bluuebunny/crossref_metadata_2025 huggingface dataset:
Refined structure model of rare earth silicide nanowires on Si(001)
Authors: Appelfeller Stephan , Heggemann Jonas , Niermann Tore , Lehmann Michael , Dähne Mario
Published: March 2019

The internal atomic structure of terbium silicide nanowires on Si(001) is determined by scanning tunneling microscopy and high-resolution transmission electron microscopy. It is found that room temperature capping by amorphous silicon does not affect the original nanowire structure. Atomically resolved transmission electron microscopy data supported by image simulations demonstrate that the nanowires consist of two silicide layers high hexagonal TbSi2 with the c-axis aligned in the nanowire direction, in contrast to previous assumptions. An analogous atomic structure is predicted for related nanowires of other trivalent rare earth elements because of their chemical similarity.
Effect of interaction between a particle cluster and a single particle on particle motion and distribution during sedimentation: A numerical study
Authors: Hu Junjie , Guo Zhaoli
Published: March 2019

The interaction between a particle cluster and a single particle during sedimentation is studied with the lattice Boltzmann method, where the effects of the initial distance and particle number on the motion and distribution of the particle cluster are investigated. Compared to the case without the single particle, the motion and distribution of the particle cluster are affected significantly due to the effect of the single particle. Due to the interaction between the particle cluster and the single particle, the particle-particle interaction becomes stronger; compared to the case without the single particle, the velocity fluctuation of the particle cluster is much more intensive. Besides, the particle cluster is scattered by the single particle, and the distribution of the particle cluster becomes more inhomogeneous.
Enhanced bioconjugation on sputtered palladium nano-thin-film electrode
Authors: Chang Chia-Yu , Chen Wei , Su Chien-Hao , Chang Pang-Chia , Huang Yun-Tzu , Hsu Kuo-Chen , Yuan Chiun-Jye , Chang Chia-Ching
Published: March 2019

A highly reactive surface with an enhanced ability for chemical bonding relies on the presence of specifically coordinated atoms and step edges at the surface. In this study, an electrode with a unique Stranski-Krastanov-like thin film, with an epitaxial sputtering of a palladium (Pd) nanoparticle double layer on the polyethylene terephthalate substrate, was developed. On the surface of this flexible Pd-nano-thin-film (NTF) electrode with a (1 1 1) containing surface, DNA probes can be quickly immobilized in as short a period as 20 min, which is 24 times faster than that on the gold electrode. A DNA-based anticancer compound (ACC) sensing and screening process that would use the DNA functionalized Pd-NTF electrode as the biosensor was then proposed. Interestingly, the developed biosensor could detect DNA and ACCs, such as doxorubicin, tetra-O-methyl nordihydroguaiaretic acid, and Taxol via interactions with solutions containing 1 μl ACCs within 11 min, and the sensitivity of the ACC solution is ∼0.1 μM (∼36 pg per-test), as detected by electrochemical impedance spectroscopy. Moreover, this highly reactive surface can be used in regular sensors and other interfaces, in scientific applications.
The dynamics of Laplace-like resonances
Authors: Celletti Alessandra , Paita Fabrizio , Pucacco Giuseppe
Published: March 2019

The three inner Galilean satellites of Jupiter—Io, Europa, and Ganymede—are observed to move in a particular dynamical configuration, which is commonly known as the Laplace resonance. These satellites are characterized by a 2:1 ratio between the mean longitudes of Io-Europa and Europa-Ganymede. Another dynamical configuration, known as the de Sitter resonance, occurs when the longitude of Ganymede is fixed, instead of rotating like in the Laplace resonance. Besides studying the Laplace and de Sitter resonances, we also consider their generalizations to the case in which the mean longitudes of the first two satellites are in a ratio k:j, while those of the second and third satellites are in a ratio m:n with k,j,m,n∈Z+ and |j−k|, |n−m|≤2. We derive a model apt to describe such resonant configurations. We make an extensive study of the structural stability of the resonances; we show that the libration of the Laplace resonant angle is deeply affected by small variations of some quantities, most notably the semimajor axes and the oblateness. A remarkable result is that in several cases, the standard Laplace resonance of the Galilean satellites displays a regular behavior in comparison to other resonances characterized by different mean longitude ratios, which instead show a rather chaotic behavior even on short time scales. This result provides a motivation to support why the Galilean satellites are found in the actual Laplace resonance.
Worth of wetlands: revised global monetary values of coastal and inland wetland ecosystem services
Authors: Davidson N. C. , van Dam A. A. , Finlayson C. M. , McInnes R. J.
Published: March 2019

