bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum carotenoid concentrations and their association with ethnic differences in type 2 diabetes within the Healthy Life in an Urban Setting (HELIUS) study
Authors: Flores Sanchez P , Muilwijk M , Nicolaou M , Snijder MB , Peters RJG , van Valkengoed IGM
Published: May 2020

Objective:

Studies have reported an inverse association between a diet rich in fruits and vegetables and type 2 diabetes (T2D), but data on high-risk ethnic minority groups is limited. We investigated whether serum carotenoids, as biomarkers for fruit and vegetable intake, mediate ethnic differences in the prevalence of T2D.

Design:

Age-adjusted serum carotenoid concentrations were compared using ANCOVA. A cross-sectional analysis was performed using Cox regression to estimate prevalence ratios (PR) and their 95 % CI of the association between serum carotenoid concentrations and T2D. To study whether serum carotenoids potentially mediate the differences in the prevalence of T2D across ethnic groups, we compared PR of the model including known risk factors and the model additionally adjusted for serum carotenoid concentrations using the Dutch group as reference.

Setting:

A study among six ethnic groups living in Amsterdam, the Netherlands.

Participants:

Data on 204 Dutch, 203 South Asian Surinamese, 204 African Surinamese, 203 Turkish and 200 Moroccan-origin participants from the Healthy Life in an Urban Setting (HELIUS) study were used.

Results:

Serum carotenoid concentrations differed across ethnic groups. After adjusting for confounders, the serum concentrations of total carotenoids (PR 0·67, 95 % CI 0·54, 0·84), α-carotene (PR 0·57, 95 % CI 0·42, 0·77), β-carotene (PR 0·45, 95 % CI 0·32, 0·63) and β-cryptoxanthin (PR 0·73, 95 % CI 0·58, 0·92) were inversely associated with T2D. Despite the associations, serum carotenoids did not mediate the ethnic differences in the prevalence of T2D.

Conclusions:

The limited contribution of serum carotenoids to ethnic differences in T2D suggests that a focus on increasing fruit and vegetable intake alone will not likely eliminate ethnic differences in T2D prevalence.
Splitting Epistemic Logic Programs
Authors: CABALAR PEDRO , FANDINNO JORGE , FARIÑAS DEL CERRO LUIS
Published: May 2020

Epistemic logic programs constitute an extension of the stable model semantics to deal with new constructs called subjective literals. Informally speaking, a subjective literal allows checking whether some objective literal is true in all or some stable models. As it can be imagined, the associated semantics has proved to be non-trivial, since the truth of subjective literals may interfere with the set of stable models it is supposed to query. As a consequence, no clear agreement has been reached and different semantic proposals have been made in the literature. Unfortunately, comparison among these proposals has been limited to a study of their effect on individual examples, rather than identifying general properties to be checked. In this paper, we propose an extension of the well-known splitting property for logic programs to the epistemic case. We formally define when an arbitrary semantics satisfies the epistemic splitting property and examine some of the consequences that can be derived from that, including its relation to conformant planning and to epistemic constraints. Interestingly, we prove (through counterexamples) that most of the existing approaches fail to fulfill the epistemic splitting property, except the original semantics proposed by Gelfond 1991 and a recent proposal by the authors, called Founded Autoepistemic Equilibrium Logic.
Design and qualification of Ku-band-radiating chains for receive active array antennas of flexible telecommunication satellites
Authors: Pascale Vincenzo , Maiarelli Davide , D'Agristina Luciano , Gatti Nicola
Published: May 2020

Airbus Italia recently developed enhanced passive components as key elements for its telecommunication Ku-band antenna product lines, tailored to reconfigurable payloads. This paper describes the design and qualification of a dual linear polarization Ku-band-radiating chain, developed for the DRA receive (Rx) active antennas embarked on the Eutelsat Quantum satellite. The feed chain covers the entire Ku-band frequency range allocated for fixed satellite services providing receive functionality and embedding sharp rejection features over the adjacent transmit band. The proposed design provides high radiation efficiency (>90%) and polarization purity (XPD > 33 dB), together with low RF losses and flat group-delay variation over a 13% fractional bandwidth, keeping a compact size and reduced axial length. The unit has been optimized for high reproducibility in high volume productions, typical of large DRA applications, for which stringent mass and dimensional constraints, as well as excellent amplitude and phase tracking among similar units, are key features. Details of the feed chain design and an overview of RF and environmental qualification test results are presented.
Development of Reading Abilities in Children with ADHD Following fNIRS-Neurofeedback or EMG-Biofeedback
Authors: Blume Friederike , Quixal Martí , Hudak Justin , Dresler Thomas , Gawrilow Caterina , Ehlis Ann-Christine
Published: May 2020

Abstract. Children with attention deficit/hyperactivity disorder (ADHD) show deficient reading skills, which, like ADHD symptoms, are associated with limitations in neurocognitive abilities. Neurofeedback (NF) aims to improve the latter, to alleviate ADHD symptoms, and to promote school and reading performances. Whether frontal lobe-NF based on functional near-infrared spectroscopy (fNIRS) and electromyogram (EMG)-biofeedback (BF), however, improve reading abilities of children with ADHD and whether these changes are associated with changes in neurocognitive abilities, has not yet been clarified. It was also unclear whether embedding trainings in virtual reality (VR) could increase their effectiveness. These questions were examined using data of 35 children with ADHD (6–11 years) who participated in 15 sessions of fNIRS-NF in VR, fNIRS-NF in 2D, or EMG-BF in VR. On average, children's reading performance improved in all training groups. Stronger improvements were found after VR trainings. Improvements in reading natural words were, on a trend level, accompanied by decreasing attention, while improvements in reading pseudowords were accompanied by improved sustained attention and response inhibition. The results suggest that fNIRS-NF and EMG-BF effectively improve reading abilities of children with ADHD, especially when training in VR.
Dissolved Thorium Isotope Evidence for Export Productivity in the Subtropical North Pacific During the Late Quaternary
Authors: Liu Ruolin , Wang Maoyu , Li Weiqiang , Shi Xuefa , Chen Tianyu
Published: May 2020

