bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretreatment lymphocytopenia is an adverse prognostic biomarker in advanced‐stage ovarian cancer
Authors: Lee Yong Jae , Chung Young Shin , Lee Jung‐Yun , Nam Eun Ji , Kim Sang Wun , Kim Sunghoon , Kim Young Tae
Published: January 2019

The aim of this study was to investigate the prognostic significance of lymphocytopenia in advanced‐stage ovarian cancer. We retrospectively reviewed 506 patients with advanced‐stage ovarian cancer at Yonsei Cancer Hospital. This study included two cohorts of patients: a neoadjuvant chemotherapy (NAC) group (N = 247) and a primary debulking surgery (PDS) group (N = 259). The absolute lymphocyte count was recorded before treatment. A receiver operating characteristic (ROC) curve analysis was used to determine the cutoff for defining lymphocytopenia in the NAC cohort and followed by multivariate analysis. Subsequently, lymphocytopenia was assessed in the PDS cohort by multivariate analysis. A further analysis was performed to evaluate the absolute lymphocyte count as a continuous variable. An absolute lymphocyte count of 1.49 × 109/L was determined as the cutoff for the ROC curve analysis in the NAC cohort, and the multivariate analysis revealed that lymphocytopenia was an independent prognostic factor for poor progression‐free survival (PFS) [hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.07‐2.11] and overall survival (OS) (HR, 2.02; 95% CI, 1.21‐3.40). In the PDS cohort, the multivariate analysis showed that lymphocytopenia was an independent prognostic factor for poor PFS (HR, 1.73; 95% CI, 1.20‐2.49) and OS (HR, 1.87; 95% CI, 1.27‐2.75). The absolute lymphocyte count was a significant factor when analyzed as a continuous variable in both the NAC and PDS cohorts. Pretreatment lymphocytopenia is an independent adverse prognostic factor in patients with advanced‐stage ovarian cancer.
Na3V2(PO4)3/N‐doped Carbon Nanocomposites with Sandwich Structure for Cheap, Ultrahigh‐Rate, and Long‐Life Sodium‐Ion Batteries
Authors: Yang Wenhao , He Wen , Zhang Xudong , Yang Guihua , Ma Jingyun , Wang Yaoyao , Wang Chunlian
Published: January 2019

A new nanocomposite composed of ultrathin Na3V2(PO4)3/N‐doped carbon sheets with stable sandwich structure is reported. The material is synthesized using laminar vanadium metal‐organic frameworks (V‐MOFs) as the precursor and multifunction sodium lignosulfonate (SLS) as the organic ligand for the V‐MOFs and the carbon source. The synthetic mechanism and the influence of the SLS and Na contents on the electrochemical properties are investigated, and the Na‐ion insertion/extraction mechanism in the sandwich framework structure is established. The nanocomposite with the molar ratio: V2O5/SLS/Na2CO3=2 : 1.5 : 1.7, used as a cathode material for sodium‐ion batteries, not only exhibits the best discharge capacity (117.3 mA h g−1 at the 0.1 C rate), but also ultra‐high rate performances (82 mAh g−1 at 100 C, 78 mAh g−1 at 200 C and 54 mAh g−1 at 250 C) and a long cycling life (retains 40 mAh g−1 at 200 C over 6000 cycles) because of its unique nanostructure.
High Ion Conducting Solid Composite Electrolytes with Enhanced Interfacial Compatibility for Lithium Metal Batteries
Authors: Feng Haoyu , Ma Cheng , Dai Kuan , Kuang Guichao , Ivey Douglas G. , Wei Weifeng
Published: January 2019

The utilization of lithium metal anodes is crucial for further advancement of the energy density of lithium batteries. Solid electrolytes with high ionic conductivity at ambient temperature and good mechanical strength are key to realizing the large‐scale application of solid‐state lithium‐metal batteries. In particular, the formation of a homogeneous and stable solid‐electrolyte interphase is crucial for improving the safety and coulombic efficiency of lithium‐metal batteries. Herein, a solid composite electrolyte design based on a cyclic carbonate‐cyclic ether copolymer is exploited. The cyclic carbonate segments in the solid composite electrolyte provide high mechanical integrity, whereas the cyclic ether groups promote the dissociation of lithium salts and the formation of a stable solid‐electrolyte interphase. Thus, the solid composite electrolyte exhibits a high ionic conductivity of 1.58×10−4 S cm−1 and a high lithium transference number of 0.55 at room temperature. Furthermore, optimization of the solid‐electrolyte interphase composition and the inhibition of lithium dendrites are demonstrated. Most importantly, excellent rate capability and cycling stability at room temperature and below (10 °C) are achieved in solid‐state lithium‐metal batteries with the solid composite electrolyte.
Chiral separation of aliphatic primary amino alcohols as o‐phthaldialdehyde/mercaptoethanol derivatives on polysaccharide‐based chiral stationary phases
Authors: Douša Michal
Published: January 2019

