bluuebunny/crossref_metadata_2025 huggingface dataset:
Transitional climate mortality: slower warming may result in increased climate‐induced mortality in some systems
Authors: Buma Brian
Published: April 2018

The potential for climate change to cause mass tree mortality in forested systems by pushing environmental conditions past physiological tolerance thresholds is well documented. Less well studied is damage and mortality associated with climatic transitions, where mortality is less on either side of the transition; the shift from freezing winter conditions to thawed winter conditions in temperate and high latitudes is a clear example. “Transitional climate mortality” is sporadic, but widespread, associated with exposure to mortality during these climatic transitions, and triggered by proximal weather events like a hard freeze after a period of above freezing temperatures. Interestingly, this suggests that slower warming could result in more intensive mortality because of extended exposure to potential mortality events. The concept is tested using a well‐studied species (Callitropsis nootkatensis) on the US/Canadian Pacific coast. To identify the transitional mortality zone, statistical modeling combined with a current mortality map and bioclimatic variables was used. This process identified the −5° to 0°C zone (mean temperature of the coldest month) as particularly associated with transitional mortality. Weather station data from multiple locations were used to validate observations. Four GCMs (General Circulation Model) and two future warming scenarios (representative concentration pathway 2.6 and 8.5) were used to estimate time and spatial extent of exposure at broad scales; slower warming results in more intensive cumulative exposure than faster warming. Finally, by combining the observed mortality zone with weather station data a generalizable binomial model was tested as a means to estimate potential future mortality. This model is applicable to any system where the transitional mortality zone (e.g., temperature range) and the frequency of proximal mortality triggers are known. This type of mortality phenomena has been understudied but may be a large driver of future forest change, given the frequency of mortality events and the ubiquity of the freeze–thaw transition across temperate systems globally.
Effect of nicotine and alpha‐7 nicotinic modulators on visceral pain‐induced conditioned place aversion in mice
Authors: Bagdas D. , Meade J.A. , Alkhlaif Y. , Muldoon P.P. , Carroll F.I. , Damaj M.I.
Published: April 2018

Background

Preclinical assays of affective and sensorial aspects of nociception play a key role in research on both the neurobiology of pain and the development of novel analgesics. Therefore, we investigated the effects of nicotine and alpha‐7 nicotinic acetylcholine receptor (nAChR) modulators in the negative affective and sensory components of visceral pain in mice.

Methods and Results

Intraperitoneal acetic acid (AA) administration resulted in a robust stretching behaviour and conditioned place aversion (CPA) in mice. We observed a dose‐dependent reduction in AA‐induced stretching and CPA by the nonselective nAChRs agonist nicotine. Mecamylamine, a nonselective nAChRs agonist, was able to block its effects; however, hexamethonium, a peripherally restricted nonselective nicotinic antagonist, was able to block nicotine's effect on stretching behaviour but not on CPA. In addition, systemic administration of α7 nAChR full agonists PHA543613 and PNU282987 was failed to block stretching and CPA behaviour induced by AA. However, the α7 nAChR‐positive allosteric modulator PNU120596 blocked AA‐induced CPA in a dose‐dependent manner without reducing stretching behaviours.

Conclusions

Our data revealed that while nonselective nAChR activation induces antinociceptive properties on the sensorial and affective signs of visceral pain in mice, α7 nAChRS activation has no effect on these responses. In addition, nonselective nAChR activation‐induced antinociceptive effect on stretching behaviour was mediated by central and peripheral mechanisms. However, the effect of nonselective nAChR activation on CPA was mediated centrally. Furthermore, our data suggest a pivotal role of allosteric modulation of α7 nAChRS in the negative affective, but not sensory, component of visceral pain.

Significance

The present results suggest that allosteric modulation of α7 nAChR may provide new strategies in affective aspects of nociception.
Carbon/Li4Ti5O12 Composite Spheres Prepared Using Chinese Yam as Carbon Source with Ultrahigh Capacity as Anode Materials for Lithium Ion Batteries
Authors: Liang Tingting , Liu Xuehua , Liu Xiaowei , Guan Xianggang , Wang Chao , Fu Aiping , Li Yanhui , Guo Peizhi , Li Hongliang
Published: April 2018

Spinel structured Li4Ti5O12 (LTO) spheres modified with carbon (Carbon/LTO composites) using Chinese yam (CY) as carbon source have been obtained by a hydrothermal method combining with a calcining at 700 °C in N2 atmosphere. The influences of the additions of CY on the morphology, structure, carbon content and also the electrochemical properties of the resulted carbon/LTO composite spheres have been investigated in details. SEM and TEM investigations show that all the composites possess spherical morphology and consist of nanosized Li4Ti5O12 crystals modified with carbon. With the increase of CY additions, the size of Li4Ti5O12 primary crystals decrease gradually, and reach to a turn over point and then the crystal size turn to large ones when the CY content increased further. It has been demonstrated that carbon modification of Li4Ti5O12 with Chinese yam as carbon source could efficiently improve the electrochemical performance of Li4Ti5O12. One of the composite sample named as C/LTO‐10 shows an ultrahigh initial specific capacity of about 211.9 mAh ⋅ g−1 at a current density of 1 C. It shows excellent cycle performance and maintains a specific capacity of 184.5 mAh ⋅ g−1 even after 300 cycles. A specific capacity of 123.5 mAh ⋅ g−1 still could be delivered at a high current density of 30 C, exhibiting also superior rate capability.
Sliding Angle Characterization of Physicochemical and Roughness Changes of GDL Surfaces after Fuel Cell Operation
Authors: Planes E. , De Moor G. , Bas C. , Flandin L.
Published: April 2018

