bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Resolution Simulation Study Exploring the Potential of Radars, Crowdsourced Personal Weather Stations, and Commercial Microwave Links to Monitor Small‐Scale Urban Rainfall
Authors: de Vos L. W. , Raupach T. H. , Leijnse H. , Overeem A. , Berne A. , Uijlenhoet R.
Published: December 2018

Many applications in urban areas require high‐resolution rainfall measurements. Typical operational weather radars can provide rainfall intensities at 1‐km2 grid cells every 5 min. Opportunistic sensing with commercial microwave links yields path‐averaged rainfall intensities (typically 0.1–10 km) within urban areas. Additionally, large amounts of urban in situ rainfall measurements from amateur weather observers are obtainable in real‐time. The accuracy of these three techniques is evaluated for an urban study area of 20 × 20 km, taking into account their respective network layouts and sampling characteristics. We use two simulated rainfall events described in terms of drop size distributions on a 100‐m grid and with a temporal resolution of 30 s. Accurate radar rainfall estimation with the Z‐R relationship relies heavily on an appropriate choice of parameters, and a dual‐polarization strategy is more suitable for higher intensities. Under ideal measurement conditions, the weather station network is the most promising, with a Pearson correlation coefficient above 0.86 and a relative bias below 4% for 100‐m rainfall estimates at 5‐min resolution. Microwave link rainfall observations contain the largest error, shown by a consistently larger coefficient of variation. The accuracy of all techniques improves when considering rainfall at larger scales, especially by increasing time intervals, with the strongest improvements found for microwave links for which errors are largely caused by their temporal sampling. Sparser networks are examined, showing that the decline in measurement accuracy only becomes significant when the link and station network density are reduced to less than half their levels in Amsterdam.
Cultural Considerations for Autonomy and Medical Adherence in a Young Palestinian American Muslim Female With Spina Bifida: A Longitudinal Case Study in a Research Context
Authors: Ohanian Diana M. , Stiles-Shields Colleen , Afzal Khalid I. , Driscoll Colleen F. Bechtel , Papadakis Jaclyn Lennon , Stern Alexa , Starnes Meredith , Holmbeck Grayson N.
Published: December 2018

This case study examines the unique presentation of a young Palestinian American Muslim female who is a part of an ongoing longitudinal study examining family and peer relationships, psychological adjustment, and neuropsychological functioning in youth with spina bifida. Throughout 10 years of data collection, Palestinian-Arab culture and Islamic faith have consistently emerged as important factors that can be considered when interpreting this participant’s general level of autonomy, medical autonomy, medical adherence, and psychological adjustment. This case study examines important aspects of adaptive and independent functioning for youth with spina bifida and how this family’s culture interacts with these different domains of functioning. In order to fully capture this family’s distinct lived experience, this case study reviews both quantitative data and qualitative data, highlighting the importance of considering context when performing clinical research. Moreover, it explores potential conflicts between an Arab collectivist family structure and Western biomedical ethics and suggests how clinicians might navigate these conflicts and bolster culturally rooted strengths of families and patients from non-Western backgrounds.

Implications for Impact Statement

This case study examines the unique presentation of a young Palestinian American Muslim female with spina bifida myelomeningocele using data gathered from a longitudinal research study. Specifically, this case study explores how the participant’s faith and culture interact with different areas of adaptive functioning. This case study hopes to highlight potential conflicts that could arise between clinicians and patients related to differences between an Arab collectivist family structure and Western biomedical ethics.
Three Integrated Elements of Empowerment: HIV Prevention With Sub-Saharan African Adolescent Females Involved in Transactional Sex
Authors: Feldstein Ewing Sarah W. , Bryan Angela D. , Alicante Tutu , Korthuis P. Todd , Hudson Karen A. , Lovejoy Travis I.
Published: December 2018

While the term “transactional sex” has garnered increased attention, little is known about what it truly encompasses, or how it leads to HIV risk within the specific developmental period of adolescence. We therefore introduce a model to characterize why girls in in sub-Saharan Africa engage in transactional sex, and how this may contribute to their decisions around how, whether, and when to implement HIV/sexually transmitted infection (STI) prevention efforts. This model forms the foundation for our adolescent-specific HIV prevention efforts for young girls in sub-Saharan Africa. Within this topical review, we detail how this intervention has been adapted for cross-cultural fit and congruence, as well as for developmental factors in transactional sex decision-making, including practical avenues to navigate peer and partner risk. Together, this model and related HIV prevention program focus on empowering young girls in sub-Saharan Africa as they begin to make decisions about whether and when to engage in transactional sex, by providing girls with critical HIV risk reduction skills during this time of rapid transition into HIV/STI risk behavior.

