bluuebunny/crossref_metadata_2025 huggingface dataset:
Campylobacteriosis associated with the consumption of unpasteurised milk: findings from a sentinel surveillance site
Authors: Davys G. , Marshall J. C. , Fayaz A. , Weir R. P. , Benschop J.
Published: February 2020

Campylobacteriosis is the most common notifiable disease in New Zealand. While the risk of campylobacteriosis has been found to be strongly associated with the consumption of undercooked poultry, other risk factors include rainwater-sourced drinking water, contact with animals and consumption of raw dairy products. Despite this, there has been little investigation of raw milk as a risk factor for campylobacteriosis. Recent increases in demand for untreated or ‘raw’ milk have also raised concerns that this exposure may become a more important source of disease in the future. This study describes the cases of notified campylobacteriosis from a sentinel surveillance site. Previously collected data from notified cases of raw milk-associated campylobacteriosis were examined and compared with campylobacteriosis cases who did not report raw milk consumption. Raw milk campylobacteriosis cases differed from non-raw milk cases on comparison of age and occupation demographics, with raw milk cases more likely to be younger and categorised as children or students for occupation. Raw milk cases were more likely to be associated with outbreaks than non-raw milk cases. Study-suggested motivations for raw milk consumption (health reasons, natural product, produced on farm, inexpensive or to support locals) were not strongly supported by cases. More information about the raw milk consumption habits of New Zealanders would be helpful to better understand the risks of this disease, especially with respect to increased disease risk observed in younger people. Further discussion with raw milk consumers around their motivations may also be useful to find common ground between public health concerns and consumer preferences as efforts continue to manage this ongoing public health issue.
Sinus Superflex DS© early collapse in systemic arterial duct
Authors: Betrián-Blasco Pedro , Marti-Aguasca Gerard , Giralt-Garcia Gemma
Published: February 2020

We implanted two sinus Superflex DS© stents in a systemic non-stenotic arterial duct of a newborn with hypoplastic left heart syndrome. Forty-eight hours later an important collapse of the stent was detected and treated with a balloon expandable stent. Sinus Superflex DS© has been specifically designed for systemic ducts. This complication generates doubts about its radial force in this scenario.
Going Dutch? Lessons from the Outcome-Based Political Science Curriculum in the Netherlands
Authors: Breuning Marijke
Published: February 2020

Dutch political science curricula integrate the acquisition of knowledge of the discipline and transferable skills. This makes it an interesting case for US political science education, especially in light of Wahlke’s (1991) recommendations for a structured political science curriculum that incorporates skills training in addition to knowledge of the field. Although some of Wahlke’s recommendations were widely adopted, US political science curricula remain relatively loosely structured and often do not explicitly focus on transferable skills.

This article argues that the Dutch example may help US programs revisit how to best achieve learning outcomes that allow students to acquire both knowledge and transferable skills. This is not an argument for “going Dutch” wholesale; instead, the article suggests modest modifications to US political science curricula.
Diet quality, nutrient intakes and biochemical status of New Zealand women of childbearing age according to alcohol consumption patterns
Authors: Parackal Sherly , Smith Claire , Skidmore Paula
Published: February 2020

Objective:

To investigate associations between alcohol consumption patterns and diet quality, nutrient intakes and biochemical profile of women of childbearing age.

Design:

Nutrient intake data from 24 h diet recalls, alcohol consumption data and diet quality from the Dietary Habits Questionnaire, and biochemical analyses from the cross-sectional 2008/09 Adult Nutrition Survey in New Zealand.

Setting:

New Zealand households.

Participants:

New Zealand women aged 18–45 years (n1124).

Results:

All analyses were completed using Stata and survey weights were used to allow for the complex survey design to produce population estimates. Multinomial logistic regression models were used to examine the associations between drinking patterns and the variables of interest, with ‘infrequent moderate/light’ drinkers being the reference category. The findings indicate that alcohol-consuming women of childbearing age tend to replace food energy with alcohol energy (P= 0·022). ‘More frequent heavy’ and ‘more frequent moderate/light’ drinkers had higher intakes of total, mono- and polyunsaturated fats with the latter group also consuming higher levels of saturated fats (P< 0·05). Women who were ‘infrequent moderate/light’ drinkers had relatively better diet quality, nutrient intakes and adequate biochemical status in comparison to other drinkers and abstainers. ‘Infrequent heavy’ drinkers, who were predominantly younger in age, had lower serum vitamin B12levels (P= 0·01) with a higher proportion of women in this category having below-recommended levels of serum folate (P< 0·05).

