bluuebunny/crossref_metadata_2025 huggingface dataset:
Homology-Based Interactions between Small RNAs and Their Targets Control Dominance Hierarchy of Male Determinant Alleles of Self-Incompatibility in Arabidopsis lyrata
Authors: Yasuda Shinsuke , Kobayashi Risa , Ito Toshiro , Wada Yuko , Takayama Seiji
Published: June 2021

Self-incompatibility (SI) is conserved among members of the Brassicaceae plant family. This trait is controlled epigenetically by the dominance hierarchy of the male determinant alleles. We previously demonstrated that a single small RNA (sRNA) gene is sufficient to control the linear dominance hierarchy in Brassica rapa and proposed a model in which a homology-based interaction between sRNAs and target sites controls the complicated dominance hierarchy of male SI determinants. In Arabidopsis halleri, male dominance hierarchy is reported to have arisen from multiple networks of sRNA target gains and losses. Despite these findings, it remains unknown whether the molecular mechanism underlying the dominance hierarchy is conserved among Brassicaceae. Here, we identified sRNAs and their target sites that can explain the linear dominance hierarchy of Arabidopsis lyrata, a species closely related to A. halleri. We tested the model that we established in Brassica to explain the linear dominance hierarchy in A. lyrata. Our results suggest that the dominance hierarchy of A. lyrata is also controlled by a homology-based interaction between sRNAs and their targets.
CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis
Authors: Loreth Desiree , Schuette Moritz , Zinke Jenny , Mohme Malte , Piffko Andras , Schneegans Svenja , Stadler Julia , Janning Melanie , Loges Sonja , Joosse Simon A. , Lamszus Katrin , Westphal Manfred , Müller Volkmar , Glatzel Markus , Matschke Jakob , Gebhardt Christoffer , Schneider Stefan W. , Belczacka Iwona , Volkmer Beate , Greinert Rüdiger , Yaspo Marie-Laure , Harter Patrick N. , Pantel Klaus , Wikman Harriet
Published: June 2021

Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies.
Macrophage Polarization States in the Tumor Microenvironment
Authors: Boutilier Ava J. , Elsawa Sherine F.
Published: June 2021

The M1/M2 macrophage paradigm plays a key role in tumor progression. M1 macrophages are historically regarded as anti-tumor, while M2-polarized macrophages, commonly deemed tumor-associated macrophages (TAMs), are contributors to many pro-tumorigenic outcomes in cancer through angiogenic and lymphangiogenic regulation, immune suppression, hypoxia induction, tumor cell proliferation, and metastasis. The tumor microenvironment (TME) can influence macrophage recruitment and polarization, giving way to these pro-tumorigenic outcomes. Investigating TME-induced macrophage polarization is critical for further understanding of TAM-related pro-tumor outcomes and potential development of new therapeutic approaches. This review explores the current understanding of TME-induced macrophage polarization and the role of M2-polarized macrophages in promoting tumor progression.
Analysis and Functional Verification of PoWRI1 Gene Associated with Oil Accumulation Process in Paeonia ostii
Authors: Sun Jing , Chen Tian , Liu Mi , Zhao Daqiu , Tao Jun
Published: June 2021

The plant transcription factor WRINKLED1 (WRI1), a member of AP2/EREBP, is involved in the regulation of glycolysis and the expression of genes related to the de novo synthesis of fatty acids in plastids. In this study, the key regulator of seed oil synthesis and accumulation transcription factor gene PoWRI1 was identified and cloned, having a complete open reading frame of 1269 bp and encoding 422 amino acids. Subcellular localization analysis showed that PoWRI1 is located at the nucleus. After the expression vector of PoWRI1 was constructed and transformed into wild-type Arabidopsis thaliana, it was found that the overexpression of PoWRI1 increased the expression level of downstream target genes such as BCCP2, KAS1, and PKP-β1. As a result, the seeds of transgenic plants became larger, the oil content increased significantly, and the unsaturated fatty acid content increased, which provide a scientific theoretical basis for the subsequent use of genetic engineering methods to improve the fatty acid composition and content of plant seeds.
Drug Evaluation Based on a Multi-Channel Cell Chip with a Horizontal Co-Culture
Authors: Kim Gyeong-Ji , Lee Kwon-Jai , Choi Jeong-Woo , An Jeung Hee
Published: June 2021

