bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of methylated differentially expressed miRNAs and immune infiltrate profile in EBV-associated gastric cancer
Authors: Zhu Mansheng , Liang Qixiang , Chen Tao , Kong Qian , Ye Gengtai , Yu Shitong , Li Xunjun , He Qinglie , Liu Hao , Hu Yanfeng , Yu Jiang , Li Guoxin 
Published: January 2021

Abstract
Background
The recent discovery of cancer/tissue specificity of miRNA has indicated its great potential as a therapeutic target. In Epstein–Barr virus-associated gastric cancer (EBVaGC), host genes are affected by extensive DNA methylation, including miRNAs. However, the role of methylated miRNA in the development of EBVaGC and immune cell infiltration has largely remained elusive.

Results
After crossmatching the DNA methylation and expression profile of miRNA and mRNA in the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas Research Network (TCGA), we discovered that miR-129-2-3p was significantly suppressed due to hypermethylation on its enhancer in EBVaGC. The differentially expressed genes (DEGs) added up to 30, among which AKAP12 and LARP6 were predicted to be the target genes of miR-129-2-3p and negatively correlated with patients’ survival. Accordingly, miR-129-2-3p was significantly down-regulated in tumor samples in 26 (65%) out of 40 cases in our cohort (P < 0.0001). The proliferation, migration and invasion functions of GC cells were significantly promoted when transfected with miR-129-2-3p inhibitor and suppressed when transfected with mimics or treated with 5-aza-2′-deoxycytidine. Moreover, a comprehensive regulation network was established by combining the putative transcription factors, miRNA-mRNA and protein–protein interaction (PPI) analysis. Pathway enrichment analysis showed that cytokine activity, especially CCL20, was the most prominent biological process in EBVaGC development. Immune cell infiltration analysis demonstrated CD4+ T cell, macrophage and dendritic cell infiltrates were significantly enriched for the prognostic-indicated hub genes.

Conclusion
This study has provided a comprehensive analysis of differentially expressed miRNAs and mRNAs associated with genome-wide DNA methylation by integrating multi-source data including transcriptome, methylome and clinical data from GEO and TCGA, QPCR of tumor samples and cell function assays. It also gives a hint on the relationships between methylated miRNA, DEGs and the immune infiltration. Further experimental and clinical investigations are warranted to explore the underlying mechanism and validate our findings.
Generation of dyskeratosis congenita-like hematopoietic stem cells through the stable inhibition of DKC1
Authors: Carrascoso-Rubio Carlos , Zittersteijn Hidde A. , Pintado-Berninches Laura , Fernández-Varas Beatriz , Lozano M. Luz , Manguan-Garcia Cristina , Sastre Leandro , Bueren Juan A. , Perona Rosario , Guenechea Guillermo 
Published: January 2021

AbstractDyskeratosis congenita (DC) is a rare telomere biology disorder, which results in different clinical manifestations, including severe bone marrow failure. To date, the only curative treatment for the bone marrow failure in DC patients is allogeneic hematopoietic stem cell transplantation. However, due to the toxicity associated to this treatment, improved therapies are recommended for DC patients. Here, we aimed at generating DC-like human hematopoietic stem cells in which the efficacy of innovative therapies could be investigated. Because X-linked DC is the most frequent form of the disease and is associated with an impaired expression of DKC1, we have generated DC-like hematopoietic stem cells based on the stable knock-down of DKC1 in human CD34+ cells with lentiviral vectors encoding for DKC1 short hairpin RNAs. At a molecular level, DKC1-interfered CD34+ cells showed a decreased expression of TERC, as well as a diminished telomerase activity and increased DNA damage, cell senescence, and apoptosis. Moreover, DKC1-interfered human CD34+ cells showed defective clonogenic ability and were incapable of repopulating the hematopoiesis of immunodeficient NSG mice. The development of DC-like hematopoietic stem cells will facilitate the understanding of the molecular and cellular basis of this inherited bone marrow failure syndrome and will serve as a platform to evaluate the efficacy of new hematopoietic therapies for DC.
Current use of inotropes in circulatory shock
Authors: Scheeren Thomas W. L. , Bakker Jan , Kaufmann Thomas , Annane Djillali , Asfar Pierre , Boerma E. Christiaan , Cecconi Maurizio , Chew Michelle S. , Cholley Bernard , Cronhjort Maria , De Backer Daniel , Dubin Arnaldo , Dünser Martin W. , Duranteau Jacques , Gordon Anthony C. , Hajjar Ludhmila A. , Hamzaoui Olfa , Hernandez Glenn , Kanoore Edul Vanina , Koster Geert , Landoni Giovanni , Leone Marc , Levy Bruno , Martin Claude , Mebazaa Alexandre , Monnet Xavier , Morelli Andrea , Payen Didier , Pearse Rupert M. , Pinsky Michael R. , Radermacher Peter , Reuter Daniel A. , Sakr Yasser , Sander Michael , Saugel Bernd , Singer Mervyn , Squara Pierre , Vieillard-Baron Antoine , Vignon Philippe , Vincent Jean-Louis , van der Horst Iwan C. C. , Vistisen Simon T. , Teboul Jean-Louis 
Published: January 2021

