bluuebunny/crossref_metadata_2025 huggingface dataset:
Crowding Shifts the FMN Recognition Mechanism of Riboswitch Aptamer from Conformational Selection to Induced Fit
Authors: Rode Ambadas B. , Endoh Tamaki , Sugimoto Naoki
Published: April 2018

In bacteria, the binding between the riboswitch aptamer domain and ligand is regulated by environmental cues, such as low Mg2+ in macrophages during pathogenesis to ensure spatiotemporal expression of virulence genes. Binding was investigated between the flavin mononucleotide (FMN) riboswitch aptamer and its anionic ligand in the presence of molecular crowding agent without Mg2+ ion, which mimics pathogenic conditions. Structural, kinetic, and thermodynamic analyses under the crowding revealed more dynamic conformational rearrangements of the FMN riboswitch aptamer compared to dilute Mg2+‐containing solution. It is hypothesized that under crowding conditions FMN binds through an induced fit mechanism in contrast to the conformational selection mechanism previously demonstrated in dilute Mg2+solution. Since these two mechanisms involve different conformational intermediates and rate constants, these findings have practical significance in areas such as drug design and RNA engineering.
Control of the Spin Dynamics of Single‐Molecule Magnets by using a Quasi One‐Dimensional Arrangement
Authors: Katoh Keiichi , Yamashita Satoshi , Yasuda Nobuhiro , Kitagawa Yasutaka , Breedlove Brian K. , Nakazawa Yasuhiro , Yamashita Masahiro
Published: April 2018

Magnetic dipole interactions are dominate in quasi one‐dimensional (1D) molecular magnetic materials, in which TbNcPc units (Tb3+=terbium(III) ion, Nc2−=naphthalocyaninato, Pc2−=phthalocyaninato) adopt a structure similar to TbPc2 single‐molecule magnets (SMMs). The magnetic properties of the [TbNcPc]0/+ (neutral 1 and cationic 2) with 1D structures are significantly different from those of a magnetically diluted sample (3). In particular, the magnetic relaxation time (τ) of 2 in the low‐temperature region is five orders of magnitude slower than that of 3. Furthermore, the coercivity (HC) of 2 remained up to about 20 K. The single‐ion anisotropy of Tb3+ ions in a 1D structure and the magnetic dipole interactions acting among molecules determines the direction of the magnetic properties. These results show that the spin dynamics can be improved by manipulating the arrangement of SMMs in the solid state.
Azo dye with nitrogen donor sets of atoms and its metal complexes: Synthesis, characterization, DFT, biological, anticancer and Molecular docking studies
Authors: Mahmoud Walaa H. , Sayed Fatma N. , Mohamed Gehad G.
Published: April 2018

An azo derivative was synthesized by coupling diazotized 2,6‐diaminopyridine with p‐dimethyl amino benzaldehyde and this new ligand formed a series of metal complexes with Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) salts. These complexes were characterized on the basis of elemental analyses, molar conductance, infrared spectroscopy, UV–Vis, 1H NMR, mass spectrometry, electronic spectra, magnetic susceptibility and ESR spectral studies, conductivity measurements, thermogravimetric analyses (TG‐DTG). The molecular and electronic structure of the azo ligand was optimized theoretically and the quantum chemical parameters were calculated. The ligand and its metal complexes were subjected to X‐ray powder diffraction study. The thermal stability of the ligand and its metal complexes was examined by thermogravimetry. The ligand and its complexes were tested for their in vitro antimicrobial activity, some of the complexes showed good antimicrobial activities against some selected bacterial and fungal strains. Anticancer activity of the ligand and its metal complexes are evaluated against human cancer (MCF‐7 cells viability). Molecular docking was used to predict the binding between azo ligand and the receptors of nucleoside diphosphate kinase of Staphylococcus aureus (3Q8U) and (3HB5) which is breast cancer mutant oxidoreductase. The docking study provided useful structural information for inhibition studies.
Self‐assembly properties of Salamo‐type trinuclear Cu(II) and Co(II) complexes based on the regulation of H+/OHˉ
Authors: Dong Xiu‐Yan , Wang Bao‐Jun , Kang Quan‐Peng , Dong Wen‐Kui
Published: April 2018

A novel naphthalenediol‐based bis(salamo)‐type tetraoxime compound (H4L) was designed and synthesized. Two new supramolecular complexes, [Cu3(L)(μ‐OAc)2] and [Co3(L)(μ‐OAc)2(MeOH)2]·4CHCl3 were synthesized by the reaction of H4L with Cu(II) acetate dihydrate and Co(II) acetate dihydrate, respectively, and were characterized by elemental analyses and X‐ray crystallography. In the Cu(II) complex, Cu1 and Cu2 atoms located in the N2O2 sites, and are both penta‐coordinated, and Cu3 atom is also penta‐coordinated by five oxygen atoms. All the three Cu(II) atoms have geometries of slightly distorted tetragonal pyramid. In the Co(II) complex, Co1 and Co3 atoms located in the N2O2 sites, and are both penta‐coordinated with geometries of slightly distorted triangular bipyramid and distorted tetragonal pyramid, respectively, while Co2 atom is hexa‐coordinated by six oxygen atoms with a geometry of slightly distorted octahedron. These self‐assembling complexes form different dimensional supramolecular structures through inter‐ and intra‐molecular hydrogen bonds. The coordination bond cleavages of the two complexes have occurred upon the addition of the H+, and have reformed again via the neutralization effect of the OH−. The changes of the two complexes response to the H+/OH− have observed in the UV–Vis and 1H NMR spectra.
Antibacterial activity of transition metal complexes with a tridentate NNO amoxicillin derived Schiff base. Synthesis and characterization
Authors: Anacona J.R. , Mago Kysbel , Camus Juan
Published: April 2018

