bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary Cortisol Concentrations, Grit, and the Effect of Time
Authors: Wong Matthew L. , Peters Gregory , Joseph Joshua W. , Chung Arlene , Sanchez Leon D.
Published: April 2019

Background

Stress is a common experience in the emergency department (ED) and is a balance of personal capabilities versus demands. Residency training is meant to improve individuals’ capabilities and therefore may attenuate an individual's stress response. Grit is a personality trait that may attenuate stress in individuals. In this study we explore the relationship between time of year, postshift salivary cortisol concentrations, and the influence of grit among attendings and residents in an academicED.

Methods

Thirty‐nine residents and 17 attendings were enrolled and followed for two academic years at an urban academic medical center. Postwork salivary cortisol samples were collected quarterly, and Duckworth 12‐point Grit Scales were administered annually. Data from the relative quarters of the first and second years were combined, and the results were analyzed using descriptive statistics and generalized estimating equations.

Results

We analyzed 216 cortisol samples and 87 grit scores over 2 academic years. Between the first and fourth quarters of the academic year, the percentage of subjects with a detectable postshift cortisol sample decreased from 47.6% (30 of 62) to 18.4% (9 of 49). In the fourth academic quarter compared to the first, the odds that an individual had a detectable cortisol were significantly lower overall (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.10 to 0.59, p = 0.01), including the subset of only trainees (OR = 0.26, 95%CI = 0.07 to 0.88, p = 0.01), and adjusting for grit did not meaningfully change theORs.

Conclusion

Over the course of the academic year, the odds that an individual's postshift salivary cortisol concentration will be above detectable concentration significantly decrease over time, and this relationship is not confounded by grit.
Synthesis of Heteroaryl Iodanes(III) via ipso‐Substitution Reactions Using Iodine Triacetate Assisted by HFIP
Authors: Matsuoka Keitaro , Komami Narumi , Kojima Masahiro , Yoshino Tatsuhiko , Matsunaga Shigeki
Published: April 2019

The synthesis of monoaryl‐λ3‐iodanes generally requires the oxidation of iodoarenes, but the functional group compatibility is often problematic when using oxidizable substrates such as heteroaromatic compounds. Although electrophilic aromatic substitution or ipso‐substitution reactions using iodine tricarboxylates have been studied as an alternative synthetic route to dicarboxyiodoarenes, several common heteroaromatic substrates such as indoles, quinolines, (benzo)furans, and (benzo)thiophenes have not been investigated to date. Here, we report that ipso‐substitution reactions of heteroaromatic stannanes using I(OAc)3 in the presence of 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) effectively provide diacetoxyiodoarenes, which can be converted into the corresponding iodonium ylides or be directly used in a one‐pot iodoarylation reaction.
Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders
Authors: Posset Roland , Gropman Andrea L. , Nagamani Sandesh C. S. , Burrage Lindsay C. , Bedoyan Jirair K. , Wong Derek , Berry Gerard T. , Baumgartner Matthias R. , Yudkoff Marc , Zielonka Matthias , Hoffmann Georg F. , Burgard Peter , Schulze Andreas , McCandless Shawn E. , Garcia‐Cazorla Angeles , Seminara Jennifer , Garbade Sven F. , Kölker Stefan ,   for the Urea Cycle Disorders Consortium and the European Registry and Network for Intoxication Type Metabolic Diseases Consortia Study Group
Published: April 2019

Objective

Individuals with urea cycle disorders (UCDs) often present with intellectual and developmental disabilities. The major aim of this study was to evaluate the impact of diagnostic and therapeutic interventions on cognitive outcomes in UCDs.

Methods

This prospective, observational, multicenter study includes data from 503 individuals with UCDs who had comprehensive neurocognitive testing with a cumulative follow‐up of 702 patient‐years.

Results

The mean cognitive standard deviation score (cSDS) was lower in symptomatic than in asymptomatic (p < 0.001, t test) individuals with UCDs. Intellectual disability (intellectual quotient < 70, cSDS < −2.0) was associated with the respective subtype of UCD and early disease onset, whereas height of the initial peak plasma ammonium concentration was inversely associated with neurocognitive outcomes in mitochondrial (proximal) rather than cytosolic (distal) UCDs. In ornithine transcarbamylase and argininosuccinate synthetase 1 deficiencies, we did not find evidence that monoscavenger therapy with sodium or glycerol phenylbutyrate was superior to sodium benzoate in providing cognitive protection. Early liver transplantation appears to be beneficial for UCDs. It is noteworthy that individuals with argininosuccinate synthetase 1 and argininosuccinate lyase deficiencies identified by newborn screening had better neurocognitive outcomes than those diagnosed after the manifestation of first symptoms.

Interpretation

Cognitive function is related to interventional and non‐interventional variables. Early detection by newborn screening and early liver transplantation appear to offer greater cognitive protection, but none of the currently used nitrogen scavengers was superior with regard to long‐term neurocognitive outcome. Further confirmation could determine these variables as important clinical indicators of neuroprotection for individuals with UCDs. ANN NEUROL 2019
Immobilization of cerium (IV) and erbium (III) in mesoporous MCM‐41: Two novel and highly active heterogeneous catalysts for the synthesis of 5‐substituted tetrazoles, and chemo‐ and homoselective oxidation of sulfides
Authors: Molaei Somayeh , Ghadermazi Mohammad
Published: April 2019