Conclusions:

Alcohol consumption, especially heavy drinking patterns, may compromise nutritional status of women of childbearing age.
Behandlungsmöglichkeiten für Vorschulkinder mit traumatischen Erfahrungen: Eine systematische Literaturübersicht
Authors: Stauffer Anika , Petermann Franz , Metzner Franka , Vasileva Mira
Published: February 2020

Zusammenfassung. Zu den Folgen traumatischer Erfahrungen im Vorschulalter gehören Symptome der posttraumatischen Belastungsstörung und weitere psychosoziale Folgen. Ziel dieses Reviews ist es, einen systematischen Überblick über die internationalen evidenz-basierten Behandlungsmöglichkeiten für Vorschulkinder (0 – 6 Jahre) mit traumatischen Erfahrungen zu geben. Dafür wurde eine systematische Literaturrecherche in den Datenbanken PsycInfo, Psyndex, Web of Science sowie in Registern für klinische Evaluationsstudien durchgeführt. Die Wirksamkeit der Interventionsprogramme zum Abbau von Symptomen des Kindes und die Qualität der dazugehörigen Studien wurden systematisch analysiert. Es konnten insgesamt 13 Interventionsmaßnahmen zur Behandlung von jungen Kindern mit traumatischen Erfahrungen identifiziert werden. Die Qualität der Evaluationsstudien wurde als mittelmäßig bis gering eingeschätzt. Wirksame Interventionen basierten auf unterschiedlichen Verfahren: Traumafokussierte kognitive Verhaltenstherapie, EMDR sowie expressive Techniken. Die Ergebnisse zeigen, dass sowohl kognitiv wenig anspruchsvolle Techniken als auch Methoden der traumafokussierten kognitiven Verhaltenstherapie erfolgreich bei der Traumabehandlung von Kindern im Vorschulalter eingesetzt werden können. Außerdem hatten Maßnahmen, bei denen die Eltern stark in die Therapie einbezogen wurden, positive Effekte bei der Reduktion der kindlichen Symptomatik. Insgesamt zeigt die Literaturrecherche, dass noch hochqualitative Evaluationsstudien und Implementierungsprojekte im Bereich der Traumabehandlung bei Vorschulkindern notwendig sind.
Niedrigschwellige traumafokussierte Gruppeninterventionen für traumatisierte Jugendliche mit Fluchterfahrung: Der Einfluss von nicht-suizidalem selbstverletzendem Verhalten und Suizidalität
Authors: Sukale Thorsten , Rassenhofer Miriam , Kirsch Veronica , Pfeiffer Elisa
Published: February 2020

Zusammenfassung. Um dem hohen Bedarf an traumafokussierten Interventionen für traumatisierte Kinder und Jugendliche gerecht zu werden, wurden in den letzten Jahren gestufte Versorgungsansätze mit niedrigschwelligen (Gruppen-)Interventionen als Lösung der Versorgungslücke vorgeschlagen und zunehmend wissenschaftlich evaluiert. Im vorliegenden Beitrag wird eine Studie zur differenziellen Wirksamkeit der traumafokussierten Gruppenmaßnahme „Mein Weg“ vorgestellt, die auf Jugendliche mit Fluchterfahrung abzielt. Neben der Häufigkeit des Auftretens von nicht-suizidalem selbstverletzendem Verhalten (NSSV) und Suizidgedanken und -handlungen wird ermittelt, ob dies die Posttraumatischen Suizidgedanken, die Posttraumatischen Stresssymptome (PTSS) und die depressive Symptomatik bei Jugendlichen, die an der „Mein Weg“-Maßnahme teilnahmen, beeinflusst haben. An der Studie nahmen insgesamt N = 99 fast ausschließlich männliche Jugendliche im Alter von 14 bis 19 Jahren teil. Die Jugendlichen füllten zu mehreren Erhebungszeitpunkten Fragebögen zur entsprechenden Symptomatik (CATS und PHQ-9) aus. Die Ergebnisse zeigen, dass 44.4 % der Jugendlichen von NSSV und Suizidalität berichten. Die Symptomverläufe der Gruppen unterscheiden sich zu keinem Messzeitpunkt signifikant voneinander. Es wird daraus geschlossen, dass Jugendliche mit und ohne NSSV und Suizidalität in Hinblick auf PTSS und depressive Symptome gleichermaßen von der Maßnahme profitieren.
Combining VR and Biofeedback
Authors: Rockstroh Christoph , Blum Johannes , Göritz Anja S.
Published: February 2020

Abstract. This study explored the effects of combining virtual reality (VR) and biofeedback on the restorativeness of the created experience as judged by the user and the user’s sense of presence. In a between-subjects experiment, we disentangled the effects of display type (VR vs. computer screen) and biofeedback (electrodermal activity biofeedback vs. no biofeedback) in the context of immersive simulated relaxation environments. After a stress induction, 94 healthy participants were randomly assigned to one of four relaxing treatments. There were no treatment-specific differences in subjective stress or physiological arousal. However, VR compared with computer screen increased the sense of presence and, partly, perceived restorativeness. When combined with VR, biofeedback increased physical presence and, in part, perceived restorativeness. The study offers insight that allows for the identification of future research avenues.
Delineating Environmental Stresses to Primary Production of U.S. Forests From Tree Rings: Effects of Climate Seasonality, Soil, and Topography
Authors: Dannenberg Matthew P. , Song Conghe , Wise Erika K. , Pederson Neil , Bishop Daniel A.
Published: February 2020