We developed a multi-channel cell chip containing a three-dimensional (3D) scaffold for horizontal co-culture and drug toxicity screening in multi-organ culture (human glioblastoma, cervical cancer, normal liver cells, and normal lung cells). The polydimethylsiloxane (PDMS) multi-channel cell chip (PMCCC) was based on fused deposition modeling (FDM) technology. The architecture of the PMCCC was an open-type cell chip and did not require a pump or syringe. We investigated cell proliferation and cytotoxicity by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and analysis of oleanolic acid (OA)-treated multi-channel cell chips. The results of the MTT and LDH assays showed that OA treatment in the multi-channel cell chip of four cell lines enhanced chemoresistance of cells compared with that in the 2D culture. Furthermore, we demonstrated the feasibility of the application of our multi-channel cell chip in various analysis methods through Annexin V-fluorescein isothiocyanate/propidium iodide staining, which is not used for conventional cell chips. Taken together, the results demonstrated that the PMCCC may be used as a new 3D platform because it enables simultaneous drug screening in multiple cells by single point injection and allows analysis of various biological processes.
Investigation of the Detailed AMPylated Reaction Mechanism for the Huntingtin Yeast-Interacting Protein E Enzyme HYPE
Authors: Liu Meili , Huai Zhe , Tan Hongwei , Chen Guangju
Published: June 2021

AMPylation is a prevalent posttranslational modification that involves the addition of adenosine monophosphate (AMP) to proteins. Exactly how Huntingtin-associated yeast-interacting protein E (HYPE), as the first human protein, is involved in the transformation of the AMP moiety to its substrate target protein (the endoplasmic reticulum chaperone binding to immunoglobulin protein (BiP)) is still an open question. Additionally, a conserved glutamine plays a vital key role in the AMPylation reaction in most filamentation processes induced by the cAMP (Fic) protein. In the present work, the detailed catalytic AMPylation mechanisms in HYPE were determined based on the density functional theory (DFT) method. Molecular dynamics (MD) simulations were further used to investigate the exact role of the inhibitory glutamate. The metal center, Mg2+, in HYPE has been examined in various coordination configurations, including 4-coordrinated, 5-coordinated and 6-coordinated. DFT calculations revealed that the transformation of the AMP moiety of HYPE with BiP followed a sequential pathway. The model with a 4-coordinated metal center had a barrier of 14.7 kcal/mol, which was consistent with the experimental value and lower than the 38.7 kcal/mol barrier of the model with a 6-coordinated metal center and the 31.1 kcal/mol barrier of the model with a 5-coordinated metal center. Furthermore, DFT results indicated that Thr518 residue oxygen directly attacks the phosphorus, while the His363 residue acts as H-bond acceptor. At the same time, an MD study indicated that Glu234 played an inhibitory role in the α-inhibition helix by regulating the hydrogen bond interaction between Arg374 and the Pγ of the ATP molecule. The revealed sequential pathway and the inhibitory role of Glu234 in HYPE were inspirational for understanding the catalytic and inhibitory mechanisms of Fic-mediated AMP transfer, paving the way for further studies on the physiological role of Fic enzymes.
Effect of Endothelial Culture Medium Composition on Platelet Responses to Polymeric Biomaterials
Authors: Lau Skadi , Maier Anna , Braune Steffen , Gossen Manfred , Lendlein Andreas
Published: June 2021

Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT.
Bifunctional Role of CrkL during Bone Remodeling
Authors: Kim Jung Ha , Kim Kabsun , Kim Inyoung , Seong Semun , Kook Hyun , Kim Kyung Keun , Koh Jeong-Tae , Kim Nacksung
Published: June 2021

Coupled signaling between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial to the maintenance of bone homeostasis. We previously reported that v-crk avian sarcoma virus CT10 oncogene homolog-like (CrkL), which belongs to the Crk family of adaptors, inhibits bone morphogenetic protein 2 (BMP2)-mediated osteoblast differentiation, while enhancing receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated whether CrkL can also regulate the coupling signals between osteoblasts and osteoclasts, facilitating bone homeostasis. Osteoblastic CrkL strongly decreased RANKL expression through its inhibition of runt-related transcription factor 2 (Runx2) transcription. Reduction in RANKL expression by CrkL in osteoblasts resulted in the inhibition of not only osteoblast-dependent osteoclast differentiation but also osteoclast-dependent osteoblast differentiation, suggesting that CrkL participates in the coupling signals between osteoblasts and osteoclasts via its regulation of RANKL expression. Therefore, CrkL bifunctionally regulates osteoclast differentiation through both a direct and indirect mechanism while it inhibits osteoblast differentiation through its blockade of both BMP2 and RANKL reverse signaling pathways. Collectively, these data suggest that CrkL is involved in bone homeostasis, where it helps to regulate the complex interactions of the osteoblasts, osteoclasts, and their coupling signals.
Calcium-Deficiency during Pregnancy Affects Insulin Resistance in Offspring
Authors: Takaya Junji
Published: June 2021

