bluuebunny/crossref_metadata_2025 huggingface dataset:
Axonal abnormalities in vanishing white matter
Authors: Klok Melanie D. , Bugiani Marianna , de Vries Sharon I. , Gerritsen Wouter , Breur Marjolein , van der Sluis Sophie , Heine Vivi M. , Kole Maarten H. P. , Baron Wia , van der Knaap Marjo S.
Published: March 2018

Objective

We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter.

Methods

Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single‐ and double‐mutant mice and patient brain tissue. In addition, astrocyte‐forebrain co‐culture studies were performed.

Results

In the corpus callosum of Eif2b5‐mutant mice, myelin sheath thickness, axonal diameter, and G‐ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G‐ratio in Eif2b5‐mutant mice. In more severely affected Eif2b4‐Eif2b5 double‐mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5‐mutant mice. Co‐cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal.

Interpretation

In vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention.
As the Levee Breaks: Entrusting the Surreal Mississippi
Authors: Russell Elizabeth Williams
Published: March 2018

New Orleans‐based architect and landscape architect Elizabeth Williams Russell spends her days working in the hinterland of the Mississippi. Fully aware that the river's massive power cannot be tamed for long, she has developed ways to speculate and work with it in a surreal way – as she explains here.
Silver Parrots: Mischievous Characters and Feathered Aerialists
Authors: Kulper Perry
Published: March 2018

Through their juxtapositions of strangeness and paradox with familiarity and everydayness, the Surrealists' vision changed the world. It has certainly transformed the work of Perry Kulper, an architect and Associate Professor at the University of Michigan. Citing his influences, which extend back over half a millennium to proto‐Surrealists such as Hieronymus Bosch, he presents some of his recent drawings on themes ranging from a digital exquisite corpse to a metaphorical resort proposal for birds.
Bioinspired Trans‐Scale Functional Interface for Enhanced Enzymatic Dynamics and Ultrasensitive Detection of microRNA
Authors: Ye Lei , Yang Fan , Ding Yuanlin , Yu Haibin , Yuan Lin , Dai Qi , Sun Yujie , Wu Xiaoxue , Xiang Yang , Zhang Guo‐Jun
Published: March 2018

Protein interactions with specific nucleic acid sequences are crucial in cell growth. Inspired by such binding events that often occur at nanoscale biointerface, here a trans‐scale functional interface capable of considerably enhancing in vitro DNA‐enzyme interaction is reported. Using a screen‐printed electrode with nanoroughened carbon surface, the high‐curvature gold nanostructures in a single electrodeposition step can be programmed. In this process, a synergistic effect is found between nanoroughened carbon and polyelectrolyte multilayer enabling the formation of high‐stability and high‐curvature nanostructures. More importantly, these fractal nanostructures effectively overcome neighboring probes aggregation at high density and allow the probes to be more freely accessed by target molecules. As compared to its planar counterparts, this nanostructuring interface demonstrates faster enzymatic dynamics that enables ultrasensitive detection of microRNA with a detection limit of 35 × 10−18
m. Such an efficient trans‐scale biosensing interface has also accurately differentiated the patients with rheumatic arthritis from the health ones, signifying its great potential in precision medicine.
Ultrafast Growth of Large 2D Silver Nanosheets by Highly Ordered Biological Template at Air/Gel Interface
Authors: Jang Hyung‐Seok , Seong Baekhoon , Zang Xining , Lee Hyungdong , Bae Jin Woo , Cho Dae‐Hyun , Kao Emmeline , Yang Chen , Kang Giho , Liu Yumeng , Park Hyun Sung , Byun Doyoung , Lin Liwei
Published: March 2018

The growth of large and high‐quality 2D nanomaterials is challenging due to the formation of defects from dislocations, disinclinations, and symmetry‐breaking instabilities. In this study it is demonstrated that biological template can be utilized to align the molecular orientation for large grain size in the synthesis of the high‐quality 2D silver nanostructure. The solvent assisted multilayering phenomenon of hydrogel forms biological template at the air/gel interface and supports the silver salts to grow laterally and largely in a 2D manner between the scaffold layers with a nominal thickness of 4.4 ± 0.3 nm. This solution‐based deposition mechanism is demonstrated based on droplet, spin‐coating, and electrohydrodynamic jet printing schemes for robust and flexible conductive thin films or patterns.
Controlling the Growth of Ni3S2 Anode with Tunable Sodium Storage
Authors: Song Xiaosheng , Li Xifei , Bai Zhimin , Yan Bo , Li Dejun
Published: March 2018

The influences of acids on the surface of nickel foam and its effect on the growth of nickel sulfide are studied. Treated by sulfuric acid, oxalic acid, and phosphoric acid, three Ni foams are fabricated with different surface states containing different surface roughness and different surface layers with nickel salts. By controlling the reaction conditions, three Ni3S2 morphological structures with nanosheets, clustered nanosheets, and nanoparticles are designed on these preprocessed Ni foams. The applications of these Ni3S2/Ni electrodes for sodium ion batteries are examined in detail. The findings provide a new idea for the control of the solid–liquid reaction interface, which highly affect the morphologies of Ni3S2.
A Highly Sensitive Flexible Capacitive Tactile Sensor with Sparse and High‐Aspect‐Ratio Microstructures
Authors: Wan Yongbiao , Qiu Zhiguang , Hong Ying , Wang Yan , Zhang Jianming , Liu Qingxian , Wu Zhigang , Guo Chuan Fei
Published: March 2018