Primary production is the entry point of energy and carbon into ecosystems, but modeling responses of primary production to “environmental stress” (i.e., reductions of primary production from nonoptimal environmental conditions) remains a key challenge and source of uncertainty in our understanding of Earth's carbon cycle. Here we develop an approach for estimating annual “environmental stress” from tree rings based on the proportion of the optimal diameter growth rate (from species‐specific allometric equations) that is realized in a given year. We assessed climatic, topographic, and soil drivers of environmental stress, as well as their interactions, using both empirical model experiments and linear mixed effect models. Climate gradients and interannual climate variability dominated spatial and temporal variability of environmental stress in much of the western United States, where the tree‐ring environmental stress index was positively correlated with antecedent climatic water balance (precipitation minus potential evapotranspiration) and negatively correlated with temperature and vapor pressure deficit. Excluding topographic and soil information from empirical models reduced their ability to capture spatial gradients in environmental stress, particularly in the eastern United States, where growth was not as strongly limited by climate. Mean climate conditions and topographic characteristics had significant interaction effects with the climatic water balance, indicating an increasing importance of winter moisture for warmer and drier sites and as elevation and topographic wetness index increased. These results suggest that including effects of antecedent climate (particularly in dry regions) and site topographic and soil characteristics could improve parameterization of environmental stress effects in primary production models.
Dynamic Sea Level Variability Due to Seasonal River Discharge: A Preliminary Global Ocean Model Study
Authors: Piecuch Christopher G. , Wadehra Riley
Published: February 2020

River discharge
is an important driver of the coastal ocean circulation. However, the influence of variable
effects on large‐scale sea level
related to ocean dynamics is not well understood. We perform numerical experiments using a coarse (
°) global ocean state estimate to quantify
effects on the seasonal cycle in dynamic
over the global ocean. Forcing by
drives substantial dynamic
signals (
 cm) on regional scales around major rivers (e.g., Amazon, Ganges, Brahmaputra, Irrawaddy, Ob, Lena, and Yenisei). Modeled
changes largely reflect halosteric (salinity) effects, which are partly affected by transport processes involving planetary waves and advection. The modeled
response to
is informative for interpreting
observations from satellite altimetry and tide gauges, explaining 10–20% of the regional‐scale seasonal data variance around some major rivers. Future
studies should consider finer‐resolution models and
forcing on nonseasonal time scales of relevance to climate.
Future Interactions Between Sea Level Rise, Tides, and Storm Surges in the World's Largest Urban Area
Authors: De Dominicis Michela , Wolf Judith , Jevrejeva Svetlana , Zheng Peng , Hu Zhan
Published: February 2020

The Pearl River Delta contains the world's largest urban area in both size and population. It is a low‐lying flood‐prone coastal environment exposed to sea level rise (SLR) and extreme water levels caused by typhoons. A Finite Volume Community Ocean Model implementation for the South China Sea and the Pearl River Delta is used to understand how future SLR, tides, and typhoon storm surges will interact and affect coastal inundation. The SLR signal and extreme surge levels provide the major contributions to flooding; however, amplification of tides could exceed 0.5 m for 2.1 m SLR and should be considered when planning future coastal defences. On the other hand, if typhoons like Hato or Mangkhut, the latest and strongest ones hitting the area, were to happen in the future, a surge level reduction up to 0.5 m could be expected in coastal areas.
Timing of exercise for muscle strength and physical function in men initiating ADT for prostate cancer
Authors: Newton Robert U. , Galvão Daniel A. , Spry Nigel , Joseph David , Chambers Suzanne K. , Gardiner Robert A. , Hayne Dickon , Taaffe Dennis R.
Published: February 2020

Background

Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) results in adverse effects, including reduced muscle strength and physical function, potentially compromising daily functioning. We examined whether it was more efficacious to commence exercise at the onset of ADT rather than later in treatment to counter declines in strength and physical function.

Methods

One-hundred-and-four men with PCa (68.3 ± 7.0 years) initiating ADT were randomised to immediate exercise (IMX, n = 54) or delayed exercise (DEL, n = 50) for 12 months. IMX comprised 6 months of supervised resistance/aerobic/impact exercise initiated at the onset of ADT with a 6-month follow-up. DEL comprised 6 months of usual care followed by 6 months of resistance/aerobic/impact exercise. Upper and lower body muscle strength and physical function were assessed at baseline, 6 and 12 months.

Results

There was a significant difference for all strength measures at 6 months favouring IMX (P < 0.001), with net differences in leg press, seated row and chest press strength of 19.9 kg (95% CI, 12.3–27.5 kg), 5.6 kg (3.8–7.4 kg) and 4.3 kg (2.7–5.8 kg), respectively. From 7 to 12 months, DEL increased in all strength measures (P < 0.001), with no differences between groups at 12 months. Similarly, physical function improved (P < 0.001) in IMX compared with DEL at 6 months for the 6-m fast walk (−0.2, 95% CI −0.3 to −0.1 s), 400-m walk (−9.7, −14.8 to −4.6 s), stair climb (−0.4, −0.6 to −0.2 s) and chair rise (−1.0, −1.4 to −0.7 s), with no differences between groups by 12 months, except for the 6-m fast walk (P < 0.001).