The vast area of the North Pacific subtropical gyre (NPSG) makes it an important region in exporting biogenic particles and carbon to the deep ocean. Nevertheless, we remain largely ignorant on its past changes in export productivity, leaving an important gap in the understanding of ocean‐climate interactions during the late Quaternary. Here, we take a novel approach to study the particle export via reconstruction of dissolved 230Th/232Th based on ferromanganese crusts in deep waters of the NPSG at 3.8‐ and 2.8‐km water depth, respectively. The U‐series data indicate stable growth rates of both samples and a rather small variability of their initial (230Th/232Th) in the last ca. 0.7 Myr. These glacial–interglacial integrated values are only about half of the modern dissolved (230Th/232Th) in the deep NPSG, reflecting increased dust dissolution and also particle scavenging related to ~10–40% higher average export productivity than today.
Detailed Seismic Bathymetry Beneath Ekström Ice Shelf, Antarctica: Implications for Glacial History and Ice‐Ocean Interaction
Authors: Smith Emma C. , Hattermann Tore , Kuhn Gerhard , Gaedicke Christoph , Berger Sophie , Drews Reinhard , Ehlers Todd A. , Franke Dieter , Gromig Rapahel , Hofstede Coen , Lambrecht Astrid , Läufer Andreas , Mayer Christoph , Tiedemann Ralf , Wilhelms Frank , Eisen Olaf
Published: May 2020

The shape of ice shelf cavities are a major source of uncertainty in understanding ice‐ocean interactions. This limits assessments of the response of the Antarctic ice sheets to climate change. Here we use vibroseis seismic reflection surveys to map the bathymetry beneath the Ekström Ice Shelf, Dronning Maud Land. The new bathymetry reveals an inland‐sloping trough, reaching depths of 1,100 m below sea level, near the current grounding line, which we attribute to erosion by palaeo‐ice streams. The trough does not cross‐cut the outer parts of the continental shelf. Conductivity‐temperature‐depth profiles within the ice shelf cavity reveal the presence of cold water at shallower depths and tidal mixing at the ice shelf margins. It is unknown if warm water can access the trough. The new bathymetry is thought to be representative of many ice shelves in Dronning Maud Land, which together regulate the ice loss from a substantial area of East Antarctica.
Methane’s Rising: What Can We Do to Bring It Down?
Authors: Nisbet Euan
Published: May 2020

Reducing methane emissions is critical for addressing climate warming, but which are the easiest and most cost-effective ways to do this?
Evaluation of the Consistency of ECMWF Ensemble Forecasts
Authors: Richardson David S. , Cloke Hannah L. , Pappenberger Florian
Published: May 2020

An expected benefit of ensemble forecasts is that a sequence of consecutive forecasts valid for the same time will be more consistent than an equivalent sequence of individual forecasts. Inconsistent (jumpy) forecasts can cause users to lose confidence in the forecasting system. We present a first systematic, objective evaluation of the consistency of the European Centre for Medium‐Range Weather Forecasts (ECMWF) ensemble using a measure of forecast divergence that takes account of the full ensemble distribution. Focusing on forecasts of the North Atlantic Oscillation and European Blocking regimes up to 2 weeks ahead, we identify occasional large inconsistency between successive runs, with the largest jumps tending to occur at 7–9 days lead. However, care is needed in the interpretation of ensemble jumpiness. An apparent clear flip‐flop in a single index may hide a more complex predictability issue which may be better understood by examining the ensemble evolution in phase space.
Impact of HPV vaccination on cervical screening performance: a population-based cohort study
Authors: Lei Jiayao , Ploner Alexander , Lehtinen Matti , Sparén Pär , Dillner Joakim , Elfström K. Miriam
Published: May 2020

Background

Human papillomavirus (HPV) vaccination is predicted to lower the positive predictive value (PPV) of cytology.

Methods

We included 153,250 girls born between 1989 and 1993, resident in Sweden since the introduction of HPV vaccines (October 2006) and attending cervical screening at age 23 years. We assessed their first cytology and following histopathological diagnosis using Swedish National Cervical Screening Registry (NKCx). By linkage with the national Swedish HPV vaccination registry, we determined PPV of abnormal cytology for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and the differences with 95% confidence intervals (CIs) according to vaccination status.

Results

The PPV of high-grade cytology for CIN2+ was 69.9% (95% CI, 67.9–71.9), 64.9% (95% CI, 59.8–69.8) and 57.4% (95% CI, 50.9–63.7) among women unvaccinated, initiating vaccination at age 17–22 years and initiating vaccination before age 17 years, corresponding to reduction in PPV by 8% (95% CI, 0–15%) and 17% (95% CI, 7–26%) in vaccinated groups after adjustment for birth cohort, respectively.