The effect of proton exchange membrane fuel cell (PEMFC) operation on physicochemical properties and roughness of gas diffusion layers (GDL) was evaluated in this work. In addition to static contact angle measurements commonly used for GDLs, sliding angle measurements were also performed on a membrane electrode assembly (MEA) both new and used in service within commercial PEMFC. These latter revealed significant changes after 4,000 h in service that were not detectable with the static counterparts. The main novelty of this study is to correlate the contact and sliding angle measurements and to combine them with various modeling approaches developed for modeled surfaces. After 4,000 h of aging, it was thus shown that the surface of the GDLs became more hydrophilic, contrary to the roughness, which remains unchanged.
Animalizing the disadvantaged, mechanizing the wealthy: The convergence of socio‐economic status and attribution of humanity
Authors: Sainz Mario , Martínez Rocío , Moya Miguel , Rodríguez‐Bailón Rosa
Published: April 2018

Differences between groups in socio‐economic status (SES) are becoming more salient nowadays. In this context, we examined the animalistic and mechanistic dehumanization that both low and high‐SES groups may experience respectively by conducting three studies. In study 1, we manipulated the SES of two fictitious groups (low vs. high‐SES) and measured the humanity ascribed to them. Results showed that the low‐SES group was animalized in comparison with the high‐SES group, which was mechanized. In study 2, we manipulated the humanity of two fictitious groups by describing them as animals or machines and measured the perceived SES of the groups. Participants tended to attribute lower SES to the group described as animals and higher SES to the group described as machines. Finally, in study 3, we used an Implicit Association Test to replicate the results of studies 1 and 2. Taken together, these studies show that low‐SES groups are considered as animal‐like whereas high‐SES groups are seen as robot‐like. We discuss the implications of these findings in relation to the justification of income inequality within our society.
Label‐free bacterial colony detection and viability assessment by continuous‐wave terahertz transmission imaging
Authors: Yang Xiang , Shi Jia , Wang Yuye , Yang Ke , Zhao Xiang , Wang Guiyu , Xu Degang , Wang Yunxia , Yao Jianquan , Fu Weiling
Published: April 2018

Timely and accurate bacterial detection is critical for various health and safety applications, which promotes the continuous development of versatile optical sensors for bacterial investigations. Here, we report a new strategy for bacterial colony sensing using terahertz (THz) imaging with minimal assay procedures. The proposed method utilizes the acute sensitivity of THz wave to the changes in the water content and cellular structures. Single bacterial colonies of 4 bacterial species were directly distinguished using THz imaging by utilizing their differences in THz absorption. In addition, the distribution of mixed bacterial samples has been demonstrated by THz imaging, which demonstrated that the target bacterium could be easily recognized. Furthermore, we investigated the differentiation of bacterial viability, which indicated that bacteria under different living states could be distinguished by THz imaging because of their different hydration levels and cellular structures. Our results suggest that THz imaging has the potential to be used for mixed bacterial sample detection and bacterial viability assessment in a label‐free and nondestructive manner.
The Bi/Bi2WO6 heterojunction with stable interface contact and enhanced visible‐light photocatalytic activity for phenol and Cr(VI) removal
Authors: Jia Jia , Xue Peng , Wang Ruimiao , Bai Xue , Hu Xiaoyun , Fan Jun , Liu Enzhou
Published: April 2018

BACKGROUND

Semiconductor photocatalysis is the most promising green and energy‐saving technology for environmental remediation. Unfortunately, photocatalysis nanotechnology for its practical application is often challenged by the low capturing ability for visible light and use of expensive noble metals. In this work, we report the non‐noble Bi nanoparticles assembled on Bi2WO6 with enhanced visible‐light photocatalytic activity for decontamination of phenol and hexavalent chromium in water.

RESULTS

The 3% Bi/Bi2WO6 composite had the highest photocatalytic activity compared to pristine Bi2WO6, which could completely decompose phenol into small products within 120 min. More importantly, the Cr(VI) removal rate of the 3% Bi/Bi2WO6 catalyst in the presence of triethanolamine (TEOA, 2%) after irradiation for 12 min was up to 96.2%.