Implications for Impact Statement

While “transactional sex” has gained recent attention, little is known about what it means, particularly for adolescent girls in sub-Saharan Africa, and how it is connected to critical health behaviors, including unprotected sex that leads to HIV. This is important, given that adolescents (ages <21) have very low rates of uptake and adherence to HIV prevention even when those options are available.
Considerations for the Cross-Cultural Adaptation of an Advance Care Planning Guide for Youth With Cancer
Authors: Arruda-Colli Marina Noronha Ferraz de , Sansom-Daly Ursula , Santos Manoel Antônio dos , Wiener Lori
Published: December 2018

Adolescent and young adults’ (AYAs’) involvement in advance care planning and end-of-life discussions may enhance the decision-making process, reduce stress, and improve the patient’s quality of life. Given the importance of establishing adequate communication and having culturally appropriate tools to introduce advance care planning, our article describes the cross-cultural adaptation of the advance care planning guide, Voicing My CHOiCES™, in Australia and in Brazil. In Brazil, the process involved initially translating the document to Portuguese followed by evaluation by a group of providers and patients (aged 18–39) undergoing cancer treatment. The document was revised based on the feedback received, then back-translated to English and discussed with Voicing My CHOiCES authors to refine the final version in Portuguese. In Australia, a multiperspective interview-based study was undertaken with AYA cancer patients/survivors (aged 15–25), siblings, parents, and a range of health care providers from the oncology setting to determine the perceived acceptability of the tool within the Australian clinical context. These interviews pointed to a variety of recommended adaptations ranging from the aesthetic and linguistic, through to the restructuring of content within the tool. Adaptations for the Australian setting were then revised in an iterative capacity within several focus groups of AYA participants and health care providers. The processes used in both countries highlight ways to engage youth living with a life-limiting illness in conversations about advance care planning and how to develop culturally appropriate clinical tools.

Implications for Impact Statement

Engaging youth living with a life-limiting illness in conversations about advance care planning is critical to ensure that goals of care are understood and respected. Adapting gold-standard interventions to suit the unique cultural needs of different clinical contexts is essential in order to enable both patients and their health care providers to take “ownership” on how these sensitive interactions unfold. Closely examining the process of how two different cultures went through the cross-cultural adaptation of the planning guide, Voicing My CHOiCES provides guidance for others who may wish to adapt communication tools in the future.
International Patients: Lessons Learned From a Pediatric Psychology and International Medicine Collaboration
Authors: Chopko Stephanie , Klostermann Susan , Veloski Margaret , Sherman Colleen , Harrison Roger , Shroff Pendley Jennifer
Published: December 2018

The objective of this article is to describe the experience of pediatric psychologists in providing psychological testing and assessment services for patients referred via the International Medicine Program at Nemours Children’s Health System/A. I. DuPont Hospital for Children in Wilmington, Delaware. A brief history of the development of these services, information regarding the types of patients served by this program, and an overview of the process designed in collaboration with the International Medicine Program is provided as a guide for implementation at other institutions. Rates of referrals have increased over the time the department has been accepting referrals for international patients. In 2017, 15% of the total referrals that the International Medicine Program received regarding services at the hospital were for psychological testing. Over 90% of referrals resulted in a scheduled appointment. Overall, the program has resulted in positive feedback from families as well as providers who see patients for testing. Key to the program’s success appears to be the relationships with stakeholders both within and outside of the hospital system. The specific benefits for training of psychology predoctoral interns and postdoctoral fellows are highlighted.

Implications for Impact Statement

This article describes an interdisciplinary collaboration in a pediatric hospital setting to develop a psychological testing and assessment service for international patients seeking care in the United States. The article highlights the specific resources of the relevant departments and features of the program that have facilitated programmatic growth, for example, a strong partnership with the International Medicine office, a streamlined workflow, and a condensed evaluation process for families. Finally, it reviews the challenges that have been encountered and offers suggestions for other hospitals looking to develop such programs.
Expanding Pediatric Psychology: Perspectives of International Trainees
Authors: Sato Tetsuo “Ted” , Abdullah Habib , Bernabe Emily , Dewey Laura
Published: December 2018

Culturally appropriate, evidence-based assessments and interventions are necessary to reduce mental health and pediatric psychology disparities worldwide. Currently, there are limited opportunities for psychologists from other countries to learn clinical skills in the United States and adapt evidence-based practices to their home countries. The purpose of this paper is to share the personal perspectives of pediatric psychology international trainees and highlight opportunities for future training. We will also review how training programs may be adapted to ensure the successful dissemination of culturally applicable, evidence-based approaches in the trainees’ home countries. Considerations for training international trainees and future research potential are also discussed. A current Japanese trainee who intends to return to his home country (Japan) and a former Emirati trainee who recently returned to his home country (United Arab Emirates) reviewed the current state of pediatric psychology in their countries and shared their personal training experiences in the field of pediatric psychology in the United States. By highlighting different international trainee perspectives, we have recognized that there is a need for ongoing research that addresses how our current training guidelines support international students in pediatric psychology. International trainees in pediatric psychology are well positioned to have a positive impact in their home countries and support the global outreach of evidenced-based psychological assessment and intervention. It is crucial that the field of pediatric psychology commits to training international trainees appropriately so that they can contribute to reducing mental health disparities worldwide.