Conclusion

The PPV of cytology for CIN2+ decreased among vaccinated women, and the decrease was stronger for girls vaccinated at younger ages. A switch from cytology to HPV testing might potentially improve the screening performance.
Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines
Authors: Kagohara Luciane T. , Zamuner Fernando , Davis-Marcisak Emily F. , Sharma Gaurav , Considine Michael , Allen Jawara , Yegnasubramanian Srinivasan , Gaykalova Daria A. , Fertig Elana J.
Published: May 2020

Background

Identifying potential resistance mechanisms while tumour cells still respond to therapy is critical to delay acquired resistance.

Methods

We generated the first comprehensive multi-omics, bulk and single-cell data in sensitive head and neck squamous cell carcinoma (HNSCC) cells to identify immediate responses to cetuximab. Two pathways potentially associated with resistance were focus of the study: regulation of receptor tyrosine kinases by TFAP2A transcription factor, and epithelial-to-mesenchymal transition (EMT).

Results

Single-cell RNA-seq demonstrates heterogeneity, with cell-specific TFAP2A and VIM expression profiles in response to treatment and also with global changes to various signalling pathways. RNA-seq and ATAC-seq reveal global changes within 5 days of therapy, suggesting early onset of mechanisms of resistance; and corroborates cell line heterogeneity, with different TFAP2A targets or EMT markers affected by therapy. Lack of TFAP2A expression is associated with HNSCC decreased growth, with cetuximab and JQ1 increasing the inhibitory effect. Regarding the EMT process, short-term cetuximab therapy has the strongest effect on inhibiting migration. TFAP2A silencing does not affect cell migration, supporting an independent role for both mechanisms in resistance.

Conclusion

Overall, we show that immediate adaptive transcriptional and epigenetic changes induced by cetuximab are heterogeneous and cell type dependent; and independent mechanisms of resistance arise while tumour cells are still sensitive to therapy.
MCL-1Matrix maintains neuronal survival by enhancing mitochondrial integrity and bioenergetic capacity under stress conditions
Authors: Anilkumar Ujval , Khacho Mireille , Cuillerier Alexanne , Harris Richard , Patten David A. , Bilen Maria , Iqbal Mohamed Ariff , Guo Ding Yuan , Trudeau Louis-Eric , Park David S. , Harper Mary-Ellen , Burelle Yan , Slack Ruth S.
Published: May 2020

Mitochondria play a crucial role in neuronal survival through efficient energy metabolism. In pathological conditions, mitochondrial stress leads to neuronal death, which is regulated by the anti-apoptotic BCL-2 family of proteins. MCL-1 is an anti-apoptotic BCL-2 protein localized to mitochondria either in the outer membrane (OM) or inner membrane (Matrix), which have distinct roles in inhibiting apoptosis and promoting bioenergetics, respectively. While the anti-apoptotic role for Mcl1 is well characterized, the protective function of MCL-1 Matrix remains poorly understood. Here, we show MCL-1OM and MCL-1Matrix prevent neuronal death through distinct mechanisms. We report that MCL-1Matrix functions to preserve mitochondrial energy transduction and improves respiratory chain capacity by modulating mitochondrial oxygen consumption in response to mitochondrial stress. We show that MCL-1Matrix protects neurons from stress by enhancing respiratory function, and by inhibiting mitochondrial permeability transition pore opening. Taken together, our results provide novel insight into how MCL-1Matrix may confer neuroprotection under stress conditions involving loss of mitochondrial function.
Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes
Authors: Seiller Carolane , Maiga Sophie , Touzeau Cyrille , Bellanger Céline , Kervoëlen Charlotte , Descamps Géraldine , Maillet Laurent , Moreau Philippe , Pellat-Deceunynck Catherine , Gomez-Bougie Patricia , Amiot Martine
Published: May 2020

Multiple myeloma is a plasma cell malignancy that escapes from apoptosis by heterogeneously over-expressing anti-apoptotic BCL2 proteins. Myeloma cells with a t(11;14) translocation present a particular vulnerability to BCL2 inhibition while a majority of myeloma cells relies on MCL1 for survival. The present study aimed to determine whether the combination of BCL2 and MCL1 inhibitors at low doses could be of benefit for myeloma cells beyond the single selective inhibition of BCL2 or MCL1. We identified that half of patients were not efficiently targeted neither by BCL2 inhibitor nor MCL1 inhibitor. Seventy percent of these myeloma samples, either from patients at diagnosis or relapse, presented a marked increase of apoptosis upon low dose combination of both inhibitors. Interestingly, primary cells from a patient in progression under venetoclax treatment were not sensitive ex vivo to neither venetoclax nor to MCL1 inhibitor, whereas the combination of both efficiently induced cell death. This finding suggests that the combination could overcome venetoclax resistance. The efficacy of the combination was also confirmed in U266 xenograft model resistant to BCL2 and MCL1 inhibitors. Mechanistically, we demonstrated that the combination of both inhibitors favors apoptosis in a BAX/BAK dependent manner. We showed that activated BAX was readily increased upon the inhibitor combination leading to the formation of BAK/BAX hetero-complexes. We found that BCLXL remains a major resistant factor of cell death induced by this combination. The present study supports a rational for the clinical use of venetoclax/S63845 combination in myeloma patients with the potential to elicit significant clinical activity when both single inhibitors would not be effective but also to overcome developed in vivo venetoclax resistance.
Building and identifying highly active oxygenated groups in carbon materials for oxygen reduction to H2O2
Authors: Han Gao-Feng , Li Feng , Zou Wei , Karamad Mohammadreza , Jeon Jong-Pil , Kim Seong-Wook , Kim Seok-Jin , Bu Yunfei , Fu Zhengping , Lu Yalin , Siahrostami Samira , Baek Jong-Beom
Published: May 2020