Prenatal malnutrition is known to affect the phenotype of the offspring through changes in epigenetic regulation. Growing evidence suggests that epigenetics is one of the mechanisms by which nutrients and minerals affect metabolic traits. Although the perinatal period is the time of highest phenotypic plasticity, which contributes largely to developmental programming, there is evidence of nutritional influence on epigenetic regulation during adulthood. Calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. Cortisol, the most important glucocorticoid, is considered to lead to insulin resistance and metabolic syndrome. 11β-hydroxysteroid dehydrogenase-1 is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. This brief review aims to identify the effects of Ca deficiency during pregnancy and/or lactation on insulin resistance in the offspring. Those findings demonstrate that maternal Ca deficiency during pregnancy may affect the epigenetic regulation of gene expression and thereby induce different metabolic phenotypes. We aim to address the need for Ca during pregnancy and propose the scaling-up of clinical and public health approaches that improved pregnancy outcomes.
Immune Aging and Immunotherapy in Cancer
Authors: Kaiser Melanie , Semeraro Maria Donatella , Herrmann Markus , Absenger Gudrun , Gerger Armin , Renner Wilfried
Published: June 2021

Immune functions decline as we age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy, but also spawned great interest in identifying predictive biomarkers, since only one third of patients show treatment response. The aging process extensively affects the adaptive immune system and thus T cells, which are the main target of ICB. In this review, we address age-related changes regarding the adaptive immune system with a focus on T cells and their implication on carcinogenesis and ICB. Differences between senescence, exhaustion, and anergy are defined and current knowledge, treatment strategies, and studies exploring T cell aging as a biomarker for ICB are discussed. Finally, novel approaches to improve immunotherapies and to identify biomarkers of response to ICB are presented and their potential is assessed in a comparative analysis.
Extending the Toolkit for Beauty: Differential Co-Expression of DROOPING LEAF-Like and Class B MADS-Box Genes during Phalaenopsis Flower Development
Authors: Lucibelli Francesca , Valoroso Maria , Theißen Günter , Nolden Susanne , Mondragon-Palomino Mariana , Aceto Serena
Published: June 2021

The molecular basis of orchid flower development is accomplished through a specific regulatory program in which the class B MADS-box AP3/DEF genes play a central role. In particular, the differential expression of four class B AP3/DEF genes is responsible for specification of organ identities in the orchid perianth. Other MADS-box genes (AGL6 and SEP-like) enrich the molecular program underpinning the orchid perianth development, resulting in the expansion of the original “orchid code” in an even more complex gene regulatory network. To identify candidates that could interact with the AP3/DEF genes in orchids, we conducted an in silico differential expression analysis in wild-type and peloric Phalaenopsis. The results suggest that a YABBY DL-like gene could be involved in the molecular program leading to the development of the orchid perianth, particularly the labellum. Two YABBY DL/CRC homologs are present in the genome of Phalaenopsis equestris, PeDL1 and PeDL2, and both express two alternative isoforms. Quantitative real-time PCR analyses revealed that both genes are expressed in column and ovary. In addition, PeDL2 is more strongly expressed the labellum than in the other tepals of wild-type flowers. This pattern is similar to that of the AP3/DEF genes PeMADS3/4 and opposite to that of PeMADS2/5. In peloric mutant Phalaenopsis, where labellum-like structures substitute the lateral inner tepals, PeDL2 is expressed at similar levels of the PeMADS2-5 genes, suggesting the involvement of PeDL2 in the development of the labellum, together with the PeMADS2-PeMADS5 genes. Although the yeast two-hybrid analysis did not reveal the ability of PeDL2 to bind the PeMADS2-PeMADS5 proteins directly, the existence of regulatory interactions is suggested by the presence of CArG-boxes and other MADS-box transcription factor binding sites within the putative promoter of the orchid DL2 gene.
Therapeutic Effect of a Newly Isolated Lytic Bacteriophage against Multi-Drug-Resistant Cutibacterium acnes Infection in Mice
Authors: Lam Ho Yin Pekkle , Lai Meng-Jiun , Chen Ting-Yu , Wu Wen-Jui , Peng Shih-Yi , Chang Kai-Chih
Published: June 2021

Acne vulgaris, which is mostly associated with the colonization of Cutibacterium acnes (C. acnes), is a common skin inflammatory disease in teenagers. However, over the past few years, the disease has extended beyond childhood to chronically infect approximately 40% of adults. While antibiotics have been used for several decades to treat acne lesions, antibiotic resistance is a growing crisis; thus, finding a new therapeutic target is urgently needed. Studies have shown that phage therapy may be one alternative for treating multi-drug-resistant bacterial infections. In the present study, we successfully isolated a C. acnes phage named TCUCAP1 from the skin of healthy volunteers. Morphological analysis revealed that TCUCAP1 belongs to the family Siphoviridae with an icosahedral head and a non-contractile tail. Genome analysis found that TCUCAP1 is composed of 29,547 bp with a G+C content of 53.83% and 56 predicted open reading frames (ORFs). The ORFs were associated with phage structure, packing, host lysis, DNA metabolism, and additional functions. Phage treatments applied to mice with multi-drug-resistant (MDR) C.-acnes-induced skin inflammation resulted in a significant decrease in inflammatory lesions. In addition, our attempt to formulate the phage into hydroxyethyl cellulose (HEC) cream may provide new antibacterial preparations for human infections. Our results demonstrate that TCUCAP1 displays several features that make it an ideal candidate for the control of C. acnes infections.
Molecular and Neural Mechanism of Dysphagia Due to Cancer
Authors: Okuni Ikuko , Otsubo Yuta , Ebihara Satoru
Published: June 2021