Two well‐ordered 2D‐hexagonal cerium (IV) and erbium (III) embedded functionalized mesoporous MCM‐41(MCM‐41@Serine/Ce and MCM‐41@Serine/Er) have been developed via functionalization of mesoporous MCM‐41. The surface modification method has been used in the preparation of serine‐grafted MCM‐41 and led to the development of MCM‐41@Serine. The reaction of MCM‐41@Serine with Ce (NH4)2(NO3)6·2H2O or ErCl3·6H2O in ethanol under reflux led to the organization of MCM‐41@Serine/Ce and MCM‐41@Serine/Er catalysts. The structures of these catalysts were determined using scanning electron microscopy, mapping, energy‐dispersive X‐ray spectroscopy, Fourier transform‐infrared, thermogravimetric analysis, X‐ray diffraction, inductively coupled plasma, and Brunauer–Emmett–Teller analysis. These MCM‐41@Serine/Ce and MCM‐41@Serine/Er catalysts show outstanding catalytic performance in sulfides oxidation and synthesis of 5‐substituted tetrazoles. These catalysts can be recycled for seven repeated reaction runs without showing a considerable decrease in catalytic performance.
Theoretical insight into the photodeactivation pathway of the tetradentate Pt (II) complex with different inductive substituents
Authors: Wu Zhixiang , Xie Tao , Luo Yafei , Zhuo Wei , Gu Jinke , Yan Xiao , Sun Xin , Zuo Ke , Liu Xingyu , Gan Ya , Liang Li , He Gang , Liu Wei , Gou Xiaojun , Tang Dianyong , Shi Hubing , Hu Jianping
Published: April 2019

Density functional theory (DFT) and time‐dependent density functional theory (TD‐DFT) both were used to explore the impacts of different inductive substituents on the photophysical properties, radiative/nonradiative processes and photodeactivation mechanism for the Pt (II) complex with novel spiro‐arranged tetradentate ligand. Spectrum simulations show that the electron donor methoxyl (‐OCH3) group can cause the emission wavelength to red‐shift but have little effect on the absorption spectrum. In the simulation of the radiative decay process for the tetradentate Pt (II) complex, the singlet‐triplet splitting energy is reduced by the introduction of substituents with strong electron‐releasing capability (i.e., from the original trifluoromethyl (‐CF3) group to ‐OCH3 group), accompanied with a lower radiative rate constant (kr). The analyses of non‐radiative decay processes show that the substitution of ‐OCH3 group on azole rings reduces the energy barriers of thermally activated non‐radiative photodeactivation pathway, which in turn increases the temperature‐dependent non‐radiative rate constants (knr(T)). In addition, the substitution of ‐CF3 by ‐OCH3 group slightly weakens molecular rigidity and enhances the Huang‐Rhys factor, but decreases the SOC between the triplex excited (T) state and the ground (S0) state. Thereby, the two complexes may have the similar temperature‐independent non‐radiative rate constant (knr’). This work offers theoretical guidance for the design and optimization of the efficient organic light emitting diode (OLED) materials based on the structure of tetradentate Pt (II) complexes.
Data fusion‐based descriptor approach for attitude estimation under accelerated maneuvers
Authors: Makni Aida , Kibangou Alain Y. , Fourati Hassen
Published: April 2019

This paper proposes the design of an attitude estimation algorithm for a rigid body subject to accelerated maneuvers. Unlike the current literature where the process model is usually driven by triaxial gyroscope measurements, we investigate a new formulation of the state‐space model where the process model is given by triaxial accelerometer measurements. The observation model is given by triaxial gyroscope and magnetometer measurements. The proposed model is written as a descriptor system and takes the external acceleration sensed by the accelerometer into account. Based on this model, a Quaternion Descriptor Filter (QDF) is developed and its performance is evaluated through simulations and experimental tests in pedestrian navigation.
State estimation for stochastic time‐varying multisensor systems with multiplicative noises: Centralized and decentralized data fusion
Authors: Rahmani Mehdi , Abolhasani Mahdi
Published: April 2019

In this paper, the state estimation problems, including filtering and one‐step prediction, are solved for uncertain stochastic time‐varying multisensor systems by using centralized and decentralized data fusion methods. Uncertainties are considered in all parts of the state space model as multiplicative noises. For the first time, both centralized and decentralized estimators are designed based on the regularized least‐squares method. To design the proposed centralized fusion estimator, observation equations are first rewritten as a stacked observation. Then, an optimal estimator is obtained from a regularized least‐squares problem. In addition, for decentralized data fusion, first, optimal local estimators are designed, and then fusion rule is achieved by solving a least‐squares problem. Two recursive equations are also obtained to compute the unknown covariance matrices of the filtering and prediction errors. Finally, a three‐sensor target‐tracking system is employed to demonstrate the effectiveness and performance of the proposed estimation approaches.
Tryptamine–Triazole Hybrid Compounds for Selective Butyrylcholinesterase Inhibition
Authors: Son Minky , Lee Haneul , Jeon Cheolmin , Kang Yujung , Park Chanin , Lee Keun Woo , Park Jeong Ho
Published: April 2019

Tryptamine–triazole hybrid compounds (11–18) were synthesized via click reaction between tryptamine azide and propargylated natural compounds. Their cholinesterase inhibitory activity was evaluated. Among the eight compounds, compound 11 showed the most potent inhibitory activity [IC50 = 0.42 ± 0.29 μM for equine butyrylcholinesterase (BuChE) and 1.96 ± 0.15 μM for human BuChE]. From the molecular modeling study, compound 11 was bound to the catalytic anionic site, anionic subsite, peripheral anionic subsite, acyl‐binding pocket, and oxyanion hole of human or horse BuChE by forming a hairpin or U‐shaped structure. The Lineweaver‐Burk plot of compound 11 against BuChE suggests a mixed type of inhibition which corresponds well with the molecular modeling study.
Pharmacokinetics of salvianolic acid B, rosmarinic acid and Danshensu in rat after pulmonary administration of Salvia miltiorrhiza polyphenolic acid solution
Authors: Lu Peng , Xing Yue , Xue Zhifeng , Ma Zhe , Zhang Bing , Peng Hui , Zhou Qi (Tony) , Liu Hongfei , Liu Zhidong , Li Jiawei
Published: April 2019