From the reaction of amoxicillin (1) antibiotic with 2,6−diaminopyridine (2) an amoxicillin−based Schiff base (HL) (3) was obtained and its transition metal Schiff base complexes were synthesized. Spectroscopic and physicochemical techniques, namely, UV−Vis, FT−IR, 1H−NMR, EPR, mass spectrometry, molar conductance, magnetic susceptibility, molecular modelling, together with elemental and thermal analyses, were used to characterize the synthesized compounds. Spectral and magnetic data suggested an octahedral geometry for all the complexes and the general formulae [ML(H2O)3][PF6] (M(II) = Mn2+ (4), Co2+ (5), Ni2+ (6), Cu2+ (7), Zn2+ (8), was proposed for them, where L represents deprotonated tridentate NNO amoxycillin−derived Schiff base. All compounds were screened for antibacterial activity by using agar disc diffusion method. The zinc(II) complex exhibited promising bactericidal activity against E. coli and S. aureus.
Antioxidative vs cytotoxic activities of organotin complexes bearing 2,6‐di‐tert‐butylphenol moieties
Authors: Antonenko T.A. , Shpakovsky D.B. , Vorobyov M.A. , Gracheva Yu.A. , Kharitonashvili E.V. , Dubova L.G. , Shevtsova E.F. , Tafeenko V.A. , Aslanov L.A. , Iksanova A.G. , Shtyrlin Yu.G. , Milaeva E.R.
Published: April 2018

Two series of organotin(IV) complexes with Sn–S bonds on the base of 2,6‐di‐tert‐butyl‐4‐mercaptophenol (L1SH) of formulae Me2Sn(L1S)2 (1); Et2Sn(L1S)2 (2); Bu2Sn(L1S)2 (3); Ph2Sn(L1S)2 (4); (L1)2Sn(L1S)2 (5); Me3Sn(L1S) (6); Ph3Sn(L1S) (7) (L1 = 3,5‐di‐tert‐butyl‐4‐hydroxyphenyl), together with the new ones [Me3SnCl(L2)] (8), [Me2SnCl2(L2)2] (9) (L2 = 2‐(N‐3′,5′‐di‐tert‐butyl‐4′‐hydroxyphenyl)‐iminomethylphenol) were used to study their antioxidant and cytotoxic activity. Novel complexes 8, 9 of MenSnCl4 − n (n = 3, 2) with Schiff base were synthesized and characterized by 1H, 13C NMR, IR and elemental analysis. The crystal structures of compounds 8 and 9 were determined by X‐ray diffraction analysis. The distorted tetrahedral geometry around the Sn center in the monocrystals of 8 was revealed, the Schiff base is coordinated to the tin(IV) atom by electrostatic interaction and formation of short contact Sn–O 2.805 Å. In the case of complex 9 the distorted octahedron coordination of Sn atom is formed. The antioxidant activity of compounds as radical scavengers and reducing agents was proved spectrophotometrically in tests with stable radical DPPH, reduction of Cu2+ (CUPRAC method) and interaction with superoxide radical‐anion. Moreover, compounds have been screened for in vitro cytotoxicity on eight human cancer cell lines. A high activity against all cell lines with IC50 values 60–160 nM was determined for the triphenyltin complex 7, while the introduction of Schiff base decreased the cytotoxicity of the complexes. The influence on mitochondrial potential and mitochondrial permeability for the compounds 8 and 9 has been studied. It is shown that studied complexes depolarize the mitochondria but don't influence the calcium‐induced mitochondrial permeability transition.
Effect of high‐temperature annealing on the microstructure and mechanical properties of polypropylene with shish kebab or spherulite structure
Authors: Mi Dashan , Zhou Man , Hou Fengyi , Zhang Jie
Published: April 2018

Various annealing temperatures below, near, or above the melting temperature were used to anneal polypropylene with oriented shish kebab and isolated spherulite structures in this work. The results showed that a high annealing temperature decreases the time needed to achieve the ideal material property. When the annealing temperature is near or above the melting temperature, the impact strength would be 1.6 times improved by partial melting and recrystallization. The crystal structure of the oriented shish kebab or isolated spherulite structures was improved when annealed at 150 °C, whereas annealing at 165 or 170 °C recombined the crystal lamellae of the structure. Moreover, the high crystallinity and thick lamellae improved the impact and yield strength values of the spherulite structure. However, excessively high crystallinity and thick lamellae in the oriented shish kebab structure did not result in good mechanical performance. Therefore, the prediction of mechanical properties for the shish kebab structure based on crystallinity and lamellar thickness is not feasible. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46465.
The Carotid Sinus Nerve—Structure, Function, and Clinical Implications
Authors: Porzionato Andrea , Macchi Veronica , Stecco Carla , De Caro Raffaele
Published: April 2018

