bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exact variance component tests for longitudinal microbiome studies
Authors: Zhai Jing , Knox Kenneth , Twigg Homer L. , Zhou Hua , Zhou Jin J. 
Published: January 2019

AbstractIn metagenomic studies, testing the association between microbiome composition and clinical outcomes translates to testing the nullity of variance components. Motivated by a lung human immunodeficiency virus (HIV) microbiome project, we study longitudinal microbiome data by using variance component models with more than two variance components. Current testing strategies only apply to models with exactly two variance components and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to (a) test the association of the overall microbiome composition in a longitudinal design and (b) detect the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has a correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of HIV‐infected patients and reveal two interesting genera Prevotella and
Veillonella associated with forced vital capacity. Our findings shed light on the impact of the lung microbiome on HIV complexities. The method is implemented in the open‐source, high‐performance computing language
Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.
Late Quaternary deformation in parts of the Belt of Schuppen of Dimapur and Peren districts, Nagaland, NE India
Authors: Moiya Jaowang N. , Luirei Khayingshing , Longkumer Limasanen , Kothyari Girish Ch. , Thong Glenn T. 
Published: January 2019

Geomorphic evidences and geochronology suggest recent tectonic activity in the Belt of Schuppen of Dimapur and Peren districts of Nagaland. Multiple levels of strath terraces forming remarkable geomorphic expressions are observed along the Chathe and Jharnapani river valleys. They indicate episodic uplift of the hanging‐wall blocks of the thrust systems. The major lineaments prominently trend parallel to the NE–SW regional thrusts, some being perpendicular or oblique. Active normal faults displacing bedrock and overlying fill sediments point to recent tectonic activity. The parallel and trellis drainage patterns are lineament‐controlled. Uplift of the terrain is evident from successive palaeochannels of the Chathe River younging towards the southwest. Three major aggradational phases of the terrace sediments are inferred from optically stimulated luminescence (OSL) chronology, the oldest beginning around 21 ka, the second around 11–7 ka, and the youngest between 3.5 and 1 ka. A sand lens of a tilted strath terrace exposed between Kukidolong and Chumukedima is dated at 7 ka, indicating tectonic events after 7 ka. Five major phases of bedrock uplift/incision have been estimated during 20 ka (0.13 mm/year), 11 ka (0.92 mm/year), 9 ka (2.29 mm/year), 6 ka (0.67 mm/year), and 1.8 ka (2.6 mm/year). Transverse topographic symmetry and asymmetry factor data suggest tilting towards the NE and SW. Other morphometric indices, such as channel sinuosity, stream length gradient index, valley floor to valley height ratio, and mountain front sinuosity, suggest that the area is tectonically active, which corroborates field observations.
A novel myelin protein zero transgenic zebrafish designed for rapid readout of in vivo myelination
Authors: Preston Marnie A. , Finseth Lisbet T. , Bourne Jennifer N. , Macklin Wendy B. 
Published: January 2019

AbstractDemyelination occurs following many neurological insults, most notably in multiple sclerosis (MS). Therapeutics that promote remyelination could slow the neurological decline associated with chronic demyelination; however, in vivo testing of candidate small molecule drugs and signaling cascades known to impact myelination is expensive and labor intensive. Here, we describe the development of a novel zebrafish line which uses the putative promoter of Myelin Protein Zero (mpz), a major structural protein in myelin, to drive expression of Enhanced Green Fluorescent Protein (mEGFP) specifically in the processes and nascent internodes of myelinating glia. We observe that changes in fluorescence intensity in Tg(mpz:mEGFP) larvae are a reliable surrogate for changes in myelin membrane production per se in live larvae following bath application of drugs. These changes in fluorescence are strongly predictive of changes in myelin‐specific mRNAs [mpz, 36K and myelin basic protein (mbp)] and protein production (Mbp). Finally, we observe that certain drugs alter nascent internode number and length, impacting the overall amount of myelin membrane synthesized and a number of axons myelinated without significantly changing the number of myelinating oligodendrocytes. These studies demonstrate that the Tg(mpz:mEGFP) reporter line responds effectively to positive and negative small molecule regulators of myelination, and could be useful for identifying candidate drugs that specifically target myelin membrane production in vivo. Combined with high throughput cell‐based screening of large chemical libraries and automated imaging systems, this transgenic line is useful for rapid large scale whole animal screening to identify novel myelinating small molecule compounds in vivo.
Does state ownership hurt or help minority shareholders? International evidence from control block acquisitions
Authors: Heugens Pursey P. M. A. R. , Sauerwald Steve , Turturea Roxana , van Essen Marc 
Published: January 2019