The one-step electrochemical synthesis of H2O2 is an on-site method that reduces dependence on the energy-intensive anthraquinone process. Oxidized carbon materials have proven to be promising catalysts due to their low cost and facile synthetic procedures. However, the nature of the active sites is still controversial, and direct experimental evidence is presently lacking. Here, we activate a carbon material with dangling edge sites and then decorate them with targeted functional groups. We show that quinone-enriched samples exhibit high selectivity and activity with a H2O2 yield ratio of up to 97.8 % at 0.75 V vs. RHE. Using density functional theory calculations, we identify the activity trends of different possible quinone functional groups in the edge and basal plane of the carbon nanostructure and determine the most active motif. Our findings provide guidelines for designing carbon-based catalysts, which have simultaneous high selectivity and activity for H2O2 synthesis.
Demographic and genetic factors influence the abundance of infiltrating immune cells in human tissues
Authors: Marderstein Andrew R. , Uppal Manik , Verma Akanksha , Bhinder Bhavneet , Tayyebi Zakieh , Mezey Jason , Clark Andrew G. , Elemento Olivier
Published: May 2020

Despite infiltrating immune cells having an essential function in human disease and patients’ responses to treatments, mechanisms influencing variability in infiltration patterns remain unclear. Here, using bulk RNA-seq data from 46 tissues in the Genotype-Tissue Expression project, we apply cell-type deconvolution algorithms to evaluate the immune landscape across the healthy human body. We discover that 49 of 189 infiltration-related phenotypes are associated with either age or sex (FDR < 0.1). Genetic analyses further show that 31 infiltration-related phenotypes have genome-wide significant associations (iQTLs) (P < 5.0 × 10−8), with a significant enrichment of same-tissue expression quantitative trait loci in suggested iQTLs (P < 10−5). Furthermore, we find an association between helper T cell content in thyroid tissue and aCOMMD3/DNAJC1regulatory variant (P = 7.5 × 10−10), which is associated with thyroiditis in other cohorts. Together, our results identify key factors influencing inter-individual variability of immune infiltration, to provide insights on potential therapeutic targets.
Nanoengineering room temperature ferroelectricity into orthorhombic SmMnO3 films
Authors: Choi Eun-Mi , Maity Tuhin , Kursumovic Ahmed , Lu Ping , Bi Zenxhing , Yu Shukai , Park Yoonsang , Zhu Bonan , Wu Rui , Gopalan Venkatraman , Wang Haiyan , MacManus-Driscoll Judith L.
Published: May 2020

Orthorhombic RMnO3 (R = rare-earth cation) compounds are type-II multiferroics induced by inversion-symmetry-breaking of spin order. They hold promise for magneto-electric devices. However, no spontaneous room-temperature ferroic property has been observed to date in orthorhombic RMnO3. Here, using 3D straining in nanocomposite films of (SmMnO3)0.5((Bi,Sm)2O3)0.5, we demonstrate room temperature ferroelectricity and ferromagnetism with TC,FM ~ 90 K, matching exactly with theoretical predictions for the induced strain levels. Large in-plane compressive and out-of-plane tensile strains (−3.6% and +4.9%, respectively) were induced by the stiff (Bi,Sm)2O3 nanopillars embedded. The room temperature electric polarization is comparable to other spin-driven ferroelectric RMnO3 films. Also, while bulk SmMnO3 is antiferromagnetic, ferromagnetism was induced in the composite films. The Mn-O bond angles and lengths determined from density functional theory explain the origin of the ferroelectricity, i.e. modification of the exchange coupling. Our structural tuning method gives a route to designing multiferroics.
Author Correction: Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
Authors: Seo Ji A. , Kang Min-Cheol , Yang Won-Mo , Hwang Won Min , Kim Sang Soo , Hong Soo Hyun , Heo Jee-In , Vijyakumar Achana , de Moura Leandro Pereira , Uner Aykut , Huang Hu , Lee Seung Hwan , Lima Inês S. , Park Kyong Soo , Kim Min Seon , Dagon Yossi , Willnow Thomas E. , Aroda Vanita , Ciaraldi Theodore P. , Henry Robert R. , Kim Young-Bum
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Clinical utility of 24-h rapid trio-exome sequencing for critically ill infants
Authors: Wang Huijun , Qian Yanyan , Lu Yulan , Qin Qian , Lu Guoping , Cheng Guoqiang , Zhang Ping , Yang Lin , Wu Bingbing , Zhou Wenhao
Published: May 2020

Genetic diseases are a leading cause of death in infants in the intensive care setting; therefore, rapid and accurate genetic diagnosis is desired. To validate 24-h trio-exome sequencing (TES), samples from probands and their parents were processed by the AmpliSeq /Ion S5XL platform in a hospital clinical laboratory. Infants from the intensive care unit (ICU) suspected of having a genetic disease were enrolled. Regular and 24-h TES using the Agilent SureSelect capture kit/Illumina platform were performed on all samples in parallel. Of 33 enrolled infants, 23 received positive results with rapid TES, and an additional two diagnoses were achieved with regular TES. Among the 23 diagnosed patients, 10 experienced changes in medical management, such as hematopoietic stem cell transplant. Ten diagnosed cases were discharged prior to receiving the regular TES results; six received timely symptom control, and four withdrew medical support. Rapid TES enabled faster time to diagnosis, which resulted in an overall decrease in length of hospital stay. The 24-h TES can serve as a rapid response tool for patients with suspected monogenic disorders and can guide clinical decision-making in urgent cases.
A systematic review and meta-analysis of bone loss in space travelers
Authors: Stavnichuk Mariya , Mikolajewicz Nicholas , Corlett Tatsuya , Morris Martin , Komarova Svetlana V.
Published: May 2020

