bluuebunny/crossref_metadata_2025 huggingface dataset:
MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
Authors: Munkhbaatar Enkhtsetseg , Dietzen Michelle , Agrawal Deepti , Anton Martina , Jesinghaus Moritz , Boxberg Melanie , Pfarr Nicole , Bidola Pidassa , Uhrig Sebastian , Höckendorf Ulrike , Meinhardt Anna-Lena , Wahida Adam , Heid Irina , Braren Rickmer , Mishra Ritu , Warth Arne , Muley Thomas , Poh Patrina S. P. , Wang Xin , Fröhling Stefan , Steiger Katja , Slotta-Huspenina Julia , van Griensven Martijn , Pfeiffer Franz , Lange Sebastian , Rad Roland , Spella Magda , Stathopoulos Georgios T. , Ruland Jürgen , Bassermann Florian , Weichert Wilko , Strasser Andreas , Branca Caterina , Heikenwalder Mathias , Swanton Charles , McGranahan Nicholas , Jost Philipp J.
Published: September 2020

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
Robust metal ion-chelated polymer interfacial layer for ultraflexible non-fullerene organic solar cells
Authors: Qin Fei , Wang Wen , Sun Lulu , Jiang Xueshi , Hu Lin , Xiong Sixing , Liu Tiefeng , Dong Xinyun , Li Jing , Jiang Youyu , Hou Jianhui , Fukuda Kenjiro , Someya Takao , Zhou Yinhua
Published: September 2020

Achieving high power conversion efficiency and good mechanical robustness is still challenging for the ultraflexible organic solar cells. Interlayers simultaneously having good mechanical robustness and good chemical compatibility with the active layer are highly desirable. In this work, we present an interlayer of Zn2+-chelated polyethylenimine (denoted as PEI-Zn), which can endure a maximum bending strain over twice as high as that of ZnO and is chemically compatible with the recently emerging efficient nonfullerene active layers. On 1.3 μm polyethylene naphthalate substrates, ultraflexible nonfullerene solar cells with the PEI-Zn interlayer display a power conversion efficiency of 12.3% on PEDOT:PSS electrodes and 15.0% on AgNWs electrodes. Furthermore, the ultraflexible cells show nearly unchanged power conversion efficiency during 100 continuous compression-flat deformation cycles with a compression ratio of 45%. At the end, the ultraflexible cell is demonstrated to be attached onto the finger joint and displays reversible current output during the finger bending-spreading.
Molecular impact of launch related dynamic vibrations and static hypergravity in planarians
Authors: de Sousa Nídia , Caporicci Marcello , Vandersteen Jeroen , Rojo-Laguna Jose Ignacio , Saló Emili , Adell Teresa , Auletta Gennaro , van Loon Jack J.W.A.
Published: September 2020

Although many examples of simulated and real microgravity demonstrating their profound effect on biological systems are described in literature, few reports deal with hypergravity and vibration effects, the levels of which are severely increased during the launch preceding the desired microgravity period. Here, we used planarians, flatworms that can regenerate any body part in a few days. Planarians are an ideal model to study the impact of launch-related hypergravity and vibration during a regenerative process in a “whole animal” context. Therefore, planarians were subjected to 8.5 minutes of 4 g hypergravity (i.e. a human-rated launch level) in the Large Diameter Centrifuge (LDC) and/or to vibrations (20–2000 Hz, 11.3 Grms) simulating the conditions of a standard rocket launch. The transcriptional levels of genes (erg-1, runt-1, fos, jnk, and yki) related with the early stress response were quantified through qPCR. The results show that early response genes are severely deregulated after static and dynamic loads but more so after a combined exposure of dynamic (vibration) and static (hypergravity) loads, more closely simulating real launch exposure profiles. Importantly, at least four days after the exposure, the transcriptional levels of those genes are still deregulated. Our results highlight the deep impact that short exposures to hypergravity and vibration have in organisms, and thus the implications that space flight launch could have. These phenomena should be taken into account when planning for well-controlled microgravity studies.
Curved digital X-ray detectors
Authors: van Breemen Albert J.J.M. , Simon Matthias , Tousignant Olivier , Shanmugam Santhosh , van der Steen Jan-Laurens , Akkerman Hylke B. , Kronemeijer Auke , Ruetten Walter , Raaijmakers Rob , Alving Lex , Jacobs Jan , Malinowski Pawel E. , De Roose Florian , Gelinck Gerwin H.
Published: September 2020

A curved image sensor on plastic foil has been developed for cone beam computed tomography (CBCT) X-ray imaging. The image sensor of about 6 × 8 cm2 size has been built on a thin polyimide foil with an indium gallium zinc oxide (IGZO) backplane and an organic photodetectors (OPD) frontplane. A flexible cesium iodide (CsI) scintillator has been attached to the optical sensor with 480 × 640 pixels of 126 µm size. Dark current density of the OPD was low with less than 10−7 mA/cm2 at −2 V, while an external quantum efficiency (EQE) of about 50% was reached in the visible wavelength range matched to the scintillator output. The image quality of the digital X-ray detector allowed for 3D reconstruction images of a bone phantom on a rotating stage with a lab setup. The curved detector with 32 cm curvature radius opens up the path for very compact CBCT gantries with largely reduced footprint.
Mining genetic and transcriptomic data using machine learning approaches in Parkinson’s disease
Authors: Su Chang , Tong Jie , Wang Fei
Published: September 2020