Cancer is one of the most common causes of death worldwide. Along with the advances in diagnostic technology achieved through industry–academia partnerships, the survival rate of cancer patients has improved dramatically through treatments that include surgery, radiation therapy, and pharmacotherapy. This has increased the population of cancer “survivors” and made cancer survivorship an important part of life for patients. The senses of taste and smell during swallowing and cachexia play important roles in dysphagia associated with nutritional disorders in cancer patients. Cancerous lesions in the brain can cause dysphagia. Taste and smell disorders that contribute to swallowing can worsen or develop because of pharmacotherapy or radiation therapy; metabolic or central nervous system damage due to cachexia, sarcopenia, or inflammation can also cause dysphagia. As the causes of eating disorders in cancer patients are complex and involve multiple factors, cancer patients require a multifaceted and long-term approach by the medical care team.
Interactions of Chemically Synthesized Ferrihydrite Nanoparticles with Human Serum Transferrin: Insights from Fluorescence Spectroscopic Studies
Authors: Chilom Claudia G. , Sandu Nicoleta , Iftimie Sorina , Bălăşoiu Maria , Rogachev Andrey , Orelovich Oleg , Stolyar Sergey
Published: June 2021

Human serum transferrin (HST) is a glycoprotein involved in iron transport that may be a candidate for functionalized nanoparticles to bind and target cancer cells. In this study, the effects of the simple and doped with cobalt (Co) and copper (Cu) ferrihydrite nanoparticles (Fh-NPs, Cu-Fh-NPs, and Co-Fh-NPs) were studied by spectroscopic and molecular approaches. Fluorescence spectroscopy revealed a static quenching mechanism for all three types of Fh-NPs. All Fh-NPs interacted with HST with low affinity, and the binding was driven by hydrogen bonding and van der Waals forces for simple Fh-NPs and by hydrophobic interactions for Cu-Fh-NPs and Co-Fh-NPs binding, respectively. Of all samples, simple Fh-NPs bound the most to the HST binding site. Fluorescence resonance energy transfer (FRET) allowed the efficient determination of the energy transfer between HST and NPs and the distance at which the transfer takes place and confirmed the mechanism of quenching. The denaturation of the HST is an endothermic process, both in the case of apo HST and HST in the presence of the three types of Fh-NPs. Molecular docking studies revealed that Fh binds with a low affinity to HST (Ka = 9.17 × 103 M−1) in accord with the fluorescence results, where the interaction between simple Fh-NPs and HST was described by a binding constant of 9.54 × 103 M−1.
Newborn Screening for Congenital Hypothyroidism in Japan
Authors: Minamitani Kanshi
Published: June 2021

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual impairment or failure to thrive by early identification and treatment. In Japan, newborn screening programs for CH were introduced in 1979, and the clinical guidelines for newborn screening of CH were developed in 1998, revised in 2014, and are currently undergoing further revision. Newborn screening strategies are designed to detect the elevated levels of thyroid stimulating hormone (TSH) in most areas of Japan, although TSH and free thyroxine (FT4) are often measured simultaneously in some areas. Since 1987, in order not to observe the delayed rise in TSH, additional rescreening of premature neonates and low birth weight infants (<2000 g) at four weeks of life or when their body weight reaches 2500 g has been recommended, despite a normal initial newborn screening. Recently, the actual incidence of CH has doubled to approximately 1:2500 in Japan as in other countries. This increasing incidence is speculated to be mainly due to an increase in the number of mildly affected patients detected by the generalized lowering of TSH screening cutoffs and an increase in the number of preterm or low birth weight neonates at a higher risk of having CH than term infants.
An Online Iterative Linear Quadratic Approach for a Satisfactory Working Point Attainment at FERMI
Authors: Bruchon Niky , Fenu Gianfranco , Gaio Giulio , Hirlander Simon , Lonza Marco , Pellegrino Felice Andrea , Salvato Erica
Published: June 2021

