bluuebunny/crossref_metadata_2025 huggingface dataset:
Delineating the Role of Substituents on the Coordination Behavior of Aroylhydrazone Ligands in PdII Complexes and their Influence on Suzuki–Miyaura Coupling in Aqueous Media
Authors: Vignesh Arumugam , Shalini Chinnuswamy , Dharmaraj Nallasamy , Kaminsky Werner , Karvembu Ramasamy
Published: August 2019

Reactions of piperonal aroylhydrazone ligands (HL1–HL4) with [PdCl2(PPh3)2] in CH3OH and CHCl3 afforded four new Pd(II) complexes (1–4) featuring diverse coordination behaviors. These complexes 1–4 were fully characterized by elemental analyses, UV/Visible, FT‐IR and 1H/13C NMR spectra. The variant coordination modes of piperonal aroylhydrazone ligands with Pd(II) ion in these complexes were unambiguously confirmed by single‐crystal XRD study. Though the ligands HL1–HL4 are of similar nature, one of them (HL4) possessing an electron withdrawing nitro group as substitution in the peripheral part of the hydrazone displayed an uncommon ligation towards the palladium ion. An experimentally observed molecular architects were in turn rationalized by density functional theory (DFT) calculations as well as natural bonding analysis (NBO). All these Pd(II) complexes were evaluated for their catalytic potential towards Suzuki–Miyaura cross‐coupling reaction of sterically congested arylboronic acids with (hetero)arylhalides under an open‐flask conditions in aqueous media with low catalyst loading. Advantageously, the selected catalyst was active up to five cycles without significant loss in activity.
Effects of injection strategies on low‐speed marine engines using the dual fuel of high‐pressure direct‐injection natural gas and diesel
Authors: Liu Haifeng , Li Jingrui , Wang Jietuo , Wu Chaohui , Liu Bo , Dong Jingjin , Liu Teng , Ye Ying , Wang Hu , Yao Mingfa
Published: August 2019

Pilot‐ignited high‐pressure direct‐injection (HPDI) natural gas engines have drawn much attention since being proposed, as these engines can maintain high performance and lead to clean combustion compared with conventional diesel engines. This prospective concept is not only used in vehicle engines but also used in large‐scale marine engines. In this study, the effects of injection strategies of dual fuels on combustion characteristics and emissions were investigated using the computational fluid dynamics (CFD) code CONVERGE coupled with a reduced n‐heptane/methane mechanism. The results showed that the effects of absolute injection timing (AIT) on the combustion characteristics and emissions are similar to those of traditional diesel engines. As the AIT varies from advanced by 4°CA to retarded by 4°CA, the peak values of the in‐cylinder pressure and temperature decrease gradually. However, a conventional trade‐off between NOx and soot/CO/HC/ISFC emissions can also be observed as the AIT is retarded. In contrast, relative injection timing (RIT) has more complicated impacts on the combustion and emissions characteristics. The in‐cylinder temperature distribution and concentration stratification change as the gas jet initially interacts with the pilot flame. The effects of the gas injection timing on the combustion characteristics and indicated specific fuel consumption are also similar to those of the AIT, but the emissions are quite different. The pilot injection timing shows minimal influence on the main combustion process. Better performance can be obtained with partially premixed combustion with a slightly late injection timing compared with that of the original (ORG) base case.
Pressure pulse wave attenuation model coupling waveform distortion and viscous dissipation for blockage detection in pipeline
Authors: Chu Jiawei , Yang Lei , Liu Yu , Song Yongchen , Yu Tianbo , Lv Xin , Li Qingping , Zhao Jiafei
Published: August 2019

Safety issues are always a major concern in the oil and gas transportation facilities. Equipment damages are frequently encountered due to solid deposition such as gas hydrate deposition. A fast and efficient detection of the location, length, and rate of the accumulating blockage will significantly help relieve the potential risk. Most existing pressure wave‐based models suffer the difficulty to properly predict the blockage percentage arising from the ignorance of the wave attenuation. In the present work, an attenuation model to describe the transportation of the pressure pulse wave in gas is developed; the effects of waveform distortion and absorption as a result of the nonlinear effect and viscous dissipation are collectively considered for the first time. A simplified procedure to couple the wave attenuation in the model is proposed. The results show that the model can remarkably improve the prediction accuracy of blockage percentage by reducing the errors from −9.0% to −4.2%. Moreover, the attenuation process of the pressure pulse wave is determined to consist of three stages. The effect of waveform distortion on amplitude mainly occurs in the second stage, when our proposed model shows an improved prediction. The performance of the proposed model will help the early warning of the blockage in the pipelines and effectively avoid the potential injury and financial loss.
Plant Uptake of Per- and Polyfluoroalkyl Acids under a Maximum Bioavailability Scenario
Authors: Lasee Steven , Subbiah Seenivasan , Thompson William A. , Karnjanapiboonwong Adcharee , Jordan Juliette , Payton Paxton , Anderson Todd A.
Published: August 2019

