bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, Double‐Blind, Controlled Study to Evaluate Safety and Pharmacokinetics of Single Ascending Doses of ASP5354, an Investigational Imaging Product, in Healthy Adult Volunteers
Authors: Murase Tosei , Takizawa Masaomi , Galitz Lawrence , Flach Stephen , Murray Valene , Gufford Brandon , Suwa Akira 
Published: August 2021

AbstractIntraoperative ureter identification helps reduce the risk of ureteral injury. Currently, no suitable agents for real‐time ureter visualization are approved. ASP5354 (TK‐1) is a novel indocyanine green derivative. In this first‐in‐human phase 1, double‐blind, sequential ascending‐dose study, urethral catheters were placed in 6 healthy volunteers who were randomized to single‐dose, intravenous ASP5354 0.1 mg (n = 4) or placebo (n = 2). Sequential dose escalations to 0.5‐, 2‐, 8‐, and 24‐mg ASP5354 in new cohorts were contingent upon Dose‐Escalation Committee approval after review of pharmacokinetic (PK) and safety data. Blood and urine samples were collected over 24 hours following dose administration. Objectives were to assess the safety/tolerability and PK of ASP5354. Treatment‐emergent adverse events (TEAEs) were reported in 3 (15%) and 2 (20%) participants in the ASP5354 and placebo groups, respectively. In the former, there were 6 TEAEs (5/6 grade 1‐2). One ASP5354 participant experienced grade 3 pyelonephritis, attributed to the catheter. No TEAEs were related to ASP5354. Mean plasma terminal elimination half‐life ranged from 2.1 to 3.6 hours, with near complete urinary excretion of unchanged ASP5354 within 24 hours after administration. Linear and dose‐proportional PK were observed. These results support further evaluation of ASP5354 at doses up to 24 mg for intraoperative near‐infrared fluorescence ureter visualization.
Epigenetic programming underpins B‐cell dysfunction in peanut and multi‐food allergy
Authors: Imran Samira , Neeland Melanie R , Koplin Jennifer , Dharmage Shyamali , Tang Mimi LK , Sawyer Susan , Dang Thanh , McWilliam Vicki , Peters Rachel , Perrett Kirsten P , Novakovic Boris , Saffery Richard 
Published: August 2021

AbstractObjectiveRates of IgE‐mediated food allergy (FA) have increased over the last few decades, and mounting evidence implicates disruption of epigenetic profiles in various immune cell types in FA development. Recent data implicate B‐cell dysfunction in FA; however, few studies have examined epigenetic changes within these cells.MethodsWe assessed epigenetic and transcriptomic profiles in purified B cells from adolescents with FA, comparing single‐food‐allergic (peanut only), multi‐food‐allergic (peanut and ≥1 other food) and non‐allergic (control) individuals. Adolescents represent a phenotype of persistent and severe FA indicative of a common immune deviation.ResultsWe identified 144 differentially methylated probes (DMPs) and 116 differentially expressed genes (DEGs) that distinguish B cells of individuals with FA from controls, including differential methylation of the PM20D1 promoter previously associated with allergic disorders. Subgroup comparisons found 729 DMPs specific to either single‐food‐ or multi‐food‐allergic individuals, suggesting epigenetic distinctions between allergy groups. This included two regions with increased methylation near three S100 genes in multi‐food‐allergic individuals. Ontology results of DEGs specific to multi‐food‐allergic individuals revealed enrichment of terms associated with myeloid cell activation. Motif enrichment analysis of promoters associated with DMPs and DEGs showed differential enrichment for motifs recognised by transcription factors regulating B‐ and T‐cell development, B‐cell lineage determination and TGF‐β signalling pathway between the multi‐food‐allergic and single‐food‐allergic groups.ConclusionOur data highlight epigenetic changes in B cells associated with peanut allergy, distinguishing features of the epigenome between single‐food‐ and multi‐food‐allergic individuals and revealing differential developmental pathways potentially underpinning these distinct phenotypes.
Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2‐Hippo signaling pathway
Authors: Zhang Yi , He Long‐Jun , Huang Lin‐Lin , Yao Sheng , Lin Nan , Li Ping , Xu Hui‐Wen , Wu Xi‐Wen , Xu Jian‐Liang , Lu Yi , Li Yan‐Jie , Zhu Sen‐Lin 
Published: August 2021