Implications for Impact Statement

Of psychology interns, 4–7% do not have American or Canadian citizenships, and many of them plan to return to their home countries and contribute to pediatric psychology by disseminating evidence-based practices globally. Reflecting on international trainee experiences highlights opportunities to support both their training in pediatric psychology and their transition to their home countries.
Plasmonic mid-infrared third harmonic generation in germanium nanoantennas
Authors: Fischer Marco P. , Riede Aaron , Gallacher Kevin , Frigerio Jacopo , Pellegrini Giovanni , Ortolani Michele , Paul Douglas J. , Isella Giovanni , Leitenstorfer Alfred , Biagioni Paolo , Brida Daniele
Published: December 2018

We demonstrate third harmonic generation in plasmonic antennas consisting of highly doped germanium grown on silicon substrates and designed to be resonant in the mid-infrared frequency range that is inaccessible with conventional nonlinear plasmonic materials. Owing to the near-field enhancement, the result is an ultrafast, subdiffraction, coherent light source with a wavelength tunable between 3 and 5 µm, and ideally overlapping with the fingerprint region of molecular vibrations. To observe the nonlinearity in this challenging spectral window, a high-power femtosecond laser system equipped with parametric frequency conversion in combination with an all-reflective confocal microscope setup is employed. We demonstrate spatially resolved maps of the linear scattering cross section and the nonlinear emission of single isolated antenna structures. A clear third-order power dependence as well as mid-infrared emission spectra prove the nonlinear nature of the light emission. Simulations support the observed resonance length of the double-rod antenna and demonstrate that the field enhancement inside the antenna material is responsible for the nonlinear frequency mixing.
Neurostructural correlate of math anxiety in the brain of children
Authors: Kucian Karin , McCaskey Ursina , O’Gorman Tuura Ruth , von Aster Michael
Published: December 2018

Adequate mathematical competencies are currently indispensable in professional and social life. However, mathematics is often associated with stress and frustration and the confrontation with tasks that require mathematical knowledge triggers anxiety in many children. We examined if there is a relationship between math anxiety and changes in brain structure in children with and without developmental dyscalculia. Our findings showed that math anxiety is related to altered brain structure. In particular, the right amygdala volume was reduced in individuals with higher math anxiety. In conclusion, math anxiety not only hinders children in arithmetic development, but it is associated with altered brain structure in areas related to fear processing. This emphasizes the far-reaching outcome emotional factors in mathematical cognition can have and encourages educators and researchers alike to consider math anxiety to prevent detrimental long-term consequences on school achievement and quality of life, especially in children with developmental dyscalculia.
Constructing exact representations of quantum many-body systems with deep neural networks
Authors: Carleo Giuseppe , Nomura Yusuke , Imada Masatoshi
Published: December 2018

Obtaining accurate properties of many-body interacting quantum matter is a long-standing challenge in theoretical physics and chemistry, rooting into the complexity of the many-body wave-function. Classical representations of many-body states constitute a key tool for both analytical and numerical approaches to interacting quantum problems. Here, we introduce a technique to construct classical representations of many-body quantum systems based on artificial neural networks. Our constructions are based on the deep Boltzmann machine architecture, in which two layers of hidden neurons mediate quantum correlations. The approach reproduces the exact imaginary-time evolution for many-body lattice Hamiltonians, is completely deterministic, and yields networks with a polynomially-scaling number of neurons. We provide examples where physical properties of spin Hamiltonians can be efficiently obtained. Also, we show how systematic improvements upon existing restricted Boltzmann machines ansatze can be obtained. Our method is an alternative to the standard path integral and opens new routes in representing quantum many-body states.
Drug and disease signature integration identifies synergistic combinations in glioblastoma
Authors: Stathias Vasileios , Jermakowicz Anna M. , Maloof Marie E. , Forlin Michele , Walters Winston , Suter Robert K. , Durante Michael A. , Williams Sion L. , Harbour J. William , Volmar Claude-Henry , Lyons Nicholas J. , Wahlestedt Claes , Graham Regina M. , Ivan Michael E. , Komotar Ricardo J. , Sarkaria Jann N. , Subramanian Aravind , Golub Todd R. , Schürer Stephan C. , Ayad Nagi G.
Published: December 2018

Glioblastoma (GBM) is the most common primary adult brain tumor. Despite extensive efforts, the median survival for GBM patients is approximately 14 months. GBM therapy could benefit greatly from patient-specific targeted therapies that maximize treatment efficacy. Here we report a platform termed SynergySeq to identify drug combinations for the treatment of GBM by integrating information from The Cancer Genome Atlas (TCGA) and the Library of Integrated Network-Based Cellular Signatures (LINCS). We identify differentially expressed genes in GBM samples and devise a consensus gene expression signature for each compound using LINCS L1000 transcriptional profiling data. The SynergySeq platform computes disease discordance and drug concordance to identify combinations of FDA-approved drugs that induce a synergistic response in GBM. Collectively, our studies demonstrate that combining disease-specific gene expression signatures with LINCS small molecule perturbagen-response signatures can identify preclinical combinations for GBM, which can potentially be tested in humans.
Author Correction: Thermal transport crossover from crystalline to partial-crystalline partial-liquid state
Authors: Zhou Yanguang , Xiong Shiyun , Zhang Xiaoliang , Volz Sebastian , Hu Ming
Published: December 2018

The original version of this Article incorrectly omitted an affiliation of Sebastian Volz: ‘LIMMS/CNRS-IIS(UMI2820) Institute of Industrial Science, University of Tokyo 4-6-1 Komaba, Meguro-ku Tokyo 153-8505 JAPAN’. This has now been corrected in both the PDF and HTML versions of the Article.
Blocking-cyclization technique for precise synthesis of cyclic polymers with regulated topology
Authors: Chen Jie , Li Hongfei , Zhang Hengchen , Liao Xiaojuan , Han Huijing , Zhang Lidong , Sun Ruyi , Xie Meiran
Published: December 2018