Highly sensitive flexible tactile sensors that can be fabricated in a low cost and efficient way are in great demand for intelligent soft robotics and friendly human–machine interaction. Herein, a highly sensitive flexible tactile sensor is developed by using bionic micropatterned polydimethylsiloxane (m‐PDMS) replicated from lotus leaf. The m‐PDMS substrate consists of high‐aspect‐ratio and low‐density microtowers, and is covered by ultrathin silver nanowires as a bottom electrode. The capacitive sensing device is constructed by sandwiching the bottom electrode, a colorless polyimides dielectric layer, and a top electrode, and exhibits a high sensitivity of ≈1.2 k Pa−1, a ultralow limit of detection <0.8 Pa, and a fast response time of 36 ms. The finite‐elemental analysis indicates that the sparse and high‐aspect‐ratio microtowers are critical to achieve high sensitivity, low limit of detection, and fast response to external stimulus. The flexible tactile sensor also exhibits high robustness: it can be tested for at least 100 000 cycles without showing fatigue. More importantly, the flexible tactile sensors are potentially useful in intelligent soft robots, health monitoring, and motion detection. Besides, the fabrication strategy may offer a guideline to design other microstructures for improving the performance of flexible tactile sensors.
RNAi‐mediated reduction of hepatic Tmprss6 diminishes anemia and secondary iron overload in a splenectomized mouse model of β‐thalassemia intermedia
Authors: Schmidt Paul J. , Liu Kaifeng , Visner Gary , Fitzgerald Kevin , Fishman Shannon , Racie Tim , Hettinger Julia L. , Butler James S. , Fleming Mark D.
Published: March 2018

Diminished β‐globin synthesis in β‐thalassemia is associated with ineffective erythropoiesis, leading to secondary iron overload caused by inappropriately low levels of hepcidin and to splenomegaly in the symptomatic thalassemias. Splenectomy is often employed in patients with β‐thalassemia to reduce hemolysis. Expression of the iron regulatory peptide hormone hepcidin is repressed by the serine proteaseTMPRSS6. Hepcidin induction by RNAi‐mediated inhibition ofTMPRSS6 expressionreduces iron overload and mitigates anemia in murine models of β‐thalassemia intermedia. To interrogate the efficacy of RNAi‐mediated reduction ofTmprss6in splenectomized β‐thalassemia, splenectomized β‐thalassemicHbbth3/+animals were treated with a GalNAc‐conjugated siRNA targetingTmprss6(GalNAc‐Tmprss6) and their hematological and iron parameters monitored. We demonstrate that treatment with GalNAc‐Tmprss6 significantly diminishesTmprss6expression and appropriately elevates hepcidin expression in splenectomizedHbbth3/+animals. Similar to unsplenectomized animals, treated animals have markedly improved anemia due to diminished ineffective erythropoiesis and reduced iron loading in both serum and tissue. These results suggest that RNAi‐mediated reduction ofTmprss6may have positive outcomes even in splenectomized β‐thalassemia patients.
Rutheniumkatalysierte Kaskadenanellierung von Indol mit Propargylalkoholen
Authors: Kaufmann Julia , Jäckel Elisabeth , Haak Edgar
Published: March 2018

Mehrere Bindungen bildende Kaskadentransformationen und Eintopfprozesse bieten schnellen Zugang zu naturstoffartigen Gerüsten aus einfachen Präkursoren. Diese atomökonomischen Prozesse sind wertvolle Werkzeuge für die Organische Synthese und die Wirkstoffsuche. Hier berichten wir über rutheniumkatalysierte Kaskadenanellierungen von Indol mit leicht verfügbaren Propargylalkoholen. Dadurch sind diverse Carbazole, Cyclohepta[b]indole und weitere fusionierte Polycyclen schnell und mit hoher Selektivität zugänglich. Ein bifunktionaler Rutheniumkomplex eines redox‐gekoppelten Cyclopentadienonliganden fungiert als gemeinsamer Katalysator für die unterschiedlichen Kaskadenumwandlungen die auftreten.
Common Patterns in Chaperone Interactions with a Native Client Protein
Authors: He Lichun , Hiller Sebastian
Published: March 2018

Many molecular chaperones are promiscuous and interact with a wide range of unfolded, quasi‐native, and native client proteins. The mechanisms by which chaperones interact with the highly diverse structures of native clients thus remain puzzling. In this work, we investigate at the atomic level how three ATP‐independent chaperones interact with a β‐sheet‐rich protein, the Fyn SH3 domain. The results reveal that the chaperone Spy recognizes the locally frustrated surface of the client Fyn SH3 and that the interaction is transient and highly dynamic, leaving the chaperone‐interacting surface on Fyn SH3 solvent accessible. The two alternative molecular chaperones SurA and Skp recognize the same locally frustrated surface of the Fyn SH3 domain. These results indicate dynamic recognition of frustrated segments as a common mechanism underlying the chaperone–native client interaction, which also provides a basis for chaperone promiscuousness.
Fabrication of sustained‐release and antibacterial citronella oil‐loaded composite microcapsules based on Pickering emulsion templates
Authors: Wang Jingguang , Li Xin , Chen Minjie , Chen Zhenming , Wu Hong , Zhang Peng , Yuan Teng , Yang Zhuohong , Hu Yang
Published: March 2018

