bluuebunny/crossref_metadata_2025 huggingface dataset:
Computer-based tailored dietary counselling improves the nutrient adequacy of the diet of French pregnant women: a randomised controlled trial
Authors: Bianchi Clélia M. , Mariotti François , Lluch Anne , Journet Claire , Stehr Yaëlle , Beaussier Hélène , Fournier Julien , Dervaux Stéphane , Cohen-Tanuggi Dylan , Reulet Elodie , Verger Eric O. , Azria Elie , Huneau Jean-François
Published: October 2019

During pregnancy, mothers-to-be should adapt their diet to meet increases in nutrient requirements. Pregnant women appear to be keener to adopt healthier diets, but are not always successful. The objective of the present study was to determine whether a guided, stepwise and tailored dietary counselling programme, designed using an optimisation algorithm, could improve the nutrient adequacy of the diet of pregnant women, beyond generic guidelines. Pregnant women (n 80) who attended Notre-Dame-de-Bon-Secours Maternity Clinic were randomly allocated to the control or intervention arm. Dietary data were obtained twice from an online 3-d dietary record. The nutrient adequacy of the diet was calculated using the PANDiet score, a 100-point diet quality index adapted to the specific nutrient requirements for pregnancy. Women were supplied with generic dietary guidelines in a reference booklet. In the intervention arm, they also received nine sets of tailored dietary advice identified by an optimisation algorithm as best improving their PANDiet score. Pregnant women (n 78) completed the 12-week dietary follow-up. Initial PANDiet scores were similar in the control and intervention arms (60·4 (sd 7·3) v. 60·3 (sd 7·3), P = 0·92). The PANDiet score increased in the intervention arm (+3·6 (sd 9·3), P = 0·02) but not in the control arm (−0·3 (sd 7·3), P = 0·77), and these changes differed between arms (P = 0·04). In the intervention arm, there were improvements in the probabilities of adequacy for α-linolenic acid, thiamin, folate and cholesterol intakes (P < 0·05). Tailored dietary counselling using a computer-based algorithm is more effective than generic dietary counselling alone in improving the nutrient adequacy of the diet of French women in mid-pregnancy.
Comparing saliva and urine samples for measuring breast milk intake with the2H oxide dose-to-mother technique among children 2–4 months old
Authors: Matsiko Eric , Hulshof Paul J. M. , van der Velde Laura , Kenkhuis Marlou-Floor , Tuyisenge Lisine , Melse-Boonstra Alida
Published: October 2019

Saliva and urine are the two main body fluids sampled when breast milk intake is measured with the2H oxide dose-to-mother technique. However, these two body fluids may generate different estimates of breast milk intake due to differences in isotope enrichment. Therefore, we aimed to assess how the estimated amount of breast milk intake differs when based on saliva and urine samples and to explore whether the total energy expenditure of the mothers is related to breast milk output. We used a convenience sample of thirteen pairs of mothers and babies aged 2–4 months, who were exclusively breastfed and apparently healthy. To assess breast milk intake, we administered doubly labelled water to the mothers and collected saliva samples from them, while simultaneously collecting both saliva and urine from their babies over a 14-d period. Isotope ratio MS was used to analyse the samples for2H and18O enrichments. Mean breast milk intake based on saliva samples was significantly higher than that based on urine samples (854·5v. 812·8 g/d,P= 0·029). This can be attributed to slightly higher isotope enrichments in saliva and to a poorer model fit for urine samples as indicated by a higher square root of the mean square error (14·6v. 10·4 mg/kg,P= 0·001). Maternal energy expenditure was not correlated with breast milk output. Our study suggests that saliva sampling generates slightly higher estimates of breast milk intake and is more precise as compared with urine and that maternal energy expenditure does not influence breast milk output.
The role of narrow-band imaging in parathyroid surgery: a preliminary evaluation in five parathyroid adenoma cases
Authors: Saibene A M , Bulfamante A M , Lozza P , De Pasquale L
Published: October 2019

Background

Narrow-band imaging uses selective haemoglobin light absorption to emphasise vascular visualisation and capillary networks.

Objective

This study aimed to evaluate the application of this technique to parathyroid surgery.

Method

This preliminary evaluation was carried out on five consecutive patients with single parathyroid adenoma being considered for minimally invasive video-assisted parathyroidectomy. The adenomas were checked for narrow-band imaging vascular patterns. Minimally invasive video-assisted parathyroidectomy was then carried out in accordance with our standard protocol.

Results

In four out of the five cases, narrow-band imaging integrated the white endoscopic light and direct vision, but in one case narrow-band imaging allowed distinction between the hidden neoplastic tissue and the surrounding structures thanks to the different vascular patterns.

Conclusion

Narrow-band imaging was helpful in properly identifying adenoma. It is suggested that this technique be considered as a means for surgeons to improve their confidence in selected surgical treatments and to improve treatment quality.
Antipsychotic drugs v. barbiturates or benzodiazepines used as active placebos for schizophrenia: a systematic review and meta-analysis
Authors: Siafis Spyridon , Deste Giacomo , Ceraso Anna , Mussoni Christian , Vita Antonio , Hasanagic Senad , Schneider-Thoma Johannes , Papazisis Georgios , Davis John M , Leucht Stefan
Published: October 2019

Background

Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.