A sensitive chiral high performance liquid chromatography (HPLC) method for the determination of aliphatic primary amino alcohol isomers with o‐phthaldialdehyde/mercaptoethanol precolumn derivatization has been developed and validated. Seven chiral columns were tested in a reversed phase mode. Excellent enantioseparation with the resolution more than 2.0 was achieved on Chiralcel OJ‐3R. The effect of various chromatographic conditions including column temperature, acetonitrile content in the mobile phase, buffer pH, buffer concentration, and buffer type in the mobile phase on the retention and the selectivity was investigated. The final mobile phase consisted of binary mixture of 20mM ammonium formate solution with acetonitrile (75:25; v/v). The analyses were performed at mobile phase flow rate of 1.0 mL/min and the column temperature of 40°C. The fluorescence detection was performed at excitation wavelength of 345 nm and emission wavelength of 450 nm. The developed method was fully validated in terms of linearity, sensitivity, accuracy, precision, intermediate precision, and selectivity according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines using internal normalization procedure. The proposed chiral method was proved to be highly sensitive, simple, and rapid and was successfully applied to the determination of D‐Valinol content in commercially available samples of L‐Valinol.
ENPRO Data Integration: Extending DEXPI Towards the Asset Lifecycle
Authors: Wiedau Michael , von Wedel Lars , Temmen Heiner , Welke Richard , Papakonstantinou Nikolaos
Published: January 2019

Chemical plants are engineered to yield high output, while also complying to regulations. In initial R&D phases, experts gather large amounts of information to ensure an optimal design. Here, the influence of the optimization of the process on planning and operation of the plant is important. However, during operation of the facility, little of the information required for R&D work is available in electronic and interoperable form. It is described how this challenge can be overcome by a systematic data integration approach using international standards, centered around the DEXPI working group.
Effect of Biochar and Amendments on Pb and As Phytotoxicity and Phytoavailability in a Technosol
Authors: Nandillon Romain , Miard Florie , Lebrun Manhattan , Gaillard Marie , Sabatier Stéphane , Bourgerie Sylvain , Battaglia‐Brunet Fabienne , Morabito Domenico
Published: January 2019

Phytostabilization has been proposed as a promising tool for long‐term management of polluted sites. Optimization of the process efficiency involves choosing suitable amendments to allow both efficient plant growth and the immobilization of contaminants. The objectives of this study are to evaluate the effect of amendments on (i) the physicochemical properties of technosol and (ii) the mobility and phyto‐availability of metal(loid)s. A dwarf bean growth test is conducted on technosols amended with compost, garden soil, slag, and biochar. The physicochemical properties of soil pore water (SPW) are determined as well as the phyto‐available concentrations of metal(loid)s by simple extraction tests. All amendments used are able to increase SPW pH and electrical conductivity, allowing a decrease in the lead concentration in SPW by 90% and the lead phytoavailable part by 93%. However, for all amendments, SPW As concentration increased. Lastly, the amendments improve bean growth and tend to decrease the metal(oid) concentrations in aerial organs. As concentration in roots did not decrease whereas Pb concentration decreased. Metal(loid) concentrations of Pb accumulated in the aerial parts of beans and their extractable concentrations show a significant positive correlation with the extraction procedures. In contrast, the phytoavailable As shows a weak correlation with As concentrations in the aerial parts. The 1‐M NH4NO3 extraction procedure is the most appropriate and provides the most useful indications of the phyto‐availability for the studied elements.
Identification of the Binding Site of Apical Membrane Antigen 1 (AMA1) Inhibitors Using a Paramagnetic Probe
Authors: Akter Mansura , Drinkwater Nyssa , Devine Shane M. , Drew Simon C. , Krishnarjuna Bankala , Debono Cael O. , Wang Geqing , Scanlon Martin J. , Scammells Peter J. , McGowan Sheena , MacRaild Christopher A. , Norton Raymond S.
Published: January 2019

Apical membrane antigen 1 (AMA1) is essential for the invasion of host cells by malaria parasites. Several small‐molecule ligands have been shown to bind to a conserved hydrophobic cleft in Plasmodium falciparum AMA1. However, a lack of detailed structural information on the binding pose of these molecules has hindered their further optimisation as inhibitors. We have developed a spin‐labelled peptide based on RON2, the native binding partner of AMA1, to probe the binding sites of compounds on PfAMA1. The crystal structure of this peptide bound to PfAMA1 shows that it binds at one end of the hydrophobic groove, leaving much of the binding site unoccupied and allowing fragment hits to bind without interference. In paramagnetic relaxation enhancement (PRE)‐based NMR screening, the 1H relaxation rates of compounds binding close to the probe were enhanced. Compounds experienced different degrees of PRE as a result of their different orientations relative to the spin label while bound to AMA1. Thus, PRE‐derived distance constraints can be used to identify binding sites and guide further hit optimisation.
Scaling deep learning without increasing batchsize
Authors: Heye Alexander
Published: January 2019

Deep learning has proven itself to be a difficult problem in the HPC space. Although the algorithm can scale very efficiently with a sufficiently large batchsize, the efficacy of training tends to decrease as the batchsize grows. Scaling the training of a single model may be effective in narrow fields such as image classification, but more generalizable options can be achieved when considering alternate methods of parallelism and the larger workflow surrounding neural network training. Hyperparameter optimization, data set segmentation, hierarchical fine tuning, and model parallelism can all provide significant scaling capacity without increasing batchsize and can be paired with a traditional, single‐model scaling approach for a multiplicative scaling improvement. This paper intends to further define and examine these scaling techniques in how they perform individually and how combining them can provide significant improvements in overall training times.
A scalable and secure RFID mutual authentication protocol using ECC for Internet of Things
Authors: Naeem Muhammad , Chaudhry Shehzad Ashraf , Mahmood Khalid , Karuppiah Marimuthu , Kumari Saru
Published: January 2019