Interest has been renewed in the anatomy and physiology of the carotid sinus nerve (CSN) and its targets (carotid sinus and carotid body, CB), due to recent proposals of surgical procedures for a series of common pathologies, such as carotid sinus syndrome, hypertension, heart failure, and insulin resistance. The CSN originates from the glossopharyngeal nerve soon after its appearance from the jugular foramen. It shows frequent communications with the sympathetic trunk (usually at the level of the superior cervical ganglion) and the vagal nerve (main trunk, pharyngeal branches, or superior laryngeal nerve). It courses on the anterior aspect of the internal carotid artery to reach the carotid sinus, CB, and/or intercarotid plexus. In the carotid sinus, type I (dynamic) carotid baroreceptors have larger myelinated A‐fibers; type II (tonic) baroreceptors show smaller A‐ and unmyelinated C‐fibers. In the CB, afferent fibers are mainly stimulated by acetylcholine and ATP, released by type I cells. The neurons are located in the petrosal ganglion, and centripetal fibers project on to the solitary tract nucleus: chemosensory inputs to the commissural subnucleus, and baroreceptor inputs to the commissural, medial, dorsomedial, and dorsolateral subnuclei. The baroreceptor component of the CSN elicits sympatho‐inhibition and the chemoreceptor component stimulates sympatho‐activation. Thus, in refractory hypertension and heart failure (characterized by increased sympathetic activity), baroreceptor electrical stimulation, and CB removal have been proposed. Instead, denervation of the carotid sinus has been proposed for the “carotid sinus syndrome.” Anat Rec, 302:575–587, 2019. © 2018 Wiley Periodicals, Inc.
Statistical methods for network surveillance
Authors: Jeske Daniel R. , Stevens Nathaniel T. , Tartakovsky Alexander G. , Wilson James D.
Published: April 2018

The term network surveillance is defined in general terms and illustrated with many examples. Statistical methodologies that can be used as tools for network surveillance are discussed. Details for 3 illustrative examples that address network security, surveillance for data network failures, and surveillance of email traffic flows are presented. Some open areas of research are identified.
Critical Review: Surface Water and Stormwater Quality Impacts of Cured‐In‐Place Pipe Repairs
Authors: Ra Kyungyeon , Teimouri Sendesi Seyedeh Mahboobeh , Howarter John A. , Jafvert Chad T. , Donaldson Bridget M. , Whelton Andrew J.
Published: April 2018

Cured‐in‐place pipe (CIPP) technology has been used to rehabilitate sanitary sewer, storm sewer, and drinking water pipes. However, utilities, regulators, and health officials have raised environmental, occupational, and public health concerns regarding chemical emissions into air and water. To better understand emissions into water, available literature was reviewed. Water contamination has been documented in 10 states and Canada because of the release of uncured resin, solvents, manufacturing byproducts, and wastes during and after construction. Odor, fish kill, and drinking water contamination incidents have been reported. The few field‐ and bench‐scale studies available show that a variety of volatile organic compounds and semivolatile organic compounds have been released into water and contamination was detected for several months. CIPP waste was acutely toxic to aquatic organisms. Chemical release is likely influenced by formulation, installation, and environmental conditions. CIPP installation and inspection recommendations were suggested. Studies are needed to develop evidence‐based construction and monitoring practices to minimize risks.
Characterization and epitope mapping of a panel of monoclonal antibodies against HIV‐1 matrix protein
Authors: Zhang Zhiqing , Zhang Feng , Bai Shimeng , Qiao Jiaming , Shen Honglin , Huang Fang , Gao Shuangquan , Li Shaowei , Gu Ying , Xia Ningshao
Published: April 2018

The HIV‐1 Gag precursor protein (p55) is the main structural protein comprising the matrix (MA/p17), capsid (CA/p24), and nucleocapsid (NC/p7) proteins, and is uniquely responsible for virion assembly within the virus life cycle. The MA protein plays a critical role in plasma membrane targeting and envelope glycoprotein (Env) uptake during virion assembly. Yet, when viral infection occurs, the MA protein may also be involved in virion uncoating, dissociating from the plasma membrane, and participating in the nuclear importation process. Thus, the MA protein contains a reversibly membrane‐binding signal and varied conformation to govern its subcellular localization and biological functions. However, these purported different conformations of the MA protein during assembly are poorly understood, especially in terms of its function as a component of the precursor protein. In this study, we characterized a panel of monoclonal antibodies against MA that showed discrete reactivity to p55, an intermediate (p41), and the final p17 mature form. We suggest that these antibodies could be used to track the different conformations of MA during the HIV‐1 life cycle, particularly during HIV‐1 assembly and maturation, and contribute to structure determination of MA or MA precursors. These antibodies would also have clinical value, including serving for therapeutic strategy to interfere AIDS progression, reagent in diagnostic kit for the detection of virion‐free p17 or p17 derived from virion lysate.
Selektiver Tiefenabtrag von radioaktiv dekontaminiertem Stahlbeton im kerntechnischen Rückbau
Authors: Kaiser Sonja , Cousseau Frédéric , Braun Jonas , Hess Ulrich
Published: April 2018

Beim Rückbau von kerntechnischen Bauwerken werden hochbewehrte Betongebäude so dekontaminiert, dass anschließend der überwiegende Anteil der Gesamtmasse dem normalen Recyclingkreislauf zugeführt werden kann. Hierfür bedarf es selektiver Abtragsmethoden, um möglichst wenig radioaktiven Abfall endlagern zu müssen. Für den Oberflächenabtrag von Beton stehen bereits zahlreiche Werkzeuge und Abtragsmethoden zur Verfügung. Diese Werkzeuge stoßen jedoch an ihre Grenzen, wenn es darum geht, Kontamination zu entfernen, die tief in die Gebäudestruktur (z. B. durch Risse) eingedrungen ist, oder wenn metallische Einbauten wie Ankerplatten, Dübel, Schienen u. a. verbaut sind. Ein Problem besteht aktuell beim lokal begrenzten Tiefenabtrag von Stahlbetonen, sodass die entstehenden Oberflächen im Anschluss frei messbar sind.