The attainment of a satisfactory operating point is one of the main problems in the tuning of particle accelerators. These are extremely complex facilities, characterized by the absence of a model that accurately describes their dynamics, and by an often persistent noise which, along with machine drifts, affects their behaviour in unpredictable ways. In this paper, we propose an online iterative Linear Quadratic Regulator (iLQR) approach to tackle this problem on the FERMI free-electron laser of Elettra Sincrotrone Trieste. It consists of a model identification performed by a neural network trained on data collected from the real facility, followed by the application of the iLQR in a Model-Predictive Control fashion. We perform several experiments, training the neural network with increasing amount of data, in order to understand what level of model accuracy is needed to accomplish the task. We empirically show that the online iLQR results, on average, in fewer steps than a simple gradient ascent (GA), and requires a less accurate neural network to achieve the goal.
Combine-Net: An Improved Filter Pruning Algorithm
Authors: Wang Jinghan , Li Guangyue , Zhang Wenzhao
Published: June 2021

The powerful performance of deep learning is evident to all. With the deepening of research, neural networks have become more complex and not easily generalized to resource-constrained devices. The emergence of a series of model compression algorithms makes artificial intelligence on edge possible. Among them, structured model pruning is widely utilized because of its versatility. Structured pruning prunes the neural network itself and discards some relatively unimportant structures to compress the model’s size. However, in the previous pruning work, problems such as evaluation errors of networks, empirical determination of pruning rate, and low retraining efficiency remain. Therefore, we propose an accurate, objective, and efficient pruning algorithm—Combine-Net, introducing Adaptive BN to eliminate evaluation errors, the Kneedle algorithm to determine the pruning rate objectively, and knowledge distillation to improve the efficiency of retraining. Results show that, without precision loss, Combine-Net achieves 95% parameter compression and 83% computation compression on VGG16 on CIFAR10, 71% of parameter compression and 41% computation compression on ResNet50 on CIFAR100. Experiments on different datasets and models have proved that Combine-Net can efficiently compress the neural network’s parameters and computation.
Visual Active Learning for Labeling: A Case for Soundscape Ecology Data
Authors: Hilasaca Liz Huancapaza , Ribeiro Milton Cezar , Minghim Rosane
Published: June 2021

Labeling of samples is a recurrent and time-consuming task in data analysis and machine learning and yet generally overlooked in terms of visual analytics approaches to improve the process. As the number of tailored applications of learning models increases, it is crucial that more effective approaches to labeling are developed. In this paper, we report the development of a methodology and a framework to support labeling, with an application case as background. The methodology performs visual active learning and label propagation with 2D embeddings as layouts to achieve faster and interactive labeling of samples. The framework is realized through SoundscapeX, a tool to support labeling in soundscape ecology data. We have applied the framework to a set of audio recordings collected for a Long Term Ecological Research Project in the Cantareira-Mantiqueira Corridor (LTER CCM), localized in the transition between northeastern São Paulo state and southern Minas Gerais state in Brazil. We employed a pre-label data set of groups of animals to test the efficacy of the approach. The results showed the best accuracy at 94.58% in the prediction of labeling for birds and insects; and 91.09% for the prediction of the sound event as frogs and insects.
Improving Imbalanced Land Cover Classification with K-Means SMOTE: Detecting and Oversampling Distinctive Minority Spectral Signatures
Authors: Fonseca Joao , Douzas Georgios , Bacao Fernando
Published: June 2021

Land cover maps are a critical tool to support informed policy development, planning, and resource management decisions. With significant upsides, the automatic production of Land Use/Land Cover maps has been a topic of interest for the remote sensing community for several years, but it is still fraught with technical challenges. One such challenge is the imbalanced nature of most remotely sensed data. The asymmetric class distribution impacts negatively the performance of classifiers and adds a new source of error to the production of these maps. In this paper, we address the imbalanced learning problem, by using K-means and the Synthetic Minority Oversampling Technique (SMOTE) as an improved oversampling algorithm. K-means SMOTE improves the quality of newly created artificial data by addressing both the between-class imbalance, as traditional oversamplers do, but also the within-class imbalance, avoiding the generation of noisy data while effectively overcoming data imbalance. The performance of K-means SMOTE is compared to three popular oversampling methods (Random Oversampling, SMOTE and Borderline-SMOTE) using seven remote sensing benchmark datasets, three classifiers (Logistic Regression, K-Nearest Neighbors and Random Forest Classifier) and three evaluation metrics using a five-fold cross-validation approach with three different initialization seeds. The statistical analysis of the results show that the proposed method consistently outperforms the remaining oversamplers producing higher quality land cover classifications. These results suggest that LULC data can benefit significantly from the use of more sophisticated oversamplers as spectral signatures for the same class can vary according to geographical distribution.
Distributed Hypothesis Testing over Noisy Broadcast Channels
Authors: Salehkalaibar Sadaf , Wigger Michèle
Published: June 2021

