bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel recurrent PHF1‐TFE3 fusions in ossifying fibromyxoid tumors
Authors: Suurmeijer Albert J. H. , Song Wangzhao , Sung Yun‐Shao , Zhang Lei , Swanson David , Fletcher Christopher D. M. , Dickson Brendan C. , Antonescu Cristina R. 
Published: March 2019

AbstractOssifying fibromyxoid tumor (OFMT) is an uncommon mesenchymal neoplasm of uncertain differentiation and intermediate malignant potential. Recurrent PHF1 gene rearrangements are detected in up to 80% of OFMTs. We describe the clinicopathologic features of five OFMTs harboring a novel PHF1‐TFE3 fusion. In two cases, RNA sequencing identified a fusion transcript composed of PHF1 exon 11 fused to TFE3 exon 3, whereas in a third case PHF1 exon 12 was fused to TFE3 exon 7. A FISH break‐apart assay revealed rearrangements in both PHF1 and TFE3 genes in all cases. The cohort included three males and two females with a median age of 64 years. One OFMT originated in the scapula, while four occurred in the deep soft tissues. Two OFMTs had typical features, whereas three were classified as malignant. Despite uniform cytologic features and fibromyxoid stroma compatible with an OFMT diagnosis, none showed a peripheral shell of lamellar bone. S100 expression was focally present in only one case, while desmin was positive in three cases. All tumors showed strong nuclear immunopositivity for TFE3. All three malignant OFMTs developed metastases, either regionally or to the lung. One patient died of disease 1 year after diagnosis, while the remaining two are alive with disease. In summary, we report novel recurrent PHF1‐TFE3 fusions in a subset of OFMTs with aggressive clinical behavior. The PHF1‐TFE3 fusions resulted in consistent protein TFE3 overexpression which can be used as a reliable screening tool, adding OFMT as another tumor driven by TFE3 oncogenic activation pathway.
Neural mechanisms of vibrotactile categorization
Authors: Malone Patrick S. , Eberhardt Silvio P. , Wimmer Klaus , Sprouse Courtney , Klein Richard , Glomb Katharina , Scholl Clara A. , Bokeria Levan , Cho Philip , Deco Gustavo , Jiang Xiong , Bernstein Lynne E. , Riesenhuber Maximilian 
Published: March 2019

AbstractThe grouping of sensory stimuli into categories is fundamental to cognition. Previous research in the visual and auditory systems supports a two‐stage processing hierarchy that underlies perceptual categorization: (a) a “bottom‐up” perceptual stage in sensory cortices where neurons show selectivity for stimulus features and (b) a “top‐down” second stage in higher level cortical areas that categorizes the stimulus‐selective input from the first stage. In order to test the hypothesis that the two‐stage model applies to the somatosensory system, 14 human participants were trained to categorize vibrotactile stimuli presented to their right forearm. Then, during an fMRI scan, participants actively categorized the stimuli. Representational similarity analysis revealed stimulus selectivity in areas including the left precentral and postcentral gyri, the supramarginal gyrus, and the posterior middle temporal gyrus. Crucially, we identified a single category‐selective region in the left ventral precentral gyrus. Furthermore, an estimation of directed functional connectivity delivered evidence for robust top‐down connectivity from the second to first stage. These results support the validity of the two‐stage model of perceptual categorization for the somatosensory system, suggesting common computational principles and a unified theory of perceptual categorization across the visual, auditory, and somatosensory systems.
A Personal Reflection on the Chemistry‐Biology Interface
Authors: Tawfik Dan S. 
Published: March 2019

AbstractChemists, including the most prominent ones, have always had a profound interest in living systems and biomolecules. Here, I describe few historical endeavors at the interface of Chemistry and Biology that inspired me and shaped my research interests. These examples highlight the uniqueness of implementing a chemist's mindset to fundamental biological questions, by obtaining biological insight via structure‐function analyses and by implementing the fundamentals of physical chemistry. I therefore see Chemical Biology as the study of biological systems and molecules with the mindset of a chemist, and in my case, of a physical organic chemist. To me, addressing biological questions with the toolset and mindset of a chemist seems so obvious and natural that there may be no need to define a specialized sub‐discipline.
Computer aided automated detection and classification of brain tumors using CANFIS classification method
Authors: Johnpeter Jasmine Hephzipah , Ponnuchamy Thirumurugan 
Published: March 2019

