bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Fat Diet Triggers a Reduction in Body Fat Mass in Female Mice Deficient for Utx demethylase
Authors: Ota Kazushige , Komuro Akiyoshi , Amano Hisayuki , Kanai Akinori , Ge Kai , Ueda Takeshi , Okada Hitoshi 
Published: July 2019

AbstractObesity increases the risk of metabolic disorders like diabetes mellitus and dyslipidemia. However, how metabolic status is sensed and regulates cellular behavior is unclear. Utx is an H3K27 demethylase that influences adipocyte function in vitro. To examine its role in vivo, we generated mice lacking Utx in adipocytes (UtxAKO). Although all UtxAKO mice grew normally on a normal chow diet (NCD), female UtxAKO mice on a high fat diet (HFD) showed striking reductions in body fat compared to control mice (Ctrl). Gene expression profiling of adipose tissues of HFD-fed UtxAKO female mice revealed decreased expression of rate-limiting enzymes of triacylglycerol synthesis but increased expression of those of cholesterol/steroid hormone synthesis. Moreover, these animals resisted adiposity induced by ovariectomy and exhibited increased estrogen in visceral adipose tissues. Thus, upon HFD feeding, Utx regulates lipid metabolism in adipose tissues by influencing the local hormonal microenvironment. Conversely, Utx deficiency skews lipid catabolism to enhance cholesterol/steroid hormone production and repress obesity.
Identification of GSK3β inhibitor kenpaullone as a temozolomide enhancer against glioblastoma
Authors: Kitabayashi Tomohiro , Dong Yu , Furuta Takuya , Sabit Hemragul , Jiapaer Shabierjiang , Zhang Jiakang , Zhang Guangtao , Hayashi Yasuhiko , Kobayashi Masahiko , Domoto Takahiro , Minamoto Toshinari , Hirao Atsushi , Nakada Mitsutoshi 
Published: July 2019

AbstractCancer stem cells are associated with chemoresistance and rapid recurrence of malignant tumors, including glioblastoma (GBM). Although temozolomide (TMZ) is the most effective drug treatment for GBM, GBM cells acquire resistance and become refractory to TMZ during treatment. Therefore, glioma stem cell (GSC)-targeted therapy and TMZ-enhancing therapy may be effective approaches to improve GBM prognosis. Many drugs that suppress the signaling pathways that maintain GSC or enhance the effects of TMZ have been reported. However, there are no established therapies beyond TMZ treatment currently in use. In this study, we screened drug libraries composed of 1,301 existing drugs using cell viability assays to evaluate effects on GSCs, which led to selection of kenpaullone, a kinase inhibitor, as a TMZ enhancer targeting GSCs. Kenpaullone efficiently suppressed activity of glycogen synthase kinase (GSK) 3β. Combination therapy with kenpaullone and TMZ suppressed stem cell phenotype and viability of both GSCs and glioma cell lines. Combination therapy in mouse models significantly prolonged survival time compared with TMZ monotherapy. Taken together, kenpaullone is a promising drug for treatment of GBM by targeting GSCs and overcoming chemoresistance to TMZ.
Evidence for potassium transport activity of Arabidopsis KEA1-KEA6
Authors: Tsujii Masaru , Kera Kota , Hamamoto Shin , Kuromori Takashi , Shikanai Toshiharu , Uozumi Nobuyuki 
Published: July 2019