This paper studies binary hypothesis testing with a single sensor that communicates with two decision centers over a memoryless broadcast channel. The main focus lies on the tradeoff between the two type-II error exponents achievable at the two decision centers. In our proposed scheme, we can partially mitigate this tradeoff when the transmitter has a probability larger than 1/2 to distinguish the alternate hypotheses at the decision centers, i.e., the hypotheses under which the decision centers wish to maximize their error exponents. In the cases where these hypotheses cannot be distinguished at the transmitter (because both decision centers have the same alternative hypothesis or because the transmitter’s observations have the same marginal distribution under both hypotheses), our scheme shows an important tradeoff between the two exponents. The results in this paper thus reinforce the previous conclusions drawn for a setup where communication is over a common noiseless link. Compared to such a noiseless scenario, here, however, we observe that even when the transmitter can distinguish the two hypotheses, a small exponent tradeoff can persist, simply because the noise in the channel prevents the transmitter to perfectly describe its guess of the hypothesis to the two decision centers.
Literature Review of Location-Based Mobile Games in Education: Challenges, Impacts and Opportunities
Authors: Ribeiro Fernando Reinaldo , Silva Arlindo , Silva Ana Paula , Metrôlho José
Published: June 2021

With the universal use of mobile computing devices, there has been a notable increase in the number of mobile applications developed for educational purposes. Gamification strategies offer a new set of tools to educators and, combined with the location services provided by those devices, allow the creation of innovative location-based mobile learning experiences. In this literature review, we conduct an analysis of educational mobile location-based games. The review includes articles published from January of 2010 to October of 2020, and from 127 records screened, 26 articles were analysed in full-text form. This analysis allowed us to answer the following six predefined research questions: Who are the target audiences for location-based games? In which subjects are location-based games most used? Which strategies are implemented with mobile devices to improve the student’s learning process? What are the main impacts of location-based games on students’ learning? What are the main challenges to the development of location-based games for education? What future tendencies and research opportunities can be identified from the analysis of the current state of the art?
A Dy(III) Fluorescent Single-Molecule Magnet Based on a Rhodamine 6G Ligand
Authors: Miao Lin , Liu Mei-Jiao , Ding Man-Man , Zhang Yi-Quan , Kou Hui-Zhong
Published: June 2021

The complexes of lanthanide metals, especially dysprosium, can generally exhibit excellent magnetic properties. By means of modifying ligands, dual functions or even multi-functions can be achieved. Here, we synthesized an eight-coordinate Dy(III) complex 1, [Dy(HL-o)2(MeOH)2](ClO4)3·4.5MeOH, which is single-molecule magnet (SMM), and the introduction of the rhodamine 6G chromophore in the ring-opened ligand HL-o realizes ligand-centered fluorescence in addition to SMM. Magnetic measurements and ab initio calculations indicate that the magnetic relaxation for complex 1 should be due to the Raman relaxation process. Studies on magneto-structural correlationship of the rhodamine salicylaldehyde hydrazone Dy(III) complexes show that the calculated energy of the first Kramers Doublet (EKD1) is basically related to the Ophenoxy-Dy-Ophenoxy bond angle, i.e., the larger Ophenoxy-Dy-Ophenoxy bond angle corresponds to a larger EKD1.
Annotating the Insect Regulatory Genome
Authors: Asma Hasiba , Halfon Marc S.
Published: June 2021

An ever-growing number of insect genomes is being sequenced across the evolutionary spectrum. Comprehensive annotation of not only genes but also regulatory regions is critical for reaping the full benefits of this sequencing. Driven by developments in sequencing technologies and in both empirical and computational discovery strategies, the past few decades have witnessed dramatic progress in our ability to identify cis-regulatory modules (CRMs), sequences such as enhancers that play a major role in regulating transcription. Nevertheless, providing a timely and comprehensive regulatory annotation of newly sequenced insect genomes is an ongoing challenge. We review here the methods being used to identify CRMs in both model and non-model insect species, and focus on two tools that we have developed, REDfly and SCRMshaw. These resources can be paired together in a powerful combination to facilitate insect regulatory annotation over a broad range of species, with an accuracy equal to or better than that of other state-of-the-art methods.
Efficacy of Two Neonicotinoid Insecticides against Invasive Wood Borer Aromia bungii Larvae in Dietary Toxicity Test
Authors: Sunamura Eiriki , Tamura Shigeaki , Taki Hisatomo , Sato Hiroki , Shoda-Kagaya Etsuko , Urano Tadahisa
Published: June 2021