Conclusion

Exercise either at the onset or after 6 months of ADT preserves/enhances muscle strength and physical function. However, to avoid initial treatment-related adverse effects on strength and function, exercise therapy should be implemented with initiation of ADT.
Organizing genome engineering for the gigabase scale
Authors: Bartley Bryan A. , Beal Jacob , Karr Jonathan R. , Strychalski Elizabeth A.
Published: February 2020

Genome-scale engineering holds great potential to impact science, industry, medicine, and society, and recent improvements in DNA synthesis have enabled the manipulation of megabase genomes. However, coordinating and integrating the workflows and large teams necessary for gigabase genome engineering remains a considerable challenge. We examine this issue and recommend a path forward by: 1) adopting and extending existing representations for designs, assembly plans, samples, data, and workflows; 2) developing new technologies for data curation and quality control; 3) conducting fundamental research on genome-scale modeling and design; and 4) developing new legal and contractual infrastructure to facilitate collaboration.
Human large-scale cooperation as a product of competition between cultural groups
Authors: Handley Carla , Mathew Sarah
Published: February 2020

A fundamental puzzle of human evolution is how we evolved to cooperate with genetically unrelated strangers in transient interactions. Group-level selection on culturally differentiated populations is one proposed explanation. We evaluate a central untested prediction of Cultural Group Selection theory, by assessing whether readiness to cooperate between individuals from different groups corresponds to the degree of cultural similarity between those groups. We documented the normative beliefs and cooperative dispositions of 759 individuals spanning nine clans nested within four pastoral ethnic groups of Kenya—the Turkana, Samburu, Rendille and Borana. We find that cooperation between groups is predicted by how culturally similar they are, suggesting that norms of cooperation in these societies have evolved under the influence of group-level selection on cultural variation. Such selection acting over human evolutionary history may explain why we cooperate readily with unrelated and unfamiliar individuals, and why humans’ unprecedented cooperative flexibility is nevertheless culturally parochial.
Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase
Authors: Palmieri Erika M. , Gonzalez-Cotto Marieli , Baseler Walter A. , Davies Luke C. , Ghesquière Bart , Maio Nunziata , Rice Christopher M. , Rouault Tracey A. , Cassel Teresa , Higashi Richard M. , Lane Andrew N. , Fan Teresa W.-M. , Wink David A. , McVicar Daniel W.
Published: February 2020

Profound metabolic changes are characteristic of macrophages during classical activation and have been implicated in this phenotype. Here we demonstrate that nitric oxide (NO) produced by murine macrophages is responsible for TCA cycle alterations and citrate accumulation associated with polarization.13C tracing and mitochondrial respiration experiments map NO-mediated suppression of metabolism to mitochondrial aconitase (ACO2). Moreover, we find that inflammatory macrophages reroute pyruvate away from pyruvate dehydrogenase (PDH) in an NO-dependent and hypoxia-inducible factor 1α (Hif1α)-independent manner, thereby promoting glutamine-based anaplerosis. Ultimately, NO accumulation leads to suppression and loss of mitochondrial electron transport chain (ETC) complexes. Our data reveal that macrophages metabolic rewiring, in vitro and in vivo, is dependent on NO targeting specific pathways, resulting in reduced production of inflammatory mediators. Our findings require modification to current models of macrophage biology and demonstrate that reprogramming of metabolism should be considered a result rather than a mediator of inflammatory polarization.
Spatiotemporal functional organization of excitatory synaptic inputs onto macaque V1 neurons
Authors: Ju Niansheng , Li Yang , Liu Fang , Jiang Hongfei , Macknik Stephen L. , Martinez-Conde Susana , Tang Shiming
Published: February 2020

The integration of synaptic inputs onto dendrites provides the basis for neuronal computation. Whereas recent studies have begun to outline the spatial organization of synaptic inputs on individual neurons, the underlying principles related to the specific neural functions are not well understood. Here we perform two-photon dendritic imaging with a genetically-encoded glutamate sensor in awake monkeys, and map the excitatory synaptic inputs on dendrites of individual V1 superficial layer neurons with high spatial and temporal resolution. We find a functional integration and trade-off between orientation-selective and color-selective inputs in basal dendrites of individual V1 neurons. Synaptic inputs on dendrites are spatially clustered by stimulus feature, but functionally scattered in multidimensional feature space, providing a potential substrate of local feature integration on dendritic branches. Furthermore, apical dendrite inputs have larger receptive fields and longer response latencies than basal dendrite inputs, suggesting a dominant role for apical dendrites in integrating feedback in visual information processing.
DNA unwinding mechanism of a eukaryotic replicative CMG helicase
Authors: Yuan Zuanning , Georgescu Roxana , Bai Lin , Zhang Dan , Li Huilin , O’Donnell Michael E.
Published: February 2020

High-resolution structures have not been reported for replicative helicases at a replication fork at atomic resolution, a prerequisite to understanding the unwinding mechanism. The eukaryotic replicative CMG (Cdc45, Mcm2-7, GINS) helicase contains a Mcm2-7 motor ring, with the N-tier ring in front and the C-tier motor ring behind. The N-tier ring is structurally divided into a zinc finger (ZF) sub-ring followed by the oligosaccharide/oligonucleotide-binding (OB) fold ring. Here we report the cryo-EM structure of CMG on forked DNA at 3.9 Å, revealing that parental DNA enters the ZF sub-ring and strand separation occurs at the bottom of the ZF sub-ring, where the lagging strand is blocked and diverted sideways by OB hairpin-loops of Mcm3, Mcm4, Mcm6, and Mcm7. Thus, instead of employing a specific steric exclusion process, or even a separation pin, unwinding is achieved via a “dam-and-diversion tunnel” mechanism that does not require specific protein-DNA interaction. The C-tier motor ring contains spirally configured PS1 and H2I loops of Mcms 2, 3, 5, 6 that translocate on the spirally-configured leading strand, and thereby pull the preceding DNA segment through the diversion tunnel for strand separation.
Deep learning approach based on dimensionality reduction for designing electromagnetic nanostructures
Authors: Kiarashinejad Yashar , Abdollahramezani Sajjad , Adibi Ali
Published: February 2020