Aus diesem Bedarf entstand das Forschungsprojekt DefAhS (Definierter Abtrag hochbewehrter Stahlbetonstrukturen) als Kooperation zwischen der Herrenknecht AG, Kraftanlagen Heidelberg GmbH, der Leibniz Universität Hannover und dem Karlsruher Institut für Technologie. Gefördert wird das Projekt durch das Programm FORKA – Forschung für den Rückbau kerntechnischer Anlagen – des Bundesministeriums für Bildung und Forschung.
School counsellors’ beliefs regarding collaboration with parents of students with special educational needs in Flanders: Parents as partners or opposites?
Authors: Bodvin Kathleen , Verschueren Karine , Struyf Elke
Published: April 2018

The literature shows that a good collaboration between the school and parents of students with special educational needs (SEN) is not always present. However, school counsellors must collaborate with SEN students’ parents to organise guidance trajectories for their child. This article examines school counsellors’ experiences when collaborating with parents of SEN students and the factors they perceive as contributing to good or difficult collaboration. Four focus groups in mainstream education (N = 50) and one focus group in special education (N = 14) were conducted in Flanders. A thematic analysis indicated that school counsellors generally find it difficult to collaborate with parents of SEN students and that an expert attitude can emerge. The role of these parents is described as limited, which is even preferred by some school counsellors. A deficit view is recognised and the reasons for poor collaboration are mainly situated on the parents’ side, such as parents that need more processing time to accept the SEN of their child and that show distrust towards the school. School counsellors spontaneously referred to parents’ low socioeconomic and ethnic minority status as complicating factors for collaboration. They seem to feel incompetent to overcome these collaboration difficulties. Various recommendations for schools are formulated.
Single pass diafiltration integrated into a fully continuous mAb purification process
Authors: Rucker‐Pezzini Joanna , Arnold Lindsay , Hill‐Byrne Kevin , Sharp Tom , Avazhanskiy Maksim , Forespring Chris
Published: April 2018

The concept of continuous manufacturing has gained significant interest from the biopharmaceutical industry over the past several years. Benefits include increased manufacturing productivity, improved quality control, reduction in plant footprint, and more flexible management of facility capacity. There are several technologies currently available that enable continuous processing for chromatography and ultrafiltration. However, a single pass diafiltration design that meets the required small molecule clearance and has been integrated into a fully continuous monoclonal antibody purification process has not been previously published. Here, the theory and design of a 3‐stage single pass diafiltration step is presented. Buffer exchange greater than 99.75% was experimentally demonstrated. Several critical design aspects were incorporated to minimize system complexity and reduce the buffer volume requirements. Lastly, single pass diafiltration was demonstrated in a pilot scale continuous process with uninterrupted flow from the bioreactor through the formulation step. This work illustrates the feasibility of incorporating a single pass diafiltration step into an end‐to‐end continuous protein purification process.
Quantitatively characterizing drug‐induced arrhythmic contractile motions of human stem cell‐derived cardiomyocytes
Authors: Hoang Plansky , Huebsch Nathaniel , Bang Shin Hyuk , Siemons Brian A. , Conklin Bruce R. , Healy Kevin E. , Ma Zhen , Jacquir Sabir
Published: April 2018

Quantification of abnormal contractile motions of cardiac tissue has been a noteworthy challenge and significant limitation in assessing and classifying the drug‐induced arrhythmias (i.e., Torsades de pointes). To overcome these challenges, researchers have taken advantage of computational image processing tools to measure contractile motion from cardiomyocytes derived from human induced pluripotent stem cells (hiPSC‐CMs). However, the amplitude and frequency analysis of contractile motion waveforms does not produce sufficient information to objectively classify the degree of variations between two or more sets of cardiac contractile motions. In this paper, we generated contractile motion data from beating hiPSC‐CMs using motion tracking software based on optical flow analysis, and then implemented a computational algorithm, phase space reconstruction (PSR), to derive parameters (embedding, regularity, and fractal dimensions) to further characterize the dynamic nature of the cardiac contractile motions. Application of drugs known to cause cardiac arrhythmia induced significant changes to these resultant dimensional parameters calculated from PSR analysis. Integrating this new computational algorithm with the existing analytical toolbox of cardiac contractile motions will allow us to expand current assessments of cardiac tissue physiology into an automated, high‐throughput, and quantifiable manner which will allow more objective assessments of drug‐induced proarrhythmias.
Interobserver variability in the classification of appendicitis during laparoscopy
Authors: van den Boom A L , de Wijkerslooth E M L , Mauff K A L , Dawson I , van Rossem C C , Toorenvliet B R , Wijnhoven B P L
Published: April 2018

Background

The intraoperative classification of appendicitis dictates the patient's postoperative management. Prolonged antibiotic prophylaxis is recommended for complex appendicitis (gangrenous, perforated, abscess), whereas preoperative prophylaxis suffices for simple appendicitis. Distinguishing these two conditions can be challenging. The aim of this study was to assess interobserver variability in the classification of appendicitis during laparoscopy.