A sensitive and accurate LC–MS/MS method was established for quantifying salvianolic acid B (Sal B), rosmarinic acid (Ros A) and Danshensu (DA) in rat plasma. Salvia miltiorrhiza polyphenolic acid (SMPA), active water‐soluble ingredients isolated and purified from Salvia miltiorrhiza Bge included Sal B, Ros A and DA. The pharmacokinetic analysis of Sal B, Ros A and DA after pulmonary administration of SMPA solution to rat was performed by LC–MS/MS. Results from the pharmacokinetic studies showed that the peak concentration of DA was 21.85 ± 6.43 and 65.39 ± 3.83 ng/mL after pulmonary and intravenous administration, respectively. DA was not detected at 2 h after administration. The absolute bioavailabilities of Sal B and Ros A were respectively 50.37 ± 27.04 and 89.63 ± 12.16% after pulmonary administration of 10 mg/kg SMPA solution in rats. The absolute bioavailability of Sal B increased at least 10‐fold after pulmonary administration, compared with oral administration. It was concluded that the newly established LC–MS/MS method was suitable for describing the pharmacokinetic characteristics of Sal B, Ros A and DA in rat after pulmonary administration of SMPA solution. The data from this study will provide a preclinical insight into the feasibility of pulmonary administration of SMPA.
Improvements in single‐use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance
Authors: Kelly Paul S. , Dorival‐García Noemi , Paré Samantha , Carillo Sara , Ta Christine , Alarcon Miguez Antonio , Coleman Orla , Harper Emma , Shannon Maeve , Henry Michael , Connolly Lisa , Clynes Martin , Meleady Paula , Bones Jonathan , Barron Niall
Published: April 2019

Single‐use technologies, in particular disposable bioreactor bags, have become integral within the biopharmaceutical community. However, safety concerns arose upon the identification of toxic leachable compounds derived from the plastic materials. Although the leachable bis(2,4‐di‐tert‐butylphenyl)‐phosphate (bDtBPP) has been previously shown to inhibit CHO cell growth, it is critical to determine if other compounds like this are still present in subsequent generations of films for industrial application. This study compares the performance of CHO cells, CHO‐K1, and CHO‐DP12, cultured in media conditioned in an older single‐use bioreactor (SUB) film (F‐1) and a newer generation film (F‐2) from the same vendor. CHO cells cultured in media conditioned for 7 days in the F‐1 film demonstrated significantly reduced growth and antibody productivity profiles when compared to controls and media conditioned for the same time period in the newer F‐2 film. Proteomic profiling of CHO cells cultured in the F‐1 conditioned media identified differentially expressed proteins involved in oxidative stress response as well as compromised ATP synthesis. These potentially metabolically compromised cells exhibited reduced oxidative phosphorylation activity as well as lower glycolytic metabolism, characteristic of slower growing cells. Nonvolatile and metal leachables analysis of film extracts by LC–MS revealed a reduction in the abundance of the analyzed leachates from F‐2 films when compared to F‐1 films including bDtBPP, potentially explaining improved CHO cell growth in F‐2 conditioned media. Furthermore, in vitro endocrine disruptor testing of the known leachable revealed this molecule to possess the potential to act as an androgen antagonist. This study demonstrates an improvement in the materials composition used in modern generations of SUBs for safe application in the bioprocess.
Implementation of an experimental and computational tool set to study protein‐mAb interactions
Authors: Ranjan Swarnim , Chung Wai Keen , Zhu Min , Robbins David , Cramer Steven M.
Published: April 2019

This work focused on the development of a combined experimental and computational tool set to study protein‐mAb interactions. A model protein library was first screened using cross interaction chromatography to identify proteins with the strongest retention. Fluorescence polarization was then employed to study the interactions and thermodynamics of the selected proteins—lactoferrin, pyruvate kinase, and ribonuclease B with the mAb. Binding affinities of lactoferrin and pyruvate kinase to the mAb were seen to be relatively salt insensitive in the range examined. Further, a strong entropic contribution was observed, suggesting the importance of hydrophobic interactions. On the other hand, ribonuclease B‐mAb binding was seen to be enthalpically driven and salt sensitive, indicating the importance of electrostatic interactions. Protein–protein docking was then carried out and the results identified the CDR region on the mAb as an important binding site for all three proteins. The binding interfaces identified for the mAb‐lactoferrin and mAb‐pyruvate kinase systems were found to contain complementary hydrophobic and oppositely charged clusters on the interacting regions which were indicative of both hydrophobic and electrostatic interactions. On the other hand, the binding site on ribonuclease B was predominantly positively charged with minimal hydrophobicity. This resulted in an alignment with negatively charged clusters on the mAb, supporting the contention that these interactions were primarily electrostatic in nature. Importantly, these computational results were found to be consistent with the fluorescence polarization data and this combined approach may have utility in examining mAb‐HCP interactions which can often complicate the downstream processing of biologics. © 2019 American Institute of Chemical Engineers
A phase II clinical study of 13‐deoxy, 5‐iminodoxorubicin (GPX‐150) with metastatic and unresectable soft tissue sarcoma
Authors: Van Tine Brian A. , Agulnik Mark , Olson Richard D. , Walsh Gerald M. , Klausner Arthur , Frank Nicole E. , Talley Todd T. , Milhem Mohammed M.
Published: April 2019

Background

13‐Deoxy, 5‐iminodoxorubicin (GPX‐150) is a doxorubicin (DOX) analog synthesized to reduce the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible, cumulative dose‐dependent cardiotoxicity of DOX. In a preclinical chronic models and a phase I clinical study of GPX‐150, no irreversible, cumulative dose‐dependent cardiotoxicity was demonstrated. Recent studies suggest that DOX cardiotoxicity may be mediated, at least in part, by the poisoning of topoisomerase IIβ.

