bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs
Authors: Patial Sonika , Lewis Brandon W. , Vo Thao , Choudhary Ishita , Paudel Kshitiz , Mao Yun , Singamsetty Dhruthi , Brombacher Frank , Saini Yogesh 
Published: July 2021

AbstractIncreased eosinophil recruitment is a hallmark feature of eosinophilic disorders. Here, we delineated the key molecular and cellular players involved in physiological eosinophilic recruitment during normal postnatal lung development in mice. Physiological eosinophilic recruitment was consistently present in 7-, 10-, and 15-day-old neonatal mice, but not in 42-day-old mice. This feature was completely abolished in interleukin 33 (IL-33)-, interleukin 2 receptor gamma chain (IL2rγ)-, and interleukin 4 receptor alpha (IL4Rα)-knockout mice, but not in recombination activating gene 1 (Rag1)-knockout mice demonstrating an indispensable role for IL-33, innate lymphoid cells (ILCs), and IL4Rα in eosinophil recruitment. Interestingly, myeloid-specific IL4Rα-deficient (mye-IL4Rα−/−) mice had significantly reduced eosinophilia in the airspaces that was associated with reduced levels of IL-4 and IL-5 in the bronchoalveolar lavage fluid (BALF). Further, we tested the effect of myeloid-specific IL4Rα deficiency on IL-13-induced eosinophil recruitment into adult lung airspaces. Eosinophil recruitment into the airspaces was elevated in IL-13-treated WT mice but not in IL-13-treated mye-IL4Rα−/− mice. Consistent with the degree of eosinophilia, the BALF levels of eosinophil recruitment-associated cytokines were significantly elevated in IL-13-treated WT but not in IL-13-treated mye-IL4Rα−/− mice. These data establish that myeloid-IL4Rα is an indispensable component of the IL-33-ILCsIL-13-IL4Rα axis of eosinophil recruitment.
Evidence for the expression of TRPM6 and TRPM7 in cardiomyocytes from all four chamber walls of the human heart
Authors: Andriulė Inga , Pangonytė Dalia , Almanaitytė Mantė , Patamsytė Vaiva , Kuprytė Milda , Karčiauskas Dainius , Mubagwa Kanigula , Mačianskienė Regina 
Published: July 2021

AbstractThe expression of the channels-enzymes TRPM6 and TRPM7 in the human heart remains poorly defined, and TRPM6 is generally considered not to be expressed in cardiomyocytes. We examined their expression at protein and mRNA levels using right atrial samples resected from patients (n = 72) with or without ischemic heart disease (IHD) and samples from all chamber walls of explanted human hearts (n = 9). TRPM6 and TRPM7 proteins were detected using immunofluorescence on isolated cardiomyocytes, ELISA on tissue homogenates, and immunostaining of cardiac tissue, whereas their mRNAs were detected by RT-qPCR. Both TRPM6 and TRPM7 were present in all chamber walls, with TRPM7 being more abundant. TRPM6 was co-expressed with TRPM7. The expression levels were dependent on cell incubation conditions (presence or absence of divalent cations, pH of the extracellular milieu, presence of TRP channel inhibitors 2-aminoethoxydiphenyl-borate and carvacrol). These drugs reduced TRPM7 immunofluorescence but increased that of TRPM6. TRPM6 and TRPM7 expression was increased in tissues from IHD patients. This is the first demonstration of the presence and co-expression of TRPM6 and TRPM7 in cardiomyocytes from all chamber walls of the human heart. The increased TRPM6 and TRPM7 expression in IHD suggests that the chanzymes are involved in the pathophysiology of the disease.
A network approach to rank countries chasing sustainable development
Authors: Sciarra Carla , Chiarotti Guido , Ridolfi Luca , Laio Francesco 
Published: July 2021

AbstractIn 2015, the United Nations established the Agenda 2030 for sustainable development, addressing the major challenges the world faces and introducing the 17 Sustainable Development Goals (SDGs). How are countries performing in their challenge toward sustainable development? We address this question by treating countries and Goals as a complex bipartite network. While network science has been used to unveil the interconnections among the Goals, it has been poorly exploited to rank countries for their achievements. In this work, we show that the network representation of the countries-SDGs relations as a bipartite system allows one to recover aggregate scores of countries’ capacity to cope with SDGs as the solutions of a network’s centrality exercise. While the Goals are all equally important by definition, interesting differences self-emerge when non-standard centrality metrics, borrowed from economic complexity, are adopted. Innovation and Climate Action stand as contrasting Goals to be accomplished, with countries facing the well-known trade-offs between economic and environmental issues even in addressing the Agenda. In conclusion, the complexity of countries’ paths toward sustainable development cannot be fully understood by resorting to a single, multipurpose ranking indicator, while multi-variable analyses shed new light on the present and future of sustainable development.
Tumor collagen framework from bright-field histology images predicts overall survival of breast carcinoma patients
Authors: Morkunas Mindaugas , Zilenaite Dovile , Laurinaviciene Aida , Treigys Povilas , Laurinavicius Arvydas 
Published: July 2021