In this work, the citronella oil (CTO)‐loaded composite microcapsules with hydroxyapatite (HAp)/quaternary ammonium salt of chitosan (HACC)/sodium alginate (SA) shells are facilely and effectively fabricated by templating citronella oil‐in‐water Pickering emulsions, which are stabilized with HAp nanoparticles. The microcapsule composite shells are prepared by the electrostatic adsorption of HACC and SA, and then chelation interaction of alginate and Ca2+ ions released from HAp nanoparticles. Scanning electronic microscope observation shows that the microcapsules have a spherical shape. Thereafter, Fourier transform infrared spectroscopy and thermal gravimetric analysis results indicate that CTO is successfully loaded into the microcapsules, and the related CTO‐loaded microcapsules possess the thermal stability. Moreover, the in vitro release study of CTO shows that the microcapsules have sustained release activity, and the related CTO release profiles can be well described by Rigter–Peppas model. The antimicrobial assays of microcapsules display the antibacterial effect of CTO‐loaded microcapsules against Staphylococcus aureus and Escherichia coli. Overall, this study opens up new potentiality for unstable active ingredient as an environmental friendly and ingenious microencapsulation in food and agriculture applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46386.
Paul Ehrlich und der Nobelpreis. Die Konstruktion wissenschaftlicher Exzellenz
Authors: Hüntelmann Axel Cäsar
Published: March 2018

Paul Ehrlich and the Nobel Prize. The Construction of Scientific Excellence. From the first award in 1901 until now the Nobel Prize was and is valued as the highest recognition of the scientific community for the outstanding – excellent – scientific work of a researcher. And insofar, winning the Nobel Prize was a highlight in Paul Ehrlich's life. But from the first nomination in 1901 until 1908, when he was awarded the prize, it was a long way. Between these years Ehrlich had been nominated 89 times by 80 scientists all over the world. The article sketches how excellence has been constructed by using the example of Paul Ehrlich. On the one hand, scientific networks are a precondition for being nominated by colleagues, on the other hand, excellence had been valuated and constructed in complex valuation processes and administrative procedures. The article presents first an overview over the nominations of Paul Ehrlich – who nominated him for what reasons? Moreover, the chapter sketches the relations between some nominators and Paul Ehrlich. After he had been nominated, the nominations were evaluated by members of the Nobel committee. The second part follows the complex procedures of evaluation to find the most excellent scientific work in accordance to Nobel's will. Finally, the Nobel Prize is embedded in broader network relations and the moral and relational economy of networks, which is exemplified by describing Paul Ehrlich relations to Carl Julius Salomonsen.
Multicentre study evaluating the surgical learning curve for posterior retroperitoneoscopic adrenalectomy
Authors: Vrielink O M , Engelsman A F , Hemmer P H J , de Vries J , Vorselaars W M C M , Vriens M R , Karakatsanis A , Hellman P , Sywak M S , van Leeuwen B L , El Moumni M , Kruijff S
Published: March 2018

Background

Posterior retroperitoneoscopic adrenalectomy has gained international popularity in the past decade. Despite major advantages, including shorter duration of operation, minimal blood loss and decreased postoperative pain, many surgeons still prefer laparoscopic transperitoneal adrenalectomy. It is likely that the unfamiliar anatomical environment, smaller working space and long learning curve impede implementation. The present study assessed the number of procedures required to fulfil the surgical learning curve for posterior retroperitoneoscopic adrenalectomy.

Methods

The first consecutive posterior retroperitoneoscopic adrenalectomies performed by four surgical teams from university centres in three different countries were analysed. The primary outcome measure was duration of operation. Secondary outcomes were conversion to an open or laparoscopic transperitoneal approach, complications and recovery time. The learning curve cumulative sum (LC-CUSUM) was used to assess the learning curves for each surgical team.

Results

A total of 181 surgical procedures performed by four surgical teams were analysed. The median age of the patients was 57 (range 15–84) years and 61·3 per cent were female. Median tumour size was 25 (range 4–85) mm. There were no significant differences in patient characteristics and tumour size between the teams. The median duration of operation was 89 (range 29–265) min. There were 35 perioperative and postoperative complications among the 181 patients (18·8 per cent); 17 of 27 postoperative complications were grade 1. A total of nine conversions to open procedures (5·0 per cent) were observed. The LC-CUSUM analysis showed that competency was achieved after a range of 24–42 procedures.

Conclusion

In specialized endocrine surgical centres between 24 and 42 procedures are required to fulfil the entire surgical learning curve for the posterior retroperitoneoscopic adrenalectomy.
Quantification of amlodipine and atorvastatin in human plasma by UPLC–MS/MS method and its application to a bioequivalence study
Authors: Rezk Mamdouh R. , Badr Kamal A.
Published: March 2018

A robust, rapid and sensitive UPLC–MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple‐reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC–MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1–10 ng/mL for AML and 0.05–50 ng/mL for ATO. Intra‐day and inter‐day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers.
Industrial symbiosis within eco‐industrial parks: Sustainable development for Borg El‐Arab in Egypt
Authors: ElMassah Suzanna
Published: March 2018

