bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of a 31‐gene expression profile test in cutaneous melanomas of the head and neck
Authors: Gastman Brian R. , Zager Jonathan S. , Messina Jane L. , Cook Robert W. , Covington Kyle R. , Middlebrook Brooke , Gerami Pedram , Wayne Jeffrey D. , Leachman Sancy , Vetto John T. 
Published: January 2019

AbstractBackgroundWe report the performance of a gene expression profile test to classify the recurrence risk of cutaneous melanoma tumors of the head and neck as low‐risk Class 1 or high‐risk Class 2.MethodsOf note, 157 primary head and neck cutaneous melanoma tumors were identified. Survival analyses were performed using Kaplan‐Meier and Cox methods.ResultsGene expression profile class and node status stratified tumors into significantly different 5‐year survival groups by Kaplan‐Meier method (P < .0001 for all end points), and both were independent predictors of recurrence in multivariate analysis. Overall, 74% of distant metastases and 88% of melanoma‐specific deaths had Class 2 risk.ConclusionThe gene expression profile test identifies cases at increased risk for metastasis and death independent of a clinically or pathologically negative nodal status, suggesting that incorporation of this molecular tool could improve clinical management of patients with head and neck cutaneous melanoma, especially in those with a negative sentinel lymph node biopsy.
Follow‐up of large thyroid nodules without surgery: Patient selection and long‐term outcomes
Authors: Cohen Oded , Zornitzki Taiba , Yarkoni Tom Raz , Lahav Yonatan , Schindel Doron , Halperin Doron , Yehuda Moshe 
Published: January 2019

AbstractBackgroundThe management of large thyroid nodules remains controversial. Mandatory resection is recommended by some authors.MethodsAll patients with thyroid nodules ≥3 cm between January 2009 and January 2013 were followed until August 2017. Follow‐up data were collected using an integrated hospital‐community system.ResultsA total of 141 nodules were included. Of these, 37/141 (26%) nodules were initially referred to surgery, resulting in a 32% malignancy rate (12/37). The remaining 104/141 (74%) were referred to follow‐up. During the follow‐up period, 24 additional operations were done, resulting in a 4% malignancy rate (1/24). An indication of nonbenign cytology was significantly associated with malignancy compared with other indications. Median follow‐up was 53.5 months. No patient developed regional or distal diseases. The mean change in nodule size during the follow‐up period was a 7% reduction, with no significant trend of change over time.ConclusionCareful patient selection based on clinical, sonographic, and cytologic features can reduce diagnostic surgery allowing for safe follow‐up of large thyroid nodules without surgery.
Formal [4+1] Cycloaddition of o‐Aminobenzyl Chlorides with Isocyanides: Synthesis of 2‐Amino‐3‐Substituted Indoles
Authors: Jong Jacobus A. W. , Bao Xu , Wang Qian , Zhu Jieping 
Published: January 2019

AbstractReaction of substituted o‐aminobenzyl chlorides with isocyanides in the presence of a weak base (NaHCO3) at room temperature afforded the diversely functionalized 2‐aminoindoles in good to excellent yields. A formal [4+1] cycloaddition of the in situ generated aza‐ortho‐xylylenes with isocyanides accounted for the reaction outcome.
Flow field downstream of individual aquatic plants—Experiments in a natural river with Potamogeton crispus L. and Myriophyllum spicatum L.
Authors: Przyborowski Łukasz , Łoboda Anna Maria , Bialik Robert Józef , Västilä Kaisa 
Published: January 2019

AbstractFlow disturbances generated by individual patches of submerged, flexible aquatic vegetation were investigated for two naturally growing macrophyte species, Potamogeton crispus L. and Myriophyllum spicatum L., in a sandy lowland river. Through acoustic Doppler velocimetry, 24 vertical profiles of the 3D velocity field were recorded downstream of each of the patches. The morphological features and biomechanical properties of the plants were also evaluated. The experiments showed the relationship between biomechanical characteristics and turbulence statistics. M. spicatum, which was stiffer and therefore less prone to dynamic reconfiguration, showed a greater effect on velocity damping, causing an increase in Reynold stresses, turbulence intensities, and turbulent kinetic energy downstream of the patch. These effects were present in regions both above and below plant height. In contrast for P. crispus, these effects were present only below plant height. The stiffer plant produced a mixing layer in its wake similar to that of dense plant canopies. The patch of less stiff and more streamlined P. crispus with longer leaves presented a much weaker effect on the flow. In contrast to previous studies conducted with rigid plant surrogates, we concluded that reconfiguration of the living flexible plants allows the plants to minimize drag forces, and therefore, their influence on the flow field was weaker than the effects reported for rigid surrogates.
Dual oocyte retrieval and embryo transfer in the same cycle for women with premature ovarian insufficiency
Authors: Hatirnaz Safak , Ata Baris , Hatırnaz Ebru , Basbug Alper , Tannus Samer 
Published: January 2019