AbstractWithin the tumor microenvironment, specifically aligned collagen has been shown to stimulate tumor progression by directing the migration of metastatic cells along its structural framework. Tumor-associated collagen signatures (TACS) have been linked to breast cancer patient outcome. Robust and affordable methods for assessing biological information contained in collagen architecture need to be developed. We have developed a novel artificial neural network (ANN) based approach for tumor collagen segmentation from bright-field histology images and have tested it on a set of tissue microarray sections from early hormone receptor-positive invasive ductal breast carcinoma stained with Sirius Red (1 core per patient, n = 92). We designed and trained ANNs on sets of differently annotated image patches to segment collagen fibers and extracted 37 features of collagen fiber morphometry, density, orientation, texture, and fractal characteristics in the entire cohort. Independent instances of ANN models trained on highly differing annotations produced reasonably concordant collagen segmentation masks and allowed reliable prognostic Cox regression models (with likelihood ratios 14.11–22.99, at p-value < 0.05) superior to conventional clinical parameters (size of the primary tumor (T), regional lymph node status (N), histological grade (G), and patient age). Additionally, we noted statistically significant differences of collagen features between tumor grade groups, and the factor analysis revealed features resembling the TACS concept. Our proposed method offers collagen framework segmentation from bright-field histology images and provides novel image-based features for better breast cancer patient prognostication.
Dynamic selective auditory attention detection using RNN and reinforcement learning
Authors: Geravanchizadeh Masoud , Roushan Hossein 
Published: July 2021

AbstractThe cocktail party phenomenon describes the ability of the human brain to focus auditory attention on a particular stimulus while ignoring other acoustic events. Selective auditory attention detection (SAAD) is an important issue in the development of brain-computer interface systems and cocktail party processors. This paper proposes a new dynamic attention detection system to process the temporal evolution of the input signal. The proposed dynamic SAAD is modeled as a sequential decision-making problem, which is solved by recurrent neural network (RNN) and reinforcement learning methods of Q-learning and deep Q-learning. Among different dynamic learning approaches, the evaluation results show that the deep Q-learning approach with RNN as agent provides the highest classification accuracy (94.2%) with the least detection delay. The proposed SAAD system is advantageous, in the sense that the detection of attention is performed dynamically for the sequential inputs. Also, the system has the potential to be used in scenarios, where the attention of the listener might be switched in time in the presence of various acoustic events.
Imaging multiple sclerosis pathology at 160 μm isotropic resolution by human whole-brain ex vivo magnetic resonance imaging at 3 T
Authors: Weigel Matthias , Dechent Peter , Galbusera Riccardo , Bahn Erik , Nair Govind , Lu Po-Jui , Kappos Ludwig , Brück Wolfgang , Stadelmann Christine , Granziera Cristina 
Published: July 2021

AbstractPostmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans. Though challenging—and almost exclusively performed at 7 T field strength—depicting the tissue architecture of the entire brain in fine detail is invaluable since it enables the study of neuroanatomy and uncovers important pathological features in neurological disorders. The objectives of the present work were (1) to develop a 3D isotropic ultra-high-resolution imaging approach for human whole-brain ex vivo acquisitions working on a standard clinical 3 T MRI system; and (2) to explore the sensitivity and specificity of this concept for specific pathoanatomical features of multiple sclerosis. The reconstructed images demonstrate unprecedented resolution and soft tissue contrast of the diseased human brain at 3 T, thus allowing visualization of sub-millimetric lesions in the different cortical layers and in the cerebellar cortex, as well as unique cortical lesion characteristics such as the presence of incomplete/complete iron rims, and patterns of iron accumulation. Further details such as the subpial molecular layer, the line of Gennari, and some intrathalamic nuclei are also well distinguishable.
Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives
Authors: Jasiewicz Beata , Kozanecka-Okupnik Weronika , Przygodzki Michał , Warżajtis Beata , Rychlewska Urszula , Pospieszny Tomasz , Mrówczyńska Lucyna 
Published: July 2021

