruit and vegetables. Parenting styles were classified as authoritative, authoritarian, permissive or disengaged using two parenting dimensions (warmth and control). The moderating roles of parenting arrangements, indexed by number of parents in the home and maternal employment status, were assessed. Associations were examined using multinomial regression.

Setting

Data were from the infant and child cohorts in the Longitudinal Study of Australian Children.

Participants

Children aged 4–5 years from both cohorts (infant:n3607; child:n4661) were included.

Results

Compared with children of disengaged mothers, children of authoritative mothers consumed most unhealthy foods less frequently, and fruit and vegetables more frequently. Results suggested parenting arrangements and mothers’ working status may moderate associations between parenting styles and SSB, takeaway foods, takeaway snacks and fruit consumption.

Conclusions

These findings suggest that authoritative parenting style is associated with a higher consumption of fruit and vegetables and a lower consumption of unhealthy foods among children. However, parenting arrangements and the mothers’ working status may influence these relationships. Further research is required to examine the influence of other potential moderators of parenting style/food consumption relationships such as household time and resource limitations.
Public pension wealth and household asset holdings: new evidence from Belgium
Authors: Lefebvre Mathieu , Perelman Sergio
Published: January 2019

It has been long suggested that public pension wealth may crowd out household savings. However, there remains controversy about the extent of this displacement effect. In this paper we use an original microsimulation model based on retrospective survey data collected through the third wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) to estimate the displacement effect of public pension wealth on other wealth in Belgium. Combining this rich dataset with an accurate estimation of the individual pension entitlements allows us to circumvent some of the main measurement error problems faced by previous studies. We estimate that an extra euro of public pension wealth is associated with about 14–25 cent decline in households’ non-pension wealth.
Emission Characteristics of Primary Brown Carbon Absorption From Biomass and Coal Burning: Development of an Optical Emission Inventory for China
Authors: Tian Jie , Wang Qiyuan , Ni Haiyan , Wang Meng , Zhou Yaqing , Han Yongming , Shen Zhenxing , Pongpiachan Siwatt , Zhang Ningning , Zhao Zhuzi , Zhang Qian , Zhang Yue , Long Xin , Cao Junji
Published: January 2019

Brown carbon (BrC) affects the Earth's radiative balance due to its strong light absorption at short wavelengths. A custom‐made combustion chamber was used to simulate biomass and coal burning and to investigate the emission characteristics of BrC absorption. Absorption Ångström exponents (AAEs) at the wavelength pair of 370 and 880 nm ranged from 1.19 to 3.25, suggesting the possible existence of BrC in biomass‐ and coal‐burning emissions. Based on the assumption that AAEBC = 1.0, BrC from biomass burning contributed to 41–85% of the total particles light absorption at 370 nm, which is much higher than that from coal burning (15–18%). The estimated absorption emission factors of BrC at 370 nm for biomass and coal burning were 15–47 and 2–13 m2/kg, respectively. A 10 × 10 km gridded BrC optical emission inventory for biomass and coal burning in China for 2015 was developed based on the measured absorption emission factors of BrC values and high‐resolution activity data. The total annual BrC absorption cross section emissions from biomass and residential coal burning were 4,194 Gm2 (relative uncertainty at the 95% confidence level of −33.2, 41.2%) and 615 Gm2 (−39.3, 40.1%), respectively. These results should be useful for improving estimates of the radiative effects of BrC in China.
Quantitative High‐Resolution Reexamination of a Hypothesized Ocean Shoreline in Cydonia Mensae on Mars
Authors: Sholes Steven F. , Montgomery David R. , Catling David C.
Published: January 2019

Primary support for ancient Martian oceans has relied on qualitative interpretations of hypothesized shorelines on relatively low‐resolution images and data. We present a toolkit for quantitatively identifying paleoshorelines using topographic, morphological, and spectroscopic evaluations. In particular, we apply the validated topographic expression analysis of Hare et al. (2001,https://doi.org/10.1029/2001JB000344) for the first time beyond Earth, focusing on a test case of putative shoreline features along the Arabia level in northeast Cydonia Mensae, as first described by Clifford and Parker (2001,https://doi.org/10.1006/icar.2001.6671). Our results show these curvilinear features are inconsistent with a wave‐generated shoreline interpretation. The topographic expression analysis identifies a few potential shoreline terraces along the historically proposed contacts, but these tilt in different directions, do not follow an equipotential surface (even accounting for regional tilting), and are not laterally continuous. Lineaments appear blocky in nature at small scales, and they bifurcate, truncate, and merge along track. These features are more consistent with material boundaries for lithological units exposed along a degraded crater wall. These results do not preclude the existence of an ancient hemispheric ocean, but the geophysical and high‐resolution topographic data at this site do not support such an interpretation.
The Integrated Prevention Model of Pain—Chronic Pain Prevention in the Primary Care Setting
Authors: Salamon Katherine S. , Cullinan Colleen C.
Published: January 2019