Abstract
Background
Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock.

Methods
From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions.

Results
A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement).

Conclusion
Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.
Sign-changing solutions for Schrödinger–Kirchhoff-type fourth-order equation with potential vanishing at infinity
Authors: Guan Wen , Zhang Hua-Bo 
Published: January 2021

AbstractThe purpose of this paper is to study the existence of sign-changing solution to the following fourth-order equation:$$ \Delta ^{2}u- \biggl(a+ b \int _{\mathbb{R}^{N}} \vert \nabla u \vert ^{2}\,dx \biggr) \Delta u+V(x)u=K(x)f(u) \quad\text{in } \mathbb{R}^{N}, $$Δ2u−(a+b∫RN|∇u|2dx)Δu+V(x)u=K(x)f(u)in RN,where$5\leq N\leq 7$5≤N≤7,$\Delta ^{2}$Δ2denotes the biharmonic operator,$K(x), V(x)$K(x),V(x)are positive continuous functions which vanish at infinity, and$f(u)$f(u)is only a continuous function. We prove that the equation has a least energy sign-changing solution by the minimization argument on the sign-changing Nehari manifold. If, additionally,fis an odd function, we obtain that equation has infinitely many nontrivial solutions.
Sufficient and necessary conditions for oscillation of linear fractional-order delay differential equations
Authors: Meng Qiong , Jin Zhen , Liu Guirong 
Published: January 2021

AbstractThis paper studies the linear fractional-order delay differential equation$$ {}^{C}D^{\alpha }_{-}x(t)-px(t-\tau )= 0, $$D−αCx(t)−px(t−τ)=0,where$0<\alpha =\frac{\text{odd integer}}{\text{odd integer}}<1$0<α=odd integerodd integer<1,$p, \tau >0$p,τ>0,${}^{C}D_{-}^{\alpha }x(t)=-\Gamma ^{-1}(1-\alpha )\int _{t}^{\infty }(s-t)^{- \alpha }x'(s)\,ds$D−αCx(t)=−Γ−1(1−α)∫t∞(s−t)−αx′(s)ds. We obtain the conclusion that$$ p^{1/\alpha } \tau >\alpha /e $$p1/ατ>α/eis a sufficient and necessary condition of the oscillations for all solutions of Eq. (*). At the same time, some sufficient conditions are obtained for the oscillations of multiple delays linear fractional differential equation. Several examples are given to illustrate our theorems.
Study of composite fractional relaxation differential equation using fractional operators with and without singular kernels and special functions
Authors: Zafar Azhar Ali , Awrejcewicz Jan , Mazur Olga , Riaz Muhammad Bilal 
Published: January 2021

AbstractOur aim in this article is to solve the composite fractional relaxation differential equation by using different definitions of the non-integer order derivative operator $D_{t}^{\alpha }$

