bluuebunny/crossref_metadata_2025 huggingface dataset:
Pap smears with glandular cell abnormalities: Are they detected by rapid prescreening?
Authors: Kanber Yonca , Charbonneau Michele , Auger Manon
Published: September 2015

BACKGROUND

Rapid prescreening (RPS) is one of the quality assurance (QA) methods used in gynecologic cytology. The efficacy of RPS has been previously studied but mostly with respect to squamous lesions; in fact, there has been no study so far specifically looking at the sensitivity of RPS for detecting glandular cell abnormalities.

METHODS

A total of 80,565 Papanicolaou (Pap) smears underwent RPS during a 25‐month period. A sample was designated as “review for abnormality” (R) if any abnormal cells (at the threshold of atypical squamous cells of undetermined significance/atypical glandular cells [AGC]) were thought to be present or was designated as negative (N) if none were detected. Each sample then underwent full screening (FS) and was designated as either R or N and also given a cytologic interpretation.

RESULTS

The final cytologic interpretation was a glandular cell abnormality (≥AGC) in 107 samples (0.13%); 39 of these (36.4%) were flagged as R on RPS. Twenty‐four patients (33.8%) out of 71 who had histologic follow‐up were found to harbor a high‐grade squamous intraepithelial lesion or carcinoma; 13 of those 24 Pap smears (54.2%) had been flagged as R on RPS. Notably, 11 AGC cases were picked up by RPS only and not by FS and represented false‐negative cases; 2 of these showed endometrial adenocarcinoma on histologic follow‐up.

CONCLUSIONS

Pap smears with glandular cell abnormalities are often flagged as abnormal by RPS, and this results in a sensitivity of 36.4% (at the AGC threshold). Most importantly, some cases of AGC are detected on Pap smears by RPS only, and this demonstrates that RPS is a valuable QA method. Cancer (Cancer Cytopathol) 2015;123:739–744. © 2015 American Cancer Society.
Binding Selectivity of Macrocycle Ionophores in Ionic Liquids versus Aqueous Solution and Solvent‐free Conditions
Authors: Gámez Francisco , Hortal Ana R. , Hurtado Paola , Avilés‐Moreno Juan R. , Hamad Said , Martínez‐Haya Bruno
Published: September 2015

The understanding of supramolecular recognition in room‐temperature ionic liquids (RTILs) is key to develop the full potential of these materials. In this work, we provide insights into the selectivity of the binding of alkali metal cations by standard cyclodextrin and calixarene macrocycles in RTILs. A direct laser desorption/ionization mass spectrometry approach is employed to determine the relative abundances of the inclusion complexes formed through competitive binding in RTIL solutions. The results are compared with the binding selectivities measured under solvent‐free conditions and in water/methanol solutions. Cyclodextrins and calixarenes in which the peripheral OH groups are substituted by bulkier side groups preferentially bind to Cs+. Such specific ionophoric behavior is substantially enhanced by solvation effects in the RTIL. This finding is rationalized with the aid of quantum mechanical calculations, in terms of the conformational features and steric interactions that drive the solvation of the inclusion complexes by the bulky RTIL counterions.
Development of mathematical model for signal‐dependent linear adaptive level‐based sampling
Authors: Srivastava Abhinav , Srinivasan K.
Published: September 2015

A mathematical model for linear adaptive level‐based sampling is developed in this paper. The proposed mathematical model provides a gradual change in quantization size and maintains time difference between two successive samples greater than or equal to loop delay of the system. This model is developed to minimize signal slope overload distortion as well as reduction in quantization noise. The proposed mathematical model is demonstrated in MATLAB simulation environment. Simulation results are compared with level‐based sampling and adaptive level‐based sampling based on bit‐level compression. Copyright © 2015 John Wiley & Sons, Ltd.
Text Filtering for Harmful Document Classification Using Three‐Word Co‐Occurrence and Large‐Scale Data Processing
Authors: OTSUKA TAKANOBU , DENG DEYUE , ITO TAKAYUKI
Published: September 2015

Young people are increasingly using the Internet. However, this creates the problem that the material they encounter may adversely affect them. Therefore we propose a method of automatically classifying harmful sentences. Research on information filtering has been improving the performance of filters by introducing co‐occurrence information. Extended from two words co‐occurrence information, which is commonly studied in such work, we have created training data using co‐occurrence information with three words. However, compared with two‐word co‐occurrence information, the processing time becomes a problem because of the increase in the amount of training data. In addition, we have found that noise caused by the increase in co‐occurrences exceeds the capacity of double‐precision floating‐point calculations. We improved processing speed by implementing a text filtering system with three‐word co‐occurrence using a Bayesian filter in order to parallelize a fast MyISAM database. In addition, by using BigDecimal to remove the noise caused by the increase in the number of co‐occurrences, we achieved a high F‐value.
High‐Speed Performance Evaluation of a Large‐Scale Shared‐Bus Digital System
Authors: KONDO MASAFUMI , YOKOGAWA TOMOYUKI , SATO YOICHIRO , ARIMOTO KAZUTAMI
Published: September 2015