Very recently, Alamr et al (J. Supercomput 1‐14 doi: 10.1007/s11227‐016‐1861‐1) presented a radio frequency identifier (RFID) authentication protocol for the Internet of Things (IoT) through elliptic curve cryptography (ECC). They claimed the protocol to achieve several security properties and thwart all known attacks. However, this paper shows that their scheme is having correctness and scalability issues. The reader in their protocol can accommodate only one tag, which is not desirable in the IoT environments. The paper finally suggests an improvement to cater the correctness and scalability issues.
Functional responses in habitat selection: clarifying hypotheses and interpretations
Authors: Holbrook Joseph D. , Olson Lucretia E. , DeCesare Nicholas J. , Hebblewhite Mark , Squires John R. , Steenweg Robin
Published: January 2019

A fundamental challenge in habitat ecology and management is understanding the mechanisms generating animal distributions. Studies of habitat selection provide a lens into such mechanisms, but are often limited by unrealistic assumptions. For example, most studies assume that habitat selection is constant with respect to the availability of resources, such that habitat use remains proportional to availability. To the contrary, a growing body of work has shown the fallacy of this assumption, indicating that animals modify their behavior depending on the context at broader scales. This has been termed a functional response in habitat selection. Furthermore, a diversity of methods is employed to model functional responses in habitat selection, with little attention to how methodology might affect scientific and conservation conclusions. Here, we first review the conceptual and statistical foundations of methods currently used to model functional responses and clarify the ecological tests evaluated within each approach. We then use a combination of simulated and empirical data sets to evaluate the similarities and differences among approaches. Importantly, we identified multiple statistical issues with the most widely applied approaches to understand functional responses, including: (1) a complex and important role of random‐ or individual‐level intercepts in adjusting individual‐level regression coefficients as resource availability changes and (2) a sensitivity of results to poorly informed individual‐level coefficients estimated for animals with low availability of a given resource. Consequently, we provide guidance on applying approaches that are insensitive to these issues with the goal of advancing our understanding of animal habitat ecology and management. Finally, we characterize the management implications of assuming similarity between the current approaches to model functional responses with two empirical data sets of federally threatened species: Canada lynx (Lynx canadensis) in the United States and woodland caribou (Rangifer tarandus caribou) in Canada. Collectively, our assessment helps clarify the similarities and differences among current approaches and, therefore, assists the integration of functional responses into the mainstream of habitat ecology and management.
Blunted emotion‐modulated startle reflex in anorexia nervosa
Authors: Brockmeyer Timo , Pellegrino Judith , Maier Christoph , Münch Hannah M. , Harmer Catherine J. , Walther Stephan , Herzog Wolfgang , Friederich Hans‐Christoph
Published: January 2019

Objective

Patients with anorexia nervosa (AN) often show difficulties in the perception, expression, and regulation of emotions and a strong avoidance of aversive feelings. According to psychobiological models, dietary restraint and accompanying weight loss may serve as a maladaptive mechanism of emotion regulation by attenuating aversive emotional states in AN, thereby contributing to the maintenance of the disorder.

Method

Twenty‐seven women with AN and 26 age‐matched healthy women were shown short film‐clips to elicit fear, sadness, amusement, and neutral emotional states. Eyeblink startle response was measured by electromyography in reaction to startle‐eliciting acoustic stimuli presented 12 times binaurally during each film‐clip.

Results

As compared to healthy controls, patients with AN showed a blunted startle response to the fear‐ but not to the sadness‐eliciting stimulus.

Discussion

The findings support the assumption that underweight is associated with attenuated emotional reactivity to fear‐eliciting material in AN. This is in line with the hypothesis that starvation and low body weight constitute a maladaptive mechanism of emotion regulation in AN, contributing to the maintenance of the disorder.
The Role of Electron‐Donor Substituents in the Family of OPBAN‐Cu Water Oxidation Catalysts: Effect on the Degradation Pathways and Efficiency
Authors: de Aguirre Adiran , Garrido‐Barros Pablo , Funes‐Ardoiz Ignacio , Maseras Feliu
Published: January 2019

The efficiency of the OPBAN‐Cu (OPBAN= tetraanionic derivative of 1,2‐phenylene bis(oxamic acid)) water oxidation catalyst family has been studied by DFT calculations. We have explored four different tetraamidate copper complexes [(L1–4)Cu]2– (where L1 is N1,N1′‐(1,2‐phenylene)bis(N2‐methyloxalamidate) and L2–4 are variations of the same ligand with electron donating groups in the ring backbone), determining the redox active character of the ligand in the activation process and the Single Electron Transfer‐Water Nucleophilic Attack (SET‐WNA) mechanism for the O–O bond formation step. Interestingly, the stability of the two‐center three‐electron (2c3e–) intermediate, common in the four reactions, correlates with the experimental efficiency. Additionally, we explored two pathways of catalyst degradation: the attack of a hydroxyl anion to the phenyl cation radical of the ligand and the degradation by protonation of the amidate groups when pH decreases. This last step is supported by cyclic voltammetry pH‐dependent experiments.
A Novel Aqueous Extraction for Camellia Oil by Emulsified Oil: A Frozen/Thawed Method
Authors: Yang Jian‐Yuan , Li Jing , Wang Mei , Zou Xian‐Guo , Peng Bin , Yin Yu‐Long , Deng Ze‐Yuan
Published: January 2019