In this study, we have re-estimated the 2011 global monetary values of natural wetland ecosystem services using new information on the areas of different coastal and inland wetland classes, and included estimates for forested wetlands. The 2011 global monetary value of natural wetland ecosystem services is now estimated at Int$47.4 trillion per year, 43.5% of the value of all natural biomes. Despite forming only ~15% of global natural wetland area, coastal wetlands are estimated to deliver 43.1% (Int$20.4 trillion per year) of the total global ecosystem services monetary value of all natural wetland classes. There is a need to further refine these value estimates by factoring in other determinants of wetland ecosystem service monetary value, by disaggregating unit monetary values to each wetland class and by updating unit monetary values with more recent sources, especially for ecosystem services with no, or few, value estimates.
Effects of local anthropogenic stressors on a habitat cascade in an estuarine seagrass system
Authors: Siciliano Alfonso , Schiel David R. , Thomsen Mads S.
Published: March 2019

Recent research has shown that co-occurring primary and secondary habitat-forming species typically support higher biodiversity than do monocultures of the primary habitat-former alone. However, these ‘habitat cascades’ may not be universal and it is important to know whether, when and where positive effects on biodiversity from secondary habitat-forming species change to negative effects. Here, we tested how anthropogenic stressors (fertilisation and sedimentation) and unattached secondary habitat-forming Ulva seaweeds affected the primary habitat-forming seagrass, Zostera muelleri, and its associated invertebrates in the Avon–Heathcote Estuary, New Zealand. We experimentally stressed Zostera by adding different fertilisation and sediment levels. Fertilisation had little impact, whereas even low sedimentation levels had strong negative effects on Zostera and its associated fauna. In a second experiment, sediments and Ulva were added to seagrass beds and unvegetated mudflats to test whether sediment stress modifies habitat cascades. We found again strong negative effects of sediments on Zostera, irrespective of spatio-temporal conditions, and that negative effects of sediments on invertebrates were enhanced in the presence of the secondary habitat former. These results highlighted that anthropogenic stressors can destabilise habitat cascades; processes that may be of particular importance in estuaries that are characterised by low biodiversity and stressful environmental conditions.
Roles of poly (ADP-ribose) polymerase 1 activation and cleavage in induction of multi-oocyte ovarian follicles in the mouse by 3-nitropropionic acid
Authors: Wei Quanwei , Wu Guoyun , Xing Jun , Mao Dagan , Hutz Reinhold J. , Shi Fangxiong
Published: March 2019

3-nitropropionic acid (3-NPA) is known to be a mitochondrial toxin produced by plants and fungi, which may produce DNA damage in cells. However, studies of its reproductive toxicology are lacking. We know that poly(ADP-ribose) polymerase (PARP) plays an important role in a large variety of physiological processes and is involved in DNA repair pathways. The present study was therefore aimed at exploring the involvement of PARP-1 activation and cleavage after 3-NPA stimulation in female mice. We observed an increased number of atretic follicles and multi-oocyte follicles (MOFs) after treatment with 3-NPA and serum concentrations of 17β-oestradiol and progesterone were significantly reduced. Our results provide evidence that PARP-1 cleavage and activational signals are involved in pathological ovarian processes stimulated by 3-NPA. In addition, total superoxide dismutase, glutathione peroxidase and catalase activities were significantly increased, whereas succinate dehydrogenase was decreased in a dose-dependent manner. Results from our in vitro study similarly indicated that 3-NPA inhibited the proliferation of mouse granulosa cells and increased apoptosis in a dose-dependent manner. In summary, 3-NPA induces granulosa cell apoptosis, follicle atresia and MOFs in the ovaries of female mice and causes oxidative stress so as to disrupt endogenous hormonal systems, possibly acting through PARP-1 signalling.
Poisson mixed models for predicting number of fires
Authors: Boubeta Miguel , Lombardía María José , Marey-Pérez Manuel , Morales Domingo
Published: March 2019

Wildfires are considered one of the main causes of forest destruction. In recent years, the number of forest fires and burned area in Mediterranean regions have increased. This problem particularly affects Galicia (north-west of Spain). Conventional modelling of the number of forest fires in small areas may have a high error. For this reason, four area-level Poisson mixed models with time effects are proposed. The first two models contain independent time effects, whereas the random effects of the other models are distributed according to an autoregressive process AR(1). A parametric bootstrap algorithm is given to measure the accuracy of the plug-in predictor of fire number under the temporal models. A significant prediction improvement is observed when using Poisson regression models with random time effects. Analysis of historical data finds significant meteorological and socioeconomic variables explaining the number of forest fires by area and reveals the presence of a temporal correlation structure captured by the area-level Poisson mixed model with AR(1) time effects.
Feral-horse impacts on corroboree frog habitat in the Australian Alps
Authors: Foster C. N. , Scheele B. C.
Published: March 2019