Although many studies have evaluated the fate of per- and polyfluoroalkyl acids (PFAAs) in aquatic environments, few have observed their fate in terrestrial environments. It has been proposed that ingestion could be a major PFAA exposure route for humans. We determined PFAA uptake in radish, carrot, and alfalfa under a maximum bioavailability scenario. Bioconcentration factors (BCFs) were determined in the edible tissue of radish (perfluorobutanesulfonate [PFBS] = 72; perfluorohexanesulfonate [PFHxS] = 13; perfluoroheptanoate [PFHpA] = 65; perfluorooctanoate [PFOA] = 18; perfluorooctanesulfonate [PFOS] = 2.9; and perfluorononanoate [PFNA] = 9.6), carrot (PFBS = 5.9; PFHxS = 1.1; PFHpA = 29; PFOA = 3.1; PFOS = 1; and PFNA = 1.4), and alfalfa (PFBS = 107; PFHxS = 12; PFHpA = 91; PFOA = 10; PFOS = 1.4; and PFNA = 1.7). Some of these PFAA BCFs are as much as 2 orders of magnitude higher than those measured previously in plants grown in biosolid-amended soils. Environ Toxicol Chem 2019;38:2497–2502. © 2019 SETAC

Abstract

What is the potential for bioconcentration of per- and polyfluoroalkyl acids (PFAAs) in plant tissue under maximum availability? PFBS = perfluorobutanesulfonate; PFHxS = perfluorohexanesulfonate; PFHpA = perfluoroheptanoate; PFOA = perfluorooctanoate; PFOS = perfluorooctanesulfonate; PFNA = perfluorononanoate.
On the performance of dual‐branch selection diversity combining in α−κ−μ fading environments
Authors: Kapucu Nuri
Published: August 2019

In this paper, the performance of a dual‐branch selection combining (SC) system is analyzed over α−κ−μ fading channels. First, an outage probability (OP) expression is presented for a dual‐branch diversity with the SC scheme in α−κ−μ fading channels by using cumulative distribution function (CDF). By using the probability density function (PDF) and CDF of α−κ−μ distribution, the PDF of total output instantaneous signal‐to‐noise ratio (SNR) is obtained which is subsequently utilized for the analysis of the considered system. Based on this PDF expression, bit error probability (BEP) expressions are derived with the use of a simple and tight upper bound approximation of Gaussian Q‐function. In addition to these, we propose analytical effective capacity (EC) expressions for a dual‐branch SC system under α−κ−μ fading conditions. Then, we present simplified expressions for the OP, BEP, and EC at high SNR. Finally, we illustrate the OP, BEP (for binary phase shift keying and quadrature phase shift keying modulation formats), and EC performances for different configurations of α, κ, and μ parameters. In order to validate our analytical results, comparisons between the exact simulations and analytical results are also provided.
SDN‐based failure detection and recovery mechanism for 5G core networks
Authors: Panev Strahil , Latkoski Pero
Published: August 2019

In today's Long‐Term Evolution (LTE) implementations, there is no guarantee for a given latency in the network. Furthermore, the LTE architecture does not distinguish between services that require a certain level of latency performance, from the services that do not have stringent latency requirements. The upcoming fifth generation (5G) of mobile networks is currently still being standardized to accommodate many services and applications, which have very diverse requirements. There is a plethora of already defined use cases that require very small latency, in the region of 1 ms to 20 ms. The fault recovery mechanisms in the 5G core network must support and enable the services for reaching the low latency values. In this paper, we present an optimized protocol for fast failure detection and recovery that is implemented directly in the user plane and is suitable for the 5G Evolved Packet Core. We present a protocol that uses the OpenFlow's fast‐failure mechanism for local faults and a more advanced mechanism with stateful user plane recovery protocol that is activated only in the case of remote faults. The designed algorithm was validated by simulations performed in Mininet. The simulation results prove that the proposed solution can achieve fast fault recovery times and can be implemented in the future 5G core networks.
Fire suppression performance of a new type of composite superfine dry powder
Authors: Li Hangchen , Feng Li , Du Dexu , Guo Xinxin , Hua Min , Pan Xuhai
Published: August 2019

To enhance the performance of existing dry powders and ensure process security, a new type of dry powder based on ammonium dihydrogen phosphate (NH4H2PO4) was prepared. The prepared composite superfine dry powder was denoted as NH4H2PO4/zeolite composite in this paper. The effectiveness of commercial ABC dry powder, superfine dry powder, and the NH4H2PO4/zeolite composite in fire suppression were compared in a small‐sized fire‐extinguishing chamber. Laboratory‐scale tests showed that the NH4H2PO4/zeolite composite had considerably superior fire‐extinguishing efficiency to that of commercial ABC dry powder and superfine dry powder, along with shorter average extinguishing time and less average mass of powders consumed. In addition, the NH4H2PO4/zeolite composite also displayed much improved toxic gas suppression ability. The physical and chemical characteristics of commercial ABC dry powder, superfine dry powder, and the NH4H2PO4/zeolite composite were characterized using a range of techniques of laser particle size analysis, scanning electron microscopy, thermogravimetric analysis, and differential scanning calorimetry. Based on the analysis results, the improved fire suppression performance of the NH4H2PO4/zeolite composite can be ascribed to smaller particle size, larger surface area, and a special chemical decomposition process.
Predicting exchange rates in Asia: New insights on the accuracy of survey forecasts
Authors: Kunze Frederik
Published: August 2019