In this paper, we demonstrate a computationally efficient new approach based on deep learning (DL) techniques for analysis, design and optimization of electromagnetic (EM) nanostructures. We use the strong correlation among features of a generic EM problem to considerably reduce the dimensionality of the problem and thus, the computational complexity, without imposing considerable errors. By employing the dimensionality reduction concept using the more recently demonstrated autoencoder technique, we redefine the conventional many-to-one design problem in EM nanostructures into a one-to-one problem plus a much simpler many-to-one problem, which can be simply solved using an analytic formulation. This approach reduces the computational complexity in solving both the forward problem (i.e., analysis) and the inverse problem (i.e., design) by orders of magnitude compared to conventional approaches. In addition, it provides analytic formulations that, despite their complexity, can be used to obtain intuitive understanding of the physics and dynamics of EM wave interaction with nanostructures with minimal computation requirements. As a proof-of-concept, we applied such an efficacious method to design a new class of on-demand reconfigurable optical metasurfaces based on phase-change materials (PCMs). The experimental results of the fabricated devices are in good agreement with those predicted by the proposed approach. We envision that the integration of such a DL-based technique with full-wave commercial software packages offers a powerful toolkit to facilitate the analysis, design, and optimization of the EM nanostructures as well as explaining, understanding, and predicting the observed responses in such structures. It will thus enable to solve complex design problems that could not be solved with existing techniques.
Flexible inorganic bioelectronics
Authors: Chen Ying , Zhang Yingchao , Liang Ziwei , Cao Yu , Han Zhiyuan , Feng Xue
Published: February 2020

Flexible inorganic bioelectronics represent a newly emerging and rapid developing research area. With its great power in enhancing the acquisition, management and utilization of health information, it is expected that these flexible and stretchable devices could underlie the new solutions to human health problems. Recent advances in this area including materials, devices, integrated systems and their biomedical applications indicate that through conformal and seamless contact with human body, the measurement becomes continuous and convenient with yields of higher quality data. This review covers recent progresses in flexible inorganic bio-electronics for human physiological parameters’ monitoring in a wearable and continuous way. Strategies including materials, structures and device design are introduced with highlights toward the ability to solve remaining challenges in the measurement process. Advances in measuring bioelectrical signals, i.e., the electrophysiological signals (including EEG, ECoG, ECG, and EMG), biophysical signals (including body temperature, strain, pressure, and acoustic signals) and biochemical signals (including sweat, glucose, and interstitial fluid) have been summarized. In the end, given the application property of this topic, the future research directions are outlooked.
Quantum computing with exciton-polariton condensates
Authors: Ghosh Sanjib , Liew Timothy C. H.
Published: February 2020

Exciton-polariton condensates have attractive features for quantum computation, e.g., room temperature operation, high dynamical speed, ease of probe, and existing fabrication techniques. Here, we present a complete theoretical scheme of quantum computing with exciton-polariton condensates formed in semiconductor micropillars. Quantum fluctuations on top of the condensates are shown to realize qubits, which are externally controllable by applied laser pulses. Quantum tunneling and nonlinear interactions between the condensates allow SWAP, square-root-SWAP and controlled-NOT gate operations between the qubits.
A chromosome-scale reference genome for Giardia intestinalis WB
Authors: Xu Feifei , Jex Aaron , Svärd Staffan G.
Published: February 2020

Giardia intestinalis is a protist causing diarrhea in humans. The first G. intestinalis genome, from the WB isolate, was published more than ten years ago, and has been widely used as the reference genome for Giardia research. However, the genome is fragmented, thus hindering research at the chromosomal level. We re-sequenced the Giardia genome with Pacbio long-read sequencing technology and obtained a new reference genome, which was assembled into near-complete chromosomes with only four internal gaps at long repeats. This new genome is not only more complete but also better annotated at both structural and functional levels, providing more details about gene families, gene organizations and chromosomal structure. This near-complete reference genome will be a valuable resource for the Giardia community and protist research. It also showcases how a fragmented genome can be improved with long-read sequencing technology completed with optical maps.
Author Correction: Systematic assessment of prescribed medications and short-term risk of myocardial infarction – a pharmacopeia-wide association study from Norway and Sweden
Authors: Sen Abhijit , Vardaxis Ioannis , Lindqvist Bo Henry , Brumpton Ben Michael , Strand Linn Beate , Bakken Inger Johanne , Vatten Lars Johan , Romundstad Pål Richard , Ljung Rickard , Mukamal Kenneth Jay , Janszky Imre
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy
Authors: Bhere Deepak , Arghiani Nahid , Lechtich Esther Revai , Yao Yizheng , Alsaab Sarah , Bei Fengfeng , Matin Maryam M. , Shah Khalid
Published: February 2020

