bluuebunny/crossref_metadata_2025 huggingface dataset:
An interspecies comparative study of invasive electrophysiological functional connectivity
Authors: Casimo Kaitlyn , Levinson Lila H. , Zanos Stavros , Gkogkidis C. Alexis , Ball Tonio , Fetz Eberhard , Weaver Kurt E. , Ojemann Jeffrey G.
Published: November 2017

Introduction

Resting‐state connectivity patterns have been observed in humans and other mammal species, and can be recorded using a variety of different technologies. Functional connectivity has been previously compared between species using resting‐state fMRI, but not in electrophysiological studies.

Methods

We compared connectivity with implanted electrodes in humans (electrocorticography) to macaques and sheep (microelectrocorticography), which are capable of recording neural data at high frequencies with spatial precision. We specifically examined synchrony, implicated in functional integration between regions.

Results

We found that connectivity strength was overwhelmingly similar in humans and monkeys for pairs of two different brain regions (prefrontal, motor, premotor, parietal), but differed more often within single brain regions. The two connectivity measures, correlation and phase locking value, were similar in most comparisons. Connectivity strength agreed more often between the species at higher frequencies. Where the species differed, monkey synchrony was stronger than human in all but one case. In contrast, human and sheep connectivity within somatosensory cortex diverged in almost all frequencies, with human connectivity stronger than sheep.

Discussion

Our findings imply greater heterogeneity within regions in humans than in monkeys, but comparable functional interactions between regions in the two species. This suggests that monkeys may be effectively used to probe resting‐state connectivity in humans, and that such findings can then be validated in humans. Although the discrepancy between humans and sheep is larger, we suggest that findings from sheep in highly invasive studies may be used to provide guidance for studies in other species.
Cytotoxic Triterpenoids from Roots of Actinidia chinensis
Authors: Wei Liu‐Bin , Ma Si‐Yuan , Liu Hong‐Xing , Huang Chu‐Sheng , Liao Na
Published: November 2017

Phytochmical investigation of roots of Actinidia chinensisPlanch. led to the isolation triterpenoids 1 – 16, including a new compound 2α,3α,23,24‐tetrahydroxyursa‐12,20(30)‐dien‐28‐oic acid (1). Their structures were identified on the basis of spectroscopic analysis, including 1D‐ and 2D‐NMR, HR‐ESI mass spectrometry, and by comparison with the literatures. The cytotoxicities of triterpenoids 1 – 16 against a panel of cultured human cancer cell lines (HepG2, A549, MCF‐7, SK‐OV‐3, and HeLa) were evaluated. The new compound 1 exhibited moderate antitumor activities with IC50 values of 19.62 ± 0.81, 18.86 ± 1.56, 45.94 ± 3.62, 62.41 ± 2.29, and 28.74 ± 1.07 μm, respectively. The experiment data might be available to explain the use of roots of A. chinensis to treat various cancers in traditional Chinese medicine.
Functional plurihormonal adrenal oncocytoma: case report and literature review
Authors: Costanzo Pablo René , Paissan Andrea Laura , Knoblovits Pablo
Published: November 2017

Key Clinical Message

We present a 27‐year‐old woman with an adrenal oncocytoma. This is a very rare entity. We provide a review of the clinical, biochemical and pathological features of cases reported in the literature.
Molecular Engineering of MnII Diamine Diketonate Precursors for the Vapor Deposition of Manganese Oxide Nanostructures
Authors: Maccato Chiara , Bigiani Lorenzo , Carraro Giorgio , Gasparotto Alberto , Seraglia Roberta , Kim Jiyeon , Devi Anjana , Tabacchi Gloria , Fois Ettore , Pace Giuseppe , Di Noto Vito , Barreca Davide
Published: November 2017

Molecular engineering of manganese(II) diamine diketonate precursors is a key issue for their use in the vapor deposition of manganese oxide materials. Herein, two closely related β‐diketonate diamine MnII adducts with different fluorine contents in the diketonate ligands are examined. The target compounds were synthesized by a simple procedure and, for the first time, thoroughly characterized by a joint experimental–theoretical approach, to understand the influence of the ligand on their structures, electronic properties, thermal behavior, and reactivity. The target compounds are monomeric and exhibit a pseudo‐octahedral coordination of the MnII centers, with differences in their structure and fragmentation processes related to the ligand nature. Both complexes can be readily vaporized without premature side decompositions, a favorable feature for their use as precursors for chemical vapor deposition (CVD) or atomic layer deposition applications. Preliminary CVD experiments at moderate growth temperatures enabled the fabrication of high‐purity, single‐phase Mn3O4 nanosystems with tailored morphology, which hold great promise for various technological applications.
Pillar[5]arene‐Based Supramolecular Organic Framework with Multi‐Guest Detection and Recyclable Separation Properties
Authors: Lin Qi , Fan Yan‐Qing , Mao Peng‐Peng , Liu Lu , Liu Juan , Zhang You‐Ming , Yao Hong , Wei Tai‐Bao
Published: November 2017