Patients and Methods

An open‐label, single‐arm phase II clinical study in metastatic and unresectable soft tissue sarcoma (STS) patients was initiated to further evaluate the efficacy and safety of GPX‐150, including cardiac function, specifically left ventricular ejection fraction (LVEF).

Results

GPX‐150 was administered at 265 mg/m2 every 3 weeks for up to 16 doses with prophylactic G‐CSF until progression, death, or patient withdrawal from the study. GPX‐150 exhibited efficacy assessed as progression‐free survival (PFS) rates of 38% and 12% at 6 and 12 months and an overall survival rate of 74% and 45% at 6 and 12 months. GPX‐150–treated patients did not develop any evidence of irreversible, cumulative dose‐dependent chronic cardiotoxicity. Toxicities included grade 3 anemia, neutropenia, and one grade 4 leukopenia. Correlative analysis demonstrated that GPX‐150 was more selective than DOX for the inhibition of topoisomerase IIα over IIβ in vitro.

Conclusion

These results suggest future studies are warranted to further evaluate the clinical efficacy of GPX‐150 in STS, perhaps at doses higher than 265 mg/m2.
Incidence and risk factors for acute kidney injury following autologous stem cell transplantation for multiple myeloma
Authors: Andronesi Andreea G. , Tanase Alina D. , Sorohan Bogdan M. , Craciun Oana G. , Stefan Laura , Varady Zsofia , Lipan Lavinia , Obrisca Bogdan , Truica Alexandra , Ismail Gener
Published: April 2019

Acute kidney injury (AKI) is a common complication after allogeneic stem cell transplantation; however, its incidence and outcome in patients transplanted for multiple myeloma (MM) is unknown. We evaluated the incidence, severity, and risk factors for AKI within the first 30 days after autologous stem cell transplantation (ASCT) for MM. We prospectively followed 185 consecutive patients with MM, without chronic renal replacement therapy, who underwent ASCT; 12.5% of patients had MM‐associated amyloidosis. AKI occurred in 19 (10.3%) patients, 8 ± 3 days after ASCT, with 18 patients (9.7%) stage 1 and one patient (0.6%) stage 2 AKI. The development of AKI was not associated with reduced overall survival and recovery of kidney function was evident in 68.4% of patients at 3 months. In Cox regression analysis, preexisting–chronic kidney disease (HR 7.01, CI 95% 2.04‐24.09; P = 0.002), serum beta2 microglobulin (HR 3.05, CI 95% 1.10‐8.44; P = 0.03), and mucositis grade 3/4 (HR 1.29, CI 95% 1.08‐1.53; P = 0.003) were independent risk factors for AKI. Our results suggest that AKI occurs with low incidence and reduced severity after ASCT for MM. Prophylactic measures in patients with preexisting–kidney failure may further reduce this risk.
Crystallization of Cephradine Polymorphs and Hydrates from Mixed Solvents of Methanol and Water
Authors: Ostergaard Iben , Lopez de Diego Heidi , Qu Haiyan
Published: April 2019

Cephradine monohydrate (CPH) crystallizes with a needle‐like shape which leads to severe agglomeration and slow filtration. Effects of different operating conditions on the particle size and shape as well as the filterability of the crystal products are described. The solubility and stability of one anhydrate of cephradine (CPA1) and CPH as a function of temperature and water activity was investigated in different methanol and water mixtures. A solvent‐mediated transformation from CPH to CPA1 was observed at water mole fractions below 0.2–0.35 depending on the temperature. The crystallization behavior of CPH was studied by linear cooling and antisolvent crystallization. Lowering the cooling rate and addition of seeds led to an increase in particle size and improvement of filterability.
Quantitative Measurements of the Critical Impeller Speed for Solid‐Liquid Suspensions
Authors: Ye Guichuan , Nienow Alvin W. , Alberini Federico
Published: April 2019

A quantitative methodology for particle suspension assessment is presented. A new parameter, fmov/tot, the ratio of the mean number of moving particles to the total number of particles, is introduced to evaluate the minimum speed required to just suspend solids. This approach is tested to investigate the impact of impeller clearance on the minimum impeller speed, Njs, in a vessel when using a radial flow Rushton turbine. Flow patterns and power numbers obtained experimentally and computationally support the suspension findings. Image analysis is an appropriate method for determining Njs. Lowering the impeller clearance reduces the speed required for particle suspension with a change of flow pattern from a radial discharge with two loops to a single loop scouring the vessel base. The power number also falls markedly at the two‐to‐one loop transition as does the strain rate near the base.
Hoher Durchsatz und maximale Prozesssicherheit
Authors: Kern Norbert
Published: April 2019