Methods

Short video recordings taken during laparoscopy for suspected appendicitis were shown to surgeons and surgical residents. They were asked to: classify the appendix as indicative of no, simple or complex appendicitis; categorize the appendix as normal, phlegmonous, gangrenous, perforated and/or abscess; and decide whether they would prescribe postoperative antibiotics. Inter-rater reliability was evaluated using Fleiss' κ score and the S* statistic.

Results

Some 80 assessors participated in the study. Video recordings of 20 patients were used. Interobserver agreement was minimal for both the classification of appendicitis (κ score 0·398, 95 per cent c.i. 0·385 to 0·410) and the decision to prescribe postoperative antibiotic treatment (κ score 0·378, 0·362 to 0·393). Agreement was slightly higher when published criteria were applied (κ score 0·552, 0·537 to 0·568).

Conclusion

There is considerable variability in the intraoperative classification of appendicitis and the decision to prescribe postoperative antibiotic treatment.
Meta-analysis evaluating music interventions for anxiety and pain in surgery
Authors: Kühlmann A Y R , de Rooij A , Kroese L F , van Dijk M , Hunink M G M , Jeekel J
Published: April 2018

Background

This study aimed to evaluate anxiety and pain following perioperative music interventions compared with control conditions in adult patients.

Methods

Eleven electronic databases were searched for full-text publications of RCTs investigating the effect of music interventions on anxiety and pain during invasive surgery published between 1 January 1980 and 20 October 2016. Results and data were double-screened and extracted independently. Random-effects meta-analysis was used to calculate effect sizes as standardized mean differences (MDs). Heterogeneity was investigated in subgroup analyses and metaregression analyses. The review was registered in the PROSPERO database as CRD42016024921.

Results

Ninety-two RCTs (7385 patients) were included in the systematic review, of which 81 were included in the meta-analysis. Music interventions significantly decreased anxiety (MD –0·69, 95 per cent c.i. –0·88 to –0·50; P < 0·001) and pain (MD –0·50, –0·66 to –0·34; P < 0·001) compared with controls, equivalent to a decrease of 21 mm for anxiety and 10 mm for pain on a 100-mm visual analogue scale. Changes in outcome corrected for baseline were even larger: MD –1·41 (–1·89 to –0·94; P < 0·001) for anxiety and –0·54 (–0·93 to –0·15; P = 0·006) for pain. Music interventions provided during general anaesthesia significantly decreased pain compared with that in controls (MD –0·41, –0·64 to –0·18; P < 0·001). Metaregression analysis found no significant association between the effect of music interventions and age, sex, choice and timing of music, and type of anaesthesia. Risk of bias in the studies was moderate to high.

Conclusion

Music interventions significantly reduce anxiety and pain in adult surgical patients.
Time to redefine the intramammary lymph node as a separate entity?
Authors: Green M. , Tafazal H. , Swati B. , Vidya R.
Published: April 2018

The lymphatic drainage for the majority of primary breast tumors is to the axillary lymph nodes (ALNs). Some, however, drain to the so‐called extra‐axillary basins, namely the internal mammary, supra‐ and infraclavicular regions. Another potential drainage route includes the intramammary lymph nodes (IMLNs). Current guidance suggests IMLNs should be considered as part of the axillary group, potentially affecting axillary management. However, due to evolution in imaging and advancement in technology, IMLNs may now be distinguished more accurately pre‐operatively. There are currently no published guidelines for the management of IMLNs in the United Kingdom. The authors suggest that it is time to reclassify IMLNs as a separate focus of cancer and treat it as a separate entity. Clin. Anat. 31:684–687, 2018. © 2018 Wiley Periodicals, Inc.
Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System
Authors: Sanagawa Akimasa , Hotta Yuji , Kataoka Tomoya , Maeda Yasuhiro , Kondo Masahiro , Kawade Yoshihiro , Ogawa Yoshihiro , Nishikawa Ryohei , Tohkin Masahiro , Kimura Kazunori
Published: April 2018

We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular‐targeted drugs). We focused on molecular‐targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab‐containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology.
Adjuvant radiotherapy and chemotherapy improve survival in patients with pancreatic adenocarcinoma receiving surgery: adjuvant chemotherapy alone is insufficient in the era of intensity modulation radiation therapy
Authors: Hsieh Mao‐Chih , Chang Wei‐Wen , Yu Hsin‐Hsien , Lu Chang‐Yun , Chang Chia‐Lun , Chow Jyh‐Ming , Chen Shee‐Uan , Cheng Yunfeng , Wu Szu‐Yuan
Published: April 2018

In the era of intensity modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of adjuvant therapies such as adjuvant concurrent chemoradiotherapy (CCRT), adjuvant sequential chemotherapy and radiotherapy (CT‐RT), and adjuvant CT alone in resectable pancreatic adenocarcinoma (PA). Through propensity score matching, we designed a nationwide, population‐based, head‐to‐head cohort study to determine the effects of dissimilar adjuvant treatments on resectable PA. We minimized the confounding of various adjuvant treatment outcomes among the following resectable PA groups of patients from the Taiwan Cancer Registry database: group 1, adjuvant CCRT; group 2, adjuvant sequential CT‐RT; and group 3, adjuvant CT alone. All the studied techniques are IMRTs. The matching process yielded a final cohort of 588 patients (196, 196, and 196 patients in groups 1, 2, and 3, respectively). In both univariate and multivariate Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of death derived for the adjuvant CCRT and adjuvant sequential CT‐RT cohorts compared with the adjuvant CT alone cohort were 0.398 (0.314–0.504) and 0.307 (0.235–0.402), respectively. A combination of adjuvant IMRT and CT for resectable PA treatment improves survival to a greater extent than does adjuvant CT alone.
Establishment of a nine‐gene prognostic model for predicting overall survival of patients with endometrial carcinoma
Authors: Ying Jianchao , Wang Qian , Xu Teng , Lyu Jianxin
Published: April 2018