AbstractArabidopsis thaliana contains the putative K+ efflux transporters KEA1-KEA6, similar to KefB and KefC of Escherichia coli. KEA1-KEA3 are involved in the regulation of photosynthetic electron transport and chloroplast development. KEA4-KEA6 mediate pH regulation of the endomembrane network during salinity stress. However, the ion transport activities of KEA1-KEA6 have not been directly characterized. In this study, we used an E. coli expression system to examine KEA activity. KEA1-KEA3 and KEA5 showed bi-directional K+ transport activity, whereas KEA4 and KEA6 functioned as a K+ uptake system. The thylakoid membrane-localized Na+/H+ antiporter NhaS3 from the model cyanobacterium Synechocystis is the closest homolog of KEA3. Changing the putative Na+/H+ selective site of KEA3 (Gln-Asp) to that of NhaS3 (Asp-Asp) did not alter the ion selectivity without loss of K+ transport activity. The first residue in the conserved motif was not a determinant for K+ or Na+ selectivity. Deletion of the possible nucleotide-binding KTN domain from KEA3 lowered K+ transport activity, indicating that the KTN domain was important for this function. The KEA3-G422R mutation discovered in the Arabidopsis dpgr mutant increased K+ transport activity, consistent with the mutant phenotype. These results indicate that Arabidopsis KEA1-KEA6 act as K+ transport systems, and support the interpretation that KEA3 promotes dissipation of ΔpH in the thylakoid membrane.
Realization of Bidirectional, Bandwidth-Enhanced Metamaterial Absorber for Microwave Applications
Authors: Stephen Lincy , Yogesh N. , Subramanian V. 
Published: July 2019

AbstractThe ever-increasing interest towards metamaterial absorbers owes to its remarkable features such as ultra-thin nature and design flexibility. Subduing the inherent narrow bandwidth of such absorbers is the prime goal in metamaterial absorber research, as this can widen the applications areas. A greater challenge is to construct bidirectional absorber, which provides direction-insensitive absorption, as most of the existing designs exhibit single sided absorption due to the complete metal film used in the design. This work presents the realization of a bidirectional, bandwidth-enhanced metamaterial absorber with basic elements such as strips and squares optimized to have adjacent resonances leading to a bandwidth-enhanced absorption. The structural evolution of the constituent metallic components towards the formation of bandwidth-enhanced absorption is described. The bidirectional absorber exhibits more than 90% absorption between 13.40 GHz and 14.25 GHz from the two incident directions. The mechanism of absorption is studied with the surface current analysis and the effective parameters of the structure. The choice of the metallic components with four-fold rotation symmetry renders the proposed design to be polarization independent and wide-angle receptive. The numerical studies are verified experimentally at microwave frequencies, which shows a good agreement between them.
Novel acoustic flat focusing based on the asymmetric response in parity-time-symmetric phononic crystals
Authors: Yang Hang , Zhang Xin , Liu Yuechang , Yao Yuanwei , Wu Fugen , Zhao Degang 
Published: July 2019

AbstractWe present a two-dimensional (2D) parity-time-symmetric (PT-symmetry) phononic crystals (PCs) with balanced gain and loss medium. Using the super cell method of rectangular lattice, we exhibit the thresholdless spontaneous PT-symmetry breaking in the band structure. The numerical results show that the asymmetric scattering properties obviously occur in a non-Hermitian system. At two specific incident frequencies, unidirectional reflectionless and perfect transmission behaviors exist individually in opposite directions, which are accompanied by a phase transition of π. Based on the generalized Snell’s law, combining such a PT-symmetric medium, we design a novel metamaterial crystal for PT-symmetric acoustic flat focusing. Its focus frequency can also be modulated by the gain/loss parameter. The novel flat focusing based on the PT-symmetry that we propose opens a new door for high-dimensional applications of non-Hermitian metamaterials in acoustic wave manipulation.
ToF-SIMS mediated analysis of human lung tissue reveals increased iron deposition in COPD (GOLD IV) patients
Authors: Najafinobar Neda , Venkatesan Shalini , von Sydow Lena , Klarqvist Magnus , Olsson Henric , Zhou Xiao-Hong , Cloonan Suzanne M. , Malmberg Per 
Published: July 2019

