bluuebunny/crossref_metadata_2025 huggingface dataset:
A population‐based study of chronic myeloid leukemia patients treated with imatinib in first line
Authors: Castagnetti Fausto , Di Raimondo Francesco , De Vivo Antonio , Spitaleri Antonio , Gugliotta Gabriele , Fabbiano Francesco , Capodanno Isabella , Mannina Donato , Salvucci Marzia , Antolino Agostino , Marasca Roberto , Musso Maurizio , Crugnola Monica , Impera Stefana , Trabacchi Elena , Musolino Caterina , Cavazzini Francesco , Mineo Giuseppe , Tosi Patrizia , Tomaselli Carmela , Rizzo Michele , Siragusa Sergio , Fogli Miriam , Ragionieri Riccardo , Zironi Alessandro , Soverini Simona , Martinelli Giovanni , Cavo Michele , Vigneri Paolo , Stagno Fabio , Rosti Gianantonio , Baccarani Michele
Published: October 2016

Chronic myeloid leukemia (CML) treatment is based on company‐sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first‐line therapy. These studies included patients selected according to many inclusion–exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real‐life), inclusion–exclusion criteria do not exist, and the treatment outcome does not only depend on the choice of first‐line TKI but also on second‐ and third‐line TKIs. To investigate in a real‐life setting the response and the outcome on first‐line imatinib, with switch to second generation TKIs in case of unsatisfying response or intolerance, we analyzed all newly diagnosed patients (N = 236), living in two Italian regions, registered in a prospective study according to population‐based criteria and treated front‐line with imatinib. A switch from imatinib to second‐generation TKIs was reported in 14% of patients for side effects and in 24% for failure or suboptimal response, with an improvement of molecular response in 57% of them. The 5‐year overall survival (OS) and leukemia‐related survival (LRS) were 85% and 93%, respectively; the 4‐year rates of MR3.0 and MR4.0 were 75% and 48%, respectively. Cardiovascular complications were reported in 4% of patients treated with imatinib alone and in 6% of patients receiving nilotinib as second‐line. Older age (≥70 years) affected OS, but not LRS. These data provide an unbiased reference on the CML management and on the results of TKI treatment in real‐life, according to ELN recommendations, using imatinib as first‐line treatment and second‐generation TKIs as second‐line therapy. Am. J. Hematol. 92:82–87, 2017. © 2016 Wiley Periodicals, Inc.
Secular trends of physical growth and abdominal adiposity of school children and adolescents living at a moderate altitude in Peru
Authors: Cossio‐Bolaños Marco , de Arruda Miguel , Andruske Cynthia Lee , Luarte‐Rocha Cristian , Gómez‐Campos Rossana
Published: October 2016

Objective

Identify changes in physical growth and abdominal adiposity at an interval of 14 years in children and adolescents living at a moderate altitude in Peru.

Materials and Methods

The data comes from two cross‐sectional studies carried out in the city of Arequipa, Peru, located at a moderate altitude of 2,320 meters. In 2001, 473 males and 482 females were assessed, and in 2015, 432 males and 403 females between 6.0 and 12.9 years old were evaluated. Data were collected in public state schools and measured using the anthropometric variables for weight, height, and waist circumference. Body mass index (BMI) was calculated according to age and sex.

Results

Positive trends for weight were identified for both males and females at all ages (p < .001). For height, significant increases were observed in males for all ages. No significant increases (p > .05) occurred in height for females between the ages of 6 and 8 years. However, commencing at age 9 until 12 years, females showed positive and significant increases (p < .001) in height. In 2015, BMI and waist circumference increased significantly for both sexes at all ages.

Discussion

Between 2001 and 2015, positive trends in physical growth and abdominal adiposity were identified for children and adolescents living in Arequipa, Peru. These changes may be associated with the rapid economic development in the country.
Febrile infection‐related epilepsy syndrome treated with anakinra
Authors: Kenney‐Jung Daniel L. , Vezzani Annamaria , Kahoud Robert J. , LaFrance‐Corey Reghann G. , Ho Mai‐Lan , Muskardin Theresa Wampler , Wirrell Elaine C. , Howe Charles L. , Payne Eric T.
Published: October 2016

Febrile infection‐related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin‐1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super‐refractory status epilepticus secondary to FIRES. Anakinra was well tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES. Further studies are required to assess anakinra efficacy and dosing, and to further delineate disease etiology. Ann Neurol 2016;80:939–945
A composite approach for remediation of cane distillery spent wash using chitosan modified biomass, electrolysis, and Oscillatoria boryana
Authors: Venkatachalam Dhanapal , Kaliappa Gounder Subramanian
Published: October 2016