High-throughput techniques have generated abundant genetic and transcriptomic data of Parkinson’s disease (PD) patients but data analysis approaches such as traditional statistical methods have not provided much in the way of insightful integrated analysis or interpretation of the data. As an advanced computational approach, machine learning, which enables people to identify complex patterns and insight from data, has consequently been harnessed to analyze and interpret large, highly complex genetic and transcriptomic data toward a better understanding of PD. In particular, machine learning models have been developed to integrate patient genotype data alone or combined with demographic, clinical, neuroimaging, and other information, for PD outcome study. They have also been used to identify biomarkers of PD based on transcriptomic data, e.g., gene expression profiles from microarrays. This study overviews the relevant literature on using machine learning models for genetic and transcriptomic data analysis in PD, points out remaining challenges, and suggests future directions accordingly. Undoubtedly, the use of machine learning is amplifying PD genetic and transcriptomic achievements for accelerating the study of PD. Existing studies have demonstrated the great potential of machine learning in discovering hidden patterns within genetic or transcriptomic information and thus revealing clues underpinning pathology and pathogenesis. Moving forward, by addressing the remaining challenges, machine learning may advance our ability to precisely diagnose, prognose, and treat PD.
Comparing health status between patients with COPD in primary, secondary and tertiary care
Authors: de Klein Mieke M. , Peters Jeannette B. , van ’t Hul Alex J. , Akkermans Reinier P. , in ’t Veen Johannes C. , Vercoulen Jan H. , Bischoff Erik W. , Schermer Tjard R.
Published: September 2020

In this study, we compare health status between COPD patients treated in three different care levels in the Netherlands and assess determinants that influence their health status. We applied the Nijmegen Clinical Screening Instrument to measure eight health status subdomains in primary (n = 289), secondary (n = 184) and tertiary care (n = 433) COPD patient cohorts. Proportions of patients with severe problems in ≥3 subdomains are 47% in primary, 71% in secondary and 94% in tertiary care. Corrected for patient characteristics, differences between the care levels are statistically significant for nearly all health status subdomains. The pooled cohort data show female sex, age, FEV1 % predicted and BMI to be determinants of one or more subdomains. We conclude that the proportion of COPD patients with severe health status problems is substantial, not just in tertiary care but also in primary and secondary care. Use of detailed health status information may support patient-tailored COPD care.
Experimental demonstration of measurement-device-independent measure of quantum steering
Authors: Zhao Yuan-Yuan , Ku Huan-Yu , Chen Shin-Liang , Chen Hong-Bin , Nori Franco , Xiang Guo-Yong , Li Chuan-Feng , Guo Guang-Can , Chen Yueh-Nan
Published: September 2020

Within the framework of quantum refereed steering games, quantum steerability can be certified without any assumption on the underlying state nor the measurements involved. Such a scheme is termed the measurement-device-independent (MDI) scenario. Here, we introduce a measure of steerability in an MDI scenario, i.e., the result merely depends on the observed statistics and the quantum inputs. We prove that such a measure satisfies the convex steering monotone. Moreover, it is robust against not only measurement biases but also losses. We also experimentally estimate the amount of the measure with an entangled photon source. As two by-products, our experimental results provide lower bounds on an entanglement measure of the underlying state and an incompatible measure of the involved measurement. Our research paves a way for exploring one-side device-independent quantum information processing within an MDI framework.
Signature of gate-controlled magnetism and localization effects at Bi2Se3/EuS interface
Authors: Mathimalar Subramanian , Sasmal Satyaki , Bhardwaj Archit , Abhaya Sekar , Pothala Rajasekhar , Chaudhary Saurabh , Satpati Biswarup , Raman Karthik V.
Published: September 2020

Proximity of a topological insulator (TI) surface with a magnetic insulator (MI) can open an exchange gap at the Dirac point leading to exploration of surface quantum anomalous Hall effect. An important requirement to observe the above effect is to prevent the topological breakdown of the surface states (SSs) due to various interface coupling effects and to tune the Fermi level at the interface near the Dirac point. In this work, we demonstrate the growth of high-quality c-axis oriented strain-free layered films of TI, Bi2Se3, on amorphous SiO2 substrate in proximity to an MI, europium sulfide (EuS), that show stronger weak anti-localization response from the surface than previous studies with epitaxially interfaced heterostructures. Importantly, we find gate and magnetic field cooling modulated localization effects in the SSs, attributed to the position of interface Fermi level within the band gap that is also corroborated from our positron annihilation spectroscopy measurements. Furthermore, our experiments provide a direct evidence of gate-controlled enhanced interface magnetism in EuS arising from the carrier mediated Ruderman–Kittel–Kasuya–Yosida interactions across the Bi2Se3/EuS interface. These findings demonstrate the existence of complex interfacial phenomena affecting the localization response of the SSs that might be important in proximity engineering of the TI surface to observe surface quantum Hall effects.
Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against Burkholderia mallei
Authors: Tapia Daniel , Sanchez-Villamil Javier I. , Torres Alfredo G.
Published: September 2020