Objective: Chronic pain is a significant problem that affects a large percentage of children around the world ( King et al., 2011 ). It is widely accepted that pediatric chronic pain can lead to functional impairment, including decreased school attendance, social withdrawal, and decreased participation in extracurricular activities ( Huguet & Miró, 2008 ; Perquin et al., 2000 ). However, there is a paucity of research examining prevention of chronic pain in children and adolescents ( King et al., 2011 ). Because pain accounts for 20–40% of primary care appointments during childhood and adolescence ( De Inocencio, 2004 ), understanding how to identify youth on the trajectory to chronic pain and provide targeted treatment is essential. Methods: This paper proposes a model of integrating cognitive-behavioral therapy for pain management into a primary care setting as a secondary prevention technique to reduce the incidence of pediatric chronic pain. Case illustrations are utilized to highlight intervening points within primary care. Results: Using principles from Kazak’s (2006) Pediatric Psychosocial Prevention Health Model, integrated primary care providers may be in an ideal position to reduce the incidence of pediatric chronic pain and subsequent financial, social, emotional, and educational burden. Conclusions: The Integrated Prevention Model for Pain offers a way to prevent pediatric chronic pain at the primary care level. Recommendations at the various intervention levels, implementation strategies, and future directions are provided.

Implications for Impact Statement

Chronic pain is a significant problem that leads to a negative impact on the life of the adolescent and their family. This paper aims to explore a model of integrating treatment for pain into primary care settings to decrease the number of youth affected by pediatric chronic pain.
Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: the impact of other vaginal pathogens living as neighbors
Authors: Castro Joana , Machado Daniela , Cerca Nuno
Published: January 2019

Bacterial vaginosis (BV) is characterized by a highly structured polymicrobial biofilm, which is strongly adhered to the vaginal epithelium and primarily consists of the bacterium Gardnerella vaginalis. However, despite the presence of other BV-associated bacteria, little is known regarding the impact of other species on BV development. To gain insight into BV progress, we analyzed the ecological interactions between G. vaginalis and 15 BV-associated microorganisms using a dual-species biofilm model. Bacterial populations were quantified using a validated peptide nucleic acid fluorescence in situ hybridization approach. Furthermore, biofilm structure was analyzed by confocal laser scanning microscopy. In addition, bacterial coaggregation ability was determined as well as the expression of key virulence genes. Remarkably, our results revealed distinct biofilm structures between each bacterial consortium, leading to at least three unique dual-species biofilm morphotypes. Furthermore, our transcriptomic findings seem to indicate that Enterococcus faecalis and Actinomyces neuii had a higher impact on the enhancement of G. vaginalis virulence, while the other tested species had a lower or no impact on G. vaginalis virulence. This study casts a new light on how BV-associated species can modulate the virulence aspects of G. vaginalis, contributing to a better understanding of the development of BV-associated biofilms.
Bulk tissue cell type deconvolution with multi-subject single-cell expression reference
Authors: Wang Xuran , Park Jihwan , Susztak Katalin , Zhang Nancy R. , Li Mingyao
Published: January 2019

Knowledge of cell type composition in disease relevant tissues is an important step towards the identification of cellular targets of disease. We present MuSiC, a method that utilizes cell-type specific gene expression from single-cell RNA sequencing (RNA-seq) data to characterize cell type compositions from bulk RNA-seq data in complex tissues. By appropriate weighting of genes showing cross-subject and cross-cell consistency, MuSiC enables the transfer of cell type-specific gene expression information from one dataset to another. When applied to pancreatic islet and whole kidney expression data in human, mouse, and rats, MuSiC outperformed existing methods, especially for tissues with closely related cell types. MuSiC enables the characterization of cellular heterogeneity of complex tissues for understanding of disease mechanisms. As bulk tissue data are more easily accessible than single-cell RNA-seq, MuSiC allows the utilization of the vast amounts of disease relevant bulk tissue RNA-seq data for elucidating cell type contributions in disease.
Tuning and mechanistic insights of metal chalcogenide molecular catalysts for the hydrogen-evolution reaction
Authors: McAllister James , Bandeira Nuno A. G. , McGlynn Jessica C. , Ganin Alexey Y. , Song Yu-Fei , Bo Carles , Miras Haralampos N.
Published: January 2019