AbstractIntrinsic resistance to CDK4/6 inhibitors hinders their clinical utility in cancer treatment. Furthermore, the predictive markers of CDK4/6 inhibitors in gastric cancer (GC) remain incompletely described. Here, we found that PAX6 expression was negatively correlated with the response to palbociclib in vitro and in vivo in GC. We observed that the PAX6 expression level was negatively correlated with the overall survival of GC patients and further showed that PAX6 can promote GC cell proliferation and the cell cycle. The cell cycle is regulated by the interaction of cyclins with their partner serine/threonine cyclin‐dependent kinases (CDKs), and the G1/S‐phase transition is the main target of CDK4/6 inhibitors. Therefore, we tested whether PAX6 expression was correlated with the GC response to palbociclib. We found that PAX6 hypermethylates the promoter of LATS2 and inactivates the Hippo pathway, which upregulates cyclin D1 (CCND1) expression. This results in a suppressed response to palbociclib in GC. Furthermore, we found that the induction of the Hippo signaling pathway or treatment with a DNA methylation inhibitor could overcome PAX6‐induced palbociclib resistance in GC. These findings uncover a tumor promoter function of PAX6 in GC and establish overexpressed PAX6 as a mechanism of resistance to palbociclib.
Visibility of early gastric cancer in texture and color enhancement imaging
Authors: Abe Seiichiro , Yamazaki Takayuki , Hisada Izumi Tanimoto , Makiguchi Mai Ego , Yoshinaga Shigetaka , Sato Tomoya , Nonaka Satoru , Suzuki Haruhisa , Oda Ichiro , Saito Yutaka 
Published: August 2021

AbstractObjectiveThere are little data regarding the efficacy of texture and color enhancement imaging (TXI) for early gastric cancer (EGC) diagnosis. This study aimed to compare the color difference and visibility of EGC between white light imaging (WLI) and TXI.MethodsThis study included 20 EGCs of 18 patients undergoing endoscopic submucosal dissection. Still images of EGC in WLI, TXI mode 1 (with color enhancement), and TXI mode 2 (without color enhancement), which were consistent in distance, angle, and air insufflation, were constructed by computer simulation. The center of the lesion, eight equal peripheral points 5 mm outside the lesion, and eight inner points two‐thirds of the distance from peripheral points to the EGC lesion center were annotated. Mean color differences (ΔE) of the area between peripheral and inner points per lesion in WLI, TXI mode 1, and TXI mode 2 were analyzed. In addition, four endoscopists independently scored the visibility of EGC images of TXI mode 1 and 2 compared with WLI.ResultsClinicopathological characteristics were as follows: 0‐IIa/0‐IIb/0‐IIc/0‐IIa+IIc = 6/1/11/2, reddish/pale = 10/10, differentiated/undifferentiated = 18/2, median tumor size = 13.5 mm. Mean ΔE ± SD = WLI/TXI mode1/TXI mode2 = 10.3 ± 4.7, 15.5 ± 7.8, and 12.7 ± 6.1, respectively. Mean ΔE was significantly higher in TXI mode 1 than in WLI. Visibility (improved/no change/decreased) was 7/13/0 and 4/16/0 in TXI mode 1 and 2, respectively. The visibility was significantly more commonly improved in the macroscopic type 0‐IIc or 0‐IIb than in 0‐IIa or IIa+IIc in TXI mode 1.ConclusionsTXI could improve the visibility of EGC compared with WLI.
Cobalt‐Catalyzed Asymmetric 1,4‐Reduction of β,β‐Dialkyl α,β‐Unsaturated Esters with PMHS
Authors: Lu Dongpo , Lu Peng , Lu Zhan 
Published: August 2021

AbstractA cobalt‐catalyzed asymmetric reduction of β,β‐dialkyl α,β‐unsaturated esters with polymethylhydrosiloxane (PMHS) was reported to deliver the corresponding esters containing a chiral trialkyl carbon center at β‐position with up to 97 % yield and 98 % ee. The chiral tridentate ligand oxazoline iminopyridine (OIP) could perform well for the asymmetric reduction instead of chiral bidentate ligands. This operationally simple protocol shows a broad scope of substrates using one equivalent of readily available PMHS as a cheap and easy‐to‐handle reductive reagent.
Fuel flexibility of solid oxide fuel cells
Authors: Weber Andre 
Published: August 2021