The selective detection and separation of target ions or molecules is an intriguing issue. Herein, a novel supramolecular organic framework (SOF‐THBP) was constructed by bis‐thioacetylhydrazine functionalized pillar[5]arenes. The SOF‐THBP shows a fluorescent response for Fe3+, Cr3+, Hg2+ and Cu2+ ions. The xerogel of SOF‐THBP shows excellent recyclable separation properties for these metal ions and the absorption rates were up to 99.29 %. More interestingly, by rationally introducing these metal ions into the SOF‐THBP, a series of metal‐ion‐coordinated SOFs (MSOFs) such as MSOF‐Fe, MSOF‐Hg and MSOF‐Cu were constructed. These metal ions coordinated MSOFs could selectively sense F−, Br−, and l‐Cys, respectively. The detection limits of these MSOFs for F−, Br− and l‐Cys were about 10−8 m.
Depolymerization of Poly(phosphinoboranes): From Polymers to Lewis Base Stabilized Monomers
Authors: Marquardt Christian , Hegen Oliver , Vogel Ariane , Stauber Andreas , Bodensteiner Michael , Timoshkin Alexey Y. , Scheer Manfred
Published: November 2017

We report on depolymerization reactions of poly(phosphinoboranes). The cleavage of the polymers [H2PBH2]n (2 a), [tBuHPBH2]n (2 c), [PhHPBH2]n (2 e) and the oligomer [Ph2PBH2]n (2 b), with strong Lewis bases (LBs), in particular with NHCs, leads to the corresponding monomeric phosphanylboranes R1R2PBH2LB. It is observed that the depolymerization depends on the strength and stability of the LBs as well as on the substitution pattern of the poly(phosphinoboranes). The solid state structures of the monomeric phosphinoboranes H2PBH2NHCMe (NHC=N‐heterocyclic carbene) (4 a), H2PBH2NHCdipp (5 a) and tBuHPBH2NHCMe (4 c) were determined. DFT calculations support the experimentally observed reaction behavior.
Influence of the Anion on the Oxidation of 5‐Hydroxymethylfurfural by Using Ionic‐Polymer‐Supported Platinum Nanoparticle Catalysts
Authors: Siankevich Sviatlana , Mozzettini Simone , Bobbink Felix , Ding Shipeng , Fei Zhaofu , Yan Ning , Dyson Paul J.
Published: November 2017

Invited for this month's cover are the groups of Prof. Paul J. Dyson at Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland and Prof. Ning Yan at National University of Singapore, Singapore. The cover shows the catalytic conversion of 5‐hydroxymethylfurfural (5‐HMF) into 2,5‐furandicarboxylic acid catalyzed by platinum nanoparticles stabilized by polymeric imidazolium salts. The catalyst is represented by a nanoparticle footprint. The background represents a potential source of biomass. Read the full text of the article at 10.1002/cplu.201700344.
Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open‐Label, Randomized Study
Authors: Adkison Kimberly , Wolstenholme Allen , Lou Yu , Zhang Zhiping , Eld Amy , Perger Teodora , Vangerow Harald , Hayward Katy , Shaefer Mark , McCoig Cynthia
Published: November 2017

In children aged ≤4 years, the relative bioavailability of lamivudine oral solution was 37% lower than that of a tablet formulation. An open‐label, four‐way crossover study was conducted in healthy adults to evaluate the effect of sorbitol, a common liquid excipient, on the pharmacokinetics of lamivudine oral solution (ClinicalTrials.gov identifier, NCT02634073). Sixteen subjects were randomized to one of four sequences consisting of four doses of lamivudine 300 mg (10 mg/mL) alone or with sorbitol 3.2, 10.2, or 13.4 g. Sorbitol 3.2, 10.2, and 13.4 g decreased lamivudine maximum concentration (Cmax) by 28%, 52%, and 55% and area under the concentration–time curve from time 0 to 24 h (AUC0‐24) by 20%, 39%, and 44%, respectively. Three subjects (19%) reported five nonserious adverse events (one drug‐related). The dose‐dependent effects of sorbitol on lamivudine Cmax and AUC0‐24 reveal an absorption‐based interaction that may decrease lamivudine exposure in patients coadministered sorbitol‐containing medicines.
Regional patterns of increasing Swiss needle cast impacts on Douglas‐fir growth with warming temperatures
Authors: Lee E. Henry , Beedlow Peter A. , Waschmann Ronald S. , Tingey David T. , Cline Steven , Bollman Michael , Wickham Charlotte , Carlile Cailie
Published: November 2017

The fungal pathogen,Phaeocryptopus gaeumannii, causing Swiss needle cast (SNC) occurs wherever Douglas‐fir is found but disease damage is believed to be limited in the U.S. Pacific Northwest (PNW) to the Coast Range of Oregon and Washington (Hansen et al.,Plant Disease, 2000,84, 773; Rosso & Hansen,Phytopathology, 2003,93, 790; Shaw, et al.,Journal of Forestry, 2011,109, 109). However, knowledge remains limited on the history and spatial distribution ofSNCimpacts in thePNW. We reconstructed the history ofSNCimpacts on mature Douglas‐fir trees based on tree‐ring width chronologies from western Oregon. Our findings show thatSNCimpacts on growth occur wherever Douglas‐fir is found and is not limited to the coastal fog zone. The spatiotemporal patterns of growth impact fromSNCdisease were synchronous across the region, displayed periodicities of 12–40 years, and strongly correlated with winter and summer temperatures and summer precipitation. The primary climatic factor limiting pathogen dynamics varied spatially by location, topography, and elevation.SNCimpacts were least severe in the first half of the 20th century when climatic conditions during the warm phase of the Pacific Decadal Oscillation (1924–1945) were less conducive to pathogen development. At low‐ to mid‐elevations,SNCimpacts were most severe in 1984–1986 following several decades of warmer winters and cooler, wetter summers including a high summer precipitation anomaly in 1983. At high elevations on the west slope of the Cascade Range,SNCimpacts peaked several years later and were the greatest in the 1990s, a period of warmer winter temperatures. Climate change is predicted to result in warmer winters and will likely continue to increaseSNCseverity at higher elevations, north along the coast from northern Oregon to British Columbia, and inland where low winter temperatures currently limit growth of the pathogen. Our findings indicate thatSNCmay become a significant forest health problem in areas of thePNWbeyond the coastal fog zone.
Early warning signals precede cyanobacterial blooms in multiple whole‐lake experiments
Authors: Wilkinson Grace M. , Carpenter Stephen R. , Cole Jonathan J. , Pace Michael L. , Batt Ryan D. , Buelo Cal D. , Kurtzweil Jason T.
Published: November 2017