Methods

Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).

Results

Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a ‘good’ response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36–3.41; I2 = 48.9) and ‘any’ response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35–3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on ‘any’ response (74.7% v. 65%; RR 1.15; 95% CI 0.82–1.62).

Conclusions

Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.
THE RELIEF AND TEXT OFIGII31 298: LEUKON AND HIS SONS IN ATHENS AND MYTILENE
Authors: Braund David
Published: October 2019

This article examines an important document in the history of Athens’ relations with the rulers of the Bosporus, namely the stele on which we have the decree (IGII31 298) and its relief. The article argues that, in their different ways, both the decree and the relief stress the same theme – continuity. The relief portrays the two sons of Leukon, who have succeeded to the throne, on which they sit, holding a sceptre, while their father (deceased, of course) stands and gazes over them. This figure is not their brother (as scholars usually assert, as if fact). Therefore, in addition to the particular case of this stele, with all its importance for the relationship between Athens and the Bosporans, there is also a more general conclusion on the theme of the interaction of the two main features of the stele, namely the written decree and the relief which stands above it. That kind of interaction has been a matter of considerable discussion in recent years. In this instance, at any rate, we have – on the present argument – what is in essence the same emphasis in both written decree and relief. Their consistent stress on continuity in the relationship between Athens and the rulers of the Bosporus does leave some uncertainty (particularly in our understanding of the treatment of Apollonios, who is omitted from the relief and from the decree itself), but there seems to be nothing here to undermine or disrupt the shared emphasis on continuity in the decree and the relief. Finally, brief attention is paid to a small fragment of an inscription from Mytilene (IGXII 2 3) and its historical value for the study of Athenian relations with the Bosporus.
THE CURRENT ACCOUNT OF THE SPANISH ECONOMY, 1850-2016: WAS IT OPTIMAL?
Authors: Bajo-Rubio Oscar , Esteve Vicente
Published: October 2019

We analyse the possible optimality of the path followed by the current account of the Spanish economy over a very long period of almost 170 years (1850-2016), according to the intertemporal approach to the current account and using a present-value model. In particular, from the estimation of a bivariate vector autoregression model for the current account, we attempt to assess the extent to which the latter has been used to smooth private consumption over time in the presence of temporary shocks that the economy might suffer. In general, evidence does not seem to be particularly favourable to the validity of the model over the period of analysis.
Images, emotions, and international politics: the death of Alan Kurdi
Authors: Adler-Nissen Rebecca , Andersen Katrine Emilie , Hansen Lene
Published: October 2019

How are images, emotions, and international politics connected? This article develops a theoretical framework contributing to visuality and emotions research in International Relations. Correcting the understanding that images cause particular emotional responses, this article claims that emotionally laden responses to images should be seen as performed in foreign policy discourses. We theorise images as objects of interpretation and contestation, and emotions as socially constituted rather than as individual ‘inner states’. Emotional bundling – the coupling of different emotions in discourse – helps constitute political subjectivities that both politicise and depoliticise. Through emotional bundling political leaders express their experiences of feelings shared by all humans, and simultaneously articulate themselves in authoritative and gendered subject positions such as ‘the father’. We illustrate the value of our framework by analysing the photographs of Alan Kurdi, a three-year-old Syrian-Kurdish boy who drowned in September 2015. ‘Kurdi’ became an instant global icon of the Syrian refugee crisis. World leaders expressed their personal grief and determination to act, but within a year, policies adopted with direct reference to Kurdi's tragic death changed from an open-door approach to attempts to stop refugees from arriving. A discursive-performative approach opens up new avenues for research on visuality, emotionality, and world politics.
WINNER PLAYS COMPETITION MODELS
Authors: Cao Yang , Ross Sheldon M.
Published: October 2019

Suppose there are n players in an ongoing competition, with player i having value vi, and suppose that a game between i and j is won by i with probability vi/(vi + vj). Consider the winner plays competition where in each stage two players play a game, and the winner keeps playing in the next game. We consider two models for choosing its opponent, analyze both models as Markov chains, and determine their stationary probabilities as well as other quantities of interest.
Foodborne viral outbreaks associated with frozen produce
Authors: Nasheri Neda , Vester Adrian , Petronella Nicholas
Published: October 2019

Over the past decade, frozen fruits have been a major vehicle of foodborne illnesses mainly attributed to norovirus (NoV) and hepatitis A virus (HAV) infections. Fresh produce may acquire viral contamination by direct contact with contaminated surface, water or hands, and is then frozen without undergoing proper decontamination. Due to their structural integrity, foodborne viruses are able to withstand hostile conditions such as desiccation and freezing, and endure for a long period of time without losing their infectivity. Additionally, these foods are often consumed raw or undercooked, which increases the risk of infection. Herein, we searched published literature and databases of reported outbreaks as well as the databases of news articles for the viral outbreaks associated with the consumption of frozen produce between January 2008 and December 2018; recorded the worldwide distribution of these outbreaks; and analysed the implication of consumption of different types of contaminated frozen food. In addition, we have briefly discussed the factors that contribute to an increased risk of foodborne viral infection following the consumption of frozen produce. Our results revealed that frozen fruits, especially berries and pomegranate arils, contributed to the majority of the outbreaks, and that most outbreaks were reported in industrialised countries.
The Physical and Mental Health Challenges Experienced by 9/11 First Responders and Recovery Workers: A Review of the Literature
Authors: Smith Erin C. , Holmes Lisa , Burkle Frederick M.
Published: October 2019

