bluuebunny/crossref_metadata_2025 huggingface dataset:
A.01 Parkinson’s disease prognosis by early motor subtypes
Authors: Hey N , Rajput ML , Rajput AH , Rajput A
Published: June 2018

Background: Studies of autopsy-confirmed cases suggest that Parkinson’s disease (PD) prognosis can be predicted using motor symptom severity at first visit. We evaluated the association between motor symptom subtype at first visit and severity at eight years disease duration among clinically-diagnosed cases at the Saskatchewan Movement Disorder Program. Methods: Retrospective data review identified 374 patients with first visit within three years of symptom onset, a clinical diagnosis of idiopathic PD, and a follow-up visit eight years after symptom onset. Subtypes were grouped as tremor-dominant (TD) if tremor was greater than rigidity and bradykinesia, akinetic-rigid (AR) if rigidity or bradykinesia was greater than tremor, and mixed (MX) if patient was neither TD nor AR based on assessment of all four limbs. Primary outcome was disease severity as measured by Hoehn & Yahr score at eight years after symptom onset. Results: The most common subtype was AR (n=164) followed by MX (n=156). TD was least common (n=54). There was no significant difference between subtypes in H&Y scores at eight years disease duration. Conclusions: These findings suggest that early PD prognosis cannot be predicted based on motor symptoms in all four limbs at first visit. Earlier studies had longer follow-up and future studies will examine progression at longer periods of disease duration.
C.03 Surgical complications with and without image guidance: meta-analysis of Ommaya reservoir insertions
Authors: Lau JC , Kosteniuk SE , Walker T , Iansavitchene A , Macdonald DR , Megyesi JF
Published: June 2018

Background: There remains an important role for consolidating evidence on the utility of image guidance (IG) in neurosurgery. In 1963, Ayub Ommaya proposed a surgical technique for the -placement of a subcutaneous reservoir and pump to allow access to intraventricular cerebrospinal fluid. In this study, we sought to compile evidence from the literature about surgical outcome in ORI with and without IG. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Overall surgical complication rate was considered a primary outcome and further classified into specific complication categories. Results: 40 studies were identified, including our own series, for a total of 1947 independent ORI procedures. Pooled rates of outcome for IG compared to non-IG were 6.0% versus 13.6% for overall complications; 2.0% versus 2.8% for catheter malfunction; 1.9% versus 2.3% for catheter malposition; 0.5% versus 4.0% for early infection; 4.3% versus 9.4% for any infection; and 0.4% versus 1.4% for mortality. Conclusions: We observed that IG ORI resulted in improved accuracy and decreased complications compared to non-IG. To our knowledge, this study comprises the largest observational analysis of operative outcomes demonstrating evidence for the utility of IG.
Lumpen Politics? A Day in “El Hueco”
Authors: Gandolfo Daniella
Published: June 2018

The market of El Hueco in downtown Lima sits inside a large pit dug out for the foundation of a state building that was never built. The below-ground corridors and crammed vending stalls in this poorly regulated market are usually flooded with shoppers, yet government officials and the media frequently condemn it as a vile and dangerous place. But how and why does El Hueco offend? Through an ethnographic account of a day's events, cast against a discussion of Marxism's “lumpenproletariat” and Hernando de Soto's “informality,” I argue that implicit in El Hueco's challenge of state bureaucracy is a class critique that resists conventional class analysis and that affirms the “lumpen” as a politics in its own right. “Lumpen” here does not refer to categories of people but to a resource that can be appropriated and deployed freely. Linked to the anti-political tactics of President Alberto Fujimori in the 1990s, lumpen as a resource has changed the face of postwar Lima by defying and deforming from within the bourgeois ideals of urban development and bureaucratic form. It has also arguably changed the face of politics and played a role in the revival of fujimorismo during and since the 2016 presidential elections.
The Flying Newspapermen and the Time-Space of Late Colonial Nigeria
Authors: James Leslie
Published: June 2018

Recent scholarship on Indian, African, and Caribbean political thinkers and leaders emphasizes the era leading up to and immediately after decolonization as one saturated with awareness of time and history. While much of this scholarship focuses on temporalities that open up the future, this article instead foregrounds imaginings of the present in the currency of news reports. By examining newspaper reports, we can attend in a different way to renderings of time and freedom. This article applies theoretical work on genre and addressivity to analyze how location, space, and time were simultaneously grounded and overcome by Nigerian newspaper columnists, and how this dynamic of bounded transcendence facilitated an array of social and political projects in the time-space of 1930s and 1940s colonial Nigeria. The pseudonymous writers examined in this article applied the trope of flying to exist in an alternate reality. Each “reporter” outstripped the normal logic of time and space through their ability to “jump” from place to place, and even to be in more than one place at once. By existing, as they claimed, “everywhere and nowhere” they literally and figuratively rose above the material reality of the everyday, thus ordaining an exclusive capacity for revelation.
The Foundation: Design, Time, and Possibility in 1960s Nairobi
Authors: Magaziner Daniel
Published: June 2018