This paper explores how industrial symbiosis within eco‐industrial parks (EIPs) can help advance sustainable development in Egypt. Based on industrial ecology theory, this study focuses on the industrial zone of Borg El‐Arab near Alexandria and explores possibilities to transform it, or parts of it, into an EIP. It identifies opportunities for possible by‐product exchange in the third industrial zone of Borg El‐Arab, which has the highest solid waste output. The study then presents a pilot model of a brownfield EIP and suggests that the benefits from exchange of by‐products would be enhanced even further if some factories are created to close the loop of industrial processes in the zone (brick production, animal feed, fish farms, and organic fertilizer production). These conclusions confirm that there is potential to improve environmental performance of the Borg El‐Arab Industrial City and align it with national and global sustainable development goals.
Massive pericardial effusion caused by hypothyroidism
Authors: Schmitt Willian , Roque David , Germano Ana
Published: March 2018

Key Clinical Message

Although mild pericardial effusion is a usual finding in patients with hypothyroidism, massive pericardial effusion or pericardial tamponade is rare and customarily related to severe hypothyroidism. The diagnosis of hypothyroidism should be considered in the differential of patients presenting with unexplained pericardial effusion, even when signs and symptoms of hypothyroidism are nonexistent.
Diagnostic challenges in a patient with an occult insulinoma:68 Ga‐DOTA‐exendin‐4 PET/CT and 68Ga‐DOTATATE PET/CT
Authors: Bongetti Elisa , Lee Melissa H. , Pattison David A , Hicks Rodney J. , Norris Richard , Sachithanandan Nirupa , MacIsaac Richard J
Published: March 2018

Key Clinical Message

Despite growing evidence for GLP‐1R molecular‐based imaging, successful localization of insulinomas may require the use of multiple imaging modalities. Not all benign insulinomas express the GLP‐1R as expected. Our case demonstrates that there is a still an important role for traditional methods for the anatomical localization of an insulinoma.
Understanding the Roles of Sulfur Dopants in Carbonaceous Electrocatalysts for the Oxygen Reduction Reaction: The Relationship between Catalytic Activity and Work Function
Authors: Shin Heejong , Kang Narae , Kang Daye , Kang Jin Soo , Ko Ju Hong , Lee Doo Hun , Park Subin , Son Seung Uk , Sung Yung‐Eun
Published: March 2018

We prepared a series of hollow sulfur‐doped carbons with diverse S contents through the carbonization of microporous organic networks (MONs), which were synthesized through the Sonogashira coupling of thiophene moieties with different numbers of S atoms as building blocks. This preparation method enabled the doping level to be controlled without inducing any notable differences in textural and morphological characteristics, and these S‐doped carbons did not show any notable differences in the chemical properties of carbon, regardless of the sulfur content. We used these well‐controlled MON‐derived carbons as a model to elucidate the role of sulfur dopants in the oxygen reduction reaction (ORR) and to investigate the relationship between the activities and work functions of carbonaceous catalysts. By excluding the effect of electrical properties of the S‐doped carbon catalysts using conducting agents, we could successfully verify that increasing the number of dopants led to an enhancement in the ORR activities, and the high applicability of work function as the activity descriptor was also demonstrated. We believe that our experimental observations will provide a deeper understanding of carbonaceous electrocatalysts with p‐block dopants, and the investigations performed in this study are also anticipated to serve as a rational guideline in designing carbonaceous catalysts for various electrochemical reactions.
Identifying On‐Surface Site‐Selective Chemical Conversions by Theory‐Aided NEXAFS Spectroscopy: The Case of Free‐Base Corroles on Ag(111)
Authors: Aldahhak H. , Paszkiewicz M. , Rauls E. , Allegretti F. , Tebi S. , Papageorgiou A. C. , Zhang Y.‐Q. , Zhang L. , Lin T. , Paintner T. , Koch R. , Schmidt W. G. , Barth J. V. , Schöfberger W. , Müllegger S. , Klappenberger F. , Gerstmann U.
Published: March 2018

We demonstrate here that theory‐assisted near‐edge X‐ray absorption fine‐structure (NEXAFS) spectroscopy enables the site‐sensitive monitoring of on‐surface chemical reactions, thus, providing information not accessible by other techniques. As a prototype example, we have used free‐base 5,10,15‐tris(pentafluorophenyl)corroles (3H‐TpFPC) adsorbed on Ag(111) and present a detailed investigation of the angle‐dependent NEXAFS of this molecular species as well as of their thermally induced derivatives. For this, we have recorded experimental C and N K‐edge NEXAFS spectra and interpret them based on XAS cross‐section calculations by using a continuous fraction approach and core‐hole including multiprojector PAW pseudopotentials within DFT. We have characterized the as‐deposited low temperature (200 K) phase and unraveled the subsequent changes induced by dehydrogenation (at 330 K) and ring‐closure reactions (at 430 K). By exemplarily obtaining profound insight into the on‐surface chemistry of free‐base corrolic species adsorbed on a noble metal this work highlights how angle‐dependent XAS combined with accurate theoretical modeling can serve for the investigation of on‐surface reactions, whereby even highly similar molecular structures, such as tautomers and isomers, can be distinguished.
Modeling of Conversion Hysteresis Phenomena for Pt/Pd‐based Diesel Oxidation Catalysts
Authors: Dubbe Hendrik , Eigenberger Gerhart , Nieken Ulrich
Published: March 2018