Endometrial carcinoma (EC) is the most common malignant tumor of the female genital tract in developed countries. The prognosis of early stage EC is favorable, but a subset faces high risk of cancer progression or recurrence. EC has a poor prognosis upon progression to advanced or metastatic stages. Therefore, our goal is to build a robust prognostic model for predicting overall survival (OS) in EC patients. In this study, 1571 genes were identified as being associated with OS based on genomewide expression profiles using a training dataset. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these genes were involved in various cancer‐related signaling pathways. Nine signature genes were further selected using stepwise selection, and their potential role in the development of EC was demonstrated by performing differential expression analysis between EC and normal uterine tissues. A prognostic model that aggregated these nine signature genes was ultimately established and effectively divided EC patients into two risk groups. OS for patients in the high‐risk group was significantly poorer compared with that of the low‐risk group. This nine‐gene model was subsequently validated and evaluated using the TCGA dataset and shown to have a high discriminating power to distinguish EC patients with an elevated risk of mortality based on the FIGO staging system and other prognostic factors. This study provides a novel prognostic model for the identification of EC patients with elevated risk of mortality and will help to improve our understanding of the underlying mechanisms involved in prognostic EC factors.
A group‐based approach for gaze behavior of virtual crowds incorporating personalities
Authors: Ağıl Umut , Güdükbay Uğur
Published: April 2018

Predicting interest points of virtual characters and accurately simulating their gaze behavior play a significant role for realistic crowd simulations. We propose a saliency model that enables virtual agents to produce plausible gaze behavior. The model measures the effects of distinct saliency features implemented by examining the state‐of‐the‐art perception studies. When predicting an agent's interest point, we compute the saliency scores by using a weighted sum function for other agents and environment objects in the field of view of the agent for each frame. Then, we determine the most salient entity for each agent in the scene; thus, agents gain a visual understanding of their environment. Besides, our model introduces new aspects to crowd perception, such as perceiving characters as groups of people and applying social norms on crowd gaze behavior, effects of agent personality on gaze, gaze copy phenomena, and effects of agent velocity on attention. For evaluation, we compare the resulting saliency gaze model with real‐world crowd behavior in captured videos. In the experiments, we simulate the gaze behavior in real crowds. The results show that the proposed approach generates plausible gaze behaviors and is easily adaptable to varying scenarios for virtual crowds.
TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF‐κB signaling
Authors: Li Caixia , Zhao Bing , Lin Caizhao , Gong Zhiping , An Xiaoxia
Published: April 2018

This study aimed to investigate the effects of triggering receptor expressed on myeloid cell‐2 (TREM2) on the production of pro‐inflammatory mediators and cytokines induced by lipopolysaccharide (LPS) in BV2 microglia. TREM2 expression or TREM2‐specific siRNA were used to induce TREM2 overexpression or silencing. The BV2 cells were pre‐treated with the PI3 K inhibitor of LY294002 for 1 h and stimulated with LPS for 24 h. Then, the cell viability, apoptosis, phagocytosis, nitric oxide (NO), lactate dehydrogenase (LDH), and cytokine production, as well as the activation of AKT and NF‐kB were determined, respectively. We found LPS stimulation significantly reduced BV2 cell viability, enhanced BV2 cell phagocytosis and apoptosis compared to the control groups. In addition, LPS stimulation significantly increased the production of NO, LDH, TNF‐α, IL‐1β, and the activation of AKT and NF‐kB, while decreased the levels of IL‐10 and TGF‐β1. However, these pro‐inflammatory effects were significantly attenuated by TREM2 overexpression or pre‐treatment with LY294002, while enhanced by TREM2 silencing. Thus, we concluded that TREM2 inhibited neuroinflammation by down‐regulating PI3 K/AKT and NF‐kB signaling in BV2 microglia. Above all, therapeutic enhanced TREM2 expression may be a new strategy for intervention of neuroinflammatory diseases.
Lefty promotes the proliferation and invasion of trophoblast cells by inhibiting nodal expression
Authors: Li Hong , Cao Rui , Bai Liang , Qiao Xin‐min , Zhao Yong‐qin
Published: April 2018

Trophoblast cells play a vital role in embryo implantation. Exploring cytokines secreted by trophoblast cells will be significant in revealing the molecular mechanism of embryo implantation. In vitro‐cultured trophoblast cells treated with Lefty revealed that Lefty could downregulate the expression of Nodal while promoting the expression of MMP‐2 and MMP‐9. Thus, Lefty may promote the proliferation and invasion of trophoblast cells, thereby reducing the amount of apoptosis of these cells. Lefty siRNA knockdown or overexpression of Nodal showed opposite effects to treatment with Lefty. When trophoblast cells overexpressing Nodal were treated with Lefty, Nodal expression increased, and MMP‐2 and MMP‐9 expression was still promoted. Additionally, the proliferation and invasion of trophoblast cells were upregulated, and trophoblast apoptosis was reduced. Together, these data reveal that Lefty can promote the proliferation and invasion of trophoblast cells and inhibit their apoptosis by downregulating Nodal expression while promoting the expression of MMP‐2 and MMP‐9. This finding provides new proof for the mechanism of trophoblast cell invasion in decidua.
Buprenorphine first line, then methadone recommended for all youth in U.S.‐funded study
Authors: Knopf Alison
Published: April 2018