Emulsion is inevitable during the aqueous extraction of oil from oilseeds. In this study, a new aqueous extraction method for camellia oil is investigated. During the extraction, the emulsified oil is collected, frozen, and thawed, and the free oil is obtained (AEEF). The optimal processing conditions are as follows: three times as much water as camellia seed powder (w/w), grinding at 70 °C for 6 min, repeating 2 cycles to collect the emulsified oil; then the emulsified oil is frozen (−20 °C) /thawed (50 °C) for 2 cycles. The yield of camellia oil is 89.37 ± 0.51%, which is significantly higher (p < 0.05) than that of microwave‐assisted aqueous enzymatic extraction (MAAEE, 83.05 ± 1.14%), and is similar to that of cold press extraction (CPE, 90.85 ± 2.05%), as well as solvent extraction (SE) coupled with refining. Additionally, the total oxidation value (TOTOX) of the free oil extracted by using AEEF (AEEF‐Oil, 6.82 ± 0.12%) is significantly lower (p < 0.05) than those of MAAEE, CEP, or SE. In comparison to SE‐Oil and CEP‐Oil, AEEF‐Oil has higher (p < 0.05) contents of α‐tocopherol and squalene, and lower (p < 0.05) benzo(a)pyrene contents, and contains more favorable natural volatile compounds. The results indicate that the novel AEEF may be a promising aqueous extraction method.

Practical Application: The novel aqueous extraction method for camellia oil by emulsified oil – frozen/thawed has acceptable oil yields. The obtained camellia oil has high levels of bioactive components, low contents of hazardous substances, and more characteristic volatile flavor compounds. AEEF is an improved aqueous extraction technology for edible oil without refining and using n‐hexane, which could be potentially applied in industrial production of camellia oil due to its safety, nutrition, and environment‐friendly treatments.

Aqueous extraction is a promising technique for edible oil extraction from oilseeds. The novel technology of aqueous extraction for camellia oil through emulsified oil – frozen/thawed (AEEF) is investigated. In comparison to solvent extraction, cold press extraction, and microwave‐assisted aqueous enzymatic extraction of camellia oil, the obtained camellia oil by AEEF has an acceptable oil yield, high quality, and nutritional value. AEEF is a safe, simple and environmental‐friendly aqueous extraction technology.
Metal‐based additives “acetylferrocene and ruthenium polypyridyl complex” to improve performance and emission characteristics of ci engine
Authors: Resitoglu Ibrahim Aslan
Published: January 2019

Metal‐based fuel additives have been promising alternative choice to improve diesel engine performance and emission characteristics. Many studies have been performed on use of metal‐based fuel additives such as magnesium, platinum, titanium, and cerium in diesel engine. Unlike conventional metal‐based additives, Acetylferrocene and Ruthenium polypyridyl complex may be alternative metal‐based additives for diesel. This study intends to investigate performance and emission variations of a diesel engine powered by diesel blended with Acetylferrocene and Ruthenium polypyridyl complex additives. In accordance with this purpose, a single cylinder, direct injection diesel engine was used to test these alternative metal additives. Results showed that Acetylferrocene and Ruthenium polypyridyl complex were effective to improve emission characteristics without causing degradation in performance. CO and Soot emissions were showed decrease up to 40% and 32%, respectively, and the fuel consumption characteristic of engine was improved with additives. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13146, 2019
Late Triassic high‐Mg diorites and associated mafic dikes from the southern Zhangguangcai Range (NE China): Melting of juvenile arc crust and subarc mantle lithosphere
Authors: Li Yong‐Fei , Qin Jiang‐Feng , Lai Shao‐Cong , Sun Shou‐Liang , Zhang Ze‐Zhong , Gao Xiao‐Yong , Ju Yin‐Juan , Zhang Tao , Wang Xing‐Ying
Published: January 2019

The Lesser Xing'an–Zhangguangcai Range is located in the eastern part of the Central Asian Orogenic Belt (CAOB). Early Mesozoic igneous rocks in this area can place constraints on the crustal growth mechanism in the Northeastern China. This paper reports a suite of Late Triassic high‐Mg diorites and mafic dikes from the southern Lesser Xing'an–Zhangguangcai Range. The mafic dikes have younger zircon U–Pb ages of 195 ± 2 Ma. They display intermediate SiO2 (50.58% to 58.20%) and high Na2O/K2O ratios of 1.90 to 3.20, low A/CNK ratios of 0.75 to 0.84, low (87Sr/86Sr)i ratios of 0.7045 to 0.7046, and high εNd(t) values of +3.1 to +3.5. Most zircons in the mafic dikes exhibit positive εHf(t) values from +8.6 to +16.0, with single‐stage Hf model ages ranging from 0.2 to 0.5 Ga in combination with their enrichment in LREE and LILEs and depletion in HFSEs. They are considered to be formed by melting of metasomatized subarc lithosphere mantle. The diorite and quartz diorite have older zircon U–Pb ages of 200 ± 3 and 202 ± 2 Ma, respectively. They have SiO2 = 54.45% to 61.18%, Al2O3 = 17.16% to 19.10%, TiO2 = 0.74% to 1.13%, and Mg# = 46.6 to 49.5, and they also display moderately depleted Sr–Nd (εNd(t) = +2.3 to +4.3) and zircon Lu–Hf (εHf(t) = +8.6 to +16.0) isotopic compositions. These features suggest that they were formed by melting of juvenile arc crust in active continental margin. Considering the occurrence of the contemporaneous and latter igneous rocks in the Zhangguangcai Range, we argue that the diorite, quartz diorite, and mafic dikes from the Lengshan area were also related to the westward subduction of Palaeo‐Pacific Plate (Izanagi Plate) beneath the Eurasian Plate. The strike‐like fault along the eastern margin of the Songneng–Zhuangguangcai Block may play an important role in the genesis of diorite melt.
The supplementary motor area modulates interhemispheric interactions during movement preparation
Authors: Welniarz Quentin , Gallea Cécile , Lamy Jean‐Charles , Méneret Aurélie , Popa Traian , Valabregue Romain , Béranger Benoît , Brochard Vanessa , Flamand‐Roze Constance , Trouillard Oriane , Bonnet Cécilia , Brüggemann Norbert , Bitoun Pierre , Degos Bertrand , Hubsch Cécile , Hainque Elodie , Golmard Jean‐Louis , Vidailhet Marie , Lehéricy Stéphane , Dusart Isabelle , Meunier Sabine , Roze Emmanuel
Published: January 2019