Burkholderia mallei (Bm) is a facultative intracellular pathogen and the etiological agent of glanders, a highly infectious zoonotic disease occurring in equines and humans. The intrinsic resistance to antibiotics, lack of specific therapy, high mortality, and history as a biothreat agent, prompt the need of a safe and effective vaccine. However, the limited knowledge of protective Bm-specific antigens has hampered the development of a vaccine. Further, the use of antigen-delivery systems that enhance antigen immunogenicity and elicit robust antigen-specific immune responses has been limited and could improve vaccines against Bm. Nanovaccines, in particular gold nanoparticles (AuNPs), have been investigated as a strategy to broaden the repertoire of vaccine-mediated immunity and as a tool to produce multivalent vaccines. To synthesize a nano-glycoconjugate vaccine, six predicted highly immunogenic antigens identified by a genome-wide bio- and immuno-informatic analysis were purified and coupled to AuNPs along with lipopolysaccharide (LPS) from B. thailandensis. Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.
High-density EEG of auditory steady-state responses during stimulation of basal forebrain parvalbumin neurons
Authors: Hwang Eunjin , Han Hio-Been , Kim Jung Young , Choi Jee Hyun
Published: September 2020

We present high-density EEG datasets of auditory steady-state responses (ASSRs) recorded from the cortex of freely moving mice with or without optogenetic stimulation of basal forebrain parvalbumin (BF-PV) neurons, known as a subcortical hub circuit for the global workspace. The dataset of ASSRs without BF-PV stimulation (dataset 1) contains raw 36-channel EEG epochs of ASSRs elicited by 10, 20, 30, 40, and 50 Hz click trains and time stamps of stimulations. The dataset of ASSRs with BF-PV stimulation (dataset 2) contains raw 36-channel EEG epochs of 40-Hz ASSRs during BF-PV stimulation with latencies of 0, 6.25, 12.5, and 18.75 ms and time stamps of stimulations. We provide the datasets and step-by-step tutorial analysis scripts written in Python, allowing for descriptions of the event-related potentials, spectrograms, and the topography of power. We complement this experimental dataset with simulation results using a time-dependent perturbation on coupled oscillators. This publicly available dataset will be beneficial to the experimental and computational neuroscientists.
C. elegans episodic swimming is driven by multifractal kinetics
Authors: Ikeda Yusaku , Jurica Peter , Kimura Hiroshi , Takagi Hiroaki , Struzik Zbigniew R. , Kiyono Ken , Arata Yukinobu , Sako Yasushi
Published: September 2020

Fractal scaling is a common property of temporal change in various modes of animal behavior. The molecular mechanisms of fractal scaling in animal behaviors remain largely unexplored. The nematode C. elegans alternates between swimming and resting states in a liquid solution. Here, we report that C. elegans episodic swimming is characterized by scale-free kinetics with long-range temporal correlation and local temporal clusterization, namely consistent with multifractal kinetics. Residence times in actively-moving and inactive states were distributed in a power law-based scale-free manner. Multifractal analysis showed that temporal correlation and temporal clusterization were distinct between the actively-moving state and the inactive state. These results indicate that C. elegans episodic swimming is driven by transition between two behavioral states, in which each of two transition kinetics follows distinct multifractal kinetics. We found that a conserved behavioral modulator, cyclic GMP dependent kinase (PKG) may regulate the multifractal kinetics underlying an animal behavior. Our combinatorial analysis approach involving molecular genetics and kinetics provides a platform for the molecular dissection of the fractal nature of physiological and behavioral phenomena.
Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study
Authors: Groot Hilde E. , van de Vegte Yordi J. , Verweij Niek , Lipsic Erik , Karper Jacco C. , van der Harst Pim
Published: September 2020

Small-scale studies have suggested a link between the human gut microbiome and highly prevalent diseases. However, the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown. We aimed to determine the spectrum of diseases that are linked to the human gut microbiome through the utilization of its genetic determinants as a proxy for its composition. 180 single nucleotide polymorphisms (SNPs) known to influence the human gut microbiome were used to assess the association with health and disease outcomes in 422,417 UK Biobank participants. Potential causal estimates were obtained using a Mendelian randomization (MR) approach. From the total sample analysed (mean age was 57 ± 8 years), 194,567 (46%) subjects were male. Median exposure was 66-person years (interquartile range 59–72). Eleven SNPs were significantly associated with 28 outcomes (Bonferroni corrected P value < 4.63·10−6) including food intake, hypertension, atopy, COPD, BMI, and lipids. Multiple SNP MR pointed to a possible causal link between Ruminococcus flavefaciens and hypertension, and Clostridium and platelet count. Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, although challenges remain in establishing causal relationships.
Standardized massage interventions as protocols for the induction of psychophysiological relaxation in the laboratory: a block randomized, controlled trial
Authors: Meier Maria , Unternaehrer Eva , Dimitroff Stephanie J. , Benz Annika B. E. , Bentele Ulrike U. , Schorpp Sabine M. , Wenzel Maya , Pruessner Jens C.
Published: September 2020