In recent years, insecticide trunk injection was put into practical use for controlling wood boring pests. However, few studies have investigated the dose–response relationships between insecticides and wood–boring pests in detail. This study used two commercial formulations of the neonicotinoid insecticides thiamethoxam and dinotefuran and investigated their dose–response relationships with invasive wood borer Aromia bungii (Coleoptera: Cerambycidae) larvae. Neonates and late instar larvae were reared with an artificial diet containing different insecticide concentrations (0.01–100 ppm) in the laboratory, and their diet excavation activity, survival rate, and weight change were recorded. Diet excavation immediately dropped in larvae exposed to high concentrations of thiamethoxam or dinotefuran (≥1 ppm in neonates and ≥10 ppm in late instar larvae). The weight and survival rate gradually declined over 12 weeks in late instar larvae. These results suggest that the two neonicotinoids intoxicate and debilitate A. bungii larvae gradually to death. In practical use, rapid suppression of A. bungii wood boring damage can be expected by trunk injection of neonicotinoid insecticides. However, a relatively long-term retention of the insecticides may be required to kill large larvae. Neonates may be controlled with lower insecticide dosage and shorter exposure than larger larvae.
Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma
Authors: Czauderna Carolin , Kirstein Martha M. , Tews Hauke C. , Vogel Arndt , Marquardt Jens U.
Published: June 2021

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.
Bevacizumab Arrests Osteoarthritis Progression in a Rabbit Model: A Dose-Escalation Study
Authors: Vadalà Gianluca , Ambrosio Luca , Cattani Caterina , Bernardini Roberta , Giacalone Antonino , Papalia Rocco , Denaro Vincenzo
Published: June 2021

Cartilage neoangiogenesis holds a prominent role in osteoarthritis (OA) pathogenesis. This study aimed to assess the efficacy bevacizumab, an antibody against vascular endothelial growth factor and inhibitor of angiogenesis, in a rabbit OA model. Animals were divided into four groups: one receiving a sham intra-articular knee injection and three groups undergoing 5, 10, and 20 mg intra-articular bevacizumab injections. The effect of the antibody on articular cartilage and synovium was assessed through histology and quantified with the Osteoarthritis Research Society International (OARSI) scores. Immunohistochemistry was performed to investigate type 2 collagen, aggrecan, and matrix metalloproteinase 13 (MMP-13) expression. Bevacizumab treatment led to a significant reduction of cartilage degeneration and synovial OA changes. Immunohistochemistry revealed significantly lower cartilage MMP-13 expression levels in all experimental groups, with the one receiving 20 mg bevacizumab showing the lowest. The antibody also resulted in increased production of aggrecan and type 2 collagen after administration of 5, 10, and 20 mg. The group treated with 20 mg showed the highest levels of type 2 collagen, while aggrecan content was even higher than in the healthy cartilage. Intra-articular bevacizumab has been demonstrated to effectively arrest OA progression in our model, with 20 mg being the most efficacious dose.
Anti-Inflammatory Drugs in Patients with Ischemic Heart Disease
Authors: Pello Lázaro Ana María , Blanco-Colio Luis M. , Franco Peláez Juan Antonio , Tuñón José
Published: June 2021

Inflammation has long been known to play a role in atherogenesis and plaque complication, as well as in some drugs used in therapy for atherosclerotic disease, such as statins, acetylsalicylic acid, and modulators of the renin-angiotensin system, which also have anti-inflammatory effects. Furthermore, inflammatory biomarkers have been demonstrated to predict the incidence of cardiovascular events. In spite of this, and with the exception of acetylsalicylic acid, non-steroidal anti-inflammatory drugs are unable to decrease the incidence of cardiovascular events and may even be harmful to the cardiovascular system. In recent years, other anti-inflammatory drugs, such as canakinumab and colchicine, have shown an ability to reduce the incidence of cardiovascular events in secondary prevention. Colchicine could be a potential candidate for use in clinical practice given its safety and low price, although the results of temporary studies require confirmation in large randomized clinical trials. In this paper, we discuss the evidence linking inflammation with atherosclerosis and review the results from various clinical trials performed with anti-inflammatory drugs. We also discuss the potential use of these drugs in routine clinical settings.
Systemic Adverse Events and Use of Antipyretics Predict the Neutralizing Antibody Positivity Early after the First Dose of ChAdOx1 Coronavirus Disease Vaccine
Authors: Park Ji Young , Choi Seong-Ho , Chung Jin-Won , Hwang Min-Hyung , Kim Min-Chul
Published: June 2021

Vaccination is considered crucial for the eradication of the coronavirus disease (COVID-19). In our medical center in Korea, most health care workers (HCWs) were vaccinated with the ChAdOx1 COVID-19 vaccine. After vaccination, many HCWs complained of adverse events (AEs). However, it remains unclear whether the production of neutralizing antibodies (NAb) was affected. Therefore, here, we aimed to evaluate AEs and early NAb production in relatively healthy Asians who received the ChAdOx1 vaccine and determine the effect of AEs and antipyretics on early NAb production against COVID-19. Of the 182 Korean HCWs who received the first dose of ChAdOx1 vaccine, 172 (94.5%) experienced ≥1 adverse events and 148 (81.3%) tested positive for NAb 33–40 days after the vaccination. NAb-positive vaccine recipients reported systemic AEs and consumed acetaminophen more frequently than NAb-negative recipients. We identified an association between antibody response and COVID-19 vaccine-related AEs. In conclusion, most ChAdOx1 vaccine recipients reported AEs in our medical center.
Conduction Disorders during Sinus Rhythm in Relation to Atrial Fibrillation Persistence
Authors: van der Does Willemijn F. B. , Heida Annejet , van der Does Lisette J. M. E. , Bogers Ad J. J. C. , de Groot Natasja M. S.
Published: June 2021