To evaluate the performance of a large‐scale digital system, the system can be modeled by stochastic timed Petri nets (STPN) and a performance index can be estimated based on the number of iterations in a Petri net simulation. When the performance evaluation is carried out in a large distributed environment, parallel calculation with incidence matrices for the STPN can make the Petri net simulation more efficient. In this paper, we propose an ordering method for the incidence matrices to reduce the communication costs in the parallel calculation of matrix operations. For this purpose, we first propose a method of blocking the incidence matrices based on the structure of the system by taking into consideration synchronous and asynchronous buses as structural elements. We also propose a method for converting submatrices of the incidence matrices into band matrices. This method is based on breadth‐first search in the STPN as represented by the submatrices. Finally, we demonstrate the benefits of ordering on the time required for a performance evaluation by carrying out a performance evaluation using the incidence matrices generated under the proposed method. In addition, we show that the ordering method can reduce the communication costs in a large distributed environment by estimating the utilization rate of calculation nodes.
Signature of circulating microRNAs in patients with acute heart failure
Authors: Ovchinnikova Ekaterina S. , Schmitter Daniela , Vegter Eline L. , ter Maaten Jozine M. , Valente Mattia A.E. , Liu Licette C.Y. , van der Harst Pim , Pinto Yigal M. , de Boer Rudolf A. , Meyer Sven , Teerlink John R. , O'Connor Christopher M. , Metra Marco , Davison Beth A. , Bloomfield Daniel M. , Cotter Gadi , Cleland John G. , Mebazaa Alexandre , Laribi Said , Givertz Michael M. , Ponikowski Piotr , van der Meer Peter , van Veldhuisen Dirk J. , Voors Adriaan A. , Berezikov Eugene
Published: September 2015

Aims

Our aim was to identify circulating microRNAs (miRNAs) associated with acute heart failure (AHF).

Methods and results

Plasma miRNA profiling included 137 patients with AHF from 3 different cohorts, 20 with chronic heart failure (CHF), 8 with acute exacerbation of COPD, and 41 healthy controls. Levels of circulating miRNAs were measured using quantitative reverse transcription–polymerase chain reaction (qRT–PCR). Plasma levels of miRNAs in patients with AHF were decreased compared with CHF patients or healthy subjects, whereas no significant changes were observed between acute COPD patients and controls. Fifteen miRNAs found in the discovery phase to differ most significantly between healthy controls and patients with AHF were further investigated in an extended cohort of 100 AHF patients at admission and a separate cohort of 18 AHF patients at different time points. Out of these 15 miRNAs, 12 could be confirmed in an additional AHF validation cohort and 7 passed the Bonferroni correction threshold (miR‐18a‐5p, miR‐26b‐5p, miR‐27a‐3p, miR‐30e‐5p, miR‐106a‐5p, miR‐199a‐3p, and miR‐652‐3p, all P < 0.00005). A further drop in miRNA levels within 48 h after AHF admission was associated with an increased risk of 180‐day mortality in a subset of the identified miRNAs.

Conclusions

Declining levels of circulating miRNAs were associated with increasing acuity of heart failure. Early in‐hospital decreasing miRNA levels were predictive for mortality in a subset of miRNAs in patients with AHF. The discovered miRNA panel may serve as a launch‐pad for molecular pathway studies to identify new pharmacological targets and miRNA‐based therapies.
Neurons and T cells: Understanding this interaction for inflammatory neurological diseases
Authors: Yshii Lidia , Gebauer Christina , Bernard‐Valnet Raphaël , Liblau Roland
Published: September 2015

Central nervous system (CNS) inflammation occurs in a large number of neurological diseases. The type and magnitude of CNS inflammation, as well as the T‐cell contribution, vary depending on the disease. Different animal models of neurological diseases have shown that T cells play an important role in CNS inflammation. Furthermore, recent studies of human neurological disorders have indicated a significant role for T cells in disease pathology. Nevertheless, how individual T‐cell subsets affect neuronal survival, damage and/or loss remains largely unclear. In this review we discuss the processes by which T cells mediate either beneficial or deleterious effects within the CNS, with emphasis on the direct interaction between T cells and neurons, as occurs in multiple sclerosis, paraneoplastic cerebellar degeneration, and viral encephalitis. The therapeutic approaches targeting T cells and their mediators as treatment for neurological diseases are also described here.
Polyhalide Ions (Br82– and I2Br62–) and Chains (···Br3–···Br2··· and ···IBr4–···) Stabilised by Using Cu(dafone)32+ as Counter Ion (dafone = 4,5‐Diazafluoren‐9‐one)
Authors: Babu Ramavath , Bhargavi Govindugari , Rajasekharan Melath V.
Published: September 2015

Two new iodobromides [I2Br62– (analogue of I82– and Br82–) and IBr4– (analogue of Br5– and I2Br3–)] and new chains formed from Br3–, Br2 and IBr4– have been obtained in three compounds all containing the same CuII tris‐chelate cation Cu(dafone)32+ {[Cu(dafone)3](Br3)(Br5) (1), [Cu(dafone)3](Br5)(Br8)0.5·CH3CN (2) and [Cu(dafone)3](IBr4)(I2Br6)0.5·CH3CN (3)} by a procedure employing bromine, iodine, CuII bromide and dafone in acetonitrile. The formation of chains and isolated polyhalide ions is facilitated by templating with the tris‐chelate cation. The Raman spectra of the polyhalides and EPR and other spectral characteristics of the fluxional CuII complex cation are presented.
Optimal Synthesis of Faujasite‐Type Zeolites with a Hierarchical Porosity from Natural Clay
Authors: Ltaief Olfa Ouled , Siffert Stéphane , Poupin Christophe , Fourmentin Sophie , Benzina Mourad
Published: September 2015