The production of hydrogen through water splitting using earth-abundant metal catalysts is a promising pathway for converting solar energy into chemical fuels. However, existing approaches for fine stoichiometric control, structural and catalytic modification of materials by appropriate choice of earth abundant elements are either limited or challenging. Here we explore the tuning of redox active immobilised molecular metal-chalcoxide electrocatalysts by controlling the chalcogen or metal stoichiometry and explore critical aspects of the hydrogen evolution reaction (HER). Linear sweep voltammetry (LSV) shows that stoichiometric and structural control leads to the evolution of hydrogen at low overpotential with no catalyst degradation over 1000 cycles. Density functional calculations reveal the effect of the electronic and structural features and confer plausibility to the existence of a unimolecular mechanism in the HER process based on the tested hypotheses. We anticipate these findings to be a starting point for further exploration of molecular catalytic systems.
Plasmodium vivax transcriptomes reveal stage-specific chloroquine response and differential regulation of male and female gametocytes
Authors: Kim Adam , Popovici Jean , Menard Didier , Serre David
Published: January 2019

Studies ofPlasmodium vivaxgene expression are complicated by the lack of in vitro culture system and the difficulties associated with studying clinical infections that often contain multiple clones and a mixture of parasite stages. Here, we characterize the transcriptomes ofP. vivaxparasites from 26 malaria patients. We show that most parasite mRNAs derive from trophozoites and that the asynchronicity ofP. vivaxinfections is therefore unlikely to confound gene expression studies. Analyses of gametocyte genes reveal two distinct clusters of co-regulated genes, suggesting that male and female gametocytes are independently regulated. Finally, we analyze gene expression changes induced by chloroquine and show that this antimalarial drug efficiently eliminates mostP. vivaxparasite stages but, in contrast toP. falciparum, does not affect trophozoites.
Influence of young cement water on the corrosion of the International Simple Glass
Authors: Mann Colleen , Ferrand Karine , Liu Sanheng , Eskelsen Jeremy R. , Pierce Eric , Lemmens Karel , Corkhill Claire
Published: January 2019

Understanding the corrosion of nuclear waste glass is critical to predicting its safe disposal within a geological facility. The corrosion mechanisms and kinetics of the International Simple Glass, a simplified version of high-level nuclear waste glass, was shown to be significantly influenced by a high pH cement solution representative of disposal conditions. We provide the first microscopic characterisation of the porous, Zr-rich aluminoalkali-silica gel corrosion layer that was observed. Ca, Na and K from the cement solution were incorporated into the corrosion layer to charge compensate Si, Al and Zr species; the incorporation of Al was postulated to result in precipitation of an aluminosilicate-rich gel with large voids, facilitating rapid transport of species through the gel layer and significantly enhancing the corrosion rate. Precipitation of Al-containing zeolite and phyllosilicate phases was also observed, indicating that cementitious solutions may promote the detrimental ‘rate resumption’ stage of glass corrosion.
Main ecological drivers of woody plant species richness recovery in secondary forests in China
Authors: Liu Xiaofei , Garcia-Ulloa John , Cornioley Tina , Liu Xuehua , Wang Zhiheng , Garcia Claude
Published: January 2019

Identifying drivers behind biodiversity recovery is critical to promote efficient ecological restoration. Yet to date, for secondary forests in China there is a considerable uncertainty concerning the ecological drivers that affect plant diversity recovery. Following up on a previous published meta-analysis on the patterns of species recovery across the country, here we further incorporate data on the logging history, climate, forest landscape and forest attribute to conduct a nationwide analysis of the main drivers influencing the recovery of woody plant species richness in secondary forests. Results showed that regional species pool exerted a positive effect on the recovery ratio of species richness and this effect was stronger in selective cutting forests than that in clear cutting forests. We also found that temperature had a negative effect, and the shape complexity of forest patches as well as the percentage of forest cover in the landscape had positive effects on the recovery ratio of species richness. Our study provides basic information on recovery and resilience analyses of secondary forests in China.
lncRNA transcriptional initiation induces chromatin remodeling within a limited range in the fission yeast fbp1 promoter
Authors: Senmatsu Satoshi , Asada Ryuta , Abe Takuya , Hoffman Charles S. , Ohta Kunihiro , Hirota Kouji
Published: January 2019