Context Introduced herbivores can have a substantial impact on native plants and animals, particularly in ecosystems that do not share a recent evolutionary history with similar herbivore species. The feral horse, Equus caballus, has a widespread but patchy distribution in Australia, with large populations present in national parks in the Australian Alps. There are few peer-reviewed studies of the impacts of feral horses on ecosystems in this region. However, impacts could be substantial, particularly in wetland and riparian environments that are focal points for horse activity and sensitive to trampling and physical disturbance. Aims In the present study, we used replicated horse exclosures to investigate the effects of feral horses on breeding habitat of the critically endangered northern corroboree frog, Pseudophryne pengilleyi, in the Australian Alps. Methods Pseudophryne pengilleyi constructs nests and lays eggs in dense litter surrounding small, seasonally flooded wetland pools. In 2010, we sampled the litter depth adjacent to pools at eight long-term P. pengilleyi monitoring sites. In 2011, horse exclosures were established at each of the eight sites, such that less than half of the wetland area was inside the exclosure. In 2015, we measured litter depth surrounding pools inside and outside the exclosures, as well as at three additional sites where feral horses were absent. Key results We found that the pool-edge litter was 1.9 times deeper in areas without horses (inside horse-exclosure plots and horse-free sites) than in areas accessible to horses (unfenced areas in horse-occupied sites). Conclusions Our study has presented experimental evidence that horse grazing and trampling reduce breeding-habitat quality for P. pengilleyi, which could result in reduced reproduction success. Implications Ensuring the persistence of high-quality habitat is crucial for the conservation of P. pengilleyi, particularly given the severity of the decline of this species associated with chytrid fungus. Our results have provided direct evidence of a negative feral-horse impact on the habitat of a threatened animal species in the Australian Alps.
The Problem of Pain: Additive Analgesic Effect of Tramadol and Buprenorphine in a Patient with Opioid use Disorder
Authors: Montalvo Cristina , Genovese Nicolas , Renner John
Published: March 2019

Background: There is a paucity of published literature on the optimal treatment of pain in patients on buprenorphine treatment (BT) for opioid use disorder. Using this case report, we hope to demonstrate that tramadol may represent an effective treatment option for pain in patients on BT while encouraging future clinical trials. Case: The patient is a 56-year-old Caucasian male with a history of opiate use disorder on treatment with buprenorphine/naloxone 8/2 mg 2 times a day (BID) who was followed in an outpatient general psychiatry clinic that specializes in patients with co-occurring substance use disorders. Although maintaining sobriety from opioids, the patient continued to struggle with acute on chronic pain secondary to osteoarthritis that had left him walking with a cane. The patient was started on tramadol 50 mg 3 times a day (TID) for acute pain by his primary care physician (PCP) while he awaited surgical intervention. He reported analgesic effect with buprenorphine/naloxone but noted that it did not last the full period between his doses. He reported further improvement in his pain along with greater daily functioning with the additional use of tramadol, without side effects or withdrawal symptoms. Discussion: Current recommendations for pain management in patients on BT include discontinuation of BT therapy and/or addition of an adjunctive opioid analgesic (including additional buprenorphine/naloxone) while continuing agonist medication for treatment of opioid use disorder. However, determining which medication to use can be difficult, as there has been no literature examining this issue. In this case, the combination of buprenorphine and tramadol demonstrated an additive analgesic effect. Randomized control studies need to be performed to further understand the changes in pain measurement in patients on BT with tramadol compared with other adjunctive analgesic medications.
Progress in the genomics and genome-wide study of sake yeast
Authors: Akao Takeshi
Published: March 2019

Completion of the whole genome sequence of a laboratory yeast strain Saccharomyces cerevisiae in 1996 ushered in the development of genome-wide experimental tools and accelerated subsequent genetic study of S. cerevisiae. The study of sake yeast also shared the benefit of such tools as DNA microarrays, gene disruption-mutant collections, and others. Moreover, whole genome analysis of representative sake yeast strain Kyokai no. 7 was performed in the late 2000s, and enabled comparative genomics between sake yeast and laboratory yeast, resulting in some notable finding for of sake yeast genetics. Development of next-generation DNA sequencing and bioinformatics also drastically changed the field of the genetics, including for sake yeast. Genomics and the genome-wide study of sake yeast have progressed under these circumstances during the last two decades, and are summarized in this article.

Abbreviations: AFLP: amplified fragment length polymorphism; CGH: comparative genomic hybridization; CNV: copy number variation; DMS: dimethyl succinate; DSW: deep sea water; LOH: loss of heterozygosity; NGS: next generation sequencer; QTL: quantitative trait loci; QTN: quantitative trait nucleotide; SAM: S-adenosyl methionine; SNV: single nucleotide variation
Administrative coordination capacity; does the wickedness of policy areas matter?
Authors: Christensen Tom , Lægreid Ole Martin , Lægreid Per
Published: March 2019

