bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic geneNR4A1as a potential therapeutic target for non‐smoking female non‐small cell lung cancer patients
Authors: Sun Rong , Bao Min‐Yue , Long Xin , Yuan Yuan , Wu Miao‐Miao , Li Xin , Bao Jin‐Ku 
Published: February 2019

BackgroundAlthough cigarette smoking is considered one of the key risk factors for lung cancer, 15% of male patients and 53% of female patients with lung cancer are non‐smokers. Metabolic changes are critical features of cancer. Therapeutic target identification from a metabolic perspective in non‐small cell lung cancer (NSCLC) tissue of female non‐smokers has long been ignored.ResultsBased on microarray data retrieved from Affymetrix expression arrays E‐GEOD‐19804, we found that the downregulated genes in non‐smoking female NSCLC patients tended to participate in protein/amino acid and lipid metabolism, while upregulated genes were more involved in protein/amino acid and carbohydrate metabolism. Combining nutrient metabolic co‐expression, protein–protein interaction network construction and overall survival assessment, we identifiedNR4A1andTIE1as potential therapeutic targets for NSCLC in female non‐smokers. To accelerate the drug development for non‐smoking female NSCLC patients, we identified nilotinib as a potential agonist targetingNR4A1encoded protein by molecular docking and molecular dynamic stimulation. We also show that nilotinib inhibited proliferation and induced senescence of cells in non‐smoking female NSCLC patients in vitro.ConclusionsThese results not only uncover nutrient metabolic characteristics in non‐smoking female NSCLC patients, but also provide a new paradigm for identifying new targets and drugs for novel therapy for such patients.
inlabru: an R package for Bayesian spatial modelling from ecological survey data
Authors: Bachl Fabian E. , Lindgren Finn , Borchers David L. , Illian Janine B. 
Published: February 2019

Abstract

Spatial processes are central to many ecological processes, but fitting models that incorporate spatial correlation to data from ecological surveys is computationally challenging. This is particularly true of point pattern data (in which the primary data are the locations at which target species are found), but also true of gridded data, and of georeferenced samples from continuous spatial fields.

We describe here the R package inlabru that builds on the widely used RINLA package to provide easier access to Bayesian inference from spatial point process, spatial count, gridded, and georeferenced data, using integrated nested Laplace approximation (INLA, Rue et al., 2009).

The package provides methods for fitting spatial density surfaces and estimating abundance, as well as for plotting and prediction. It accommodates data that are points, counts, georeferenced samples, or distance sampling data.

This paper describes the main features of the package, illustrated by fitting models to the gorilla nest data contained in the package spatstat (Baddeley, & Turner, 2005), a line transect survey dataset contained in the package dsm (Miller, Rexstad, Burt, Bravington, & Hedley, 2018), and to a georeferenced sample from a simulated continuous spatial field.
Genetically heterogeneous mice exhibit a female survival advantage that is age‐ and site‐specific: Results from a large multi‐site study
Authors: Cheng Catherine J. , Gelfond Jonathan A. L. , Strong Randy , Nelson James F. 
Published: February 2019

AbstractThe female survival advantage is a robust characteristic of human longevity. However, underlying mechanisms are not understood, and rodent models exhibiting a female advantage are lacking. Here, we report that the genetically heterogeneous (UM‐HET3) mice used by the National Institute on Aging Interventions Testing Program (ITP) are such a model. Analysis of age‐specific survival of 3,690 control ITP mice revealed a female survival advantage paralleling that of humans. As in humans, the female advantage in mice was greatest in early adulthood, peaking around 350 days of age and diminishing progressively thereafter. This persistent finding was observed at three geographically distinct sites and in six separate cohorts over a 10‐year period. Because males weigh more than females and bodyweight is often inversely related to lifespan, we examined sex differences in the relationship between bodyweight and survival. Although present in both sexes, the inverse relationship between bodyweight and longevity was much stronger in males, indicating that male mortality is more influenced by bodyweight than is female mortality. In addition, male survival varied more across site and cohort than female survival, suggesting greater resistance of females to environmental modulators of survival. Notably, at 24 months the relationship between bodyweight and longevity shifted from negative to positive in both sexes, similar to the human condition in advanced age. These results indicate that the UM‐HET3 mouse models the human female survival advantage and provide evidence for greater resilience of females to modulators of survival.
The value of ongoing venture capital investment to newly listed firms
Authors: Hsu Wei‐Huei , Owen Sian , Suchard Jo‐Ann 
Published: February 2019