This article explores the history of an experiment in architectural education that took place at what is today the University of Nairobi, between 1965 and 1967. Organized by Selby Mvusi, a South African industrial designer, and Derek Morgan, a British expatriate architect, what was known as the “Foundation Course” was both an experiment in architectural education in postcolonial Africa and a serious attempt to think through the African experience of time and equip students with the tools to recognize and respond to the unique conditions of the postcolonial African present. Based on archival sources, including those in private collections, and oral interviews, the article situates the Foundation Course within African intellectual history as an exercise in social theory and phenomenology. I examine the content of Mvusi and Morgan's intellectual partnership and project by tracing their individual trajectories, and especially the pedagogical scheme they developed at Nairobi, which came to focus more on humanity in dialogue with the material environment than on material objects themselves. I trace the intellectual lineages of their concepts and explore their articulation within the postcolonial university until the course was cancelled in 1967. I conclude by considering how Mvusi imagined the Foundation Course as a laboratory for both being and building in postcolonial Africa, drawing from a conference paper he delivered just weeks before he died in 1967.
Effect of fluctuations on mean-field dynamos
Authors: Alexakis A. , Fauve S. , Gissinger C. , Pétrélis F.
Published: June 2018

We discuss the effect of different types of fluctuations on dynamos generated in the limit of scale separation. We first recall that the magnetic field observed in the VKS (von Karman flow of liquid sodium) experiment is not the one that would be generated by the mean flow alone and that smaller scale turbulent fluctuations therefore play an important role. We then consider how velocity fluctuations affect the dynamo threshold in the framework of mean-field magnetohydrodynamics. We show that the detrimental effect of turbulent fluctuations observed with many flows disappears in the case of helical flows with scale separation. We also find that fluctuations of the electrical conductivity of the fluid, for instance related to temperature fluctuations in convective flows, provide an efficient mechanism for dynamo action. Finally, we conclude by describing an experimental configuration that could be used to test the validity of mean-field magnetohydrodynamics in strongly turbulent flows.
Personalisation, customisation and bricolage: how people with dementia and their families make assistive technology work for them
Authors: Gibson Grant , Dickinson Claire , Brittain Katie , Robinson Louise
Published: June 2018

Assistive technologies (ATs) are being ‘mainstreamed’ within dementia care, where they are promoted as enabling people with dementia to age in place alongside delivering greater efficiencies in care. AT provision focuses upon standardised solutions, with little known about how ATs are used by people with dementia and their carers within everyday practice. This paper explores how people with dementia and carers use technologies in order to manage care. Findings are reported from qualitative semi-structured interviews with 13 people with dementia and 26 family carers. Readily available household technologies were used in conjunction with and instead of AT to address diverse needs, replicating AT functions when doing so. Successful technology use was characterised by ‘bricolage’ or the non-conventional use of tools or methods to address local needs. Carers drove AT use by engaging creatively with both assistive and everyday technologies, however, carers were not routinely supported in their creative engagements with technology by statutory health or social care services, making bricolage a potentially frustrating and wasteful process. Bricolage provides a useful framework to understand how technologies are used in the everyday practice of dementia care, and how technology use can be supported within care. Rather than implementing standardised AT solutions, AT services and AT design in future should focus on how technologies can support more personalised, adaptive forms of care.
Siegel families with application to class fields
Authors: Koo Ja Kyung , Shin Dong Hwa , Yoon Dong Sung
Published: June 2018

We investigate certain families of meromorphic Siegel modular functions on which Galois groups act in a natural way. By using Shimura's reciprocity law we construct some algebraic numbers in the ray class fields of CM-fields in terms of special values of functions in these Siegel families.
Childhood dietary trajectories and adolescent cardiovascular phenotypes: Australian community-based longitudinal study
Authors: Kerr Jessica A , Gillespie Alanna N , Gasser Constantine E , Mensah Fiona K , Burgner David , Wake Melissa
Published: June 2018

Objective

With the intention to inform future public health initiatives, we aimed to determine the extent to which typical childhood dietary trajectories predict adolescent cardiovascular phenotypes.

Design

Longitudinal study. Exposure was determined by a 4 d food diary repeated over eight waves (ages 4–15 years), coded by Australian Dietary Guidelines and summed into a continuous diet score (0–14). Outcomes were adolescent (Wave 8, age 15 years) blood pressure, resting heart rate, pulse wave velocity, carotid intima-media thickness, retinal arteriole-to-venule ratio. Latent class analysis identified ‘typical’ dietary trajectories from childhood to adolescence. Adjusted linear regression models assessed relationships between trajectories and cardiovascular outcomes, adjusted for a priori potential confounders.

Setting

Community sample, Melbourne, Australia.

Subjects

Children (n 188) followed from age 4 to 15 years.

Results

Four dietary trajectories were identified: unhealthy (8 %); moderately unhealthy (25 %); moderately healthy (46 %); healthy (21 %). There was little evidence that vascular phenotypes associated with the trajectories. However, resting heart rate (beats/min) increased (β; 95 % CI) across the healthy (reference), moderately healthy (4·1; −0·6, 8·9; P=0·08), moderately unhealthy (4·5; −0·7, 9·7; P=0·09) and unhealthy (10·5; 2·9, 18·0; P=0·01) trajectories.