Dysregulation of miRNA expression has been implicated in cancer. Numerous strategies have been explored to modulate miR but sub-optimal delivery and inability to concurrently target multiple pathways involved in tumor progression have limited their efficacy. In this study, we explored the potential co-modulation of upregulated miR-21 and downregulated miR-7 to enhance therapeutic outcomes in heterogenic tumor types. We first engineered lentiviral (LV) and adeno-associated viral (AAV) vectors that preferentially express anti-sense miR against miR-21(miRzip-21) and show that modulating miR-21 via miRzip extensively targets tumor cell proliferation, migration and invasion in vitro in a broad spectrum of cancer types and has therapeutic efficacy in vivo. Next, we show a significantly increased expression of caspase-mediated apoptosis by simultaneously downregulating miR-21 and upregulating miR-7 in different tumor cells. In vivo co-treatment with AAV-miRzip-21 and AAV-miR-7 in mice bearing malignant brain tumors resulted in significantly decreased tumor burden with a corresponding increase in survival. To our knowledge, this is the first study that demonstrates the therapeutic efficacy of simultaneously upregulating miR-7 and downregulating miR-21 and establishes a roadmap towards clinical translation of modulating miRs for various cancer types.
CDX-301: a novel medical countermeasure for hematopoietic acute radiation syndrome in mice
Authors: Satyamitra Merriline , Cary Lynnette , Dunn Dylan , Holmes-Hampton Gregory P. , Thomas Lawrence J. , Ghosh Sanchita P.
Published: February 2020

Bone marrow failure and hematopoietic damage is one of the major consequences of irradiation-induced lethality. There is an immediate need to develop medical countermeasures (MCMs) to combat irradiation-induced lethality. We tested the efficacy of CDX-301, developed by Celldex Therapeutics Inc., in mice exposed to Co-60 gamma total body irradiation (TBI). The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to TBI. A single dose of CDX-301 administered 24 h prior to 24 h post–exposure conferred significant survival. Accelerated recovery from irradiation-induced peripheral blood cytopenia, bone marrow damage as well as apoptosis in sternum was observed in mice pre-treated with CDX-301. Analysis of splenocytes revealed alterations in T cell profiles that were dependent on the time of drug administration. Prophylactic treatment of CDX-301 resulted in increased splenic CD3+ T cells, specifically CD4+T helper cells, compared to splenocytes from non-irradiated mice. These results indicate that CDX-301 is a promising radiation countermeasure and demonstrate its capability to protect cells within hematopoietic organs. These data support potential use of CDX-301, both pre- and post-radiation, against hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.
Author Correction: Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR−/− mice fed on high-fat diet
Authors: Liu Lin , Liang Chenxi , Wang Xiaowei , Ding Xiayu , Lu Yingjing , Dong Jinghui , Han Mei , Yang Hongyuan , Gao Mingming , Liao Jiawei
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Multimodal X-ray imaging of nanocontainer-treated macrophages and calcium distribution in the perilacunar bone matrix
Authors: Stachnik Karolina , Warmer Martin , Mohacsi Istvan , Hennicke Vincent , Fischer Pontus , Meyer Jan , Spitzbart Tobias , Barthelmess Miriam , Eich Jacqueline , David Christian , Feldmann Claus , Busse Björn , Jähn Katharina , Schaible Ulrich E. , Meents Alke
Published: February 2020

Studies of biological systems typically require the application of several complementary methods able to yield statistically-relevant results at a unique level of sensitivity. Combined X-ray fluorescence and ptychography offer excellent elemental and structural imaging contrasts at the nanoscale. They enable a robust correlation of elemental distributions with respect to the cellular morphology. Here we extend the applicability of the two modalities to higher X-ray excitation energies, permitting iron mapping. Using a long-range scanning setup, we applied the method to two vital biomedical cases. We quantified the iron distributions in a population of macrophages treated with Mycobacterium-tuberculosis-targeting iron-oxide nanocontainers. Our work allowed to visualize the internalization of the nanocontainer agglomerates in the cytosol. From the iron areal mass maps, we obtained a distribution of antibiotic load per agglomerate and an average areal concentration of nanocontainers in the agglomerates. In the second application we mapped the calcium content in a human bone matrix in close proximity to osteocyte lacunae (perilacunar matrix). A concurrently acquired ptychographic image was used to remove the mass-thickness effect from the raw calcium map. The resulting ptychography-enhanced calcium distribution allowed then to observe a locally lower degree of mineralization of the perilacunar matrix.
Phylogenomic Perspective on a Unique Mycobacterium bovis Clade Dominating Bovine Tuberculosis Infections among Cattle and Buffalos in Northern Brazil
Authors: Conceição Marília Lima da , Conceição Emilyn Costa , Furlaneto Ismari Perini , Silva Sandro Patroca da , Guimarães Arthur Emil dos Santos , Gomes Pedro , Boschiroli María Laura , Michelet Lorraine , Kohl Thomas Andreas , Kranzer Katharina , Francez Loreno da Costa , Lima Luana Nepomuceno Gondim Costa , Portugal Isabel , Perdigão João , Lima Karla Valéria Batista
Published: February 2020