Classification of atrial fibrillation (AF) is currently based on clinical characteristics. However, classifying AF using an objective electrophysiological parameter would be more desirable. The aim of this study was to quantify parameters of atrial conduction during sinus rhythm (SR) using an intra-operative high-resolution epicardial mapping approach and to relate these parameters to clinical classifications of AF. Patients were divided according to the standard clinical classification and spontaneous termination of AF episodes. The HATCH score, a score predictive of AF progression, was calculated, and surface ECGs were evaluated for signs of interatrial block. Conduction disorders mainly differed at Bachmann’s bundle (BB). Activation time (AT) at BB was longer in persistent AF patients (AT-BB: 75 (53–92) ms vs. 55 (40–76) ms, p = 0.017), patients without spontaneous termination of AF episodes (AT-BB: 53.5 (39.6–75.8) ms vs. 72.0 (49.6–80.8) ms, p = 0.009) and in patients with a P-wave duration ≥ 120 ms (64.3 (52.3–93.0) ms vs. 50.5 (39.6–56.6) ms, p = 0.014). HATCH scores also correlated positively to AT-BB (rho 0.326, p = 0.029). However, discriminatory values of electrophysiological parameters, as calculated using ROC-curves, were limited. These results may reflect shortcomings of clinical classifications and further research is needed to establish an objective substrate-based classification of AF.
Quality of Life in European Older Adults of SHARE Wave 7: Comparing the Old and the Oldest-Old
Authors: Oliver Amparo , Sentandreu-Mañó Trinidad , Tomás José M. , Fernández Irene , Sancho Patricia
Published: June 2021

CASP-12 (Control, Autonomy, Self-realization, and Pleasure scale) is one of the most common internationally used measures for quality of life in older adults, although its structure is not clearly established. Current research aims to test the factor structure of the CASP-12, so as to provide evidence on reliability and external validity, and to test for measurement invariance across age groups. Data from 61,355 Europeans (≥60 years old) from the Survey of Health, Ageing and Retirement in Europe wave 7 were used. CASP-12, EURO-D (European depression scale), self-perceived health, and life satisfaction measurements were included. Reliability and validity coefficients, competing confirmatory factor models, and standard measurement invariance routine were estimated. A second-order factor model with the original factor structure was retained. The scale showed adequate reliability coefficients except for the autonomy dimension. The correlation coefficients for external validity were all statistically significant. Finally, CASP-12 is scalar invariant across age. We conclude that the best-fitting factor structure retained allows using CASP-12 either by factors, or as an overall score, depending on the research interests. Findings related to CASP-12 measurement invariance encourage its use in the oldest-old too. When comparing the dimensions across age groups, as people age, autonomy slightly increases and the rest of the dimensions decline.
Usefulness of the Novel Snare-over-the-Guidewire Method for Transpapillary Plastic Stent Replacement (with Video)
Authors: Yoshida Akihiro , Takenaka Mamoru , Takashima Kota , Tanaka Hidekazu , Okamoto Ayana , Yamazaki Tomohiro , Nakai Atsushi , Omoto Shunsuke , Minaga Kosuke , Kamata Ken , Yamao Kentaro , Komeda Yoriaki , Nishida Naoshi , Kudo Masatoshi
Published: June 2021

Unsuccessful stent replacement in transpapillary biliary drainage with plastic stents (PSs) has a significant impact on patient prognosis; thus, a safe and reliable replacement method is required. We aimed to compare the snare-over-the-guidewire (SOG) method, wherein the PS lumen is used as an access route to the biliary tract and the PS is removed with a snare inserted via the inserted guidewire, with the conventional side-of-stent (SOS) method, wherein the biliary approach is performed from the side of the PS. This retrospective single-center study included 244 consecutive patients who underwent biliary PS replacement between January 2018 and July 2020. The procedural success rates were compared between the two methods. A predictive analysis of unsuccessful PS replacement was also performed. The procedural success rate in the SOG group was significantly higher than that in the SOS group (p = 0.026). In the proximal biliary stenosis lesion, the same trend was observed (p = 0.025). Multivariate analysis also showed that the SOS method (p = 0.0038), the presence of proximal biliary stenosis (p < 0.0001), and parapapillary diverticulum (p = 0.0007) were predictors of unsuccessful PS replacement. The SOG method may be useful for biliary PS replacement, especially in cases of proximal hilar bile duct stenosis.