Based on a survey of civil servants in the Norwegian central government, this article describes perceptions of coordination capacity and examines to what degree the variations in perceived coordinating capacity can be explained by structural and cultural features. In particular, it focuses on the significance of wicked policy areas. Overall the coordination capacity is weaker in wicked policy areas than in other policy areas. Controlling for other features the coordination capacity is primarily related to cultural factors, such as mutual trust, level of conflict, and identification with the central government. Some structural features, such as administrative level, also have an effect.
Proteomic analysis reveals procoagulant properties of cigarette smoke‐induced extracellular vesicles
Authors: Benedikter Birke J. , Bouwman Freek G. , Heinzmann Alexandra C. A. , Vajen Tanja , Mariman Edwin C. , Wouters Emiel F. M. , Savelkoul Paul H. M. , Koenen Rory R. , Rohde Gernot G. U. , van Oerle Rene , Spronk Henri M. , Stassen Frank R. M.
Published: March 2019

Airway epithelial cells secrete extracellular vesicles (EVs) under basal conditions and when exposed to cigarette smoke extract (CSE). Getting insights into the composition of these EVs will help unravel their functions in homeostasis and smoking‐induced pathology. Here, we characterized the proteomic composition of basal and CSE‐induced airway epithelial EVs. BEAS‐2B cells were left unexposed or exposed to 1% CSE for 24 h, followed by EV isolation using ultrafiltration and size exclusion chromatography. Isolated EVs were labelled with tandem mass tags and their proteomic composition was determined using nano‐LC‐MS/MS. Tissue factor (TF) activity was determined by a factor Xa generation assay, phosphatidylserine (PS) content by prothrombinase assay and thrombin generation using calibrated automated thrombogram (CAT). Nano‐LC‐MS/MS identified 585 EV‐associated proteins with high confidence. Of these, 201 were differentially expressed in the CSE‐EVs according to the moderated t‐test, followed by false discovery rate (FDR) adjustment with the FDR threshold set to 0.1. Functional enrichment analysis revealed that 24 proteins of the pathway haemostasis were significantly up‐regulated in CSE‐EVs, including TF. Increased TF expression on CSE‐EVs was confirmed by bead‐based flow cytometry and was associated with increased TF activity. CSE‐EVs caused faster and more thrombin generation in normal human plasma than control‐EVs, which was partly TF‐, but also PS‐dependent. In conclusion, proteomic analysis allowed us to predict procoagulant properties of CSE‐EVs which were confirmed in vitro. Cigarette smoke‐induced EVs may contribute to the increased cardiovascular and respiratory risk observed in smokers.
The El Niño impact on maize yields is amplified in lower income teleconnected countries
Authors: Ubilava David , Abdolrahimi Maryam
Published: March 2019

We use a multiple-regime panel smooth transition regression to examine the economic and climatic sources of the nonuniform relationship between El Niño Southern Oscillation (ENSO) and maize yields around the globe. While the yield effect is predominantly observed in strongly teleconnected countries, it is amplified in lower income countries, which we attribute to possible lack of resilience to ENSO—induced weather shocks. Both El Niño-like and La Niña-like conditions result in maize yield reduction, but it is during El Niño events when maize yields drop by up to 20% in most affected countries. Because in many of these countries maize is an important agricultural crop, the presented results are of interest to researchers and policy makers in the areas of world nutrition and international aid. Moreover, because larger share of maize is produced by high income weakly teleconnected countries, the observed geographic heterogeneity of the El Niño impact offers possible benefits from global risk sharing. These findings also offer insights to climate change economics, as possible increased frequency of the ENSO cycle may negatively impact maize production in strongly teleconnected low income countries.
Deforestation displaced: trade in forest-risk commodities and the prospects for a global forest transition
Authors: Pendrill Florence , Persson U Martin , Godar Javier , Kastner Thomas
Published: March 2019

While many developed countries are increasing their forest cover, deforestation is still rife in the tropics and subtropics. With international trade in forest-risk commodities on the rise, it is becoming increasingly important to consider between-country trade linkages in assessing the drivers of—and possible connections between—forest loss and gain across countries. Previous studies have shown that countries that have undergone a forest transition (and are now increasing their forest cover) tend to displace land use outside their borders. However, lack of comprehensive data on deforestation drivers imply that it has not been possible to ascertain whether this has accelerated forest loss in sourcing countries. To remedy this, we present a land-balance model that quantifies deforestation embodied in production of agricultural and forestry commodities at country level across the tropics and subtropics, subsequently tracing embodied deforestation to countries of apparent consumption using a physical, country-to-country trade model. We find that in the period 2005–2013, 62% (5.5 Mha yr−1) of forest loss could be attributed to expanding commercial cropland, pastures and tree plantations. The commodity groups most commonly associated with deforestation were cattle meat, forestry products, oil palm, cereals and soybeans, though variation between countries and regions was large. A large (26%) and slightly increasing share of deforestation was attributed to international demand, the bulk of which (87%) was exported to countries that either exhibit decreasing deforestation rates or increasing forest cover (late- or post-forest transition countries), particularly in Europe and Asia (China, India, and Russia). About a third of the net forest gains in post-forest transition countries was in this way offset by imports of commodities causing deforestation elsewhere, suggesting that achieving a global forest transition will be substantially more challenging than achieving national or regional ones.
Shape convergence for aggregate tiles in conformal tilings
Authors: Kenyon R. , Stephenson K.
Published: March 2019