Research SummaryWe argue that state ownership is a crucial policy instrument for alleviating what is perhaps the most important principal–principal (PP) agency problem around the globe: private benefits of control (PBC). Our results illustrate that states reduce PBC in the companies in which they acquire controlling ownership positions. We also examine how legal and political institutions influence the extent to which states accomplish this goal. Antiself‐dealing legal regulations make states more effective in their efforts to constrain PBC, while political constraints make them less effective. Regimes with high state capacity appear not to prioritize PBC reduction. We test and corroborate these ideas in a sample of 1,354 control transactions across 54 countries.Managerial SummaryThe one‐sided appropriation of wealth by dominant owners is arguably the biggest threat to minority shareholders around the globe. An important question that has thus far remained unaddressed is whether state ownership of firms increases or decreases the extraction of these so‐called PBC. By investigating a large number of transactions involving the transfer of corporate control in 54 countries, we find that state acquirers of controlling ownership positions generally respect minority shareholder rights more than other types of new controlling shareholders. This effect is stronger in countries with strong legal protection of minority shareholders. However, political constraints make it more challenging for state acquirers to keep PBC in check while “strong” states may (mis)use the firms they invest in as policy vehicles.
IMRT‐based treatment of unknown primary malignancy of the head and neck: Outcomes and improved toxicity with decreased mucosal dose and larynx sparing
Authors: LaVigne Anna W. , Margalit Danielle N. , Rawal Bhupendra , Puzanov Maria , Annino Donald J. , Goguen Laura A. , Sher David J. , Schoenfeld Jonathan D. , Chau Nicole G. , Lorch Jochen H. , Rabinowits Guilherme , Haddad Robert I. , Tishler Roy B. 
Published: January 2019

AbstractBackgroundRadiation therapy for squamous cell cancer of the head and neck with unknown primary (head and neck CUP) has been associated with significant levels of swallowing toxicity. We examined the effect of changes in mucosal dose on development of laryngeal strictures and percutaneous endoscopic gastrostomy (PEG) dependence.MethodsRetrospective analysis of 58 patients with head and neck CUP treated with intensity‐modulated radiation therapy (IMRT) at the Dana Farber Cancer Institute from August 2004 through July 2013.ResultsThere were no significant differences between any recurrences for groups treated to 56 versus ≥60 Gy to the mucosal surfaces. However, mucosal dose and chemotherapy type were associated with stricture on multivariable analysis; median PEG dependence was decreased for patients treated to 56 Gy. A larynx‐sparing approach was associated with improved outcomes for strictures and PEG use.ConclusionIn this single institution study, a 56 Gy IMRT‐based mucosal dose demonstrated significant improvements in swallowing toxicity. Additional benefit was seen with larynx‐sparing IMRT.
Impact of retropharyngeal lymph node dissection in the surgical treatment of hypopharyngeal cancer
Authors: Teshima Masanori , Otsuki Naoki , Shinomiya Hirotaka , Morita Naruhiko , Furukawa Tatsuya , Morimoto Koichi , Nakamura Tetsu , Hashikawa Kazunobu , Kiyota Naomi , Sasaki Ryohei , Nibu Ken‐ichi 
Published: January 2019

