bluuebunny/crossref_metadata_2025 huggingface dataset:
World Health Organization‐defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management
Authors: Gotlib Jason
Published: October 2017

Disease overview

The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end‐organ damage.

Diagnosis

Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm3 and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ‐hybridization, flow immunocytometry, and T‐cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder.

Risk stratification

Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi‐molecular classification scheme of disease subtypes which includes the major category “myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1‐JAK2,” and the “MPN subtype, chronic eosinophilic leukemia, not otherwise specified” (CEL, NOS). Lymphocyte‐variant hypereosinophilia is an aberrant T‐cell clone‐driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.

Risk‐adapted therapy

The goal of therapy is to mitigate eosinophil‐mediated organ damage. For patients with milder forms of eosinophilia (e.g., < 1500/mm3) without symptoms or signs of organ involvement, a watch and wait approach with close‐follow‐up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first‐line therapy for patients with lymphocyte‐variant hypereosinophilia and HES. Hydroxyurea and interferon‐alpha have demonstrated efficacy as initial treatment and steroid‐refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported for limited numbers of patients. The use of antibodies against interleukin‐5 (IL‐5) (mepolizumab), the IL‐5 receptor (benralizumab), and CD52 (alemtuzumab), as well as other targets on eosinophils remains an active area of investigation.
Patient, disease, and treatment factors associated with overall survival in esthesioneuroblastoma
Authors: Carey Ryan M. , Godovchik Joseph , Workman Alan D. , Kuan Edward C. , Parasher Arjun K. , Chen Jinbo , Palmer James N. , Adappa Nithin D. , Newman Jason G. , Brant Jason A.
Published: October 2017

Background

Esthesioneuroblastomas (ENB) are uncommon and data regarding outcomes are often limited to single‐institution series. The National Cancer Database (NCDB), which contains outcomes information from treatment centers across the United States, represents an opportunity to evaluate outcomes for rare diseases such as ENB across multiple institutions.

Methods

The NCDB was queried for location codes corresponding to the nasal cavity and paranasal sinuses and the histology code for ENB. Multivariate analyses were performed to evaluate for contributing factors to overall survival.

Results

A total of 1225 patients with ENB met the inclusion criteria. The 5‐year overall survival was 76.2% (95% confidence interval [CI], 73.4‐79.0%). Overall survival was associated with Kadish stage, grade, treatment sequence, margin status, Charlson/Deyo score, age, and gender (p < 0.05). Multivariate analysis demonstrated that, compared with surgery alone, surgery followed by radiation without chemotherapy had improved all‐cause mortality (odds ratio [OR], 0.61; 95% CI, 0.40‐0.95). Surgery with chemotherapy alone was associated with increased odds of all‐cause mortality (OR, 4.86; 95% CI, 2.31‐10.25). Multivariate subanalysis for Kadish stages A and B demonstrated no difference in survival between surgery and surgery followed by radiation, but surgery followed by chemoradiation had worse overall survival (OR, 3.03; 95% CI, 1.07‐8.56). For Kadish stage C, surgery followed by radiation had improved overall survival compared with surgery alone (OR, 0.44; 95% CI, 0.24‐0.81).

Conclusion

The most common treatment for ENB is surgery followed by radiation, which is associated with the highest overall survival. The role of adjunctive chemotherapy needs to be re‐evaluated in further studies.
Single‐Molecule Observation of the Photoregulated Conformational Dynamics of DNA Origami Nanoscissors
Authors: Willner Elena M. , Kamada Yuu , Suzuki Yuki , Emura Tomoko , Hidaka Kumi , Dietz Hendrik , Sugiyama Hiroshi , Endo Masayuki
Published: October 2017

We demonstrate direct observation of the dynamic opening and closing behavior of photocontrollable DNA origami nanoscissors using high‐speed atomic force microscopy (HS‐AFM). First the conformational change between the open and closed state controlled by adjustment of surrounding salt concentration could be directly observed during AFM scanning. Then light‐responsive moieties were incorporated into the nanoscissors to control these structural changes by photoirradiation. Using photoswitchable DNA strands, we created a photoresponsive nanoscissors variant and were able to distinguish between the open and closed conformations after respective irradiation with ultraviolet (UV) and visible (Vis) light by gel electrophoresis and AFM imaging. Additionally, these reversible changes in shape during photoirradiation were directly visualized using HS‐AFM. Moreover, four photoswitchable nanoscissors were assembled into a scissor–actuator‐like higher‐order object, the configuration of which could be controlled by the open and closed switching induced by irradiation with UV and Vis light.
Mechanism‐Based Inhibitors of the Human Sirtuin 5 Deacylase: Structure–Activity Relationship, Biostructural, and Kinetic Insight
Authors: Rajabi Nima , Auth Marina , Troelsen Kathrin R. , Pannek Martin , Bhatt Dhaval P. , Fontenas Martin , Hirschey Matthew D. , Steegborn Clemens , Madsen Andreas S. , Olsen Christian A.
Published: October 2017

The sirtuin enzymes are important regulatory deacylases in a variety of biochemical contexts and may therefore be potential therapeutic targets through either activation or inhibition by small molecules. Here, we describe the discovery of the most potent inhibitor of sirtuin 5 (SIRT5) reported to date. We provide rationalization of the mode of binding by solving co‐crystal structures of selected inhibitors in complex with both human and zebrafish SIRT5, which provide insight for future optimization of inhibitors with more “drug‐like” properties. Importantly, enzyme kinetic evaluation revealed a slow, tight‐binding mechanism of inhibition, which is unprecedented for SIRT5. This is important information when applying inhibitors to probe mechanisms in biology.
Ein einfach herzustellender elektrochemischer Flussmikroreaktor: effiziente Isoindolinon‐Synthese und Funktionalisierung im Fluss
Authors: Folgueiras‐Amador Ana A. , Philipps Kai , Guilbaud Sébastien , Poelakker Jarno , Wirth Thomas
Published: October 2017