AbstractChronic obstructive pulmonary disease (COPD) is a debilitating lung disease that is currently the third leading cause of death worldwide. Recent reports have indicated that dysfunctional iron handling in the lungs of COPD patients may be one contributing factor. However, a number of these studies have been limited to the qualitative assessment of iron levels through histochemical staining or to the expression levels of iron-carrier proteins in cells or bronchoalveolar lavage fluid. In this study, we have used time of flight secondary ion mass spectrometry (ToF-SIMS) to visualize and relatively quantify iron accumulation in lung tissue sections of healthy donors versus severe COPD patients. An IONTOF 5 instrument was used to perform the analysis, and further multivariate analysis was used to analyze the data. An orthogonal partial least squares discriminant analysis (OPLS-DA) score plot revealed good separation between the two groups. This separation was primarily attributed to differences in iron content, as well as differences in other chemical signals possibly associated with lipid species. Further, relative quantitative analysis revealed twelve times higher iron levels in lung tissue sections of COPD patients when compared to healthy donors. In addition, iron accumulation observed within the cells was heterogeneously distributed, indicating cellular compartmentalization.
Independent Predictors of Cardiac Mortality and Hospitalization for Heart Failure in a Multi-Ethnic Asian ST-segment Elevation Myocardial Infarction Population Treated by Primary Percutaneous Coronary Intervention
Authors: Bulluck Heerajnarain , Zheng Huili , Chan Mark Y. , Foin Nicolas , Foo David C. , Lee Chee W. , Lim Soo T. , Sahlen Anders , Tan Huay C. , Tan Jack W. , Tong Khim L. , Wong Aaron S. , Wong Philip E. , Yeo Khung K. , Foo Ling L. , Chua Terrance S. , Koh Tian H. , Hausenloy Derek J. 
Published: July 2019

AbstractWe aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.
Fast stimulated Raman and second harmonic generation imaging for intraoperative gastro-intestinal cancer detection
Authors: Sarri Barbara , Canonge Rafaël , Audier Xavier , Simon Emma , Wojak Julien , Caillol Fabrice , Cador Cécile , Marguet Didier , Poizat Flora , Giovannini Marc , Rigneault Hervé 
Published: July 2019

AbstractConventional haematoxylin, eosin and saffron (HES) histopathology, currently the ‘gold-standard’ for pathological diagnosis of cancer, requires extensive sample preparations that are achieved within time scales that are not compatible with intra-operative situations where quick decisions must be taken. Providing to pathologists a close to real-time technology revealing tissue structures at the cellular level with HES histologic quality would provide an invaluable tool for surgery guidance with evident clinical benefit. Here, we specifically develop a stimulated Raman imaging based framework that demonstrates gastro-intestinal (GI) cancer detection of unprocessed human surgical specimens. The generated stimulated Raman histology (SRH) images combine chemical and collagen information to mimic conventional HES histopathology staining. We report excellent agreements between SRH and HES images acquire on the same patients for healthy, pre-cancerous and cancerous colon and pancreas tissue sections. We also develop a novel fast SRH imaging modality that captures at the pixel level all the information necessary to provide instantaneous SRH images. These developments pave the way for instantaneous label free GI histology in an intra-operative context.
A composite of platelet-like orientated BiVO4 fused with MIL-125(Ti): Synthesis and characterization
Authors: Hlophe Philani Vusumuzi , Mahlalela Lwazi Charles , Dlamini Langelihle Nsikayezwe 
Published: July 2019

AbstractThe development of heterojunctions is the current focus of the scientific community as these materials are visible light active and the staggered positioning of their band edges combats electron-hole recombination which is the downside of most photocatalysts. In this work, a two- step hydrothermal synthesis protocol was utilized to fabricate a novel observable-light active material, composed of platelet-like BiVO4 and a titanium-based metal organic framework (MOF) called MIL-125(Ti). The tuning of specific morphologies, such as platelet-like in BiVO4, provides the exposure of most reactive facets which are more reactive towards photooxidation of organics in water, thus increasing their efficiency. The as-synthesized heterojunction was characterized by Transmission electron microscopy (TEM), scanning transmission microscopy (SEM), X-Ray diffraction (XRD), Raman spectroscopy, ultraviolet-visible diffuse reflectance spectra (UV-Vis DRS), X-Ray photoelectron spectroscopy (XPS) and photoluminescence (PL) spectra. The formation of the heterojunction lead to a positive shift of the 3-2 Bi:Ti valence band (VB) (1.78 eV) when compared to 1.27 eV VB position of BiVO4. The PL and photoelectrochemical measurements revealed that the heterojunction photocatalyst designated 3-2 Bi-Ti demonstrated inhibited recombination rate (platelet-like BiVO4 > 3-2 Bi:Ti (PM) > MIL-125 > 1–1 Bi:Ti > 2–3 Bi:Ti > 3-2 Bi:Ti) and highly efficient interfacial charge shuttle between platelet-like BiVO4 and MIL-125(Ti) through the formed n-n junction.
Differences in prognostic relevance of rectal magnetic resonance imaging findings before and after neoadjuvant chemoradiotherapy
Authors: Song Kwang-Seop , Lee Dong Woon , Kim Bun , Hur Bo Yun , Kim Min Jung , Kim Min Ju , Hong Chang Won , Park Sung Chan , Park Hyoung-Chul , Sohn Dae Kyung , Kim Byung Chang , Han Kyung Su , Oh Jae Hwan 
Published: July 2019