AbstractObjectivesTo evaluate the impact of retropharyngeal lymph node (RPLN) dissection in the surgical treatment of hypopharyngeal cancer.MethodsBetween 2007 and 2016, 98 previously untreated patients with pathological diagnosed hypopharyngeal squamous cell carcinoma underwent total pharyngolaryngectomy and bilateral neck dissection at Kobe University Hospital. Bilateral dissection of RPLN was simultaneously performed in all patients. Pharynx was reconstructed with free jejunal transfer in 94 patients and primarily closed in 4 patients. Postoperative chemoradiotherapy was performed in patients with high risk factors including metastasis to RPLN, multiple lymph node metastasis, extranodal invasion, and/or positive/close surgical margins.ResultsThe median follow‐up period was 25 months ranging from 1 to 105 months. RPLN adenopathy was preoperatively identified in 9 patients in FDG‐positron emission tomography. All of them had pathologically diagnosed RPLN metastases, which had been controlled in all patients during the observation periods. Among the other 89 patients, 7 patients had RPLN metastasis. The 2‐year overall survival rates of the patients with and without RPLN metastasis were 65.7% and 69.8% (P = .61), respectively.ConclusionsIn the present study, patients with RPLN metastasis showed equally favorable oncological outcome compared with patients without RPLN metastasis. At least, ipsilateral RPLN dissection should be considered in the surgical treatment of advanced hypopharyngeal cancer and multiple neck lymph node metastasis regardless of primary subsite.
Impact of lymph node sampling on survival in cN0 major salivary gland adenoid cystic carcinoma
Authors: Qian Zhen Jason , Chen Michelle M. , Divi Vasu , Megwalu Uchechukwu C. 
Published: January 2019

AbstractBackgroundThe role of elective neck dissection in the management of major salivary gland adenoid cystic carcinoma is unclear.MethodsData were retrospectively extracted from the National Cancer Center Database. The study cohort included 1504 patients with adenoid cystic carcinoma of major salivary glands with clinical N0 necks who were treated with surgery between 2004 and 2014. The cohort was divided into four groups based on number of lymph nodes (LNs) examined on pathology: 0, 1‐8, 9‐17, and ≥18 LNs.ResultsThe rate of occult nodal metastasis was 9.0%. Number of LNs removed was not associated with survival (Reference, 0 LNs; HR = 0.98, 95% CI 0.73‐1.32 for 1‐8 LNs; HR = 1.22, 95% CI 0.80‐1.88 for 9‐17 LNs; HR = 0.94, 95% CI 0.61‐1.46 for ≥18 LNs) after adjusting for important covariates.ConclusionsLN sampling is not associated with survival in cN0 major salivary gland ACC.
Prognostic significance of tumor budding, tumor‐stroma ratio, cell nests size, and stroma type in laryngeal and pharyngeal squamous cell carcinomas
Authors: Karpathiou Georgia , Vieville Marine , Gavid Marie , Camy Florian , Dumollard Jean Marc , Magné Nicolas , Froudarakis Marios , Prades Jean Michel , Peoc'h Michel 
Published: January 2019

AbstractBackgroundDespite immune microenvironment of head and neck squamous cell carcinoma (HNSCC) has been studied, there are no sufficient data on the role of tumor stroma factors. The aim of the study was to explore the prognostic and predictive role of these factors in a large series of HNSCC.MethodsThis is a retrospective study of 266 patients with laryngeal and pharyngeal SCC. Clinical data were correlated with the following histological parameters: tumor‐stroma ratio (TSR), tumor budding activity (BA), cell nests size (CNS), and stroma type.ResultsStroma‐rich tumors, tumor budding, smaller CNS at core and front area, and fibroblastic stroma type, were all adverse prognostic factors (P < 0.0001, 0.001, 0.003, 0.001, 0.007, respectively). Stroma‐poor tumors and with larger CNS showed good response to induction chemotherapy (P = 0.009 and 0.02, respectively).ConclusionsTSR, tumor budding, CNS, and stroma type are important prognostic and predictive factors in laryngeal and pharyngeal SCC.
Adjuvant external beam radiotherapy for locally invasive papillary thyroid cancer
Authors: Megwalu Uchechukwu C. , Orloff Lisa A. , Ma Yifei 
Published: January 2019

AbstractBackgroundThe goal of this study was to assess the impact of adjuvant external beam radiotherapy (EBRT) on survival in patients with locally invasive papillary thyroid carcinoma.MethodsPropensity score analysis was performed on 870 patients with surgically resected T4 papillary thyroid carcinoma, identified in the Surveillance, Epidemiology, and End Results Database between 1988 and 2013.ResultsEBRT was associated with worse overall survival (OS) (HR 1.60, 95% CI 1.18‐2.16) and disease‐specific survival (DSS) (HR 1.58, 1.09‐2.30). Subset analysis of patients with major extrathyroidal invasion showed that EBRT was associated with worse OS (HR 1.53, 95% CI 1.04‐2.25), but not with DSS (HR 1.57, 95% CI 0.99‐2.50).ConclusionAdjuvant EBRT, in the initial management of locally invasive papillary thyroid cancer, was not associated with a survival benefit. Future studies are needed to determine which subset of patients may benefit from adjuvant EBRT.
Using Decision Analysis to Provide Integrated, Transparent Trade‐off Analysis
Authors: Specking Eric 
Published: January 2019