Elektrochemie im Fluss ist eine effiziente Methode zur Erzeugung radikalischer Zwischenstufen. Ein elektrochemischer Flussmikroreaktor wurde entwickelt, um die Effizienz von elektrochemischen Flussreaktionen zu verbessern. Mit diesem Gerät werden nur wenig oder keine Leitelektrolyte benötigt, wodurch die Prozesse kostengünstiger werden und saubereres Produkt entsteht. Dies wird anhand einer einfachen Synthese von Amidylradikalen gezeigt, die in intramolekularen Hydroaminierungen zu Isoindolinonen umgesetzt werden. Die Kombination mit Inline‐Massenspektrometrie ermöglicht eine einfachere Kombination verschiedener chemischer Schritte in einem einzigen Flussprozess.
An Easy‐to‐Machine Electrochemical Flow Microreactor: Efficient Synthesis of Isoindolinone and Flow Functionalization
Authors: Folgueiras‐Amador Ana A. , Philipps Kai , Guilbaud Sébastien , Poelakker Jarno , Wirth Thomas
Published: October 2017

Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow process.
Brief Report: Association of Natural Killer Cell Ligand Polymorphism HLA–C Asn80Lys With the Development of Anti‐SSA/Ro–Associated Congenital Heart Block
Authors: Ainsworth Hannah C. , Marion Miranda C. , Bertero Tiziana , Brucato Antonio , Cimaz Rolando , Costedoat‐Chalumeau Nathalie , Fredi Micaela , Gaffney Patrick , Kelly Jennifer , Levesque Kateri , Maltret Alice , Morel Nathalie , Ramoni Veronique , Ruffatti Amelia , Langefeld Carl D. , Buyon Jill P. , Clancy Robert M.
Published: October 2017

Objective

Fetal exposure to maternal anti‐SSA/Ro antibodies is necessary but not sufficient for the development of autoimmune congenital heart block (CHB), suggesting that other factors, such as fetal genetic predisposition, are important. Given the previously described association between major histocompatibility complex alleles and CHB risk, we undertook the present study to test the hypothesis that a variant form of HLA–C Asn80Lys, which binds with high affinity to an inhibitory killer cell immunoglobulin‐like receptor (KIR) and thus renders natural killer (NK) cells incapable of restricting inflammation, contributes to the development of CHB.

Methods

Members of 192 pedigrees in the US and Europe (194 cases of CHB, 91 unaffected siblings, 152 fathers, 167 mothers) and 1,073 out‐of‐study controls were genotyped on the Immunochip single‐nucleotide polymorphism microarray. Imputation was used to identify associations at HLA–C Asn80Lys (Asn, C1; Lys, C2) and KIR. Tests for association were performed using logistic regression. McNemar's test and the pedigree disequilibrium test (PDT) were used for matched analyses between affected and unaffected children.

Results

Compared with out‐of‐study controls of the same sex, the C2 allele was less frequent in the mothers (odds ratio [OR] 0.63, P = 0.0014) and more frequent in the fathers (OR 1.40, P = 0.0123), yielding a significant sex‐by‐C2 interaction (P = 0.0002). The C2 allele was more frequent in affected siblings than in unaffected siblings (OR 3.67, P = 0.0025), which was consistent with the PDT results (P = 0.016); these results were observed in both sexes and across the US and European cohorts. There was no difference in the frequency of the inhibitory KIR genotype (KIR AA) between affected and unaffected children (P = 0.55).

Conclusion

These data establish C2 as a novel genetic risk factor associated with CHB. This observation supports a model in which fetuses with C2 ligand expression and maternal anti‐SSA/Ro positivity may have impaired NK cell surveillance, resulting in unchecked cardiac inflammation and scarring.
Germinal Center B Cells Are Essential for Collagen‐Induced Arthritis
Authors: Dahdah Albert , Habir Katrin , Nandakumar Kutty Selva , Saxena Amit , Xu Bingze , Holmdahl Rikard , Malin Stephen
Published: October 2017

Objective

Rheumatoid arthritis (RA) is considered to be a prototypical autoimmune disorder. Several mechanisms have been proposed for the known pathologic function of B cells in RA, including antigen presentation, cytokine secretion, and humoral immunity. The aim of this study was to address the function of B lymphocytes in experimental arthritis.

Methods

We mapped the adaptive immune response following collagen‐induced arthritis (CIA). We subsequently monitored these responses and disease outcomes in genetically modified mouse strains that lack mature B cell or germinal center (GC) functionality in a B cell–intrinsic manner.

Results

Following primary immunization, the draining lymph nodes broadly reacted against type II collagen (CII) with the formation of GCs and T cell activation. Mice that lacked mature B cell function were fully protected against CIA and had a severely attenuated ability to mount isotype‐switched humoral immune responses against CII. Almost identical results were observed in mice that were selectively deficient in GC responses. Importantly, GC‐deficient mice were fully susceptible to collagen antibody–induced arthritis.