AbstractWe examine whether the market values continuing venture capital (VC) investor involvement in firms post‐IPO. Compared to the US, Australian VC investors exit their investments post‐IPO by on‐market sales rather than distribution of holdings to their investors. Lockup periods tend to be longer and ownership thresholds for reporting trades lower. We find that the market responds positively to buy transactions, negatively to sell transactions of VC investors and negatively to the resignation of VC directors. These results are consistent with VC investors in the firm having a positive influence and creating value from which the VCs and other shareholders benefit.
Factors affecting the success of artificial pack formation in an endangered, social carnivore: the African wild dog
Authors: Marneweck C. , Becker P. A. , Beverley G. , Davies‐Mostert H. T. , du Plessis C. , Forssman K. , Graf J. , Gusset M. , Hofmeyr M. , Kelly C. , Kilian P. J. , Marchal A. F. J. , Marneweck D. G. , Marnewick K. , Owen C. , Postiglione G. , Slotow R. , Somers M. J. , Szykman Gunther M. , van Dyk G. , Whittington‐Jones B. , Parker D. M. 
Published: February 2019

AbstractSocial integration is an important factor when reintroducing group‐living species, but examples of the formation of social groups before reintroduction are largely lacking. African wild dogs Lycaon pictus are endangered, and reintroductions have become a routine part of range expansion in South Africa. Wild dogs form packs that are essential to their reproduction and survival, and artificial pack formation is often required before reintroduction. We examined the proximate (i.e. social integration) and ultimate (i.e. reproduction) success of 43 artificial pack formation attempts in the South African managed metapopulation, between 1995 and 2018. The top (and dominant) model for proximate success included an interaction between total group size and an initial separation fence. Larger groups took longer to integrate, irrespective of initial separation, whereas smaller groups brought together immediately integrated faster than those that were initially separated. The top models for ultimate success included an interaction between the proportion of males and number of days spent in the pre‐release enclosure, the total number of days in the enclosure and an interaction between the proportion of captive‐sourced individuals and the total number of days in the enclosure. Ultimate success increased when packs spent less time in the enclosure, especially if those packs had a low proportion of males (i.e. female biased) or included >25% captive‐sourced individuals. Neither the size of the artificially created pack nor the season in which the pack was released affected ultimate success. The success of social integration and reproductive success of artificially formed packs in this study was higher than for natural pack formations. We provide guidelines for optimizing future artificial pack formation in wild dogs for reintroduction success. Our results serve as an example of the practical importance of social behavior in successfully implementing conservation measures for group‐living species.
Underestimated mitochondrial diversity in gypsy moth Lymantria dispar from Asia
Authors: Zhao Jie , Wu Yunke , Kurenshchikov Dmitry K. , Ilyinykh Alexandr V. , Shi Juan 
Published: February 2019