Recent findings in the conversion behavior of diesel oxidation catalysts (DOCs) show a strong dependence between performance and oxidation state of the catalyst. Furthermore, a slow and reversible change of catalyst oxidation state has been observed under cyclic temperature changes with realistic exhaust gas conditions, which can result in a significant inverse hysteresis during light‐off and subsequent light‐out. In this contribution, an existing 1D global kinetic model for Pt‐only DOCs is developed further, considering CO and hydrocarbon interaction. It is also applied to a Pd‐only and PtPd‐alloyed catalyst.
Health‐related quality of life in patients with chronic myeloid leukemia receiving first‐line therapy with nilotinib
Authors: Efficace Fabio , Castagnetti Fausto , Martino Bruno , Breccia Massimo , D'Adda Mariella , Angelucci Emanuele , Stagno Fabio , Cottone Francesco , Malato Alessandra , Trabacchi Elena , Capalbo Silvana Franca , Gobbi Marco , Visani Giuseppe , Salvucci Marzia , Capodanno Isabella , Tosi Patrizia , Tiribelli Mario , Scortechini Anna Rita , Levato Luciano , Maino Elena , Binotto Gianni , Gugliotta Gabriele , Vignetti Marco , Baccarani Michele , Rosti Gianantonio
Published: March 2018

BACKGROUND

Although a wealth of efficacy and safety data is available for many tyrosine kinase inhibitors used in chronic myeloid leukemia (CML), there is a dearth of information on their impact on patients' health‐related quality of life (HRQOL). The primary objective of this study was to evaluate HRQOL and fatigue outcomes in patients with CML receiving first‐line therapy with nilotinib.

METHODS

This was a multicenter, prospective study enrolling 130 patients with chronic‐phase CML. HRQOL and fatigue were evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30) and its validated Fatigue module at the baseline and then at 3, 6, 12, 18, and 24 months. The primary prespecified HRQOL endpoints defined in the study protocol for longitudinal analysis were the Physical Functioning, Social Functioning, Role Functioning, and Fatigue scales. The remaining scales were investigated on an exploratory basis.

RESULTS

The rate of baseline compliance with the HRQOL assessment was 95.4% (124 of 130), and the rate of overall compliance with HRQOL forms was 91%. Among the 4 prespecified primary HRQOL endpoints, statistically significant improvements over time were found for Physical Functioning (P = .013), Role Functioning (P = .004), and Fatigue (P < .001). Clinically meaningful improvements were found already 3 months after the treatment start. The baseline patient self‐reported fatigue severity was an independent predictive factor for the achievement of a major molecular response with an odds ratio of 0.960 (95% confidence interval, 0.934‐0.988; P = .005).

CONCLUSIONS

For most patients, HRQOL improvements with nilotinib occur during the early phase of therapy and are maintained over time. Also, a more systematic HRQOL evaluation during the diagnostic workup of CML may help to predict clinical outcomes. Cancer 2018;124:2228‐37. © 2018 American Cancer Society.
Programmed death ligand 1 testing in non–small cell lung carcinoma cytology cell block and aspirate smear preparations
Authors: Noll Bryce , Wang Wei‐Lien , Gong Yun , Zhao Jun , Kalhor Neda , Prieto Victor , Staerkel Gregg , Roy‐Chowdhuri Sinchita
Published: March 2018

BACKGROUND

Immune checkpoint inhibitors targeting the programmed cell death 1 (PD‐1) receptor and its ligand, programmed death ligand 1 (PD‐L1), have emerged as a therapeutic approach for patients with non–small cell lung carcinoma (NSCLC). PD‐L1 expression, assessed by immunohistochemistry (IHC), is used to select patients for PD‐1/PD‐L1 inhibitor therapy. Most studies have been performed with histology specimens, with limited data available on the performance in cytology specimens. This study evaluated PD‐L1 in cytology specimens and compared the results with those from paired core‐needle biopsy for concordance.

METHODS

Forty‐one NSCLC fine‐needle aspiration cases that had paired core‐needle biopsy specimens with PD‐L1 IHC were selected. A Papanicolaou‐stained direct smear and a cell block section from each case were stained with a Dako PD‐L1 pharmDx antibody (clone 22C3). Only slides with 100 or more tumor cells (37 smears and 38 cell blocks) were evaluated. Tumor proportion scores (TPS) were assessed on the basis of the partial/complete membranous staining of tumor cells and were correlated with those of paired core‐needle biopsy.

RESULTS

All 9 smears that were negative for PD‐L1 staining showed 100% concordance with the paired core‐needle biopsy, whereas 28 smears with PD‐L1 expression showed a similar TPS, except for 1 smear that was discordant. In contrast, 10 negative paired core‐needle biopsy cases corresponded to 9 concordant negative cell blocks, whereas 1 cell block had a TPS of 1% to 5%. The remaining 28 cell blocks demonstrated PD‐L1 expression, with 22 cases showing a TPS similar to that of the paired core‐needle biopsy, whereas 6 cell blocks were discordant, likely because of intratumoral heterogeneity.