Health and disease are strongly linked to psychophysiological states. While stress research strongly benefits from standardized stressors, no established protocol focuses on the induction of psychophysiological relaxation. To maintain health, functioning regenerative systems are however likely as important as functioning stress systems. Thus, the identification of validated relaxation paradigms is needed. Here, we investigated whether standardized massages are capable of reliably inducing physiological and psychological states of relaxation. Relaxation was indicated by changes in high frequency heart rate variability (HF-HRV), a vagally-mediated heart rate variability component, and repeated ratings of subjective relaxation, and stress levels. Sixty healthy women were randomly assigned to a vagus nerve massage (n = 19), a soft shoulder massage (n = 22), or a resting control group (n = 19). During the intervention, HF-HRV and subjective relaxation increased, while subjective stress decreased significantly in all groups. Both massage interventions elicited significantly higher HF-HRV compared to the control group. Accordingly, both massage protocols increased psychophysiological relaxation, and may serve as useful tools in future research. However, future work will have to determine which of several protocols might be used as a gold standard to induce a psychophysiological state of relaxation in the laboratory.
IL-36 receptor antagonist deficiency resulted in delayed wound healing due to excessive recruitment of immune cells
Authors: Saito Kenta , Iwata Yohei , Fukushima Hidehiko , Watanabe Soichiro , Tanaka Yoshihito , Hasegawa Yurie , Akiyama Masashi , Sugiura Kazumitsu
Published: September 2020

Loss-of-function homozygous or compound heterozygous mutations in IL36RN, which encodes interleukin-36 receptor antagonist (IL-36Ra), have been implicated in the pathogenesis of various skin disorders. Previous findings showed that IL-36γ promoted wound healing in mice; however, the pathogenic role of IL-36Ra in wound healing remains unclear. We elucidated the role of IL-36Ra, a regulator of IL-36 in tissue repair by investigating the recruitment of inflammatory cells and cytokine production in the absence of IL-36Ra. Full-thickness excisional wounds were made on the back of Il36rn−/− mice and healing was assessed by monitoring macroscopic wound sizes, numbers of infiltrated cells, and gene expression of inflammatory cytokines. Macroscopic wound healing, re-epithelialization, and granulation tissue formation were delayed by 3 days post-injury in Il36rn−/− mice. This delay was associated with increased infiltrations of neutrophils and macrophages, and increased expression of cytokines, such as IL-36γ, C-X-C motif chemokine ligand 1 (CXCL1), and transforming growth factor (TGF)-β. Importantly, administration of TAK-242, a toll-like receptor 4 (TLR4) inhibitor, caused normalization of wound healing in Il36rn−/− mice, abrogating the initial delay in tissue repair. These results showed that targeting TLR4- mediated infiltrations of immune cells and cytokine production could be beneficial in regulating wound healing in IL-36Ra-deficient skin disorders.
Synthesis of hybrid amorphous/crystalline SnO2 1D nanostructures: investigation of morphology, structure and optical properties
Authors: Matysiak Wiktor , Tański Tomasz , Smok Weronika , Polishchuk Oleg
Published: September 2020

The aim of the study was to prepare SnO2 nanowires via a combination of electrospinning and the sol–gel method from a polyvinylpyrrolidone (PVP)/dimetylformamide (DMF)/ethanol(EtOH)/tin(IV) chloride pentahydrate (SnCl4·5H2O) solution. The morphology, structure and chemical composition of the obtained PVP/SnO2 nanofibers and SnO2 nanowires were examined using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) as well as a scanning electron microscope (SEM) with an energy dispersive spectrometer (EDX). The optical property analysis was performed on the basis of UV–Vis spectra of absorbance as a function of the wavelength, based on which the rated values of band gaps of the fabricated 1D nanostructures were determined. The morphology analysis showed that the obtained amorphous SnO2 nanowires with crystalline protuberances were characterized by a diameter of 50 to 120 nm. Results demonstrated that nanowires with a ratio of 1:1 precursor to polymer in the spinning solution were characterized by the smallest diameter after calcination and the smallest energy gap of 3.3 eV among all investigated samples. The rest of the studied materials were characterized by a larger energy gap (3.8 and 3.9 eV).
Associations between cardiac function and retinal microvascular geometry among Chinese adults
Authors: Huang Lihua , Chen Wei-Qing , Aris Izzuddin M. , Teo Louis L. Y. , Wong Tien Yin , Koh Angela S. , Li Ling-Jun
Published: September 2020

Abnormal retinal microvascular geometry has been associated with cardiac remodeling and heart failure. However, its relation to cardiac function, prior to clinical disease has not been explored. In this cross-sectional study, 50 participants (mean age 62.5 ± 11.7 years) without cardiovascular disease (CVD) were recruited from the Cardiac Ageing Study. Transthoracic echocardiography imaging was performed to measure cardiac function indices, and retinal imaging was used to measure retinal vascular caliber and retinal vascular geometric indices. Multiple linear regressions were applied to examine associations between indices of cardiac function and retinal microvasculature, adjusting for age, sex, body mass index, mean blood pressure and comorbidity (i.e. hypertension, diabetes and dyslipidemia). After adjusting for confounders, each unit decrease in peak systolic septal mitral annular velocity (Septal S′) indicating poorer left function was associated with smaller retinal venular branching angle (β: − 2.69°; 95% CI − 4.92, − 0.46). Furthermore, each unit increase in peak velocity flow in late diastole by atrial contraction (MV A Peak) indicating poorer left atrial function was associated with lower retinal venular fractal dimension (− 0.13Df; − 0.25, − 0.004). Our findings suggested a relationship between poorer cardiac function and suboptimal retinal microvascular geometry, among Chinese without CVD.
Characteristics of hydrate-bound gas retrieved at the Kedr mud volcano (southern Lake Baikal)
Authors: Hachikubo Akihiro , Minami Hirotsugu , Yamashita Satoshi , Khabuev Andrey , Krylov Alexey , Kalmychkov Gennadiy , Poort Jeffrey , De Batist Marc , Chenskiy Alexandr , Manakov Andrey , Khlystov Oleg
Published: September 2020