AbstractOne of the major advantages of SOFCs is their high fuel flexibility. Next to natural gas and hydrogen, which are today's most common fuels for SOFC‐systems and cell‐/stack‐testing respectively, various other fuels are applicable as well. In the literature, a number of promising results show that available fuels as propane, butane, ammonia, gasoline, diesel etc. can be applied. Here, the performance of an anode supported cell operated in specialized single cell test benches with different gaseous and liquid fuels and reformates thereof is presented. Fuels as ammonia, dissolved urea (AddBlueTM), methane/steam and ethanol/water mixtures can directly be fed to the cell, whereas propane and diesel require external reforming. It is shown that in case of a stable fuel supply the cell performance with such fuels is similar to that of appropriate mixtures of H2, N2, CO, CO2, and steam, if the impact of endothermic reforming or decomposition reactions is considered. Even though a stable fuel cell operation with such fuels is possible in a single cell test bench, it should be pointed out that an appropriate fuel processing will be mandatory on the system level.
Differential interaction with TREM2 modulates microglial uptake of modified Aβ species
Authors: Joshi Pranav , Riffel Florian , Satoh Kanayo , Enomoto Masahiro , Qamar Seema , Scheiblich Hannah , Villacampa Nàdia , Kumar Sathish , Theil Sandra , Parhizkar Samira , Haass Christian , Heneka Michael T. , Fraser Paul E. , St George‐Hyslop Peter , Walter Jochen 
Published: August 2021

AbstractRare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by the progressive accumulation of aggregated forms of amyloid β peptides (Aβ). Aβ peptides are generated by proteolytic processing of the amyloid precursor protein (APP). Heterogeneity in proteolytic cleavages and additional post‐translational modifications result in the production of several distinct Aβ variants that could differ in their aggregation behavior and toxic properties. Here, we sought to assess whether post‐translational modifications of Aβ affect the interaction with TREM2. Biophysical and biochemical methods revealed that TREM2 preferentially interacts with oligomeric Aβ, and that phosphorylation of Aβ increases this interaction. Phosphorylation of Aβ also affected the TREM2 dependent interaction and phagocytosis by primary microglia and in APP transgenic mouse models. Thus, TREM2 function is important for sensing phosphorylated Aβ variants in distinct aggregation states and reduces the accumulation and deposition of these toxic Aβ species in preclinical models of Alzheimer's disease.
Foldable high‐strength electrode enabled by nanosheet subunits for advanced sodium‐ion batteries
Authors: Wang Hanwei , Fu Jinzhou , Wang Chao , Zhang Ruiwang , Li Yingying , Yang Yushan , Li Haobo , Sun Qingfeng , Li Huiqiao 
Published: August 2021

AbstractPower sources with strong mechanical properties and high‐energy density are highly desirable for the next‐generation flexible electronics. However, the challenge arises from the current electrode structure design, which is unable to bring both satisfactory mechanical and electrochemical properties with high active materials content and mass. Herein, we reported novel flexible, high‐strength, and mechanically stable TiO2‐based film electrodes for advanced sodium‐ion batteries, achieving an ultrahigh strength (up to ≈60 MPa) and commercial‐level areal capacity (4.5 mAh cm−2). Highly‐dispersed TiO2 and interlaced carbon nanotube (CNT) networks are embedded in the sheet‐liked cellulose to form porous, high‐conductive, and high‐active TiO2‐C nanosheets that is basic building subunits of TiO2‐C films, allowing the films with structural robustness and origami‐level flexibility. This strategy reconciles the contradiction between mechanical properties and active material content in flexible electrodes, and the fabricated electrode with a high TiO2 content of >65% can be bent more than 11 000 times without breaking. Meanwhile, good capacity and excellent cycle stability (0.02‰ capacity‐decay rate over 9000 cycles) of TiO2‐C film under a higher active content (75%) has well satisfied the demands of flexible energy storage devices for electrochemical performances. This TiO2‐C subunit assembly methodology demonstrates enormous potential in high‐strength/toughness flexible electrode construction for flexible electronics.image
Automatic detection of basal cell carcinoma by hyperspectral imaging
Authors: Calin Mihaela Antonina , Parasca Sorin Viorel 
Published: August 2021