CONCLUSIONS

The results show that NSCLC cytology samples evaluated for PD‐L1 have high concordance with paired core‐needle biopsy samples and can be used for assessing PD‐L1 expression. Cancer Cytopathol 2018;126:342‐52. © 2018 American Cancer Society.
The structure identification of a diphenhydramine‐related impurity in methamphetamine
Authors: Liu Cuimei , Jia Wei , Han Yu , Hua Zhendong
Published: March 2018

Some methamphetamine (MA) crystals contain pharmaceutical impurities resulting from the co‐ingredients of medicines used for extracting ephedrine/pseudoephedrine. These pharmaceutical impurities and their related byproducts can reflect the trends in precursor chemicals and manufacturing sources. In this research, 1 pharmaceutical‐impurity‐related byproduct was detected in several seized MA samples synthesized by I/P (Nagai, Moscow, or Hypo) method. Its structure was postulated through the analysis of fragment ions in electron ionization (EI) mass spectrum. The impurity was further synthesized and analyzed using electrospray ionization–collision‐induced dissociation (ESI–CID) mass spectrum and nuclear magnetic resonance (NMR), and finally determined to be N1,N1,N2‐trimethyl‐N2‐(1‐phenylpropan‐2‐yl)ethane‐1,2‐diamine. The impurity was inferred to be generated by the reaction of MA and the breakdown of diphenhydramine, a co‐ingredient of medicines used for extracting ephedrine/pseudoephedrine. Simulation MA synthetic experiments via Nagai, Moscow, and Hypo methods using ephedrine and diphenhydramine as starting materials were performed to prove our presumption. The presence of the impurity indicates that these MA samples were manufactured from pharmaceutical containing ephedrine/pseudoephedrine and diphenhydramine.
Comparing men and women with binge‐eating disorder and co‐morbid obesity
Authors: Lydecker Janet A. , Grilo Carlos M.
Published: March 2018

Objective

This study examined differences in clinical presentation of men and women with binge‐eating disorder (BED) who participated in treatment research at a medical‐school based program.

Method

Participants were 682 adults (n = 182 men, n = 500 women) with DSM‐IV‐defined BED. Doctoral‐level research clinicians assessed eating‐disorder psychopathology, including BED diagnosis, using the Structured Clinical Interview for DSM‐IV Disorders (SCID) and Eating Disorder Examination (EDE) interview. Research clinicians measured height and weight and participants completed a battery of established self‐report measures.

Results

Men had significantly higher body mass index (BMI) than women; women had significantly higher eating‐disorder psychopathology (EDE scales and global score) and depression than men. Differences in eating‐disorder psychopathology and depression remained higher for women than men after adjusting for race/ethnicity and BMI. Frequency of binge‐eating episodes, subjective binge‐eating episodes, and overeating episodes did not differ significantly by sex. Women had younger ages of onset for dieting and binge‐eating behaviors than men but ages of onset for obesity and BED did not significantly differ between men and women.

Discussion

There are some sex differences in clinical presentation and age‐of‐onset timeline of adults with BED. Men and women develop obesity and BED (at diagnostic threshold) around the same age but women begin dieting and binge‐eating behaviors earlier than men. At presentation for treatment for BED, men and women did not differ in binge‐eating frequency and although men and women differed significantly on BMI and eating‐disorder psychopathology, the magnitude of these differences was quite modest.
Baseline diastolic pressure gradient and pressure reduction in chronic heart failure patients implanted with the CardioMEMS™ HF sensor
Authors: Wolfson Aaron M. , Grazette Luanda , Saxon Leslie , Nazeer Haider , Shavelle David M. , Jermyn Rita
Published: March 2018

Aims

Remote haemodynamic monitoring (RHM) decreases hospitalization rates in patients with chronic heart failure (HF). Many patients with chronic HF develop pulmonary hypertension (PH) secondary to left heart disease with some acquiring combined pre‐capillary and post‐capillary PH (Cpc‐PH). The efficacy of RHM in achieving pulmonary pressure reductions in patients with Cpc‐PH vs. isolated post‐capillary PH (Ipc‐PH) is unknown. The purpose of this study is to evaluate whether a higher baseline diastolic pressure gradient (DPGbaseline) measured at the time of CardioMEMS™ HF sensor implantation is associated with lower reductions in pulmonary artery diastolic pressures (PADP).

Methods and results

This was a retrospective analysis of 32 patients meeting clinical indications for CardioMEMS™ implantation. DPGbaseline categorized patients as Cpc‐PH (DPG ≥ 7 mmHg) or Ipc‐PH (DPG < 7 mmHg). Minimum achievable PADP (PADPmin) and ∆PADP (PADPbaseline − PADPmin) were determined. Pearson's correlation analysis and comparison of mean pressure changes were assessed. Median age was 69 years, and median left ventricular ejection fraction (LVEF) was 25%. Eight patients (25%) had a LVEF ≥40%. Twenty‐five patients (78%) met criteria for Ipc‐PH and seven (22%) for Cpc‐PH. Neither PADPmin (ρ = 0.27; P = 0.13) nor ΔPADP (ρ = 0.07; P = 0.72) was correlated with DPGbaseline. A trend towards higher ΔPADP was seen in Cpc‐PH vs. Ipc‐PH patients (15.2 vs. 9.88 mmHg; P = 0.12). There was a moderate positive correlation between baseline PADP and ΔPADP [ρ = 0.55 (0.26–0.76); P < 0.001].