Ecosystem regime shifts are abrupt changes from one dynamical state to another, such as the shift from a clear‐water state to an algal bloom state in lakes. These transitions are hard to forecast but theory suggests that early warning indicators can predict impending regime shifts that may allow for management intervention to prevent or mitigate an unwanted change. The efficacy of early warning indicators has been demonstrated in modeling and laboratory experiments, but rarely in the field, where environmental drivers are numerous and interacting. It is unclear if early warning indicators are observable or timely enough to allow for intervention under these conditions. We performed six whole‐lake experimental nutrient additions to test the utility of early warning indicators for predicting the regime shift from a clear‐water state to a cyanobacteria‐dominated state. The lakes were monitored for increases in resilience indicators including rises in standard deviation and autocorrelation of algal pigments and dissolved oxygen saturation. A statistical method, quickest detection, determined when resilience indicators in manipulated lakes deviated substantially from those in a reference ecosystem. Blooms occurred in five of the six lake‐years. Although there was substantial variability in bloom size and timing, at least one indicator foreshadowed the peak chlorophyll a concentration in all instances. Early warnings occurred 1–57 d prior to a bloom, which in some instances, may allow managers to notify the public or intervene to prevent blooms. The resilience indicators generally identified changes in resilience over time within a lake and also ranked large differences in resilience among lakes. Our findings suggest that resilience indicators can be useful for classifying ecosystems on a landscape and across time with respect to proximity to a critical threshold.
Enabling Efficient Late‐Stage Functionalization of Drug‐Like Molecules with LC‐MS and Reaction‐Driven Data Processing
Authors: Yao Huifang , Liu Yong , Tyagarajan Sriram , Streckfuss Eric , Reibarkh Mikhail , Chen Kuanchang , Zamora Ismael , Fontaine Fabien , Goracci Laura , Helmy Roy , Bateman Kevin P. , Krska Shane W.
Published: November 2017

Late‐stage functionalization (LSF) through C–H functionalization of drug leads is a powerful synthetic strategy for drug discovery. A key challenge in LSF is that multiple regioisomeric products are often generated, which requires slow and laborious product isolation and structure confirmation steps. To address this, an analytical approach using LC‐HR‐MS/MS coupled with automated chemically aware data processing was developed. Using this method to analyse reaction screening arrays based on three common C–H functionalization chemistries with a set of marketed drugs, the relative amount and localization of chemical modification could be determined for each regioisomeric product generated in the screening. This approach allows one to construct a workflow in which the various regioisomeric products of a given transformation are triaged according to their site of modification, allowing downstream isolation and structure elucidation efforts to focus on those analogues of highest interest, leading to an overall increase in productivity of the LSF strategy.
Co2SnO4/Carbon Nanotubes Composites: A Novel Approach for Electrochemical Sensing of Hydrogen Peroxide
Authors: Yedinak E. , Venegas C. J. , Brito T. P. , Ruiz‐León D. , Bollo S.
Published: November 2017

For the first time Co2SnO4 (CTO)/Carbon nanotubes (CNT) composites were prepared and used to modify glassy carbon electrodes for the amperometric determination of hydrogen peroxide. The catalytic activity of composites towards the oxidation of hydrogen peroxide was dependent on the quantity of CNT present in the composite and to the pH of the medium. The pure cobalt stannate phase with a ratio of 3 : 1 (CTO:CNT) exhibited the best catalytic activity towards hydrogen peroxide oxidation at low potentials (0.200 and 0.500 V). A linear relationship between current and hydrogen peroxide concentration was obtained with a sensitivity of 95 and 258 μA mM−1 and a detection limit of 0.130 and 0.08 μM respectively.
Toxicological characterization of ZnO nanoparticles in malignant and non‐malignant cells
Authors: Moratin Helena , Scherzad Agmal , Gehrke Thomas , Ickrath Pascal , Radeloff Katrin , Kleinsasser Norbert , Hackenberg Stephan
Published: November 2017