By linking measures of forecast accuracy as well as testing procedures with regard to forecast rationality this paper investigates aggregated survey forecasts with forecast horizons of 3, 12, and 24 months for the exchange rates of the Chinese yuan, the Hong Kong dollar, the Japanese yen, and the Singapore dollar vis‐à‐vis the US dollar and, hence, for four different currency regimes. The rationality of the exchange rate predictions is initially assessed utilizing tests for unbiasedness and efficiency which indicate that the investigated forecasts are irrational in the sense that the predictions are biased. As one major contribution of this paper, it is subsequently shown that these results are not consistent with an alternative, less restrictive, measure of rationality. Investigating the order of integration of the time series as well as cointegrating relationships, this empirical evidence supports the conclusion that the majority of forecasts are in fact rational. Regarding forerunning properties of the predictions, the results are rather mediocre, with shorter term forecasts for the tightly managed USD/CNY FX regime being one exception. As one additional important and novel evaluation result, it can be concluded, that the currency regime matters for the quality of exchange rate forecasts.
Determinants of Nikkei futures mispricing in international markets: Dividend clustering, currency risk, and transaction costs
Authors: Qin Jieye , Green Christopher J. , Sirichand Kavita
Published: August 2019

This paper develops a comprehensive modified cost‐of‐carry model to study the mispricing of Nikkei 225 index futures contracts traded in Osaka, Singapore, and Chicago based on a new 19‐year data set. Using this improved model, we find that dividend clustering, currency risk, and transaction costs all play an essential role in the estimation of Nikkei mispricing. An exponential smooth transition autoregressive‐GARCH model is used to describe the international dynamics of Nikkei mispricing. The results indicate that generally mean reversion in mispricing and limits to arbitrage are driven more by transaction costs than by heterogeneous investors.
Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer
Authors: Van Arsdale Anne , Patterson Nicole E. , Maggi Elaine C. , Agoni Lorenzo , Van Doorslaer Koenraad , Harmon Bryan , Nevadunsky Nicole , Kuo Dennis Y.S. , Einstein Mark H. , Lenz Jack , Montagna Cristina
Published: August 2019

Cervical carcinogenesis, the second leading cause of cancer death in women worldwide, is caused by multiple types of human papillomaviruses (HPVs). To investigate a possible role for HPV in a cervical carcinoma that was HPV‐negative by PCR testing, we performed HPV DNA hybridization capture plus massively parallel sequencing. This detected a subgenomic, URR‐E6‐E7‐E1 segment of HPV70 DNA, a type not generally associated with cervical cancer, inserted in an intron of the B‐cell lymphoma/leukemia 11B (BCL11B) gene in the human genome. Long range DNA sequencing confirmed the virus and flanking BCL11B DNA structures including both insertion junctions. Global transcriptomic analysis detected multiple, alternatively spliced, HPV70‐BCL11B, fusion transcripts with fused open reading frames. The insertion and fusion transcripts were present in an intraepithelial precursor phase of tumorigenesis. These results suggest oncogenicity of HPV70, identify novel BCL11B variants with potential oncogenic implications, and underscore the advantages of thorough genomic analyses to elucidate insights into HPV‐associated tumorigenesis.
Physical activities attenuate the negative cognitive impact from white matter hyperintensities in stroke and TIA patients with low education
Authors: Wong Adrian , Yiu Stanley , Lam Bonnie Yin Ka , Leung Kam Tat , Shi Lin , Lo Eugene , Abrigo Jill , Au Lisa Wc , Lau Alexander , Mok Vincent
Published: August 2019

Background

The objective of this study is to examine the effects of recent regular participation leisure activities upon cognitive functions between 3 and 6 months after stroke or transient ischemic attack (TIA). We also explored whether the cognitive effects interacted with the severity of white matter hyperintensities (WMH), a marker of cerebral white matter disease, in patients with low or high education.

Methods

Two‐hundred and ninety‐two subjects with mean age of 66.1 (11.0) years were recruited at median 161(131‐180) days post index event. WMH volume was evaluated using a semi‐automated method on MRI brain. Cognitive functions were measured using the Montreal Cognitive Assessment (MoCA). Multivariable linear regression analysis was conducted to explore the associations between leisure activity participation with WMH and the moderating effects of leisure activities upon relationship between WMH and MoCA. Analyses were further stratified by low (<6 years) or high education (≥6 years). All models were adjusted with age, sex, and years of education.

Results

Physical activity (PA), but not intellectual activity (IA), was negatively related to WMH volume (P < .05). IA exerted a main effect on MoCA performance (b = 3.21, P < .001). PA, but not IA, significantly interacted with WMH volume (b = −0.18, P < .01) on MoCA performance, but the interaction was only significant in the lower education group (b = 0.28, P < .01) but not in the higher education group.