Ring-closure and ring-expansion techniques are the two routes for extensive synthesis of cyclic polymers. Here, we report an alternative blocking-cyclization technique referred to as the third route to prepare cyclic polymers with regulated ring size and ring number by ring-opening metathesis polymerization of di- and monofunctional monomers in a one-pot process, where the polymer intermediates bearing two single-stranded blocks are efficiently cyclized by the cyclizing unit of propagated ladderphane to generate corresponding mono-, bis-, and tricyclic polymers, and the well-defined ladderphane structure plays a crucial role in forming the cyclic topology. Monocyclic polymer is further modified via Alder-ene reaction and the cyclic molecular topology is clearly demonstrated. The diversity features of cyclic polymers are comprehensively revealed. This strategy has broken through the limitations of previous two cyclizing routes, and indeed opens a facile and popular way to various cyclic polymers by commercial Grubbs catalyst and conventional metathesis polymerization.
Templated synthesis of cubic crystalline single networks having large open-space lattices by polymer cubosomes
Authors: La Yunju , Song Jeongeun , Jeong Moon Gon , Cho Arah , Jin Seon-Mi , Lee Eunji , Kim Kyoung Taek
Published: December 2018

The synthesis of biophotonic crystals of insects, cubic crystalline single networks of chitin having large open-space lattices, requires the selective diffusion of monomers into only one of two non-intersecting water-channel networks embedded within the template, ordered smooth endoplasmic reticulum (OSER). Here we show that the topology of the circumferential bilayer of polymer cubosomes (PCs)—polymeric analogues to lipid cubic membranes and complex biological membranes—differentiate between two non-intersecting pore networks embedded in the cubic mesophase by sealing one network at the interface. Consequently, single networks having large lattice parameters (>240 nm) are synthesized by cross-linking of inorganic precursors within the open network of the PCs. Our results pave the way to create triply periodic structures of open-space lattices as photonic crystals and metamaterials without relying on complex multi-step fabrication. Our results also suggest a possible answer for how biophotonic single cubic networks are created, using OSER as templates.
TAC-seq: targeted DNA and RNA sequencing for precise biomarker molecule counting
Authors: Teder Hindrek , Koel Mariann , Paluoja Priit , Jatsenko Tatjana , Rekker Kadri , Laisk-Podar Triin , Kukuškina Viktorija , Velthut-Meikas Agne , Fjodorova Olga , Peters Maire , Kere Juha , Salumets Andres , Palta Priit , Krjutškov Kaarel
Published: December 2018

Targeted next-generation sequencing (NGS) methods have become essential in medical research and diagnostics. In addition to NGS sensitivity and high-throughput capacity, precise biomolecule counting based on unique molecular identifier (UMI) has potential to increase biomolecule detection accuracy. Although UMIs are widely used in basic research its introduction to clinical assays is still in progress. Here, we present a robust and cost-effective TAC-seq (Targeted Allele Counting by sequencing) method that uses UMIs to estimate the original molecule counts of mRNAs, microRNAs, and cell-free DNA. We applied TAC-seq in three different clinical applications and compared the results with standard NGS. RNA samples extracted from human endometrial biopsies were analyzed using previously described 57 mRNA-based receptivity biomarkers and 49 selected microRNAs at different expression levels. Cell-free DNA aneuploidy testing was based on cell line (47,XX, +21) genomic DNA. TAC-seq mRNA profiling showed identical clustering results to transcriptome RNA sequencing, and microRNA detection demonstrated significant reduction in amplification bias, allowing to determine minor expression changes between different samples that remained undetermined by standard NGS. The mimicking experiment for cell-free DNA fetal aneuploidy analysis showed that TAC-seq can be applied to count highly fragmented DNA, detecting significant (p = 7.6 × 10−4) excess of chromosome 21 molecules at 10% fetal fraction level. Based on three proof-of-principle applications we demonstrate that TAC-seq is an accurate and highly potential biomarker profiling method for advanced medical research and diagnostics.
Diverse Electronic and Magnetic Properties of Chlorination-Related Graphene Nanoribbons
Authors: Nguyen Duy Khanh , Tran Ngoc Thanh Thuy , Nguyen Thanh Tien , Lin Ming-Fa
Published: December 2018

The dramatic changes in electronic and magnetic properties are investigated using the first-principles calculations for halogen(X: Cl, Br, I, At)-adsorbed graphene nanoribbons. The rich and unique features are clearly revealed in the atoms-dominated electronic band structures, spin arrangement/magnetic moment, spatial charge distribution, and orbital- and spin-projected density of states. Halogen adsorptions can create the non-magnetic, ferromagnetic or anti-ferromagnetic metals, being mainly determined by concentrations and edge structures. The number of holes per unit cell increases with the adatom concentrations. Furthermore, magnetism becomes nonmagnetic when the adatom concentration is beyond 60% adsorption. There are many low-lying spin-dependent van Hove singularities. The diversified properties are attributed to the significant X-C bonds, the strong X-X bonds, and the adatom- and edge-carbon-induced spin states.
Visualizing the heterogeneous breakdown of a fractal microstructure during compaction by neutron dark-field imaging
Authors: Harti R. P. , Valsecchi J. , Trtik P. , Mannes D. , Carminati C. , Strobl M. , Plomp J. , Duif C. P. , Grünzweig C.
Published: December 2018