Die neue Rührwerkskugelmühle Visconomic+ wurde speziell für die Verarbeitung von hochviskosen Produkten entwickelt. Die neue Spaltgeometrie sorgt zusammen mit der Stiftanordnung für eine maximale Strömungsbelastbarkeit. Durch diese Kombination werden eine frühzeitige Kompaktierung der Mahlkörper und eine Überhitzung des Produkts vermieden. Die Rotor‐ und Statorkühlung gewährleistet zudem eine optimale Temperaturführung.
Gas‐Feststoff‐Reaktionen im Test
Authors: Leffelsend Nicola
Published: April 2019

Bei Schwing Technologies stehen thermochemische Umsetzungen von pulverförmigen Partikeln, granulierten Feststoffen oder Komponentengemischen für die Lebensmittel‐, Chemie‐, Kunststoff‐, Kosmetik‐, Pharma‐ und Energie‐Industrie im Focus. Jüngstes Beispiel ist das Forschungsprojekt Twist, für das der Hersteller aus Neukirchen‐Vluyn gemeinsam mit der TU München thermochemische Energiespeicher‐Technologie für industrielle Langzeitspeicher in der Stromerzeugung entwickelt. Für diese und viele weitere Anwendungen garantieren die wartungsarmen und energieeffizienten Wirbelschichtreaktoren eine kontrolliert einheitliche, reproduzierbare, effiziente Materialbearbeitung bis zu 1100 °C.
In einem Messwert steckt eine ganze Menge mehr
Authors: Rosenberger Kristina
Published: April 2019

In der Prozessindustrie kommt es auf die Anlagenverfügbarkeit sowie die Steigerung von Effizienz und Sicherheit für eine nachhaltige Wettbewerbsfähigkeit an. Industrieumfragen zeigen, dass die Erwartung der Prozessindustrie an die Messtechnik hoch sind. Erfahren Sie in diesem Beitrag, was Feldgeräte von Endress+Hauser leisten können und wie sie den Erwartungen der Branche gerecht werden. Mit ihren Funktionen zu Diagnose, Verifikation und Monitoring liefern die Messgeräte weit mehr als ein reines 420 mA Signal.
Extending expressed RNA genomics from surgical decision making for cytologically indeterminate thyroid nodules to targeting therapies for metastatic thyroid cancer
Authors: Ali Syed Z. , Siperstein Allan , Sadow Peter M. , Golding Allan C. , Kennedy Giulia C. , Kloos Richard T. , Ladenson Paul W.
Published: April 2019

The Afirma Genomic Sequencing Classifier (GSC) is a rule‐out test for malignancy/noninvasive follicular thyroid neoplasms with papillary‐like nuclear features among patients with Bethesda category III/IV nodules, whereas the complimentary Xpression Atlas provides genomic insights from a curated panel of 511 genes among GSC suspicious and Bethesda category V/VI nodules. Together, they facilitate personalized treatment decisions based on genomic insights derived from the transcriptome of the biopsied target and extend the diagnostic and therapeutic reach of cytopathologists and fine‐needle aspiration biopsy sample collection.
Recyclable Nanoporous Materials with Ordered Tunnels Self‐Assembled from α‐ and γ‐Cyclodextrins
Authors: Li Qingxuan , Wang Jin , Ye Lin , Zhang Aiying , Zhang Xuetong , Feng Zengguo
Published: April 2019

A straightforward method to create nanoporous materials via the self‐assembly of macrocyclic molecules (MCMs) is proposed and fulfilled by using cyclodextrins (CD) as building blocks. Due to molecular geometry, α‐CD forms a hexagonal nanoporous crystal, whereas γ‐CD forms a cuboid crystal. The resulting products are confirmed by FTIR, 1H NMR and solid‐state 13C NMR to be solely built up by CDs. Well‐defined and monodisperse nano‐tunnels are formed in nanoporous materials by the template‐free, face‐to‐face self‐assembly of CDs, with diameters around 0.8 or 0.5 nm equal to the diameter of the CD cavities. Moreover, the nanoporous structure of the CD is reversible controlled simply by switching temperature in DMF, indicating that the nanoporous CDs could be recyclable used and recovered. These characteristic properties and behaviors of the nanoporous CDs made them to be an ideal green material for absorption, separation as well as CD recovery.
A dose titration study of fentanyl buccal soluble film for breakthrough cancer pain in Taiwan
Authors: Chiou Tzeon‐Jye , Chao Ta‐Chung , Chao Tsu‐Yi , Huang Jen‐Seng , Chang Yi‐Fang , Wang Cheng‐Hsu
Published: April 2019

Background

Fentanyl buccal soluble film (FBSF), a new formulation of fentanyl, is developed for the treatment of breakthrough pain (BTP) in opioid‐tolerant patients with cancer.

Aims

This study aimed to assess the feasible dose range of FBSF required for Taiwanese population.

Methods and results

This was an open‐label, multicenter, noncomparative study. Cancer patients who were aged 20 years or older and had a stable regimen equivalent to 60 to 1000 mg/day of oral morphine, 20 to 120 mg/day of intravenous morphine, or 25 to 300 μg/h of transdermal fentanyl for at least 1 week were enrolled. The primary endpoint was the feasible dose range of FBSF. Secondary endpoints included difference in pain intensity at 30 minutes (PID30), percentage of episodes requiring rescue medication, and overall satisfaction. Adverse events (AEs) and serious AEs (SAEs) were recorded for safety measurements. The final effective dose in the per‐protocol (PP) population (n = 30) ranged from 200 to 800 μg, of which 26 subjects (86.7%) achieved an effective dose range of 200 to 400 μg. Among the 283 BTP episodes recorded in the maintenance period, the mean PID30 was 4.0, and only 13 events (4.6%) required rescue medication. For 63.6% of the BTP episodes, patients rated their satisfaction as good to excellent. Only 5% of AEs were considered drug‐related.