AbstractObjectiveTo compare dual oocyte retrieval with minimal ovarian stimulation and embryo transfer in the same menstrual cycle versus conventional ovarian stimulation among women with premature ovarian insufficiency (POI).MethodsA retrospective study of 51 women with POI attending a reproductive center in Turkey between 2013 and 2015. Women with an ovarian follicle of 12 mm or larger early in the follicular phase who underwent oocyte retrieval followed by an immediate cycle of ovarian stimulation (group 1, n=14) were compared with those who received conventional ovarian stimulation (group 2, n=37). Both groups underwent subsequent ovarian stimulation cycles to obtain optimally two embryos for transfer.ResultsThe groups had similar baseline parameters. Serum estradiol was higher in group 1 (P<0.001); total number of oocyte retrievals was higher in group 2 (P<0.001); and total number of oocytes retrieved was similar (P=0.192). Group 1 had more higher‐quality embryos (P=0.031). There was a non‐significant trend toward higher live birth rates in the dual trigger group (28% vs 8%, P=0.08).ConclusionRescuing growing follicles early in the follicular phase combined with subsequent ovarian stimulation and embryo transfer in the same cycle resulted in fewer oocyte retrieval cycles and might potentially improve reproductive outcomes.
Joint Association Analysis Identified 18 New Loci for Bone Mineral Density
Authors: Pei Yu-Fang , Liu Lu , Liu Tao-Le , Yang Xiao-Lin , Zhang Hong , Wei Xin-Tong , Feng Gui-Juan , Hai Rong , Ran Shu , Zhang Lei 
Published: January 2019

ABSTRACT

Bone mineral density (BMD) at various skeletal sites have shared genetic determinants. In the present study, aiming to identify shared loci associated with BMD, we conducted a joint association study of a genomewide association study (GWAS) and a meta-analysis of BMD at different skeletal sites: (i) a single GWAS of heel BMD in 142,487 individuals from the UK Biobank, and (ii) a meta-analysis of 30 GWASs of total body (TB) BMD in 66,628 individuals from the Genetic Factors for Osteoporosis (GEFOS) Consortium. The genetic correlation coefficient of the two traits was estimated to be 0.57. We performed joint association analysis with a recently developed statistical method multi-trait analysis of GWAS (MTAG) to account for trait heterogeneity and sample overlap. The joint association analysis combining samples of up to 209,115 individuals identified 18 novel loci associated with BMD at the genomewide significance level (α = 5.0 × 10–8), explaining an additional 0.43% and 0.60% of heel-BMD and TB-BMD heritability, respectively. The vast majority of the identified lead SNPs or their proxies exerted local expression quantitative trait loci (cis-eQTL) activity. Credible risk variants, defined as those SNPs located within 500 kilobases (kb) of the lead SNP and with p values within two orders of magnitude of the lead SNP, were enriched in transcription factor binding sites (p = 3.58 × 10–4) and coding regions (p = 5.71 × 10–4). Fifty-six candidate genes were prioritized at these novel loci using multiple sources of information, including several genes being previously reported to play a role in bone biology but not reported in previous GWASs (PPARG, FBN2, DEF6, TNFRSF19, and NFE2L1). One newly identified gene, SCMH1, was shown to upregulate the expression of several bone biomarkers, including alkaline phosphatase (ALP), collagen type 1 (COL-I), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2), in mouse osteoblastic MC3T3-E1 cells, highlighting its regulatory role in bone formation. Our results may provide useful candidate genes for future functional investigations. © 2019 American Society for Bone and Mineral Research.
Colon Cancer‐Associated Transcripts 1 and 2: Roles and functions in human cancers
Authors: Ghafouri‐Fard Soudeh , Taheri Mohammad 
Published: January 2019