Expansion of treatment for adolescents and young adults — ages 15 to 25 — with opioid use disorders (OUDs) is critical at a time when there are increasing overdoses, as well as significant barriers to care, researchers write in the current issue of the American Journal of Drug and Alcohol Abuse. Extensive literature on the adult population shows that medication‐assisted treatment (MAT) is an important, even essential, aspect of care for OUDs for most youth. The researchers looked at the dilemmas and questions regarding MAT for youth, and proposed possible solutions.
A model for increasing access to behavioral health services in low‐ and middle‐income countries
Authors: Walters Anne
Published: April 2018

This month's commentary comes to you from Eldoret, Kenya, where a group of child clinical psychologists and child and adolescent psychiatry fellows from Brown Medical School are completing a rotation in global mental health. We are collaborating with Kenyan colleagues in the Psychiatry and Behavioral Sciences Department at the Moi University School of Medicine, learning about providing mental health services in resource‐poor settings, and hoping to provide some training in treatments that are more commonly provided in the United States.
The Cost of Disruptive Intervention in Developmental Math
Authors: Manning Terri Mulkins
Published: April 2018

This chapter examines how student success allows a college to recoup their funding loss from a costly reform effort in developmental math education.
Exercise echocardiography in valve disease
Authors: Ilardi F. , Sugimoto T. , Dulgheru E. R. , Go Y. Y. , Marchetta S. , Contu L. , Lancellotti P.
Published: April 2018

Evidence supporting the use of exercise echocardiography to identify the true hemodynamic consequences of valvular heart disease (VHD) is progressively accumulating. From a clinical standpoint, the evaluation of VHD limited to resting conditions often underestimates the full clinical impact of the lesion. Exercise echocardiography has proved to be an important clinical tool in the risk stratification and the decision making of patients with VHD. It is very useful in case of discrepancy between symptoms and severity of valve lesion. Moreover, the evaluation of dynamic components of VHD, ventricular function, and exercise capacity provides clinician additive prognostic value that can be really helpful in the management planning of these patients.
Role of the deformation imaging in the evaluation of patients with cardiomyopathy
Authors: Papadopoulos C. H.
Published: April 2018

Cardiomyopathies are a heterogeneous group of diseases recognized by specific patterns of myocardial morphology and function. Myocardial deformation imaging, using strain and strain rate as main parameters, is a novel echocardiographic method for the evaluation of global and regional myocardial function. Speckle tracking imaging is currently the best technique for the evaluation of myocardial deformation in the longitudinal, radial, and circumferential axis. The aim of the following review was to analyze the potential role of the deformation imaging in the evaluation of cardiomyopathies, focusing on the recent developments regarding the differential and early diagnosis as well as the prognosis of the disease.
Recent advances in cardiac gene therapy strategies targeting advanced heart failure
Authors: Chen C. , Seeger T. , Termglinchan V. , Karakikes I.
Published: April 2018

Heart failure (HF) is the common sequela of many cardiovascular diseases. Although device‐based treatments and pharmacotherapies have improved patient survival, current standard therapies are far from optimal, and do not address the molecular mechanisms underlying HF pathogenesis. In the last decade, cardiac gene therapy has emerged as an innovative experimental therapeutic strategy for the treatment of advanced HF. Increasing insights into the molecular pathophysiology and improvements in gene targeting approaches provide novel therapeutic modalities. In this review we focus on the recent developments in cardiac gene therapy strategies targeting advanced HF. We emphasize ongoing clinical trials, and discuss the limitations and future evolution of the field.
Cell therapy for cardiac diseases
Authors: Tseliou E.
Published: April 2018

Cardiac injury and loss of functional cardiomyocytes result in cardiac pump failure, the leading cause of morbidity and mortality in the world. Endogenous regeneration of the injured heart holds great promise but is very limited in the human heart. Various strategies have been developed to boost replacement of the lost cardiomyocytes including stem cells and cellular reprogramming. In this review we will discuss the progress in cardiac regeneration field, the advantages and disadvantages of each cell type and how a combinatorial approach with regards to current drug treatment could enhance cardiac regeneration.
Effect of tempering moisture and infrared heating temperature on the functionality of Desi chickpea and hull‐less barley flours
Authors: Bai Tian , Stone Andrea K. , Nickerson Michael T.
Published: April 2018

Background and objectives

The effect of seed tempering moisture (20% moisture content or left un‐tempered) and infrared heating surface temperature (115 or 135°C) on the functional properties of Desi chickpea and hull‐less barley was investigated.

Findings

Tempering and infrared heating reduced the protein solubility in both flours, whereas the ability to bind oil was unaffected. Both flours had increased water binding abilities in response to tempering and infrared heating. In the case of chickpea flour, the emulsion activity (EA) increased when the seeds were tempered and heated to 135°C, whereas both emulsion and foaming stability remained unchanged with all processing conditions. Tempering before infrared heating decreased the foaming capacity of chickpea flour. In contrast, barley flour showed a decrease in both EA and stability, and became nonfoaming with infrared heating with and without tempering.