The increasing usage of zinc oxide nanoparticles (ZnO‐NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO‐NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non‐malignant cells. Therefore, human head and neck squamous cell carcinoma‐derived FaDu cells were incubated with 4–20 µg/ml of ZnO‐NPs for 1–48 hr and tested for cell viability, cell cycle alterations, apoptosis and caspase‐3 gene expression as a sensitive marker of molecular apoptotic processes with regard to time‐ and dose‐dependent effects. Human mesenchymal bone marrow stem cells were used as non‐malignant representatives to examine oxidative stress‐related genotoxicity. Results showed a significant reduction in cell viability as well as dose‐ and time‐dependent increase of apoptotic cells following nanoparticle treatment. Likewise, caspase‐3 gene expression enhanced already before first apoptotic cells were detectable. It could be observed that doses that were cytotoxic in tumor cells did not reduce viability in stem cells. However, the same concentrations already induced significant DNA damage. The findings of the study suggest to keep a more critical eye on the use of nanoparticles as anti‐cancer agents. Yet, additional in vivo studies are needed to assess safety concerns for consumers and patients. Environ. Mol. Mutagen. 59:247–259, 2018. © 2017 Wiley Periodicals, Inc.
An efficient algorithm for identifying pulse‐like ground motions based on significant velocity half‐cycles
Authors: Zhai Changhai , Li Cuihua , Kunnath Sashi , Wen Weiping
Published: November 2017

Ground motions with strong velocity pulses are of particular interest to structural earthquake engineers because they have the potential to impose extreme seismic demands on structures. Accurate classification of records is essential in several earthquake engineering fields where pulse‐like ground motions should be distinguished from nonpulse‐like records, such as probabilistic seismic hazard analysis and seismic risk assessment of structures. This study proposes an effective method to identify pulse‐like ground motions having single, multiple, or irregular pulses. To effectively characterize the intrinsic pulse‐like features, the concept of an energy‐based significant velocity half‐cycle, which is visually identifiable, is first presented. Ground motions are classified into 6 categories according to the number of significant half‐cycles in the velocity time series. The pulse energy ratio is used as an indicator for quantitative identification, and then the energy threshold values for each type of ground motions are determined. Comprehensive comparisons of the proposed approach with 4 benchmark identification methods are conducted, and the results indicate that the methodology presented in this study can more accurately and efficiently distinguish pulse‐like and nonpulse‐like ground motions. Also presented are some insights into the reasons why many pulse‐like ground motions are not detected successfully by each of the benchmark methods.
Anterior thalamic nuclei lesions have a greater impact than mammillothalamic tract lesions on the extended hippocampal system
Authors: Perry Brook A. L. , Mercer Stephanie A. , Barnett Sophie C. , Lee Jungah , Dalrymple‐Alford John C.
Published: November 2017

The anterior thalamic nuclei (ATN), mammillary bodies and their interconnecting fiber tract, the mammillothalamic tract (MTT), are important components of an extended hippocampal circuit for episodic memory. In humans, damage to the MTT or ATN in many disorders is associated with severe anterograde amnesia and it is assumed that their influence on memory is functionally equivalent. The relative influence of these two structures on memory has not, however, been assessed explicitly. Here, a direct comparison found that only ATN lesions impaired spatial reference memory in rats. ATN lesions produced more severe deficits on spatial working memory and reduced zif268 expression to a greater degree and in more corticolimbic sites than did MTT lesions. Conversely, MTT lesions reduced NeuN cell counts in all three subregions of the MB to a greater extent than did ATN lesions, so their relative impact cannot be explained by retrograde neuropathology of the MB. Hence ATN injury causes a more critical dysfunction than would be expected by an emphasis on the indirect influence of brainstem inputs to the extended memory system. The greater ATN lesion deficits found here may represent the consequence of disruption to the direct connections of the ATN with both hippocampal and cortical sites.
Multicontrast endomyocardial imaging by single‐channel high‐resolution cross‐polarization optical coherence tomography
Authors: Yao Xinwen , Gan Yu , Ling Yuye , Marboe Charles C. , Hendon Christine P.
Published: November 2017

A single‐channel high‐resolution cross‐polarization (CP) optical coherence tomography (OCT) system is presented for multicontrast imaging of human myocardium in one‐shot measurement. The intensity and functional contrasts, including the ratio between the cross‐ and co‐polarization channels as well as the cumulative retardation, are reconstructed from the CP‐OCT readout. By comparing the CP‐OCT results with histological analysis, it is shown that the system can successfully delineate microstructures in the myocardium and differentiate the fibrotic myocardium from normal or ablated myocardium based on the functional contrasts provided by the CP‐OCT system. The feasibility of using A‐line profiles from the 2 orthogonal polarization channels to identify fibrotic myocardium, normal myocardium and ablated lesion is also discussed.
Performance of density functionals for modeling vapor liquid equilibria of CO2 and SO2
Authors: Goel Himanshu , Windom Zachary W. , Jackson Amber A. , Rai Neeraj
Published: November 2017

Vapor liquid equilibria (VLE) and condensed phase properties of carbon dioxide and sulfur dioxide are calculated using first principles Monte Carlo (FPMC) simulations to assess the performance of several density functionals, notably PBE‐D3, BLYP‐D3, PBE0‐D3, M062X‐D3, and rVV10. GGA functionals were used to compute complete vapor liquid coexistence curves (VLCCs) to estimate critical properties, while the hybrid and nonlocal van der Waals functionals were used only for computing density at a single state point due to the high computational cost. Our results show that the BLYP‐D3 functional performs well in predicting VLE properties for both molecules when compared with other functionals. In the liquid phase, pair correlation functions reveal that there is not a significant difference in the location of the peak for the first solvation shell while the peak heights are different for different functionals. Overall, the BLYP‐D3 functional is a good choice for modeling VLE of acidic gases with significant environmental implications such as CO2 and SO2. © 2017 Wiley Periodicals, Inc.
The roles of Wnt/β‐catenin pathway in tissue development and regenerative medicine
Authors: Majidinia Maryam , Aghazadeh Javad , Jahanban‐Esfahlani Rana , Yousefi Bahman
Published: November 2017