AbstractThe long noncoding RNAs (lncRNAs) Colon Cancer‐Associated Transcripts 1 and 2 (CCAT1 and CCAT2) are located in a recurrently amplified region in cancers. Their proximity with the Myc oncogene and their interactions with its promoter provided further evidence for their contribution in the tumorigenesis processes. Several cell line and clinical studies have shown upregulation of these lncRNAs in diverse malignancies. Moreover, some single nucleotide variants within these genes have been associated with cancer risk or therapeutic response in different populations. Besides, these two lncRNAs act as sponges for some tumor suppressor microRNAs (miRNAs), thus promoting cancer evolution. In the current study, we review recent literature about their expression level, interaction with cancer‐related pathways, their role in determination of cell fate and their contribution in malignant phenotype characteristics. Taken together, the current literature shows that these lncRNAs are putative targets for design of novel treatment strategies. Moreover, their expression levels in biopsied samples, exosomes, and sera of patients might be applied as diagnostic biomarkers or markers for patient follow‐up.
Suppression of OSCC malignancy by oral glands derived‐PIP identified by iTRAQ combined with 2D LC‐MS/MS
Authors: Wang Qibo , Zhi Yuan , Ren Wenhao , Li Shaoming , Dou Zhichao , Xing Xiaoming , Quan Xinyu , Wang Yuting , Jiang Chunmiao , Liang Xiao , Gao Ling , Zhi Keqian 
Published: January 2019

AbstractOral squamous cell carcinoma (OSCC) is the most common malignancy in head and neck cancer and a global cause of cancer‐related death. Due to the poor survival rates associated with OSCC, there is a growing need to develop novel technologies and predictive biomarkers to improve disease diagnosis. The identification of new cellular targets in OSCC tumors will benefit such developments. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)‐based proteomics analysis combined with 2‐dimensional liquid chromatography and tandem mass spectrometry (2D LC‐MS/MS) were used to identify differentially expressed proteins (DEPs) between tumor and normal tissues. Of the DEPs detected, the most significantly downregulated protein in OSCC tissue was prolactin‐inducible protein (PIP). Clonogenic and 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) experiments showed that the proliferation capacity of OSCC cells overexpressing PIP decreased due to cell cycle arrest at the G0/G1 checkpoint. Wound‐healing and transwell assay further showed that PIP overexpression also reduced the migration and invasion of OSCC cells. Immunohistochemistry (IHC) was used to analyze the expression in OSCC, indicating that PIP may be secreted by glandular cells and have an inhibitory effect on OSCC cells to produce. In western blot analysis, silencing studies confirmed that PIP mediates these effects through the AKT/mitogen‐activated protein kinase (MAPK) signaling axis in OSCC cells. Taken together, this study reveals PIP as a key mediator of OSCC cell growth, migration, and invasion through its effect on AKT/MAPK signaling.
Wnt signaling pathway in osteoporosis: Epigenetic regulation, interaction with other signaling pathways, and therapeutic promises
Authors: Amjadi‐Moheb Fatemeh , Akhavan‐Niaki Haleh 
Published: January 2019

AbstractWnt is a major signaling pathway involved in multifaceted roles of various biological processes. Bones are dynamic tissues which are able to remodel and maintain the tissue homeostasis. Wnt signaling cascade leads to the promotion of bone formation and suppression of bone resorption, leading to a balance in bone remodeling. Recent evidence has reinforced the inevitable role of Wnt signaling in osteoporosis. The complex genetic and epigenetic regulations of Wnt signaling factors and their interaction with other master signaling pathways such as TGF‐β, BMP, PI3K/AKT, and Hedgehog outline their importance in diagnosis and treatment of osteoporosis. In this review, we highlighted the recent advances in function of Wnt signaling‐related epigenetic regulation, different signaling pathways interacting with Wnt, and their roles in osteoporosis. Finally, we discussed novel promises in molecular targeted therapy of osteoporosis.
miR‐9: From function to therapeutic potential in cancer
Authors: Khafaei Mostafa , Rezaie Ehsan , Mohammadi Ali , Shahnazi Gerdehsang Payam , Ghavidel Sara , Kadkhoda Sepideh , Zorrieh Zahra Atieh , Forouzanfar Narjes , Arabameri Hossein , Tavallaie Mahmood 
Published: January 2019