Conclusions

In patients with stroke/TIA, IA confers general cognitive benefits. Regular participation in PA negatively correlated with WMH volume. In patients with low education, PA increases resilience against vascular cognitive impairment.
Surgical approaches for infratemporal fossa tumor resection: Fifteen years' experience of a single center
Authors: Yafit Daniel , Duek Irit , Abu‐Ghanem Sara , Ungar Omer J. , Wengier Anat , Moshe‐Levyn Helena , Yanko‐Arzi Ravit , Zaretski Arik , Margalit Nevo , Abergel Avraham , Muhanna Nidal , Fliss Dan M.
Published: August 2019

Background

The aims of this study were to report our center's experience with infratemporal fossa (ITF) tumors, to review the treatment modalities and outcomes.

Methods

Data of patients that underwent resection of ITF tumors in a single tertiary referral medical center were collected and analyzed.

Results

Sixty‐three patients were included. Sarcoma was the most common pathology (18; 29%). The most common surgical approach was the preauricular‐orbitozygomatic approach (24; 38%), followed by endoscopic, craniofacial resection, and combined approaches. Forty‐seven patients (75%) required reconstruction, 23 (49%) involving free tissue transfer. Thirty‐five patients (76%) with malignant lesions required adjuvant therapy consisting of radiotherapy, chemotherapy, or both. Thirty‐three patients suffered from complications related to surgery or adjuvant therapy. The three‐ and five‐years survival rates for malignancy were 82% and 66%, respectively.

Conclusion

Complete surgical resection of ITF involving tumors is feasible, providing good long‐term survival. Multidisciplinary approach is the key for success.
Aggressive large B‐cell lymphoma triggered by a parvovirus B19 infection in a previously healthy child
Authors: Olivier‐Gougenheim Laura , Dijoud Frederique , Traverse‐Glehen Alexandra , Benezech Sarah , Bertrand Yves , Latour Sylvain , Frobert Emilie , Domenech Carine
Published: August 2019

In absence of red blood cells disease or immune defect, parvovirus B19 (PVB‐19) is usually considered as a benign condition. Here, we report the case of a 10‐year‐old boy, previously healthy, presenting with a PVB‐19 infection revealed by a bicytopenia and a voluminous axillary adenopathy. Pathophysiology examination showed reactional lymphoid population. Nine months later and in the absence of remission, a new biopsy of the same adenopathy revealed a Hodgkin lymphoma with area of T‐cell rich aggressive large B‐cell lymphoma. This case suggests PVB‐19 as potential trigger of this malignant childhood hemopathy. Although no definitive conclusion can be drawn, our clinical case questions the role of PVB‐19 in lymphomagenesis.
Influence of cooling medium characteristics on embedded tube fusion condition in the process of embedded tube sand mold casting
Authors: Gao Zengli , Gong Benkui , Niu Jianping , Liu Yunteng
Published: August 2019

Embedded copper tube sand mold casting is the main manufacturing method of iron‐making blast furnace copper cooling stave, comparing embedded copper tube outer wall temperature with copper melting point is used to judge the fusion between liquid copper and embedded copper tube. On the basis that the computational model is reliable though experimental proof, the paper studies the influence of cooling medium characteristics on the embedded copper tube outer wall temperature. The calculated results show that the cooling medium thermal physical properties play a vital role on heat transfer between the liquid and embedded copper tube in the process of casting and determine the embedded copper tube outer wall temperature and the fusion. Through the numerical research, the cooling medium with suitable physical properties is found, adjusting the cooling media Reynolds number is an effective way to regulate the embedded tube outer wall temperature to the temperature required for fusion; in addition, modifying the cooling medium temperature entering the embedded tube is also a means adjusting the embedded tube outer wall temperature and improving the fusion between the embedded tube and liquid copper, but the method is not easy to operate in practice.
Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status
Authors: Gangkofner Dominik S. , Holzinger Dana , Schroeder Lea , Eichmüller Stefan B. , Zörnig Inka , Jäger Dirk , Wichmann Gunnar , Dietz Andreas , Broglie Martina A. , Herold‐Mende Christel , Dyckhoff Gerhard , Boscolo‐Rizzo Paolo , Ezic Jasmin , Marienfeld Ralf B. , Möller Peter , Völkel Gunnar , Kraus Johann M. , Kestler Hans A. , Brunner Cornelia , Schuler Patrick J. , Wigand Marlene , Theodoraki Marie N. , Doescher Johannes , Hoffmann Thomas K. , Pawlita Michael , Butt Julia , Waterboer Tim , Laban Simon
Published: August 2019

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)‐positive and HPV‐negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue‐saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV‐positive and HPV‐negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer‐testis antigens, 5 cancer‐retina antigens and 8 oncogenes) and 29 HPV‐antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV‐positive and 209 HPV‐negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c‐myc, LAGE‐1, MAGE‐A1, ‐A3, ‐A4, NY‐ESO‐1, SpanX‐a1 and p53. AR to MAGE‐A3, MAGE‐A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue‐sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV‐positive and HPV‐negative HNSCC.
How to detect illegal corporate insider trading? A data mining approach for detecting suspicious insider transactions
Authors: Esen M. Fevzi , Bilgic Emrah , Basdas Ulkem
Published: August 2019