Conclusions

Individualized dose titration is recommended for BTP management for patients' benefit. Overall, FBSF was effective and well tolerated and was positively correlated with patients' background opioid dose for persistent pain management.
Photosensitized Retinal Isomerization in Rhodopsin Mediated by a Triplet State
Authors: Valentini Alessio , Nucci Martina , Frutos Luis Manuel , Marazzi Marco
Published: April 2019

Direct 11‐cis to all‐trans retinal photoisomerization within rhodopsin is well known to be the initial chemical reaction triggering the process of vision in mammalians, such as bovine. Nevertheless, deep‐sea fish are known to use chlorophyll derivatives as photosensitizers in order to see deep‐red light, at wavelengths where retinal does not absorb. Also, some photodynamic therapy treatments were shown to enhance the vision of patients in dim light conditions. Energy transfer from the photosensitizer to rhodopsin was therefore proposed as a mechanism to populate the triplet state of the retinal chromophore. Herein, by means of hybrid quantum mechanics‐coupled‐molecular mechanics modeling techniques, we give insights into the possible energy mechanism and describe the retinal isomerization mediated by the lowest‐lying triplet state. Especially, we show how a few kcal/mol energy barrier separates a T1 minimum from a S0/T1 intersection region, hence proposing an equilibrium between phosphorescence and isomerization processes. Moreover, the eventual self‐production of singlet oxygen, constituting a potential danger for the integrity of rhodopsin, is discussed.
“Immuno‐flowFISH” for the Assessment of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia
Authors: Hui Henry Y.L. , Clarke Kathryn M. , Fuller Kathryn A. , Stanley Jason , Chuah Hun H. , Ng Teng Fong , Cheah Chan , McQuillan Andrew , Erber Wendy N.
Published: April 2019

Imaging flow cytometry is emerging as a diagnostic tool for the assessment of leukemia. It has the functionality of standard flow cytometry and generates high‐resolution digital images of each cell with quantifiable numerical data. We demonstrate the use of an automated high‐throughput method for performing fluorescence in situ hybridization (FISH) on immunophenotyped whole cells in suspension and analyzed by imaging flow cytometry, a technique called “Immuno‐flowFISH”. The aim of this study was to demonstrate the application of immuno‐flowFISH for the detection of chromosomal abnormalities in CLL, specifically trisomy 12 and del(17p). Mononuclear cells were isolated and immunophenotyped with fluorescently conjugated CD3, CD5, and CD19 monoclonal antibodies. Following fixation, cells were permeabilized, dsDNA denatured and hybridized with chromosome 12 or 17 enumeration (CEP 12 and CEP17) and 17p12 locus‐specific FISH probes. Cells were analyzed on the Amnis ImageStream®X Mark II to assess the number and percent FISH‐positive CLL cells and the ratio of FISH spot counts for CD5/CD19‐positive CLL cells to CD3/CD5‐positive T cells (FISH “mean spot ratio”). Deletion of 17p was detected in about 8% of cases to date, with del(17p) ranged from 3.5–22.8% and the FISH “mean spot ratio” 0.86–0.96. Immuno‐flowFISH also detected a minimal residual disease case with +12 with a limit of detection of 0.13% and a rare case that presented with atypical phenotype and cytogenetics. Immuno‐flowFISH could detect del(17p) in phenotypically identified CD5/CD19‐positive B‐cells. The 100‐fold increase in analyzed cells, as well as the addition of cell phenotype increased the sensitivity and specificity over current clinical FISH testing. Furthermore, immuno‐flowFISH analysis demonstrated specific utility in unique clinical scenarios such as residual disease and atypical biology cases which may be of significant benefit with regards to prognostication and MRD analysis. The method will assist in therapeutic decision making and disease monitoring for many hematological malignancies. © 2019 International Society for Advancement of Cytometry
Evidence for frequency‐dependent selection maintaining polymorphism in the Batesian mimic Papilio polytes in multiple islands in the Ryukyus, Japan
Authors: Tsurui‐Sato Kaori , Sato Yukuto , Kato Emi , Katoh Mitsuho , Kimura Ryosuke , Tatsuta Haruki , Tsuji Kazuki
Published: April 2019

Batesian mimicry is a well‐studied adaptation for predation avoidance, in which a mimetic species resembles an unpalatable model species. Batesian mimicry can be under positive selection because of the protection gained against predators, due to resemblance to unpalatable model species. However, in some mimetic species, nonmimetic individuals are present in populations, despite the benefits of mimicry. The mechanism for evolution of such mimetic polymorphism remains an open question. Here, we address the hypothesis that the abundance of mimics is limited by that of the models, leading to mimetic polymorphism. In addition, other forces such as the effects of common ancestry and/or isolation by distance may explain this phenomenon. To investigate this question, we focused on the butterfly, Papilio polytes, that exhibits mimetic polymorphism on multiple islands of the Ryukyus, Japan, and performed field surveys and genetic analysis. We found that the mimic ratio of P. polytes was strongly correlated with the model abundance observed on each of the five islands, suggesting negative frequency‐dependent selection is driving the evolution of polymorphism in P. polytes populations. Molecular phylogenetic analysis indicated that the southern island populations are the major source of genetic diversity, and the middle and northern island populations arose by relatively recent migration. This view was also supported by mismatch distribution and Tajima's D analyses, suggesting a recent population expansion on the middle and northern islands, and stable population persistence on the southern islands. The frequency of the mimetic forms within P. polytes populations is thus explained by variations in the model abundance rather than by population structure. Thus, we propose that predation pressure, rather than neutral forces, have shaped the Batesian mimicry polymorphism in P. polytes observed in the Ryukyus.
Life table invasion models: spatial progression and species‐specific partitioning
Authors: Zhao Zihua , Hui Cang , Plant Richard E. , Su Min , Carpenter Tim , Papadopoulos Nikos , Li Zhihong , Carey James R.
Published: April 2019