Introduction:

In the years following the September 11, 2001 terrorist attacks in New York (USA), otherwise known as 9/11, first responders and recovery workers began experiencing a range of physical and mental health challenges. Publications documenting these provide an important evidence-base identifying exposure-related health challenges associated with environmental exposures from the World Trade Center (WTC) site and describe the key lessons learned regarding both physical and mental health challenges (including symptoms and defined conditions) from the 9/11 disaster response.

Methods:

A systematic literature review was conducted using the MEDLINE, PubMed, CINAHL, and PsychInfo databases (September 11, 2001 to September 11, 2018) using relevant search terms, truncation symbols, and Boolean combination functions. Publications were limited to journal articles that documented the physical or mental health challenges of 9/11 on first responders or recovery workers.

Results:

A total of 156 publications were retrieved by the search strategy. The majority (55%) reported a quantitative methodology, while only seven percent reported the use of a qualitative research methodology. Firefighters were the group of responders most frequently reported in the literature (35%), while 37% of publications reported on research that included a mix of first responders and recovery workers. Physical health was the focus of the majority of publications (57%). Among the challenges, respiratory issues were the physical health condition most frequently reported in publications, while posttraumatic stress disorder (PTSD) was the most frequent mental health condition reported on. Publications were published in a broad range of multi-disciplinary journals (n = 75).

Discussion:

These findings will go some way to filling the current gap in the 9/11 evidence-base regarding the understanding of the long-term health challenges for first responders and recovery workers.
From Klingon to Colbertian: Using Artificial Languages to Study Word Learning
Authors: Hayakawa Sayuri , Ning Siqi , Marian Viorica
Published: October 2019

Vocabulary acquisition is a critical part of learning a new language. Yet, due to structural, historical, and individual variability associated with natural languages, isolating the impact of specific factors on word learning can be challenging. Artificial languages are versatile tools for addressing this problem, allowing researchers to systematically manipulate properties of the language and control for learners’ past experiences. Here, we review how artificial languages have been used to study bilingual word learning, with a particular focus on the influences of language input (e.g., word properties) and language experience (e.g., bilingualism). We additionally discuss the advantages and limitations of artificial languages for bilingual research and suggest resources for researchers considering the use of artificial languages. Used and interpreted properly, artificial language studies can inform our understanding of a wide range of factors relevant to word learning.
Unpacking Impasse-Related Experience during Insight
Authors: Shen Wangbing , Yuan Yuan , Lu Fang , Liu Chang , Luo Jing , Zhou Zhijin
Published: October 2019

Mental impasse has long been recognized as a hallmark of creative insight, but its precise role has been unexplored. The aim of the present work, consisting of two studies, was to experimentally probe mental impasse perspective from insight experience, namely impasse-related experience during insight. In Study 1, participants were requested to complete a compound remote association task and a forced-choice subjective experience depiction task that could provide data on impasse-related experience. The results showed that reports of negative experience, such as feelings of loss (t = –5.51, p < .001, Cohen d = 1.07) and personal experience (mirrored by ‘other’ response; t = –2.62, p < .05, Cohen d = 0.48), were more common in the impasse condition than in the no-impasse condition; correspondingly positive affect and positive cognitive experiences such as happiness (t = 4.20, p < .001, Cohen d = 0.77), ease (t = 5.90, p < .001, Cohen d = 1.20), certainty (t = 7.46, p < .001, Cohen d = 1.36) and calmness (t = 4.42, p < .001, Cohen d = 0.81) were experienced more frequently in the no-impasse condition. These findings were replicated in Study 2, in which participants were invited to solve a set of classic insight problems and to freely report any feelings of being at an impasse. Across two studies, this work suggests that impasse-related experience during insight problem solving is multi-faceted and consists of negative affective and cognitive components. The implications of these findings are discussed.
The Indian Ocean Deep Meridional Overturning Circulation in Three Ocean Reanalysis Products
Authors: Jayasankar T. , Murtugudde R. , Eldho T.I.
Published: October 2019