Conclusions

Decreased PADP reduction was not seen in Cpc‐PH vs. Ipc‐PH patients. Higher PADPbaseline was associated with greater ΔPADP. Larger studies are needed to elaborate our findings.
Unusual Heteronuclear Uranyl Clusters with Aliphatic Monocarboxylate Ligands and Coordination Modes of Crotonate, Butyrate, and Valerate Ions
Authors: Savchenkov Anton V. , Vologzhanina Anna V. , Pushkin Denis V. , Serezhkina Larisa B.
Published: March 2018

Two compounds with unusual architectures of uranyl complexes were synthesized and then studied by single‐crystal X‐ray diffraction and FTIR spectroscopy. Compound Ba2[UO2(C3H5COO)3]4·2C3H5COOH·7H2O (I) is constructed of neutral hexanuclear clusters {Ba2[UO2(C3H5COO)3]4(C3H5COOH)2(H2O)4} containing crotonate ions. Compound Sr(H2O)6{Na[UO2(i‐C3H7COO)3]3} (II) is constructed of anionic tetranuclear clusters {Na[UO2(i‐C3H7COO)3]3}2– containing isobutyrate ions. These and other examples of heteronuclear clusters imply that the alkali and alkaline‐earth metal atoms in these structures are not just charge‐balancing ions, but truly drive the formation of polynuclear units. The analysis of the coordination modes of crotonate, butyrate, and valerate ions in the crystal structures of all coordination compounds from the Cambridge Structural Database (CSD) allowed the identification of the structural role of these ligands. The results of the analysis show that the bridging function is in fact the most common function for crotonate, butyrate, and valerate ions in known crystal structures. Information on the possible and preferred coordination modes of ligands is extremely important for crystal structure prediction and crystal engineering.
Synthesis, Structure, and Magnetic Properties of a Family of Complexes Containing a {CoII2DyIII} Pivalate Core and a Pentanuclear CoII4DyIII Derivative
Authors: Kiskin Mikhail , Zorina‐Tikhonova Ekaterina , Kolotilov Sergey , Goloveshkin Alexander , Romanenko Galina , Efimov Nikolay , Eremenko Igor
Published: March 2018

Invited for the cover of this issue is research led by Mikhail Kiskin from the Russian Academy of Sciences, Moscow, Russian Federation, in collaboration with the National Academy of Sciences of Ukraine, Kiev, Ukraine. The cover image shows the synthesis, structure, and magnetic properties of a family of complexes containing a Co2Dy trinuclear core.
Should macroeconomic information be released during trading breaks in futures markets?
Authors: Frino Alex , Garcia Michael
Published: March 2018

This study examines the impact of releasing macroeconomic information during trading breaks versus during continuous trading in futures markets. Recently, the Chicago Mercantile Exchange changed its trading hours, while the United States Department of Agriculture changed the release time of its monthly report. These changes provide a natural experiment for assessing the role of trading breaks in futures markets. In this study, price volatility and bid‐ask spreads are found to be abnormally elevated and market depth abnormally low for a longer period during the continuous trading period. Therefore, releasing macroeconomic information during trading breaks in futures markets improves market quality.
Telephone‐based management of chronic pain in older adults in an integrated care program
Authors: Helstrom Amy , Haratz Josh , Chen Shirley , Benson Amy , Streim Joel , Oslin David
Published: March 2018

Objective

Few studies have explored behavioral strategies for managing chronic pain in older adults. Pain Care Management (PCM) is a telephone‐based behavioral intervention for chronic pain. The present study examined chronic pain characteristics among older adults and tested the delivery of PCM as an adjunct to depression and anxiety care management.

Methods

Participants were drawn from a state‐sponsored program offering care management services to community members aged 65 and older who were prescribed a psychotropic medication by a primary care provider. Chronic pain information was collected for all participants in the state program (N = 250) and treatment outcome data were collected for a subset with significant chronic pain. Eighty participants with high chronic pain interference were offered PCM and compared to 80 participants with chronic pain who received monitoring only on depression, anxiety, and pain interference outcomes.

Results

Chronic pain was identified in 14% of older adults newly prescribed a psychotropic medication. Compared to monitoring only, PCM participants had higher odds of seeing a reduction of 2 or more points in pain interference at 6 months. Pain care management participants' anxiety scores significantly decreased over the study period.

Conclusions

Older adults treated with psychotropic medications often also experience chronic pain that interferes with daily activities. A telephone‐based care management intervention is acceptable and feasible with an older community‐based population and can lead to improvements in anxiety symptoms and interference from chronic pain. Further research will help to refine interventions that may help improve symptoms and increase functioning with this population.
The neural correlates of morphological complexity processing: Detecting structure in pseudowords
Authors: Schuster Swetlana , Scharinger Mathias , Brooks Colin , Lahiri Aditi , Hartwigsen Gesa
Published: March 2018

Morphological complexity is a highly debated issue in visual word recognition. Previous neuroimaging studies have shown that speakers are sensitive to degrees of morphological complexity. Two‐step derived complex words (bridging through bridgeN > bridgeV > bridging) led to more enhanced activation in the left inferior frontal gyrus than their 1‐step derived counterparts (running through runV > running). However, it remains unclear whether sensitivity to degrees of morphological complexity extends to pseudowords. If this were the case, it would indicate that abstract knowledge of morphological structure is independent of lexicality. We addressed this question by investigating the processing of two sets of pseudowords in German. Both sets contained morphologically viable two‐step derived pseudowords differing in the number of derivational steps required to access an existing lexical representation and therefore the degree of structural analysis expected during processing. Using a 2 × 2 factorial design, we found lexicality effects to be distinct from processing signatures relating to structural analysis in pseudowords. Semantically‐driven processes such as lexical search showed a more frontal distribution while combinatorial processes related to structural analysis engaged more parietal parts of the network. Specifically, more complex pseudowords showed increased activation in parietal regions (right superior parietal lobe and left precuneus) relative to pseudowords that required less structural analysis to arrive at an existing lexical representation. As the two sets were matched on cohort size and surface form, these results highlight the role of internal levels of morphological structure even in forms that do not possess a lexical representation.
Noninvasive extraction of microsecond‐scale dynamics from human motor cortex
Authors: Koponen Lari M. , Nieminen Jaakko O. , Mutanen Tuomas P. , Ilmoniemi Risto J.
Published: March 2018