Biological invasions are increasingly being considered important spatial processes that drive global changes, threatening biodiversity, regional economies, and ecosystem functions. A unifying conceptual model of the invasion dynamics could serve as a useful tool for comparison and classification of invasion processes involving different species across large geographic ranges. By dividing these geographic ranges that are subject to invasions into discrete spatial units, we here conceptualize the invasion process as the transition from pristine to invaded spatial units. We use California cities as the spatial units and a long‐term database of invasive tropical tephritids to characterize the invasion patterns. A new life‐table method based on insect demography, including the progression model of invasion stage transition and the species‐specific partitioning model of multispecies invasions, was developed to analyze the invasion patterns. The progression model allows us to estimate the probability and rate of transition for individual cities from pristine to infested stages and subsequently differentiate the first year of detection from detection recurrences. Importantly, we show that the interval of invasive tephritid recurrence in a city declines with increasing invasion stages of the city. The species‐specific partitioning model revealed profound differences in invasion outcome depending on which tephritid species was first detected (and then locally eradicated) in the early stage of invasion. Taken together, we discuss how these two life‐table invasion models can cast new light on existing invasion concepts; in particular, on formulating invasion dynamics as the state transition of cities and partitioning species‐specific roles during multispecies invasions. These models provide a new set of tools for predicting the spatiotemporal progression of invasion and providing early warnings of recurrent invasions for efficient management.
Fragility function development and seismic loss assessment of expansion joints
Authors: Otsuki Yu , Kurata Masahiro , Skalomenos Konstantinos A. , Ikeda Yoshiki , Akazawa Motoki
Published: April 2019

Expansion joints are used as a special connection equipment between adjacent buildings to accommodate the relative motions generated by wind, thermal, or earthquake loads, but they often exhibit damage during severe earthquakes. The level of damage and safety factors required to avoid loss of function are not well considered in current design practices. The objective of this paper is to provide quantitative information on the seismic damage probability of common expansion joints and the associated repair costs. The designer and engineer can refer to this information as a basis for decision making in the selection of expansion joints. Four common types of expansion joints are considered: high‐ and standard‐performance floor and wall expansion joints, whose damage states have been evaluated recently by the authors through shaking table tests. First, the fragility functions of expansion joints for seven damage patterns are developed utilizing the test results. Next, the vulnerability of expansion joints installed between adjacent building models is assessed via incremental dynamic analysis. The recommended level of safety factor to ensure the function of expansion joints is discussed. Finally, a procedure for cost‐effective selection of expansion joints is introduced, where case studies are examined using buildings with different characteristics. The presented results are deemed to be beneficial for improving the design practice of expansion joints and for reducing future seismic loss.
Simultaneous Analysis of Multiclass Contaminants of Emerging Concern in Sediments by Liquid Chromatography with Tandem Quadrupole Mass Spectrometry
Authors: Rashid Azhar , Wang Yuwen , Li Yan , Yu Chang-Ping , Sun Qian
Published: April 2019

A quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based extraction and simultaneous dispersive solid-phase extraction (dSPE) clean-up method was developed for contaminants of emerging concern (CECs) in sediment samples. Hydration with a phosphate buffer (pH 2.0) and salting out with NaCl and MgSO4 facilitated the extraction and liquid–liquid portioning of the aqueous and organic phases. Cleanup of the extracts was achieved by florisil and C18 (1:1) sorbents in dSPE with minimal compromise of the analytes. The extracts were clean enough for determination by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The procedure was validated for preservatives, blood lipid regulators, analgesics and anti-inflammatory drugs, plasticizers, and other classes of CECs in sediment matrix spiked at 6 levels between 1- and 40-fold concentrations for CECs of varying analytical sensitivities. The recovery values were generally between approximately 27 and 120% and the relative standard deviation (%RSD) values were below 20% at 10- , 20- , and 40-fold spiking levels, albeit the recoveries for some analytes dropped at low spike concentrations. The method showed high sensitivity where the method detection limits (MDLs) were at low ppb levels for the majority of the analytes that ranged between 0.002 and 1.93 µg/kg. The method performance was also compared with well-established US Environmental Protection Agency (USEPA) Method 1694 by analyzing sediment samples collected from Yundang Lagoon (Xiamen, China) with field-incurred CEC residues. The sediment samples were detected with residues of parabens, gemfibrozil, ketoprofen, naproxen, fenoprofen, diclofenac, miconazole, carbamazepine, benzophenon-3, glibenclamide, sildinafil citrate, and some bisphenol analogues. Environ Toxicol Chem 2019;38:1409–1422. © 2019 SETAC
Diabetes mellitus, genetic variants in the insulin‐like growth factor pathway and colorectal cancer risk
Authors: de Kort Sander , Simons Colinda C.J.M. , van den Brandt Piet A. , Janssen‐Heijnen Maryska L.G. , Sanduleanu Silvia , Masclee Ad A.M. , Weijenberg Matty P.
Published: April 2019