The time mean Indian Ocean (IO) deep meridional overturning circulation (MOC) is compared across three ocean reanalysis products (ORAS4, GECCO2, and GFDL). The MOC stream functions obtained by vertically integrating the mass flux across a latitude‐depth section in three products are found to be significantly different from each other. Detailed analysis suggests that ORAS4 delivers the best depiction of IO MOC. The inferred IO deep MOC consists of two deep and strong counterclockwise cells located south of 30°S and around 10°S, respectively. The geostrophic component along with the barotropic or external mode dominates the former, and a combination of Ekman and geostrophic components dominates the latter. GECCO2 depicts a steady decline in the northward meridional transport in the bottom layer and a consequent reduction in the MOC strength. The tropical thermocline in GECCO2 responds to this MOC variability leading to rapid and monotonic warming of the tropical IO.
Spatiotemporal Profiling of Tropical Cyclones Genesis and Favorable Environmental Conditions in the Western Pacific Basin
Authors: Lu Mengqian , Xiong Rui
Published: October 2019

We analyze the spatiotemporal variations of tropical cyclone (TC) genesis and associated environmental conditions over the western North Pacific with a series of data science techniques, including Gaussian kernel estimator, wavelet, cross‐wavelet coherence, and regression analyses. There are significant semiannual and annual variations of TC genesis over the northern South China Sea and oceanic areas east of the Philippines. Variations on the El Niño–Southern Oscillation timescale are prominent between 5–10°N, 155–160°E. With reconstructed TC series on those frequencies, we further quantify the influences of environmental variables on the primary TC signals over western North Pacific. Over northern South China Sea and oceanic areas east of the Philippines, 40% of the reconstructed TC variance can be explained by vertical shear of zonal wind, relative humidity, and absolute vorticity. The reconstructed TC series near (160°E, 7°N) has strong but varying in‐phase relationships with El Niño–Southern Oscillation, which provides deeper insight into their nonstationary and nonlinear relations than their modest correlation.
Ionospheric Response to Disturbed Winds During the 29 October 2003 Geomagnetic Storm in the Brazilian Sector
Authors: Bravo M.A. , Batista I.S. , Souza J.R. , Foppiano A.J.
Published: October 2019

Modeling the ionosphere during disturbed periods is one of the most challenging tasks due to the complexity of the phenomena that affect the electric fields and the whole thermosphere environment. It is well known that both, prompt penetration electric fields and large amounts of energy deposited in the polar region during disturbed periods, produce significant disturbances in the global electron density distribution, in particular, in the equatorial ionization anomaly development. Besides, the disturbance dynamo, traveling atmospheric disturbances, and traveling ionospheric disturbances also affect the equatorial ionization anomaly density distribution. In this work we use the Sheffield University Plasmasphere‐Ionosphere Model at Instituto Nacional de Pesquisas Espaciais, to simulate the drastic effects that were observed at the low‐latitude ionosphere in the Brazilian region during a very intense magnetic storm event, the so‐called 2003 Halloween storms. In the absence of measured vertical drift during the storm, a new vertical drift deduced from the interplanetary electric field combined with the time variation of the F region virtual height is used as input. The simulation results showed that, in the case of the disturbed thermospheric wind, the ionospheric observations are better explained when a novel traveling wave‐like disturbance propagating from north to south, at a velocity equal to 300 m/s, is considered.
Texture and Composition of Titan's Equatorial Sand Seas Inferred From Cassini SAR Data: Implications for Aeolian Transport and Dune Morphodynamics
Authors: Lucas A. , Rodriguez S. , Lemonnier F. , Le Gall A. , MacKenzie S. , Ferrari C. , Paillou P. , Narteau C.
Published: October 2019

The texture, composition, and morphology of dunes observed in the equatorial regions of Titan may reflect present and/or past climatic conditions. Determining the physio‐chemical properties and the morphodynamics of Titan's dunes is therefore essential to understanding of the climatic and geological history of the largest moon of Saturn. We quantitatively derived average surface properties of dune and interdune areas (texture and composition) from modeling of the microwave backscattered signal and Monte Carlo inversion of the despeckled Cassini/Synthetic Aperture Radar data over Titan's three largest sand seas: Belet, Shangri‐La, and Fensal. We present the first analysis of the backscatter functions extracted from despeckled Synthetic Aperture Radar images that cover such a large range in incidence angles, including data from the beginning of the Cassini mission up to its Grand Finale. We show that dunes and interdunes have significantly different physical properties. Dunes are found to be more microwave absorbent than interdunes. Additionally, potential secondary bedforms, such as ripples and avalanches, may have been detected, providing potential evidence for currently active dunes and sediment transport. Our modeling shows that the interdunes have multiscale roughnesses with higher dielectric constants than the dunes which have a low dielectric constant consistent with organic sand. The radar brightness of the interdunes can be explained by the presence of a shallow layer of significantly larger organic grains, possibly nonmobilized by the winds. Together, our findings suggest that Titan's sand seas evolve under the current multidirectional wind regimes with dunes that elongate with their crests aligned in the residual drift direction.
Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study
Authors: Burger Jan A. , Barr Paul M. , Robak Tadeusz , Owen Carolyn , Ghia Paolo , Tedeschi Alessandra , Bairey Osnat , Hillmen Peter , Coutre Steven E. , Devereux Stephen , Grosicki Sebastian , McCarthy Helen , Simpson David , Offner Fritz , Moreno Carol , Dai Sandra , Lal Indu , Dean James P. , Kipps Thomas J.
Published: October 2019

RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5–0.8 mg/kg for ≤12 cycles. With a median (range) follow-up of 60 months (0.1–66), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098–0.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266–0.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047–0.145]; OS: HR [95% CI]: 0.366 [0.181–0.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time.
Temperature-dependent changes to host–parasite interactions alter the thermal performance of a bacterial host
Authors: Padfield Daniel , Castledine Meaghan , Buckling Angus
Published: October 2019

Thermal performance curves (TPCs) are used to predict changes in species interactions, and hence, range shifts, disease dynamics and community composition, under forecasted climate change. Species interactions might in turn affect TPCs. Here, we investigate how temperature-dependent changes in a microbial host–parasite interaction (the bacterium Pseudomonas fluorescens, and its lytic bacteriophage, SBW Φ2) changes the host TPC and the ecological and evolutionary mechanisms underlying these changes. The bacteriophage had a narrower thermal tolerance for infection, with their critical thermal maximum ~6 °C lower than those at which the bacteria still had high growth. Consequently, in the presence of phage, the host TPC changed, resulting in a lower maximum growth rate. These changes were not just driven by differences in thermal tolerance, with temperature-dependent costs of evolved resistance also playing a major role: the largest cost of resistance occurred at the temperature at which bacteria grew best in the absence of phage. Our work highlights how ecological and evolutionary mechanisms can alter the effect of a parasite on host thermal performance, even over very short timescales.
Ten novel insertion/deletion variants in MECP2 identified in Japanese patients with Rett syndrome
Authors: Takeshita Eri , Iida Aritoshi , Abe-Hatano Chihiro , Nakagawa Eiji , Sasaki Masayuki , Inoue Ken , Goto Yu-ichi
Published: October 2019

Rett syndrome (RTT) is an X-linked progressive and severe neurological disorder caused by mutations in the gene encoding methyl CpG binding protein 2 (MECP2). Among the 49 typical RTT patients examined, we identified 10 novel and eight known insertion/deletion variants, and 31 known pathogenic variants in MECP2. The pathogenic variants presented here should be a useful resource for examining the correlation between the genotypes and phenotypes of RTT.
CUTseq is a versatile method for preparing multiplexed DNA sequencing libraries from low-input samples
Authors: Zhang Xiaolu , Garnerone Silvano , Simonetti Michele , Harbers Luuk , Nicoś Marcin , Mirzazadeh Reza , Venesio Tiziana , Sapino Anna , Hartman Johan , Marchiò Caterina , Bienko Magda , Crosetto Nicola
Published: October 2019

Current multiplexing strategies for massively parallel sequencing of genomic DNA mainly rely on library indexing in the final steps of library preparation. This procedure is costly and time-consuming, because a library must be generated separately for each sample. Furthermore, library preparation is challenging in the case of fixed samples, such as DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues. Here we describe CUTseq, a method that uses restriction enzymes and in vitro transcription to barcode and amplify genomic DNA prior to library construction. We thoroughly assess the sensitivity and reproducibility of CUTseq in both cell lines and FFPE samples, and demonstrate an application of CUTseq for multi-region DNA copy number profiling within single FFPE tumor sections, to assess intratumor genetic heterogeneity at high spatial resolution. In conclusion, CUTseq is a versatile and cost-effective method for library preparation for reduced representation genome sequencing, which can find numerous applications in research and diagnostics.
High-speed domain wall racetracks in a magnetic insulator
Authors: Vélez Saül , Schaab Jakob , Wörnle Martin S. , Müller Marvin , Gradauskaite Elzbieta , Welter Pol , Gutgsell Cameron , Nistor Corneliu , Degen Christian L. , Trassin Morgan , Fiebig Manfred , Gambardella Pietro
Published: October 2019

Recent reports of current-induced switching of ferrimagnetic oxides coupled to heavy metals have opened prospects for implementing magnetic insulators into electrically addressable devices. However, the configuration and dynamics of magnetic domain walls driven by electrical currents in insulating oxides remain unexplored. Here we investigate the internal structure of the domain walls in Tm3Fe5O12 (TmIG) and TmIG/Pt bilayers, and demonstrate their efficient manipulation by spin–orbit torques with velocities of up to 400 ms−1 and minimal current threshold for domain wall flow of 5 × 106 A cm−2. Domain wall racetracks are defined by Pt current lines on continuous TmIG films, which allows for patterning the magnetic landscape of TmIG in a fast and reversible way. Scanning nitrogen-vacancy magnetometry reveals that the domain walls of TmIG thin films grown on Gd3Sc2Ga3O12 exhibit left-handed Néel chirality, changing to an intermediate Néel–Bloch configuration upon Pt deposition. These results indicate the presence of interfacial Dzyaloshinskii–Moriya interaction in magnetic garnets, opening the possibility to stabilize chiral spin textures in centrosymmetric magnetic insulators.
On-demand orbital maneuver of multiple soft robots via hierarchical magnetomotility
Authors: Won Sukyoung , Kim Sanha , Park Jeong Eun , Jeon Jisoo , Wie Jeong Jae
Published: October 2019