Conclusions

Infrared heating has both positive and negative effects on the functional properties of Desi chickpea and hull‐less barley flours.

Significance and novelty

Findings from this work will help direct ingredient processors to process seeds to achieve different functionalities which is important for food product development purposes.
Direct Synthesis of Nitrogen, Phosphorus, and Sulfur Tri‐doped Carbon Nanorods as Highly Efficient Oxygen Reduction and Evolution Electrocatalysts
Authors: Ren Jin‐Tao , Yuan Zhong‐Yong
Published: April 2018

The growing energy and environmental crisis calls for renewable systems for energy production and conversion. Herein, polyaniline‐derived porous carbon nanorods tri‐doped with N, P, and S (NPSC) are directly fabricated by the one‐pot polymerization of aniline and diphenylamine‐4‐sulfonic acid induced by organophosphonic acid and subsequent pyrolysis at 900 °C. The nanorods exhibit high‐efficiency electrochemical oxygen reduction and oxygen evolution activity in alkaline electrolyte, along with strong durability and methanol tolerance. The synergistic effect among the tri‐doped elements and the related porosity can account for the superior electrocatalytic capacity of the fabricated catalysts. Particularly, a Zn–air battery assembled with the fabricated NPSC as the cathode shows a peak power density of 122 mW cm−2 and superior stability, presenting a promising potential for sustainable energy devices, particularly regenerative metal–air batteries and fuel cells.
A Multi‐Component Reaction towards the Development of Highly Modular Hydrogelators
Authors: Sauvée Claire , Ström Anna , Haukka Matti , Sundén Henrik
Published: April 2018

Herein we report a multi‐component reaction approach for the development of a new class of hydrogelators based on the OxoTriphenylHexanOate (OTHO) backbone. A focused library of OTHOs has been synthesized and their hydrogelation features evaluated. The two most potent hydrogelators were studied by rheology revealing different stiffness, appearances and thixotropic behavior of the gels. The new gelators showcase the versatility of the OTHO backbone as a platform for the design of functionalized hydrogels with tunable gel properties.
Aggregation‐Enhanced Emission and Thermally Activated Delayed Fluorescence of Derivatives of 9‐Phenyl‐9H‐Carbazole: Effects of Methoxy and tert‐Butyl Substituents
Authors: Grybauskaite‐Kaminskiene Gintare , Volyniuk Dmytro , Mimaite Viktorija , Bezvikonnyi Oleksandr , Bucinskas Audrius , Bagdziunas Gintautas , Grazulevicius Juozas V.
Published: April 2018

Derivatives of 9‐phenyl‐9H‐carbazole were synthesized as efficient emitters exhibiting both thermally activated delayed fluorescence and aggregation‐induced emission enhancement. Effects of methoxy and tert‐butyl substituents at the different positions of carbazolyl groups on the properties of the emitters were studied. Depending on the substitutions, photoluminescence quantum yields (PLQY) of non‐doped solid films of the compounds ranged from 17 % to 53 % which were much higher than those observed for the solutions in low‐polarity solvent toluene. Compounds substituted at C‐3 and C‐6 positions of carbazole moiety by methoxy‐ and tert‐butyl‐ groups showed the highest solid‐state PLQY. Ionization potentials of the studied derivatives in solid‐state were found to be in the short range of 5.75–5.89 eV. Well‐balanced hole and electron mobilities were detected for tert‐butyl‐substituted compound. They exceeded 10−4 cm2 (V×s)−1 at electric fields higher than 3×105 V cm−1. Two compounds with the highest solid‐state PLQYs showed higher efficiencies in non‐doped organic light‐emitting diodes than in the doped devices. Maximum external quantum efficiency of 7.2 % and brightness of 15000 cd m−2 were observed for the best device.
Host–Host Interactions Control Self‐assembly and Switching of Triple and Double Decker Stacks of Tricarbazole Macrocycles Co‐assembled with anti‐Electrostatic Bisulfate Dimers
Authors: Dobscha James R. , Debnath Sibali , Fadler Rachel E. , Fatila Elisabeth M. , Pink Maren , Raghavachari Krishnan , Flood Amar H.
Published: April 2018

Hierarchical assembly provides a route to complex architectures when using building blocks with strong and structurally well‐defined recognition elements. These rules are traditionally expressed using cationic templates with reliable metal‐ligand bonding but use of anions is rare on account of weak anion–host contacts. We investigate an approach that relies on host–host interactions to fortify assemblies formed between bisulfate anion dimers, [HSO4⋅⋅⋅HSO4]2−, and shape‐persistent macrocycles called tricarbazole triazolophanes. These macrocycles have significant self‐association. In chloroform, they form high fidelity, triple‐decker stacks with bisulfate dimers. The strength of host–host interactions allows for preferential formation of the 3:2 tricarb:bisulfate architecture over an ion‐paired architecture seen with analogous macrocycles with much weaker self‐association. Solvent was expected and found to tune host–host contacts enabling formation of a 2:2 complex and solvent‐driven switching between triple‐ and double‐stacked structures. Crystallography of the 2:2:2 complex supports the idea that significant host–host interactions with tricarb arises from dipole‐stabilized π‐stacking. Computational studies were also conducted further highlighting the importance of host–host interactions in stacked complexes of tricarb. These findings unambiguously verify the importance of host–host interactions in the assembly and stability of discrete, responsive anion‐templated architectures.