Genetic variation in the insulin‐like growth factor (IGF) pathway may further increase the risk of colorectal cancer (CRC) associated with type 2 diabetes mellitus (T2DM). Joint effects of T2DM and genetic variation in the IGF pathway on CRC risk can increase mechanistic insights. Participants from the Netherlands Cohort Study (n = 120, 852) completed a baseline questionnaire in 1986 when 55–69 years old (case–cohort, nsubcohort = 5,000, ncases = 3,441 after 16.3 years follow‐up). Self‐reported DM at baseline with onset at ≥30 years was classified as T2DM. Eighteen single nucleotide polymorphisms (SNPs) from the IGF pathway were aggregated in a genetic risk score (GRS). Cox proportional hazard ratios (HRs) for CRC were estimated according to combinations of T2DM status with GRS tertiles and categories of an IGF1 19‐CA repeat polymorphism. Baseline T2DM prevalence was 3.1% in subcohort members and 3.8% in CRC cases. Comparison of combined categories with non‐T2DM individuals in the lowest GRS tertile as reference showed that those in the highest GRS tertiles with and without T2DM had significantly increased CRC risks, particularly those with T2DM (HR = 2.28, 95% CI: 1.11, 4.66). As compared to IGF1 19‐CA wild‐type carriers without T2DM, carrying two IGF1 19‐CA variant repeat alleles were associated with a significantly decreased CRC risk in those without T2DM (HR = 0.76, 95% CI: 0.63–0.91). This association was absent when T2DM was present. Our study of joint effects indicated that the presence of unfavorable alleles in the IGF pathway may further increase the risk of CRC associated with T2DM.
MiR‐16‐1‐3p and miR‐16‐2‐3p possess strong tumor suppressive and antimetastatic properties in osteosarcoma
Authors: Maximov Vadim V. , Akkawi Rania , Khawaled Saleh , Salah Zaidoun , Jaber Lina , Barhoum Ahlam , Or Omer , Galasso Marco , Kurek Kyle C. , Yavin Eylon , Aqeilan Rami I.
Published: April 2019

Osteosarcoma (OS) is an aggressive malignancy affecting mostly children and adolescents. MicroRNAs (miRNAs) play important roles in OS development and progression. Here we found that miR‐16‐1‐3p and miR‐16‐2‐3p “passenger” strands, as well as the “lead” miR‐16‐5p strand, are frequently downregulated and possess strong tumor suppressive functions in human OS. Furthermore, we report different although strongly overlapping functions for miR‐16‐1‐3p and miR‐16‐2‐3p in OS cells. Ectopic expression of these miRNAs affected primary tumor growth, metastasis seeding and chemoresistance and invasiveness of human OS cells. Loss‐of‐function experiments verified tumor suppressive functions of these miRNAs at endogenous levels of expression. Using RNA immunoprecipitation (RIP) assays, we identify direct targets of miR‐16‐1‐3p and miR‐16‐2‐3p in OS cells. Moreover, validation experiments identified FGFR2 as a direct target for miR‐16‐1‐3p and miR‐16‐2‐3p. Overall, our findings underscore the importance of passenger strand miRNAs, at least some, in osteosarcomagenesis.
3D brain tumor segmentation in MRI images based on a modified PSO technique
Authors: Gtifa Wafa , Hamdaoui Fayçal , Sakly Anis
Published: April 2019

Three‐dimensional (3D) brain tumor segmentation is a clinical requirement for brain tumor diagnosis and radiotherapy planning. This is a challenging task due to variation in type, size, location, and shape of tumors. Several methods such as particle swarm optimization (PSO) algorithm formed a topological relationship for the slices that converts 2D images into 3D magnetic resonance imaging (MRI) images which does not provide accurate results and they depend on the number of input sections, positions, and the shape of the MRI images. In this article, we propose an efficient 3D brain tumor segmentation technique called modified particle swarm optimization. Also, segmentation results are compared with Darwinian particle swarm optimization (DPSO) and fractional‐order Darwinian particle swarm optimization (FODPSO) approaches. The experimental results show that our method succeeded 3D segmentation with 97.6% of accuracy rate more efficient if compared with the DPSO and FODPSO methods with 78.1% and 70.21% for the case of T1‐C modality.
Whole‐body MRI of bone marrow: A review
Authors: Hynes John P. , Hughes Nicola , Cunningham Patricia , Kavanagh Eoin C. , Eustace Stephen J.
Published: April 2019

Technical advances in the last two decades have allowed rapid, high‐resolution whole‐body magnetic resonance imaging (WBMRI). MRI allows unparalleled visualization and detail in the imaging of bone marrow and surrounding soft tissues. The properties of nuclear magnetic resonance allow superb characterization of bone marrow constituents. WBMRI allows superb characterization of the different types of bone marrow and their natural evolution during the life cycle. Diffusion‐weighted WBMRI is an exciting development that adds functional information to anatomical detail. The mainstay of WBMRI for bone marrow abnormalities to date has centered upon staging multiple myeloma and other hematologic bone marrow conditions, and as a valuable tool in quantifying skeletal metastases. Increasingly, WBMRI is being utilized in a variety of additional malignant and nonmalignant conditions. Due to the absence of ionizing radiation, WBMRI represents a valuable screening tool in areas such as malignant transformation in hereditary multifocal exostoses or for the development of ischemic marrow insult in at‐risk patients. An additional novel area of use includes postmortem WBMRI for characterization of skeletal injuries. This article provides a state‐of‐the‐art and current review of WBMRI of the bone marrow and highlights potential future areas of development.

Level of Evidence: 5

Technical Efficacy Stage: 3

J. MAGN. RESON. IMAGING 2019. J. Magn. Reson. Imaging 2019;50:1687–1701.