Magnetic soft robots facilitate the battery-free remote control of soft robots. However, parallel control of multiple magnetic robots is challenging due to interference between robots and difficult maneuvers. Here we present the orbital maneuvering of manifold magnetic soft robots. Magneto-induced motion (magnetomotility) that includes the hierarchy of rotation and resultant revolution allows for the independent control of the robot’s velocity and orbital radius. The soft robot achieves a speed of 60 body length (BL) s−1, which is approximately 50, 000 times faster with 1/7 the weight of the current lightest legged soft robot. The hierarchical magnetomotility is suitable for versatile locomotion such as stairs and uphill climbing, underwater and above water swimming. Owing to their swimming functionality, a swarm of such soft robots is capable of transportation of cargo. On-demand orbital maneuvering of magnetic soft robots provides a new methodology for concurrent actuation of multiple robots exhibiting collective behaviors.
Rapid single-wavelength lightsheet localization microscopy for clarified tissue
Authors: Chu Li-An , Lu Chieh-Han , Yang Shun-Min , Liu Yen-Ting , Feng Kuan-Lin , Tsai Yun-Chi , Chang Wei-Kun , Wang Wen-Cheng , Chang Shu-Wei , Chen Peilin , Lee Ting-Kuo , Hwu Yeu-Kuang , Chiang Ann-Shyn , Chen Bi-Chang
Published: October 2019

Optical super-resolution microscopy allows nanoscale imaging of protein molecules in intact biological tissues. However, it is still challenging to perform large volume super-resolution imaging for entire animal organs. Here we develop a single-wavelength Bessel lightsheet method, optimized for refractive-index matching with clarified specimens to overcome the aberrations encountered in imaging thick tissues. Using spontaneous blinking fluorophores to label proteins of interest, we resolve the morphology of most, if not all, dopaminergic neurons in the whole adult brain (3.64 × 107 µm3) of Drosophila melanogaster at the nanometer scale with high imaging speed (436 µm3 per second) for localization. Quantitative single-molecule localization reveals the subcellular distribution of a monoamine transporter protein in the axons of a single, identified serotonergic Dorsal Paired Medial (DPM) neuron. Large datasets are obtained from imaging one brain per day to provide a robust statistical analysis of these imaging data.
Functional profiling of single CRISPR/Cas9-edited human long-term hematopoietic stem cells
Authors: Wagenblast Elvin , Azkanaz Maria , Smith Sabrina A. , Shakib Lorien , McLeod Jessica L. , Krivdova Gabriela , Araújo Joana , Shultz Leonard D. , Gan Olga I. , Dick John E. , Lechman Eric R.
Published: October 2019

In the human hematopoietic system, rare self-renewing multipotent long-term hematopoietic stem cells (LT-HSCs) are responsible for the lifelong production of mature blood cells and are the rational target for clinical regenerative therapies. However, the heterogeneity in the hematopoietic stem cell compartment and variable outcomes of CRISPR/Cas9 editing make functional interrogation of rare LT-HSCs challenging. Here, we report high efficiency LT-HSC editing at single-cell resolution using electroporation of modified synthetic gRNAs and Cas9 protein. Targeted short isoform expression of the GATA1 transcription factor elicit distinct differentiation and proliferation effects in single highly purified LT-HSC when analyzed with functional in vitro differentiation and long-term repopulation xenotransplantation assays. Our method represents a blueprint for systematic genetic analysis of complex tissue hierarchies at single-cell resolution.
Metamorphic pressure variation in a coherent Alpine nappe challenges lithostatic pressure paradigm
Authors: Luisier Cindy , Baumgartner Lukas , Schmalholz Stefan M. , Siron Guillaume , Vennemann Torsten
Published: October 2019

Pressure–temperature–time paths obtained from minerals in metamorphic rocks allow the reconstruction of the geodynamic evolution of mountain ranges under the assumption that rock pressure is lithostatic. This lithostatic pressure paradigm enables converting the metamorphic pressure directly into the rock’s burial depth and, hence, quantifying the rock’s burial and exhumation history. In the coherent Monte Rosa tectonic unit, Western Alps, considerably different metamorphic pressures are determined in adjacent rocks. Here we show with field and microstructural observations, phase petrology and geochemistry that these pressure differences cannot be explained by tectonic mixing, retrogression of high-pressure minerals, or lack of equilibration of mineral assemblages. We propose that the determined pressure difference of 0.8 ± 0.3 GPa is due to deviation from lithostatic pressure. We show with two analytical solutions for compression- and reaction-induced stress in mechanically heterogeneous rock that such pressure differences are mechanically feasible, supporting our interpretation of significant outcrop-scale pressure gradients.
Timing and origin of natural gas accumulation in the Siljan impact structure, Sweden
Authors: Drake Henrik , Roberts Nick M. W. , Heim Christine , Whitehouse Martin J. , Siljeström Sandra , Kooijman Ellen , Broman Curt , Ivarsson Magnus , Åström Mats E.
Published: October 2019