Bone loss in space travelers is a major challenge for long-duration space exploration. To quantify microgravity-induced bone loss in humans, we performed a meta-analysis of studies systematically identified from searching Medline, Embase, Web of Science, BIOSIS, NASA Technical reports, and HathiTrust, with the last update in November 2019. From 25 articles selected to minimize the overlap between reported populations, we extracted post-flight bone density values for 148 individuals, and in-flight and post-flight biochemical bone marker values for 124 individuals. A percentage difference in bone density relative to pre-flight was positive in the skull, +2.2% [95% confidence interval: +1.1, +3.3]; neutral in the thorax/upper limbs, −0.7% [−1.3, −0.2]; and negative in the lumbar spine/pelvis, −6.2 [−6.7, −5.6], and lower limbs, −5.4% [−6.0, −4.9]. In the lower limb region, the rate of bone loss was −0.8% [−1.1, −0.5] per month. Bone resorption markers increased hyperbolically with a time to half-max of 11 days [9, 13] and plateaued at 113% [108, 117] above pre-flight levels. Bone formation markers remained unchanged during the first 30 days and increased thereafter at 7% [5, 10] per month. Upon landing, resorption markers decreased to pre-flight levels at an exponential rate that was faster after longer flights, while formation markers increased linearly at 84% [39, 129] per month for 3–5 months post-flight. Microgravity-induced bone changes depend on the skeletal-site position relative to the gravitational vector. Post-flight recovery depends on spaceflight duration and is limited to a short post-flight period during which bone formation exceeds resorption.
Sources of seasonal wetland methane emissions in permafrost regions of the Qinghai-Tibet Plateau
Authors: Zhang Shunyao , Zhang Fugui , Shi Zeming , Qin Aihua , Wang Huiyan , Sun Zhongjun , Yang Zhibin , Zhu Youhai , Pang Shouji , Wang Pingkang
Published: May 2020

In this study, systematic soil methane cycle geochemical monitoring was carried out in a typical gas hydrate region in the Qinghai-Tibet Plateau. Soil gas samples were collected for hydrocarbon components and carbon isotope analysis. Meanwhile, soil-methane fluxes from the upper active layer (20–30 cm) were monitored during six months of one year. The results of this research provide evidence of a new source of methane emission from wetland soils in permafrost regions: gas hydrate release. Sites with large methane emissions were found using flux monitoring, the characteristics of thermogenic methane were identified using carbon isotope tracing, and the relationship between emission by soils and effusion from gas hydrates was determined through correlation analyses of soil-adsorbed hydrocarbons. Seasonal variation of methane emissions are also discussed by considering the emission of bacterial methane, thermogenic methane, and the absorption of methane from the soil active layer. These comprehensive findings provide valuable information for carbon cycle research of wetlands in permafrost regions.
Factors governing outbreak dynamics in a forest intensively managed for mountain pine beetle
Authors: Kunegel-Lion Mélodie , Lewis Mark A.
Published: May 2020

Mountain pine beetle (MPB) outbreaks have caused major economic losses and ecological consequences in North American pine forests. Ecological and environmental factors impacting MPB life-history and stands susceptibility can help with the detection of MPB infested trees and thereby, improve control. Temperatures, water stress, host characteristics, and beetle pressure are among those ecological and environmental factors. They play different roles on MPB population dynamics at the various stages of an outbreak and these roles can be affected by intensive management. However, to make detailed connections between ecological and environmental variables and MPB outbreak phases, a deeper quantitative analysis on local scales is needed. Here, we used logistic regressions on a highly-detailed and georeferenced data set to determine the factors driving MPB infestations for the different phases of the current isolated MPB outbreak in Cypress Hills. While we showed that the roles of ecological and environmental factors in a forest intensively controlled for MPB are consistent with the literature for uncontrolled forests, we determined how these factors shifted through onset, peak, and collapse phases of the intensively controlled forest. MPB presence mostly depends on nearby beetle pressure, notably for the outbreak peak. However additional weather and host variables are necessary to achieve high predictive ability for MPB outbreak locations. Our results can help managers make appropriate decisions on where and how to focus their effort, depending on which phase the outbreak is in.
Characterization of a novel automated microfiltration device for the efficient isolation and analysis of circulating tumor cells from clinical blood samples
Authors: Yee-de León Juan F. , Soto-García Brenda , Aráiz-Hernández Diana , Delgado-Balderas Jesús Rolando , Esparza Miguel , Aguilar-Avelar Carlos , Wong-Campos J. D. , Chacón Franco , López-Hernández José Y. , González-Treviño A. Mauricio , Yee-de León José R. , Zamora-Mendoza Jorge L. , Alvarez Mario M. , Trujillo-de Santiago Grissel , Gómez-Guerra Lauro S. , Sánchez-Domínguez Celia N. , Velarde-Calvillo Liza P. , Abarca-Blanco Alejandro
Published: May 2020