Regenerative medicine is a translational field which combines tissue engineering and molecular biology to construct spare organs or help injured or defective tissues to regenerate or restore their normal functions. This is particularly important with specific organs such as heart, central nervous system, retina, or limbs which possess very limited regenerative capacity. As such, regenerative medicine has received peculiar attention in the last decade. In this regard, Wnt/β‐catenin signaling pathway has been subject to intensive research, since it plays many essential roles in the regulation of the progenitor cell fate, developmental decisions, proliferation during embryonic development, and adult tissue homeostasis. In this paper, we will briefly introduce Wnt/β‐catenin signaling pathway and discuss how it integrally contributes to both stem and cancer stem cell maintenance. Finally, we summarize the current understanding of the role of Wnt/β‐catenin signaling in the development and regeneration of heart, lung, liver, bone, and cartilage.
High fat diet‐induced oxidative stress blocks hepatocyte nuclear factor 4α and leads to hepatic steatosis in mice
Authors: Yu Dongsheng , Chen Gang , Pan Minglin , Zhang Jia , He Wenping , Liu Yang , Nian Xue , Sheng Liang , Xu Bin
Published: November 2017

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease with manifestation of over‐accumulation of fat in liver. Increasing evidences indicate that NAFLD may be in part caused by malfunction of very low density lipoprotein (VLDL) secretion. Hepatocyte nuclear factor 4α (HNF4α), a nuclear receptor protein, plays an important role in sustain hepatic lipid homeostasis via transcriptional regulation of genes involved in secretion of VLDL, such as apolipoprotein B (ApoB). However, the exact functional change of HNF4α in NAFLD remains to be elucidated. In the present study, we found that high fat diet (HFD) induced cytoplasmic retention of HNF4α in hepatocytes, which led to down‐regulation of hepatic ApoB expression and its protein level in serum, as well as reduced secretion of VLDL. We further revealed that oxidative stress, elevated in fatty liver, was the key factor inducing the cytoplasmic retention of HNF4α in hepatocytes by activating protein kinase C (PKC)‐mediated phosphorylation in HNF4α. Thus, our findings reveal a novel mechanism underlying HFD‐induced fatty liver that oxidative stress impairs function of HNF4α on ApoB expression and VLDL secretion via PKC activation, eventually promoting fat accumulation in the liver. Therefore, oxidative stress/PKC/HNF4α pathway may be a novel target to treat diet‐induced fatty liver.
Therapeutic potency of mTOR signaling pharmacological inhibitors in the treatment of proinflammatory diseases, current status, and perspectives
Authors: Soltani Arash , Bahreyni Amirhossein , Boroumand Nadia , Roshan Mostafa karimi , Khazaei Majid , Ryzhikov Mikhail , Soleimanpour Saman , Avan Amir , Hassanian Seyed Mahdi
Published: November 2017

Mammalian target of rapamycin (mTOR) signaling pathway controls cell energy metabolism. There is an interplay between mTOR and proinflammatory signaling pathways, supporting the role of the pathway in the pathogenesis of inflammatory diseases. Inhibition of mTOR signaling using specific pharmacological inhibitors could offer therapeutic promise in several inflammatory‐associated diseases. In this review, we summarize recent findings on the regulatory effects of mTOR signaling on inflammation and the therapeutic potency of mTOR pharmacological inhibitors in the treatment of inflammatory diseases including cancer, neurodegenerative diseases, atherosclerosis, sepsis, and rheumatoid arthritis for a better understanding and hence a better management of these diseases.
The current status and perspectives regarding the clinical implication of intracellular calcium in breast cancer
Authors: Tajbakhsh Amir , Pasdar Alireza , Rezaee Mehdi , Fazeli Mostafa , Soleimanpour Saman , Hassanian Seyed Mahdi , FarshchiyanYazdi Zahra , Younesi Rad Tayebe , Ferns Gordon A. , Avan Amir
Published: November 2017

Calcium ions (Ca2+) act as second messengers in intracellular signaling. Ca2+ pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca2+ as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca2+ also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells. In breast cancer, the disruption of intracellular: Ca2+ homeostasis may cause tumor progression by affecting key factors/pathways including phospholipase C (PLC), inositol 1,4,5‐trisphosphate (IP3), calmodulin (CaM), nuclear factor of activated T‐cells (NFAT), calpain, calmodulin‐dependent protein kinase II (CaMKII), mitogen‐activated protein kinase (MAPK), epithelial‐mesenchymal transition (EMT), vascular endothelial growth factor (VEGF), poly (ADP‐Ribose) polymerase‐1 (PARP1), estrogen, and estrogen receptor. Because the foregoing molecules play crucial roles in breast cancer, the factors/pathways influencing intracellular Ca2+ concentrations are putative targets for cancer treatment, using drugs such as Mephebrindole, Tilapia piscidin 4, Nifetepimine, Paricalcitol, and Prednisolone. We have explored the factors/pathways which are related to breast cancer and Ca2+ homeostasis and signaling in this review, and also discussed their potential as biomarkers for breast cancer staging, prognosis, and therapy.
Epithelial cell adhesion molecule fragments and signaling in primary human liver cells
Authors: Gerlach Jörg C. , Foka Hubert G. , Thompson Robert L. , Gridelli Bruno , Schmelzer Eva
Published: November 2017