CONCLUSIONS

The improved photocatalytic performance could be due to the fast transfer of photogenerated charge carried by the formation of an anti‐barrier layer at the interface between metal Bi nanoparticles and the n‐type Bi2WO6 semiconductor; the enhancement of electron energy may be attributed to the localized surface plasmon resonance properties of Bi nanoparticles, as well as conspicuously strengthened and broad light‐capturing ability across the whole visible‐light range. This strategy could provide some inspiration for the design of other Bi‐based semiconductor heterostructures for decomposing harmful organic pollutants in wastewater and purifying hazardous gases in the air. © 2018 Society of Chemical Industry
Synthesis, Characterization, and Screening for Anti‐inflammatory and Antimicrobial Activity of Novel Indolyl Chalcone Derivatives
Authors: Sayed Mostafa , Kamal El‐Dean Adel M. , Ahmed Mostafa , Hassanien Reda
Published: April 2018

Because of the great biological importance of substituted indole derivatives, in the present study, a series of pyrazolylindole, thiazolylindole, and pyrimidinylindole derivatives have been synthesized with good yield. The precursor indolyl chalcone 2a–d was prepared by reaction of 3‐chloro‐1H‐indole‐2‐carbaldehyde 1 with different ketones. Then, compounds 3b–d, 4, and 5a–d have been synthesized by the reaction of chalcones 2a–d with hydrazine, phenylhydrazine, and thiosemicarbazide. When the chalcone derivative 2b subjected to react with hydroxylamine hydrochloride gave isoxazolylindole derivative 6b. N‐thiazolidine pyrazolyl indole 7 was obtained by reacting compound 5a with ethyl chloroacetate. On the other hand, when chalcone derivative 2b allowed to react with urea and thiourea gave the corresponding pyrimidinylindole derivatives 8 and 9. Finally, when chalcone derivative 2b reacted with ethyl cyanoacetate or malononitrile gave pyridinylindole derivatives 10 and 11. The structures of the all synthesized compounds were elucidated on the basis of spectral analysis infrared, NMR, and mass spectroscopy. Some of the synthesized compounds were screened for their antimicrobial and anti‐inflammatory activity. Compound 4b was the highest antibacterial activity against all strains of bacteria with values higher than those of the corresponding reference antibiotics (ciprofloxacin and levofoxacin, respectively) and almost the same as (gemifloxacin, moxifloxacin, clindamycin, gentamycin, and streptomycin). Compounds 4, 5, 6, and 7 showed high anti‐inflammatory activity compared with the standard drug indomethacin.
How far are we from viral hepatitis elimination service coverage targets?
Authors: Hutin Yvan J‐F , Bulterys Marc , Hirnschall Gottfried O
Published: April 2018

Introduction

In 2016, the Global Health Sector Strategy (GHSS) on viral hepatitis called for elimination of viral hepatitis as a major public health threat by 2030 (i.e. 90% reduction in incidence and 65% in mortality). In 2017, WHO's first‐ever Global Hepatitis Report presented the baseline values for each of the core indicators of the strategy. We review the challenges and opportunities that lie ahead in order to reach the 2030 service coverage targets.

Discussion

Three‐dose coverage of hepatitis B vaccine in infancy reached 84% in 2015 (2030 target: 90%); however, only 39% received the timely birth dose (2030 target: 90%). Blood safety (97% of blood units screened with quality assurance, 2030 target: 100%) and injection safety (5% unsafe injections, 2030 target: 0%) had made substantial progress while harm reduction fell short (27 syringe and needle sets distributed per person who injects drugs per year, 2030 target: 300). Worldwide, 9% and 20% of the HBV‐ and HCV‐infected population respectively, were aware of their status (2030 targets: 90%). In the short term, to reach the 2020 target of diagnosing 50% of those infected, 107 million HBV infected persons and 15 million HCV infected persons should be urgently diagnosed. Overall, in 2015, less than 10% of known infected persons were on HBV treatment or had started HCV treatment (2030 targets: 80%).

Conclusions

The prevention component of elimination is on track with respect to hepatitis B vaccination, blood safety, and injection safety. However, coverage of the hepatitis B vaccine timely birth dose requires a substantial increase, particularly in sub‐Saharan Africa, and harm reduction needs to be taken to scale as injecting drug use accounts for a third of mortality from HCV infection. A promising but limited start in hepatitis testing and treatment needs to be followed by immediate and sustained action so that we reach the service coverage targets required to achieve elimination by 2030. Treating persons coinfected with HIV and hepatitis viruses is particularly urgent and needs to be promoted in the context of the HIV response.
Counselor–Advocate–Scholar Model: Changing the Dominant Discourse in Counseling
Authors: Ratts Manivong J. , Greenleaf Arie T.
Published: April 2018

Discourse represents the languages, ideas, and images that together shape one's understanding of the world. In counseling, discourse determines clinical practice. The authors posit that dominant discourse in counseling promotes an intrapsychic status quo that discounts the relationship between individuals and their environment, which often leads to office‐bound interventions that are inadequate in addressing issues of oppression. The counselor–advocate–scholar model (Ratts & Pedersen, ) is introduced to expand current discourse to include advocacy and research to better address systems of oppression.

El discurso representa los idiomas, ideas e imágenes que, en su conjunto, dan forma a nuestra comprensión del mundo. En la consejería, el discurso determina la práctica clínica. Los autores proponen que el discurso dominante en la consejería promueve un status quo intrapsíquico que no tiene en cuenta la relación entre los individuos y su medio, lo que con frecuencia lleva a intervenciones limitadas a la oficina que no resuelven de forma adecuada los problemas relacionados con la opresión. Se introduce el modelo consejero‐defensor‐investigador (Ratts & Pedersen, ) para expandir el discurso actual de forma que incluya la defensoría e investigación, y así abordar mejor los sistemas de opresión.
“It's Like Power to Move”: Black Students’ Psychosocial Experiences in Black Studies Courses at a Predominantly White Institution
Authors: Chapman‐Hilliard Collette , Beasley Samuel T.
Published: April 2018

This study examined Black students’ experiences in culture‐centered courses that focused on the historical and contemporary experiences of Blacks in America and across the African diaspora. Using a qualitative approach, the authors investigated the perceptions of how Black Studies courses shaped the psychosocial experiences and identity development of Black students (N = 24) at a predominantly White institution. Data from semistructured focus group interviews revealed several themes, including psychological empowerment, self‐determination, counterspaces, and community perpetuity. The authors suggest ways counselors and educators can support Black students’ psychosocial development and provide outreach to diverse student populations.