Structural properties of cohesive powders are dominated by their microstructural composition. Powders with a fractal microstructure show particularly interesting properties during compaction where a microstructural transition and a fractal breakdown happen before compaction and force transport. The study of this phenomenon has been challenging due to its long-range effect and the subsequent necessity to characterize these microstructural changes on a macroscopic scale. For the detailed investigation of the complex nature of powder compaction for various densification states along with the heterogeneous breakdown of the fractal microstructure we applied neutron dark-field imaging in combination with a variety of supporting techniques with various spatial resolutions, field-of-views and information depths. We used scanning electron microscopy to image the surface microstructure in a small field-of-view and X-ray tomography to image density variations in 3D with lower spatial resolution. Non-local spin-echo small-angle neutron scattering results are used to evaluate fitting models later used as input parameters for the neutron dark-field imaging data analysis. Finally, neutron dark-field imaging results in combination with supporting measurements using scanning electron microscopy, X-ray tomography and spin-echo small angle scattering allowed us to comprehensively study the heterogeneous transition from a fractal to a homogeneous microstructure of a cohesive powder in a quantitative manner.
The frequencies of micronuclei, nucleoplasmic bridges and nuclear buds as biomarkers of genomic instability in patients with urothelial cell carcinoma
Authors: Podrimaj-Bytyqi Arjeta , Borovečki Ana , Selimi Qerim , Manxhuka-Kerliu Suzana , Gashi Goneta , Elezaj Isa R.
Published: December 2018

Bladder urothelial cell carcinoma (UCC) is an increasingly prevalent cancer worldwide, and thus, gaining a better understanding of its identifiable risk factors is a global priority. This study addressed this public health need with the understanding that cancer-initiating events, such as chromosome breakage, loss and rearrangement, can be reasonably used as biomarkers to evaluate an individual’s cancer risk. Overall, forty bladder cancer patients and twenty controls were evaluated for genomic instability. To the best of the investigators’ knowledge, this is the first study to perform micronucleus (MN) assays simultaneously in urothelial exfoliated cells (UEC), buccal exfoliated cells (BEC), and peripheral blood lymphocytes (PBL) in first-diagnosed, non-smoker bladder UCC patients. Additionally, the frequency of nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL was evaluated. The MN frequencies in UEC, BEC, and PBL, as well as the frequencies of NPBs and NBUDs, were significantly higher in patients than in controls. In conclusion, MN assays, particularly in UEC, may be used to identify individuals who are at high risk of developing UCC, as single or as additional triage test to UroVysion FISH test. Our results further validate the efficacy of biomarkers, such as MN, NPBs, and NBUDs, as predictors of genomic instability.
Evaluation of relationships between onychomycosis and vascular diseases using sequential pattern mining
Authors: Bang Chul Hwan , Yoon Jae Woong , Lee Hyun Ji , Lee Jun Young , Park Young Min , Lee Suk Jun , Lee Ji Hyun
Published: December 2018

Onychomycosis (OM) is a common nail disease. Although controversial, vascular diseases are considered independent predictors of OM and vice versa. Sequential pattern mining (SPM) has not been previously used for statistical analysis in dermatology, but it is an efficient method for identifying frequent association rules in multiple sequential data sets. The aim of our study was to identify the relationship between OM and vascular diseases in the real world through a population-based study using SPM. We obtained population-based data recorded from 2002 to 2013 by the Health Insurance Research and Assessment Agency. Cases of vascular-related disease and OM were identified using the diagnostic codes of the International Classification of Diseases 10th Revision, version 2010. SPM measures were based on comorbidity and duration values. We estimated 3-year risk for progression from OM to vascular disease and vice versa using logistic regression. Patients with varicose veins and peripheral vascular disease had higher OM comorbidity (comorbidity: 1.26% and 0.69%, respectively) than did those with other vascular diseases. Patients diagnosed with varicose veins and peripheral vascular disease were diagnosed with OM after 25.50 and 55.10 days, respectively, which was a shorter duration than that observed for other diseases. Patients with OM were at higher risk for peripheral vascular disease (adjusted odds ratio (aOR) 1.199 [95% confidence interval (CI) 1.151–1.249]) and varicose veins (aOR 1.150 [95% CI 1.063–1.245]). Patients with peripheral vascular disease (aOR 1.128 [95% CI 1.081–1.177]) were at higher risk for OM, while patients with varicose veins had no significant risk for OM. Careful consideration of varicose veins or peripheral vascular disease is required for proper management of comorbidities in patients with OM.
Identification of cytochrome P450 monooxygenase genes and their expression in response to high temperature in the alligatorweed flea beetle Agasicles hygrophila (Coleoptera: Chrysomelidae)
Authors: Zhang Hong , Zhao Meiting , Liu Yiran , Zhou Zhongshi , Guo Jianying
Published: December 2018