Given a polygonal substitution tiling

T
T

of the plane with subdivision rule

τ
\tau

, we study the conformal tilings

T
n

T_n

associated with

τ
n

T

\tau ^nT

. We prove, under the assumption that there is somewhere a non-real similarity mapping one tile to another, that aggregate tiles within

T
n

T_n

converge in shape as

n
→
∞

n\rightarrow \infty

to their associated Euclidean tiles in

T
T

.
PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry
Authors: Boudreau Vincent , Chen Richard , Edwards Alan , Sulaimain Muhammad , Maddox Paul S.
Published: March 2019

Across most sexually reproducing animals, centrosomes are provided to the oocyte through fertilization and must be positioned properly to establish the zygotic mitotic spindle. How centrosomes are positioned in space and time through the concerted action of key mitotic entry biochemical regulators, including protein phosphatase 2A (PP2A-B55/SUR-6), biophysical regulators, including dynein, and the nuclear lamina is unclear. Here, we uncover a role for PP2A-B55/SUR-6 in regulating centrosome separation. Mechanistically, PP2A-B55/SUR-6 regulates nuclear size before mitotic entry, in turn affecting nuclear envelope–based dynein density and motor capacity. Computational simulations predicted the requirement of PP2A-B55/SUR-6 regulation of nuclear size and nuclear-envelope dynein density for proper centrosome separation. Conversely, compromising nuclear lamina integrity led to centrosome detachment from the nuclear envelope and migration defects. Removal of PP2A-B55/SUR-6 and the nuclear lamina simultaneously further disrupted centrosome separation, leading to unseparated centrosome pairs dissociated from the nuclear envelope. Taking these combined results into consideration, we propose a model in which centrosomes migrate and are positioned through the concerted action of PP2A-B55/SUR-6–regulated nuclear envelope–based dynein pulling forces and centrosome–nuclear envelope tethering. Our results add critical precision to models of centrosome separation relative to the nucleus during spindle formation in cell division.
Post–Modern Epidemiology: When Methods Meet Matter
Authors: Davey Smith George
Published: March 2019

In the last third of the 20th century, etiological epidemiology within academia in high-income countries shifted its primary concern from attempting to tackle the apparent epidemic of noncommunicable diseases to an increasing focus on developing statistical and causal inference methodologies. This move was mutually constitutive with the failure of applied epidemiology to make major progress, with many of the advances in understanding the causes of noncommunicable diseases coming from outside the discipline, while ironically revealing the infectious origins of several major conditions. Conversely, there were many examples of epidemiologic studies promoting ineffective interventions and little evident attempt to account for such failure. Major advances in concrete understanding of disease etiology have been driven by a willingness to learn about and incorporate into epidemiology developments in biology and cognate data science disciplines. If fundamental epidemiologic principles regarding the rooting of disease risk within populations are retained, recent methodological developments combined with increased biological understanding and data sciences capability should herald a fruitful post–Modern Epidemiology world.
Dr.VAE: improving drug response prediction via modeling of drug perturbation effects
Authors: Rampášek Ladislav , Hidru Daniel , Smirnov Petr , Haibe-Kains Benjamin , Goldenberg Anna
Published: March 2019

Motivation

Individualized drug response prediction is a fundamental part of personalized medicine for cancer. Great effort has been made to discover biomarkers or to develop machine learning methods for accurate drug response prediction in cancers. Incorporating prior knowledge of biological systems into these methods is a promising avenue to improve prediction performance. High-throughput cell line assays of drug-induced transcriptomic perturbation effects are a prior knowledge that has not been fully incorporated into a drug response prediction model yet.

Results

We introduce a unified probabilistic approach, Drug Response Variational Autoencoder (Dr.VAE), that simultaneously models both drug response in terms of viability and transcriptomic perturbations. Dr.VAE is a deep generative model based on variational autoencoders. Our experimental results showed Dr.VAE to do as well or outperform standard classification methods for 23 out of 26 tested Food and Drug Administration-approved drugs. In a series of ablation experiments we showed that the observed improvement of Dr.VAE can be credited to the incorporation of drug-induced perturbation effects with joint modeling of treatment sensitivity.

Availability and implementation

Processed data and software implementation using PyTorch (Paszke et al., 2017) are available at: https://github.com/rampasek/DrVAE.

Supplementary information

Supplementary data are available at Bioinformatics online.
Integration of methylation QTL and enhancer–target gene maps with schizophrenia GWAS summary results identifies novel genes
Authors: Wu Chong , Pan Wei
Published: March 2019

Motivation

Most trait-associated genetic variants identified in genome-wide association studies (GWASs) are located in non-coding regions of the genome and thought to act through their regulatory roles.