ABSTRACTThe development of abnormal cells in human brain leads to the formation of tumors. This article proposes an efficient approach for brain tumor detection and segmentation using image fusion and co‐active adaptive neuro fuzzy inference system (CANFIS) classification method. The brain MRI images are fused and the dual tree complex wavelet transform is applied on the fused image. Then, the statistical features, local ternary pattern features and gray level co‐occurrence matrix features. These extracted features are classified using CANFIS classification approach for the classification of source brain MRI image into either normal or abnormal. Further, morphological operations are applied on the abnormal brain MRI image for segmenting the tumor regions. The proposed methodology is evaluated with respect to the performance metrics sensitivity, specificity, positive predictive value, negative predictive value, tumor segmentation accuracy with detection rate. The proposed image fusion based brain tumor detection and classification methodology stated in this article achieves 96.5% of average sensitivity, 97.7% of average specificity, 87.6% of positive predictive value, 96.6% of negative predictive value, and 98.8% of average accuracy.
Centimeter‐scale growth of two‐dimensional layered high‐mobility bismuth films by pulsed laser deposition
Authors: Yang Zhibin , Wu Zehan , Lyu Yongxin , Hao Jianhua 
Published: March 2019

AbstractEver since discovery of graphene, two‐dimensional (2D) materials become a new tool box for information technology. Among the 2D family, ultrathin bismuth (Bi) has attracted a great deal of attention in recent years due to its unique topological insulating properties and large magnetoresistance. However, the scalable synthesis of layered Bi ultrathin films is rarely been reported, which would greatly restrict further fundamental investigation and practical device development. Here, we demonstrate the direct growth of homogeneous and centimeter‐scale layered Bi films by pulsed laser deposition (PLD) technique. The as‐grown Bi film exhibits high‐purity phase and good crystallinity. In addition, both (111) and (110)‐oriented Bi films can be synthesized by precisely controlling the processing temperature. The characterization of optical properties shows a thickness dependent band gaps (0.075‐0.2 eV). Moreover, Bi thin‐film‐based field‐effect transistors have been demonstrated, exhibiting a large carrier mobility of 220 cm2 V−1 s−1. Our work suggests that the PLD‐grown Bi films would hold the potential to develop spintronic applications, electronic and optoelectronic devices used for information science and technology.
Fast and reliable determination of Escherichia coli susceptibility to antibiotics: Infrared microscopy in tandem with machine learning algorithms
Authors: Sharaha Uraib , Rodriguez‐Diaz Eladio , Sagi Orli , Riesenberg Klaris , Salman Ahmad , Bigio Irving J. , Huleihel Mahmoud 
Published: March 2019

AbstractAntimicrobial drugs have an important role in controlling bacterial infectious diseases. However, the increasing resistance of bacteria to antibiotics has become a global health care problem. Rapid determination of antimicrobial susceptibility of clinical isolates is often crucial for the optimal antimicrobial therapy. The conventional methods used in medical centers for susceptibility testing are time‐consuming (>2 days). Two bacterial culture steps are needed, the first is used to grow the bacteria from urine on agar plates to determine the species of the bacteria (~24 hours). The second culture is used to determine the susceptibility by growing colonies from the first culture for another 24 hours. Here, the main goal is to examine the potential of infrared microscopy combined with multivariate analysis, to reduce the time it takes to identify Escherichia coli susceptibility to antibiotics and to determine the optimum choice of antibiotic to which the bacteria will respond. E coli colonies of the first culture from patients with urinary tract infections (UTI) were examined for the bacterial susceptibility using Fourier‐transform infrared (FTIR). Our results show that it is possible to determine the optimum choice of antibiotic with better than 89% sensitivity, in the time span of few minutes, following the first culture.
Sulfated hyaluronan‐containing artificial extracellular matrices promote proliferation of keratinocytes and melanotic phenotype of melanocytes from the outer root sheath of hair follicles
Authors: Schneider Marie , Rother Sandra , Möller Stephanie , Schnabelrauch Matthias , Scharnweber Dieter , Simon Jan‐Christoph , Hintze Vera , Savkovic Vuk 
Published: March 2019