AbstractMalignant neoplasms are regarded as the main cause of death around the world; hence, many research studies were conducted to further perceive molecular mechanisms, treatment, and cancer prognosis. Cancer is known as a major factor for health‐related problems in the world. The main challenges associated with these diseases are prompt diagnosis, disease remission classification and treatment status forecast. Therefore, progressing in such areas by developing new and optimized methods with the help of minimally invasive biological markers such as circular microRNAs (miRNAs) can be considered important. miRNA interactions with target genes have specified their role in development, apoptosis, differentiation, and proliferation and also, confirm direct miRNA function in cancer. Different miRNAs expression levels in various types of malignant neoplasms have been observed to be associated with prognosis of various carcinomas. miR‐9 seems to implement opposite practices in different tissues or under various cancer incidences by influencing different genes. Aberrant miR‐9 levels have been observed in many cancer types. Therefore, we intended to investigate the precise role of miR‐9 in patients with malignant neoplasms. To this end, in this study, we attempted to examine different studies to clarify the overall role of miR‐9 as a prognostic marker in several human tumors. The presented data in this study can help us to find the novel therapeutic avenues for treatment of human cancers.
Exploring differences in Statics Concept Inventory scores among students and practitioners
Authors: Brown Shane , Lutz Ben , Perova‐Mello Natasha , Ha Oai 
Published: January 2019

AbstractBackgroundConceptual understanding is critical to both engineering education and practice. In fact, many undergraduate courses focus on developing students' knowledge and understanding of core engineering concepts. At the same time, a growing body of literature points to substantial gaps across educational and professional practice contexts, including how problems are embodied and solved.PurposeThe purpose of this study was to explore potential differences in conceptual understanding across engineering students and professional engineers. To do so, we compared the responses of civil engineering practitioners to the Statics Concept Inventory (SCI) to those of engineering students enrolled in statics courses.Design/MethodWe administered the SCI to 95 practicing civil engineers and compared their responses to an existing dataset from 1,372 engineering students. We conducted three comparisons: overall SCI score, concept subscores, and item‐by‐item.ResultsStudents generally outperformed engineers on the SCI in terms of overall performance. However, on closer inspection, students' superior performance appears to be driven by differences in knowledge or understanding of specific statics concepts rather than a stronger understanding in general.ConclusionsWe caution against interpretations that imply students have a better understanding of statics concepts. Instead, our results suggest that differences in the way concepts are situated and applied across school and workplace contexts might account for the differences in the performance observed. These findings raise critical questions regarding the nature of concepts and the immutability of common academic representations, and point to the need for further qualitative and exploratory work investigating concepts in practice.
Interleukin-5 induces apoptotic defects in CD4+ T cells of patients with allergic rhinitis
Authors: Luo Xiang-Qian , Ma Fei , Wang Shuai , Zhao Mei-Zhen , Shao Jian-Bo , Geng Xiao-Rui , Liu Jiang-Qi , Mo Li-Hua , Guan Li , Liu Zhi-Gang , Liu Da-Bo , Yang Ping-Chang 
Published: January 2019

Abstract
T helper (Th)2 polarization plays an important role in the pathogenesis of allergic diseases; the underlying mechanism remains to be further investigated. B cell lymphoma protein-2 like protein-12 (Bcl2L12) has the anti-apoptotic function. This study aims to elucidate the contribution of Bcl2L12 to Th2 polarization in patients with allergic rhinitis (AR). In this study, human CD4+ T cells were isolated from blood samples collected from AR patients and healthy control (HC) subjects. The immune response profiles of CD4+ T cells were analyzed by immunologic approaches. The results showed that AR CD4+ T cells (CD4+ T cells collected from AR patients) showed defects of apoptosis. The expression of FasL in AR CD4+ T cells was lower than that of HC CD4+ T cells. Serum IL-5 levels were negatively correlated with the expression of FasL in AR CD4+ T cells. Exposure of CD4+ T cells to IL-5 in the culture suppressed the expression of FasL and increased the expression of Bcl2L12. IL-5 increased the levels of Bcl2L12 in CD4+ T cells, the latter bound to the FasL promoter to prevent FasL gene transcription. Inhibition of Bcl2L12 restored the apoptosis machinery in AR CD4+ T cells. In conclusion, overexpression of Bcl2L12 in CD4+ T cells compromises the apoptosis machinery; the latter can be restored by inhibition of Bcl2L12. BcL2L12 in CD4+ T cells may be a novel target for the treatment of AR and other allergic disorders.
Loss of RHBDF2 results in an early-onset spontaneous murine colitis
Authors: Geesala Ramasatyaveni , Schanz Willow , Biggs Mikayla , Dixit Garima , Skurski Joseph , Gurung Prajwal , Meyerholz David K , Elliott David , Issuree Priya D , Maretzky Thorsten 
Published: January 2019