Results

To account for enriched association signals in DNA regulatory elements, we propose a novel and general gene-based association testing strategy that integrates enhancer-target gene pairs and methylation quantitative trait locus data with GWAS summary results; it aims to both boost statistical power for new discoveries and enhance mechanistic interpretability of any new discovery. By reanalyzing two large-scale schizophrenia GWAS summary datasets, we demonstrate that the proposed method could identify some significant and novel genes (containing no genome-wide significant SNPs nearby) that would have been missed by other competing approaches, including the standard and some integrative gene-based association methods, such as one incorporating enhancer-target gene pairs and one integrating expression quantitative trait loci.

Availability and implementation

Software: wuchong.org/egmethyl.html

Supplementary information

Supplementary data are available at Bioinformatics online.
Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer
Authors: Makabe Takeshi , Arai Eri , Hirano Takuro , Ito Nanako , Fukamachi Yukihiro , Takahashi Yoriko , Hirasawa Akira , Yamagami Wataru , Susumu Nobuyuki , Aoki Daisuke , Kanai Yae
Published: March 2019

The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among ‘transcriptional factors’. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.
Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus–infected and Exposed, Uninfected Youth
Authors: Moscicki Anna-Barbara , Karalius Brad , Tassiopoulos Katherine , Yao Tzy-Jyun , Jacobson Denise L , Patel Kunjal , Purswani Murli , Seage George R ,   Pediatric HIV/AIDS Cohort Study, Yogev Ram , Sanders Margaret Ann , Malee Kathleen , Hunter Scott , Shearer William , Paul Mary , Cooper Norma , Harris Lynnette , Purswani Murli , Baig Mahboobullah Mirza , Villegas Alma , Puga Ana , Navarro Sandra , Garvie Patricia A , Blood James , Burchett Sandra K , Karthas Nancy , Kammerer Betsy , Wiznia Andrew , Burey Marlene , Shaw Ray , Auguste Raphaelle , Dieudonne Arry , Bettica Linda , Johnson Juliette , Chen Janet S , Bulkley Maria Garcia , Ivey Latreaca , Grant Mitzie , Knapp Katherine , Allison Kim , Wilkins Megan , Russell-Bell Jamie , Acevedo-Flores Midnela , Rios Heida , Olivera Vivian , Silio Margarita , Gabriel Medea , Sirois Patricia , Spector Stephen A , Norris Kim , Nichols Sharon , McFarland Elizabeth , Cagwin Eric , Barr Emily , Katai Alisa , Scott Gwendolyn , Alvarez Grace , Fernandez Gabriel , Cuadra Anai
Published: March 2019

Background

Persons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth.

Methods

This is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts.

Results

Seroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively.

Conclusion

Antibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.
Early Initiation of Anti-TNF is Associated with Favourable Long-term Outcome in Crohn’s Disease: 10-Year-Follow-up Data from the Swiss IBD Cohort Study
Authors: Frei Roy , Fournier Nicolas , Zeitz Jonas , Scharl Michael , Morell Bernhard , Greuter Thomas , Schreiner Philipp , Misselwitz Benjamin , Safroneeva Ekaterina , Schoepfer Alain M , Vavricka Stephan R , Rogler Gerhard , Biedermann Luc
Published: March 2019

Background and Aims

The optimal timing of treatment escalation in Crohn’s disease [CD] remains a challenging issue, and very little is known about its long-term development following early versus late administration of anti-TNF antibodies. The long-term outcome of Swiss CD patients was comparatively assessed in an up to 10-year follow-up, using patients participating in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS].

Methods

Prospectively collected SIBDCS patient data, including disease history, baseline characteristics at enrolment, and course of disease, were analysed in patients with early versus late [<24 versus ≥24 months after diagnosis] and no anti-TNF treatment.

Results

A reduced risk of developing bowel stenosis was found in patients who received early anti-TNF treatment. This association was seen in patients overall and also in the subgroups of CD patients without pre-existing complications [Log-rank test: p < 0.001].

Furthermore, osteoporosis and anaemia were observed significantly less frequently in patients who received early anti-TNF treatment, compared with either patients who received treatment late [p < 0.001 and p = 0.046, respectively] or were never [p < 0.001 for both] treated with anti-TNF antibodies. Patients with early anti-TNF administration sought medical consultations significantly less often, including gastroenterologists in private practice [p = 0.017], ambulatory [outpatient] hospital visits [p = 0.038], and a composite of any medical visits [p = 0.001]. The percentage of patients unable to work was lowest for early-anti-TNF–treated patients, in comparison with patients who were treated late or never [3.6% vs 8.8% vs 3.7%, p = 0.016].