AbstractThe purpose of this study was to test the ability of hyperspectral imaging (HSI) combined with unsupervised anomaly detectors to automatically differentiate basal cell carcinoma (BCC) from normal skin. Hyperspectral images of the face of a female patient with a BCC of the lower lip were acquired using a visible/near‐infrared HSI system and two anomaly detection algorithms (Reed‐Xiaoli and Reed‐Xiaoli/Uniform Target hybrid anomaly detectors) were used to detect pathological tissue from normal skin. The results revealed that the receiver operating characteristic curve of the Reed‐Xiaoli/Uniform Target hybrid detector was higher than that of the Reed‐Xiaoli detector in the range of false positive rates between 0 and 0.8. The area under curve values were good (0.7074 and 0.8607, respectively) with Reed‐Xiaoli/Uniform Target hybrid detector performing better. In conclusion, HSI combined with either of two anomaly detectors can play a promising role in the automated screening of BCC.
Intracellular density is a novel indicator of differentiation stages of murine osteoblast lineage cells
Authors: Itoh Yuki , Itoh Shousaku , Naruse Haruna , Kagioka Takumi , Hue Mai Thi , Abe Makoto , Hayashi Mikako 
Published: August 2021

AbstractOsteoblasts are primary bone‐making cells originating from mesenchymal stem cells (MSCs) in the bone marrow. The differentiation of MSCs to mature osteoblasts involves an intermediate stage called preosteoblasts, but the details of this process remain unclear. This study focused on the intracellular density of immature osteoblast lineage cells and hypothesized that the density might vary during differentiation and might be associated with the differentiation stages of osteoblast lineage cells. This study aimed to clarify the relationship between intracellular density and differentiation stages using density gradient centrifugation. Primary murine bone marrow stromal cell cultures were prepared in an osteogenic induction medium, and cells were separated into three fractions (low, intermediate, and high‐density). The high‐density fraction showed elevated expression of osteoblast differentiation markers (Sp7, Col1a1, Spp1, and Bglap) and low expression of MSC surface markers (Sca‐1, CD73, CD105, and CD106). In contrast, the low‐density fraction showed a high expression of MSC surface markers. These results indicated that intracellular density increased during differentiation from preosteoblasts to committed osteoblasts. Intracellular density may be a novel indicator for osteoblast differentiation stages. Density gradient centrifugation is a novel technique to study the process by which preosteoblasts transform into bone‐forming cells.
Two novel semiconducting B2CO monolayers with high carrier mobilities
Authors: Li Feng , Han Weibo , Cao Zhi , Ji Shilei , Wang Haiyun , Wang Lixia , Wu Hong , Zhu Yuping , Pu Yong 
Published: August 2021

AbstractThe design of new two‐dimensional (2D) materials with moderate band gaps and high carrier mobility is an important aspiration for materials innovation. Recent studies have shown that boron and oxygen atoms can be integrated into the graphene lattice to form a stable B–C–O monolayer structure. To search for the most energetically stable configuration for 2D B–C–O, here, we theoretically propose two new 2D B–C–O crystal structures with a stoichiometric ratio of 2:1:1, namely monolayer (1 L) C3v‐ and C2v‐B2CO. Two configurations have 0.09 and 0.03 eV/unit cell lower energies than the reported 1 L Cs‐B2CO configuration (Nanoscale 2016, 8, 8910). This result is further confirmed by particle swarm optimization (PSO) calculations. According to the chemical bonding analysis, 1 L C3v‐B2CO with a quasi‐planar configuration has the lowest energy, which is consisted of three strong B′–O σ‐bonds, three B″–C σ‐bonds, and one B′–C σ‐bond. As a result, 2D B2CO has an ultra‐high mechanical strength of ~366 J m−2, comparable to graphene ~352 J m−2. In addition, 1 L C3v‐B2CO is a semiconductor with an HSE06 bandgap of 2.57 eV, and it has a high electron mobility of up to ~150 cm2 v−1 s−1. The high kinetic and thermodynamic stabilities of both 1 L C3v‐ and C2v‐B2CO were confirmed according to phonon dispersion and molecular dynamic simulation. Comparable to that of crystalline silicon, 1 L C3v‐B2CO also shows a high light absorption intensity in the 400–550 nm region. Therefore, 2D C3v‐B2CO will have promising applications in semiconductor devices and photodetectors.
Mirroring, monitoring, modelling, belonging, and distancing: Psychosocial processes in an online support group of breast cancer patients
Authors: Montali Lorenzo , Zulato Edoardo , Frigerio Alessandra , Frangi Elisa , Camussi Elisabetta 
Published: August 2021