State‐of‐the‐art noninvasive electromagnetic recording techniques allow observing neuronal dynamics down to the millisecond scale. Direct measurement of faster events has been limited to in vitro or invasive recordings. To overcome this limitation, we introduce a new paradigm for transcranial magnetic stimulation. We adjusted the stimulation waveform on the microsecond scale, by varying the duration between the positive and negative phase of the induced electric field, and studied corresponding changes in the elicited motor responses. The magnitude of the electric field needed for given motor‐evoked potential amplitude decreased exponentially as a function of this duration with a time constant of 17 µs. Our indirect noninvasive measurement paradigm allows studying neuronal kinetics on the microsecond scale in vivo.
Endothelial progenitor cells contribute to neovascularization of non‐small cell lung cancer via histone deacetylase 7‐mediated cytoskeleton regulation and angiogenic genes transcription
Authors: Wei Ye , Zhou Fangzheng , Zhou Haibo , Huang Jing , Yu Dandan , Wu Gang
Published: March 2018

To supply tumor tissues with nutrients and oxygen, endothelial progenitor cells (EPCs) home to tumor sites and contribute to neovascularization. Although the precise mechanism of EPCs‐induced neovascularization remains poorly understood in non‐small cell lung cancer (NSCLC), histone deacetylase 7 (HDAC7) is considered as a critical regulator. To explore the function of HDAC7 in neovascularization induced by EPCs, tube formation assay, immunofluorescence, microarray, Western blot analysis and animal models were performed. In vitro, HDAC7 abrogation led to the activation of Rho‐associated coiled‐coil containing protein kinase/myosin light chain 2 pathway concomitant with ERK dephosphorylation, causing the instability of cytoskeleton and collapse of tube formation. In vivo, absence of HDAC7 impaired the vascular lumen integrity and decreased the functional blood perfusion, inhibiting the growth of tumor. At the level of transcription, HDAC7 silencing upregulated antiangiogenic genes and suppressed proangiogenic genes collectively, turning off the angiogenic switch during vessel formation. Taken together, HDAC7 plays a dual role in maintaining the structural and nonstructural functions of EPCs. Our work demonstrates the molecular mechanism by which HDAC7 contributes to the angiogenic property of EPCs and provides a rational basis for specific targeting of antiangiogenic strategies in lung cancer.
Increased concentration of serum periostin is associated with poor outcome of patients with aneurysmal subarachnoid hemorrhage
Authors: Luo Weijian , Wang Hao , Hu Jiliang
Published: March 2018

Objective

To explore the role of serum periostin in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Method

We conducted a retrospective study and 124 aSAH patients treated in Shenzhen People's hospital during March 1st 2015 to December 30th 2016 were included. Baseline information, neurological status and clinical outcome were recorded. Blood samples on admission were collected and enzyme linked immunosorbent assay (ELISA) kits were used to detect the serum level of periostin. Spearman's Correlation Analysis was used to analyze the correlation between periostin and clinical severity. Receiver operating characteristic (ROC) curve was performed to investigate variables’ prognostic value in patients with aSAH.

Results

The average age of patients included was 57.23 years old. Preliminary analysis revealed that serum periostin was significantly correlated with clinical severity. Patients with poor outcome at 12 months had higher level of periostin than patients with good outcome. Multivariate logistic regression analysis showed elevated level of periostin was significantly associated with poor outcome and the AUC was 0.85 for periostin in predicting poor outcome of patient with aSAH.

Conclusion

Elevated serum periostin concentrations are significantly associated with clinical severity and poor outcome of aSAH patients, which indicate serum periostin can be used as a prognostic biomarker in patients with aSAH.
A comparison of procedures for unpairing conditioned reflexive motivating operations
Authors: Kettering Tracy L. , Neef Nancy A. , Kelley Michael E. , Heward William L.
Published: March 2018

This study compared the effectiveness of two procedures to reduce behavior evoked by a reflexive conditioned motivating operation (CMO‐R). Task demands were shown to evoke escape‐maintained problem behavior for 4 students with disabilities. Alternative communication responses were taught as an appropriate method to request escape and this treatment combined with extinction for problem behavior led to decreases in problem behavior for all students. A beeping timer was then arranged to temporally precede the task demand to create a CMO‐R that evoked communication responses. When data showed that the sound of the timer was functioning as a CMO‐R, two methods to reduce behavior evoked by a CMO‐R—extinction unpairing and noncontingent unpairing—were evaluated. Results indicated that noncontingent unpairing was an effective method to reduce the evocative effects of the CMO‐R. Extinction produced unsystematic effects across participants. Results are discussed in terms of abolishing CMOs and the implications of CMOs.
Temporary and Permanent Effects of Remittances on Economic Growth in Ecuador
Authors: Pontarollo Nicola , Mendieta Muñoz Rodrigo
Published: March 2018

This article analyses the temporary and permanent effects of remittances on subnational economic growth in Ecuador. We find that both effects are statistically significant. However, while the size of first is negligible, the magnitude of the permanent effect is inversely related to the stage of development. Copyright © 2018 John Wiley & Sons, Ltd.