Conclusion

We identified GC formation and anticollagen antibody production as the key pathogenic functions of B cells in CIA. The role of B cells in RA is likely to be more complex. However, targeting the GC reaction could allow for therapeutic interventions that are more refined than general B cell depletion.
An empirical investigation on search engine ad disclosure
Authors: Lewandowski Dirk , Kerkmann Friederike , Rümmele Sandra , Sünkler Sebastian
Published: October 2017

This representative study of German search engine users (N = 1,000) focuses on the ability of users to distinguish between organic results and advertisements on Google results pages. We combine questions about Google's business with task‐based studies in which users were asked to distinguish between ads and organic results in screenshots of results pages. We find that only a small percentage of users can reliably distinguish between ads and organic results, and that user knowledge of Google's business model is very limited. We conclude that ads are insufficiently labelled as such, and that many users may click on ads assuming that they are selecting organic results.
Coaxial Carbon/MnO2 Hollow Nanofibers as Sulfur Hosts for High‐Performance Lithium‐Sulfur Batteries
Authors: Ni Lubin , Zhao Gangjin , Wang Yanting , Wu Zhen , Wang Wei , Liao Yunyun , Yang Guang , Diao Guowang
Published: October 2017

Lithium‐sulfur (Li‐S) batteries have recently attracted a large amount of attention as promising candidates for next‐generation high‐power energy storage devices because of their high theoretical capacity and energy density. However, the shuttle effect of polysulfides and poor conductivity of sulfur are still vital issues that constrain their specific capacity and cyclic stability. Here, we design coaxial MnO2‐graphitic carbon hollow nanofibers as sulfur hosts for high‐performance lithium‐sulfur batteries. The hollow C/MnO2 coaxial nanofibers are synthesized via electrospinning and carbonization of the carbon nanofibers (CNFs), followed by an in situ redox reaction to grow MnO2 nanosheets on the surface of CNFs. The inner graphitic carbon layer not only maintains intimate contact with sulfur and outer MnO2 shell to significantly increase the overall electrical conductivity but also acts as a protective layer to prevent dissolution of polysulfides. The outer MnO2 nanosheets restrain the shuttle effect greatly through chemisorption and redox reaction. Therefore, the robust S@C/MnO2 nanofiber cathode delivers an extraordinary rate capability and excellent cycling stability with a capacity decay rate of 0.044 and 0.051 % per cycle after 1000 cycles at 1.0 C and 2.0 C, respectively. Our present work brings forward a new facile and efficient strategy for the functionalization of inorganic metal oxide on graphitic carbons as sulfur hosts for high performance Li‐S batteries.
A Novel trans‐1‐(9‐Anthryl)‐2‐phenylethene Derivative Containing a Phenanthroimidazole Unit for Application in Organic Light‐Emitting Diodes
Authors: Zhou Nonglin , Wang Shirong , Xiao Yin , Li Xianggao
Published: October 2017

Aryl‐substituted phenanthroimidazoles (PIs) have attracted tremendous attention in the field of organic light‐emitting diodes (OLEDs), because they are simple to synthesize and have excellent thermal properties, high photoluminescence quantum yields (PLQYs), and bipolar properties. Herein, a novel blue–green emitting material, (E)‐2‐{4′‐[2‐(anthracen‐9‐yl)vinyl]‐[1,1′‐biphenyl]‐4‐yl}‐1‐phenyl‐1H‐phenanthro[9,10‐d]imidazole (APE‐PPI), containing a t‐APE [1‐(9‐anthryl)‐2‐phenylethene] core and a PI moiety was designed and synthesized. Owing to the PI skeleton, APE‐PPI possesses high thermal stability and a high PLQY, and the compound exhibits bipolar transporting characteristics, which were identified by single‐carrier devices. Nondoped blue–green OLEDs with APE‐PPI as the emitting layer show emission at λ=508 nm, a full width at half maximum of 82 nm, a maximum brightness of 9042 cd m−2, a maximum current efficiency of 2.14 cd A−1, and Commission Internationale de L'Eclairage (CIE) coordinates of (0.26, 0.55). Furthermore, a white OLED (WOLED) was fabricated by employing APE‐PPI as the blue–green emitting layer and 4‐(dicyanomethylene)‐2‐tert‐butyl‐6‐(1,1,7,7‐tetramethyljulolidin‐4‐yl‐vinyl)‐4H‐pyran (DCJTB) doped in tris‐(8‐hydroxyquinolinato)aluminum (Alq3) as the red–green emitting layer. This WOLED exhibited a maximum brightness of 10029 cd m−2, a maximum current efficiency of 16.05 cd A−1, CIE coordinates of (0.47, 0.47), and a color rendering index (CRI) of 85. The high performance of APE‐PPI‐based devices suggests that the t‐APE and PI combination can potentially be used to synthesize efficient electroluminescent materials for WOLEDs.
Weighted composite analysis and its application: an example using ENSO and geopotential height
Authors: Xie Zhiang , Duan Anmin , Tian Qun
Published: October 2017

The arbitrariness of composite analysis due to criterion of defining positive and negative events is an unsolved problem. To deal with it, a new method based on the covariance and defined as weighted composite analysis was developed in this study. Two ideal cases reveal that the new method can eliminate noise more effectively in small sample size, and has a higher signal to noise ratio than the traditional method in some cases. And a real case on the relationship between ENSO and geopotential height over East Asia in summer indicates that the new method shows some similar features with composite analyses, but can effectually avoid some inappropriate conclusions. It therefore provides an alternative approach to investigate linkages between different variables.
Rice straw as a feedstock for biofuels: Availability, recalcitrance, and chemical properties
Authors: Satlewal Alok , Agrawal Ruchi , Bhagia Samarthya , Das Parthapratim , Ragauskas Arthur J.
Published: October 2017