Este estudio examinó las experiencias de estudiantes negros en cursos centrados en la cultura que se enfocaron en las experiencias históricas y contemporáneas de personas negras en Estados Unidos y a lo largo de la diáspora africana. Usando un enfoque cualitativo, los autores investigaron las percepciones sobre cómo los cursos de Cultura Negra dieron forma a las experiencias psicosociales y al desarrollo de la identidad de estudiantes negros (N = 24) en una institución predominantemente blanca. Los datos obtenidos de entrevistas semiestructuradas en grupos de enfoque revelaron varios temas que incluyen el empoderamiento psicológico, la autodeterminación, los espacios seguros y la perpetuidad de la comunidad. Los autores sugieren distintas formas en las que los consejeros y educadores pueden apoyar el desarrollo psicosocial de los estudiantes negros y proporcionar un acercamiento a poblaciones diversas de estudiantes.
Molecular interaction of some cardiovascular drugs with human serum albumin at physiological‐like conditions: A new approach
Authors: Niaei Navid , Hasanzadeh Mohammad , Shadjou Nasrin
Published: April 2018

In the present study, the interaction of human serum albumin (HSA) with some cardiovascular drugs (CARs) under physiological conditions was investigated via the fluorescence spectroscopic and Fourier transform infrared spectroscopy. The CAR included Captopril, Timolol, Propranolol, Atenolol, and Amiodarone. Cardiovascular drugs can effectively quench the endogenous fluorescence of HSA by static quenching mechanism. The fluorescence quenching of HSA is mainly caused by complex formation of HSA with CAR. The binding reaction of CAR with HSA can be concluded that hydrophobic and electrostatic interactions are the main binding forces in the CAR‐HSA system. The results showed that CAR strongly quenched the intrinsic fluorescence of HSA through a static quenching procedure, and nonradiation energy transfer happened within molecules. Fourier transform infrared spectroscopy absorption studies showed that the secondary structure was changed according to the interaction of HSA and CAR. The binding reaction of CAR with HSA can be concluded that hydrophobic and electrostatic interactions are the main binding forces in the CAR‐HSA system. The results obtained herein will be of biological significance in pharmacology and clinical medicines.
Reproducible automated breast density measure with no ionizing radiation using fat‐water decomposition MRI
Authors: Ding Jie , Stopeck Alison T. , Gao Yi , Marron Marilyn T. , Wertheim Betsy C. , Altbach Maria I. , Galons Jean‐Philippe , Roe Denise J. , Wang Fang , Maskarinec Gertraud , Thomson Cynthia A. , Thompson Patricia A. , Huang Chuan
Published: April 2018

Background

Increased breast density is a significant independent risk factor for breast cancer, and recent studies show that this risk is modifiable. Hence, breast density measures sensitive to small changes are desired.

Purpose

Utilizing fat‐water decomposition MRI, we propose an automated, reproducible breast density measurement, which is nonionizing and directly comparable to mammographic density (MD).

Study Type

Retrospective study.

Population

The study included two sample sets of breast cancer patients enrolled in a clinical trial, for concordance analysis with MD (40 patients) and reproducibility analysis (10 patients).

Field Strength/Sequence

The majority of MRI scans (59 scans) were performed with a 1.5T GE Signa scanner using radial IDEAL‐GRASE sequence, while the remaining (seven scans) were performed with a 3T Siemens Skyra using 3D Cartesian 6‐echo GRE sequence with a similar fat‐water separation technique.

Assessment

After automated breast segmentation, breast density was calculated using FraGW, a new measure developed to reliably reflect the amount of fibroglandular tissue and total water content in the entire breast. Based on its concordance with MD, FraGW was calibrated to MR‐based breast density (MRD) to be comparable to MD. A previous breast density measurement, Fra80—the ratio of breast voxels with <80% fat fraction—was also calculated for comparison with FraGW.

Statistical Tests

Pearson correlation was performed between MD (reference standard) and FraGW (and Fra80). Test–retest reproducibility of MRD was evaluated using the difference between test–retest measures (Δ1–2) and intraclass correlation coefficient (ICC).

Results

Both FraGW and Fra80 were strongly correlated with MD (Pearson ρ: 0.96 vs. 0.90, both P < 0.0001). MRD converted from FraGW showed higher test–retest reproducibility (Δ1–2 variation: 1.1% ± 1.2%; ICC: 0.99) compared to MD itself (literature intrareader ICC ≤0.96) and Fra80.

Data Conclusion

The proposed MRD is directly comparable with MD and highly reproducible, which enables the early detection of small breast density changes and treatment response.