Conclusions

In CD patients within the SIBDCS, early anti-TNF administration was found to be associated with several indicators of a more favourable long-term outcome.
Adolescent Mental Health Problems, Behaviour Penalties, and Distributional Variation in Educational Achievement
Authors: Evensen Miriam
Published: March 2019

Prior research shows that mental health problems are linked to worse student achievements in school, but few studies address whether the consequences of such problems vary by student achievement level and the role of teachers’ grading practices in these processes. In this study, I examine the relationship between mental health problems and grade achievement at the end of compulsory education using a population-based Norwegian health survey, the Young-HUNT study, matched with administrative data. The results show a robust negative influence of attention problems and conduct problems on average grade achievement, and a positive role of internalizing problems, in fixed-effects models controlling for unobserved characteristics of school context. Further, conduct problems are more strongly related with student achievement in the lower end of the grade distribution, indicating that low-achieving students are disproportionally affected by mental health problems. I also compare grades assigned by classroom teachers with anonymously graded exams, and find that part of the negative association between externalizing problems and achievement reflect a ‘behavioural penalty’ due to teacher-bias in grading practices.
Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial
Authors: Ben-Yehuda Ori , Chen Shmuel , Redfors Björn , McAndrew Thomas , Crowley Aaron , Kosmidou Ioanna , Kandzari David E , Puskas John D , Morice Marie-Claude , Taggart David P , Leon Martin B , Lembo Nicholas J , Brown W Morris , Simonton Charles A , Dressler Ovidiu , Kappetein Arie Pieter , Sabik Joseph F , Serruys Patrick W , Stone Gregg W
Published: March 2019

Aims

The prognostic implications of periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) remain controversial. We examined the 3-year rates of mortality among patients with and without PMI undergoing left main coronary artery intervention randomized to PCI with everolimus-eluting stents vs. CABG in the large-scale, multicentre, prospective, randomized EXCEL trial.

Methods and results

By protocol, PMI was defined using an identical threshold for PCI and CABG [creatinine kinase-MB (CK-MB) elevation >10× the upper reference limit (URL) within 72 h post-procedure, or >5× URL with new Q-waves, angiographic vessel occlusion, or loss of myocardium on imaging]. Cox proportional hazards modelling was performed controlling for age, sex, hypertension, diabetes mellitus, left ventricular ejection fraction, SYNTAX score, and chronic obstructive pulmonary disease (COPD). A total of 1858 patients were treated as assigned by randomization. Periprocedural MI occurred in 34/935 (3.6%) of patients in the PCI group and 56/923 (6.1%) of patients in the CABG group [odds ratio 0.61, 95% confidence interval (CI) 0.40–0.93; P = 0.02]. Periprocedural MI was associated with SYNTAX score, COPD, cross-clamp duration and total procedure duration, and not using antegrade cardioplegia. By multivariable analysis, PMI was associated with cardiovascular death and all-cause death at 3 years [adjusted hazard ratio (HR) 2.63, 95% CI 1.19–5.81; P = 0.02 and adjusted HR 2.28, 95% CI 1.22–4.29; P = 0.01, respectively]. The effect of PMI was consistent for PCI and CABG for cardiovascular death (P  interaction = 0.56) and all-cause death (P  interaction = 0.59). Peak post-procedure CK-MB ≥10× URL strongly predicted mortality, whereas lesser degrees of myonecrosis were not associated with prognosis.

Conclusion

In the EXCEL trial, PMI was more common after CABG than PCI, and was strongly associated with increased 3-year mortality after controlling for potential confounders. Only extensive myonecrosis (CK-MB ≥10× URL) was prognostically important.
Early goal-directed haemodynamic optimization of cerebral oxygenation in comatose survivors after cardiac arrest: the Neuroprotect post-cardiac arrest trial
Authors: Ameloot Koen , De Deyne Cathy , Eertmans Ward , Ferdinande Bert , Dupont Matthias , Palmers Pieter-Jan , Petit Tibaut , Nuyens Philippe , Maeremans Joren , Vundelinckx Joris , Vanhaverbeke Maarten , Belmans Ann , Peeters Ronald , Demaerel Philippe , Lemmens Robin , Dens Jo , Janssens Stefan
Published: March 2019

Aims

During the first 6–12 h of intensive care unit (ICU) stay, post-cardiac arrest (CA) patients treated with a mean arterial pressure (MAP) 65 mmHg target experience a drop of the cerebral oxygenation that may cause additional cerebral damage. Therefore, we investigated whether an early goal directed haemodynamic optimization strategy (EGDHO) (MAP 85–100 mmHg, SVO2 65–75%) is safe and could improve cerebral oxygenation, reduce anoxic brain damage, and improve outcome when compared with a MAP 65 mmHg strategy.

Methods and results

A total of 112 out-of-hospital CA patients were randomly assigned to EGDHO or MAP 65 mmHg strategies during the first 36 h of ICU stay. The primary outcome was the extent of anoxic brain damage as quantified by the percentage of voxels below an apparent diffusion coefficient (ADC) score of 650.10−6 mm2/s on diffusion weighted magnetic resonance imaging (at day 5 ± 2 post-CA). Main secondary outcome was favourable neurological outcome (CPC score 1–2) at 180 days. In patients assigned to EGDHO, MAP (P < 0.001), and cerebral oxygenation during the first 12 h of ICU stay (P = 0.04) were higher. However, the percentage of voxels below an ADC score of 650.10−6 mm2/s did not differ between both groups [16% vs. 12%, odds ratio 1.37, 95% confidence interval (CI) 0.95–0.98; P = 0.09]. Also, the number of patients with favourable neurological outcome at 180 days was similar (40% vs. 38%, odds ratio 0.98, 95% CI 0.41–2.33; P = 0.96). The number of serious adverse events was lower in patients assigned to EGDHO (P = 0.02).