AbstractThe aim of this work was to establish improved cultivation conditions for human keratinocytes (HUKORS) and melanocytes (HUMORS) from the outer root sheath (ORS) of human hair follicles for purposes of generating an epidermal graft. To this end, the cells were cultivated on artificial extracellular matrix coatings composed of collagen (COLL) and hyaluronan (HA) with varying sulfation degrees. HUKORS and HUMORS were characterized based on their morphology and proliferation, marker gene expression, protein expression and melanin content in melanocytes. Depending on the sulfation degree, the matrices provided a favorable proliferation environment for HUKORS and improved the balance between proliferation and the exertion of melanotic phenotype (gene expression and melanin content) in HUMORS. Based on the increased gene expression of microphthalmia‐associated transcription factor, as well as the downstream‐affected melanotic genes premelanosome protein and tyrosinase in HUMORS cultivated on collagen matrices with high‐sulfated HA, we assume that sulfated HA enhanced melanotic phenotype either by directly binding the CD44 receptor or by concentrating signaling mediators on site. Being a promising cultivation environment for both HUKORS and HUMORS, collagen matrices with sulfated HA have a potential of significantly improving the development of ORS‐based epidermal grafts. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1640–1653, 2019.
Carboxymethyl kappa carrageenan‐modified decellularized small‐diameter vascular grafts improving thromboresistance properties
Authors: Ilanlou Shervin , Khakbiz Mehrdad , Amoabediny Ghasem , Mohammadi Javad , Rabbani Hodjattallah 
Published: March 2019

AbstractThe development of decellularized small‐diameter vascular grafts is a potential solution for patients requiring vascular reconstructive procedures. However, there is a limitation for acellular scaffolds due to incomplete recellularization and exposure of extracellular matrix components to whole blood resulting in platelet adhesion. To address this issue, a perfusion decellularization method was developed using a custom‐designed set up which completely removed cell nuclei and preserved three‐dimensional structure and mechanical properties of native tissue (sheep carotid arteries). Afterwards, carboxymethyl kappa carrageenan (CKC) was introduced as a novel anticoagulant in vascular tissue engineering which can inhibit thrombosis formation. The method enabled uniform immobilization of CKC on decellularized arteries as a result of interaction between amine functional groups of decellularized arteries and carboxyl groups of CKC. The CKC modified graft significantly reduced platelet adhesion from 44.53 ± 2.05% (control) to 19.57 ± 1.37% (modified) and supported endothelial cells viability, proliferation, and nitric oxide production. Overall, the novel CKC modified scaffold provides a promising solution for thrombosis formation of small‐diameter vessels and could be a potent graft for future in vivo applications in vascular bypass procedures. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1690–1701, 2019.
Expression of γ‐H2AX and patient prognosis in breast cancer cohort
Authors: Wang Beili , Zhang Zheng , Xia Shi’an , Jiang Mawei , Wang Yajie 
Published: March 2019

AbstractH2AX phosphorylation is a novel marker of DNA double‐stranded breaks. In the present study, we assessed the γ‐H2AX expression, its association with other clinicopathologic characteristics, and the prognosis in a cohort of 97 patients with breast cancer. Ninety‐seven specimens of tumor tissue and 77 adjacent normal tissues from patients with breast cancer were examined. All patients underwent modified radical mastectomy or local tumor resection without lymph node dissection. γ‐H2AX expression was assessed by standard immunohistochemistry. Patients were followed after surgery for a mean duration of 70.1 ± 18.7 months (range, 6‐93 months). The γ‐H2AX staining was positive in 27 (27.8%) patients. The positive rates of H2AX were 26.0% and 2.6% in tumor tissue and adjacent normal tissues, respectively. γ‐H2AX positive status was negatively associated with TNM staging, with 24 positive cases (32.4%) in TNM staging I‐II, while no positive cases in TNM staging III‐IV (P = 0.026). Sixteen patients (16.5%) died during the follow‐up. No significant association between γ‐H2AX expression and patient survival was detected. The unadjusted HR (hazard ratio) for γ‐H2AX positive was 0.84 (95% CI: 0.27, 2.60). In TNM staging subgroup analysis, death only occurred in γ‐H2AX negative patients. Our study is the first study to demonstrate that expression of γ‐H2AX is associated with TNM staging. Due to the small sample and limited follow‐up time, we did not observe a significant association between γ‐H2AX and patient survival. γ‐H2AX expression could be a potential biomarker for cancer diagnosis and prediction, and further studies are in need.
Alteration of circular RNA expression in rat dental follicle cells during osteogenic differentiation
Authors: Du Yu , Li Jing , Hou Yuluan , Chen Chanchan , Long Weilin , Jiang Hongwei 
Published: March 2019