Lack of routine surveillance in countries endemic for bovine tuberculosis (TB) and limited laboratory support contributes to the inability to differentiate theMycobacterium tuberculosisComplex species, leading to an underestimated burden of the disease. Here, Whole-Genome Sequencing ofMycobacterium bovisisolated from tissues with TB-like lesions obtained from cattle and buffalos at Marajó Island, Brazil, demonstrates that recent transmission ofM. bovisis ongoing at distinct sites. Moreover, theM. bovisepidemiology in this setting is herein found to be dominated by an endemic and unique clade composed of strains evolved from a common ancestor that are now genetically differentiated from otherM. bovisclades. Additionally, envisioning a rapid strain differentiation and tracing across multiple settings, 28 globally validated strain-specific SNPs were identified, three of which considered as robust markers for theM. bovisMarajó strain. In conclusion, this study contributes with data regarding the identification of a novelM. bovisphylogenetic clade responsible for ongoing transmission events in both cattle and buffalo species in Brazil, provides a framework to investigate the dissemination of this highly prevalent strain and, holds the potential to inform TB control strategies that may help to prevent the spread of bovine and zoonotic TB.
Fragility Limits Performance in Complex Networks
Authors: Pasqualetti Fabio , Zhao Shiyu , Favaretto Chiara , Zampieri Sandro
Published: February 2020

While numerous studies have suggested that large natural, biological, social, and technological networks are fragile, convincing theories are still lacking to explain why natural evolution and human design have failed to optimize networks and avoid fragility. In this paper we provide analytical and numerical evidence that a tradeoff exists in networks with linear dynamics, according to which general measures of robustness and performance are in fact competitive features that cannot be simultaneously optimized. Our findings show that large networks can either be robust to variations of their weights and parameters, or efficient in responding to external stimuli, processing noise, or transmitting information across long distances. As illustrated in our numerical studies, this performance tradeoff seems agnostic to the specific application domain, and in fact it applies to simplified models of ecological, neuronal, and traffic networks.
Functional lateralization of arithmetic processing in the intraparietal sulcus is associated with handedness
Authors: Artemenko Christina , Sitnikova Maria A. , Soltanlou Mojtaba , Dresler Thomas , Nuerk Hans-Christoph
Published: February 2020

Functional lateralization is established for various cognitive functions, but was hardly ever investigated for arithmetic processing. Most neurocognitive models assume a central role of the bilateral intraparietal sulcus (IPS) in arithmetic processing and there is some evidence for more pronounced left-hemispheric activation for symbolic arithmetic. However, evidence was mainly obtained by studies in right-handers. Therefore, we conducted a functional near-infrared spectroscopy (fNIRS) study, in which IPS activation of left-handed adults was compared to right-handed adults in a symbolic approximate calculation task. The results showed that left-handers had a stronger functional right-lateralization in the IPS than right-handers. This finding has important consequences, as the bilateral IPS activation pattern for arithmetic processing seems to be shaped by functional lateralization and thus differs between left- and right-handers. We propose three possible accounts for the observed functional lateralization of arithmetic processing.
A Precision Driver Device for Intraoperative Stimulation of a Bone Conduction Implant
Authors: Ghoncheh Mohammad , Lenarz Thomas , Maier Hannes
Published: February 2020

Semi-implantable bone conduction implants (BCI) and active middle ear implants (AMEI) for patients with sensorineural, conductive or mixed hearing loss commonly use an amplitude modulation technology to transmit power and sound signals from an external audio processor to the implant. In patients, the distance dependence of the signal amplitude is of minor importance as the skin thickness is constant and only varies between 3–7 mm. In this range, critical coupling transmission technique sufficiently reduces the variability in amplitude, but fails to provide well-defined amplitudes in many research and clinical applications such as intraoperative integrity tests where the distance range is exceeded by using sterile covers. Here we used the BCI Bonebridge (BB, Med-El, Austria) as an example to develop and demonstrate a system that synthesizes the transmission signal, determines the distance between the transmitter and the receiver implant coil and compensates transmission losses. When compared to an external audio processor (AP304) on an artificial mastoid, our system mainly decreased amplitude variability from over 11 dB to less than 3 dB for audio frequencies (0.1–10 kHz) at distances up to 15 mm, making it adequate for intraoperative and audiometric tests.
Structural and functional differentiation of bacterial communities in post-coal mining reclamation soils of South Africa: bioindicators of soil ecosystem restoration
Authors: Ezeokoli Obinna T. , Bezuidenhout Cornelius C. , Maboeta Mark S. , Khasa Damase P. , Adeleke Rasheed A.
Published: February 2020

Soil microbial communities are suitable soil ecosystem health indicators due to their sensitivity to management practices and role in soil ecosystem processes. Presently, information on structural and functional differentiation of bacterial communities in post-coal mining reclamation soils of South Africa is sparse. Here, bacterial communities in three post-coal mining reclamation soils were investigated using community-level physiological profiling (CLPP), enzyme activities, and next-generation sequencing of 16S rRNA gene. Inferences were drawn in reference to adjacent unmined soils. CLPP-based species diversity and proportionality did not differ significantly (P > 0.05) whereas activities of β-glucosidase, urease and phosphatases were significantly (P < 0.05) influenced by site and soil history (reclaimed vs unmined). Bacterial communities were influenced (PERMANOVA, P < 0.05) by soil history and site differences, with several phylotypes differentially abundant between soils. Contrastingly, predicted functional capabilities of bacterial communities were not different (PERMANOVA, P > 0.05), suggesting redundancy in bacterial community functions between reclamation and unmined soils. Silt content, bulk density, pH, electrical conductivity, Na and Ca significantly influenced soil bacterial communities. Overall, results indicate that bacterial community structure reflects underlying differences between soil ecosystems, and suggest the restoration of bacterial diversity and functions over chronological age in reclamation soils.
Aseismic mid-crustal magma reservoir at Cleveland Volcano imaged through novel receiver function analyses
Authors: Janiszewski Helen A. , Wagner Lara S. , Roman Diana C.
Published: February 2020