Only in the U.S. Stock Exchanges, the daily average trading volume is about 7 billion shares. This vast amount of trading shows the necessity of understanding the hidden insights in the data sets. In this study, a data mining technique, clustering based outlier analysis is applied to detect suspicious insider transactions. 1,244,815 transactions of 61,780 insiders are analysed, which are acquired from Thomson Financial, covering a period of January 2010–April 2017. In order to detect outliers, similar transactions are grouped into the same clusters by using a two‐step clustering based outlier detection technique, which is an integration of k‐means and hierarchical clustering. Then, it is shown that outlying transactions earn higher abnormal returns than non‐outlying transactions by using event study methodology.
Preparation of carboxylic graphene oxide‐composited polypyrrole conduits and their effect on sciatic nerve repair under electrical stimulation
Authors: Chen Xianchun , Liu Chaoyuan , Huang Zhongbing , Pu Ximing , Shang Lei , Yin Guangfu , Xue Chengjing
Published: August 2019

Carboxylic graphene oxide‐composited polypyrrole/poly‐l‐lactic acid (C‐GO/PPy/PLLA) films were fabricated by electrochemical deposition of C‐GO‐composited PPy on PLLA fibers‐film, and their conductivity and tensile strength (∼4.6 S/cm and 26.4 MPa, respectively) were stably remained after the immersion of 4 weeks, due to the hydrogen bond interaction between graphene oxide's carboxylic groups and pyrrole's imino groups. Their specific surface areas of ∼57.5 m2/g and pore volume of ∼0.02 cm3/g were significantly larger than those of PPy/PLLA films, due to the addition of C‐GO nanosheets. Then, C‐GO/PPy/PLLA conducting conduit with 2 mm inner diameter was prepared to bridge 10 mm sciatic nerve defect of rats, and the direction of fiber‐axis in the conduit was the same as the conduit central axis. Electrical stimulation (ES) of 1 V and 20 Hz through the conducting conduit was exerted on the defect site. The results of in vivo electrophysiological and histological evaluation indicated that, the sciatic nerve defect could be repaired in C‐GO/PPy/PLLA conduit, moreover the re‐innervated gastrocnemius muscle and nerve conduction in C‐GO/PPy/PLLA conduit & ES group were obviously better than the conduit without ES group. The results of transmission electron microscope analysis also demonstrated that the mean thickness of myelin sheath and diameter of axon in C‐GO/PPy/PLLA conduit & ES group were significantly larger than those without ES, suggesting that the repair efficiency of ES & conduit group was closer to that of autograft group. These results indicated the great potential of C‐GO/PPy/PLLA with the in vivo ES in the application of sciatic nerve repair.
Nicotinamide increases the sensitivity of chronic myeloid leukemia cells to doxorubicin via the inhibition of SIRT1
Authors: Pan Shan , Leng Jun , Deng Xinzhou , Ruan Honggang , Zhou Lu , Jamal Muhammad , Xiao Ruijing , Xiong Jie , Yin Qian , Wu Yingjie , Wang Meng , Yuan Wen , Shao Liang , Zhang Qiuping
Published: August 2019

The NAD‐dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD+ precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX‐resistant K562 cells (K562R) in a dose‐dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX‐induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX‐induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase‐3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1.
Peripheral blood circulating microRNA‐4636/−143 for the prognosis of cervical cancer
Authors: Yin Sheng , Yang Min , Li Xianping , Zhang Kan , Tian Jingjing , Luo Can , Bai Ruiyang , Lu Yangfan , Wang Min
Published: August 2019

Cervical cancer is the third leading cause of female death in the world. Serum microRNAs (miRNAs) are currently considered to be valuable as noninvasive cancer biomarkers, but their role in the prognosis of cervical cancer has not been elucidated. We aimed to find serum miRNAs that can be used as prognostic factors for cervical cancer. A traumatic pathological biopsy is the only reliable method for determining the severity of cervical cancer currently. Thus, noninvasive diagnostic markers are needed. The serological expression of candidate miRNAs were measured in 90 participants, including 60 patients with cervical cancer and 50 patients with cervical intraepithelial neoplasia. Two patients with cervical cancer were excluded from the study because of lack of data. miRNAs were evaluated by quantitative reverse transcription polymerase chain reaction. miR‐143/−4636 appeared specific for cervical cancer compared with cervical intraepithelial neoplasia (P < .001). The classification performance of validated miRNAs for cervical cancer [Area under the receiver operating characteristic curve (AUC) = 0.942] was better than that reached by squamous cell carcinoma antigen (SCC‐Ag; AUC = 0.727). Poor‐differentiation group has lower miR‐143/−4636 levels in serum (P < .05). miR‐4636 level was correlated gross tumor volume and the depth of invasion (P < .0001). In our study, we found a combination of miR‐143 and miR‐4636 that is independently and strongly associated with cervical cancer prognosis and can be used as a clinically prognostic factor.
Identification of novel prognostic alternative splicing signature in papillary renal cell carcinoma
Authors: Duan Yi , Zhang Dong
Published: August 2019