Long noncoding RNAs (lncRNAs) transcribed across gene promoters have been detected. These regulate transcription by mechanisms that have not been fully elucidated. We herein show that the chromatin configuration is altered into an accessible state within 290 bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation. Chromatin upstream from fbp1 is progressively altered into an open configuration, as a cascade of transcription of three overlapping mlonRNA species (-a, -b and -c in order) occurs with transcriptional initiation sites progressing 5′ to 3′ upstream of the fbp1 promoter. Initiation of the shortest mlonRNA (mlonRNA-c) induces chromatin remodeling around a transcription factor-binding site and subsequent massive induction of fbp1. We identify the cis-element required for mlonRNA-c initiation, and by changing the distance between mlonRNA-initiation site and the transcription factor-binding site, we show that mlonRNA-initiation effectively induces chromatin remodeling in a limited distance within 290 bp. These results indicate that mlonRNAs are transcribed across the fbp1 promoter as a short-range inducer for local chromatin alterations, and suggest that strict chromatin modulation is archived via stepwise mlonRNA-initiations.
Prevalence of postterm births and associated maternal risk factors in China: data from over 6 million births at health facilities between 2012 and 2016
Authors: Deng Kui , Huang Yan , Wang Yanping , Zhu Jun , Mu Yi , Li Xiaohong , Xing Aiyun , Liu Zheng , Li Mingrong , Wang Xiaodong , Liang Juan
Published: January 2019

Postterm births are associated with an increased risk of adverse perinatal outcomes, but few studies have investigated the epidemiological characteristics of postterm births. We aimed to estimate the prevalence of postterm births and examine the potential association between maternal sociodemographic and obstetric characteristics and postterm births. Data were collected from China’s National Maternal Near Miss Surveillance System, 2012–2016. A logistic regression was used to assess the association between sociodemographic and obstetric characteristics and postterm births. A Poisson regression was used to determine the crude and adjusted trends of postterm births over time across regions. Among the 6,240,830 singleton births with gestational periods of 37 weeks or longer, 1.16% were postterm. The prevalence of postterm births was significantly higher in the western region and among mothers who delivered at a level ≤2 hospital, had a lower education, or were younger. A reduced risk of postterm births was observed among primiparous women, mothers who previously had a caesarean section, mothers with pregnancy complications, and mothers with ten or more antenatal visits. The risk of postterm births decreased as the number of antenatal visits increased. The overall postterm birth rates significantly decreased from 1.49% in 2012 to 0.70% in 2016. The postterm birth rates were markedly reduced in the east, central, and west regions, and the rate of the decrease was greater in the east than in the west. Furthermore, substantial decreases were observed across regions in 2014 and 2016. In conclusion, multiple sociodemographic and obstetric factors are associated with the prevalence of postterm births. A significant decreasing trend in postterm birth rates was observed in China.
Low mutation and neoantigen burden and fewer effector tumor infiltrating lymphocytes correlate with breast cancer metastasization to lymph nodes
Authors: Wang Zhigang , Liu Wei , Chen Chong , Yang Xiaolin , Luo Yunping , Zhang Bailin
Published: January 2019

Lymph node metastasis is of major prognostic significance for breast cancer. Lymph node metastasis arises at a very early stage in some patients. Using the data downloaded from the TCGA database, we studied the differences between primary tumors with and without lymph node metastasis at the multi-omics level using bioinformatics approaches. Our study found that low mutation and neoantigen burdens correlated with lymph node metastazation of breast cancer. All three conserved domains in TP53 were mutated in lymph node-negative breast cancers, whereas only one domain was mutated in lymph node-positive samples. Mutations in microtubule-related proteins appear to help immune cells recognize tumors and inhibit their lymph node metastasis. Destroying microtubule-related proteins is a potential therapeutic strategy to inhibit lymph node metastasis of breast cancer. As the neoantigens specifically present in lymph node-positive breast cancers, MAPK10, BC9L, TRIM65, CD93, KITLG, CNPPD1, CPED1, CCDC146, TMEM185A, INO80D, and PSMD11 are potential targets for vaccine design. In the tumor microenvironment, reduced numbers of effector immune cells, especially activated memory CD4+ T cells and activated mast cells, facilitate breast cancer metastasis to the lymph nodes. According to transcriptome data, lymph node metastasis was mostly driven by gene mutation rather than by gene expression. Although differential gene expression analysis was based on lymph node metastasis status, many genes were shown to be differentially expressed based on estrogen receptor status.
A CATH domain functional family based approach to identify putative cancer driver genes and driver mutations
Authors: Ashford Paul , Pang Camilla S. M. , Moya-García Aurelio A. , Adeyelu Tolulope , Orengo Christine A.
Published: January 2019