Conclusions

Decade-long dietary trajectories did not appear to influence macro- or microvascular structure or stiffness by mid-adolescence, but were associated with resting heart rate, suggesting an early-life window for prevention. Larger studies are needed to confirm these findings, the threshold of diet quality associated with these physiological changes and whether functional changes in heart rate are followed by phenotypic change.
Universal Phonological Features
Authors: Xie Jiushu , Zhong Xiao , Xiang Yanhui , Wang Ruiming , Zhang Jun , Xie Jiawei , Mo Lei
Published: June 2018

Abstract. The Theory of universal grammar suggests that human languages may share some similarities at the phonological level. Based on this hypothesis, we further propose a language generalization effect (LGE) and hypothesize that people may inherit the universal phonological features from their native languages and then transfer them to foreign languages. To test this hypothesis, in two experiments, participants listened to a pair of normal and syllable reversed recordings (Experiments 1a–1d) or normal and phonemic reversed recordings (Experiments 2a–2d) in unknown and native languages and reported their similarities. The results indicated that participants were more sensitive to the dissimilarities of normal recordings than to reversed ones. These results suggest that participants could identify the universal phonological features from normal recordings, but not reversed ones, and then adopt these features to better verify the dissimilarities of normal recordings. In sum, the current study first proposed the LGE and reported primary evidence to support it.
Directional Bias for Vertical Integration of Motion	Trajectories
Authors: Kim Sung-Ho , Choi Jeong-Yoon
Published: June 2018

Abstract. Here we report a new ambiguous continuous motion display, in which two objects appear at the diagonally opposite corners of an imaginary square, move along the diagonal axis toward each other, and after meeting in the center, shift their trajectories to the other two diagonal corners. This display can be seen as two objects’ colliding and bouncing off each other, with two competing interpretations of trajectory configuration requiring either vertical or horizontal integration of trajectory segments. Despite the fact that both percepts are equally plausible, the current study revealed a perceptual preference toward a vertical integration interpretation. We compared this bias with the similar vertical bias in a bistable apparent motion quartet, which suggests that the directional anisotropy found here is quite a new, and distinct phenomenon in both its perceptual characteristics and underlying mechanism.
How Do Delusion-Prone Individuals Respond to Disconfirmatory Evidence?
Authors: Howe Jessica , Ross Robert , McKay Ryan , Balzan Ryan P.
Published: June 2018

Abstract. Research employing the beads task suggests that people with delusional tendencies over-adjust to disconfirmatory evidence compared to low-delusion-prone individuals. This interpretation is in tension with studies using the bias against disconfirmatory evidence (BADE) task, which provide evidence that people with delusional tendencies are less receptive to disconfirmatory evidence. It has been suggested that over-adjustment on the beads task may be driven by miscomprehension of the task. The current preliminary study aimed to minimize miscomprehension on the beads task and determine how high-delusion-prone people respond to disconfirmatory evidence on both tasks. Fifty-one undergraduate participants completed the BADE task and an adapted version of the beads task. We expected that corrective feedback on the beads task would reduce miscomprehension, and that high-delusion-prone participants would be less receptive to disconfirmatory evidence on both tasks. Our results suggest this version of the beads task improved rates of comprehension relative to previous research. However, we found no evidence that the high-delusion-prone group demonstrated elevated over-adjustment or belief inflexibility in either task. The theoretical implications of these findings are discussed.
Psychotic Symptoms Predicting Evidence Integration in Schizophrenia
Authors: Luk Jessica , Underhill Kendra , Woodward Todd S.
Published: June 2018

Abstract. A bias against disconfirmatory evidence (BADE) is a cognitive bias associated with delusions in schizophrenia. Previous studies reporting an association between reduced evidence integration and delusions used a single measure of delusion severity, typically to form patient groups. In the current study we perform an exploratory analysis to investigate whether BADE is specific to delusions or extends to other symptoms of psychosis. To address this, we used constrained principal component analysis (CPCA) on four merged BADE studies on schizophrenia to explore the component structure in the BADE task measures that is predictable from symptoms. A component reflecting evidence integration emerged, and was predicted by delusions as expected, but also by thought disorder. This provides novel methodology for cognitive neuropsychiatric investigations into the underpinnings of the symptoms of schizophrenia by enabling investigators to consider a range of symptoms alongside the one that is the target of their investigation.
Extreme Landfalling Atmospheric River Events in Arizona: Possible Future Changes
Authors: Singh Itinderjot , Dominguez Francina , Demaria Eleonora , Walter James
Published: June 2018

The semiarid Salt and Verde River Basins in Arizona are susceptible to atmospheric river (AR)‐related flooding. To understand the precipitation‐related impacts of climate change on extreme ARs affecting Arizona, a pseudo‐global warming method was used. High‐resolution control and future simulations of five intense historical AR events that affected the Salt and Verde River Basins in Central Arizona were carried out using the Weather Research and Forecasting regional climate model. The pseudo‐global warming approach for future simulations involved adding a temperature delta at different vertical levels to the historical initial and lateral boundary conditions of the input data while keeping constant relative humidity. The deltas were calculated using projected changes toward end of the 21st century from an ensemble of nine Global Climate Models for the Representative Concentration Pathway (RCP) 8.5. Future simulations showed an overall increase in vertically integrated transport of vapor and upward moisture flux at cloud base over the region for all events. The changes in precipitation at both domain and basin levels were highly spatially heterogeneous. Precipitation increased in all future simulations; but in general, this increase remained less than the increase in column‐integrated water vapor. It was found that in most cases, cloud ice content decreased while cloud water content increased, indicating the increased role of warm‐rain processes in producing precipitation in the future simulations. Freezing levels rose by more than 600 m, and this along with increased temperature and greater role of warm‐rain processes led to a decrease of more than 80% in the amount of frozen precipitation during the events.
AGU Publications Continue to Expand, Diversify, and Adapt
Authors: Hanson Brooks , Ford Barbara , Lunn Jenny
Published: June 2018