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed‐response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta‐burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.
Transoral robotic excision of laryngocele: Surgical considerations
Authors: Patel Krupal B. , Lin Chen , Kramer Scott , Fada Craig , Ozer Enver
Published: January 2019

Background

Transoral robotic surgery (TORS) has emerged as a novel, safe, and feasible procedure for the resection of malignant supraglottic laryngeal cancers. The purpose of this study was to demonstrate the surgical technique with extension of the use of TORS to excise a laryngeal cyst.

Results

Laryngeal cyst resection, along with its tract, was accomplished with preservation of both false and true vocal cords. There was no perioperative or early postoperative complications. The patient was extubated immediately after surgery. Oral diet was initiated within 24 hours. No tracheostomy was required. A video demonstration of the surgical technique is included on Head & Neck's website.

Conclusion

TORS is a safe and feasible procedure for excision of selected laryngeal cysts.
Prognostic factors in recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: Mirabile Aurora , Miceli Rosalba , Calderone Rosa Gioia , Locati Laura , Bossi Paolo , Bergamini Cristiana , Granata Roberta , Perrone Federica , Mariani Luigi , Licitra Lisa
Published: January 2019

Background

In clinical trials of recurrent and metastatic head and neck carcinoma, Argiris et al have identified prognostic factors for overall survival (OS) and progression‐free survival (PFS), weight loss, Eastern Cooperative Oncology Group performance status (ECOG‐PS), tumor primary site, tumor differentiation, prior radiotherapy, deriving a two‐group prognostic classification. This study evaluates Argiris's classification in “field‐practice” patients.

Methods

The main analysis included 327 cases; a secondary analysis excluded 31 patients with oropharyngeal carcinoma (OPC) p16‐positive and/or human papilloma virus (HPV)‐positive. OS and PFS curves were estimated with the Kaplan‐Meier method; multivariable Cox analyses were also performed.

Results

In the full series, OS was significantly different in patients with 0‐2 and ≥3 adverse features (median, 14 vs 10 months; P = .03). PFS was statistically different in the two groups (median, 7 vs 5 months; P = .02). At a multivariable analysis investigating additional prognostic features, site of relapse and disease‐free interval were significant predictors of OS and PFS.

Conclusion

The Argiris's model was confirmed in a “field‐practice” population. Moreover, we found additional putative prognostic factors.
Deficiency of Mitochondrial Glycerol 3‐Phosphate Dehydrogenase Contributes to Hepatic Steatosis
Authors: Zheng Yi , Qu Hua , Xiong Xin , Wang Yuren , Liu Xiufei , Zhang Linlin , Liao Xiaoyu , Liao Qian , Sun Zheng , Ouyang Qin , Yang Gangyi , Zhu Zhiming , Xu Jing , Zheng Hongting
Published: January 2019

Mitochondrial glycerol 3‐phosphate dehydrogenase (mGPDH) is an integral component of the respiratory chain, and recent studies have suggested that it plays an important role in hepatic glucose homeostasis. However, its function in hepatic lipid metabolism is unclear. Here, we identified a role for mGPDH in nonalcoholic fatty liver disease (NAFLD). Specifically, mGPDH expression and activity were lower in fatty livers from patients and mice with NAFLD (ob/ob, high‐fat diet [HFD] and db/db). Liver‐specific depletion of mGPDH in mice or mGPDH knockdown in cultured hepatocytes exacerbated diet‐induced triglyceride accumulation and steatosis through enhanced lipogenesis. RNA‐sequencing revealed that mGPDH regulated endoplasmic reticulum (ER)‐related proteins and processes. mGPDH deletion exacerbated tunicamycin (ER stress inducer)‐induced hepatic steatosis, whereas tauroursodeoxycholic acid (ER stress inhibitor) rescued mGPDH depletion–induced steatosis on an HFD. Moreover, ER stress induced by mGPDH depletion could be abrogated by the intracellular Ca2+ chelator 1,2‐bis (2‐aminophenoxy) ethane N,N,N´,N´‐tetraacetic acid acetoxymethyl ester, mitochondrial permeability transition pore (mPTP) inhibitor cyclosporine A, or cyclophilin‐D (Cyp‐D) knockdown. mGPDH promoting Cyp‐D ubiquitination was also observed. Finally, liver‐specific mGPDH overexpression attenuated hepatic steatosis in ob/ob and HFD mice. Conclusion: mGPDH is a pivotal regulator of hepatic lipid metabolism. Its deficiency induces ER stress by suppressing Cyp‐D ubiquitination, a key regulator of the mitochondrial Ca2+ conductance channel mPTP, and results in hepatic steatosis. mGPDH may be a potential therapeutic target for the treatment of NAFLD.
Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases
Authors: Volckmar Anna‐Lena , Leichsenring Jonas , Kirchner Martina , Christopoulos Petros , Neumann Olaf , Budczies Jan , Morais de Oliveira Cristiano Manuel , Rempel Eugen , Buchhalter Ivo , Brandt Regine , Allgäuer Michael , Talla Suranand Babu , von Winterfeld Moritz , Herpel Esther , Goeppert Benjamin , Lier Amelie , Winter Hauke , Brummer Tilman , Fröhling Stefan , Faehling Martin , Fischer Jürgen R. , Heußel Claus Peter , Herth Felix , Lasitschka Felix , Schirmacher Peter , Thomas Michael , Endris Volker , Penzel Roland , Stenzinger Albrecht
Published: January 2019