Papillary renal cell carcinoma (pRCC) is a heterogeneous disease containing multifocal or solitary tumors with an aggressive phenotype. Increasing evidence has indicated the involvement of aberrant splicing variants in renal cell cancer, while systematic profiling of aberrant alternative splicing (AS) in pRCC was lacking and largely unknown. In the current study, comprehensive profiling of AS events were performed based on the integration of pRCC cohort from the Cancer Genome Atlas database and SpliceSeq software. With rigorous screening and univariate Cox analysis, a total of 2077 prognoses AS events from 1642 parent genes were identified. Then, stepwise least absolute shrinkage and selection operator method‐penalized Cox regression analyses with 10‐fold cross‐validation followed by multivariate Cox regression were used to construct the prognostic AS signatures within each AS type. And a final 21 AS event‐based signature was proposed which showed potent prognostic capability in stratifying patients into low‐ and high‐risk subgroups (P < .0001). Furthermore, time‐dependent receiver operating characteristics curves confirmed that the final AS signature was effective and robust in predicting overall survival for pRCC patients with the area under the curve above 0.9 from 1 to 5 years. In addition, splicing correlation network was built to uncover the potential regulatory pattern among prognostic splicing factors and candidate AS events. Besides, gene set enrichment analysis revealed the involvement of these candidates AS events in tumor‐related pathways including extracellular matrix organization, oxidative phosphorylation, and P53 signaling pathways. Taken together, our results could contribute to elucidating the underlying mechanism of AS in the oncogenesis process and broaden the novel field of prognostic and clinical application of molecule‐targeted approaches in pRCC.
SETD2 reduction adversely affects the development of mouse early embryos
Authors: Li Chunling , Huang Zhenyue , Gu Ling
Published: August 2019

SET domain‐containing protein 2 (SETD2), the protein of regulating trimethylation status of histone H3 at lysine 36 (H3K36), participates in the maintenance of chromatin architecture, transcription elongation, genome stability, and other biological events. However, its function in preimplantation embryos is still obscure. In this study, specific small interfering RNA was employed to investigate the functions of SETD2. We find that deletion of SETD2 results in the developmental delay of mouse early embryos, indicative of the compromised developmental potential. Remarkably, SETD2 knockdown induces the accumulation of the DNA lesions and apoptotic blastomeres in early embryos. In addition, the methylation level of H3K36 is significantly reduced in two‐cell embryos depleted of SETD2. In summary, our data indicate that SETD2 maintains genome stability perhaps via regulating trimethylation status of H3K36, consequently controlling the embryo quality. These findings pave the avenue for understanding the cross‐talk between epigenome and SETD2 during early embryo development.
N‐end rule pathway inhibitor sensitizes cancer cells to antineoplastic agents by regulating XIAP and RAD21 protein expression
Authors: Pore Subrata K. , Ganguly Anirban , Sau Samaresh , Godeshala Sudhakar , Kanugula Anantha K. , Ummanni Ramesh , Kotamraju Srigiridhar , Banerjee Rajkumar
Published: August 2019

Anticancer drugs exert their effects on cancer cells by deregulating many pathways linked to cell cycle, apoptosis, etc. but cancer cells gradually become resistive against anticancer drugs, thereby necessitating the development of newer generation anticancer molecules. N‐end rule pathway has been shown to be involved in the degradation of many cell cycle and apoptosis‐related proteins. However, the involvements of this pathway in cancer are not well established. Recently, we developed a non‐peptide‐based N‐end rule pathway inhibitor, RF‐C11 for type 1 and 2 recognition domains of E3 ubiquitin ligases. The inhibitor significantly increased the half‐life of potential N‐degrons leading to significant physiological changes in vivo. We hypothesized RF‐C11 may be used to decipher the N‐end rule pathway's role in cancer towards the development of anticancer therapeutics. In this study, we showed that RF‐C11, barring noncancer cells, significantly sensitizes cancer cells towards different anticancer agents tested. We further find that the profound cellular sensitization to anticancer drugs was affected by (a) downregulation of X‐linked inhibitor of apoptosis protein, an antiapoptotic protein and (b) by stabilization of RAD21, and thereby inhibiting metaphase to anaphase promotion. The study shows that RF‐C11 or its analogs may be used as a novel additive in combination therapy against cancer.
Prevalence, incidence, and clinical impact of cognitive–motoric risk syndrome in Europe, USA, and Japan: facts and numbers update 2019
Authors: Maggio Marcello , Lauretani Fulvio
Published: August 2019