A review of achievements, developments, and changes in AGU Publications in the past year, and a look ahead to new features, initiatives, and growth ahead.
Frequency‐Dependent Attenuation ofPandSWaves in Southern California
Authors: Lin Yu‐Pin , Jordan Thomas H.
Published: June 2018

Accurate models of crustal attenuation structure are important for simulating seismic wavefields at high frequencies (f > 1 Hz). In this study, we collectedPandSwaveforms from 160 regional earthquakes (3.3 ≤ M ≤ 5.7) recorded at 218 broadband stations of Southern California Seismic Network and measured spectral amplitudes ofPandSwaves in the 1‐ to 10‐Hz band using integrals over wavelet transforms. We accounted for source structure and geometrical spreading by referencing the spectral amplitudes to values computed from 1‐D synthetic seismograms. We inverted the spectral amplitude ratios for a 1‐D, frequency‐dependent crustal attenuation model. When plotted against wavenumber, the depth averages of bothQPandQSare described by the same function,Q(k) = (240 ± 20) k0.40 ± 0.05(1 km−1 ≤ k ≤ 17 km−1). Our results are consistent with attenuation dominated by first‐order Born scattering from an isotropic, self‐affine distribution of elastic heterogeneities with an outer scale of ~10 km, a root‐mean‐square relative amplitude of ~8% and a fractal dimension of ~3.8. The inversions accounted for frequency‐dependent variations in the source spectra and site response. The source spectra roll off at an average rate of about 2 for both wave types. The station residuals, which reflect unresolved lateral structure, show stronger attenuation in the Los Angeles region and weaker attenuation in the batholithic terrains to the north and south, as well as in the Proterozoic terrains on the eastern side of the study region.
Structure and Formation of Anticyclonic Eddies in the Iceland Basin
Authors: Zhao Jian , Bower Amy , Yang Jiayan , Lin Xiaopei , Zhou Chun
Published: June 2018

The Iceland Basin has the most energetic eddy activities in the subpolar North Atlantic. This study documents the structure for an anticyclonic eddy in the Iceland Basin using high‐resolution hydrographic and velocity observations. The eddy core waters have lens‐like structure with warm and salty features in the upper 1,000 m. The eddy distorts the density surface by doming the upper isopycnals and deepening the ones near the permanent pycnocline. The eddy has a diameter of about 120 km with substantial barotropic component in the velocity profiles. One branch of the North Atlantic Current in the central Iceland Basin is superimposed onto the eddy, leading to asymmetric velocity structure. Satellite maps show that eddy first shows up over the western slope of the Hatton Bank and moves westward to the central Iceland Basin. The waters enclosed in the eddy core share the same properties with Subpolar Mode Waters. Similar anticyclonic eddies are also found in high‐resolution numerical model simulations, which is used to explore eddy formation. The model results reveal that the potential vorticity gradient prior to the eddy event change signs in both horizontal and vertical directions. This potential vorticity gradient structure meets the necessary condition for the barotropic and baroclinic instabilities. Further calculation of the energy conversions suggests that eddies extract mean potential energy from the large‐scale isopycnal slope and gain the mean kinetic energy in the upper ocean. Therefore, both barotropic and baroclinic instabilities are involved to support the eddy growth.
Tailoring recombinant lipases: keeping the His-tag favors esterification reactions, removing it favors hydrolysis reactions
Authors: de Almeida Janaina Marques , Moure Vivian Rotuno , Müller-Santos Marcelo , de Souza Emanuel Maltempi , Pedrosa Fábio Oliveira , Mitchell David Alexander , Krieger Nadia
Published: June 2018

We determined the effect of the His-tag on the structure, activity, stability and immobilization of LipC12, a highly active lipase from a metagenomic library. We purified LipC12 with a N-terminal His-tag and then removed the tag using tobacco etch virus (TEV) protease. Circular dichroism analysis showed that the overall structure of LipC12 was largely unaffected by His-tag removal. The specific hydrolytic activities against natural and artificial substrates were significantly increased by the removal of the His-tag. On the other hand, His-tagged LipC12 was significantly more active and stable in the presence of polar organic solvents than untagged LipC12. The immobilization efficiency on Immobead 150 was 100% for both forms of LipC12 and protein desorption studies confirmed that the His-tag does not participate in the covalent binding of the enzyme. In the case of immobilized LipC12, the His-tag negatively influenced the hydrolytic activity, as it had for the free lipase, however, it positively influenced the esterification activity. These results raise the possibility of tailoring recombinant lipases for different applications, where the His-tag may be retained or removed, as appropriate for the desired activity.
Broadband (550–1350 nm) diffuse optical characterization of thyroid chromophores
Authors: Konugolu Venkata Sekar Sanathana , Farina Andrea , Dalla Mora Alberto , Lindner Claus , Pagliazzi Marco , Mora Mireia , Aranda Gloria , Dehghani Hamid , Durduran Turgut , Taroni Paola , Pifferi Antonio
Published: June 2018