Tyrosine kinase inhibitors currently confer the greatest survival gain for nonsmall cell lung cancer (NSCLC) patients with actionable genetic alterations. Simultaneously, the increasing number of targets and compounds poses the challenge of reliable, broad and timely molecular assays for the identification of patients likely to benefit from novel treatments. Here, we demonstrate the feasibility and clinical utility of comprehensive, NGS‐based genetic profiling for routine workup of advanced NSCLC based on the first 3,000 patients analyzed in our department. Following automated extraction of DNA and RNA from formalin‐fixed, paraffin‐embedded tissue samples, parallel sequencing of DNA and RNA for detection of mutations and gene fusions, respectively, was performed using PCR‐based enrichment with an ion semiconductor sequencing platform. Overall, 807 patients (27%) were eligible for currently approved, EGFR‐/BRAF‐/ALK‐ and ROS1‐directed therapies, while 218 additional cases (7%) with MET, ERBB2 (HER2) and RET alterations could potentially benefit from experimental targeted compounds. In addition, routine capturing of comutations, e.g. TP53 (55%), KEAP1 (11%) and STK11 (11%), as well as the precise typing of fusion partners and involved exons in case of actionable translocations including ALK and ROS1, are prognostic and predictive tools currently gaining importance for further refinement of therapeutic and surveillance strategies. The reliability, low dropout rates (<5%), minimal tissue requirements, fast turnaround times (6 days on average) and lower costs of the diagnostic approach presented here compared to sequential single‐gene testing, highlight its practicability in order to support individualized decisions in routine patient care, enrollment in molecularly stratified clinical trials, as well as translational research.
Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer
Authors: Varga Zsuzsanna , Sinn Peter , Seidman Andrew D.
Published: January 2019

Many genomic assays that assess recurrence risk in early breast cancer (EBC) are prognostic, but they differ in risk group stratification, which can affect clinical utility. Prospective outcomes of >60 K patients treated based on the 21‐gene assay results have shown that chemotherapy may be safely omitted in EBC patents with low Recurrence Score (RS) results (RS < 18). Because of its extensive validation and wide clinical use, the RS assay is a common comparator in head‐to‐head studies with other assays. Published/presented studies of the RS assay performed on the same tumor samples with Breast Cancer Index (BCI), EndoPredict (EP) or EP+ clinical features (EPclin), MammaPrint (MMP) and/or Prosigna (ROR) assays were reviewed. Study findings were summarized descriptively.
Podocan affects C2C12 myogenic differentiation by enhancing Wnt/β‐catenin signaling
Authors: Liu Dan , Li Shuang , Cui Yafeng , Tong Huili , Li Shufeng , Yan Yunqin
Published: January 2019

Podocan, a small leucine‐rich repeat protein, is a negative regulator of cell proliferation. In this study, we demonstrated that podocan is involved in the differentiation of C2C12 murine myoblasts. Podocan expression increased with the progression of C2C12 differentiation. As expect, siRNA‐mediated podocan knockdown inhibited C2C12 differentiation, as indicated by inhibition of MYOG, MYH2, and desmin expression, as well as reductions in the differentiation and fusion indices. Overexpression of podocan using dCas9 technology promoted C2C12 cell differentiation. In addition, supplementation of culture medium with podocan influenced C2C12 differentiation. Podocan knockdown reduced Wnt/β‐catenin signaling, characterized by a reduction in the nuclear translocation of β‐catenin, whereas podocan overexpression had the opposite effect. Furthermore, treatment with XAV939, an inhibitor of Wnt/β‐catenin, reduced the podocan‐mediated promotion of C2C12 differentiation. Induction of muscle injury in mice by bupivacaine administration suggested that podocan may play a role in muscle regeneration. In summary, our results suggest that podocan is required for normal C2C12 differentiation and that its role in myogenesis is mediated by the Wnt/β‐catenin pathway.
SP1‐SYNE1‐AS1‐miR‐525‐5p feedback loop regulates Ang‐II‐induced cardiac hypertrophy
Authors: Wang Ye , Cao Rongyi , Yang Wenwen , Qi Bangruo
Published: January 2019