Cytochrome P450 monooxygenases (P450s) are a large class of enzymes that play essential roles in metabolic processes such as hormone synthesis and the catabolism of toxins and other chemicals in insects. In the present study, we identified 82 P450 genes using comprehensive RNA sequencing in the flea beetle Agasicles hygrophila, and all of the sequences were validated by cloning and sequencing. Phylogenetic analysis showed that the P450 genes in A. hygrophila fell into the mitochondrial clan, CYP2 clan, CYP3 clan and CYP4 clan and were classified into 20 families and 48 subfamilies. Most A. hygrophila P450 genes had high sequence homology with those from other coleopteran insects. To understand the effects of high temperatures on the metabolic processes of female and male adults, we studied the effects of two temperature regimes (constant temperature of 28 °C for 20 h with a 4-h period of high temperatures of 30 °C and 39 °C) on the expression levels of P450 genes in A. hygrophila using RT-PCR and qRT-PCR. The results showed that there were no differences in expression in 30 P450 genes between the control and high-temperature-treated A. hygrophila adults, while 22 P450 genes showed up-regulated expression and 19 P450 genes were down-regulated in A. hygrophila female adults after high-temperature treatment. For A. hygrophila male adults exposed to high temperatures, we found that 8 P450 genes had higher expression levels and 12 P450 genes had lower expression levels under the same conditions. The P450 genes are candidates that showed significantly different expression levels after high-temperature treatments in A. hygrophila adults, and further studies are needed to determine their possible roles in metabolic processes during the response to elevated temperatures.
Along-shelf connectivity and circumpolar gene flow in Antarctic silverfish (Pleuragramma antarctica)
Authors: Caccavo Jilda Alicia , Papetti Chiara , Wetjen Maj , Knust Rainer , Ashford Julian R. , Zane Lorenzo
Published: December 2018

The Antarctic silverfish (Pleuragramma antarctica) is a critically important forage species with a circumpolar distribution and is unique among other notothenioid species for its wholly pelagic life cycle. Previous studies have provided mixed evidence of population structure over regional and circumpolar scales. The aim of the present study was to test the recent population hypothesis for Antarctic silverfish, which emphasizes the interplay between life history and hydrography in shaping connectivity. A total of 1067 individuals were collected over 25 years from different locations on a circumpolar scale. Samples were genotyped at fifteen microsatellites to assess population differentiation and genetic structuring using clustering methods, F-statistics, and hierarchical analysis of variance. A lack of differentiation was found between locations connected by the Antarctic Slope Front Current (ASF), indicative of high levels of gene flow. However, gene flow was significantly reduced at the South Orkney Islands and the western Antarctic Peninsula where the ASF is absent. This pattern of gene flow emphasized the relevance of large-scale circulation as a mechanism for circumpolar connectivity. Chaotic genetic patchiness characterized population structure over time, with varying patterns of differentiation observed between years, accompanied by heterogeneous standard length distributions. The present study supports a more nuanced version of the genetic panmixia hypothesis that reflects physical-biological interactions over the life history.
Nucleus-specific X-ray stain for 3D virtual histology
Authors: Müller Mark , Kimm Melanie A. , Ferstl Simone , Allner Sebastian , Achterhold Klaus , Herzen Julia , Pfeiffer Franz , Busse Madleen
Published: December 2018

Histological investigations are indispensable with regards to the identification of structural tissue details but are limited to two-dimensional images, which are often visualized in one and the same plane for comparison reasons. Nondestructive three-dimensional technologies such as X-ray micro- and nanoCT have proven to provide valuable benefits for the understanding of anatomical structures as they allow visualization of structural details in 3D and from arbitrary viewing angles. Nevertheless, low attenuation of soft tissue has hampered their application in the field of 3D virtual histology. We present a hematein-based X-ray staining method that specifically targets the cell nuclei of cells, as demonstrated for a whole liver lobule of a mouse. Combining the novel staining protocol with the high resolving power of a recently developed nanoCT system enables the 3D visualization of tissue architecture in the nanometer range, thereby revealing the real 3D morphology and spatial distribution of the cell nuclei. Furthermore, our technique is compatible with conventional histology, as microscopic slides can be derived from the very same stained soft-tissue sample and further counter staining is possible. Thus, our methodology demonstrates future applicability for modern histopathology using laboratory X-ray CT devices.
Plasmodium falciparum infected erythrocytes can bind to host receptors integrins αVβ3 and αVβ6 through DBLδ1_D4 domain of PFL2665c PfEMP1 protein
Authors: Chesnokov Olga , Merritt Jordan , Tcherniuk Sergey O. , Milman Neta , Oleinikov Andrew V.
Published: December 2018

Major complications and mortality from Plasmodium falciparum malaria are associated with cytoadhesion of parasite-infected erythrocytes (IE). The main parasite ligands for cytoadhesion are members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. Interactions of different host receptor-ligand pairs may lead to various pathological outcomes, like placental or cerebral malaria. It has been shown previously that IE can bind integrin αVβ3. Using bead-immobilized PfEMP1 constructs, we have identified that the PFL2665c DBLδ1_D4 domain binds to αVβ3 and αVβ6. A parasite line expressing PFL2665c binds to surface-immobilized αVβ3 and αVβ6; both are RGD motif-binding integrins. Interactions can be inhibited by cyloRGDFV peptide, an antagonist of RGD-binding integrins. This is a first, to the best of our knowledge, implication of a specific PfEMP1 domain for binding to integrins. These host receptors have important physiological functions in endothelial and immune cells; therefore, these results will contribute to future studies and a better understanding, at the molecular level, of the physiological outcome of interactions between IE and integrin receptors on the surface of host cells.
Female adipose tissue-specific Bscl2 knockout mice develop only moderate metabolic dysfunction when housed at thermoneutrality and fed a high-fat diet
Authors: Mcilroy George D. , Mitchell Sharon E. , Han Weiping , Delibegović Mirela , Rochford Justin J.
Published: December 2018