Thyroid plays an important role in the endocrine system of the human body. Its characterization by diffuse optics can open new path ways in the non-invasive diagnosis of thyroid pathologies. Yet, the absorption spectra of tyrosine and thyroglobulin–key tissue constituents specific to the thyroid organ–in the visible to near infrared range are not fully available. Here, we present the optical characterization of tyrosine (powder), thyroglobulin (granular form) and iodine (aqueous solution) using a time domain broadband diffuse optical spectrometer in the 550–1350 nm range. Various systematic errors caused by physics of photo migration and sample inherent properties were effectively suppressed by means of advanced time domain diffuse optical methods. A brief comparison with various other known tissue constituents is presented, which reveals key spectral regions for the quantification of the thyroid absorbers in an in vivo scenario.
Breastfeeding and myopia: A cross-sectional study of children aged 6–12 years in Tianjin, China
Authors: Liu Shengxin , Ye Sheng , Wang Qifan , Cao Yongjun , Zhang Xin
Published: June 2018

This study aimed to determine whether an association existed between breastfeeding and myopia in children aged 6–12 years in Tianjin, China, using a cross-sectional study of 527 children. The spherical equivalent refraction (SER) and axial length (AL) were determined by ocular examination, and information regarding the children’s demographics, breastfeeding history and other myopia-related risk factors were investigated using a questionnaire. The myopia prevalence rate, mean SER, and mean AL were 53.9%, −0.99 ± 1.69 D, and 23.56 ± 1.11 mm, respectively. In total, 442 (83.9%) participants were breastfed; among the breastfed participants, 132 (29.9%) were breastfed <6 months. Children who were breastfed were less likely to have myopia (breastfeeding duration <6 months: OR = 0.399, P = 0.011; >6 months: OR = 0.502, P = 0.033, multiple logistical regression). The mean SER of children breastfed <6 months was 0.653 D more hyperopic than that of non-breastfed children (P = 0.008, multiple linear regression). No significant association was observed between breastfeeding and AL. In conclusion, breastfeeding was associated with a decreased risk of myopia among children aged 6–12 years in Tianjin. Breastfeeding during the first 6 months of infancy was associated with more hyperopic SER. Furthermore, breastfeeding was associated with myopic refraction and was not related to AL, and this association could exist in childhood.
Entomological signatures in honey: an environmental DNA metabarcoding approach can disclose information on plant-sucking insects in agricultural and forest landscapes
Authors: Utzeri Valerio Joe , Schiavo Giuseppina , Ribani Anisa , Tinarelli Silvia , Bertolini Francesca , Bovo Samuele , Fontanesi Luca
Published: June 2018

Honeydew produced from the excretion of plant-sucking insects (order Hemiptera) is a carbohydrate-rich material that is foraged by honey bees to integrate their diets. In this study, we used DNA extracted from honey as a source of environmental DNA to disclose its entomological signature determined by honeydew producing Hemiptera that was recovered not only from honeydew honey but also from blossom honey. We designed PCR primers that amplified a fragment of mitochondrial cytochrome c oxidase subunit 1 (COI) gene of Hemiptera species using DNA isolated from unifloral, polyfloral and honeydew honeys. Ion Torrent next generation sequencing metabarcoding data analysis assigned Hemiptera species using a customized bioinformatic pipeline. The forest honeydew honeys reported the presence of high abundance of Cinara pectinatae DNA, confirming their silver fir forest origin. In all other honeys, most of the sequenced reads were from the planthopper Metcalfa pruinosa for which it was possible to evaluate the frequency of different mitotypes. Aphids of other species were identified from honeys of different geographical and botanical origins. This unique entomological signature derived by environmental DNA contained in honey opens new applications for honey authentication and to disclose and monitor the ecology of plant-sucking insects in agricultural and forest landscapes.
Probabilistic Prognostic Estimates of Survival in Metastatic Cancer Patients (PPES-Met) Utilizing Free-Text Clinical Narratives
Authors: Banerjee Imon , Gensheimer Michael Francis , Wood Douglas J. , Henry Solomon , Aggarwal Sonya , Chang Daniel T. , Rubin Daniel L.
Published: June 2018

We propose a deep learning model - Probabilistic Prognostic Estimates of Survival in Metastatic Cancer Patients (PPES-Met) for estimating short-term life expectancy (>3 months) of the patients by analyzing free-text clinical notes in the electronic medical record, while maintaining the temporal visit sequence. In a single framework, we integrated semantic data mapping and neural embedding technique to produce a text processing method that extracts relevant information from heterogeneous types of clinical notes in an unsupervised manner, and we designed a recurrent neural network to model the temporal dependency of the patient visits. The model was trained on a large dataset (10,293 patients) and validated on a separated dataset (1818 patients). Our method achieved an area under the ROC curve (AUC) of 0.89. To provide explain-ability, we developed an interactive graphical tool that may improve physician understanding of the basis for the model’s predictions. The high accuracy and explain-ability of the PPES-Met model may enable our model to be used as a decision support tool to personalize metastatic cancer treatment and provide valuable assistance to the physicians.
Stem cells purified from human induced pluripotent stem cell-derived neural crest-like cells promote peripheral nerve regeneration
Authors: Kimura Hiroo , Ouchi Takehito , Shibata Shinsuke , Amemiya Tsuyoshi , Nagoshi Narihito , Nakagawa Taneaki , Matsumoto Morio , Okano Hideyuki , Nakamura Masaya , Sato Kazuki
Published: June 2018