The surplus availability of rice straw, its limited usage, and environmental pollution caused by its inefficient burning has fostered research for its valorization to biofuels. This review elucidates the current status of rice straw potential around the globe along with recent advances in revealing the critical factors responsible for its recalcitrance and chemical properties. The role and accumulation of high silica content in rice straw has been elucidated with its impact on enzymatic hydrolysis in a biorefinery environment. The correlation of different pre‐treatment approaches in modifying the physiochemical properties of rice straw and improving the enzymatic accessibility has also been discussed. This study highlights new challenges, resolutions, and opportunities for rice straw based biorefineries. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd
Meta-analysis of the impact of surgical approach on the grade of mesorectal excision in rectal cancer
Authors: Creavin B , Kelly M E , Ryan E , Winter D C
Published: October 2017

Background

The subspecialization of colorectal surgeons, and improvements in the quality of mesorectal excision have revolutionized rectal cancer surgery. With the increasing use of minimally invasive techniques, the completeness of the mesorectal excision has been questioned. This study aimed to assess the pathological outcomes of open versus laparoscopic rectal resection.

Methods

A meta-analysis of RCTs was undertaken. The primary endpoint was the adequacy of the mesorectal excision. Secondary endpoints included circumferential resection margin and distance to resection margins.

Results

Four studies were included, reporting on 2319 patients; 972 (41·9 per cent) had open and 1347 (58·1 per cent) had laparoscopic resections. Meta-analysis of adequacy of the mesorectal excision showed a small difference in achieving an intact mesorectum in favour of open surgery (risk ratio (RR) 1·06, 95 per cent c.i. 1·02 to 1·10; P = 0·001). Superficial defects were more common in laparoscopic surgery (RR 0·70, 0·54 to 0·89; P = 0·004). Deep mesorectal defects (RR 0·78, 0·51 to 1·20; P = 0·256), circumferential margin (CRM) positivity (RR 0·85, 0·62 to 1·16; P = 0·310), and distance to radial (mean difference (MD) –0·06, 95 per cent c.i. –0·10 to 0·23; P = 0·443) and distal (MD 0·03, –0·06 to 0·12; P = 0·497) margins were all similar. A complete resection (intact mesorectum, negative CRM and distal margin) was achieved in 350 of 478 patients (73·2 per cent) in the laparoscopic group and 372 of 457 (81·4 per cent) in the open group (risk difference (RD) 8 (95 per cent c.i. 3 to 13) per cent; P = 0·003). However, an acceptable mesorectum (intact or superficial defects only) was present in 1254 of 1308 (95·9 per cent) and 916 of 949 (96·5 per cent) in the laparoscopic and open groups respectively (RD 1 (–1 to 3) per cent; P = 0·263).

Conclusion

Small differences in mesorectal quality were evident between open and laparoscopic rectal resections. This may be attributable to use of laparoscopic instruments; however, to date minor defects have not affected oncological outcomes.
Randomized feasibility trial of replacing or discarding the nail plate after nail-bed repair in children
Authors: Greig A , Gardiner M D , Sierakowski A , Zweifel C J , Pinder R M , Furniss D , Cook J A , Beard D , Farrar N , Cooper C D , Jain A , Agha R , Albadry W , Cemal Y , Chadha P , Collins D , Creasy H , Din A , Ferreira M , Maggiulli F , Mitsakos A , Molina A , Pampiglione T , Pywell M , Richards K , Tavsanoglu Y , Tejero R , Vamadeva S , Wang R , Wordsworth M , Holmes W , Haeney J , Brierley N , Pardoe E , Naylor C , Laing T , Delikonstantinou I , Whybro N , Gerrish H , Gammin E
Published: October 2017

Background

Nail-bed injuries are the most common hand injury in children. Surgical dogma is to replace the nail plate after repairing the nail bed. Recent evidence suggests this might increase infection rates and returns to clinic. The aim of this feasibility trial was to inform the design and conduct of a definitive trial comparing replacing or discarding the nail plate after nail-bed repair.

Methods

This study recruited participants from four hand units in the UK between April and July 2015. Participants were children under the age of 16 years with a nail-bed injury requiring surgery. They were randomized to either having the nail plate replaced or discarded after nail-bed repair. The follow-up method was also allocated randomly (postal versus clinic). Information was collected on complications at 2 weeks and 30 days, and on nail-plate appearance at 4 months using the Zook classification. Two possible approaches to follow-up were also piloted and compared.

Results

During the recruitment phase, there were 156 potentially eligible children. Sixty were randomized in just over 3 months using remote web-based allocation. By 2 weeks, there were two infections, both in children with replaced nail plates. The nail-replaced group also experienced more complications. There was no evidence of a difference in return rates between postal and clinic follow-up.

Conclusion

Recruitment was rapid and nail-bed repair appeared to have low complication and infection rates in this pilot trial. The findings have led to revision of the definitive trial protocol, including the mode and timing of follow-up, and modification of the Zook classification.
Protection Effect of Cyanidin 3‐O‐Glucoside Against Oxidative Stress‐induced HepG2 Cell Death Through Activation of Akt and Extracellular Signal‐regulated Kinase Pathways
Authors: Park Jun Yeon , Kang Ki Sung , Lee Hae‐Jeung
Published: October 2017