D
t
α

, more specifically we employ the definitions of Caputo, Caputo–Fabrizio and Atangana–Baleanu of non-integer order derivative operators. We apply the Laplace transform method to solve the problem and express our solutions in terms of Lorenzo and Hartley’s generalised G function. Furthermore, the effects of the parameters involved in the model are graphically highlighted.
Investigation of Diagonal Strut Actions in Masonry-Infilled Reinforced Concrete Frames
Authors: Lee Seung-Jae , Eom Tae-Sung , Yu Eunjong 
Published: January 2021

AbstractThis study analytically investigated the behavior of reinforced concrete frames with masonry infills. For the analysis, VecTor2, a nonlinear finite element analysis program that implements the Modified Compression Field Theory and Disturbed Stress Field Model, was used. To account for the slip behavior at the mortar joints in the masonry element, the hyperbolic Mohr–Coulomb yield criterion, defined as a function of cohesion and friction angle, was used. The analysis results showed that the lateral resistance and failure mode of the infilled frames were significantly affected by the thickness of the masonry infill, cohesion on the mortar joint–brick interface, and poor mortar filling (or gap) on the masonry boundary under the beam. Diagonal strut actions developed along two or three load paths on the mortar infill, including the backstay actions near the tension column and push-down actions near the compression columns. Such backstay and push-down actions increased the axial and shear forces of columns, and ultimately affect the strength, ductility, and failure mode of the infilled frames.
Right place, right time? Making crime pattern theory time-specific
Authors: van Sleeuwen Sabine E. M. , Ruiter Stijn , Steenbeek Wouter 
Published: January 2021

Abstract
Objectives
Crime pattern theory and the related empirical research have remained rather a-temporal, as if the timing of routine activities and crime plays no role. Building on previous geography of crime research, we extend crime pattern theory and propose that an offender’s spatial knowledge acquired during daily routine activities is not equally applicable to all times of day.

Methods
We put this extended theory to a first empirical test by applying a discrete spatial choice model to detailed information from the Netherlands on 71 offences committed by 30 offenders collected through a unique online survey instrument. The offenders reported on their most important activity nodes and offence locations over the past year, as well as the specific times they regularly visited these locations.

Results
The results show that almost 40% of the offences are committed within the neighbourhoods of offenders’ activity nodes, increasing to 85% when including first-, second- and third-order neighbourhoods. Though not statistically significant in our small sample, the results further suggest that offenders are more likely to commit crime in neighbourhoods they have regularly visited at the same time of day than in neighbourhoods they have regularly visited at different times of day.

Conclusion
Our extension of crime pattern theory is only tentatively supported. We argue for replication research with larger samples before any firm conclusions are warranted.
Spatial differentiation of metabolism in prostate cancer tissue by MALDI-TOF MSI
Authors: Andersen Maria K. , Høiem Therese S. , Claes Britt S. R. , Balluff Benjamin , Martin-Lorenzo Marta , Richardsen Elin , Krossa Sebastian , Bertilsson Helena , Heeren Ron M. A. , Rye Morten B. , Giskeødegård Guro F. , Bathen Tone F. , Tessem May-Britt 
Published: January 2021

Abstract
Background
Prostate cancer tissues are inherently heterogeneous, which presents a challenge for metabolic profiling using traditional bulk analysis methods that produce an averaged profile. The aim of this study was therefore to spatially detect metabolites and lipids on prostate tissue sections by using mass spectrometry imaging (MSI), a method that facilitates molecular imaging of heterogeneous tissue sections, which can subsequently be related to the histology of the same section.

Methods
Here, we simultaneously obtained metabolic and lipidomic profiles in different prostate tissue types using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MSI. Both positive and negative ion mode were applied to analyze consecutive sections from 45 fresh-frozen human prostate tissue samples (N = 15 patients). Mass identification was performed with tandem MS.

Results
Pairwise comparisons of cancer, non-cancer epithelium, and stroma revealed several metabolic differences between the tissue types. We detected increased levels of metabolites crucial for lipid metabolism in cancer, including metabolites involved in the carnitine shuttle, which facilitates fatty acid oxidation, and building blocks needed for lipid synthesis. Metabolites associated with healthy prostate functions, including citrate, aspartate, zinc, and spermine had lower levels in cancer compared to non-cancer epithelium. Profiling of stroma revealed higher levels of important energy metabolites, such as ADP, ATP, and glucose, and higher levels of the antioxidant taurine compared to cancer and non-cancer epithelium.