ABSTRACTClients often ask systems engineers to communicate the complexities of their studies or to review/understand someone else's study. Exploring, evaluating, and communicating the tradespace is difficult to do, especially when reviewing others’ work, due to the lack of knowledge of the tradespace, number and types of models, the complexities of the analysis, and the adequacy of the documentation. Additionally, it is challenging to identify and demonstrate important trade‐offs found throughout the design decision process. This demonstrates a need to understand the complexities of the analysis, be able to visualize their relationships, and then be able to communicate it to others in a simplified manner that technical and non‐technical stakeholders can understand. This article describes: (1) how system engineering requires descriptive, predictive, and prescriptive analytics in early system design, (2) a framework for an integrated trade‐off analytics approach that incorporates the various analytics categories with model‐based engineering and model‐based system engineering, and (3) a decision analysis tool called the trade‐off analytics hierarchy that transparently identifies and communicates the complexities of an analysis to stakeholders.
LINC00461 promotes cell migration and invasion in breast cancer through miR‐30a‐5p/integrin β3 axis
Authors: Dong Lifeng , Qian Junbin , Chen Fangfang , Fan Yangfan , Long Jingpei 
Published: January 2019

AbstractMounting evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated and implicated in the occurrence and development of a wide range of human malignancies. LINC00461, a novel cancer‐related lncRNA, has been reported to be highly expressed and serve as oncogene in glioma; however, its biological role in breast cancer (BC) remains obscure. This study aimed to explore the role of LINC00461 in BC and elucidate the potential molecular mechanisms involved. In the current study, LINC00461 was found to be significantly upregulated in both BC tissues and cell lines. Besides, we found that high LINC00461 expression was associated with TNM stage and differentiation. Furthermore, functional studies demonstrated that LINC00461 expedited BC cell migration and invasion. Notably, LINC00461 was observed to enhance the expression of vimentin and zinc‐finger E‐box binding homeobox factor 1, suppress the expression of E‐cadherin, and promote the activation of extracellular signal‐regulated kinase and AKT signaling pathways. Mechanical investigations revealed that LINC00461 positively modulated integrin β3 (ITGB3) expression as miR‐30a‐5p sponge in BC cells. Taken together, LINC00461 exerts an oncogenic role in BC through miR‐30a‐5p/ITGB3 axis. Our data indicate that LINC00461 may be used to be a novel candidate therapeutic target and a valuable diagnostic biomarker for BC.
Celastrol protects human retinal pigment epithelial cells against hydrogen peroxide mediated oxidative stress, autophagy, and apoptosis through sirtuin 3 signal pathway
Authors: Du Zhaojiang , Zhang Wen , Wang Shengyu , Zhang Jing , He Jingang , Wang Yuan , Dong Yuhong , Huo Min 
Published: January 2019

AbstractAge‐related macular degeneration (AMD), one of the most common causes of visual impairment, often occurrs in the elderly in developed countries. Oxidative stress, autophagy, and apoptosis of retinal pigment epithelial (RPE) cells play roles in the pathogenesis of AMD. In the current study, the protective effect of celastrol against hydrogen peroxide (H2O2)‐induced oxidative stress and apoptosis was investigated using a human RPE cell line (ARPE‐19). H2O2 inhibited ARPE‐19 cells' survival and autophagy and induced their oxidative stress and apoptosis. Compared with the H2O2 group, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay showed that celastrol increased ARPE‐19 cells' survival in a dose‐ and time‐dependent manner. Further, studies have suggested that celastrol has antioxidative stress and antiapoptosis effects in H2O2‐treated ARPE‐19 cells. Also, cell autophagy is activated by celastrol in H2O2‐treated ARPE‐19 cells. Reverse transcription polymerase chain reaction and Western blot showed that celastrol elevated the messenger RNA (mRNA) and protein expression of sirtuin 3 (SIRT3) in H2O2‐induced ARPE‐19 cells. Inhibition of the level of SIRT3 by SIRT3 small interfering RNA (siRNA) reversed the effects of celastrol on oxidative stress, autophagy, and apoptosis in H2O2‐induced ARPE‐19 cells. In conclusion, these observations suggest that celastrol activates the SIRT3 pathway in RPE cells and protects against H2O2‐induced oxidative stress and apoptosis.
TCEA3 promotes differentiation of C2C12 cells via an Annexin A1‐mediated transforming growth factor‐β signaling pathway
Authors: Ge Yao , Li Shuang , Hu Xiao‐Yang , Tong Hui‐Li , Li Shu‐Feng , Yan Yun‐Qin 
Published: January 2019