A new syndrome called the ‘motoric–cognitive risk’ (MCR) syndrome has recently been proposed in older persons. According to this definition, the parallel impairment in muscle and brain function is more predictive for identifying subjects at risk of dementia than impairment a in single system alone. Epidemiological studies suggest that among older persons, enrolled in worldwide population‐based studies, 10% are affected by this syndrome, which confers a higher risk of future disability. In detail, the prevalence of MCR in Europe is around 8.0%, 7.0% in the United States, and 6.3% in Japan. The incidence of the MCR syndrome is estimated to be 65.2 per 1000 person years in adults aged 60 years or older. Many studies reported negative outcomes of the syndrome in older persons, emphasizing its clinical impact. In particular, in almost all longitudinal studies, MCR produces a three‐time increased risk of future dementia. In Europe, data from the InCHIANTI study report an increased risk of 2.74 [1.54–4.86], which is 2.49 [1.52–4.10] in the United States and 3.27 [1.55–6.90] in Japan. The studies in different continents are also consistent in showing an increased risk of all‐cause mortality, which is 1.50–1.87 in the Europeans and 1.69 [1.08–2.02] for incident disability in Japan. For the identification of the MCR syndrome, different tests and procedures have been proposed, with a final ‘core‐battery’ that includes gait speed, dual‐task gait speed, the Montreal Cognitive Assessment and Trail Making Test A and B. The criteria used to select this core‐battery were based on the best accuracy for identifying older persons at risk of negative outcomes such as dementia, falls, aging‐related disabilities, and sensitivity to interventions. The selection of these tests will allow to start studies aimed to better capture older persons at higher risk of mobility and cognitive disability. By these tests, it will be possible to better evaluate the effect of treatment composing of tailored physical exercise, nutritional suggestions, and medical therapy to overturn negative effect of both cognitive and motoric frailty. This article provides an overview of the current knowledge of the MCR syndrome.
Regulation of the firing activity by PKA‐PKC‐Src family kinases in cultured neurons of hypothalamic arcuate nucleus
Authors: Sun Xiao‐Dong , Wang Anqi , Ma Peng , Gong Shan , Tao Jin , Yu Xian‐Min , Jiang Xinghong
Published: August 2019

The cAMP‐dependent protein kinase A family (PKAs), protein kinase C family (PKCs), and Src family kinases (SFKs) are found to play important roles in pain hypersensitivity. However, more detailed investigations are still needed in order to understand the mechanisms underlying the actions of PKAs, PKCs, and SFKs. Neurons in the hypothalamic arcuate nucleus (ARC) are found to be involved in the regulation of pain hypersensitivity. Here we report that the action potential (AP) firing activity of ARC neurons in culture was up‐regulated by application of the adenylate cyclase activator forskolin or the PKC activator PMA, and that the forskolin or PMA application‐induced up‐regulation of AP firing activity could be blocked by pre‐application of the SFK inhibitor PP2. SFK activation also up‐regulated the AP firing activity and this effect could be prevented by pre‐application of the inhibitors of PKCs, but not of PKAs. Furthermore, we identified that forskolin or PMA application caused increases in the phosphorylation not only in PKAs at T197 or PKCs at S660 and PKCα/βII at T638/641, but also in SFKs at Y416. The forskolin or PMA application‐induced increase in the phosphorylation of PKAs or PKCs was not affected by pre‐treatment with PP2. The regulations of the SFK and AP firing activities by PKCs were independent upon the translocation of either PKCα or PKCβII. Thus, it is demonstrated that PKAs may act as an upstream factor(s) to enhance SFKs while PKCs and SFKs interact reciprocally, and thereby up‐regulate the AP firing activity in hypothalamic ARC neurons.
Effect of medical comorbidities on treatment regimen and survival in T3/T4 laryngeal cancer
Authors: Bollig Craig , Ahmad Jumah , Dooley Laura
Published: August 2019

Objective

Investigate the impact of medical comorbidities on treatment regimen and overall survival (OS) in patients with locally advanced laryngeal cancer.

Study Design

Retrospective Review of the National Cancer Database (NCDB).

Methods

The NCDB was queried for patients with T3 and T4 laryngeal cancer. Comorbidity scores were calculated from the Charlson‐Deyo comorbidity index (CDCI). Univariate and multivariate analyses explored the association of CDCI scores on treatment regimen and OS.

Results

14,053 patients were analyzed. 65% of patients had a CDCI score of 0, whereas 25%, 7%, and 3% had CDCI score of 1, 2, and ≥3, respectively. As patients’ CDCI increased, they became more likely to receive treatment options other than a laryngectomy or chemoradiation therapy (CRT) (P < 0.0001). Patients with CDCI ≥1 were more likely have a laryngectomy than those with CDCI 0 (P < 0.0001). In patients with T3 tumors, OS did not differ between those receiving CRT versus laryngectomy with any CDCI score. In patients with T4 tumors, laryngectomy was associated with improved OS compared to CRT across all CDCI scores except CDCI ≥3.

Conclusion

Our results support the current national guidelines with a recommendation for CRT or TL for T3 tumors and a preference for TL for T4 tumors. These outcomes are generally consistent in patients as their CDCI scores increases.

Level of Evidence

NA Laryngoscope, 130:1459–1464, 2020
Obesity May Not Affect Outcomes of Transoral Robotic Thyroidectomy: Subset Analysis of 304 Patients
Authors: Tai Dora Kai Chun , Kim Hoon Yub , Park Dawon , You Jiyoung , Kim Hong Kyu , Russell Jonathon O. , Tufano Ralph P.
Published: August 2019

Objectives/Hypothesis

Obesity is an increasing health concern worldwide. It has been associated with perioperative complications that could affect patient outcomes. Our aim was to compare surgical outcomes in obese and nonobese patients after transoral robotic thyroid (TORT) surgery.