The attack of reactive oxygen species (ROS) on unsaturated fatty acids causes peroxidation. The membranes of liver cells are rich in unsaturated fatty acids, which are a target of lipid peroxidation by free radicals. The purpose of the present study was to identify the hepatoprotective potential of Lonicera caerulea and its active compound, cyanidin 3‐O‐glucoside, on tertiary butyl hydroperoxide (tBHP)‐induced oxidative damage in HepG2 cells. L. caerulea extract and its active compound, cyanidin 3‐O‐glucoside, showed a dose‐dependent hepatoprotective effect on tBHP‐induced HepG2 cell damage. In addition, L. caerulea and cyanidin 3‐O‐glucoside inhibited the production of intracellular ROS in tBHP‐treated HepG2 cells. The protein expression of phosphorylated‐extracellular signal‐regulated kinases and Akt, which are responsible for cell protection against ROS, were increased after treatment with cyanidin 3‐O‐glucoside (50 and 100 μM) in a dose‐dependent manner. Therefore, cyanidin 3‐O‐glucoside is the active compound in L. caerulea, which is responsible for the hepatoprotective effects through the inhibition of ROS and the activation of antioxidant mechanisms.
Carbon Nanotube‐supported Pd/Ni(OH)2 Nanoparticles: Magnetically Recoverable and Reusable Catalyst for the Reduction of Nitroarenes
Authors: Kim Ji Dang , Choi Hyun Chul
Published: October 2017

Carbon nanotube‐supported magnetic nanoparticles (CNT‐Pd/Ni(OH)2) were synthesized and characterized by transmission electron microscopy (TEM), X‐ray diffraction (XRD), Auger electron spectroscopy (AES), and ultraviolet–visible (UV–vis) spectroscopy. TEM images indicated that similar sized nanoparticles (with an average size of 2.6 nm) were densely anchored on the surfaces of CNTs. The Pd and Ni contents were estimated to be approximately 3.2 and 2.5 at.%, respectively. The resulting catalyst exhibited high catalytic activity toward the reduction of nitroarenes. The catalyst was easily separated from the reaction mixture using an external magnet with no need of additional separation procedures. The recovered catalyst could be reused for 20 successive reaction runs of 4‐nitrophenol reduction. The excellent catalytic performance can be attributed to the strong interfacial adhesion between thiol‐functionalized CNT supports and Pd/Ni(OH)2 nanoparticles.
Evaluating manufacturing process profile comparability with multivariate equivalence testing: Case study of cell‐culture small scale model transfer
Authors: Cao Yang , Obeng Daniel , Hui Guodong , Xue Luting , Ren Yukun , Yu Xianjie , Wang Fei , Atwell Chad
Published: October 2017

This article studies the Generalized Mahalanobis Distance (GMD) approach proposed by Hoffelder which measures the dissimilarity of two multivariate Gaussian distributions with arbitrary covariance matrices and unequal sample sizes. This investigation demonstrated that, with appropriate adjustment, the GMD approach can achieve the targeted nominal Type I error and provide sufficient power for testing equivalence between two profile populations. The adjusted GMD approach was applied to examine the equivalence of harvest profiles between a 12L small scale model and 2000L manufacturing scale in a transfer study performed at Sanofi Specialty Care Framingham Biologics. The harvest profiles were evaluated based on three critical parameters (Productivity, Lactate Production, and Total Cell Density) and deemed practically equivalent using a pre‐defined equivalence margin per the adjusted GMD approach. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:187–195, 2018
The surgical anatomy of the sural nerve: An ultrasound study
Authors: Popieluszko Patrick , Mizia Ewa , Henry Brandon Michael , PĘkala PrzemysŁaw A. , Sanna Beatrice , Roy Joyeeta , Loukas Marios , Tomaszewski Krzysztof A.
Published: October 2017

The aim of this study was (a) to examine the anatomy of the sural nerve (SN) in a sample of 30 patients and (b) to analyze the incidence of different origins of the SN, and the distance of the SN from planned arthroscopic portals. An ultrasound (USG) examination of the SN was performed bilaterally on thirty healthy patients with no history of surgery or trauma of the lower limb. The SNs were classified into six main types of pattern, with an additional category for new and unclassified types. Each of Types 1 and 3 had two subdivisions. The distances from the superior border of the calcaneal tuberosity to the three simulated arthroscopy portal sites (Z1, Z1.5, Z2) to the SN were measured. A total of 30 patients (n = 60 limbs) with an average age of 27 ± 7.5 years were examined and the SN was visualized in all cases. The most common origin was Type 3A, accounting for 30% of limbs. Type 2 was the second most common seen in 18.3%. The distances of the SN from arthroscopic portal placement sites above the lateral malleolus were 2.07 ± 0.39 cm at the Z1 portal, 2.15 ± 0.38 cm at Z1.5, and 2.28 ± 0.33 cm at Z2. The variability in the anatomy of the SN warrants the use of USG to locate it accurately, thus preventing iatrogenic injury when portals are placed for arthroscopy, improving proper administration of anesthesia, and helping to localize the nerve for graft harvesting. Clin. Anat. 31:450–455, 2018. © 2017 Wiley Periodicals, Inc.
Investigation of umbilical venous vessels anatomy and diameters as a guideline for catheter placement in newborns
Authors: Eifinger F. , Fuchs Z. , Koerber F. , Persigehl T. , Scaal M.
Published: October 2017