The detection and analysis of circulating tumor cells (CTCs) may enable a broad range of cancer-related applications, including the identification of acquired drug resistance during treatments. However, the non-scalable fabrication, prolonged sample processing times, and the lack of automation, associated with most of the technologies developed to isolate these rare cells, have impeded their transition into the clinical practice. This work describes a novel membrane-based microfiltration device comprised of a fully automated sample processing unit and a machine-vision-enabled imaging system that allows the efficient isolation and rapid analysis of CTCs from blood. The device performance was characterized using four prostate cancer cell lines, including PC-3, VCaP, DU-145, and LNCaP, obtaining high assay reproducibility and capture efficiencies greater than 93% after processing 7.5 mL blood samples spiked with 100 cancer cells. Cancer cells remained viable after filtration due to the minimal shear stress exerted over cells during the procedure, while the identification of cancer cells by immunostaining was not affected by the number of non-specific events captured on the membrane. We were also able to identify the androgen receptor (AR) point mutation T878A from 7.5 mL blood samples spiked with 50 LNCaP cells using RT-PCR and Sanger sequencing. Finally, CTCs were detected in 8 out of 8 samples from patients diagnosed with metastatic prostate cancer (mean ± SEM = 21 ± 2.957 CTCs/mL, median = 21 CTCs/mL), demonstrating the potential clinical utility of this device.
Video-call based newborn triage system for local birth centres can be established without major instalment costs using commercially available smartphones
Authors: Okada Junichiro , Hisano Tadashi , Unno Mitsuaki , Tanaka Yukari , Saikusa Mamoru , Kinoshita Masahiro , Harada Eimei , Iwata Sachiko , Iwata Osuke
Published: May 2020

Neonates often develop transition problems after low-risk birth, precise assessment of which is difficult at primary birth centres. The aim of this study was to assess whether a video triage system can be established without a specially designed communication system between local birth centres and a tertiary neonatal intensive care unit in a region with a population of 700,000. 761 neonates who were referred to a tertiary neonatal intensive care unit were examined. During period 1 (April 2011-August 2015), only a voice call was available for consultations, whereas, during period 2 (September 2015-December 2017), a video call was additionally available. The respiratory condition was assessed based on an established visual assessment tool. A video consultation system was established by connecting personal smartphones at local birth centres with a host computer at a tertiary neonatal intensive care centre. During period 2, video-based triage was performed for 42.4% of 236 consultations at 30 birth centres. Sensitivity and specificity for predicting newborns with critical respiratory dysfunction changed from 0.758 to 0.898 and 0.684 to 0.661, respectively. A video consultation system for ill neonates was established without major instalment costs. Our strategy might improve the transportation system in both high- and low-resource settings.
Long-range Regulation of Partially Folded Amyloidogenic Peptides
Authors: Bhattacharya Shayon , Xu Liang , Thompson Damien
Published: May 2020

Neurodegeneration involves abnormal aggregation of intrinsically disordered amyloidogenic peptides (IDPs), usually mediated by hydrophobic protein-protein interactions. There is mounting evidence that formation of α-helical intermediates is an early event during self-assembly of amyloid-β42 (Aβ42) and α-synuclein (αS) IDPs in Alzheimer’s and Parkinson’s disease pathogenesis, respectively. However, the driving force behind on-pathway molecular assembly of partially folded helical monomers into helical oligomers assembly remains unknown. Here, we employ extensive molecular dynamics simulations to sample the helical conformational sub-spaces of monomeric peptides of both Aβ42 and αS. Our computed free energies, population shifts, and dynamic cross-correlation network analyses reveal a common feature of long-range intra-peptide modulation of partial helical folds of the amyloidogenic central hydrophobic domains via concerted coupling with their charged terminal tails (N-terminus of Aβ42 and C-terminus of αS). The absence of such inter-domain fluctuations in both fully helical and completely unfolded (disordered) states suggests that long-range coupling regulates the dynamicity of partially folded helices, in both Aβ42 and αS peptides. The inter-domain coupling suggests a form of intra-molecular allosteric regulation of the aggregation trigger in partially folded helical monomers. This approach could be applied to study the broad range of amyloidogenic peptides, which could provide a new path to curbing pathogenic aggregation of partially folded conformers into oligomers, by inhibition of sites far from the hydrophobic core.
Sexual Dimorphism of Metabolomic Profile in Arterial Hypertension
Authors: Goïta Yaya , Chao de la Barca Juan Manuel , Keïta Asmaou , Diarra Mamadou Bocary , Dembélé Klétigui Casimir , Chabrun Floris , Dramé Boubacar Sidiki Ibrahim , Kassogué Yaya , Diakité Mahamadou , Mirebeau-Prunier Delphine , Cissé Bakary Mamadou , Simard Gilles , Reynier Pascal
Published: May 2020

Metabolomic studies have demonstrated the existence of biological signatures in blood of patients with arterial hypertension, but no study has hitherto reported the sexual dimorphism of these signatures. We compared the plasma metabolomic profiles of 28 individuals (13 women and 15 men) with essential arterial hypertension with those of a healthy control group (18 women and 18 men), using targeted metabolomics. Among the 188 metabolites explored, 152 were accurately measured. Supervised OPLS-DA (orthogonal partial least squares-discriminant analysis) showed good predictive performance for hypertension in both sexes (Q2cum = 0.59 in women and 0.60 in men) with low risk of overfitting (p-value-CV ANOVA = 0.004 in women and men). Seventy-five and 65 discriminant metabolites with a VIP (variable importance for the projection) greater than 1 were evidenced in women and men, respectively. Both sexes showed a considerable increase in phosphatidylcholines, a decrease in C16:0 with an increase in C28:1 lysophosphatidylcholines, an increase in sphingomyelins, as well as an increase of symmetric dimethylarginine (SDMA), acetyl-ornithine and hydroxyproline. Twenty-nine metabolites, involved in phospholipidic and cardiac remodeling, arginine/nitric oxide pathway and antihypertensive and insulin resistance mechanisms, discriminated the metabolic sexual dimorphism of hypertension. Our results highlight the importance of sexual dimorphism in arterial hypertension.
The Influence of Listening to Music on Adults with Left-behind Experience Revealed by EEG-based Connectivity
Authors: Tian Yin , Ma Liang , Xu Wei , Chen Sifan
Published: May 2020