Strategies for therapeutic cell transplantation have been assessed for use in the treatment of massive peripheral nerve defects. To support safe and efficient cell transplantation, we have focused on the purification of cells using cell surface markers. Our group previously reported low-affinity nerve growth factor receptor (LNGFR)- and thymocyte antigen-1 (THY-1)-positive neural crest-like cells (LT-NCLCs), generated from human induced pluripotent stem cells (hiPSCs). In the present study, we investigated the efficacy of transplantation of hiPSC-derived LT-NCLCs in a murine massive peripheral nerve defect model. Animals with a sciatic nerve defect were treated with a bridging silicone tube prefilled with LT-NCLCs or medium in the transplantation (TP) and negative control (NC) groups, respectively. The grafted LT-NCLCs survived and enhanced myelination and angiogenesis, as compared to the NC group. Behavioral analysis indicated that motor functional recovery in the TP group was superior to that in the NC group, and similar to that in the autograft (Auto) group. LT-NCLCs promoted axonal regrowth and remyelination by Schwann cells. Transplantation of LT-NCLCs is a promising approach for nerve regeneration treatment of massive peripheral nerve defects.
Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
Authors: Chen Elijah W. , Brzostek Joanna , Gascoigne Nicholas R. J. , Rybakin Vasily
Published: June 2018

Activation of the T cell receptor (TCR) leads to the generation of a network of signaling events critical to the developmental decision making and activation of T cells. Various experimental approaches continue to identify new signaling molecules, adaptor proteins, and other regulators of TCR signaling. We propose a screening strategy for the identification of small molecules affecting TCR signaling based on the uncoupling of TCR stimulation from cellular responses in developing thymocytes. We demonstrate that this strategy successfully identifies inhibitors of kinases already shown to act downstream of TCR engagement, as well as new inhibitors. The proposed strategy is easily scalable for high throughput screening and will contribute to the identification of new druggable targets in T cell activation.
Proteomic and metagenomic insights into prehistoric Spanish Levantine Rock Art
Authors: Roldán Clodoaldo , Murcia-Mascarós Sonia , López-Montalvo Esther , Vilanova Cristina , Porcar Manuel
Published: June 2018

The Iberian Mediterranean Basin is home to one of the largest groups of prehistoric rock art sites in Europe. Despite the cultural relevance of prehistoric Spanish Levantine rock art, pigment composition remains partially unknown, and the nature of the binders used for painting has yet to be disclosed. In this work, we present the first omic analysis applied to one of the flagship Levantine rock art sites: the Valltorta ravine (Castellón, Spain). We used high-throughput sequencing to provide the first description of the bacterial communities colonizing the rock art patina, which proved to be dominated by Firmicutes species and might have a protective effect on the paintings. Proteomic analysis was also performed on rock art microsamples in order to determine the organic binders present in Levantine prehistoric rock art pigments. This information could shed light on the controversial dating of this UNESCO Cultural Heritage, and contribute to defining the chrono-cultural framework of the societies responsible for these paintings.
Exploring the amphibian exposome in an agricultural landscape using telemetry and passive sampling
Authors: Swanson Jennifer E. , Muths Erin , Pierce Clay L. , Dinsmore Stephen J. , Vandever Mark W. , Hladik Michelle L. , Smalling Kelly L.
Published: June 2018

This is the first field study of its kind to combine radio telemetry, passive samplers, and pesticide accumulation in tissues to characterize the amphibian exposome as it relates to pesticides. Understanding how habitat drives exposure in individuals (i.e., their exposome), and how that relates to individual health is critical to managing species in an agricultural landscape where pesticide exposure is likely. We followed 72 northern leopard frogs (Lithobates pipiens) in two agricultural wetlands for insight into where and when individuals are at high risk of pesticide exposure. Novel passive sampling devices (PSDs) were deployed at sites where telemetered frogs were located, then moved to subsequent locations as frogs were radio-tracked. Pesticide concentration in PSDs varied by habitat and was greatest in agricultural fields where frogs were rarely found. Pesticide concentrations in frogs were greatest in spring when frogs were occupying wetlands compared to late summer when frogs occupied terrestrial habitats. Our results indicate that habitat and time of year influence exposure and accumulation of pesticides in amphibians. Our study illustrates the feasibility of quantifying the amphibian exposome to interpret the role of habitat use in pesticide accumulation in frogs to better manage amphibians in agricultural landscapes.
Strong Solar Radiation Forces from Anomalously Reflecting Metasurfaces for Solar Sail Attitude Control
Authors: Ullery Dylan C. , Soleymani Sina , Heaton Andrew , Orphee Juan , Johnson Les , Sood Rohan , Kung Patrick , Kim Seongsin M.
Published: June 2018