Umbilical cord catheters (UCC) are important for the primary care of critically ill newborns. To analyze anatomical variations of the umbilical vein (UV) and its further course, we performed abdominal spiral‐CT examinations on stillborns. The aim of the study was to explore the high incidence of mal‐positioned UCCs and to improve their positioning. Eighteen stillborns were investigated (29.2 weeks ± 6.7 weeks (IQR)). CTs were performed using either air or contrast medium injection into the UV. We measured the diameter at the narrowest points of (i) the umbilical vein, (ii) the segmental portal vein, (iii) the left portal vein, (iv) the umbilical recess, and (v) the ductus venosus. The branching angles between (a) the umbilical vein and intrahepatic veins and (b) the ductus venosus and umbilical recess were measured. The diameter of the UV increases from 3.4 to 11 mm (median [IQR]:4.6 mm [4.2–6.9]: r2 = 0.64). The left portal vein has a larger diameter (3.6 mm [2.6–4.55]; r2 = 0.43) than the left segmental portal vein (2.3 mm [1.8–2.75]; r2 = 0.23). The diameter of the ductus venosus (2.5 mm [1.6–3.4]; r2 = 0.59) is half that of the umbilical recess (5.1 mm [3.3–6.2]; r2 = 0.43). The most obtuse angle is formed by the junction between the umbilical recess and ductus venosus (151° [133–159]; r2 = 0.001). The branch angle from the outgoing UV into the left portal vein is more obtuse (128° [123–144]; r2 = 0.0001) than that of the segmental portal vein (115° [105–119]; r2 = 0.0001). To avoid mal‐positioning, our data suggest the use of a soft catheter. The UV and its extensions are wide enough to admit a 4 Fr. catheter without complete obstruction. Clin. Anat. 31:269–274, 2018. © 2017 Wiley Periodicals, Inc.
Orbital and rotational atherectomy during percutaneous coronary intervention for coronary artery calcification
Authors: Lee Michael S. , Gordin Jonathan S. , Stone Gregg W. , Sharma Samin K. , Saito Shigeru , Mahmud Ehtisham , Chambers Jeff , Généreux Philippe , Shlofmitz Richard
Published: October 2017

Severe coronary artery calcification (CAC) increases the complexity of percutaneous coronary intervention (PCI) by inhibiting optimal stent expansion, leading to an increased risk of death, myocardial infarction, repeat revascularization, and stent thrombosis. Coronary atherectomy modifies and debulks calcified plaque to facilitate PCI. Although there is no clear consensus, and further studies are needed, the decision to perform atherectomy should be based upon the presence of fluoroscopic CAC or with the use of intravascular imaging. The management of CAC in the modern era relies on rotational and orbital atherectomy to prepare the lesion to facilitate stent delivery and optimal expansion. While the two technologies differ in equipment, technique, and mechanism of action, the available literature suggests similar efficacy and safety of the two systems, although head‐to‐head comparisons are limited. While rotational and orbital atherectomy have been shown to have excellent procedural success in terms of facilitating stent delivery, no system has been shown to reduce long‐term major adverse cardiovascular events, although the definitive trial for orbital atherectomy has not been completed. Additional trials are needed to find the population who would derive the most benefit of atherectomy and to compare the two systems in a prospective manner.
Hydrogen Production by Direct Lignin Electrolysis at Intermediate Temperatures
Authors: Hibino Takashi , Kobayashi Kazuyo , Nagao Masahiro , Teranishi Shinya
Published: October 2017

Hydrogen is produced conventionally by electrolyzing water or water vapor at onset voltages greater than 1 V, providing motivation for the development of more efficient electrolysis processes for a hydrogen economy. Numerous attempts have been made to use ethanol as a fuel for hydrogen production because this process reduces the electrolysis onset voltage significantly. However, ethanol feedstock from lignocellulose requires greater amounts of energy and results in higher production costs compared to those using starch as the feedstock. The current study describes direct lignin electrolysis at an onset voltage of ca. 0.25 V, with high current efficiencies of approximately 100 % for hydrogen production at the cathode and approximately 85 % for carbon dioxide production at the anode. Addition of H3PO4‐impregnated lignin to the anode of a PtFe/C|Sn0.9In0.1P2O7 (150 μm)|Pt/C cell enabled hydrogen production at a temperature of 150 °C.
Multifunctional Separator with Porous Carbon/Multi‐Walled Carbon Nanotube Coating for Advanced Lithium−Sulfur Batteries
Authors: Tan Lei , Li Xinhai , Wang Zhixing , Guo Huajun , Wang Jiexi , An Liang
Published: October 2017

An issue associated with lithium−sulfur (Li−S) batteries is polysulfide dissolution, leading to the serious crossover of polysulfide to the Li anode. To address this issue, we report on a multifunctional separator prepared by introducing a porous carbon/multi‐walled carbon nanotube (PC/MWCNT) composite into a commercial separator. It shows that the PC/MWCNT composite is able to enhance the interfacial interaction between the coating and the polysulfide and provides a large surface area for absorbing the polysulfide, thus improving the electrical conductivity. It has been demonstrated that the Li−S cell constructed with the PC/MWCNT composite separator results in a reversible capacity as high as 659 mAh g−1 after 200 cycles at 0.5 C, and the average capacity fading rate of the cell is about 0.138 % per cycle. The performance improvement is attributed to a reduction in the crossover rate of polysulfide through the composite separator as a result of the polysulfide absorption by PC/MWCNT layer.
Water Splitting Catalysis Studied by using Real‐Time Faradaic Efficiency Obtained through Coupled Electrolysis and Mass Spectrometry
Authors: Svengren Henrik , Chamoun Mylad , Grins Jekabs , Johnsson Mats
Published: October 2017