Cardiac hypertrophy (CH) has become a huge threat to human health. Recent years, long noncoding RNAs (lncRNAs) have been studied in human diseases, including CH. According to bioinformatics analysis, 10 lncRNAs possibly involved in the progression of CH were screened out. Among which, lncRNA SYNE1 antisense RNA 1 (SYNE1‐AS1) could be upregulated by Angiotensin II (Ang‐II) in cardiomyocytes. Thus, we chose SYNE1‐AS1 to do further study. To identify the biological function of SYNE1‐AS1 in CH, SYNE1‐AS1 was silenced in Ang‐II‐induced cardiomyocytes. Results of immunofluorescence staining demonstrated that increased cell surface area in Ang‐II‐induced cardiomyocytes was reduced by SYNE1‐AS1 knockdown. Moreover, the hypertrophic responses were attenuated by SYNE1‐AS1 knockdown. Mechanically, SYNE1‐AS1 positively regulated Sp1 transcription factor (SP1) by sponging microRNA‐525‐5p (miR‐525‐5p). On the basis of previous reports, SP1 can transcriptionally activate lncRNAs. Therefore, we investigated the interaction between SP1 and SYNE1‐AS1 promoter. Intriguingly, SYNE1‐AS1 was activated by SP1. At last, rescue assays demonstrated the function of SP1‐SYNE1‐AS1 axis in CH. In conclusion, SP1‐induced upregulation of lncRNA SYNE1‐AS1 promoted CH via miR‐525‐5p/SP1 axis.
Epigenetic mechanisms are behind the regulation of the key genes associated with the osteoblastic differentiation of the mesenchymal stem cells: The role of zoledronic acid on tuning the epigenetic changes
Authors: Marofi Faroogh , Hassanzadeh Ali , Solali Saeed , Vahedi Ghasem , Mousavi Ardehaie Reza , Salarinasab Sadegh , Aliparasti Mohammad Reza , Ghaebi Mahnaz , Farshdousti Hagh Majid
Published: January 2019

Mesenchymal stem cells (MSCs) are multipotent stem cells and show distinct features such as capability for self‐renewal and differentiation into several lineages of cells including osteoblasts, chondrocytes, and adipocytes. In this study, the methylation status of the promoter region of zinc finger and BTB domain containing 16 (ZBTB16), twist‐related protein 1(Twist1), de novo DNA methyltransferases 3A (DNMT3A), SRY‐box 9 (Sox9), osteocalcin (OCN), and peroxisome proliferator‐activated receptor γ2 (PPARγ2) genes and their messenger RNA (mRNA) expression levels were evaluated during the osteoblastic differentiation of MSCs (ODMSCs). We planned two experimental groups including zoledronic acid (ZA)‐treated and nontreated cells (negative control) which both were differentiated into the osteoblasts. Methylation level of DNA in the promoter regions was assayed by methylation‐specific‐quantitative polymerase chain reaction (MS‐qPCR), and mRNA levels of the target inhibitory/stimulatory genes during osteoblastic differentiation of MSCs were measured using real‐time PCR. During the experimental induction of ODMSCs, the mRNA expression of the OCN gene was upregulated and methylation level of its promoter region was decreased. Moreover, Sox9 and PPARγ2 mRNA levels were attenuated and their promoter regions methylation levels were significantly augmented. However, the mRNA expression of the DNMT3A was not affected during the ODMSCs though its methylation rate was increased. In addition, ZA could enhance the expression of the ZBTB16 and decrease its promoter regions methylation and on the opposite side, it diminished mRNA expression of Sox9, Twist1, and PPARγ2 genes and increased their methylation rates. Intriguingly, ZA did not show a significant impact on gene expression and methylation levels the OCN and DNMT3A. We found that methylation of the promoter regions of Sox9, OCN, and PPARγ2 genes might be one of the main mechanisms adjusting the genes expression during the ODMSCs. Furthermore, we noticed that ZA can accelerate the MSCs differentiation to the osteoblast cells via two regulatory processes; suppression of osteoblastic differentiation inhibitor genes including Sox9, Twist1, and PPARγ2, and through promotion of the ZBTB16 expression.
Identification of differentially expressed genes and biological characteristics of colorectal cancer by integrated bioinformatics analysis
Authors: Sun Guangwei , Li Yalun , Peng Yangjie , Lu Dapeng , Zhang Fuqiang , Cui Xueyang , Zhang Qingyue , Li Zhuang
Published: January 2019

Colorectal cancer (CRC) ranks as one of the most common malignant tumors worldwide. Its mortality rate has remained high in recent years. Therefore, the aim of this study was to identify significant differentially expressed genes (DEGs) involved in its pathogenesis, which may be used as novel biomarkers or potential therapeutic targets for CRC. The gene expression profiles of GSE21510, GSE32323, GSE89076, and GSE113513 were downloaded from the Gene Expression Omnibus (GEO) database. After screening DEGs in each GEO data set, we further used the robust rank aggregation method to identify 494 significant DEGs including 212 upregulated and 282 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by DAVID and the KOBAS online database, respectively. These DEGs were shown to be significantly enriched in different cancer‐related functions and pathways. Then, the STRING database was used to construct the protein–protein interaction network. The module analysis was performed by the MCODE plug‐in of Cytoscape based on the whole network. We finally filtered out seven hub genes by the cytoHubba plug‐in, including PPBP,
CCL28,
CXCL12,
INSL5,
CXCL3,
CXCL10, and
CXCL11. The expression validation and survival analysis of these hub genes were analyzed based on The Cancer Genome Atlas database. In conclusion, the robust DEGs associated with the carcinogenesis of CRC were screened through the GEO database, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for CRC.
Co3(PO4)2/Ag3PO4 with enhanced simulated sunlight photocatalytic activity toward ofloxacin degradation and mechanism insight
Authors: Geng Zhi , Yang Min , Qi Xin , Li Zhaoyang , Yang Xia , Huo Mingxin , Crittenden John C
Published: January 2019

BACKGROUND

Ofloxacin is a frequently detected fluoroquinolone antibiotic in wastewater treatment plant effluents, sea waters and surface waters. Photocatalytic technology is considered to be the most promising treatment technology for the removal of ofloxacin. However, it is a big challenge to exploit a novel sunlight‐driven photocatalyst and reveal the mechanism of ofloxacin degradation.