Processes related to eruptions at arc volcanoes are linked by structures that transect the entire crust. Imaging the mid- to lower-crustal portions (here, ~5–15 km and >15 km respectively) of these magmatic systems where intermediate storage may occur has been a longstanding challenge. Tomography, local seismic source studies, geodetic, and geochemical constraints, are typically most sensitive to shallow (<5 km) storage and/or have insufficient resolution at these depths. Geophysical methods are even further limited at frequently-erupting volcanoes where well-developed trans-crustal magmatic systems are likely to exist, due to a lack of deep seismicity. Here we show direct evidence for mid-crustal magma storage beneath the frequently erupting Cleveland volcano, Alaska, using a novel application of seismic receiver functions. We use P-s scattered waves from the Moho as virtual sources to investigate S-wave velocities between the Moho and the surface. Our forward modeling approach allows us to provide direct constraints on the geometry of low velocity regions beneath volcanoes despite having a comparatively sparse seismic network. Our results show clear evidence of mid-crustal magma storage beneath the depths of located volcanic seismicity. Future work using similar approaches will enable an unprecedented comparative examination of magmatic systems beneath sparsely instrumented volcanoes globally.
Genetic regulation of diapause and associated traits in Chilo partellus (Swinhoe)
Authors: Dhillon Mukesh K. , Hasan Fazil , Tanwar Aditya K. , Jaba Jagdish , Singh Naveen , Sharma Hari C.
Published: February 2020

Diapause is an endocrine controlled arrested metabolic state to delay development or reproduction under unfavorable conditions. To gain an understanding of importance of diapause for ecological adaptation, it is important to study regulation of diapause in insects. We examined genetics of diapause in Chilo partellus by crossing the hibernating (HD), aestivating (AD), post-hibernating (PHD), post-aestivating (PAD), and nondiapause (ND) strains. Reciprocal crosses were also made to gain full understanding of diapause regulation and the maternal effects, if any. Data were recorded on fecundity, egg hatching, larval survival, diapause induction and termination, adult emergence, and morphometrics of larvae, pupae and adults in the parents (P1, P2), F1 hybrids, and the reciprocal crosses. Genetic analysis showed that AD strain is general combiner, which also improved egg hatching, larval survival, diapause termination, adult emergence and proportion of females in the progenies. Incidence of diapause was highest in HD × AD, whereas termination was greatest in PHD × AD. However, ND strain and its reciprocal crosses with other strains did not exhibit any noticeable developmental response associated with diapause. Specific combining ability analysis suggested that where PHD and AD strains exist together there will be likely reduction in diapause incidence, increased survival with greater fitness and faster multiplication of their progenies resulting in outbreak of C. partellus. Degree of dominance estimates revealed that diapause, developmental and morphometric traits in C. partellus are governed by over dominance gene effects, and mainly depend on parental diapause history.
Accounting for soil respiration variability – Case study in a Mediterranean pine-dominated forest
Authors: Pantani Ottorino-Luca , Fioravanti Fabrizio , Stefanini Federico M. , Berni Rossella , Certini Giacomo
Published: February 2020

The number of spots to monitor to evaluate soil respiration (Rs) is often chosen on an empirical or conventional basis. To obtain an insight into the necessary number of spots to account for Rs variability in a Mediterranean pine-dominated mixed forest, we measured Rs all year long on sixteen dates with a portable gas-analyser in 50 spots per date within an area 1/3 ha wide. Linear mixed-effects models with soil temperature and litter moisture as descriptors, were fitted to the collected data and then evaluated in a Monte Carlo simulation on a progressively decreasing number of spots to identify the minimum number required to estimate Rs with a given confidence interval. We found that monitoring less than 14 spots would have resulted in a 10% probability of not fitting the model, while monitoring 20 spots would have reduced the same probability to about 5% and was the best compromise between field efforts and quality of the results. A simple rainfall index functional to select sampling dates during the summer drought is proposed.
Spin-orbit Torque Switching of Perpendicular Magnetization in Ferromagnetic Trilayers
Authors: Lee Dong-Kyu , Lee Kyung-Jin
Published: February 2020

In ferromagnetic trilayers, a spin-orbit-induced spin current can have a spin polarization of which direction is deviated from that for the spin Hall effect. Recently, magnetization switching in ferromagnetic trilayers has been proposed and confirmed by the experiments. In this work, we theoretically and numerically investigate the switching current required for perpendicular magnetization switching in ferromagnetic trilayers. We confirm that the tilted spin polarization enables field-free deterministic switching at a lower current than conventional spin-orbit torque or spin-transfer torque switching, offering a possibility for high-density and low-power spin-orbit torque devices. Moreover, we provide analytical expressions of the switching current for an arbitrary spin polarization direction, which will be useful to design spin-orbit torque devices and to interpret spin-orbit torque switching experiments.