Raw clay, which is an interstratified illite‐kaolinite, has been used as a raw material to prepare Faujasite‐type zeolites. The synthesis was based on the alkaline fusion method followed by hydrothermal treatment without the addition of any extra silica or alumina sources. The effects of various factors on the synthesis process, such as NaOH/clay ratio, crystallization time and temperature, were investigated. The results obtained underlined that these parameters determined whether or not Faujasite‐type zeolites were formed. The optimum synthesis conditions for the synthesis of a single Faujasite zeolite phase were a weight ratio of NaOH/clay of 1.2 fused at 500 °C for 2 h and crystallized at 60 °C for 24 h after homogenization for 12 h. The compounds obtained were characterized by X‐ray diffraction, FTIR spectroscopy, and scanning electron microscopy. Their textural properties were investigated by N2 adsorption/desorption measurements. The BET surface area of the product synthesized with the optimum conditions was 360 m2/g with a relatively high total pore volume of 0.33 m3/g. Toluene adsorption on the synthesized trimodal Faujasite zeolite was four times higher than on commercial zeolite. This synthesis is therefore a good way to obtain a cheap and efficient adsorbent for environmental applications.
Combined Oxidation, Deprotonation, and Metal Coordination of a Redox‐Active Guanidine Ligand
Authors: Wild Ute , Kaifer Elisabeth , Wadepohl Hubert , Himmel Hans‐Jörg
Published: September 2015

Guanidino‐functionalized aromatic compounds (GFAs) are strong organic electron donors and redox‐active ligands. The diversity of GFA chemistry results from reaction sequences that are triggered by their oxidation. This work reports on reactions of a new GFA compound, namely, 1,2,4,5‐tetrakis(N,N′‐dicyclohexylguanidino)benzene, with transition metals, and analyzes the interplay between GFA oxidation, coordination, and hydrogen‐bond formation up to deprotonation. The reaction of the new GFA with [{PdCl(C3H5)}2] led to coordination and a coupled proton‐ and electron‐transfer reaction.
Photoluminescence Modulation in Lan­thanide(III)/Pyrazine‐2,5‐dicarboxylato/Nitrato Frameworks
Authors: Cepeda Javier , Pérez‐Yáñez Sonia , Beobide Garikoitz , Castillo Oscar , García Jose Ángel , Luque Antonio
Published: September 2015

Invited for the cover of this issue is the group of Oscar Castillo at the University of the Basque Country (UPV/EHU) in Bilbao, Spain. The cover image shows the suitability of the solvent‐free method to achieve a variety of 3D coordination polymers through reaction between lanthanide nitrates and pyrazine‐2,5‐dicarboxylic acid. Some of these compounds are photoluminescent and emit bright green, brown and bright red colours that are depicted by the traffic lights.
Cation‐enhanced capillary electrophoresis separation of atropoisomer anions
Authors: Na Yun‐Cheol , Berthod Alain , Armstrong Daniel W.
Published: September 2015

CE was used to study the separation of the atropoisomers of four phosphoric acids and two sulfonic acids and the enantiomers of two phosphoric acids. All solutes are in their anionic forms in aqueous electrolytes. The chiral additives were two hydroxypropyl cyclodextrins (CDs) and cyclofructan 6 (CF6). The CDs were able to separate four solutes and the CF6 additive could separate only one: 1,1′‐binaphthyl‐2,2′‐diyl hydrogenphosphate (BHP). Since CF6 is able to bind with cations, nitrate of alkaline metals, Ba2+, and Pb2+ were added, greatly improving the BHP separation at the expense of longer migration times. There seems to be a link between CF6–cation‐binding constants and BHP resolution factors. Cation additions were also performed with CD selectors that are less prone to form complexes with cations. Significant improvements of enantiomer or atropoisomer separations were observed also associated with longer migration times. It is speculated that the anionic solutes associate with the added cations forming larger entities better differentiated by CDs.
Estonian energy supply strategy assessment for 2035 and its vulnerability to climate driven shocks
Authors: Lehtveer Mariliis , Pelakauskas Martynas , Ipbüker Cagatay , Howells Mark , Rogner H‐Holger , Das Anjana , Toomet Ott‐Siim , Tkaczyk Alan H.
Published: September 2015

Estonia is a relatively small country with a limited supply of indigenous energy resources mainly consisting of oil shale, wood, and peat. Estonia is also the only country in Europe with a dominant electricity production by burning oil shale. Around 90% of the overall electric energy production in Estonia comes from the Narva Power Plants. This presents great challenges and problems due to massive emissions of greenhouse gases into the atmosphere as well as radiological impact on the environment. Therefore, the current energy supply strategy can be considered hazardous and an unpopular choice for future energy system planning. In this article, we analyze the current energy policy as well as inclusion of new strategies to produce electricity for Estonia for a target year of 2035. We use a computer model Model for Supply Strategy Alternatives and their General Environmental Impacts (MESSAGE) to provide optimization and aim in helping the policymakers in the Estonian decision making process. We also add a specific case in the MESSAGE model to examine the ability of the current electricity supply strategy to handle climate related shocks with a special focus on cold weather in two plausible cases; single cold winter and prolonged cold winter. Results indicate that unexpected demand shocks may cause serious losses in gross domestic product (GDP). Therefore, the authors come to the conclusion that extra capacity is highly recommendable for a number of reasons. We also find that nuclear power becomes economically preferable to oil shale with a CO2 tax of €20/t. Yet moving toward nuclear or other low CO2 alternatives presents certain challenges. © 2015 American Institute of Chemical Engineers Environ Prog, 35: 469–478, 2016
Empirical Performance of Commodity Pricing Models: When is it Worthwhile to Use a Stochastic Volatility Specification?
Authors: Cortazar Gonzalo , Gutierrez Simon , Ortega Hector
Published: September 2015