Tumour sequencing identifies highly recurrent point mutations in cancer driver genes, but rare functional mutations are hard to distinguish from large numbers of passengers. We developed a novel computational platform applying a multi-modal approach to filter out passengers and more robustly identify putative driver genes. The primary filter identifies enrichment of cancer mutations in CATH functional families (CATH-FunFams) – structurally and functionally coherent sets of evolutionary related domains. Using structural representatives from CATH-FunFams, we subsequently seek enrichment of mutations in 3D and show that these mutation clusters have a very significant tendency to lie close to known functional sites or conserved sites predicted using CATH-FunFams. Our third filter identifies enrichment of putative driver genes in functionally coherent protein network modules confirmed by literature analysis to be cancer associated. Our approach is complementary to other domain enrichment approaches exploiting Pfam families, but benefits from more functionally coherent groupings of domains. Using a set of mutations from 22 cancers we detect 151 putative cancer drivers, of which 79 are not listed in cancer resources and include recently validated cancer associated genes EPHA7, DCC netrin-1 receptor and zinc-finger protein ZNF479.
Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder
Authors: Liu Simeng , Li Enyao , Sun Zhenyu , Fu Dongjun , Duan Guiqin , Jiang Miaomiao , Yu Yong , Mei Lu , Yang Pingchang , Tang Youcai , Zheng Pengyuan
Published: January 2019

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interactions and communication, restricted interests and repetitive behaviors. Several studies report a high prevalence of gastrointestinal (GI) symptoms in autistic individuals. Cumulative evidence reveals that the gut microbiota and its metabolites (especially short-chain fatty acids, SCFAs) play an important role in GI disorders and the pathogenesis of ASD. However, the composition of the gut microbiota and its association with fecal SCFAs and GI symptoms of autistic children remain largely unknown. In the present study, we sequenced the bacterial 16S rRNA gene, detected fecal SCFAs, assessed GI symptoms and analyzed the relationship between the gut microbiome and fecal SCFAs in autistic and neurotypical individuals. The results showed that the compositions of the gut microbiota and SCFAs were altered in ASD individuals. We found lower levels of fecal acetic acid and butyrate and a higher level of fecal valeric acid in ASD subjects. We identified decreased abundances of key butyrate-producing taxa (Ruminococcaceae, Eubacterium, Lachnospiraceae and Erysipelotrichaceae) and an increased abundance of valeric acid associated bacteria (Acidobacteria) among autistic individuals. Constipation was the only GI disorder in ASD children in the present study. We also found enriched Fusobacterium, Barnesiella, Coprobacter and valeric acid-associated bacteria (Actinomycetaceae) and reduced butyrate-producing taxa in constipated autistic subjects. It is suggested that the gut microbiota contributes to fecal SCFAs and constipation in autism. Modulating the gut microbiota, especially butyrate-producing bacteria, could be a promising strategy in the search for alternatives for the treatment of autism spectrum disorder.
New Insight into AuNP Applications in Tumour Treatment and Cosmetics through Wavy Annuli at the Nanoscale
Authors: Abdelsalam Sara I. , Bhatti M. M.
Published: January 2019

The purpose of this study is to probe the peristaltic propulsion of a non-Newtonian fluid model with suspended gold nanoparticles. The base fluid is considered to simulate blood using the Carreau fluid model. We model a small annulus as a tube with a peristaltic wave containing a clot propagating towards the tube wall. An external variable magnetic field is also considered in the governing flow. An approximation for long wavelengths and small Reynolds numbers is employed to formulate the governing flow problem. The resulting nonlinear equations are solved using a perturbation scheme. Series solutions are obtained for the velocity profile, temperature profile, pressure rise and streamlines. The results indicate an enhancement in the temperature profile that can be utilized in eradicating tumour cells.
Vacuum/Compression Infiltration-mediated Permeation Pathway of a Peptide-pDNA Complex as a Non-Viral Carrier for Gene Delivery in Planta
Authors: Midorikawa Keiko , Kodama Yutaka , Numata Keiji
Published: January 2019

Non-viral gene carriers have been extensively investigated as alternatives to viral vectors for gene delivery systems into animal and plant cells. A non-viral gene carrier containing a cell-penetrating peptide and a cationic sequence was previously developed for use in intact plants and plant cells; however, the permeation pathway of the gene carrier into plant cells is yet to be elucidated, which would facilitate the improvement of the gene delivery efficiency. Here, we identified the vacuum/compression infiltration-mediated permeation pathway of a non-viral gene carrier into plant tissues and cells using a complex of plasmid DNA and a peptide-based gene carrier. This complex was taken up via the hydathodes in Arabidopsis thaliana, and from root hairs in Nicotiana benthamiana. Remarkably, these structurally weak tissues are also routes of bacterial invasion in nature, suggesting that peptide-pDNA complexes invade intact plants through similar pathways as bacterial pathogens.