Abstract
The gypsy moth Lymantria dispar (L.) (Erebidae) is one of the most important agricultural and forest insect pests. It currently includes three subspecies: Lymantria dispar dispar (L.), Lymantria dispar asiatica Vnukovskij and Lymantria dispar japonica (Motschulsky). The first subspecies is known as the European gypsy moth (EGM), whereas the latter two are collectively referred to as the Asian gypsy moth (AGM).
Asian gypsy moth possesses traits that include a strong female flight capability and broader larval host range, which make it a more threatening pest than EGM when invading new areas.
To better understand the genetic structure within AGM and in particular among Chinese populations, we reconstructed a mitochondrial gene tree based on four mitochondrial protein‐coding genes (ND2, ND6, ATP6 and ATP8) from 17 Chinese locations and 21 locations from other countries.
None of the three subspecies of gypsy moth is recovered as monophyletic on the mitochondrial gene tree, likely as a result of human‐mediated transportation and a high level of cryptic genetic diversity.
Chinese populations are split into four mitochondrial clusters. Surprisingly, China I is nested within EGM and China II is the sister group of sampled EGM. China III grouped with samples from South Korea and the Russian Far East to represent the typical L. d. asiatica. China IV formed a sister relationship with the former group.
The results of the present study confirm that the recently discovered genotype from the Black Sea‐Caspian region consists of an independent mitochondrial genetic lineage from other subspecies.
Population genetic structure of Zeugodacus tau species complex in Thailand
Authors: Kitthawee Sangvorn , Julsirikul Duangta 
Published: February 2019

AbstractThe tephritid fruit fly Zeugodacus tau is a serious agriculture pest, especially of cucurbits in Thailand, where it is classified as a complex species of nine siblings (Z. tau A, B, C, D, E, F, G, I and J).
Based on single‐strand conformation polymorphism (SSCP) analysis, 33 distinct mitochondrial cytochrome c oxidase subunit I (mtCOI) haplotypes were found in three sibling species, Z. tau A, C and J, in Thailand. Genetic structure analysis of the population revealed relatively large genetic differences among these sibling species, reflecting a tendency toward speciation.
The maximum likelihood tree and median‐joining network reconstructed from the mtCOI sequences of 33 haplotypes supported the separation of these three sibling species within the Z. tau complex.
The three‐level hierarchical analysis of molecular variance based on geographical regions and the Mantel test for isolation‐by‐distance showed significant genetic structuring of the Z. tau complex in Thailand.
However, the genetic differentiation among geographical groups was rather low, which may be reasonably explained by natural and human mediated dispersal, as well as host associated differentiation.
The SSCP analysis on the population genetic structure of Z. tau species complex in the present study should benefit pest management.
Primates create seedling growth hotspots through pattern of dung deposition
Authors: Kalbitzer Urs , McInnis Victoria , Chapman Colin A. 
Published: February 2019

AbstractPrimates play important roles in tropical forests through seed dispersal and herbivory. They comprise a large part of the biomass of forest communities and tend to have clumped patterns of defecations (i.e. at favoured food trees or sleeping sites). Therefore, they may also play important roles in accelerating ecosystem nutrient cycling. Here we conduct a controlled growth experiment to quantify the effect of the addition of primate dung on the growth of both light‐demanding and shade‐tolerant seedlings over 1 year in Kibale National Park, Uganda. A mixed model analysis revealed that light‐demanding species were affected by the natural dung treatment and plants with small initial size had accelerated growth, whereas there was no effect on plant growth for shade‐tolerant species. The long‐term implications of increased dung deposition on the local tree community are unclear as shade‐tolerant species may only show an effect over the long‐term and light‐demanding species may only be able to take advantage of the increased growth if subsequently exposed to high light conditions, such as a treefall gap.
Beyond the Local Trap: New Municipalism and the Rise of the Fearless Cities
Authors: Russell Bertie 
Published: February 2019

AbstractThe Fearless Cities summit, coordinated by Barcelona en Comú in June 2017, marked the first global gathering of the nascent “new municipalist” movement. Responding to the “imperative that geographers engage critically and creatively with the way localism is being articulated”, this paper argues that the new municipalist initiatives are developing urban political strategies that successfully avoid the Local Trap. Rather than essentialising cities as inherently progressive or democratic, the municipal is instead becoming framed as a “strategic front” for developing a transformative politics of scale. Given this critical awareness, this nascent movement demonstrates how local loyalties can be mobilised as part of a progressive scalar strategy without falling into the trap of a “particular localism”. What remains to be seen is whether these initiatives are able to develop a variegated scalar strategy of transformation that retains the democratic essence that underpins them.
Translational research in retinal vascular disease. An approach
Authors: Bek Toke 
Published: February 2019