Epithelial Cell Adhesion Molecule (EpCAM), or CD326, is a trans‐membrane glycoprotein expressed by multiple normal epithelia as well as carcinoma. Human hepatic stem cells and bile duct epithelium of the liver are EpCAM positive. In tumor cell lines, its intracellular domain can be released after cleavage of the extracellular domain. Within the cell nucleus, it induces cell proliferation, but cleavage depends on cell contact. Fragments of various lengths have been described in tumor cells. Despite its described important role in proliferation in tumor cells, there is not much known about the expression and role of EpCAM fragments in primary human liver cells. Here, we demonstrate that EpCAM protein fragments and function are considerable different between tumor cells, normal fetal and adult liver cells. Contrary to previously reported findings in tumor cells, gene knockdown or treatment with an inhibitor of the cleavage enzyme ADAM17 (TACE) rather increased cell numbers in primary human fetal liver‐derived EpCAM‐positive cells. EpCAM fragment sizes were not affected by treatment with inhibitor. Knockdown of EPCAM gene expression by siRNA in sorted cells did not significantly affect proliferation‐associated genes or cell numbers. The intracellular domain could not be detected within cell nuclei of fetal and adult liver cells. In conclusion, signaling through the intracellular domain of EpCAM appears to be a mechanism that induces proliferation specifically in tumorigenic cells but not in normal primary EpCAM‐positive liver cells.
Inflammasome: Its role in traumatic brain and spinal cord injury
Authors: Mortezaee Keywan , Khanlarkhani Neda , Beyer Cordian , Zendedel Adib
Published: November 2017

Traumatic brain injury (TBI) and spinal cord injury (SCI) are pathological events that lead to neuropathological conditions which have in consequence the initiation of pro‐inflammatory cytokine production. Neuroinflammation plays a key role in the secondary phase of both TBI and SCI after initial cell death. Activation of cytoplasmic inflammasome complexes is regarded as the essential step of neuroinflammation and a key trigger for neuronal death called pyroptosis. Inflammasome complexes are involved in activation of caspase‐1 which catalyzes the cleavage of pro‐interleukins into their active forms (including interleukin‐18 [IL‐18] and IL‐1β). The focus of this article is to discuss the time‐course and regulation of inflammasome assembly and activation during TBI and SCI and their targeting in designing therapeutic approaches. We particularly focus on the inflammasomes NLRP1 and NLRP3 which play a pivotal function during TBI and SCI in the central nervous system (CNS).
Stereospecific control of peptide gas‐phase ion chemistry with cis and trans cyclo ornithine residues
Authors: Marek Aleš , Nguyen Huong T.H. , Brož Břetislav , Tureček František
Published: November 2017

We report non‐chiral amino acid residues cis‐ and trans‐1,4‐diaminocyclohexane‐1‐carboxylic acid (cyclo‐ornithine, cO) that exhibit unprecedented stereospecific control of backbone dissociations of singly charged peptide cations and hydrogen‐rich cation radicals produced by electron‐transfer dissociation. Upon collision‐induced dissociation (CID) in the slow heating regime, peptide cations containing trans‐cO residues undergo facile backbone cleavages of amide bonds C‐terminal to trans‐cO. By contrast, peptides with cis‐cO residues undergo dissociations at several amide bonds along the peptide ion backbone. Diastereoisomeric cO‐containing peptides thus provide remarkably distinct tandem mass spectra. The stereospecific effect in CID of the trans‐cO residue is explained by syn‐facially directed proton transfer from the 4‐ammonium group at cO to the C‐terminal amide followed by neighboring group participation in the cleavage of the CO―NH bond, analogous to the aspartic acid and ornithine effects. Backbone dissociations of diastereoisomeric cO‐containing peptide ions generate distinct [bn]+‐type fragment ions that were characterized by CID‐MS3 spectra. Stereospecific control is also reported for electron‐transfer dissociation of cis‐ and trans‐cO containing doubly charged peptide ions. The stereospecific effect upon electron transfer is related to the different conformations of doubly charged peptide ions that affect the electron attachment sites and ensuing N―Cα bond dissociations.
A principal component analysis based model to predict post‐monsoon tropical cyclone activity in the Bay of Bengal using oceanic Niño index and dipole mode index
Authors: Biswas H. R. , Kundu P. K.
Published: November 2017

El Niño Southern Oscillation (ENSO) and Indian Ocean dipole (IOD) play an important role in determining the weather pattern over the Indian subcontinent region. The role of ENSO and IOD on the occurrence of tropical cyclone activity during post‐monsoon season (October–December) over the Bay of Bengal (BoB) has been investigated through an objective analysis of observed data for the period of 1990–2015. Accumulated cyclone energy (ACE) index is an important measure of tropical cyclone activity over a basin for a defined period of time. Sea‐surface temperature (SST) anomalies in the Niño 3.4 region (oceanic Niño index) is negatively correlated at 95% confidence level of significance with ACE over the BoB during post‐monsoon season. Positive phase of IOD has negative impact on the tropical cyclone formation over the BoB. The ACE has large inter‐annual variability with coefficient of variation 124% for tropical cyclone activity over BoB during post‐monsoon season. Frequency distribution of annual ACE values for post‐monsoon season over the BoB indicated that cold phases of ENSO along with negative IOD index values are the most favourable for development of tropical cyclone over the BoB. Principal component regression (PCR) model developed by cross‐verification method based on training period data for 1990–2013 and ONI and DMI values of different lag periods as predictors is found to be functional for both deterministic and probabilistic prediction of ACE values of post‐monsoon season. Above‐ and below‐normal TC activities were observed in 2014 and 2015, respectively, which have been well predicted by the PCR model.
Prospective phase II trial of combination hepatic artery infusion and systemic chemotherapy for unresectable colorectal liver metastases: Long term results and curative potential
Authors: Pak Linda M. , Kemeny Nancy E. , Capanu Marinela , Chou Joanne F. , Boucher Taryn , Cercek Andrea , Balachandran Vinod P. , Kingham T. Peter , Allen Peter J. , DeMatteo Ronald P. , Jarnagin William R. , D'Angelica Michael I.
Published: November 2017