We reported the characteristics of hydrate-bound hydrocarbons in lake-bottom sediments at the Kedr mud volcano in Lake Baikal. Twenty hydrate-bearing sediment cores were retrieved, and methane-stable isotopes of hydrate-bound gases (δ13C and δ2H of − 47.8‰ to − 44.0‰ V-PDB and − 280.5‰ to − 272.8‰ V-SMOW, respectively) indicated their thermogenic origin accompanied with secondary microbial methane. Powder X-ray diffraction patterns of the crystals and molecular composition of the hydrate-bound gases suggested that structure II crystals showed a high concentration of ethane (around 14% of hydrate-bound hydrocarbons), whereas structure I crystals showed a relatively low concentration of ethane (2–5% of hydrate-bound hydrocarbons). These different crystallographic structures comprised complicated layers in the sub-lacustrine sediment, suggesting that the gas hydrates partly dissociate, concentrate ethane and form structure II crystals. We concluded that a high concentration of thermogenic ethane primarily controls the crystallographic structure of gas hydrates and that propane, iso-butane (2-methylpropane) and neopentane (2,2-dimethylpropane) are encaged into crystals in the re-crystallisation process.
The costs of removing the unsanctioned import of marine plastic litter to small island states
Authors: Burt April J. , Raguain Jeremy , Sanchez Cheryl , Brice Jude , Fleischer-Dogley Frauke , Goldberg Rebecca , Talma Sheena , Syposz Martyna , Mahony Josephine , Letori Jake , Quanz Christina , Ramkalawan Sam , Francourt Craig , Capricieuse Ivan , Antao Ash , Belle Kalsey , Zillhardt Thomas , Moumou Jessica , Roseline Marvin , Bonne Joel , Marie Ronny , Constance Edward , Suleman Jilani , Turnbull Lindsay A.
Published: September 2020

Small island states receive unprecedented amounts of the world’s plastic waste. In March 2019, we removed as much plastic litter as possible from Aldabra Atoll, a remote UNESCO World Heritage Site, and estimated the money and effort required to remove the remaining debris. We removed 25 tonnes at a cost of $224,537, which equates to around $10,000 per day of clean-up operations or $8,900 per tonne of litter. We estimate that 513 tonnes (95% CI 212–814) remains on Aldabra, the largest accumulation reported for any single island. We calculate that removing it will cost approximately $4.68 million and require 18,000 person-hours of labour. By weight, the composition is dominated by litter from the regional fishing industry (83%) and flip-flops from further afield (7%). Given the serious detrimental effects of plastic litter on marine ecosystems, we conclude that clean-up efforts are a vital management action for islands like Aldabra, despite the high financial cost and should be integrated alongside policies directed at ‘turning off the tap’. We recommend that international funding be made available for such efforts, especially considering the transboundary nature of both the marine plastic litter problem and the ecosystem services provided by biodiversity-rich islands.
Single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging for radiotherapy planning in patients with lung cancer: a meta-analysis
Authors: Lee Soo Jin , Park Hae Jin
Published: September 2020

Functional imaging modalities enable practitioners to identify functional lung regions. This analysis evaluated the feasibility of nuclear medicine imaging to avoid doses to the functional lung in radiotherapy (RT) planning for patients with lung cancer. This systematic review and meta-analysis was carried out according to PRISMA-P guidelines. A search of EMBASE and PubMed for studies published throughout the last 20 years was performed using the following search criteria: (a) ‘lung cancer’ or ‘lung malignancy’ and (b) ‘radiotherapy’ or ‘radiation therapy’ or ‘RT planning’ and (c) ‘SPECT’ or ‘single positron emission computed tomography’ or ‘functional image.’ The analyzed planning parameters were the volumes of the normal lung that have received ≥ 10 Gy and ≥ 20 Gy of radiation (V10 and V20, respectively) and the mean lung dose (MLD). We compared the planning parameters obtained from anatomical RT planning and functional RT planning using perfusion or ventilation imaging (‘V10, V20 or MLD’ in anatomical plan vs. ‘fV10, fV20 or fMLD’ in functional plan). A total of 309 patients with 344 RT plan sets from 15 publications (11 perfusion SPECT, 2 ventilation SPECT, and 1 SPECT and 1 PET with both perfusion and ventilation) were included in the meta-analysis. The standard mean differences in planning parameters in functional plans using nuclear imaging were significantly reduced compared to those of anatomical plans (P < 0.01 for all): − 0.42 (95% confidence interval (CI) − 0.78 to − 0.07) for ‘V10 vs. fV10′, − 0.41 (95% CI − 0.64 to − 0.17) for ‘V20 vs. fV20′, and − 0.24 (95% CI − 0.45 to − 0.03) for ‘MLD vs. fMLD’. In subgroup analysis, the functional plan using perfusion was significantly lower than the anatomical plan in all planning parameters, but there was no significant difference for ventilation. RT planning with nuclear functional lung imaging has potential to reduce radiation-induced lung injury. Perfusion imaging seems to be more promising than ventilation imaging for all planning parameters. There were not enough studies using ventilation imaging to determine what the effect is on the lung plan parameters.
Monte-Carlo simulations of external dose contributions from the surrounding ground areas of residential homes in a typical Northern European suburban area after a radioactive fallout scenario
Authors: Hinrichsen Yvonne , Finck Robert , Martinsson Johan , Rääf Christopher
Published: September 2020