An experimental setup and routine is presented for evaluating potential catalysts for water splitting by means of measuring the faradaic efficiency in real time through coupled potentiometry and mass spectrometry. The aim was to scale up an analytical cell unit towards the simulation of industrial conditions and generate results such as H2 production versus power input at a certain potential or current density in addition to electrochemical parameters. Three types of electrodes were tested: A) planar metal electrodes; B) metal‐foam‐based electrodes; C) porous electrodes with carbon additive. The results verify that the experimental routine yields the desired accuracy, sensitivity, and a negligible accumulation of gaseous products in the cell; thus the faradaic efficiency is measured in real time. The metal‐based electrodes of category A and B proved to be durable with low overpotentials and high gas output to power input, whereas three tested metal oxide electrodes in C revealed i) potential‐dependent deviation in the faradaic efficiency, ii) phase decomposition, and iii) an optimum operational power range.
Metal‐Catalyzed Group‐Transfer Polymerization: A Versatile Tool for Tailor‐Made Functional (Co)Polymers
Authors: Adams Friederike , Pahl Philipp , Rieger Bernhard
Published: October 2017

Accommodating the increasing demand for tailor‐made polymers is a major goal in polymer chemistry. Therefore, the investigation of polymerization techniques, which allow the precise synthesis of macromolecules is of exceptional interest. Ionic or controlled radical polymerization are capable living‐type methods for the generation of uniform polymers. However, even these approaches reach their limits in certain issues. In the last decades, group‐transfer polymerization (GTP) and especially metal‐catalyzed GTP have proven to give access to a plethora of tailor‐made homo‐ and copolymers based on α,β‐unsaturated monomers. Thereby, GTP has established its potential in the development of functional and smart polymers. This concept article highlights the most significant progress in metal‐catalyzed GTP with a focus on functional (co)polymers including different polymeric architectures and microstructures.
Static Electricity‐Responsive Supramolecular Assembly
Authors: Jintoku Hirokuni , Ihara Hirotaka , Matsuzawa Yoko , Kihara Hideyuki
Published: October 2017

Stimuli‐responsive materials can convert between molecular scale and macroscopic scale phenomena. Two macroscopic static electricity‐responsive phenomena based on nanoscale supramolecular assemblies of a zinc porphyrin derivative are presented. One example involves the movement of supramolecular assemblies in response to static electricity. The assembly of a pyridine (Py) complex of the above‐mentioned derivative in cyclohexane is drawn to a positively charged material, whereas the assembly of a 3,5‐dimethylpyridine complex is drawn to a negatively charged material. The second phenomenon involves the movement of a non‐polar solvent in response to static electrical stimulation. A cyclohexane solution containing a small quantity of the Py‐complexed assembly exhibited a strong movement response towards negatively charged materials. Based on spectroscopic measurements and electron microscope observations, it was revealed that the assembled formation generates the observed response to static electricity.
Confinement of Water Pentamers within the Crystals of a Reduced Cyclotribenzoin
Authors: Alrayyani Maymounah , Wang Xiqu , Miljanić Ognjen Š.
Published: October 2017

Reduction of cyclotribenzoin with sodium borohydride produces a cone‐shaped hexaol. Crystals of this hexaol, obtained from wet tetrahydrofuran, encapsulate clusters of five water molecules in an idealized hydrogen‐bonded arrangement. The water pentamer is stabilized by hydrogen bonding with the –OH groups of the hexaol, and [O−H⋅⋅⋅π] interactions with the benzene rings of the reduced cyclotribenzoin.
Synthesis of nano‐niosomal deferoxamine and evaluation of its functional characteristics to apply as an iron‐chelating agent
Authors: Marzban Adel , Akbarzadeh Azim , Ardestani Mehdi Shafiee , Ardestani Fatemeh , Akbari Mohsen
Published: October 2017

Deferoxamine has been widely used as an iron‐chelating agent in patients with primary or secondary iron overload deficiency. Deferoxamine is typically administered subcutaneously, intramuscularly, or intravenously by the constant infusion of the drug over 8–12 h. This process is lengthy and uncomfortable for the patients. A nano‐niosomal form of deferoxamine was prepared using the reverse phase evaporation method and evaluated on the basis of morphology, drug release, cytotoxicity, and iron‐chelating efficacy to compare with free drug formulation. The unique structure of niosome enables sustained release of the drug over extended periods. The average particle size was 136 nm and the entrapment efficiency was about 96 %. The biocompatibility of the drug‐loaded nanoparticles showed that the encapsulation of the drug in nano‐niosomes reduces the toxicity of the drug significantly. Our results indicate that the iron‐chelating ability of the entrapped deferoxamine in hepatocytes is higher than the free drug. The nano‐niosomal drug form showed more efficacies versus the free one and it could be a promising clinical intravenous system for delivery of iron‐chelating drugs such as deferoxamine.
NCCTG N0879 (Alliance): A randomized phase 2 cooperative group trial of carboplatin, paclitaxel, and bevacizumab ± everolimus for metastatic melanoma
Authors: McWilliams Robert R. , Allred Jacob B. , Slostad Jessica A. , Katipamula Rajini , Dronca Roxana S. , Rumilla Kandelaria M. , Erickson Lori A. , Bryce Alan H. , Joseph Richard W. , Kottschade Lisa A. , King David M. , Leitch John M. , Markovic Svetomir N.
Published: October 2017

BACKGROUND

Despite the success of immune checkpoint and targeted therapy, many patients with melanoma ultimately require further treatment. The combination of carboplatin, paclitaxel, and bevacizumab (CPB) has demonstrated promising activity in a single‐arm study. In the current study, the authors performed a randomized phase 2 study to confirm efficacy and to determine whether adding everolimus would increase the activity of the combination.