Background/Objectives

Combination hepatic artery infusion (HAI) and systemic (SYS) chemotherapy for unresectable CRLM results in high tumor‐response rates. This study represents an update of long‐term survival and conversion to resectability in patients with unresectable CRLM treated with HAI and SYS chemotherapy in a phase II study.

Method

The primary endpoint was complete resection. Multivariate and landmark analysis assessed the effect of complete resection on progression‐free (PFS) and overall survival (OS).

Results

From 2007 to 2012, 64 patients with median of 13 tumors were enrolled; 67% had prior chemotherapy. 33 patients (52%) were converted to resection. Median follow‐up among survivors was 81 months. Median PFS and OS were 13 and 38 months, respectively, with 5‐year‐OS of 36%. Chemotherapy‐naïve patients had 5‐year‐OS of 51%. Conversion to resection was the only independent factor prognostic of improved PFS and OS. Nine of 64 patients (14%) are NED (five since initial resection, three after resection of recurrent disease, one from chemotherapy alone) at median follow‐up of 86 months from treatment initiation, and 72 months from last operative intervention.

Conclusion

Combination HAI and SYS is an effective therapy for high‐volume unresectable CRLM, resulting in a high rate of resection, long‐term survival, and the potential for cure.
Metastasectomy following incomplete response to high‐dose interleukin‐2
Authors: Hughes Tasha , Broucek Joseph , Iodice Gail , Bommareddy Praveen K. , Basu Sanjib , Kaufman Howard L.
Published: November 2017

Objective

To evaluate our experience with metastasectomy following partial response or stable disease after treatment with high‐dose interleukin‐2 (HD IL‐2).

Methods

A total of 305 patients with metastatic renal cell carcinoma or melanoma treated with HD IL‐2 over a 12‐year period were reviewed. Age, objective response, and overall survival data were evaluated using standard RECIST criteria and Kaplan‐Meier estimates.

Results

The average age was 55.3 years (range, 15‐85) and 245 (80.3%) patients had melanoma and 60 (19.7%) had renal cell carcinoma. The objective response rate to IL‐2 for all patients was 13.6% and median survival was 16.8 months. Complete follow‐up data were available for 236 patients with 147 (62.3%) progressing after treatment and 8 (3.3%) with a complete response. Incomplete responses were seen in 81 (34.3%) patients, including 57 (24.2%) patients with stable disease and 24 (10.1%) with partial responses. Of these 81 incomplete responders, 15 (18.5%) underwent subsequent metastasectomy. Patients without surgery had overall survival of 38.2 months and median survival has not yet been reached in those who underwent metastasectomy (P = 0.026).

Conclusion

The data support prospective evaluation of metastasectomy following incomplete therapeutic responses to immunotherapy and defines a new role for surgical resection following IL‐2 and perhaps other immunotherapy regimens.
Canagliflozin stability study and ecofriendly chromatographic determination of its degradation product: A comparative study
Authors: Emam Aml A.
Published: November 2017

Canagliflozin is a newly approved drug for type II diabetes mellitus. A full stability study of canagliflozin was performed following international conference on harmonization strategies. The drug was stable against all conditions except oxidation where only one degradation product was separated and structurally elucidated using mass spectrometry and infrared spectroscopy. A green high‐performance thin‐layer chromatographic densitometric determination was developed and validated for the accurate quantification of canagliflozin and its main oxidative degradation product. Separation was performed on high‐performance aluminum plates precoated with silica gel using acetone/ethanol (80:20, v/v) as a developing system and scanning at 290 nm. Retardation factor values were 0.64 and 0.81 and linearity ranges were 0.4–3.6 and 0.2–3.2 μg/band for the drug and the degradation product, respectively. It was a matter of interest to use green solvents with no harmful effects on the environment. The comparison between the proposed and the reported high‐performance liquid chromatography method regarding greenness profile showed that the proposed method was greener and so could be used as an alternative method to the reported one with no environmental harm. Method validity was tested as per international conference on harmonization and method utility was verified by application to Invokana® tablets.
Sino‐Nasal outcome test‐22 outcomes after sinus surgery: A systematic review and meta‐analysis
Authors: Soler Zachary M. , Jones Rabun , Le Phong , Rudmik Luke , Mattos Jose L. , Nguyen Shaun A. , Schlosser Rodney J.
Published: November 2017

Objectives/Hypothesis

The goal of the study was to perform a systematic review with meta‐analysis to determine the mean change in the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) across patients who have had endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) in the literature.

Methods

A literature search was performed to identify studies that assessed SNOT‐22 scores before and after ESS in adult patients with CRS. A random effects model with inverse variance weighting was used to generate the mean change after surgery, along with the forest plot and 95% confidence interval (CI). The impact of patient‐specific factors across studies was assessed using a mixed‐effects meta‐regression.