We compare the empirical pricing performance of three models: a constant volatility model, a two‐factor stochastic volatility model, and a one‐factor stochastic volatility model with a model‐free implied variance specification. Results of applying these models to oil, copper, and gold derivatives are consistent for all commodities and highlight the relative benefits of the different models implying that in choosing the best model to implement in a real situation, careful consideration must be given to the tradeoffs between effort and precision. We believe our results are not only new, but also relevant for practitioners. © 2015 Wiley Periodicals, Inc. Jrl Fut Mark 36:457–487, 2016
Clinical and pathological parameters prognostic for increased risk of recurrence after postoperative radiotherapy for temporal bone carcinoma
Authors: Marioni Gino , Zanoletti Elisabetta , Giacomelli Luciano , Braggio Leonardo , Martini Alessandro , Mazzoni Antonio
Published: September 2015

Background

Most authors agree that radical surgery for advanced, aggressive temporal bone squamous cell carcinoma (SCC) should be followed by postoperative radiotherapy (PORT). The purpose of this study was to identify clinical and/or conventional pathological parameters capable of pinpointing patients with temporal bone SCC at higher risk of recurrence after PORT.

Methods

The investigation concerned 27 consecutive patients undergoing PORT for primary temporal bone SCC.

Results

Univariate statistics revealed a difference in the distributions for pT classification (p = .0004), pathological grade (p = .006), and dura mater involvement (p = .015) when patients were grouped by presence versus absence of recurrence after PORT. A panel of 3 parameters comprising pT classification (pT4), pathological grade (G2 or G3), and dura mater involvement demonstrated an outstanding discriminatory power (area under the curve [AUC] receiver operating characteristic [ROC] = 0.912) in predicting temporal bone SCC recurrence after PORT.

Conclusion

The panel considered had an outstanding discriminatory power in pinpointing patients at higher risk of recurrence who could benefit from stricter follow‐up protocols and postoperative chemoradiotherapy (CRT) for temporal bone SCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: 894–898, 2016
Parotid metastasis of an amelanotic melanoma of the scalp: The great masquerader
Authors: Neto Tiago , Nunes Richard , Amado Isabel , Balhau Rui , Marques Hugo , Sanz David , Mesquita Margarida , Pinto Isabel , Correia‐Sá Inês , Ferreira Artur
Published: September 2015

Background

Cutaneous melanoma is often characterized by its pigmented appearance; however, up to 8.1% of such lesions contain little or no pigmentation. Amelanotic melanomas, lesions devoid of visible pigment, present a diagnostic quandary because they can masquerade as many other skin pathologies. Recognizing amelanotic melanoma is even more clinically challenging when it is first detected as a metastasis to the secondary tissue.

Methods

We report a rare case of metastasis of an amelanotic melanoma to the parotid gland.

Results

A 75‐year‐old man presented with an 8‐month history of a painless, mobile, hardened mass in the right parotid region. Histopathological analysis of a fine‐needle aspiration biopsy of the parotid mass indicated that the mass was melanoma. Careful clinical and radiological examination revealed an 8 mm erythematous papule in the right temporal scalp, initially diagnosed by visual examination as basal cell carcinoma. After right superficial parotidectomy, neck dissection, and excision of the temporal scalp lesion, histological examination revealed the scalp lesion to be amelanotic melanoma.

Conclusion

Although metastatic amelanotic melanoma to the parotid gland is a rare diagnosis, the clinician should be familiar with this presentation to increase the likelihood of making the correct diagnosis and delivering prompt treatment. © 2015 Wiley Periodicals, Inc. Head Neck 38: E91–E94, 2016
Vocal cord paralysis predicted by neural monitoring electrophysiologic changes with recurrent laryngeal nerve compressive neuropraxic injury in a canine model
Authors: Puram Sidharth V. , Chow Harold , Wu Che‐Wei , Heaton James T. , Kamani Dipti , Gorti Gautham , Chiang Feng Yu , Dionigi Gianlorenzo , Barczyński Marcin , Schneider Rick , Dralle Henning , Lorenz Kerstin , Randolph Gregory W.
Published: September 2015

Background

Recurrent laryngeal nerve (RLN) injury is a known complication of thyroid/parathyroid surgery. Intraoperative nerve monitoring (IONM) has been used to gain more information regarding the functional status of the RLN intraoperatively; however, the electromyography (EMG) parameters of RLN after nontransection neuropraxic compressive injury remain unknown.

Methods

We developed a canine model to identify IONM EMG correlates of postoperative vocal cord paralysis (VCP) using a standardized method to simulate surgical RLN compression sufficient to cause VCP.

Results

Compression nerve injury decreased EMG amplitude and increased EMG latency, with a 60% increase in RLN threshold stimulation compared to preinjury values. If RLN amplitude decreases by 80% with an absolute amplitude of 300 μV or less in combination with a latency increase of 10% or more, then nerve injury and associated VCP is likely.