Level of Evidence: 3

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018;48:971–981.
Application of several spatial interpolation techniques to monthly rainfall data in the Calabria region (southern Italy)
Authors: Pellicone G. , Caloiero T. , Modica G. , Guagliardi I.
Published: April 2018

The spatial distribution of rainfall is paramount for water‐related research such as hydrological modelling and watershed management. The use of different interpolation methods in the same area may cause large differences and deviations from the real spatial distribution of rainfall; these differences depend on the type of chosen model, its mode of geographical management and the resolution used. In this study, different algorithms of spatial interpolation of rainfall in a region of southern Italy (Calabria) were applied and the results of geostatistical and deterministic approaches were compared in order to choose the best method for reproducing the actual precipitation field surface. In particular, inverse distance weighting (IDW), ordinary kriging (OK), kriging with external drift (KED), ordinary cokriging (COK) and empirical Bayesian kriging (EBK) were applied to produce the monthly rainfall maps of Calabria. The maps were obtained from a rainfall data set of 129 monthly rainfall series (about one station per 117 km2) collected in the period 1951–2006. Cross‐validation and visual analysis of the precipitation maps were performed to examine the results of these different models. Results clearly indicate that geostatistical methods outperform inverse distance. Moreover, among these methods, the kriging with an external drift showed the smallest error of prediction.
An Examination of College Counselors' Work With Student Sex Addiction: Training, Screening, and Referrals
Authors: Giordano Amanda L. , Cashwell Craig S.
Published: April 2018

Given the prevalence of sex addiction (SA) among collegiate populations, the authors designed this study to examine college counselors' training in SA, use of formal assessments, and referrals to support groups. Results indicated that 84.4% of college counselors (N = 77) had at least one client present with SA‐related issues in the past year. Findings suggest the need for improvement in counselor training in SA, use of formal assessments, and referral practices.
Quick Flicks: Association of Paroxysmal Kinesigenic Dyskinesia and Tics
Authors: Balint Bettina , Wiethoff Sarah , Martino Davide , del Gamba Claudia , Latorre Anna , Ganos Christos , Houlden Henry , Bhatia Kailash P.
Published: April 2018

Background

Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterised by brief attacks of chorea, dystonia, or mixed forms precipitated by sudden movement.

Methods

Observational study with a cohort of 14 PKD patients and genetic testing for PRRT2 mutations.

Results

In a series of 14 PKD patients seen in our clinic at the National Hospital of Neurology, Queen Square, from 2012–2017, we noted tics in 11 patients (79%), which stand in stark contrast to the estimated lifetime prevalence of tics estimated to reach 1%.

Conclusions

The two reasons to point out this possible association are the clinical implications and the potential opportunity of a better understanding of shared pathophysiological mechanisms of neuronal hyperexcitability.
ERCC6L2‐associated inherited bone marrow failure syndrome
Authors: Shabanova Iren , Cohen Elisa , Cada Michaela , Vincent Ajoy , Cohn Ronald D. , Dror Yigal
Published: April 2018

Background

ERCC6L2‐associated disorder has recently been described and only five patients were reported so far. The described phenotype included bone marrow, cerebral, and craniofacial abnormalities. The aim of this study was to further define the genetic and phenotypic spectrum of the disorder by summarizing the five published cases and an additional case that we identified through whole‐exome sequencing performed at the University of Toronto.

Methods

Clinical data was extracted from the Canadian Inherited Marrow Failure Registry. Whole exome sequencing was performed to identify causative mutations.

Results

All six cases had homozygous truncating mutations either at or upstream of the helicase domain of ERCC6L2. All patients displayed bone marrow failure, learning or developmental delay and microcephaly. Our patient was unique in displaying features of cerebellar disease, including ataxia and dysmetria as well as an interval deterioration of the corpus callosum and generalized volume loss on MRI. Another unique feature of our patient was retinal dystrophy with macular involvement. Along with one other patient, our patient displayed craniofacial abnormalities by presenting with low‐set prominent ears, a pointed prominent chin, and deep‐set eyes. Leukemia is common among patients with inherited bone marrow failure, but thus far, none of the patients have developed this complication.

Conclusions

ERCC6L2‐associated disorder is a multisystem disorder. The phenotype spectrum includes bone marrow failure, cerebral, and craniofacial abnormalities, as well as cerebellar and retinal abnormalities.
Simple and efficient germline copy number variant visualization method for the Ion AmpliSeq™ custom panel
Authors: Nishio Shin‐ya , Moteki Hideaki , Usami Shin‐ichi
Published: April 2018

Background

Recent advances in molecular genetic analysis using next‐generation sequencing (NGS) have drastically accelerated the identification of disease‐causing gene mutations. Most next‐generation sequencing analyses of inherited diseases have mainly focused on single‐nucleotide variants and short indels, although, recently, structure variations including copy number variations have come to be considered an important cause of many different diseases. However, only a limited number of tools are available for multiplex PCR‐based target genome enrichment.

Methods

In this paper, we reported a simple and efficient copy number variation visualization method for Ion AmpliSeq™ target resequencing data. Unlike the hybridization capture‐based target genome enrichment system, Ion AmpliSeq™ reads are multiplex PCR products, and each read generated by the same amplicon is quite uniform in length and position. Based on this feature, the depth of coverage information for each amplicon included in the barcode/amplicon coverage matrix file was used for copy number detection analysis. We also performed copy number analysis to investigate the utility of this method through the use of positive controls and a large Japanese hearing loss cohort.