AbstractThis retrospective study was designed to compare prognostic relevance of magnetic resonance imaging (MRI) findings before and after neoadjuvant chemoradiotherapy (CRT). From 2002 to 2010, 399 patients who underwent surgery after CRT for rectal cancer (≥T3) and had adequate pre-CRT (mr) and post-CRT (ymr) MRI findings were examined. Factors examined included tumour (T), lymph node (N), mesorectal fascia (MRF), extramural venous invasion (EMVI), and tumour regression grade (TRG). Two Cox proportional hazard models were created using mr and ymr findings separately for overall survival (OS), disease-free survival (DFS), and local recurrence rate (LRR). Among mr findings, only mrEMVI was a significant prognostic factor for OS and DFS. Among ymr findings, ymrN, ymrMRF, and ymrEMVI were significant prognostic factors for OS and DFS, whereas ymrMRF and ymrEMVI were significant prognostic factors for LRR. C-indices tended to be higher for ymr findings than for mr findings (OS, 0.682 vs. 0.635; DFS, 0.660 vs. 0.631; LRR, 0.701 vs. 0.617). Survival outcomes of patients having all ymr risk factors were significantly poor (5-year OS, 52.4%; 5-year DFS, 38.1%; 5-year LRR, 27.7%). ymr findings showed better prognostic significance than mr findings. Among ymr findings, ymrN, ymrMRF, and ymrEMVI were independent prognostic factors for oncologic outcomes.
Sub-threshold micropulse laser treatment reduces inflammatory biomarkers in aqueous humour of diabetic patients with macular edema
Authors: Midena Edoardo , Micera Alessandra , Frizziero Luisa , Pilotto Elisabetta , Esposito Graziana , Bini Silvia 
Published: July 2019

AbstractSubthreshold micropulse laser (SMPL) is a tissue-sparing technique whose efficacy is demonstrated for diabetic macular edema (DME) treatment. However, its mechanism of action is poorly known. A prospective observational study was performed on naïve DME patients treated with SMPL, to evaluate the changes of aqueous humor (AH) inflammatory and vaso-active biomarkers after treatments. AH samples of eighteen DME eyes were collected before and after SMPL. Ten non-diabetic AH samples served as controls. Full ophthalmic evaluation, spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography were performed in DME group. Glass chip protein array was used to quantify 58 inflammatory molecules. Central retinal thickness (CRT) and visual acuity were also monitored. Several molecules showed different concentrations in DME eyes versus controls (p value < 0.05). Fas Ligand (FasL), Macrophage Inflammatory Proteins (MIP)-1α, Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) and Vascular Endothelial Growth Factor (VEGF) were increased in DME at baseline versus controls and decreased after SMPL treatments (p < 0.05). CRT reduction and visual acuity improvement were also found. Inflammatory cytokines, mainly produced by the retinal microglia, were significantly reduced after treatments, suggesting that SMPL may act by de-activating microglial cells, and reducing local inflammatory diabetes-related response.
Comparative clinical features and short-term outcomes of gastric and small intestinal gastrointestinal stromal tumours: a retrospective study
Authors: Yang Zhengyang , Wang Feng , Liu Song , Guan Wenxian 
Published: July 2019

AbstractGastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. Recent research has shown that small intestinal GISTs exhibit more aggressive features than gastric GISTs. To compare the clinical features of gastric and small intestinal GISTs for the further prediction of different prognoses, we conducted a retrospective study. 43 patients in the small intestine group and 97 in the gastric group were collected between January 2016 and December 2017. Data on demographics, preoperative lab results, clinicopathological results and surgical management were compared between groups. Significant elements were subsequently included in logistic regression analysis for further identification. The Kaplan-Meier method and log-rank test were used to calculate the relapse-free survival (RFS) rate and cumulative survival rate. Univariable analysis demonstrated that underlying disease, gastrointestinal (GI) bleeding, lymphocyte count, haemoglobin (Hb), albumin (ALB), platelet-to-lymphocyte ratio (PLR), thrombin time (TT), National Institutes of Health (NIH) category, Dog1, surgical procedure types and postoperative hospitalization were different between the two groups. Among these factors, logistic regression analysis identified that patients in small intestinal group exhibited significantly higher GI bleeding rate (p = 0.022), NIH category (p = 0.031), longer postoperative hospitalization time (p = 0.001) with lower TT value (p = 0.030) than those in gastric group. The log-rank test indicated that the location of the GIST (p = 0.022), GIST with GI bleeding (p = 0.027) and NIH category (p = 0.031) were independent prognostic predictors for poor outcome regarding RFS. Regarding cumulative survival, only the location of the GIST (p = 0.027) was an independent prognostic predictor for poor outcome. Thus, we concluded that small intestine GISTs were associated with lower TT, recurrent GI bleeding, advanced NIH category and extended postoperative hospitalization. Nevertheless, future multicentre prospective study are expected to validate our results.
Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3β, and ERK Signalling Pathways
Authors: Ibrahim Weam W. , Abdelkader Noha F. , Ismail Hesham M. , Khattab Mahmoud M. 
Published: July 2019

AbstractThough selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer’s disease (AD), other studies have reported contradictory results, and the mechanism of action has not been fully described. This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150 mg/kg/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10 mg/kg/day, p.o) for four weeks, starting from the 7th week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid β 42, β-secretase, and p-tau, while increasing α-secretase levels. Furthermore, it decreased tumor necrosis factor-α, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose/ovariectomy-induced AD-like features through modulation of PI3K/Akt/GSK-3β, Raf-1/MEK/ERK, and JNK/c-Jun pathways.
Molecular cloning and transcriptional and functional analysis of glycogen synthase kinase-3β inHaemaphysalis longicornis(Acari, Ixodidae)
Authors: Rahman Md. Khalesur , You Myungjo 
Published: July 2019

Glycogen synthase kinase 3 (GSK-3), which belongs to the serine/threonine kinase family, regulates glycogen metabolism, Wnt signaling, hormonal regulation, and embryonic development in many eukaryotes. Here, we cloned a complete open reading frame (ORF) of glycogen synthase kinase 3β (GSK-3β) fromHaemaphysalis longicornisand characterized its transcriptional and functional status. The ORF of GSK-3β possesses 1242 nucleotides encoding a mature protein of 413 amino acid residues. GSK-3β nucleotide and protein sequences are highly conserved among different vertebrate and invertebrate animals, with identity between 47.8–100% and 63.2–88.7%, respectively. Sequence comparison showed one signature domain between the residues of 51 and 335 amino acids, which was identified as a protein kinase (serine/threonine). RT-PCR showed GSK-3β mRNA present in all developmental stages ofH. longicornis. Interestingly, a higher transcript level was observed in nymph and 7-day-old eggs compared with others by real-time PCR, indicating a role of GSK-3β in the early stages of life. The functional status of GSK-3β was characterized by RNA interference (RNAi) and caused significant (p < 0.05) reduction in feeding and reproduction, as well as an abnormality in eggs and hatching. Taken together, our results suggest that GSK-3β may be an important candidate for a multiple antigen vaccine for controlling the tick population.