Conclusion

Targeting a higher MAP in post-CA patients was safe and improved cerebral oxygenation but did not improve the extent of anoxic brain damage or neurological outcome.
Independent risk factors for disease recurrence after surgery in patients with hepatitis B virus-related hepatocellular carcinoma ≤3 cm in diameter
Authors: He Ling-Ling , Liu Xiao-Li , Zhang Shuan , Li Meng-Ge , Wang Xian-Bo , Jiang Yu-Yong , Yang Zhi-Yun
Published: March 2019

Background

Post-operative recurrence rates are high for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to explore the factors associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor (≤3 cm in diameter).

Methods

This was a retrospective study of 203 (training cohort) and 64 (validation cohort) patients newly diagnosed with HBV-related HCC who had a single small primary tumor. The first year of post-operative follow-up was examined. Factors potentially associated with HCC recurrence were identified using Cox regression analyses. A model was constructed based on the factors identified and the prognostic value of the model was evaluated using receiver operating characteristic (ROC) curve analysis and calculation of the area under the ROC curve (AUC).

Results

A history of alcoholism and serum levels of α-fetoprotein, total protein and γ-glutamyl transpeptidase (GGT) were independently associated with 1-year recurrence rate after surgery. A predictive model based on these four factors had an AUC of 0.711 (95% confidence interval, 0.643–0.772) in the training cohort and 0.727 (95% confidence interval, 0.601–0.831) in the validation cohort. The 1-year recurrence rate was significantly lower in the low-risk group than in the high-risk group in both the training cohort (17.0% vs. 49.5%, P < 0.001) and the validation cohort (43.2% vs. 74.1%, P = 0.031).

Conclusion

A history of alcoholism and serum levels of α-fetoprotein, total protein and γ-glutamyl transpeptidase were independently associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor (≤3 cm in diameter).
Numerical approximation of fractional powers of elliptic operators
Authors: Duan Beiping , Lazarov Raytcho D , Pasciak Joseph E
Published: March 2019

In this paper, we develop and study algorithms for approximately solving linear algebraic systems: ${{\mathcal{A}}}_h^\alpha u_h = f_h$, $ 0< \alpha <1$, for $u_h, f_h \in V_h$ with $V_h$ a finite element approximation space. Such problems arise in finite element or finite difference approximations of the problem $ {{\mathcal{A}}}^\alpha u=f$ with ${{\mathcal{A}}}$, for example, coming from a second-order elliptic operator with homogeneous boundary conditions. The algorithms are motivated by the method of Vabishchevich (2015, Numerically solving an equation for fractional powers of elliptic operators. J. Comput. Phys., 282, 289–302) that relates the algebraic problem to a solution of a time-dependent initial value problem on the interval $[0,1]$. Here we develop and study two time-stepping schemes based on diagonal Padé approximation to $(1+x)^{-\alpha }$. The first one uses geometrically graded meshes in order to compensate for the singular behaviour of the solution for $t$ close to $0$. The second algorithm uses uniform time stepping, but requires smoothness of the data $f_h$ in discrete norms. For both methods, we estimate the error in terms of the number of time steps, with the regularity of $f_h$ playing a major role for the second method. Finally, we present numerical experiments for ${{\mathcal{A}}}_h$ coming from the finite element approximations of second-order elliptic boundary value problems in one and two spatial dimensions.
Convex Union Representability and Convex Codes
Authors: Jeffs R Amzi , Novik Isabella
Published: March 2019

We introduce and investigate $d$-convex union representable complexes: the simplicial complexes that arise as the nerve of a finite collection of convex open sets in ${\mathbb{R}}^d$ whose union is also convex. Chen, Frick, and Shiu recently proved that such complexes are collapsible and asked if all collapsible complexes are convex union representable. We disprove this by showing that there exist shellable and collapsible complexes that are not convex union representable; there also exist non-evasive complexes that are not convex union representable. In the process we establish several necessary conditions for a complex to be convex union representable such as that such a complex $\Delta $ collapses onto the star of any face of $\Delta $, that the Alexander dual of $\Delta $ must also be collapsible, and that if $k$ facets of $\Delta $ contain all free faces of $\Delta $, then $\Delta $ is $(k-1)$-representable. We also discuss some sufficient conditions for a complex to be convex union representable. The notion of convex union representability is intimately related to the study of convex neural codes. In particular, our results provide new families of examples of non-convex neural codes.