Conclusion

These results may help surgeons to prognosticate postoperative neural function and intraoperative decision‐making regarding contralateral thyroid surgery. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1341–E1350, 2016
Mothers' Attention‐getting Utterances During Shared Book Reading: Links to Low‐income Preschoolers' Verbal Engagement, Visual Attention, and Early Literacy
Authors: Son Seung‐Hee Claire , Tineo Maria F.
Published: September 2015

This study examined associations among low‐income mothers' use of attention‐getting utterances during shared book reading, preschoolers' verbal engagement and visual attention to reading, and their early literacy skills (N = 51). Mother–child shared book reading sessions were videotaped and coded for each utterance, including attention talk, contextualized talk, de‐contextualized talk, and print talk. Preschoolers' attention during book reading was assessed using two measures: verbal engagement by using a rating scale of preschoolers' involvement in book reading discussion and visual attention by coding visual gaze. Findings indicated that mothers' attention talk was positively associated with children's verbal engagement, while maternal print talk was associated with children's visual attention. Further, low‐level maternal print talk was associated with higher early decoding scores of children when it was accompanied with high‐level maternal attention talk. Copyright © 2015 John Wiley & Sons, Ltd.
Evaluation of Groundwater Suitability for Irrigation in the Araniar River Basin, South India—A Case Study Using Gis Approach
Authors: Jasmin I. , Mallikarjuna P.
Published: September 2015

Spatial and temporal variations in the groundwater quality of the Araniar River Basin, south India, were studied to determine its suitability for irrigation through development of irrigation water quality index (IWQI) maps of post‐ and pre‐monsoon periods. The spatial thematic maps of electrical conductivity (EC), sodium absorption ratio (SAR), residual sodium carbonate (RSC) and sodium percentage (Na%) were developed using a geographic information system (GIS) and compared with the respective United States Department of Agriculture (USDA) standards. The pertinent maps of irrigation water quality parameters based on FAO‐29 guidelines were prepared, rasterized and overlaid using a GIS to develop IWQI maps for the basin. The IWQI maps indicated that 75% of the basin area possesses highly suitable irrigation water post‐monsoon, with medium suitability (90.7% of the basin) predominating during pre‐monsoon. Copyright © 2015 John Wiley & Sons, Ltd.
Assessment Of Cost‐Effective Alternatives For Improving Irrigation Systems In The Nile Delta
Authors: Abou El‐Hassan W.H. , El‐Kassar G. , Fujimaki H. , Kitamura Y. , Khater A.
Published: September 2015

Preliminary studies were conducted to test new design criteria incorporated in the Sefsafa Canal (SC) with the aim of reducing water application costs without sacrificing irrigation performance. For comparison, we also studied the Meet‐Yazied Canal (MYC) (which is run without the new techniques). The cost‐reduction measures used in this study included reduction of pump discharge rates and the use of electricity instead of diesel. We found that the location of farms along the irrigation canal had little effect on pump operation hours and amount of applied water; instead, crop patterns were the most important factor in this regard. The water use index (WUI), which is the ratio of applied water to required water, was higher in the SC than in the MYC and El‐Mesk Canal (MC). Decreasing the pump discharge increased the amount of applied water to meet crop water requirements. During the winter, the WUI values of 1.11–1.16 achieved discharge rates of 70–80 l s−1 and were considered the optimal values of WUI. Further studies are required to avoid excessive application of water during the summer. The application of new techniques prompted farmers to irrigate their fields at night, thereby reducing water losses and installation and operational costs, and promoting equitable water distribution along the entire irrigation canal and throughout the command area. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis of Novel Fused Heterocycles Based on 6‐Amino‐4‐phenyl‐2‐thioxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile
Authors: Abdel‐Ghany H. , El‐Sayed A. M. , Amer A. A. , Ahmed A. M.
Published: September 2015

Under phase transfer catalysis conditions, 6‐amino‐4‐phenyl‐2‐thioxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile (1) was allowed to react with halo compounds, acrylonitrile, chloroacetyl chloride, ethyl cyanoacetate, formamide, triethylorthoformate, or formic acid to give new derivatives of fused pyridines 2–22, respectively. Acetylation of compound 1 using acetic anhydride afforded product 23, which in turn underwent intramolecular cyclization in pyridine to give the corresponding pyrido[2,3‐d]pyrimidine 24.
Effect of trifluoroethanol on α‐crystallin: folding, aggregation, amyloid, and cytotoxicity analysis
Authors: Khan Mohd Shahnawaz , Tabrez Shams , Bhat Sheraz Ahmed , Rabbani Nayyar , Al‐Senaidy Abdulrahman M. , Bano Bilqees
Published: September 2015

α‐Crystallin, a member of small heat shock proteins, is the major structural protein within the eye lens and is believed to play an exceptional role in the stability of lens proteins and its transparency. In the current manuscript, we have investigated the effect of an organic solvent, trifluoroethanol (TFE), on the structure and function of α‐crystallin isolated from camel eye lens. Incubation of this protein with TFE changed the secondary and tertiary structures, which resulted in the aggregation of α‐crystallin as evidenced by intrinsic fluorescence, Rayleigh's scattering, Thioflavin T assay, and circular dichroism spectroscopic studies. The treatment with different concentrations of TFE led to increased exposure of hydrophobic domains of α‐crystallin, which was observed by 8‐anilino 1‐napthalene sulfonic acid extrinsic fluorescence assay. These results clearly indicate that TFE induced significant changes in the secondary and tertiary structures of α‐crystallin, leading to aggregation and amyloid formation. Furthermore, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay established the cytotoxicity of the aggregated α‐crystallin towards HepG2 cell lines through reactive oxygen species production. In conclusion, α‐crystallin protein was found to be susceptible to conformational changes by TFE, suggesting that α‐crystallin, although basically acting like a heat shock protein and functionally displaying chaperone‐like activity, might capitulate to change in lens environment induced by diseased conditions or age‐related changes, resulting in cataract formation. Copyright © 2015 John Wiley & Sons, Ltd.
Altered superficial amygdala–cortical functional link in resting state after 36 hours of total sleep deprivation
Authors: Lei Yu , Shao Yongcong , Wang Lubin , Ye Enmao , Jin Xiao , Zou Feng , Zhai Tianye , Li Wuju , Yang Zheng
Published: September 2015