RESULTS

Co3(PO4)2/Ag3PO4 composites were prepared using a facile hydrothermal synthesis method. The structural, morphological and optical properties of the composites were well characterized. Both the degradation efficiency and cyclical stability of the Co3(PO4)2/Ag3PO4 composites increased significantly under simulated sunlight irradiation when ofloxacin (OFX) or methyl orange (MO) was used as the target molecule, as compared with single‐phase Ag3PO4 and Co3(PO4)2. The reduction of antimicrobial activity for 8%Co3(PO4)2/Ag3PO4 reached 88.8% after 5 min of sunlight irradiation.

CONCLUSION

Co3(PO4)2 played a critical role in suppressing carrier recombination and provided a large number of photogenerated holes and •O2− to oxidize OFX or MO. The OFX degradation mechanism included piperazinyl dealkylation, decarboxylation and defluorination. The reduction of antimicrobial activity for degradation byproducts was obvious after simulated sunlight irradiation over Co3(PO4)2/Ag3PO4. Therefore Co3(PO4)2/Ag3PO4 is an attractive candidate for the removal of OFX. © 2019 Society of Chemical Industry
Pitch control and speed limitation during overground deceleration in lemurid primates
Authors: Miller Charlotte E. , Pinkard Henry , Johnson Laura E. , Schmitt Daniel
Published: January 2019

An animal's fitness is influenced by the ability to move safely through its environment. Recent models have shown that aspects of body geometry, for example, limb length and center of mass (COM) position, appear to set limits for pitch control in cursorial quadrupeds. Models of pitch control predict that the body shape of these and certain other primates, with short forelimbs and posteriorly positioned COM, should allow them to decelerate rapidly while minimizing the risk of pitching forward. We chose to test these models in two non‐cursorial lemurs: Lemur catta, the highly terrestrial ring‐tailed lemur, and Eulemur fulvus, the highly arboreal brown lemur. We modeled the effects of changes in limb length and COM position on maximum decelerative potential for both species, as well as collecting data on maximal decelerations across whole strides. In both species, maximum measured decelerations fell below the range of pitch‐limited deceleration values predicted by the geometric model, with the ring‐tailed lemur approaching its pitch limit more closely. Both lemurs showed decelerative potential equivalent to or higher than horses, the only comparative model currently available. These data reinforce the hypothesis that a relatively simple model of body geometry can predict aspects of maximum performance in animals. In this case, it appears that the body geometry of primates is skewed toward avoiding forward pitch in maximal decelerations.
3D‐ASL perfusion correlates with VEGF expression and overall survival in glioma patients: Comparison of quantitative perfusion and pathology on accurate spatial location‐matched basis
Authors: Pang Haopeng , Dang Xuefei , Ren Yan , Zhuang Dongxiao , Qiu Tianming , Chen Hong , Zhang Jie , Ma Ningning , Li Gang , Zhang Junhai , Wu Jinsong , Feng Xiaoyuan
Published: January 2019

Background

There is a need for an imaging‐based tool for measuring vascular endothelial growth factor (VEGF) expression and overall survival (OS) in patients with glioma.

Purpose

To assess the correlation between cerebral blood flow (CBF), measured by 3D pseudo‐continuous arterial spin‐labeling (3D‐ASL), and VEGF expression in gliomas on the basis of coregistered localized biopsy, and investigate whether CBF correlated with survival month (SM) in glioma patients.

Study Type

Prospective cohort.

Subjects

Thirty‐seven patients with gliomas from whom 63 biopsy specimens were obtained.

Sequence

3D‐ASL acquired with a 3.0T MR unit.

Assessment

Biopsy specimens were grouped as high‐grade (HGG) or low‐grade glioma (LGG). CBF measurements were spatially matched with VEGF expression by coregistered localized biopsies, and the CBF value was correlated with quantitative VEGF expression for each specimen. Patients' survival information was derived and connected with CBF.

Statistical Tests

Patients' OS was analyzed by Kaplan–Meier and Cox‐regression methods. VEGF expression and CBF were compared in both LGG and HGG. The Spearman rank correlation was calculated for CBF and VEGF expression, SM. Significance level, P < 0.05.

Results

CBF‐derived 3D‐ASL positively correlated significantly with VEGF expression in both LGG (31 specimens) and HGG (32 specimens), r = 0.604 (P < 0.001) and r = 0.665 (P < 0.001), respectively. LGG and HGG together gave a correlation coefficient r = 0.728 (P < 0.001). Median survival for LGG and HGG patients was 34.19 and 17.17 months, respectively (P = 0.037); CBF value negatively correlated significantly with SM with r = –0.714 (P < 0.001) regardless of glioma grade. CBF was an independent risk factor for OS with HR = 1.027 (P = 0.044), 1.028 (P = 0.010) for univariate/multivariate regression analysis.

Data Conclusion

CBF determined by 3D‐ASL correlates with VEGF expression in glioma and is an independent risk factor for OS in these patients.

Level of Evidence: 1

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2019;50:209–220.