AbstractTCEA3 is a member of the transcription elongation factor family that not only promotes transcription but may also participate in other cytoplasmic processes. However, its mechanisms of action remain unclear. Our previous study indicated that TCEA3 may affect muscle differentiation. In this study, we investigated the expression and localization of TCEA3 in C2C12 cells and examined the role of TCEA3 in differentiation, its interaction with other cell proteins, and mechanisms of action. We found that the expression of TCEA3 increased gradually with an increase in the number of differentiation days and that it is mainly expressed in the cytoplasm of C2C12 cells, of which it promotes differentiation. Coimmunoprecipitation experiments and western blot analysis revealed that TCEA3 interacts with Annexin A1 (ANXA1), which is located in the cytoplasm and also promotes cell differentiation. Collectively, our results indicate that TCEA3 promotes cell differentiation by interacting with ANXA1 and affecting transforming growth factor‐β signaling pathways.
Circulating cell‐free DNA release in vitro: kinetics, size profiling, and cancer‐related gene methylation
Authors: Panagopoulou Maria , Karaglani Makrina , Balgkouranidou Ioanna , Pantazi Chrisoula , Kolios George , Kakolyris Stylianos , Chatzaki Ekaterini 
Published: January 2019

AbstractCirculating cell‐free DNA (ccfDNA) is a biological entity of great interest due to its potential as liquid biopsy biomaterial carrying clinically valuable information. To better understand its nature, we studied ccfDNA in vitro in two human cancer cell lines MCF‐7 and HeLa. Normalized indexes of ccfDNA per cell population decreased over time of culture but were significantly elevated after exposure to IC50 doses of the demethylating/apoptotic agent 5‐azacytidine (5‐AZA‐CR). Fragment‐size profiling was indicative of active release, whereas exposure to 5‐AZA‐CR induced the release of additional shorter fragments, indicative of apoptosis. Finally, the methylation profile of a panel of cancer‐specific genes as assessed by quantitative methylation analysis in ccfDNA was identical to the corresponding genomic DNA and followed accurately changes caused by 5‐AZA‐CR. Overall, our in vitro findings support that ccfDNA can be a reliable biosource of clinically relevant information that can be further studied in these cell culture models.
The role of adipose TRP channels in the pathogenesis of obesity
Authors: Gao Peng , Yan Zhencheng , Zhu Zhiming 
Published: January 2019

AbstractThe prevalence of obesity is continuously increasing worldwide. Transient receptor potential (TRP) channels constitute a family of nonselective cation channels that are ubiquitously expressed in mammalian tissues, including adipose tissue. Although TRP channels might be regarded as therapeutic targets for obesity due to the inhibitory effects of their agonists on body weight and adiposity, the exact role of TRP channels in the development of obesity by modulating the function of adipose tissue has not been systemically reviewed. Multiple TRP channels are present in adipocytes and are involved in diverse aspects of cellular function, including differentiation and maturation of white adipose tissue (WAT), browning of WAT and thermogenesis of brown adipose tissue (BAT). Most of these functions are mediated by alterations in intracellular Ca2+ levels or subcellular Ca2+ signaling pathway. TRP channels influence intracellular Ca2+ dynamics through directly mediating Ca2+ entry (TRPVs and others) or store‐operated mechanisms (TRPCs). Intracellular Ca2+ displays a biphasic effect on regulation adipocyte behaviors depending on the differentiation stage, which may account for the different roles of individual TRP channels in regulation of adiposity. This review emphasizes the contribution of TRP channels to obesity and provide an in‐depth discussion on the complexity of their mechanism of actions.