A cost effective multistep bio‐physicochemical method comprising adsorption on carbon, banana pseudo‐stem (BPS), and modified chitosan hydrogels (MHPS) as adsorbents, bioremediation using Oscillatoria boryana (OB) and constant current electrolysis was employed successfully to remove oxygen demanding organic wastes, color, total dissolved solids (TDS), melanoidin, and acidic/basic impurities from distillery spent wash (DSW). The adsorbent were characterized for their structures [Shimadzu FTIR (Fourier transform–Infrared spectroscopy)−8400S], thermal stability [TGA (Thermogravimetric analyzer)‐Q 500 V20.0 Build 36] and surface morphology [ZEISS EVO series SEM (Scanning Electron Microscopy)‐EVO 50]. The percentage color reduction by visible spectrometry and residual coloring matter on platinum–cobalt color unit scale were found to be 97.2% and 250 ppm, respectively till OB bioremediation stage. The remaining residual color (2.8%) was removed in the subsequent electrolysis (1.95%) and adsorption on MHPS (0.85%) stages. The net percent reduction in color (>99%), COD (Chemical Oxygen Demand) and BOD (Biochemical Oxygen Demand) in the present composite approach for DSW treatment were found to be much higher than the reported values. Analysis of the adsorption data for the synthesized activated carbon through Langmuir and Freundlich isotherm models revealed Langmuir adsorption isotherm with pseudo‐ first‐order kinetics. The evaluated thermodynamic parameters (Van't Hoff plot) for adsorption revealed that the adsorption was spontaneous and exothermic. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44546.
Curing kinetics, thermal, and adhesive properties of acetylene‐terminated benzoxazine
Authors: Liu Caizhao , Sun Mingming , Zhang Bin , Zhang Xugang , Li Jianhui , Li Qili
Published: October 2016

The acetylene‐terminated benzoxazine monomer (BB‐apa) has been synthesized using 2,2‐bis(4‐hydroxyphenyl)butane, 3‐aminophenylacetylene, and paraformaldehyde. The structure of the monomer was characterized by FTIR spectroscopy and 1H NMR spectra, which indicated that the reactive oxazine ring and acetenyl groups existed in molecular structure of BB‐apa. The polymerization behavior was monitored by FTIR and non‐isothermal differential scanning calorimetry (DSC), which showed that the BB‐apa had completely cured with multiple polymerization mechanisms according to oxazine ring‐opening and ethynyl addition polymerization. The curing kinetics results revealed that the introduction of ethynyl groups can accelerate the ring‐opening polymerization of benzoxazine, leading to a lower curing temperature and apparent activation energy. Moreover, the thermoset derived from the BB‐apa exhibits higher thermal stability and lap shear strength (at 350 °C) with the glass transition temperature of 353 °C compared with the traditional benzoxazine polymer without ethynyl groups (BB‐a). © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44547.
“Frank” presentations as a novel research construct and element of diagnostic decision‐making in autism spectrum disorder
Authors: de Marchena Ashley , Miller Judith
Published: October 2016

Many individuals with ASD have a distinctive behavioral presentation that is recognizable within moments, a phenomenon we call “frank” ASD. This phenomenon has been discussed informally for decades, perhaps as “classic” ASD; however, there is no unitary “classic” presentation, and classic autism does not seem to correspond to level of functioning. Thus, neither “frank” nor “classic” autism has been delineated or studied as a research construct. To initiate the empirical study of frank ASD, we surveyed 151 clinicians, from a range of disciplines that diagnose ASD, about this phenomenon. Respondents completed a 13‐item questionnaire about frank ASD, which was analyzed using a mixed‐methods approach. Ninety‐seven percentage of respondents were familiar with the phenomenon. Respondents estimated that 40% of the ASD population has a frank presentation. Respondents reported the most highly specific behaviors associated with frank presentations were a general sense of impaired reciprocity, quality of eye contact, atypical vocal prosody, presence of motor mannerisms, and atypical gait or posture. In general, respondents reported detecting frank features rapidly, with the majority forming their impressions within the first ten minutes of interaction or observation. Although unstudied empirically, “frank” presentations of ASD are familiar to diagnosing clinicians, and appear to be based on behaviors both central to ASD diagnostic criteria (e.g., impaired reciprocity), and absent from diagnostic criteria (e.g., atypical gait or posture). We discuss these findings within the context of diagnostic decision‐making and behavioral phenotyping of ASD. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 653–662. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Effect of static magnetic field on pain level and expression of P2X3 receptors in the trigeminal ganglion in mice following experimental tooth movement
Authors: Zhu Yafen , Wang Shengguo , Long Hu , Zhu Jingyi , Jian Fan , Ye Niansong , Lai Wenli
Published: October 2016