AbstractThe clinical presentation of the most frequent vision threatening retinal diseases is dominated by lesions indicating that disturbances in retinal blood flow are involved in the pathogenesis of these diseases. The present review describes the experience from a translational strategy pursued to investigate retinal vascular diseases with diabetic retinopathy as the main object. The normal regulation of retinal blood flow is investigated in porcine retinal vessels in vitro and ex vivo. Subsequently, the in vitro findings are translated to clinical studies in normal persons in vivo, and it is investigated whether the mechanisms are disturbed in retinal vascular disease. This is followed by clinical intervention studies on these diseases. The approach has been used to investigate pressure autoregulation, metabolic autoregulation and vasomotion in retinal vessels. The investigations have shown that retinal vascular tone can be regulated by receptor‐specific agonists and antagonists to vasoactive compounds such as purines, prostaglandins and nitric oxide synthesis and that the vasoactive effects can be modulated by the concentration and the mode of administration of these compounds. Additionally, it has been shown that retinal precapillary arterioles and capillaries not visible by ophthalmoscopy may play an important role for the pathophysiology of retinal vascular disease and its treatment. Future studies should focus on investigating normal and pathological regulation of retinal blood flow in these smaller vessels.
Postural effects on spontaneous retinal venous pulsations in healthy individuals
Authors: Georgevsky Dana , Gangoda Sumudu V. S. , Golzan Seyyed Mojtaba 
Published: February 2019

AbstractPurposeTo assess amplitudes of spontaneous retinal venous pulsations (SVP) in three various postures (sitting, supine and lateral decubitus) in healthy individuals.MethodsThirty participants (28 ± 8 years, 25 females) were included in the study. Intraocular pressure (IOP), blood pressure (BP) and SVP's were measured at three different postures using a calibrated Tono‐Pen applanation tonometer, a digital sphygmomanometer, and a custom‐built handheld video ophthalmoscope, respectively. Retinal venous pulsations (SVP) amplitudes were extracted from the retinal videos using a custom written MATLAB algorithm. Mean arterial pressure (MAP = (systolic + 2diastolic)/3) and mean ocular perfusion pressure (MOPP = (2/3 MAP)‐IOP) were also calculated at each posture. A one‐way ANOVA was applied to each parameter to determine any significant difference for the various postural changes.ResultsMean IOP increased (p < 0.0001) and mean SVP decreased (p < 0.0001) from sitting to supine. The mean IOP (mmHg) and SVP (MU; measuring units) in sitting, supine and lateral decubitus were 16.2 ± 2, 19.4 ± 4, 19.8 ± 2 mmHg and 5.8 ± 2, 4.5 ± 2, and 4.7 ± 2 MU, respectively. Mean arterial pressure (MAP) and MOPP also decreased significantly from sitting to supine (p < 0.001, p < 0.001) and sitting to lateral decubitus (p < 0.05, p < 0.01). There were no significant differences between IOP, SVP, MAP or MOPP during a postural modification from supine to lateral decubitus.ConclusionsIn this study, we showed a significant reduction in SVP amplitudes and a significant increase in IOP from sitting to supine position in a healthy young cohort. This supports the rationale to further study such phenomenon in ocular conditions such as glaucoma to determine whether relative SVP change, for a similar postural change, can reveal early signs of vascular dysfunction.
Antitumor activity and apoptotic action of coelomic fluid from the earthworm Dendrobaena veneta against A549 human lung cancer cells
Authors: Fiołka Marta J. , Rzymowska Jolanta , Bilska Sylwia , Lewtak Kinga , Dmoszyńska‐Graniczka Magdalena , Grzywnowicz Krzysztof , Kaźmierski Wojciech , Urbanik‐Sypniewska Teresa 
Published: February 2019