Mutations affecting the BSCL2 gene cause the most severe form of congenital generalised lipodystrophy. Affected individuals almost completely lack adipose tissue and suffer from severe diabetes and metabolic complications. Likewise, mice lacking Bscl2 in all tissues have dramatically reduced adipose mass, glucose intolerance and hyperinsulinaemia. However, male adipose tissue-specific Bscl2 knockout mice fail to develop the metabolic dysfunction observed in Bscl2 null mice and BSCL2 deficient patients, despite a similar generalised lack of adipose tissues. Clinical reports indicate gender differences frequently exist in cases of lipodystrophy, with female patients more adversely affected than male patients. We therefore generated and characterised female mice lacking Bscl2 specifically in adipose tissue (Ad-B2(−/−)). We show that female Ad-B2(−/−) mice also develop early-onset lipodystrophy when fed a chow diet and are maintained under standard housing conditions (21 °C) or thermoneutrality (30 °C). Despite this, female Ad-B2(−/−) mice fail to develop severe metabolic dysfunction. Only when female Ad-B2(−/−) mice are maintained at thermoneutrality and fed a high-fat diet do subtle alterations to metabolic homeostasis manifest. This is despite a striking inability to expand adipose mass. Our findings provide further evidence that loss of Bscl2 in non-adipose tissues may contribute to the severity of metabolic dysfunction in this condition.
Essential oils sensory quality and their bioactivity against the mosquito Aedes albopictus
Authors: Bedini S. , Flamini G. , Ascrizzi R. , Venturi F. , Ferroni G. , Bader A. , Girardi J. , Conti B.
Published: December 2018

Repellents are a main tool to prevent the outbreak of mosquito-borne diseases that represents a threat for millions of people worldwide. Plant-based products are very promising, low-toxic and eco-friendly alternative to synthetic repellents. Here, we performed an olfactory screening of the essential oils (EOs) ofArtemisia verlotiorumLamotte (Asteraceae),Lavandula dentataL. (Lamiaceae), andRuta chalepensisL. (Rutaceae) for their possible use as ingredients in topical repellents. The EOs smell profiles were then matched with their repellence against the mosquitoAedes albopictus(Skuse) (Diptera Culicidae). To obtain a more complete bioactivity description, we also tested the EOs oviposition deterrence and the larvicidal activity. The best smell profile was associated withA.verlotiorumEO, whileR.chalepensisEO showed the lowest overall pleasantness. All the EOs had a significant activity as skin repellent againstAe.albopictus, deterred the oviposition in the field, and exerted a clear larvicidal activity. Beside the best smell profile,A.verlotiorumEO showed also the longest lasting repellent effect, assuring the complete protection of the treated skin againstAe.albopictusfor a time 60% longer than the synthetic repellent DEET.
Miniscule differences between sex chromosomes in the giant genome of a salamander
Authors: Keinath Melissa C. , Timoshevskaya Nataliya , Timoshevskiy Vladimir A. , Voss S. Randal , Smith Jeramiah J.
Published: December 2018

In the Mexican axolotl (Ambystoma mexicanum), sex is determined by a single Mendelian factor, yet its sex chromosomes do not exhibit morphological differentiation typical of many vertebrate taxa that possess a single sex-determining locus. As sex chromosomes are theorized to differentiate rapidly, species with undifferentiated sex chromosomes provide the opportunity to reconstruct early events in sex chromosome evolution. Whole genome sequencing of 48 salamanders, targeted chromosome sequencing and in situ hybridization were used to identify the homomorphic sex chromosome that carries an A. mexicanum sex-determining factor and sequences that are present only on the W chromosome. Altogether, these sequences cover ~300 kb of validated female-specific (W chromosome) sequence, representing ~1/100,000th of the 32 Gb genome. Notably, a recent duplication of ATRX, a gene associated with mammalian sex-determining pathways, is one of few functional (non-repetitive) genes identified among these W-specific sequences. This duplicated gene (ATRW) was used to develop highly predictive markers for diagnosing sex and represents a strong candidate for a recently-acquired sex determining locus (or sexually antagonistic gene) in A. mexicanum.
Cognitively Demanding Object Negotiation While Walking and Texting
Authors: Chopra Preeti , Castelli Darla M. , Dingwell Jonathan B.
Published: December 2018