We examine the theoretical implications of incorporating metasurfaces on solar sails, and the effect they can have on the forces applied to the sail. This would enable a significant enhancement over state-of-the- art attitude control by demonstrating a novel, propellant-free and low-mass approach to induce a roll torque on the sail, which is a current limitation in present state-of-the-art technology. We do so by utilizing anomalous optical reflections from the metasurfaces to generate a net in-plane lateral force, which can lead to a net torque along the roll axis of the sail, in addition to the other spatial movements exhibited by the sail from solar radiation pressure. We characterize this net lateral force as a function of incidence angle. In addition, the influence of the phase gradients and anomalous conversion efficiencies characteristics of the metasurfaces are independently considered. The optimum incidence angle that corresponded with the maximum net lateral-to-normal force ratio was found to be −30° for a metasurface exhibiting 75% anomalous conversion efficiency with a phase gradient of 0:71k0.
Switchable genome editing via genetic code expansion
Authors: Suzuki Toru , Asami Maki , Patel Sanjay G. , Luk Louis Y. P. , Tsai Yu-Hsuan , Perry Anthony C. F.
Published: June 2018

Multiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation and Cas9 variants have accordingly been generated whose activity responds to small ligands, temperature or light. However, these approaches are often impracticable, for example in clinical therapeutic genome editing in situ or gene drives in which environmentally-compatible control is paramount. With this in mind, we have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by the cheap lysine derivative, Lys(Boc) (BOC). Genetic code expansion permitted non-physiological BOC incorporation such that Cas9 (Cas9BOC) was expressed in a full-length, active form in cultured somatic cells only after BOC exposure. Stringently BOC-dependent, heritable editing of transgenic and native genomic loci occurred when Cas9BOC was expressed at the onset of mouse embryonic development from cRNA or Cas9BOC transgenic females. The tightly controlled Cas9 editing system reported here promises to have broad applications and is a first step towards purposed, spatiotemporal gene drive regulation over large geographical ranges.
The Association between Daytime Napping Characteristics and Bone Mineral Density in Elderly Thai Women without Osteoporosis
Authors: Saetung Sunee , Reutrakul Sirimon , Chailurkit La-or , Rajatanavin Rajata , Ongphiphadhanakul Boonsong , Nimitphong Hataikarn
Published: June 2018

Low bone mass is more prevalent with increasing age. Studies have found associations between sleep duration, sleep quality and obstructive sleep apnea and bone mineral density (BMD). However, less is known about the relationship between daytime napping and BMD. We aimed to investigate the association between daytime napping and BMD in elderly Thai women. Demographic data, lifestyle information and sleep characteristics were obtained by interviewing 387 elderly women. Weight and height were measured. Serum 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay. BMD was measured by dual-energy X-ray absorptiometry (DXA). Higher BMI and having type 2 diabetes (T2DM) were correlated with higher lumbar spine 2–4 (L2-4) BMD, while younger age, higher BMI and higher serum 25(OH)D level were correlated with higher femoral neck (FN) and total hip (TH) BMD. After adjusting for age, age at menopause, BMI, 25(OH)D level and T2DM, a higher frequency of weekly daytime napping was associated with lower FN and TH BMD but not at L2-4 BMD. Additionally, longer daytime napping duration was negatively associated with BMD at TH. In summary higher frequency and longer duration of daytime napping are associated with lower femoral BMD in elderly women. Mechanisms underlying these associations should be further explored.
Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1
Authors: Rexen Ulven Elisabeth , Trauelsen Mette , Brvar Matjaz , Lückmann Michael , Bielefeldt Line Ø. , Jensen Lisa K. I. , Schwartz Thue W. , Frimurer Thomas M.
Published: June 2018

The succinate receptor 1 (SUCNR1) is a receptor for the metabolite succinate, which functions as a metabolic stress signal in the liver, kidney, adipose tissue and the retina. However, potent non-metabolite tool compounds are needed to reveal the physiological role and pharmacological potential of SUCNR1. Recently, we published the discovery of a computationally receptor-structure derived non-metabolite SUCNR1 agonist series with high target selectivity. We here report our structure-activity exploration and optimisation that has resulted in the development of agonists with nanomolar potency and excellent solubility and stability properties in a number of in vitro assays. Ligand-guided receptor models with high discriminative power between binding of active and inactive compounds were developed for design of novel chemotypes.
Dual role of HDAC10 in lysosomal exocytosis and DNA repair promotes neuroblastoma chemoresistance
Authors: Ridinger Johannes , Koeneke Emily , Kolbinger Fiona R. , Koerholz Katharina , Mahboobi Siavosh , Hellweg Lars , Gunkel Nikolas , Miller Aubry K. , Peterziel Heike , Schmezer Peter , Hamacher-Brady Anne , Witt Olaf , Oehme Ina
Published: June 2018