Fractured rocks of impact craters may be suitable hosts for deep microbial communities on Earth and potentially other terrestrial planets, yet direct evidence remains elusive. Here, we present a study of the largest crater of Europe, the Devonian Siljan structure, showing that impact structures can be important unexplored hosts for long-term deep microbial activity. Secondary carbonate minerals dated to 80 ± 5 to 22 ± 3 million years, and thus postdating the impact by more than 300 million years, have isotopic signatures revealing both microbial methanogenesis and anaerobic oxidation of methane in the bedrock. Hydrocarbons mobilized from matured shale source rocks were utilized by subsurface microorganisms, leading to accumulation of microbial methane mixed with a thermogenic and possibly a minor abiotic gas fraction beneath a sedimentary cap rock at the crater rim. These new insights into crater hosted gas accumulation and microbial activity have implications for understanding the astrobiological consequences of impacts.
Spin transport in insulators without exchange stiffness
Authors: Oyanagi Koichi , Takahashi Saburo , Cornelissen Ludo J. , Shan Juan , Daimon Shunsuke , Kikkawa Takashi , Bauer Gerrit E. W. , van Wees Bart J. , Saitoh Eiji
Published: October 2019

The discovery of new materials that efficiently transmit spin currents has been important for spintronics and material science. The electric insulator Gd3Ga5O12 (GGG), a standard substrate for growing magnetic films, can be a spin current generator, but has never been considered as a superior conduit for spin currents. Here we report spin current propagation in paramagnetic GGG over several microns. Surprisingly, spin transport persists up to temperatures of 100 K $$\gg$$
≫
Tg = 180 mK, the magnetic glass-like transition temperature of GGG. At 5 K and 3.5 T, we find a spin diffusion length λGGG = 1.8 ± 0.2 μm and a spin conductivity σGGG = (7.3 ± 0.3) × 104 Sm−1 that is larger than that of the record quality magnet Y3Fe5O12 (YIG). We conclude that exchange stiffness is not required for efficient spin transport, which challenges conventional models and provides new material-design strategies for spintronic devices.
Transcriptome Network Analysis Identifies CXCL13-CXCR5 Signaling Modules in the Prostate Tumor Immune Microenvironment
Authors: Ohandjo Adaugo Q. , Liu Zongzhi , Dammer Eric B. , Dill Courtney D. , Griffen Tiara L. , Carey Kaylin M. , Hinton Denise E. , Meller Robert , Lillard James W.
Published: October 2019

The tumor immune microenvironment (TIME) consists of multiple cell types that contribute to the heterogeneity and complexity of prostate cancer (PCa). In this study, we sought to understand the gene-expression signature of patients with primary prostate tumors by investigating the co-expression profiles of patient samples and their corresponding clinical outcomes, in particular “disease-free months” and “disease reoccurrence”. We tested the hypothesis that the CXCL13-CXCR5 axis is co-expressed with factors supporting TIME and PCa progression. Gene expression counts, with clinical attributes from PCa patients, were acquired from TCGA. Profiles of PCa patients were used to identify key drivers that influence or regulate CXCL13-CXCR5 signaling. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expression patterns among CXCL13-CXCR5, associated genes, and key genetic drivers within the CXCL13-CXCR5 signaling pathway. The processing of downloaded data files began with quality checks using NOISeq, followed by WGCNA. Our results confirmed the quality of the TCGA transcriptome data, identified 12 co-expression networks, and demonstrated that CXCL13, CXCR5 and associated genes are members of signaling networks (modules) associated with G protein coupled receptor (GPCR) responsiveness, invasion/migration, immune checkpoint, and innate immunity. We also identified top canonical pathways and upstream regulators associated with CXCL13-CXCR5 expression and function.
C60 ions of 1 MeV are slow but elongate nanoparticles like swift heavy ions of hundreds MeV
Authors: Amekura H. , Narumi K. , Chiba A. , Hirano Y. , Yamada K. , Tsuya D. , Yamamoto S. , Okubo N. , Ishikawa N. , Saitoh Y.
Published: October 2019

This study reports that high fluence fullerene ion (C60+) irradiation of 1–6 MeV, which was made possible by a new-type of high-flux ion source, elongates metal nanoparticles (NPs) in amorphous SiO2 as efficiently as swift heavy ions (SHIs) of 200 MeV Xe14+, i.e., two orders of the magnitude higher energy ions. Comparing the irradiation effects induced by both the beams, the stopping processes of C60 ions in SiO2 are discussed in this paper. Despite of having almost the same elongation efficiency, the C60+ irradiation induced ~10 times more efficient sputtering due to the clustering enhancement and/or the synergy effect. Ion tracks of ~10.4 nm in diameter and 60–80 nm in length were observed in crystalline SiO2 under 4 MeV C60 irradiation. While the track diameter was comparable to those by SHIs of the same electronic stopping, much shorter track lengths than those predicted by a rigid C60 molecule model indicates that the fragmentation occurred due to nuclear collisions. The elongation of the metal NPs was induced only down to the depth where the tracks were observed but not beyond.
Macrofluidic recirculating model of skeletal metastasis
Authors: Osawa Takahiro , Wang Wenchu , Dai Jinlu , Keller Evan T.
Published: October 2019