AbstractA series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. The antioxidant activity of all derivatives was investigated by three in vitro antioxidant assays, and the derivative with pyrrolidinedithiocarbamate moiety was the most active as a radical scavenger and Fe3+-Fe2+ reducer. It can be stated that possible hydrogen and electron transfer mechanism is suggested for the quenching of the free radical. Moreover, the indolyl radical stabilization and the presence of unsubstituted indole nitrogen atom are mandatory for the observed antioxidant activity, which strongly depends on the type of the substituent directly connected to the methylene group at the C-3 position. Human red blood cells (RBC) have been used as a cell model to study derivatives interaction with the cell membrane. Haemolytic activity and RBC shape transformation were observed for certain derivatives in a concentration-dependent manner. However, most of the derivatives at sublytic concentration showed high cytoprotective activity against oxidative haemolysis induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The cytoprotective properties of derivatives can be explained mostly due to their interactions with the RBC membrane components. Taking together, theoretical estimations and experimental data confirm the beneficial interactions between the selected C-3 substituted indole derivatives and the RBC membrane under oxidative stress conditions. These results encourage us to further structural optimization of C-3 substituted indole derivatives as potent antioxidant compounds.
Neurotranscriptomic changes associated with chick-directed parental care in adult non-reproductive Japanese quail
Authors: Lopes Patricia C. , de Bruijn Robert 
Published: July 2021

AbstractFor many species, parental care critically affects offspring survival. But what drives animals to display parental behaviours towards young? In mammals, pregnancy-induced physiological transformations seem key in preparing the neural circuits that lead towards attraction (and reduced-aggression) to young. Beyond mammalian maternal behaviour, knowledge of the neural mechanisms that underlie young-directed parental care is severely lacking. We took advantage of a domesticated bird species, the Japanese quail, for which parental behaviour towards chicks can be induced in virgin non-reproductive adults through a sensitization procedure, a process that is not effective in all animals. We used the variation in parental responses to study neural transcriptomic changes associated with the sensitization procedure itself and with the outcome of the procedure (i.e., presence of parental behaviours). We found differences in gene expression in the hypothalamus and bed nucleus of the stria terminalis, but not the nucleus taeniae. Two genes identified are of particular interest. One is neurotensin, previously only demonstrated to be causally associated with maternal care in mammals. The other one is urocortin 3, causally demonstrated to affect young-directed neglect and aggression in mammals. Because our studies were conducted in animals that were reproductively quiescent, our results reflect core neural changes that may be associated with avian young-directed care independently of extensive hormonal stimulation. Our work opens new avenues of research into understanding the neural basis of parental care in non-placental species.
Study on landslide susceptibility mapping based on rock–soil characteristic factors
Authors: Yu Xianyu , Zhang Kaixiang , Song Yingxu , Jiang Weiwei , Zhou Jianguo 
Published: July 2021

AbstractThis study introduces four rock–soil characteristics factors, that is, Lithology, Rock Structure, Rock Infiltration, and Rock Weathering, which based on the properties of rock formations, to predict Landslide Susceptibility Mapping (LSM) in Three Gorges Reservoir Area from Zigui to Badong. Logistic regression, artificial neural network, support vector machine is used in LSM modeling. The study consists of three main steps. In the first step, these four factors are combined with the 11 basic factors to form different factor combinations. The second step randomly selects training (70% of the total) and validation (30%) datasets out of grid cells corresponding to landslide and non-landslide locations in the study area. The final step constructs the LSM models to obtain different landslide susceptibility index maps and landslide susceptibility zoning maps. The specific category precision, receiver operating characteristic curve, and 5 other statistical evaluation methods are used for quantitative evaluations. The evaluation results show that, in most cases, the result based on Rock Structure are better than the result obtained by traditional method based on Lithology, have the best performance. To further study the influence of rock–soil characteristic factors on the LSM, these four factors are divided into “Intrinsic attribute factors” and “External participation factors” in accordance with the participation of external factors, to generate the LSMs. The evaluation results show that the result based on Intrinsic attribute factors are better than the result based on External participation factors, indicating the significance of Intrinsic attribute factors in LSM. The method proposed in this study can effectively improve the scientificity, accuracy, and validity of LSM.
A theoretical framework for general design of two-materials composed diffractive fresnel lens
Authors: Lin Ming-Yen , Chuang Chih-Hao , Chou Tzu-An , Chen Chien-Yu 
Published: July 2021

AbstractNear 100% of diffractive efficiency for diffractive optical elements (DOEs) is one of the most required optical performances in broadband imaging applications. Of all flat DOEs, none seems to interest researchers as much as Two-Materials Composed Diffractive Fresnel Lens (TM-DFL) among the most promising flat DOEs. An approach of the near 100% of diffractive efficiency for TM-DFL once developed to determine the design rules mainly takes the advantage of numerical computation by methods of mapping and fitting. Despite a curved line of near 100% of diffractive efficiency can be generated in the Abbe and partial dispersion diagram, it is not able to analytically elaborate the relationship between two optical materials that compose the TM-DFL. Here, we present a theoretical framework, based on the fundaments of Cauchy's equation, Abbe number, partial dispersion, and the diffraction theory of Fresnel lens, for obtaining a general design formalism, so to perform the perfect material matching between two different optical materials for achieving the near 100% of diffractive efficiency for TM-DFL in the broadband imaging applications.
Response of compacted bentonite to hyperalkalinity and thermal history
Authors: Kale Rohini C. , Kapil Bhanwariwal , Ravi K. 
Published: July 2021