AbstractBreast cancer patients are primary users of Internet Health Forums, virtual self‐help communities where they find and share information, preoccupations, and support. Previous literature has mainly focused on analysing the contents and the outcomes of breast cancer forums' participation. In light of the Community of Practice theoretical model, our research investigated the psychosocial processes that build and shape patients' experience and participation in the forum. We conducted 16 semi‐structured email interviews with breast cancer patients recruited within a well‐established online community. Thematic analysis identified five processes—mirroring, monitoring, modelling, belonging, and distancing—that marked three phases of users' experience: initiation, participation, detachment. An interactive dynamic characterised the identified processes: the disease's experience was shaped by and, in turn, it crafted this virtual community. These community processes contributed to participants' empowerment at practical, informative, and emotional levels through the development of a shared repertoire of resources, stories, and ways of dealing with patients' recurring problems.
Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy
Authors: Morigny Pauline , Kaltenecker Doris , Zuber Julia , Machado Juliano , Mehr Lisa , Tsokanos Foivos‐Filippos , Kuzi Hanna , Hermann Chris D. , Voelkl Michael , Monogarov German , Springfeld Christoph , Laurent Victor , Engelmann Bernd , Friess Helmut , Zörnig Inka , Krüger Achim , Krijgsveld Jeroen , Prokopchuk Olga , Fisker Schmidt Søren , Rohm Maria , Herzig Stephan , Berriel Diaz Mauricio 
Published: August 2021

AbstractBackgroundCancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour‐derived and host‐derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.MethodsQuantitative secretome analysis was performed to identify specific factors characteristic of cachexia‐inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well‐established mouse models of CCx and in different cohorts of weight‐stable and weight‐losing cancer patients with different tumour entities. Genetic PLA2G7 knock‐down in tumours and pharmacological treatment using the well‐studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour‐bearing mice.ResultsHigh expression and secretion of PLA2G7 were hallmarks of cachexia‐inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock‐down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.ConclusionsOverall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre‐cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.
Maternal ethanol exposure induces behavioral deficits through oxidative stress and brain‐derived neurotrophic factor interrelation in rat offspring
Authors: Mahdinia Rahebeh , Goudarzi Iran , Lashkarbolouki Taghi , Elahdadi Salmani Mahmoud 
Published: August 2021

AbstractAlcohol consumption during pregnancy damages the central nervous system of developing fetus and results in persistent physical and neurobehavioral abnormalities, including learning and memory disorders. The hippocampus which is involved in learning and memory is highly susceptible to the ethanol neurotoxic effects. Oxidative stress is one of the mechanisms in alcohol‐induced disorders. Ethanol also interferes with the brain‐derived neurotrophic factors (BDNF) expression. Using vitamin E as a potent antioxidant, we studied the possible interrelation between oxidative stress and BDNF on cognition. Ethanol (4 g/kg) and vitamin E (100, 200, and 400 mg/kg) were given to pregnant Wistar rats on first day of gestation (GD) until weaning (28 days). Oxidative stress marker, BDNF expression, and cyclic AMP‐response binding‐protein (CREB) expression levels were measured on postnatal days (PND) 28. Object location memory (OLM) was evaluated on PND 34. Our results demonstrated that ethanol exposure significantly reduced glutathione peroxidase (GPx) activity, reduced glutathione (GSH), reduced/oxidized glutathione (GSH/GSSG) ratio, and increased superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, and carbonyl protein content in the hippocampus. Total BDNF, BDNF mRNA, and CREB expression significantly reduced in the hippocampus by ethanol exposure. Also, ethanol significantly reduced the discrimination index (DI) in the OLM test. In addition, vitamin E administration could reduce oxidative stress, increase significantly BDNF and CREB levels, and improve cognitive dysfunction induced by ethanol exposure. Collectively, results suggest that probably oxidative stress can interrelate with the BDNF system for modulating cognitive function in the ethanol‐exposed rat.