The emissions of $$^{137}\hbox {Cs}$$

137

Cs

into the environment from the nuclear accidents in Chernobyl in 1986 and Fukushima in 2011 led to the need to decontaminate large areas to avert radiation doses to the population in the affected areas. To be able to perform cost-effective and sustainable remediation, knowledge is needed about how radiation doses can be minimized through optimized interventions such that the greatest possible reduction in radiation dose is obtained with the smallest possible negative impact on the area. Theoretical calculations have been performed to determine how radiation doses in single family houses in a typical Swedish residential suburb arise from a hypothetical $$^{137}\hbox {Cs}$$

137

Cs

deposition on the ground. The intention was to highlight how remediation of different parts of the surroundings affects the radiation dose to the residents in a particular property. A Monte Carlo model of the houses and the environment in a suburban area was set up to allow calculations of the dose contributions from different contaminated ground areas such as their own property, neighbouring properties, streets and surrounding recreational areas. Calculations were performed for eleven observation points inside different rooms of the house and one observation point in the garden outside the house, for four houses in the neighbourhood, and for two types of building construction material. The influence of the time spent in different rooms of the house and the contamination of areas surrounding the house was studied. The results show that in general the main dose contribution originates from their own property, but that a significant part (30–80%, depending on the observation point) can come from other areas, showing the importance of considering the surroundings in remediation actions. More detailed analysis of the results showed that the dose contribution from a source region is in general highly dependent on the position of windows in a brick house, whereas for a wooden house the distance to the source region is also of relevance.
New perspectives on Neanderthal dispersal and turnover from Stajnia Cave (Poland)
Authors: Picin Andrea , Hajdinjak Mateja , Nowaczewska Wioletta , Benazzi Stefano , Urbanowski Mikołaj , Marciszak Adrian , Fewlass Helen , Bosch Marjolein D. , Socha Paweł , Stefaniak Krzysztof , Żarski Marcin , Wiśniewski Andrzej , Hublin Jean-Jacques , Nadachowski Adam , Talamo Sahra
Published: September 2020

The Micoquian is the broadest and longest enduring cultural facies of the Late Middle Palaeolithic that spread across the periglacial and boreal environments of Europe between Eastern France, Poland, and Northern Caucasus. Here, we present new data from the archaeological record of Stajnia Cave (Poland) and the paleogenetic analysis of a Neanderthal molar S5000, found in a Micoquian context. Our results demonstrate that the mtDNA genome of Stajnia S5000 dates to MIS 5a making the tooth the oldest Neanderthal specimen from Central-Eastern Europe. Furthermore, S5000 mtDNA has the fewest number of differences to mtDNA of Mezmaiskaya 1 Neanderthal from Northern Caucasus, and is more distant from almost contemporaneous Neanderthals of Scladina and Hohlenstein-Stadel. This observation and the technological affinity between Poland and the Northern Caucasus could be the result of increased mobility of Neanderthals that changed their subsistence strategy for coping with the new low biomass environments and the increased foraging radius of gregarious animals. The Prut and Dniester rivers were probably used as the main corridors of dispersal. The persistence of the Micoquian techno-complex in South-Eastern Europe infers that this axis of mobility was also used at the beginning of MIS 3 when a Neanderthal population turnover occurred in the Northern Caucasus.
Chemical pollution imposes limitations to the ecological status of European surface waters
Authors: Posthuma Leo , Zijp Michiel C. , De Zwart Dick , Van de Meent Dik , Globevnik Lidija , Koprivsek Maja , Focks Andreas , Van Gils Jos , Birk Sebastian
Published: September 2020

Aquatic ecosystems are affected by man-made pressures, often causing combined impacts. The analysis of the impacts of chemical pollution is however commonly separate from that of other pressures and their impacts. This evolved from differences in the data available for applied ecology vis-à-vis applied ecotoxicology, which are field gradients and laboratory toxicity tests, respectively. With this study, we demonstrate that the current approach of chemical impact assessment, consisting of comparing measured concentrations to protective environmental quality standards for individual chemicals, is not optimal. In reply, and preparing for a method that would enable the comprehensive assessment and management of water quality pressures, we evaluate various quantitative chemical pollution pressure metrics for mixtures of chemicals in a case study with 24 priority substances of Europe-wide concern. We demonstrate why current methods are sub-optimal for water quality management prioritization and that chemical pollution currently imposes limitations to the ecological status of European surface waters. We discuss why management efforts may currently fail to restore a good ecological status, given that to date only 0.2% of the compounds in trade are considered in European water quality assessment and management.
Pressure effect on the order–disorder transformation in L10 FeNi
Authors: Tian Li-Yun , Eriksson Olle , Vitos Levente
Published: September 2020