AbstractInflammatory bowel disease (IBD) is a heterogeneous group of inflammation-mediated pathologies that include Crohn’s disease and ulcerative colitis and primarily affects the colon and small intestine. Previous studies have shown that a disintegrin and metalloprotease (ADAM) 17, a membrane-bound sheddase, capable of cleaving the proinflammatory cytokine TNF and epidermal growth factor receptor ligands, plays a critical role in maintaining gut homeostasis and modulating intestinal inflammation during IBD. Rhomboid 5 homolog 2 (RHBDF2), a catalytically inactive member of the rhomboid family of intramembrane serine proteases, was recently identified as a crucial regulator of ADAM17. Here, we assessed the role of RHBDF2 in the development of colitis in the context of IL10 deficiency. Il10−/−/Rhbdf2−/− mice developed spontaneous colitis and experienced severe weight loss starting at 8 wk of age, without the need for exogenous triggers. Severity of disease pathology in Il10−/−/Rhbdf2−/− mice correlated with a dysbiotic gut microbiota and elevated Th1-associated immune responses with increased interferon gamma and IL2 production. In addition, Il10−/−/Rhbdf2−/− mice failed to maintain their epithelial cell homeostasis, although the intestinal epithelial barrier of Rhbdf2−/− mice is intact and loss of Rhbdf2 did not significantly exacerbate sensitivity to dextran sulfate sodium-induced colitis, suggesting differences in the underlying disease pathway of intestinal inflammation in this model. Taken together, our results demonstrate a critical regulatory role for RHBDF2 in the maintenance of the unique homeostasis between intestinal microbiota and host immune responses in the gut that is dysregulated during the pathogenesis of IBD.
Evaluation of the distribution and progression of intraluminal thrombus in abdominal aortic aneurysms using high‐resolution MRI
Authors: Zhu Chengcheng , Leach Joseph R. , Tian Bing , Cao Lizhen , Wen Zhaoying , Wang Yan , Liu Xinke , Liu Qi , Lu Jianping , Saloner David , Hope Michael D. 
Published: January 2019

BackgroundIntraluminal thrombus (ILT) signal intensity on MRI has been studied as a potential marker of abdominal aortic aneurysm (AAA) progression.Purpose1) To characterize the relationship between ILT signal intensity and AAA diameter; 2) to evaluate ILT change over time; and 3) to assess the relationship between ILT features and AAA growth.Study TypeProspective.SubjectsEighty AAA patients were imaged, and a subset (n = 41) were followed with repeated MRI for 16 ± 9 months.Field Strength/Sequence3D black‐blood fast‐spin‐echo sequence at 3 T.AssessmentILT was designated as "bright" if the signal was greater than 1.2 times that of adjacent psoas muscle. AAAs were divided into three groups based on ILT: Type 1: bright ILT; Type 2: isointense ILT; Type 3: no ILT. During follow‐up, an active ILT change was defined as new ILT formation or an increase in ILT signal intensity to bright; stable ILT was defined as no change in ILT type or ILT became isointense from bright previously.Statistical TestsShapiro–Wilk test; Mann–Whitney U‐test; Fisher's exact test; Kruskal‐Wallis test; Spearman's r; intraclass correlation coefficient (ICC), Cohen's kappa.ResultsAAAs with Type 1 ILT were larger than those with Types 2 and 3 ILT (5.1 ± 1.1 cm, 4.4 ± 0.9 cm, 4.2 ± 0.8 cm, P = 0.008). The growth rate of AAAs with Type 1 ILT was significantly greater than that of AAAs with Types 2 and 3 ILT (2.6 ± 2.5, 0.6 ± 1.3, 1.5 ± 0.6 mm/year, P = 0.01). During follow‐up, AAAs with active ILT changes had a 3‐fold increased growth rate compared with AAAs with stable ILT (3.6 ± 3.0 mm/year vs. 1.2 ± 1.5 mm/year, P = 0.008).Data ConclusionAAAs with bright ILT are larger in diameter and grow faster. Active ILT change is associated with faster AAA growth. Black‐blood MRI can characterize ILT features and monitor their change over time, which may provide new insights into AAA risk assessment.Level of Evidence: 2Technical Efficacy Stage: 5J. Magn. Reson. Imaging 2019;50:994–1001.