Study Design

Retrospective cohort study.

Methods

A total of 304 consecutive patients who underwent TORT between January 2012 to December 2017 were included in the study. Patients were divided into two groups according to their body mass index (BMI): BMI < 30 kg/m2 and BMI ≥30 kg/m2. Patient demographics, operative extent, pathological data, surgical outcomes, and postoperative complications were included and analyzed. A χ2 test was used to compare categorical variables, and a Student t test was used to compare changes of continuous variables between groups. Statistical significance was conferred by a two‐tailed P value of ≤.05.

Results

There were 290 patients in the non‐obese group and 14 patients in the obese group. There was no statistically significant difference between the two groups in terms of patient demographics, operative procedure, or pathological characteristics. The only statistically significant difference was for lymph node dissection (P = .012); however, for both groups, unilateral central node dissection was the most common procedure. There was also no statistically significant difference found for operative time, length of stay, pain score, or postoperative complications including TORT‐specific complications such as oral commissure tear and general complications such as recurrent nerve injury.

Conclusions

This initial experience shows that TORT appears to be a safe and feasible option for obese patients pursuing scarless thyroid surgery.

Level of Evidence

NA

Laryngoscope, 130:1343–1348, 2020
Thermal elastohydrodynamic lubrication analysis of helical gear pair under starved lubrication condition
Authors: Liu Mingyong , Zhang Jinxi , Xu Peidong , Cai Hao , Ku Haofeng , Wu Chenhui
Published: August 2019

In the present study, thermal starved elastohydrodynamic lubrication (EHL) model is developed for a helical gear pair. The influences of inlet oil‐supply layer, input speed, lubricant viscosity, and surface roughness on the lubrication behaviour are investigated. The minimum film thickness, temperature rise of teeth surfaces and oil film, and the friction coefficient are predicted along the line of action (LOA). Results show that the effects of inlet oil‐supply layer, input speed, and lubrication viscosity on the tribological performance are remarkable. Under the starved lubrication, the influence of inlet oil supply on the temperature rise is insignificant. Meanwhile, the effect of surface roughness has been discussed. It reveals that the roughness texture along the entrainment velocity direction has significant influence on the lubrication characteristics. The results provide the tribological guidance for design of a helical gear pair in engineering.
In situ synthesis of one eco‐friendly polyacrylic acid/zinc colloidal particles doped polyacrylic acid as an efficient corrosion inhibitor for iron
Authors: Gao Xiang , Li Weihua , Ma Houyi
Published: August 2019

Commonly used organic inhibitors face one common problem: Environmental friendliness and excellent inhibition efficiency cannot be simultaneously realized. Here, we report one facile method that can be used for the in situ synthesis of one stable polyacrylic acid/zinc colloidal particles (PZCPs) doped polyacrylic acid (PAA) through the electrostatic interaction between polyacrylic acid and Zn
2+ as a corrosion inhibitor of iron. The results of microstructure characterization indicated that the diameter of the colloidal particles was around 150 nm. The various electrochemical experimental results indicated that PZCPs doped PAA exhibited excellent inhibition efficiency, and the maximum inhibition efficiency was 82.3%. The PZCPs doped PAA exhibited higher inhibition efficiency than PAA because the adsorption ability of PZCPs doped PAA was stronger than that of PAA and the formed PZCPs doped PAA inhibition layer on the iron surface was thicker and denser than the PAA inhibition layer. Given the eco‐friendly, facile synthesis, excellent inhibition efficiency, and low price, this strategy to synthesize effective inhibitors will find widespread application in the anti‐corrosion industry.
Genome‐wide meta‐analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans
Authors: Do Anh N. , Zhao Wei , Baldridge Abigail S. , Raffield Laura M. , Wiggins Kerri L. , Shah Sanjiv J. , Aslibekyan Stella , Tiwari Hemant K. , Limdi Nita , Zhi Degui , Sitlani Colleen M. , Taylor Kent D. , Psaty Bruce M. , Sotoodehnia Nona , Brody Jennifer A. , Rasmussen‐Torvik Laura J. , Lloyd‐Jones Donald , Lange Leslie A. , Wilson James G. , Smith Jennifer A. , Kardia Sharon L. R. , Mosley Thomas H. , Vasan Ramachandran S. , Arnett Donna K. , Irvin Marguerite R.
Published: August 2019

Background

Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography.

Methods

We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)‐by‐drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community‐based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE‐Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta‐analyses of main effects of drugs and 2.5 million SNP‐by‐drug interaction estimates.

Results

We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p = 0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE‐Is with consistent effects across cohorts (smallest p = 4.7 × 10−8, minor allele frequency range 0.09–0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population.

Conclusions

Our study identified one locus having genome‐wide significant SNP‐by‐drug interaction effect on RWT among dCCB users in comparison to ACE‐I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.