Results

Using this method, we successfully confirmed previously reported copy number loss cases involving the STRC gene and copy number gain in trisomy 21 cases. We also performed copy number analysis of a large Japanese hearing loss cohort (2,475 patients) and identified many gene copy number variants. The most prevalent copy number variation was STRC gene copy number loss, with 129 patients carrying this copy number variation.

Conclusion

Our copy number visualization method for Ion AmpliSeq™ data can be utilized in efficient copy number analysis for the comparison of a large number of samples. This method is simple and requires only easy calculations using standard spread sheet software.
A new matrix for multiphase couplings in a membrane porous medium
Authors: Chen Xiaohui , Wang Manhui , Hicks Michael A. , Thomas Hywel R.
Published: April 2018

The empirical Darcy's law of water transport in porous media, Fick's law of chemical diffusion, and Fourier's law of thermal transport have been widely used in geophysics/geochemistry for over 150 years. However, the strong couplings between water, temperature, and chemicals in a membrane porous medium have made these laws inapplicable and present a significant hurdle to the understanding of multiphase flow in such a material. Extensive experiments over the past century have observed chemical osmosis and thermal osmosis, but a model for understanding their underlying physicochemical basis has remained unavailable, because of the highly cross‐disciplinary and multiscale‐multiphase nature of the coupling. Based on the fundamental principles of nonequilibrium thermodynamics and mixture coupling theory, a rigorously theoretical and mathematical framework is proposed and a general model accounting for all of the coupled influences is developed. This leads to a simple and robust mathematical matrix for studying multiphase couplings in a membrane porous medium when all chemical components are electrically neutral.
Causal Association of Overall Obesity and Abdominal Obesity with Type 2 Diabetes: A Mendelian Randomization Analysis
Authors: Wang Tao , Zhang Rong , Ma Xiaojing , Wang Shiyun , He Zhen , Huang Yeping , Xu Bo , Li Yangyang , Zhang Hong , Jiang Feng , Bao Yuqian , Hu Cheng , Jia Weiping
Published: April 2018

Objective

This study aimed to compare the causal effect of overall obesity and abdominal obesity on type 2 diabetes among Chinese Han individuals.

Methods

The causal relationship of BMI and waist‐to‐hip ratio (WHR) with the risk of glucose deterioration and glycemic traits was compared using two different genetic instruments based on 30 BMI loci and 6 WHR loci with Mendelian randomization (MR) in three prospective cohorts (n = 6,476).

Results

Each 1‐SD genetically instrumented higher WHR was associated with a 65.7% higher risk of glucose deterioration (95% CI = 1.069‐2.569, P = 0.024), whereas no significant association of BMI with glucose deterioration was observed. Furthermore, a causal relationship was found only between BMI and homeostatic model assessment β‐cell function (HOMA‐B) (β = 0.143, P = 0.001), and there was a nominal association with Stumvoll second‐phase insulin secretion traits (β = 0.074, P = 0.022). The significance level did not persist in sensitivity analyses, except in the causal estimate of WHR on the Gutt index in MR‐Egger (β = −0.379, P = 0.022) and the causal estimate of BMI on homeostatic model assessment β‐cell function in weighted median MR (β = 0.128, P = 0.017).

Conclusions

The data from this study support the potential causal relationship between abdominal obesity and hyperglycemia, which may be driven by aggravated insulin resistance, in contrast with the potential causal relationship between overall obesity and insulin secretion.
Acute toxicity of craniospinal irradiation with volumetric‐modulated arc therapy in children with solid tumors
Authors: Wong Kenneth K. , Ragab Omar , Tran Hung N. , Pham Anthony , All Sean , Waxer Jonathan , Olch Arthur J.
Published: April 2018

Background

Craniospinal irradiation (CSI) is an important part of curative radiation therapy (RT) for many types of pediatric brain or solid tumors. After conventional CSI, long term survivors may experience sequelae due to unintended dose to normal tissue. Volumetric modulated arc therapy (VMAT) CSI reduces off‐target doses at the cost of greater complexity and error risk, and we describe our initial experience in a group of pediatric patients with solid tumors presenting with disseminated or recurrent disease.

Procedure

Pediatric patients with brain tumors were identified at Children's Hospital Los Angeles from 2013 to 2015. Clinical characteristics, acute toxicity, and radiotherapy data were abstracted from their medical records. We identified 19 patients who received VMAT CSI. Quality assurance was performed with a cylindrical detector array and ion chamber measurements at the arc junctions.

Results

Patients had medulloblastoma or supratentorial primitive neuro‐ectodermal tumor (n = 14, 11 high risk), germ cell tumors (two), relapsed neuroblastoma (two), and atypical teratoid/rhabdoid tumor (one). The most common acute toxicity was hematologic, including leukopenia (11% grade [Gr] 2, 26% Gr 3, and 63% Gr 4), anemia (89% Gr 2), and thrombocytopenia (16% Gr 1–2, 26% Gr 3, and 37% Gr 4). Despite leukopenia, we encountered only two Gr 3 infections (urinary tract and lung). The majority required blood products (89% red blood cells and 68% platelets). Weight loss was also common (47% Gr 1 and 26% Gr 2).