AbstractCircular RNAs (circRNAs) are novel noncoding RNAs and play crucial roles in various biological processes. However, little is known about the functions of circRNAs in osteogenic differentiation. The current study aimed to investigate the differential expression of circRNAs in rat dental follicle cells (rDFCs) during osteogenic differentiation, identified by RNA high‐throughput sequencing and quantitative real‐time polymerase chain reaction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to further explore the biofunctions of circRNA biofunctions. Two hundred sixty‐six differentially‐expressed circRNAs that are involved in several important signaling pathways, including mitogen‐activated protein kinases (MAPK) and transforming growth factor‐β (TGF‐β) signaling pathways were revealed. Among these, circFgfr2 and its predicted downstream targets, miR‐133 and BMP6 (bone morphogenetic protein‐6), were identified both in vivo and in vitro. For further validation, circFgfr2 was overexpressed in rDFCs, the results showed that the expression of miR‐133 was downregulated and the expression of BMP6 was upregulated. Taken together, the results revealed the circRNA expression profiles and indicated the importance of circRNAs of rDFCs. In addition, circFgfr2 might promote osteogenesis by controlling miR‐133/BMP6, which is a potential new target for the manipulation of tooth regeneration and bone formation.
The treatment effects and the underlying mechanism of B cell translocation gene 1 on the oncogenesis of brain glioma
Authors: Qian Yu , Lu Xinyu , Li Qiaoyu , Zhao Su , Fang Dazhao 
Published: March 2019

AbstractObjectivesGlioma is characterized by cell over‐proliferation, aggressive phenotype, and angiogenesis. B cell translocation gene 1 (BTG1) works as a tumor suppressor in various cancer types. We aimed to study the functions of BTG1 in glioma development.MethodsWe tested the BTG1 expressions in various glioma cell lines. T98G and U87 cells were transfected with siBTG1 and BTG1 expression vector, respectively, then assessing cell viability, cell migration, and invasion abilities. Flow cytometry was performed to analyze apoptosis and cell cycle distribution. The status of angiogenesis was assessed by In vitro angiogenesis assay. Quantitative polymerase chain reaction and Western blot analysis were used for expression analyses. The inhibitor FH535 (20 μM) and agonist LiCl (20 mM) of the Wnt/β‐catenin pathway were introduced to treat transfected cells.ResultsBTG1 was low‐expressed in glioma cell lines. In T98G cell transfected with siBTG1, cell proliferation, migration, invasion, and angiogenesis abilities were notably increased, BTG1 silencing promoted the cell survival and cell cycle progression from G0/G1 to the S phase. In BTG overexpressed U87 cell, cell proliferation, migration, invasion, and angiogenesis abilities were significantly inhibited. In addition, cell apoptosis significantly increased and the number of G0/G1 phase cells was also significantly increased. We also found that the activation of Wnt/β‐catenin was significantly inhibited in BTG1 group. LiCl and FH535 treatments could partially reverse the effects of BTG1 on glioma cell viabilities.ConclusionOur data suggested that BTG1 functions as a tumor suppressor in glioma, and the anticancer ability of BTG1 involves the repression of the Wnt/β‐catenin pathway.
An immunophenotyping of renal clear cell carcinoma with characteristics and a potential therapeutic target for patients insensitive to immune checkpoint blockade
Authors: Zhao Weiwei , Zhao Falin , Yang Kai , Lu Yaxin , Zhang Yuanyuan , Wang Wenjie , Xie Hongyu , Deng Kui , Yang Chunyan , Rong Zhiwei , Hou Yan , Li Kang 
Published: March 2019