AbstractThe use of compacted bentonite around the high-level nuclear waste canister (HLW) inside the deep geological repository (DGR) ensures the prevention of entry of active radionuclides in the atmosphere due to its noteworthy large swelling ability. In the eventual repository, the waste canister has a high (100 °C–200 °C) temperature initially, and it reduces over a vast period, which induces a thermal history over the compacted bentonite layer. The cement/concrete layer is constructed as a bulkhead or in the vaults or to support the access of galleries between a buffer and the host rock, and it degrades over the period. The hyperalkaline fluid is created when it percolates through the cement/concrete layer and comes in contact with the compacted bentonite. The contact of hyperalkaline fluid to compacted bentonite induced with thermal history can hamper the swell pressure characteristic of the bentonite. Therefore to determine the combined effect of hyperalkalinity to the thermal history induced compacted bentonite, swell pressure testing has been conducted on two compacted Barmer bentonites (B1 and B2) specimens with an initial dry density of 1.5 Mg/m3, 1.75 Mg/m3, and 2.0 Mg/m3 and saturated with distilled water as well as with hyperalkaline cement water (W/C = 1 und pH = 12.5) and heated to 110 °C and 200 °C. When the specimens were saturated with hyperalkaline cement water, the swell pressure exerted by both bentonites was noticeably reduced compared to specimens saturated with distilled water. Nevertheless, the time taken to full saturation was longer than distilled water for samples saturated with hyperalkaline cement water. Also, the decrease in swell pressure was observed in the samples subjected to thermal history than samples, which were tested without inducing thermal history in both the cases of hyperalkaline cement water and distilled water. The microstructural observations through XRD, FESEM and EDX revealed the clogging of pores due to the presence of non-swelling minerals.
In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
Authors: Nakai Kento , Shiga Takahiro , Yasuhara Rika , Sarkar Avijite Kumer , Abe Yuka , Nakamura Shiro , Hoashi Yurie , Kotani Keisuke , Tatsumoto Shoji , Ishikawa Hiroe , Go Yasuhiro , Inoue Tomio , Mishima Kenji , Akamatsu Wado , Baba Kazuyoshi 
Published: July 2021

AbstractThe serotonin 5-HT2A receptor (5-HT2AR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HT2AR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. We found that neuronal maturity increased over time and that HTR2A expression was induced at the late stage of neuronal maturation. Furthermore, we demonstrated successful labelling of the HTR2A-positive neurons, which had fluorescence and generated repetitive action potentials in response to depolarizing currents and an inward current during the application of TCB-2, a selective agonist of 5-HT2ARs, respectively. These results indicated that our in vitro model mimicked the in vivo dynamics of 5-HT2AR. Therefore, in vitro monitoring of the function of HTR2A-positive neurons induced from hiPSCs could help elucidate the pathophysiological mechanisms of neurological diseases associated with genetic variations of the HTR2A gene.
Targeting the ‘garbage-bin’ to fight cancer: HDAC6 inhibitor WT161 has an anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU
Authors: Sergi Consolato M. 
Published: July 2021

Abstract
An imbalance between protein aggregation and protein degradation may induce ‘stress’ in the functionality of the endoplasmic reticulum (ER). There are quality control (QC) mechanisms to minimize misfolding and to eliminate misfolded proteins before aggregation becomes lethal for the cell. Proper protein folding and maturation is one of the crucial functions of the ER. Chaperones of the ER and folding enzymes guarantee correct conformational maturation of emerging secretory proteins. Histone deacetylase (HDAC) 6 (HDAC6) is a masterpiece coordinating the cell response to protein aggregate formation. The balance between HDAC6 and its partner Valosin-containing protein/p97 determines the fate of polyubiquitinated misfolded proteins. WT161 is a terrific, selective, and bioavailable HDAC6 inhibitor. WT161 selectively inhibits HDAC6 and adequately increases levels of acetylated α-tubulin. This compound induces accumulation of acetylated tubulin and cytotoxicity in multiple myeloma (MM) cells. In this journal, Sun et al. (Biosci. Rep.41, DOI: 10.1042/BSR20203905) identified that WT161 suppresses the cell growth of osteosarcoma cells. This discovery opens the door to future chemotherapeutic regimens of this bone neoplasm.