Conclusions

VMAT CSI, along with chemotherapy and anesthesia, is feasible with supportive care. Daily image‐guided RT improves accuracy and reduces the risk of spinal cord overdose without increasing treatment time. Further research is needed to determine whether reducing doses to organs, such as thyroid, heart, or hippocampus, offsets the risk of increased volume of low‐dose irradiation.
Malignant tumors misdiagnosed as benign vascular anomalies
Authors: Scorletti Federico , Hammill Adrienne , Patel Manish , Ricci Kiersten , Dasgupta Roshni
Published: April 2018

Background

Malignant soft tissue tumors are rare and difficult to diagnose in children. These can initially be misdiagnosed as benign vascular anomalies. Management of these two conditions differs drastically and delay in diagnosis may impact overall survival.

Purpose

To predict qualities that may increase the index of suspicion for malignancy in patients presenting with lesions initially considered vascular anomalies.

Methods

A retrospective review at a quaternary hemangioma and vascular malformation center of all patients who presented between 2008 and 2016 with an initial diagnosis of a benign vascular malformation, which on further work‐up was noted to be a malignancy. Demographics, clinical presentation, and laboratory and radiologic studies were analyzed.

Results

Eleven patients were identified; the median age at presentation was 2 months (0–24years). Ten out of 11 lesions had rapid growth, which prompted biopsy. Pain was an inconsistent finding (36%). Tumor markers were positive in only one case. Median follow‐up was 3 years (range 6 months to 8 years); seven patients have no evidence of disease, two patients are under treatment for progression or relapse of disease, and two patients have died.

Conclusion

Although malignant vascular tumors are rare, a clear index of suspicion needs to be maintained particularly with rapid growth or increasing symptoms. Differentiation of malignant tumor from benign lesions relies on the comprehensive evaluation of clinical manifestations, evolution of the lesion, and abnormal clinical behavior, by an experienced multidisciplinary vascular malformation team. There should be a low threshold for biopsy of unclear vascular lesions.
Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy‐induced peripheral neuropathy in adolescents: A preliminary study
Authors: Tomasello Caterina , Pinto Rita Maria , Mennini Chiara , Conicella Elena , Stoppa Francesca , Raucci Umberto
Published: April 2018

Purpose

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, in need of effective treatment. Preliminary data support the efficacy of scrambler therapy (ST), a noninvasive cutaneous electrostimulation device, in adults with CIPN. We test the efficacy, safety, and durability of ST for neuropathic pain in adolescents with CIPN.

Patients and Methods

We studied nine pediatric patients with cancer and CIPN who received ST for pain control. Each patient received 45‐min daily sessions for 10 consecutive days as a first step, but some of them required additional treatment.

Results

Pain significantly improved comparing Numeric Rate Scale after 10 days of ST (9.22 ± 0.83 vs. 2.33 ± 2.34; P < 0.001) and at the end of the optimized cycle (EOC) (9.22 ± 0.83 vs. 0.11 ± 0.33, P < 0.001). The improvement in quality of life was significantly reached on pain interference with general activity (8.67 ± 1.66 vs. 3.33 ± 2.12, P < 0.0001), mood (8.33 ± 3.32 vs. 2.78 ± 2.82, P < 0.0005), walking ability (10.00 vs. 2.78 ± 1.22, P < 0.0001), sleep (7.56 ± 2.24 vs. 2.67 ± 1.41, P < 0.001), and relations with people (7.89 ± 2.03 vs. 2.11 ± 2.03, P < 0.0002; Lansky score 26.7 ± 13.2 vs. 10 days of ST 57.8 ± 13.9, P < 0.001; 26.7 ± 13.2 vs. EOC 71.1 ± 16.2, P < 0.001).

Conclusion

Based on these preliminary data, ST could be a good choice for adolescents with CIPN for whom pain control is difficult. ST caused total relief or dramatic reduction in CIPN pain and an improvement in quality of life, durable in follow‐up. It caused no detected side effects, and can be retrained successfully. Further larger studies should be performed to confirm our promising preliminary data in pediatric patients with cancer.
FarmCPUpp: Efficient large‐scale genomewide association studies
Authors: Kusmec Aaron , Schnable Patrick S.
Published: April 2018

Genomewide association studies (GWAS) are computationally demanding analyses that use large sample sizes and dense marker sets to discover associations between quantitative trait variation and genetic variants. FarmCPU is a powerful new method for performing GWAS. However, its performance is hampered by details of its implementation and its reliance on the R programming language. In this paper, we present an efficient implementation of FarmCPU, called FarmCPUpp, that retains the R user interface but improves memory management and speed through the use of C++ code and parallel computing.
Solid nuclei and liquid droplets: A parallel treatment for 3 phase systems
Authors: Ferrone Frank A.
Published: April 2018