Cell phone related pedestrian injuries are increasing, but the underlying causes remain unclear. Here, we studied how cell phone use directly affected obstacle avoidance ability. Thirty healthy adults participated. Cognitive capacity was quantified using standard tests. Participants walked on a treadmill in a virtual reality environment with and without performing a texting-like cell phone task. Participants also navigated either ‘no’, ‘simple’ or ‘complex’ object negotiation tasks that directly manipulated the cognitive complexity of this object negotiation task. Cell phone use led to more collisions, delayed responses, and increased variability of responses when navigating objects. Mean object avoidance responses were further delayed for the cognitively more complex object negotiation task. Individuals’ baseline attentional capacity inversely predicted the number of object collisions when participants used the cell phone. Individuals with higher cognitive flexibility (i.e., better ability to switch between tasks) performed better on the cell phone task when they had to negotiate obstacles. Importantly, cognitive ability predicted performance only when both tasks (texting and negotiating objects) were being performed. Thus, using a cell phone while walking introduces a visual distraction that impairs healthy adults’ ability to respond to cognitively demanding object negotiation tasks in their environment.
Niacin, alkaloids and (poly)phenolic compounds in the most widespread Italian capsule-brewed coffees
Authors: Angelino Donato , Tassotti Michele , Brighenti Furio , Del Rio Daniele , Mena Pedro
Published: December 2018

Coffee is one of the most popular beverages worldwide and, nowadays, one of the most practical way for its preparation is by prepacked capsules. The aim of this study was comparing the content in caffeine, trigonelline, N-methylpyridinium (NMP), niacin, and chlorogenic acids of 65 different capsule-brewed coffees, commercialised by 5 of the most representative brands in Italy. Coffees were prepared from capsules following manufacturer’s instructions and analysed with an optimized UHPLC-MS/MS method able to assess all these phytochemicals in one single run. Inter-lot and capsule variability were also studied for a subset of coffee capsules. Except for decaffeinated coffees, caffeine amount accounted between 54 and 208 mg/serving. Regular espresso coffees showed higher trigonelline, NMP, and niacin concentrations than large (lungo) and decaffeinated samples, with average serving amounts of 17.96, 1.78, and 0.66 mg, respectively. Regarding chlorogenic acids, caffeoylquinic acids were the most relevant ones (20–117 mg/serving). Feruloylquinic acids were quantified between 8 and 50 mg/serving. Coumaroylquinic acids, hydroxycinnamate dimers, caffeoylshikimic acids, and caffeoylquinic lactones were also present at lower concentrations. Multivariate analysis provided comprehensive information on the phytochemical profile of the different types of coffee, showing a great variability among coffees with some brand-related insights. This study supports the need for accurately characterizing espresso coffees while investigating the beneficial effects of coffee on human health.
Individual spindle detection and analysis in high-density recordings across the night and in thalamic stroke
Authors: Mensen A. , Poryazova R. , Huber R. , Bassetti C. L.
Published: December 2018

Sleep spindles are thalamocortical oscillations associated with several behavioural and clinical phenomena. In clinical populations, spindle activity has been shown to be reduced in schizophrenia, as well as after thalamic stroke. Automatic spindle detection algorithms present the only feasible way to systematically examine individual spindle characteristics. We took an established algorithm for spindle detection, and adapted it to high-density EEG sleep recordings. To illustrate the detection and analysis procedure, we examined how spindle characteristics changed across the night and introduced a linear mixed model approach applied to individual spindles in adults (n = 9). Next we examined spindle characteristics between a group of paramedian thalamic stroke patients (n = 9) and matched controls. We found a high spindle incidence rate and that, from early to late in the night, individual spindle power increased with the duration and globality of spindles; despite decreases in spindle incidence and peak-to-peak amplitude. In stroke patients, we found that only left-sided damage reduced individual spindle power. Furthermore, reduction was specific to posterior/fast spindles. Altogether, we demonstrate how state-of-the-art spindle detection techniques, applied to high-density recordings, and analysed using advanced statistical approaches can yield novel insights into how both normal and pathological circumstances affect sleep.
Development of transgenic Caenorhabditis elegans expressing human transthyretin as a model for drug screening
Authors: Tsuda Yukimoto , Yamanaka Kunitoshi , Toyoshima Risa , Ueda Mitsuharu , Masuda Teruaki , Misumi Yohei , Ogura Teru , Ando Yukio
Published: December 2018

Familial amyloid polyneuropathy is a hereditary systemic amyloidosis caused by a mutation in the transthyretin (TTR) gene. Amyloid deposits in tissues of patients contain not only full-length TTR but also C-terminal TTR fragments. However, in vivo models to evaluate the pathogenicity of TTR fragments have not yet been developed. Here, we generated transgenic Caenorhabditis elegans strains expressing several types of TTR fragments or full-length TTR fused to enhanced green fluorescent protein in the body wall muscle cells and analyzed the phenotypes of the worms. The transgenic strain expressing residues 81–127 of TTR, which included the β-strands F and H, formed aggregates and caused defective worm motility and a significantly shortened lifespan compared with other strains. These findings suggest that the C-terminal fragments of TTR may contribute to cytotoxicity of TTR amyloidosis in vivo. By using this C. elegans model system, we found that (−)-epigallocatechin-3-gallate, a major polyphenol in green tea, significantly inhibited the formation of aggregates, the defective motility, and the shortened lifespan caused by residues 81–127 of TTR. These results suggest that our newly developed C. elegans model system will be useful for in vivo pathological analyses of TTR amyloidosis as well as drug screening.