The ordered phase of the FeNi system is known for its promising magnetic properties that make it a first-class rare-earth free permanent magnet. Mapping out the parameter space controlling the order–disorder transformation is an important step towards finding growth conditions that stabilize the $$L1_0$$

L

1
0

phase of FeNi. In this work, we study the magnetic properties and chemical order-disorder transformation in FeNi as a function of lattice expansion by utilizing ab initio alloy theory. The largest volume expansion considered here is 29% which corresponds to a pressure of $${-25}$$

-
25

GPa. The thermodynamic and magnetic calculations are formulated in terms of a long-range order parameter, which is subsequently used to find the ordering temperature as a function of pressure. We show that negative pressure promotes ordering, meaning that synthetic routes involving an increase of the volume of FeNi are expected to expand the stability field of the $$L1_0$$

L

1
0

phase.
Immune suppressed tumor microenvironment by exosomes derived from gastric cancer cells via modulating immune functions
Authors: Liu Juan , Wu Shaoxian , Zheng Xiao , Zheng Panpan , Fu Yuanyuan , Wu Changping , Lu Binfeng , Ju Jingfang , Jiang Jingting
Published: September 2020

Gastric cancer is one of the leading causes of cancer-related death due to late diagnosis with high metastatic frequency. In this study, the impact of tumor secreted exosomes on immune function in the tumor environment was investigated using exosomes isolated from gastric cancer cell lines MKN-28, MKN-45, and SGC-7901. Results show that exosomes derived from all of these cell lines changed the gene expression and cytokine secretion levels of CD8+ T cells. They also block cell cycle progression, induced apoptosis in CD8+ T cells. Image analysis of fluorescent labeled exosomes derived from three cell lines injected systemically into C57BL/6 mice revealed these exosomes primarily localize to the lungs. We further showed exosomes were mainly taken up by natural killer cells and macrophages in the lung. After long-term exposure to inject exosomes from MKN-45 cells, mice developed an immunosuppressive tumor microenvironment in the lung with increased frequency of effector memory CD4+ T and MDSC, decreased CD8+ T cell and NK frequency. This immune suppressive environment promotes gastric cancer lung metastasis. Lung metastasis sites developed after mice were exposed to exosomes isolated from all three gastric cancer cell lines when the mice were injected with MFC cells. Results suggest that exosomes derived from gastric cancer cells (especially MKN-45 and MKN-28) changed CD8+ T cell gene expression and cytokine secretion patterns to create an immunosuppressive condition for metastatic niche formation in the lung. Overall, this study provides new insights into how gastric cancer derived exosomes modulate the immune response to promote lung tumor metastasis.
A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction
Authors: Batool Fareeha , Stutz Céline , Petit Catherine , Benkirane-Jessel Nadia , Delpy Eric , Zal Franck , Leize-Zal Elisabeth , Huck Olivier
Published: September 2020

The control of inflammation and infection is crucial for periodontal wound healing and regeneration. M101, an oxygen carrier derived from Arenicola marina, was tested for its anti-inflammatory and anti-infectious potential based on its anti-oxidative and tissue oxygenation properties. In vitro, no cytotoxicity was observed in oral epithelial cells (EC) treated with M101. M101 (1 g/L) reduced significantly the gene expression of pro-inflammatory markers such as TNF-α, NF-κΒ and RANKL in P. gingivalis-LPS stimulated and P. gingivalis-infected EC. The proteome array revealed significant down-regulation of pro-inflammatory cytokines (IL-1β and IL-8) and chemokine ligands (RANTES and IP-10), and upregulation of pro-healing mediators (PDGF-BB, TGF-β1, IL-10, IL-2, IL-4, IL-11 and IL-15) and, extracellular and immune modulators (TIMP-2, M-CSF and ICAM-1). M101 significantly increased the gene expression of Resolvin-E1 receptor. Furthermore, M101 treatment reduced P. gingivalis biofilm growth over glass surface, observed with live/dead analysis and by decreased P. gingivalis 16 s rRNA expression (51.7%) (p < 0.05). In mice, M101 reduced the clinical abscess size (50.2%) in P. gingivalis-induced calvarial lesion concomitant with a decreased inflammatory score evaluated through histomorphometric analysis, thus, improving soft tissue and bone healing response. Therefore, M101 may be a novel therapeutic agent that could be beneficial in the management of P. gingivalis associated diseases.
The evolution of pueriparity maintains multiple paternity in a polymorphic viviparous salamander
Authors: Alarcón-Ríos Lucía , Nicieza Alfredo G. , Lourenço André , Velo-Antón Guillermo
Published: September 2020