The human brain has a close relationship with music. Music-induced structural and functional brain changes have been demonstrated in the healthy adult. In the present study, adults with left-behind experience (ALB) were divided into two groups. The experimental group (ALB-E) took part in the music therapy experiment with three stages, including before listening to music (pre-stage), initially listening to music (mid-stage) and after listening to music (post-stage). The control group (ALB-C) did not participate in music therapy. Scalp resting-state EEGs of ALB were recorded during the three stages. We found no significant frequency change in the ALB-C group. In the ALB-E group, only the theta power spectrum was significantly different at all stages. The topographical distributions of the theta power spectrum represented change in trends from the frontal regions to the occipital regions. The result of Granger causal analysis (GCA), based on theta frequency, showed a stronger information flow from the middle frontal gyrus to the middle temporal gyrus (MFG → MTG) in the left hemisphere at the pre-stage compared to the post-stage. Additionally, the experimental group showed a weaker information flow from inferior gyrus to superior temporal gyrus (IFG → STG) in the right hemisphere at post-test stage compared to the ALB-C group. Our results demonstrate that listening to music can play a positive role on improving negative feelings for individuals with left behind experience.
Longitudinal osmotic and neurometabolic changes in young rats with chronic cholestatic liver disease
Authors: Rackayova Veronika , Braissant Olivier , Rougemont Anne-Laure , Cudalbu Cristina , McLin Valérie A.
Published: May 2020

Type C hepatic encephalopathy (type C HE) is increasingly suspected in children with chronic liver disease (CLD), and believed to underlie long-term neurocognitive difficulties. The molecular underpinnings of type C HE in both adults and children are incompletely understood. In the present study we combined the experimental advantages of in vivo high field 1H magnetic resonance spectroscopy with immunohistochemistry to follow longitudinally over 8 weeks the neurometabolic changes in the hippocampus of animals having undergone bile duct ligation as pups. Rats who develop CLD early in life displayed pronounced neurometabolic changes in the hippocampus characterized by a progressive increase in glutamine concentration which correlated with plasma ammonia levels and a rapid decrease in brain myo-inositol. Other neurometabolic findings included a decrease in other organic osmolytes (taurine, choline-containing compounds and creatine), ascorbate and glutamate. At the cellular level, we observed an increase in glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression in the hippocampus at 4 weeks post bile duct ligation (BDL), together with astrocytic morphological alterations. These findings differ from observations in the brain of adult rats following BDL, and are in keeping with the commonly accepted theory of age-dependent vulnerability.
Stem cell delivery to kidney via minimally invasive ultrasound-guided renal artery injection in mice
Authors: Zaw Thin May , Ogunlade Olumide , Comenge Joan , Patrick P. Stephen , Stuckey Daniel J. , David Anna L. , Lythgoe Mark F. , Beard Paul , Kalber Tammy L.
Published: May 2020

Cell-based therapies are promising treatments for various kidney diseases. However, the major hurdle in initiating therapeutic responses is the inefficiency of injection routes to deliver cells to the kidney parenchyma. Systemic injection, such as intravenous injection only delivers a small proportion of cells to the kidney. Whereas direct delivery, such as renal artery injection requires surgical procedures. A minimally invasive renal artery injection was therefore developed to enhance cell delivery to kidney. In this study, luciferase expressing human adipocyte derived stem cells (ADSC) were labelled with gold nanorods (GNR) and injected into the renal artery using ultrasound guidance. The ADSCs were tracked using bioluminescence and photoacoustic imaging serially over 7 days. Imaging confirmed that the majority of signal was within the kidney, indicative of successful injection and that the cells remained viable for 3 days. Histology showed co-localization of GNRs with ADSC staining throughout the kidney with no indication of injury caused by injection. These findings demonstrate that ultrasound-guided renal artery injection is feasible in mice and can successfully deliver a large proportion of cells which are retained within the kidney for 3 days. Therefore, the techniques developed here will be useful for optimising cell therapy in kidney diseases.
Three-dimensional architecture of human diabetic peripheral nerves revealed by X-ray phase contrast holographic nanotomography
Authors: Dahlin Lars B. , Rix Kristian R. , Dahl Vedrana A. , Dahl Anders B. , Jensen Janus N. , Cloetens Peter , Pacureanu Alexandra , Mohseni Simin , Thomsen Niels O. B. , Bech Martin
Published: May 2020

A deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy. Here we demonstrate the feasibility of X-ray phase contrast holographic nanotomography to enable 3D imaging of nerves at high resolution, while covering a relatively large tissue volume. We show various subcomponents of human peripheral nerves in biopsies from patients with type 1 and 2 diabetes and in a healthy subject. Together with well-organized, parallel myelinated nerve fibres we show regenerative clusters with twisted nerve fibres, a sprouted axon from a node of Ranvier and other specific details. A novel 3D construction (with movie created) of a node of Ranvier with end segment of a degenerated axon and sprout of a regenerated one is captured. Many of these architectural elements are not described in the literature. Thus, X-ray phase contrast holographic nanotomography enables identifying specific morphological structures in 3D in peripheral nerve biopsies from a healthy subject and from patients with type 1 and 2 diabetes.
Author Correction: Ginkgolic acid inhibits fusion of enveloped viruses
Authors: Borenstein Ronen , Hanson Barbara A. , Markosyan Ruben M. , Gallo Elisa S. , Narasipura Srinivas D. , Bhutta Maimoona , Shechter Oren , Lurain Nell S. , Cohen Fredric S. , Al-Harthi Lena , Nicholson Daniel A.
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Formulation of Sugar/Hydrogel Inks for Rapid Thermal Response 4D Architectures with Sugar-derived Macropores
Authors: Ko Hyojin , Ratri Monica Cahyaning , Kim Kihoon , Jung Yeongheon , Tae Giyoong , Shin Kwanwoo
Published: May 2020