METHODS

Through the North Central Cancer Treatment Group, a total of 149 patients with unresectable AJCC 6th edition stage IV melanoma were randomized from May 2010 to May 2014 to either CPB or CPB with everolimus (CPBE). The primary endpoint was progression‐free survival (PFS), with secondary endpoints of overall survival (OS), response rate, and tolerability.

RESULTS

The CPB and CPBE treatment arms were balanced with regard to age (median age: 59 years vs 58 years) and high lactate dehydrogenase (48% vs 51%), but were unbalanced with regard to sex (male sex: 72% vs 55%; P = .03). Overall, there was no difference noted with regard to PFS, with a median PFS of 5.6 months for CPB versus 5.1 months for CPBE (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.81‐1.62 [P = .44]), or for OS, with a median OS of 14.5 months for CPB versus 10.8 months for CPBE (HR, 1.16; 95% CI, 0.84‐1.84). The confirmed response rate was 13% for CPB and 23% for CPBE (P = .13). Toxicity was higher for CPBE compared with CPB (83% for grade 3 + and 14% for grade 4 + vs 63% for grade 3 + and 11% for grade 4+, respectively) (toxicities were graded using the Cancer Therapy Evaluation Program of the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Common grade 3 + toxicities were neutropenia, leukopenia, and fatigue, which occurred in both treatment arms with comparable frequency.

CONCLUSIONS

Both experimental arms demonstrated activity, with a PFS of >5 months. However, the addition of everolimus to CPB failed to improve outcomes, with increased toxicity noted. These findings replicate the moderate antitumor activity of CPB, with future development possibly in combination with targeted or immunotherapy. Cancer 2018;124:537‐45. © 2017 American Cancer Society.
Gonadotropin‐inhibitory hormone in the flatfish, Solea senegalensis: Molecular cloning, brain localization and physiological effects
Authors: Aliaga‐Guerrero María , Paullada‐Salmerón José A. , Piquer Vanesa , Mañanós Evaristo L. , Muñoz‐Cueto José A.
Published: October 2017

Recently, gonadotropin‐inhibitory hormone (GnIH) has emerged as an important regulator of reproduction in birds and mammals. This RFamide neuropeptide has neuromodulatory functions and controls the synthesis and/or release of gonadotropin‐releasing hormone (GnRH) and gonadotropins. Although teleosts represent about half of all living vertebrates, scientific and technological advances on the Gnih system in fish are scarce, contradictory, and inconclusive. Research on the fish Gnih system appears necessary to better clarify its role in the neuroendocrine and environmental control of vertebrate reproduction. In this study, we cloned a full‐length sequence for the Gnih precursor of a flatfish, the Senegalese sole, coding for three putative Gnih peptides (ssGnih). We also generated specific antibodies against these ssGnih peptides, and used them to localize Gnih cells and their projections in the brain and pituitary. The expression of gnih was particularly evident in the diencephalon, but also in the olfactory bulbs/cerebral hemispheres, optic tectum/tegmentum, retina, and pituitary. The three antibodies used provided consistent results and showed that ssGnih‐immunoreactive perikarya were present in the olfactory bulbs, ventral telencephalon, caudal preoptic area, dorsal tegmentum and rostral rhombencephalon, and their fibers innervated the brain and pituitary profusely. Intramuscular injection of ssGnih‐3 provoked a significant reduction in gnrh‐3 and lh expression, whereas ssGnih‐2 treatment did not affect transcript levels of the main reproductive genes. Our results reveal the existence of a functional Gnih system in the sole brain, profusely innervating different brain areas and the pituitary gland, which could represent an important factor in the neuroendocrine control of flatfish reproduction.
Loop‐mediated isothermal amplification (LAMP) as an alternative to PCR: A rapid on‐site detection of gene doping
Authors: Salamin Olivier , Kuuranne Tiia , Saugy Martial , Leuenberger Nicolas
Published: October 2017

Innovation in medical research has been diverted at multiple occasions to enhance human performance. The predicted great progress in gene therapy has raised some concerns regarding its misuse in the world of sports (gene doping) for several years now. Even though there is no evidence that gene doping has ever been used in sports, the continuous improvement of gene therapy techniques increases the likelihood of abuse. Therefore, since 2004, efforts have been invested by the anti‐doping community and WADA for the development of detection methods. Several nested PCR and qPCR‐based strategies exploiting the absence of introns in the transgenic DNA have been proposed for the long‐term detection of transgene in blood. Despite their great sensitivity, those protocols are hampered by limitations of the techniques that can be cumbersome and costly. The purpose of this perspective is to describe a new approach based on loop‐mediated isothermal amplification (LAMP) for the detection of gene doping. This protocol enables a rapid and simple method to amplify nucleic acids with a high sensitivity and specificity and with a simple visual detection of the results. LAMP is already being used in clinical application for the detection of viruses or mutations. Therefore, this technique has the potential to be further developed for the detection of foreign genetic material in elite athletes. Copyright © 2017 John Wiley & Sons, Ltd.
Diastereoselective Total Synthesis of (±)‐Toxicodenane A
Authors: Kobayashi Toyoharu , Yamanoue Kotono , Abe Hideki , Ito Hisanaka
Published: October 2017

The first total synthesis of tricyclic sesquiterpene (±)‐toxicodenane A has been accomplished. This synthetic work was completed in 12 steps from dimedone through diastereoselective reductive desymmetrization of 2,2‐disubstituted 5,5‐dimethylcyclohexane‐1,3‐dione, stereocontrolled allylation, ring‐closing metathesis of a diene compound to yield bicyclic compounds that bear a seven‐membered ring, and construction of the oxygen‐bridged moiety through neighboring group assisted ring‐opening reaction of an epoxide as key steps.