Drug resistance is a leading cause for treatment failure in many cancers, including neuroblastoma, the most common solid extracranial childhood malignancy. Previous studies from our lab indicate that histone deacetylase 10 (HDAC10) is important for the homeostasis of lysosomes, i.e. acidic vesicular organelles involved in the degradation of various biomolecules. Here, we show that depleting or inhibiting HDAC10 results in accumulation of lysosomes in chemotherapy-resistant neuroblastoma cell lines, as well as in the intracellular accumulation of the weakly basic chemotherapeutic doxorubicin within lysosomes. Interference with HDAC10 does not block doxorubicin efflux from cells via P-glycoprotein inhibition, but rather via inhibition of lysosomal exocytosis. In particular, intracellular doxorubicin does not remain trapped in lysosomes but also accumulates in the nucleus, where it promotes neuroblastoma cell death. Our data suggest that lysosomal exocytosis under doxorubicin treatment is important for cell survival and that inhibition of HDAC10 further induces DNA double-strand breaks (DSBs), providing additional mechanisms that sensitize neuroblastoma cells to doxorubicin. Taken together, we demonstrate that HDAC10 inhibition in combination with doxorubicin kills neuroblastoma, but not non-malignant cells, both by impeding drug efflux and enhancing DNA damage, providing a novel opportunity to target chemotherapy resistance.
Comparative studies of alignment, alignment-free and SVM based approaches for predicting the hosts of viruses based on viral sequences
Authors: Li Han , Sun Fengzhu
Published: June 2018

Predicting the hosts of newly discovered viruses is important for pandemic surveillance of infectious diseases. We investigated the use of alignment-based and alignment-free methods and support vector machine using mononucleotide frequency and dinucleotide bias to predict the hosts of viruses, and applied these approaches to three datasets: rabies virus, coronavirus, and influenza A virus. For coronavirus, we used the spike gene sequences, while for rabies and influenza A viruses, we used the more conserved nucleoprotein gene sequences. We compared the three methods under different scenarios and showed that their performances are highly correlated with the variability of sequences and sample size. For conserved genes like the nucleoprotein gene, longer k-mers than mono- and dinucleotides are needed to better distinguish the sequences. We also showed that both alignment-based and alignment-free methods can accurately predict the hosts of viruses. When alignment is difficult to achieve or highly time-consuming, alignment-free methods can be a promising substitute to predict the hosts of new viruses.
Estimation of chimpanzee age based on DNA methylation
Authors: Ito Hideyuki , Udono Toshifumi , Hirata Satoshi , Inoue-Murayama Miho
Published: June 2018

In wild animal conservation, knowing the age of an individual animal is extremely beneficial. However, estimating the age is difficult for many species. Recently, epigenetics-based methods of estimating age have been reported. These studies were predominantly on humans with few reports on other animals, especially wild animals. In the present study, a chimpanzee (Pan troglodytes) age prediction model was developed based on the ELOVL2, CCDC102B, and ZNF423 genes that may also have application in human age prediction. Pyrosequencing was used to measure methylation in 20 chimpanzee blood samples and correlation between age and methylation status was calculated. Age and methylation of sites in ELOVL2 and CCDC102B were significantly correlated and an age prediction model was created using these genes. In the regression equation using only ELOVL2, the highest correlation coefficient was 0.741, with a mean absolute deviation (MAD) of 5.41, compared with the combination of ELOVL2 and CCDC102B, where the highest correlation coefficient was 0.742 and the MAD was 5.41. Although larger MADs were observed in chimpanzees than in humans based on these genes, the results indicate the feasibility of estimating chimpanzee age using DNA methylation, and can have implications in understanding the ecology of chimpanzees and chimpanzee conservation.
Detection of the Cell Cycle-Regulated Negative Feedback Phosphorylation of Mitogen-Activated Protein Kinases in Breast Carcinoma using Nanofluidic Proteomics
Authors: Urasaki Yasuyo , Fiscus Ronald R. , Le Thuc T.
Published: June 2018

Mitogen-activated protein kinases (MAPKs) play an important role in the regulation of cell proliferation, oncogenic transformation, and drug resistance. This study examined the capability of nanofluidic proteomics to identify aberrations in the MAPK signaling cascade, monitor its drug response, and guide the rational design of intervention strategies. Specifically, the protein post-translational modification (PTM) profiles of MEK1, MEK2, and ERK1/2 were measured in breast carcinoma and breast cancer cell lines. Nanofluidic proteomics revealed hyper-phosphorylation of MAPKs in breast carcinoma and breast cancer cells treated with kinase inhibitors that interfere with cell cycle regulation, such as dinaciclib, an inhibitor of cyclin-dependent kinases, and rigosertib, an inhibitor of polo-like kinase 1. A pMEK1 (Thr286) phosphor-isoform, which serves as a biomarker of cell cycle-regulated negative feedback phosphorylation in breast cancer cells, was detected in breast carcinoma. Inhibition of the MAPK pathway with dabrafenib, a B-Raf inhibitor, or trametinib, a MEK1/2 inhibitor, suppressed both the positively regulated phosphorylation of MAPKs and the negatively regulated phosphorylation of MEK1. Interestingly, the combinations of dabrafenib and rigosertib or trametinib and rigosertib permitted the suppression of positively regulated MAPK phosphorylation together with the promotion of negatively regulated MEK1 phosphorylation. The effectiveness of protein PTM-guided drug combinations for inhibition of the MAPK pathway remains to be experimentally tested. Via protein PTM profiling, nanofluidic proteomics provides a robust means to detect anomalies in the MAPK signaling cascade, monitor its drug response, and guide the possible design of drug combinations for MAPK pathway-focused targeting.