For solid phase self assembly into crystals or large diameter polymers, the presence of a liquid‐liquid demixing transition has been known to have an accelerating effect on the nucleation process. We present a novel approach to the description of accelerated nucleation in which the formation of solid phase aggregates and liquid‐like aggregates compete as parallel pathways to formation of dense phases. The central idea is that the small aggregates that would ultimately form the liquid phase are sufficiently labile to sample the configurations that would form the solid, so that the growing cluster begins as a liquid, and switches into growth as a solid when the aggregates have equal free energies. This can accelerate the reaction even when the liquid‐demixed state is thermodynamically unfavorable. The rate‐limiting barrier is therefore the energy at which there is a transition between liquid and solid, and the effective nucleus size is then concentration independent, even though for both nucleated demixing and nucleated crystallization, the nucleus size does depend on concentration. These ideas can be expressed in a chemical potential formalism that has been successfully used in nucleation of sickle hemoglobin, but not to our knowledge previously employed in describing LLD processes. The method is illustrated by considering existing data on Lysozyme.
Dynamical Controls for Improving Quantum Search Algorithm Through Flux Qubits System
Authors: Homid A. H. , Abdel‐Aty M. , El‐Shahat T. , Eleuch H. , Obada A.‐S. F.
Published: April 2018

A new technique was developed to generate the dynamical quantum gates, depend on the ferromagnetism and antiferromagnetism phenomena in the superconducting flux qubits system at the same interaction time. According to the dynamical controls techniques of such gates, we invoke and synthesize a new algorithm called the dynamical quantum search algorithm. The Grover algorithm was obtained at a specified time for the current algorithm. This algorithm was distinguished by accuracy in obtaining high probability of finding any marked state in a shorter time compared with Grover algorithm time. The algorithm performance was improved with respect to different values of the dynamical controls.
Roles of conserved tryptophans in trimerization of HIV‐1 membrane‐proximal external regions: Implications for virucidal design via alchemical free‐energy molecular simulations
Authors: Gossert Steven T. , Parajuli Bibek , Chaiken Irwin , Abrams Cameron F.
Published: April 2018

The Dual‐Action Virolytic Entry Inhibitors, or “DAVEI's,” are a class of recombinant fusions of a lectin, a linker polypeptide, and a 15‐residue fragment from the membrane‐proximal external region (MPER) of HIV‐1 gp41. DAVEI's trigger rupture of HIV‐1 virions, and the interaction site between DAVEI MPER and HIV‐1 lies in the gp41 component of the envelope glycoprotein Env. Here, we explore the hypothesis that DAVEI MPER engages Env gp41 in a mode structurally similar to a crystallographic MPER trimer. We used alchemical free‐energy perturbation to assess the thermodynamic roles of each of the four conserved tryptophan residues on each protomer of MPER3. We found that a W666A mutation had a large positive
for all three protomers, while W672A had a large positive
for only two of the three protomers, with the other tryptophans remaining unimportant contributors to MPER3 stability. The protomer for which W672 is not important is unique in the placement of its W666 sidechain between the other two protomers. We show that the unique orientation of this W666 sidechain azimuthally rotates its protomer away from the orientation it would have if the trimer were symmetric, resulting in the diminished interaction of this W672 with the rest of MPER3. Our findings are consistent with our previous experimental study of W‐to‐A mutants of DAVEI. This suggests that DAVEI MPER may engage HIV‐1 Env to form a mixed trimer state in which one DAVEI MPER forms a trimer by displacing a more weakly interacting protomer of the endogenous Env MPER trimer.
Ajulemic acid: potential treatment for chronic inflammation
Authors: Burstein Sumner H.
Published: April 2018

Ajulemic acid (AJA, CT‐3, IP‐751, JBT‐101, anabasum) is a first‐in‐class, synthetic, orally active, cannabinoid‐derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive. In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression. AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials in the first 3 targets demonstrated that it is safe, is a potential treatment for these orphan diseases and appears to be a potent inflammation‐resolving drug with a unique mechanism of action, distinct from the nonsteroidal anti‐inflammatory drug (NSAID), and will be useful for treating a wide range of chronic inflammatory diseases. It may be considered to be a disease‐modifying drug unlike most NSAIDs that only provide symptomatic relief. AJA is currently being evaluated in 24‐month open‐label extension studies in SSc and in skin‐predominant DM. A Phase 3 multicenter trial to demonstrate safety and efficacy in SSc has recently been initiated.
Relationship between the mode of conception and depressive symptoms during the first 6 months post‐partum in Japan
Authors: Mori Emi , Iwata Hiroko , Maehara Kunie , Sakajo Akiko , Tamakoshi Koji
Published: April 2018

Purpose

To determine whether conventional treatment and assisted reproductive technology for infertility are associated with depressive symptoms and to identify the predictors of depressive symptoms during the first 6 months' post‐partum.

Methods

A prospective cohort design was used, with the participants being recruited from 13 Japanese hospitals. Using self‐report questionnaires, a total of 2709 women (response rate: 71.9%) provided longitudinal data at five time points: during their hospital stay and at 1, 2, 4, and 6 months' post‐partum. The depressive symptoms were measured by using the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS). A logistic regression analysis was used to examine the association between the mode of conception and depressive symptoms and to identify the predictors of the depressive symptoms.

Results

There was no significant association between the mode of conception and the depressive symptoms at any time point. Six factors that were associated with the EPDS score were first‐time childbirth, emergency cesarean delivery, infant feeding, financial burden, having a male infant, and dissatisfaction with social support.

Conclusion

There was no significant relationship between the mode of conception and depressive symptoms. Nursing care should be based on individual assessments that focus on parity, the delivery method, infant feeding method, financial burden, the infant's sex, and social support, rather than on the mode of conception.