The superficial amygdala (SFA) is important in human emotion/affective processing via its strong connection with other limbic and cerebral cortex for receptive and expressive emotion processing. Few studies have investigated the functional connectivity changes of the SFA under extreme conditions, such as prolonged sleep loss, although the SFA showed a distinct functional connectivity pattern throughout the brain. In this study, resting‐state functional magnetic resonance imaging (rs‐fMRI) was employed to investigate the changes of SFA–cortical functional connectivity after 36 hr of total sleep deprivation (TSD). Fourteen healthy male volunteers aged 25.9 ± 2.3 years (range 18–28 years) enrolled in this within‐subject crossover study. We found that the right SFA showed increased functional connectivity with the right medial prefrontal cortex (mPFC) and decreased functional connectivity with the right dorsal posterior cingulate cortex (dPCC) in the resting brain after TSD compared with that during rested wakefulness. For the left SFA, decreased connectivity with the right dorsal anterior cingulate cortex (dACC) and right dPCC was found. Further regression analysis indicated that the functional link between mPFC and SFA significantly correlated with the Profile of Mood State scores. Our results suggest that the amygdala cannot be treated as a single unit in human neuroimaging studies and that TSD may alter the functional connectivity pattern of the SFA, which in turn disrupts emotional regulation. © 2015 Wiley Periodicals, Inc.
Examining the relationship between blast‐induced mild traumatic brain injury and posttraumatic stress‐related traits
Authors: Tschiffely A.E. , Ahlers S.T. , Norris J.N.
Published: September 2015

Emerging evidence suggests that mild traumatic brain injury (mTBI) resulting from blast exposure may contribute to the occurrence of posttraumatic stress disorder (PTSD) and related affective sequelae, such as anxiety and depression. Many studies have used survey techniques to describe blast exposure leading to comorbid mTBI and related persistent postconcussive symptoms (PPCS) with PTSD in military populations. Despite this, there is a lack of literature that examines possible biological mechanisms by which blast exposure contributes to the development of PTSD sequelae. This Mini‐Review addresses the current literature on potential neurophysiological changes that may contribute to PTSD‐like traits as a result of a single or multiple exposures to blast events. Evidence from clinical blast‐induced mTBI populations and animal models of blast‐induced mTBI was evaluated with an emphasis on behavioral and physiological symptoms similar to those seen in PTSD populations and models. From the analysis, we propose potential mechanisms that merit further investigation for better understanding of how blast exposures may produce a higher rate of comorbid PPCS, PTSD, and affective phenomena. An improved understanding of PTSD‐like outcomes resulting from blast exposure will ultimately help facilitate the development of future treatments and contribute to a better understanding of PTSD sequelae that develop from physical trauma. © 2015 Wiley Periodicals, Inc.
Effect of neurotrophin‐3 precursor on glutamate‐induced calcium homeostasis deregulation in rat cerebellum granule cells
Authors: Safina Dina R. , Surin Alexander M. , Pinelis Vsevolod G. , Kostrov Sergey V.
Published: September 2015

Neurotrophin‐3 (NT‐3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT‐3) and the precursor (pro‐NT‐3) forms of neurotrophin. Members of the neurotrophin family are involved in the regulation of calcium homeostasis in neurons; however, the role of NT‐3 and pro‐NT‐3 in this process remains unclear. The current study explores the effects of NT‐3 and pro‐NT‐3 on disturbed calcium homeostasis and decline of mitochondrial potential induced by a neurotoxic concentration of glutamate (Glu; 100 µM) in the primary culture of rat cerebellar granule cells. In this Glu excitotoxicity model, mature NT‐3 had no effect on the induced changes in Ca2+homeostasis. In contrast, pro‐NT‐3 decreased the period of delayed calcium deregulation (DCD) and concurrent strong mitochondrial depolarization. According to the amplitude of the increase in the intracellular free Ca2+concentration ([Ca2+]i) and Fura‐2 fluorescence quenching by Mn2+within the first 20 sec of exposure to Glu, pro‐NT‐3 had no effect on the initial rate of Ca2+entry into neurons. During the lag period preceding DCD, the mean amplitude of [Ca2+]irise was 1.2‐fold greater in the presence of pro‐NT‐3 than in the presence of Glu alone (1.67 ± 0.07 and 1.39 ± 0.04, respectively,P < 0.05). The Glu‐induced changes in Са2+homeostasis in the presence of pro‐NT‐3 likely are due to the decreased rate of Са2+removal from the cytosol during the DCD latency period. © 2015 Wiley Periodicals, Inc.
Impact of neoadjuvant chemotherapy on pathologic axillary nodal status in HER‐2 positive patients presenting with clinically node‐negative disease
Authors: Al‐Hilli Zahraa , Hieken Tina J. , Hoskin Tanya L. , Heins Courtney N. , Boughey Judy C.
Published: September 2015

Objectives

We investigated the impact of neoadjuvant chemotherapy (NAC) on axillary disease burden in clinically node‐negative (cN0) HER‐2 positive breast cancer patients.