AbstractRenal clear cell carcinoma (RCC) patients who do not achieve optimal control of progression with immune checkpoint blockade (ICB) should be further studied. Unsupervised consensus clustering was used to group 525 RCC patients based on two typical ICB pathways, CTLA‐4 and pogrammed death 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1), as well as two new discovered regulators, CMTM6 and CMTM4. Three immune molecular subtypes (IMMSs) with different clinical and immunological characteristics were identified (type I, II, and III), among which there were more stage I and low‐grade tumors in type I RCC than in type II and III. The proportion of males was highest in type II RCC. Overall survival of type II and III was similar (5.2 and 6 years) and statistically shorter than that of type I (7.6 years) before and after adjusting for age and gender. When conducting stratified analysis, our IMMSs were able to identify high‐risk patients among middle‐aged patients, males, and stage IV patients. Among the differentially expressed genes, approximately 84% were highly expressed in type II and III RCC. Genes related to ICB (CTLA‐4, CD274, and PDCD1LG2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type II and III RCC. These results documented that patients with type II and III cancer may be more sensitive to anti‐CTLA‐4 therapy, anti‐PD‐1/PD‐L1 therapy, and a combination of immunotherapies. High expression of CMTM4 in type I RCC (69%) and a statistically significant interaction of CD274 and CMTM6 indicated that CMTM4/6 might be new therapy targets for type I, who are resistant to ICB.
Modulatory effects of silibinin in cell behavior during osteogenic phenotype
Authors: Fernandes Célio Jr. da Costa , Veiga Mariana R. , Peracoli Maria Terezinha Serrão , Zambuzzi Willian F. 
Published: March 2019

AbstractNatural molecules, such as flavonoid, are very welcome strategies to modulate bone turnover. This prompted us to comprehend better the effect of silibinin on osteoblast metabolism, mainly considering intracellular pathways able to drive cell adhesion to differentiation. By exploring in vitro approaches, our data show a modulatory effect of the silibinin (200 μg/mL) on the osteoblast intracellular signaling, contributing with decisive pathways governing cell adhesion, differentiation, and further mineralization, recapitulating important stages of osteogenesis. Within the first 24 hours of adhesion (acute stage), osteoblasts respond to silibinin by rearranging their cytoskeleton and start mechanisms responsible to extracellular matrix (ECM) remodeling, which reach intense profile at 28 days of treatment (chronic stage) by favoring matrix metalloproteinases (MMPs‐2, and ‐9) activities, concomitant to mineralizing phenotype. Importantly, silibinin seems to reprogram genes related to inflammatory landscape and significantly upmodulating osteoprotegerin (>25 fold‐changes), signaling molecule involved with osteoclastogenesis. Altogether, our results show for the first time that silibinin drives in vitro osteoblast differentiation by requiring specific intracellular signaling. In conjunction, this molecular landscape contributes to understand the effect of silibinin on osteoblasts performance and open novel therapeutic possibilities to silibinin in bone disorders, such as osteoporosis.
Resistance training restores metabolic alterations induced by monosodium glutamate in a sex‐dependent manner in male and female rats
Authors: Quines Caroline B. , Jardim Natália S. , Araujo Paulo Cesar O. , Cechella José Luiz , Prado Vinicius C. , Nogueira Cristina W. 
Published: March 2019

AbstractDespite resistance exercises being associated with health outcomes, numerous issues are still unresolved and further research is required before the exercise can faithfully be prescribed as medicine. The goal of this study was to investigate whether there are sex differences in resistance training effects on metabolic alterations induced by monosodium glutamate (MSG), a model of obesity, in male and female rats. Male and female Wistar rats received MSG (4 g/kg body weight/day, s.c.) from postnatal day 1 to 10. After 10 days from MSG administration, the rats were separated into two groups: MSG‐sedentary and MSG‐exercised. At postnatal day 60, the animals started a resistance training protocol in an 80 degrees inclined vertical ladder apparatus and performed it for 7 weeks. Control rats received saline solution and were divided in saline‐sedentary and saline‐exercised. Resistance training restored all plasma biochemical parameters (glucose, cholesterol, triglycerides, aspartate aminotransferase, and alanine aminotransferase) increased in male and female rats treated with MSG. The MSG administration induced hyperglycemia associated with a decrease in the skeletal muscle glucose transporter 4 (GLUT4) levels and accompanied by deregulation in proteins, G‐6Pase, and tyrosine aminotransferase, involved in hepatic glucose metabolism of male and female rats. MSG induced dyslipidemia and lipotoxicity in the liver and skeletal muscle of male rats. Regarding female rats, lipotoxicity was found only in the skeletal muscle. The resistance training had beneficial effects against metabolic alterations induced by MSG in male and female rats, through regulation of proteins (GLUT2, protein kinase B, and GLUT4) involved in glucose and lipid pathways in the liver and skeletal muscle.