Conclusions
This study shows that specific tissue compartments within prostate cancer samples have distinct metabolic profiles and pinpoint the advantage of methodology providing spatial information compared to bulk analysis. We identified several differential metabolites and lipids that have potential to be developed further as diagnostic and prognostic biomarkers for prostate cancer. Spatial and rapid detection of cancer-related analytes showcases MALDI-TOF MSI as a promising and innovative diagnostic tool for the clinic.
A survey on generative adversarial networks for imbalance problems in computer vision tasks
Authors: Sampath Vignesh , Maurtua Iñaki , Aguilar Martín Juan José , Gutierrez Aitor 
Published: January 2021

AbstractAny computer vision application development starts off by acquiring images and data, then preprocessing and pattern recognition steps to perform a task. When the acquired images are highly imbalanced and not adequate, the desired task may not be achievable. Unfortunately, the occurrence of imbalance problems in acquired image datasets in certain complex real-world problems such as anomaly detection, emotion recognition, medical image analysis, fraud detection, metallic surface defect detection, disaster prediction, etc., are inevitable. The performance of computer vision algorithms can significantly deteriorate when the training dataset is imbalanced. In recent years, Generative Adversarial Neural Networks (GANs) have gained immense attention by researchers across a variety of application domains due to their capability to model complex real-world image data. It is particularly important that GANs can not only be used to generate synthetic images, but also its fascinating adversarial learning idea showed good potential in restoring balance in imbalanced datasets.In this paper, we examine the most recent developments of GANs based techniques for addressing imbalance problems in image data. The real-world challenges and implementations of synthetic image generation based on GANs are extensively covered in this survey. Our survey first introduces various imbalance problems in computer vision tasks and its existing solutions, and then examines key concepts such as deep generative image models and GANs. After that, we propose a taxonomy to summarize GANs based techniques for addressing imbalance problems in computer vision tasks into three major categories: 1. Image level imbalances in classification, 2. object level imbalances in object detection and 3. pixel level imbalances in segmentation tasks. We elaborate the imbalance problems of each group, and provide GANs based solutions in each group. Readers will understand how GANs based techniques can handle the problem of imbalances and boost performance of the computer vision algorithms.
Temporal evolutions of $$\text {N}_2^+$$ Meinel (1,2) band near $$1.5.\,\upmu \text {m}$$ associated with aurora breakup and their effects on mesopause temperature estimations from OH Meinel (3,1) band
Authors: Nishiyama Takanori , Taguchi Makoto , Suzuki Hidehiko , Dalin Peter , Ogawa Yasunobu , Brändström Urban , Sakanoi Takeshi 
Published: January 2021

AbstractWe have carried out ground-based NIRAS (Near-InfraRed Aurora and airglow Spectrograph) observations at Syowa station, Antarctic ($$69.0^{\circ }\text {S}$$

69
.

0
∘

S

, $$39.6^{\circ }\text {E}$$

39
.

6
∘

E

) and Kiruna ($$67.8^{\circ }\text {N}$$

67
.

8
∘

N

, $$20.4^{\circ }\text {E}$$

20
.

4
∘

E

), Sweden for continuous measurements of hydroxyl (OH) rotational temperatures and a precise evaluation of auroral contaminations to OH Meinel (3,1) band. A total of 368-nights observations succeeded for 2 winter seasons, and 3 cases in which $$\text {N}_2^+$$

N
2
+

Meinel (1,2) band around $$1.5\,\mu \text {m}$$

1.5

μ
m

was significant were identified. Focusing on two specific cases, detailed spectral characteristics with high temporal resolutions of 30 s are presented. Intensities of $$\text {N}_2^+$$

N
2
+

band were estimated to be 228 kR and 217 kR just at the moment of the aurora breakup and arc intensification during pseudo breakup, respectively. At a wavelength of $$\text {P}_1(2)$$

P
1

(
2
)

line ($$\sim 1523 \,\text {nm}$$

∼
1523

nm

), $$\text {N}_2^+$$

N
2
+

emissions were almost equal to or greater than the OH line intensity. On the other hand, at a wavelength of $$\text {P}_1(4)$$