While microfluidic systems model aspects of metastasis, they are limited to artificially created tissues of limited complexity. We set out to develop an in vitro model of tumor cell migration from a primary tumor to a distant site that allows use of tissue. Accordingly, we created a macrofluidic model using culture plate wells connected with type I collagen-coated large bore tubing and has recirculating media. Green fluorescent protein-positive prostate carcinoma cells in a hydrogel or excised tumor xenografts from mice were placed into primary tumor sites and either human bone stromal cells (HS-5) in a hydrogel or human-derived bone chips were seeded into metastatic sites. Cells from the primary sites migrated to and grew in metastatic sites. Bone enhanced growth at metastatic sites and established a CXCL12 gradient that was higher in metastatic versus primary sites. AMD3100-mediated inhibition of CXCL12 function reduced the number of cells targeting the bone at the metastatic sites. In summary, we have developed a macrofluidic metastasis model that allows incorporation of tumor and metastatic microenvironment tissues and models chemotaxis. This system allows for incorporation of tumor heterogeneity and inclusion of an intact microenvironment. These features will facilitate identification of mechanisms and therapeutics for bone metastasis.
Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells
Authors: Raymond Aaron C. , Gao Boning , Girard Luc , Minna John D. , Gomika Udugamasooriya D.
Published: October 2019

Tumors often contain a small subset of drug-resisting, self-renewing, and highly metastatic cells called tumor initiating cells or cancer stem cells (CSCs). To develop new approaches to detecting and targeting lung cancer CSCs, we applied an “unbiased” peptoid combinatorial cell screen to identify highly specific ligands that bind a CSC subpopulation of non-small cell lung cancer cells (defined by Aldefluor positivity), but not the remaining aldefluor negative cancer cells from the same preclinical model. One of the ‘hit’ peptoids bound to plectin, a structural protein, predominantly expressed intracellularly, but whose localization on the cell surface is linked to tumor invasion and metastasis. Our studies show both genotypic and phenotypic correlations between plectin and lung CSCs, as well as association of high plectin mRNA expression with poor patient survival in lung adenocarcinoma, potentially identifying plectin as a biomarker for lung CSCs.
Flying Drosophila show sex-specific attraction to fly-labelled food
Authors: Cazalé-Debat Laurie , Houot Benjamin , Farine Jean-Pierre , Everaerts Claude , Ferveur Jean-François
Published: October 2019

Animals searching for food and sexual partners often use odourant mixtures combining food-derived molecules and pheromones. For orientation, the vinegar fly Drosophila melanogaster uses three types of chemical cues: (i) the male volatile pheromone 11-cis-vaccenyl acetate (cVA), (ii) sex-specific cuticular hydrocarbons (CHs; and CH-derived compounds), and (iii) food-derived molecules resulting from microbiota activity. To evaluate the effects of these chemicals on odour-tracking behaviour, we tested Drosophila individuals in a wind tunnel. Upwind flight and food preference were measured in individual control males and females presented with a choice of two food sources labelled by fly lines producing varying amounts of CHs and/or cVA. The flies originated from different species or strains, or their microbiota was manipulated. We found that (i) fly-labelled food could attract—but never repel—flies; (ii) the landing frequency on fly-labelled food was positively correlated with an increased flight duration; (iii) male—but not female or non-sex-specific—CHs tended to increase the landing frequency on fly-labelled food; (iv) cVA increased female—but not male—preference for cVA-rich food; and (v) microbiota-derived compounds only affected male upwind flight latency. Therefore, sex pheromones interact with food volatile chemicals to induce sex-specific flight responses in Drosophila.
Variations in growth, water consumption and economic benefit of transplanted cotton after winter wheat harvest subjected to different irrigation methods
Authors: Zhang Hao , Liu Hao , Wang Shunsheng , Guo Xuan , Ge Lu , Sun Jingsheng
Published: October 2019

In the North China Plain (NCP), the utilization efficiency of cultivated land can be improved by transplanted cotton after winter wheat harvest (TCWWH). To understand the growth, water consumption and economic benefit of TCWWH under different irrigation methods, an irrigation experiment was carried out during 2013–2015 to explore the effects of border irrigation (BI), surface drip irrigation (SDI) and micro-sprinkling hose irrigation (MHI) on the plant development, water use efficiency (WUE) and economic benefit of TCWWH. The results showed that the survival rate of cotton seedlings in the SDI treatment was 12% and 7% larger than that in the BI and the MHI treatments, respectively. SDI increased plant height by 19% and 8% and increased leaf area index (LAI) by 24% and 17%, compared with BI and MHI, respectively. The highest seed cotton yield and better fibre quality were obtained in the SDI treatment, compared to the BI and the MHI treatments. Compared with BI and MHI, SDI reduced the soil evaporation and evapotranspiration (ET) in the field, and resulted in the largest WUE. The net profit generated by the SDI treatment exceeded that of the BI and the MHI treatments by 183% and 23%, respectively. Therefore, SDI can promote the growth of TCWWH and can increase the WUE and the economic benefit of TCWWH, compared with BI and MHI.