It is known that earthworm coelomic fluid (CF) can affect not only cancer but also normal cells. The study demonstrated that the CF of the earthworm Dendrobaena veneta exhibited cytotoxicity against A549 lung cancer cells but did not toward the bronchial epithelial cell line BEAS‐2B. The selective effect on the tumor cells was achieved after a short‐term CF heat pre‐treatment at 70 °C. The cytotoxic effect of the CF was time‐ and concentration‐dependent. The CF noticeably decreased the viability and affected the morphology of the A549 cells. Scanning electron microscopy revealed a different degree of destruction of the nucleus and cytoplasm of A549 cells. As determined by atomic force microscopy, the cell surface roughness increased while the cell stiffness was reduced upon the CF treatment. A twofold increase in the caspase 3, 4, 5, and 10 levels was observed in the A549 cells after the incubation with the CF. The results obtained by flow cytometry using Annexin V confirmed the proapoptotic effect of the earthworm CF on A549 lung cancer cells. The D. veneta CF and active fraction obtained with cytotoxicity toward A549 lung cancer is an interesting and promising preparation for further biological, chemical, and biomedical research.
Methadone dosing strategies in preterm neonates can be simplified
Authors: van Donge Tamara , Samiee‐Zafarghandy Samira , Pfister Marc , Koch Gilbert , Kalani Majid , Bordbar Arash , van den Anker John 
Published: February 2019

AimsA dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics (PK) of methadone is available in preterm neonates. Therefore we investigated developmental PK of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population.MethodsA single‐centre open‐label prospective study was performed to collect PK data after a single oral dose of methadone in preterm neonates. A population PK model was built to characterize developmental PK of (R)‐ and (S)‐methadone. Model‐based simulations were performed to identify a simplified dosing strategy to reach and maintain target methadone exposure.ResultsA total of 121 methadone concentrations were collected from 31 preterm neonates. A one‐compartment model with first order absorption and elimination kinetics best described PK data for (R)‐ and (S)‐methadone. Clearance increases with advancing gestational age and differs between R‐ and S‐enantiomer, being slightly higher for the former (0.244 vs 0.167 L/h). Preterm neonates reached target exposure after 48 hours with currently used dosing schedules. Output from simulations revealed that target exposures can be achieved with a simplified dosing strategy during the first 4 days of treatment.ConclusionMethadone clearance in preterm neonates increases with advancing gestational age and its disposition is influenced by its chirality. Simulations that account for developmental PK changes indicate a shorter methadone dosing strategy can maintain target exposure to control withdrawal symptoms.
The carcinogenic potential of non‐ionizing radiations: The cases of S‐50 Hz MF and 1.8 GHz GSM radiofrequency radiation
Authors: Soffritti Morando , Giuliani Livio 
Published: February 2019

AbstractEpidemiological studies have suggested that human exposure to extremely low‐frequency electromagnetic fields from the electric power and to mobile phone radiofrequency electromagnetic fields induce an increased risk of developing malignant tumours. However, no adequate laboratory data, in particular long‐term carcinogenicity bioassays to support the epidemiological evidence, have yet been available. This motivated the Ramazzini Institute to embark on a first project of four large life‐span carcinogenic bioassays conducted on over 7000 Sprague Dawley rats exposed from prenatal life until natural death to S‐50 Hz MF alone or combined with gamma radiation or formaldehyde or aflatoxin B1. Results now available from these studies, which started concurrently, have shown that exposure to Sinusoidal‐50 Hz Magnetic Field (S‐50 Hz MF) combined with acute exposure to gamma radiation or to chronic administration of formaldehyde in drinking water induces a significantly increased incidence of malignant tumours in males and females. A second project of two large life‐span carcinogenic bioassays was conducted on over 3000 Sprague Dawley rats exposed from prenatal life until natural death to 1.8 GHz GSM of mobile phone radio base station, alone or combined with acute exposure to gamma radiation. Early results from the experiment on 1.8 GHz GSM alone show a statistically significant increase in the incidence of heart malignant schwannoma among males exposed at the highest dose.