P
1

(
4
)

line ($$\sim 1542 \,\text {nm}$$

∼
1542

nm

), the OH line was not seriously contaminated and still dominant to $$\text {N}_2^+$$

N
2
+

emissions. Furthermore, we evaluated $$\text {N}_2^+$$

N
2
+

(1,2) band effects on OH rotational temperature estimations quantitatively for the first time. Auroral contaminations from $$\text {N}_2^+$$

N
2
+

(1,2) band basically lead negative bias in OH rotational temperature estimated by line-pair-ratio method with $$\text {P}_1(2)$$

P
1

(
2
)

and $$\text {P}_1(4)$$

P
1

(
4
)

lines in OH (3,1) band. They possibly cause underestimations of OH rotational temperatures up to 40 K. In addition, $$\text {N}_2^+$$

N
2
+

(1,2) band contaminations were temporally limited to a moment around the aurora breakup. This is consistent with proceeding studies reporting that enhancements of $$\text {N}_2^+$$

N
2
+

(1,2) band were observed associated with International Brightness Coefficient 2–3 auroras. It is also suggested that the contaminations would be neglected in the polar cap and the sub-auroral zone, where strong aurora intensification is less observed. Further spectroscopic investigations at these wavelengths are needed especially for more precise evaluations of $$\text {N}_2^+$$

N
2
+

(1,2) band contaminations. For example, simultaneous 2-D imaging observation and spectroscopic measurement with high spectral resolutions for airglow in OH (3,1) band will make great advances in more robust temperature estimations in the auroral zone.
Unusual enhancement of ~ 30 MeV proton flux in an ICME sheath region
Authors: Oka Mitsuo , Obara Takahiro , Nitta Nariaki V. , Yashiro Seiji , Shiota Daikou , Ichimoto Kiyoshi 
Published: January 2021

AbstractIn gradual Solar Energetic Particle (SEP) events, shock waves driven by coronal mass ejections (CMEs) play a major role in accelerating particles, and the energetic particle flux enhances substantially when the shock front passes by the observer. Such enhancements are historically referred to as Energetic Storm Particle (ESP) events, but it remains unclear why ESP time profiles vary significantly from event to event. In some cases, energetic protons are not even clearly associated with shocks. Here, we report an unusual, short-duration proton event detected on 5 June 2011 in the compressed sheath region bounded by an interplanetary shock and the leading edge of the interplanetary CME (or ICME) that was driving the shock. While < 10 MeV protons were detected already at the shock front, the higher-energy (> 30 MeV) protons were detected about four hours after the shock arrival, apparently correlated with a turbulent magnetic cavity embedded in the ICME sheath region.
Estimation of relative source locations from seismic amplitude: application to earthquakes and tremors at Meakandake volcano, eastern Hokkaido, Japan
Authors: Ogiso Masashi , Yomogida Kiyoshi 
Published: January 2021

AbstractAlthough seismic amplitudes can be used to estimate event locations for volcanic tremors and other seismic events with unclear phase arrival times, the precision of such estimates is strongly affected by site amplification factors. Therefore, reduction of the influence of site amplification will allow more precise estimation of event locations by this method. Here, we propose a new method to estimate relative event locations using seismic amplitudes. We use the amplitude ratio between two seismic events at a given station to cancel out the effect of the site amplification factor at that station. By assuming that the difference between the hypocentral distances of these events is much smaller than their hypocentral distances themselves, we derive a system of linear equations for the differences in relative event locations. This formulation is similar to that of a master event location method that uses differences in phase arrival times. We applied our new method to earthquakes and tremors at Meakandake volcano, eastern Hokkaido, Japan. Comparison of the hypocentral distributions of volcano-tectonic earthquakes obtained thereby with those obtained from phase arrival times confirmed the validity of our new method. Moreover, our method clearly identified source migration among three source regions in the tremor on 16 November 2008, consistent with previous interpretations of other geophysical observations in our study area. Our method will thus be useful for detailed analyses of seismic events whose onset times are ambiguous.