The reduction in fecundity associated with the evolution of viviparity may have far-reaching implications for the ecology, demography, and evolution of populations. The evolution of a polygamous behaviour (e.g. polyandry) may counteract some of the effects underlying a lower fecundity, such as the reduction in genetic diversity. Comparing patterns of multiple paternity between reproductive modes allows us to understand how viviparity accounts for the trade-off between offspring quality and quantity. We analysed genetic patterns of paternity and offspring genetic diversity across 42 families from two modes of viviparity in a reproductive polymorphic species, Salamandra salamandra. This species shows an ancestral (larviparity: large clutches of free aquatic larvae), and a derived reproductive mode (pueriparity: smaller clutches of larger terrestrial juveniles). Our results confirm the existence of multiple paternity in pueriparous salamanders. Furthermore, we show the evolution of pueriparity maintains, and even increases, the occurrence of multiple paternity and the number of sires compared to larviparity, though we did not find a clear effect on genetic diversity. High incidence of multiple paternity in pueriparous populations might arise as a mechanism to avoid fertilization failures and to ensure reproductive success, and thus has important implications in highly isolated populations with small broods.
Brazilian Maternal and Child Nutrition Consortium: establishment, data harmonization and basic characteristics
Authors: Carrilho Thaís Rangel Bousquet , Farias Dayana Rodrigues , Batalha Mônica Araújo , Costa Nathalia Cristina Freitas , Rasmussen Kathleen M. , Reichenheim Michael E. , Ohuma Eric O. , Hutcheon Jennifer A. , Kac Gilberto ,   Brazilian Maternal and Child Nutrition Consortium, Oliveira Adauto Emmerich , Esteves-Pereira Ana Paula , Sato Ana Paula Sayuri , da Silva Antônio Augusto Moura , Costa Bárbara Miranda Ferreira , de Moraes Claudia Leite , Saunders Claudia , Parada Cristina Maria Garcia de Lima , Rocha Daniela da Silva , Gigante Denise Petrucci , dos Santos-Neto Edson Theodoro , Lacerda Elisa Maria de Aquino , Fujimori Elizabeth , Surita Fernanda Garanhani , Gomes-Filho Isaac Suzart , Bierhals Isabel Oliveira , Capelli Jane de Carlos Santana , Cecatti José Guilherme , Vaz Juliana dos Santos , Cesar Juraci Almeida , Mastroeni Marco Fábio , Carvalhaes Maria Antonieta de Barros Leite , da Silveira Mariângela Freitas , Domingues Marlos Rodrigues , Fernandes Mayra Pacheco , Drehmer Michele , Gonzalez Mylena Maciel , Padilha Patrícia de Carvalho , Junior Renato Passini , Souza Renato Teixeira , Alves Ronaldo Fernandes Santos , Batista Rosângela Fernandes Lucena , Mastroeni Silmara Salete de Barros Silva , Saldiva Silvia Regina Dias Medici , da Cruz Simone Seixas , Morais Sirlei Siani , Mengue Sotero Serrate
Published: September 2020

Pooled data analysis in the field of maternal and child nutrition rarely incorporates data from low- and middle-income countries and existing studies lack a description of the methods used to harmonize the data and to assess heterogeneity. We describe the creation of the Brazilian Maternal and Child Nutrition Consortium dataset, from multiple pooled longitudinal studies, having gestational weight gain (GWG) as an example. Investigators of the eligible studies published from 1990 to 2018 were invited to participate. We conducted consistency analysis, identified outliers, and assessed heterogeneity for GWG. Outliers identification considered the longitudinal nature of the data. Heterogeneity was performed adjusting multilevel models. We identified 68 studies and invited 59 for this initiative. Data from 29 studies were received, 21 were retained for analysis, resulting in a final sample of 17,344 women with 72,616 weight measurements. Fewer than 1% of all weight measurements were flagged as outliers. Women with pre-pregnancy obesity had lower values for GWG throughout pregnancy. GWG, birth length and weight were similar across the studies and remarkably similar to a Brazilian nationwide study. Pooled data analyses can increase the potential of addressing important questions regarding maternal and child health, especially in countries where research investment is limited.
Validation of a novel functional test for assessing metamorphopsia using epiretinal membranes as a model
Authors: Wang Henrietta , Khuu Sieu K. , Lam Sheila , Lin Clarissa , Kalloniatis Michael , Phu Jack
Published: September 2020

Current tests for assessing metamorphopsia do not account for confounders such as perceptual filling-in and spatial redundancy, which affect its sensitivity and repeatability. This proof-of-concept study aimed to assess the performance of a novel laboratory-based psychophysical test (Line Sag Test, LST) which addresses these issues for quantification of metamorphopsia in idiopathic epiretinal membranes. The LST quantifies perpendicular metamorphopsia at three eccentricities (3°, 6°, and 9°) along eight meridians (45° steps). Metamorphopsia was assessed using the LST and Amsler grid and the hit rates of both tests for detecting metamorphopsia were compared. Normal metamorphopsia scores using the LST did not differ significantly from 0 and fell within one step-size (p = 0.500). The LST detected significantly more cases of metamorphopsia than the Amsler grid (14/21 versus 3/21) (p = 0.003). Similarly, significantly more cases of visual distortions in asymptomatic iERMs were detected using the LST than the Amsler grid (11/18 versus 0/18) (p = 0.008). The LST has a higher hit rate compared to the Amsler grid (67% versus 14%). This work demonstrates a psychophysically-robust functional test addressing perceptual confounders is more sensitive for quantifying and localising metamorphopsia in macular disease, particularly in asymptomatic disease.