Methods

We studied 215 cN0 patients with HER‐2 positive tumors. Multivariable logistic regression was used to compare NAC versus primary surgery (PS) with respect to outcome of pathologic nodal disease.

Results

Of 215 patients, 42 (20%) received NAC. NAC use correlated with higher clinical T stage (P < 0.0001) and younger age (P = 0.03) with no difference in ER/PR status or tumor grade. Despite higher clinical T stage in the NAC group, rate of pathologic positive axillary nodes was non‐significantly lower (NAC 5/42 = 11.9%, PS 27/173 = 15.6%, P = 0.54). In multivariable analysis, after adjustment for confounders including clinical T stage, age, and multifocal/multicentric disease, NAC showed significant reduction in odds of pathologic nodal disease (OR 0.26, 95%CI:0.06–0.90, P = 0.03). Further, among those with pathologic nodal disease, the number of positive nodes was lower after NAC (adjusted P = 0.03). Extranodal extension was present in 8/27 (30%) PS patients vs. 1/5 (20%) of the NAC patients (adjusted P = 0.36).

Conclusion

NAC in cN0 HER‐2 positive breast cancers reduces the rate of pathologic node‐positive disease at operation and nodal disease burden and may decrease the need for axillary node dissection. J. Surg. Oncol. 2015; 112:453–457. © 2015 Wiley Periodicals, Inc.
Two‐dimensional liquid chromatography and its application in traditional Chinese medicine analysis and metabonomic investigation
Authors: Li Zheng , Chen Kai , Guo Meng‐zhe , Tang Dao‐quan
Published: September 2015

Two‐dimensional liquid chromatography has become an attractive analytical tool for the separation of complex samples due to its enhanced selectivity, peak capacity, and resolution compared with one‐dimensional liquid chromatography. Recently, more attention has been drawn on the application of this separation technique in studies concerning traditional Chinese medicines, metabonomes, proteomes, and other complex mixtures. In this review, we aim to examine the application of two‐dimensional liquid chromatography in traditional Chinese medicine analysis and metabonomic investigation. The classification and evaluation indexes were first introduced. Then, various switching methods were summarized when used in an on‐line two‐dimensional liquid chromatography system. Finally, the applications of this separation technique in traditional Chinese medicine analysis and metabonomic investigation were discussed on the basis of specific studies.
Shifts in microbial food web structure and productivity after additions of naturally occurring dissolved organic matter: Results from large‐scale lacustrine mesocosms
Authors: Sanders Robert W. , Cooke Sandra L. , Fischer Janet M. , Fey Samuel B. , Heinze Adam W. , Jeffrey Wade H. , Macaluso Amy L. , Moeller Robert E. , Morris Donald P. , Neale Patrick J. , Olson Mark H. , Dean Pakulski J. , Porter Jason A. , Schoener Donald M. , Williamson Craig E.
Published: September 2015

Predicting the effects of dissolved organic matter (DOM) on pelagic food webs can be difficult because DOM modifies water column optics and can have contrasting effects on species across trophic levels. We combined large mesocosm, smaller‐scale experiments and autoregressive modeling driven bu DOC concentration or DOM optical quality (colored DOM, or CDOM, measured as DOC‐specific absorbance at 320 nm, SUVA320) to assess how heterotrophic and phototrophic microbial populations were altered in a temperate oligotrophic lake. DOM additions yielded DOC concentrations of 1.6 mg L−1 (control) 2.5 mg L−1, 3.0 mg L−1, and 4.3 mg L−1. Primary (PP) and bacterial (BP) production as well as heterotrophic and autotrophic protist abundances were stimulated in the higher DOM additions. BP responded rapidly to DOM additions, but unlike PP, returned to the level of controls within 2–7 d. A bioassay showed that the DOM was a nitrogen source for phytoplankton. The two models revealed that BP and edible phytoplankton were stimulated by CDOM (SUVA320), but only BP was stimulated by DOC concentration. Ultraviolet radiation (UV) inhibited protists in both models, but stimulated edible phytoplankton only in the SUVA320 model runs. These results suggest that in transparent oligotrophic lakes large influxes of terrestrial (high SUVA320) DOM will stimulate the microbial food web by providing a nutrient subsidy to bacteria and reducing exposure of protists to damaging UV. Nutrients associated with moderate DOM input may also stimulate PP relative to BP, as was observed in these and other experiments, rather than causing an overall system shift toward heterotrophy.
Selective plane illumination optical and optoacoustic microscopy for postembryonic imaging
Authors: Lin Hsiao‐Chun Amy , Chekkoury Andrei , Omar Murad , Schmitt‐Manderbach Tobias , Koberstein‐Schwarz Benno , Mappes Timo , López‐Schier Hernán , Razansky Daniel , Ntziachristos Vasilis
Published: September 2015

Intravital imaging of large specimens is intrinsically challenging for postembryonic studies. Selective plane illumination microscopy (SPIM) has been introduced to volumetrically visualize organisms used in developmental biology and experimental genetics. Ideally suited for imaging transparent samples, SPIM can offer high frame rate imaging with optical microscopy resolutions and low phototoxicity. However, its performance quickly deteriorates when applied to opaque tissues. To overcome this limitation, SPIM optics were merged with optical and optoacoustic (photoacoustic) readouts. The performance of this hybrid imaging system was characterized using various phantoms and by imaging a highly scattering ex vivo juvenile zebrafish. The results revealed the system's enhanced capability over that of conventional SPIM for high‐resolution imaging over extended depths of scattering content. The approach described here may enable future visualization of organisms throughout their entire development, encompassing regimes in which the tissue may become opaque.