Programmed, reshaping hydrogel architectures were fabricated from sugar/hydrogel inks via a three-dimensional printing method involving a stimuli-responsive polymer. We developed a new hydrogel ink composed of monomers (acrylamide [AAm]) and N-isopropylacrylamide [NIPAAm]), and sugar (mixture of glucose and sucrose) as a pore-generator, enabling to improve printability by increasing the ink’s viscoelastic properties and induce the formation of macropores in the hydrogel architectures. This study demonstrated that creating macropores in such architectures enables rapid responses to stimuli that can facilitate four-dimensional printing. We printed bilayer structures from monomer inks to which we had added sugar, and we exposed them to processes that cross-linked the monomers and leached out the sugar to create macropores. In comparison with a conventional poly(N-isopropylacrylamide) hydrogel, the macroporous hydrogels prepared using polymerization in the presence of a high concentration of sugar showed higher swelling ratios and exhibited much faster response rates to temperature changes. We used rheometry and scanning electron microscopy to characterize the properties of these inks and hydrogels. The results suggest that this method may provide a readily available route to the rapid design and fabrication of shape-morphing hydrogel architectures with potential application in soft robotics, hydrogel actuators, and tissue engineering.
HIV-1 molecular epidemiology and drug resistance-associated mutations among treatment-naïve blood donors in China
Authors: Zhao Junpeng , Lv Xiaoting , Chang Le , Ji Huimin , Harris Barbara J. , Zhang Lu , Jiang Xinyi , Guo Fei , Hackett John , Yin Peng , Cloherty Gavin A. , Rodgers Mary A. , Wang Lunan
Published: May 2020

Surveillance of human immunodeficiency virus (HIV) molecular diversity and drug resistance-associated mutations (DRMs) among treatment-naïve blood donors is critical for monitoring viral evolution and blood safety. From 2016-2017, 199 plasma samples were collected from 24 blood centers and confirmed as HIV viral load positive or serologically reactive in National Centers for Clinical Laboratories (NCCL), of which 179 were sequenced and subtyped in the gag, protease (PR)-reverse transcriptase (RT), integrase (IN) and/or envelope (env) regions. DRMs in PR-RT and IN regions were analyzed in Stanford HIVdb Program. The majority of subtypes were circulating recombinant form (CRF) 07_BC (34.6%) and CRF01_AE (32.4%); many unique recombinant forms (URFs) (39, 21.8%) and other rare CRFs were observed in the study. Notably, CRF02_AG and CRF06_cpx strains typically found in Africa were firstly identified amongst Chinese blood donors. DRMs were common, with 28 of 179 (15.6%) specimens carrying DRMs, including the PR N88S and RT K103N mutations, which have been implicated in elevated resistance to antiretroviral drugs. Furthermore, 4 HIV-1 isolates (2.4%, 4/168) had surveillance drug-resistance mutation (SDRM), including 3 nonnucleosidereverse transcriptase inhibitors (NNRTI) SDRMs (1 K101E, 2 K103N) and 1 protease inhibitor (PI) SDRM (M46I). The HIV viral diversity among blood donors observed in this study suggest that ongoing HIV-1 recombination is becoming progressively complex in China, and lots of DRMs found in the study exacerbate the primary drug resistance landscape, which highlight the necessity of timely genotypic drug resistance monitoring and molecular surveillance of HIV-1 among blood donors.
A discrete core-shell-like micro-light-emitting diode array grown on sapphire nano-membranes
Authors: Lee Seungmin , Kim Jongmyeong , Oh Jehong , Ryu Jungel , Hwang Kyungwook , Hwang Junsik , Kang Sungjin , Choi Jun Hee , Sim Young Chul , Cho Yong-Hoon , Chung Tae Hoon , Jeong Tak , Park Yongjo , Yoon Euijoon
Published: May 2020

A discrete core-shell-like micro-light-emitting diode (micro-LED) array was grown on a 100 nm-thick sapphire nano-membrane array without harmful plasma etching for chip singulation. Due to proper design for the sapphire nano-membrane array, an array of multi-faceted micro-LEDs with size of 4 μm × 16 μm was grown. Threading dislocation density in the micro-LED formed on sapphire nano-membrane was reduced by 59.6% due to the sapphire nano-membranes, which serve as compliant substrates, compared to GaN formed on a planar substrate. Enhancements in internal quantum efficiency by 44% and 3.3 times higher photoluminescence intensity were also observed from it. Cathodoluminescence emission at 435 nm was measured from c-plane multiple quantum wells (MQWs), whereas negligible emissions were detected from semi-polar sidewall facets. A core-shell-like MQWs were formed on all facets, hopefully lowering concentration of non-radiative surface recombination centers and reducing leakage current paths. This study provides an attractive platform for micro-LEDs by using sapphire nano-membrane.