Results

The final study list included 40 unique patient cohorts published from 2008 to 2016. All studies showed a statistically significant change in mean SNOT‐22 scores between baseline and postoperative time points (P < .001), ranging from 12.7 to 44.8, at an average follow‐up of 10.6 months. The summary change in mean SNOT‐22 across all studies was 24.4 (95% CI: 22.0‐26.8). After forward, step‐wise multivariate modeling, studies with higher mean preoperative SNOT‐22 score and higher asthma prevalence were associated with greater changes in SNOT‐22 score after ESS, whereas studies with longer mean follow‐up had smaller changes in SNOT‐22 score.

Conclusions

Studies evaluating quality‐of‐life outcomes after sinus surgery using the SNOT‐22 instrument universally show significant improvement after ESS. Across the published literature, the magnitude of change is quite variable and appears to be influenced by a number of factors including baseline SNOT‐22 score, asthma prevalence, and length of follow‐up. Laryngoscope, 128:581–592, 2018
Composition of microbial community in pig manure biochar‐amended soils and the linkage to the heavy metals accumulation in rice at harvest
Authors: Liang Xinqiang , Chen Lingling , Liu Ziwen , Jin Yi , He Miaomiao , Zhao Ziyi , Liu Chunlong , Niyungeko Christophe , Arai Yuji
Published: November 2017

Manure biochar (MB) is recognized to be a beneficial material for absorbing heavy metals from soil and alleviating soil degradation. However, the effects of the addition of MB on the phospholipid fatty acid concentrations and their linkage to heavy metals accumulation in rice are poorly understood. A microcosm incubation experiment was conducted to study the effects of a swine MB amendment on (a) the composition of the soil microbial community in 2 soils (clay‐loam vs. silt‐loam) and (b) heavy metals accumulation in rice grains and straws. MB amendment increased microbial diversity, and bacteria had greater magnitude of increase than did fungi in 2 soils after 98 days of incubation. The G− rather than G+ bacteria phospholipid fatty acid concentrations were significantly increased with MB amendment rates for both soils. The higher MB addition rate (1.5%) did not get more benefit for aerobic bacteria but significantly led to anaerobic bacteria proliferation as compared with the 0.5% MB treatment. The 1.5% MB addition suppressed grain and straw Pb, Cu, and As, while it increased grain and straw Cd and Zn from two soils. Significant soil type × MB rate interactions were observed in most microbial indicators (except F/B and G+) and grain Pb, grain As, and straw Zn. Linkages of bacteria (mainly as G− and/or An), actinobacteria, fungi, and protozoa (in silt‐loam soil) to the MB rate and heavy metals in rice were identified.
Comb of high‐Q Resonances in a Compact Photonic Cavity
Authors: Combrié Sylvain , Lehoucq Gaëlle , Moille Grégory , Martin Aude , De Rossi Alfredo
Published: November 2017

The optical equivalent of the quantum mechanical oscillator is demonstrated in a photonic crystal cavity, owing to the balance of the background dispersion and a bichromatic potential. Consequently, several equi‐spaced resonances with large loaded Q factors are obtained within a very tiny volume. A detailed statistical analysis is carried out by exploiting the complex reflection spectra measured with Optical Coherent Tomography. The log‐normal distribution of the intrinsic Q‐factors is centered at 0.7 million. The device is made of Ga0.5In0.5P in order to suppress the two photon absorption in the Telecom spectral range considered here. This is crucial to turn the strong localization of light into ultra‐efficient parametric interactions.
Segmentation and tracking of lung nodules via graph‐cuts incorporating shape prior and motion from 4D CT
Authors: Cha Jungwon , Farhangi Mohammad Mehdi , Dunlap Neal , Amini Amir A.
Published: November 2017

Purpose

We have developed a robust tool for performing volumetric and temporal analysis of nodules from respiratory gated four‐dimensional (4D) CT. The method could prove useful in IMRT of lung cancer.

Methods

We modified the conventional graph‐cuts method by adding an adaptive shape prior as well as motion information within a signed distance function representation to permit more accurate and automated segmentation and tracking of lung nodules in 4D CT data. Active shape models (ASM) with signed distance function were used to capture the shape prior information, preventing unwanted surrounding tissues from becoming part of the segmented object. The optical flow method was used to estimate the local motion and to extend three‐dimensional (3D) segmentation to 4D by warping a prior shape model through time. The algorithm has been applied to segmentation of well‐circumscribed, vascularized, and juxtapleural lung nodules from respiratory gated CT data.

Results

In all cases, 4D segmentation and tracking for five phases of high‐resolution CT data took approximately 10 min on a PC workstation with AMD Phenom II and 32 GB of memory. The method was trained based on 500 breath‐held 3D CT data from the LIDC data base and was tested on 17 4D lung nodule CT datasets consisting of 85 volumetric frames. The validation tests resulted in an average Dice Similarity Coefficient (DSC) = 0.68 for all test data. An important by‐product of the method is quantitative volume measurement from 4D CT from end‐inspiration to end‐expiration which will also have important diagnostic value.

Conclusion

The algorithm performs robust segmentation of lung nodules from 4D CT data. Signed distance ASM provides the shape prior information which based on the iterative graph‐cuts framework is adaptively refined to best fit the input data, preventing unwanted surrounding tissue from merging with the segmented object.