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Entrainment of vastus medialis complex activity differs between genders
Authors: Tenan Matthew S. , Hackney Anthony C. , Griffin Lisa
Published: September 2015

Introduction: That the vastus medialis oblique (VMO) is a functional unit of the vastus medialis (VM) is disputed. Delayed VMO activation predicts patellofemoral pain, which has higher rates in women. Methods: Single MUs and surface electromyogram (EMG) were collected from the VMO and VM of 9 men and 9 women. Men were tested once; women were tested during 5 menstrual phases. Coherence was assessed for motor unit (MU) firings within and between the VM and VMO using multilevel logistic models to determine statistical significance. Results: Compared with women, men have 741% (MU pairs) and 256% (MU‐EMG pairs) greater odds of common drive (0–5 Hz) coherent oscillations. MU pairs from the VMO and the dual VM/VMO complex have 228% and 212% greater odds of coherent oscillations in the beta band (15–35 Hz) compared with VM pairs. Conclusions: The VM and VMO are neurologically different muscles; control of the VM complex is sexually dimorphic. Muscle Nerve 53: 633–640, 2016
A micromechanics model for molecular diffusion in materials with complex pore structure
Authors: Timothy Jithender J. , Meschke Günther
Published: September 2015

Molecular diffusion in fully saturated porous materials is strongly influenced by the pore space, which, in general, is characterized by a complex topological structure. Hence, information on macroscopic diffusion properties requires up‐scaling of transport processes within nano‐pores and micro‐pores over several spatial scales. A new model in the framework of continuum micromechanics is proposed for predicting the effective molecular diffusivity in porous materials. Considering a representative volume element, characterizing a porous material without any information about the pore space microstructure complexity, the uniform flux is perturbed by recursively embedding shape information hierarchically in the form of the ESHELBY matrix‐inclusion morphology to obtain the effective diffusivity as a function of the recurrence level and the porosity. The model predicts a threshold value for the porosity, below which no molecular diffusion can occur because of the presence of isolated pore clusters that are not connected and unavailable for transport. The maximum porosity, below which no molecular transport is possible, is predicted as one‐third for spherical inclusions. The model allows for extensions to more complex morphologies of the inclusions. We also identify, that the effects of the micro‐structure on molecular transport are characterized by porosity dependent long‐range and short‐range interactions. The developed framework is extended to incorporate realistic pore size distributions across several spatial scales by means of a distribution function within the hierarchical homogenization scheme. Available experimental results assert the model predictions. Copyright © 2015 John Wiley & Sons, Ltd.
Accelerated echo planar J‐resolved spectroscopic imaging in prostate cancer: a pilot validation of non‐linear reconstruction using total variation and maximum entropy
Authors: Nagarajan Rajakumar , Iqbal Zohaib , Burns Brian , Wilson Neil E. , Sarma Manoj K. , Margolis Daniel A. , Reiter Robert E. , Raman Steven S. , Thomas M. Albert
Published: September 2015

The overlap of metabolites is a major limitation in one‐dimensional (1D) spectral‐based single‐voxel MRS and multivoxel‐based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two‐dimensional (2D) J‐resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four‐dimensional (4D) echo planar J‐resolved spectroscopic imaging (EP‐JRESI). The goal of the present work was to validate two different non‐linear reconstruction methods independently using compressed sensing‐based 4D EP‐JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty‐two patients with PCa with a mean age of 63.8 years (range, 46–79 years) were investigated in this study. A 4D non‐uniformly undersampled (NUS) EP‐JRESI sequence was implemented on a Siemens 3‐T MRI scanner. The NUS data were reconstructed using two non‐linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non‐cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo‐inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP‐JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites. Copyright © 2015 John Wiley & Sons, Ltd.
Intrinsic diffusion sensitivity of the balanced steady‐state free precession (bSSFP) imaging sequence
Authors: Bär Sébastien , Weigel Matthias , von Elverfeldt Dominik , Hennig Jürgen , Leupold Jochen
Published: September 2015

The purpose of this work was to analyze the intrinsic diffusion sensitivity of the balanced steady‐state free precession (bSSFP) imaging sequence, meaning the observation of diffusion‐induced attenuation of the bSSFP steady‐state signal due to the imaging gradients. Although these diffusion effects are usually neglected for most clinical gradient systems, such strong gradient systems are employed for high resolution imaging of small animals or MR Microscopy. The impact on the bSSFP signal of the imaging gradients characterized by their b‐values was analyzed with simulations and experiments at a 7T animal scanner using a gradient system with maximum gradient amplitude of approx. 700 mT/m. It was found that the readout gradients have a stronger impact on the attenuation than the phase encoding gradients. Also, as the PE gradients are varying with each repetition interval, the diffusion effects induce strong modulations of the bSSFP signal over the sequence repetition cycles depending on the phase encoding gradient table.

It is shown that a signal gain can be obtained through a change of flip angle as a new optimal flip angle maximizing the signal can be defined. The dependency of the diffusion effects on relaxation times and b‐values were explored with simulations. The attenuation increases with T2. In conclusion, diffusion attenuation of the bSSFP signal becomes significant for high resolution imaging voxel size (roughly < 100 μm) of long T2 substances. Copyright © 2015 John Wiley & Sons, Ltd.