Recent research has demonstrated that static magnetic fields (SMF) can generate an analgesic effect in different conditions. The present study explored effects of SMF on pain levels and expressions of P2X3 receptors in trigeminal ganglion (TG) in mice after experimental tooth movement (tooth movement induced by springs between teeth). Experiments were performed in male mice (body mass: 25–30 g) and divided into SMF + force group, force group, and no force group. Exposure time was over 22 h per day. Mouse Grimace Scale was used for evaluating orofacial pain levels during experimental tooth movement at 4 h and 1, 3, 7, and 14 days. Meanwhile, expression levels of P2X3 receptors in the TG were evaluated by immunohistochemistry and western blotting at same time points. We finally found that during experimental tooth movement, pain levels of mice peaked at 3 days, and then decreased. While pain levels of mice were reduced in the SMF environment at 4 h, 1 and 3 days, there was a significant difference at 1 and 3 days. Meanwhile, under the action of SMF, expression levels of P2X3 receptors in TG were significantly lower at 4 h, 3 and 7 days. These results suggest that SMF can reduce pain levels in mice, and down‐regulate P2X3 receptors in TG. Bioelectromagnetics. 38:22–30, 2017. © 2016 Wiley Periodicals, Inc.
Randomized clinical trial of sacral nerve stimulation for refractory constipation
Authors: Zerbib F , Siproudhis L , Lehur P-A , Germain C , Mion F , Leroi A-M , Coffin B , Le Sidaner A , Vitton V , Bouyssou-Cellier C , Chene G , Zerbib F , Simon M , Denost Q , Lepicard P , Lehur P-A , Meurette G , Wyart V , Kubis C , Mion F , Roman S , Damon H , Barth X , Leroi A-M , Bridoux V , Gourcerol G , Coffin B , Castel B , Gorbatchef C , Le Sidaner Anne , Mathonnet M , Vitton V , Lesavre N , Orsoni P , Siproudhis L , Brochard C , Desfourneaux V
Published: October 2016

Background

Open studies have reported favourable results for sacral nerve stimulation in the treatment of refractory constipation. Here, its efficacy was assessed in a double-blind crossover RCT.

Methods

Patients with at least two of the following criteria were included: fewer than three bowel movements per week; straining to evacuate on more than 25 per cent of attempts; or sensation of incomplete evacuation on more than 25 per cent of occasions. Response to therapy was defined as at least three bowel movements per week and/or more than 50 per cent improvement in symptoms. Responders to an initial 3-week peripheral nerve evaluation were offered permanent implantation of a pulse generator and were assigned randomly in a crossover design to two 8-week intervals of active or sham stimulation. At the end of the two trial periods, the patients received active stimulation until the final evaluation at 1 year.

Results

Thirty-six patients (34 women; mean(s.d.) age 45(14) years) underwent peripheral nerve evaluation. Twenty responded and received a permanent stimulator. A positive response was observed in 12 of 20 and 11 of 20 patients after active and sham stimulation periods respectively (P = 0·746). Pain related to the device occurred in five patients and wound infection or haematoma in three, leading to definitive removal of the pulse generator in two patients. At 1 year, 11 of the 20 patients with an implanted device continued to respond. Stimulation had no significant effect on colonic transit time.

Conclusion

These results do not support the recommendation of permanent implantation of a pulse generator in patients with refractory constipation who initially responded to temporary nerve stimulation. Registration number: NCT01629303 (http://www.clinicaltrials.gov).
Traumatic brain injury among female offenders in a prison population: results of the FleuryTBI study
Authors: Durand Eric , Watier Laurence , Lécu Anne , Fix Michel , Weiss Jean‐Jacques , Chevignard Mathilde , Pradat‐Diehl Pascale
Published: October 2016

Aim

The study was designed to estimate the prevalence of traumatic brain injury (TBI) in a French prison population of female offenders, study the variables known to be associated with TBI, and compare our results with those obtained among male offenders as described in a previous paper.

Participants

All female offenders (adults and juveniles) consecutively admitted to Fleury‐Mérogis prison over a 3‐month period were included in the study.

Method

During the admission procedure, female offenders were interviewed by healthcare staff using a self‐reported questionnaire.

Results

In all, 100 female offenders were included. The rate of self‐reported TBI was high, with a prevalence of 21%. The first cause of TBI was violence related (35%) and a majority of female offenders with a history of TBI reported having sustained more than one TBI. When compared with those who did not report a TBI, epilepsy and use of alcohol were higher among female offenders with a history of TBI. Perceived health was significantly worse for women who reported a TBI.

Conclusions

This study findings provide additional evidence that TBI among offender populations is serious and that specific actions need to be developed and implemented in correctional settings such as screening for TBI upon arrival.
Elevated cerebrospinal fluid uric acid during relapse of neuromyelitis optica spectrum disorders
Authors: Shu Yaqing , Li Haiyan , Zhang Lei , Wang Yuge , Long Youming , Li Rui , Qiu Wei , Lu Zhengqi , Hu Xueqiang , Peng Fuhua
Published: October 2016

Introduction

Previous studies have shown that serum uric acid (UA) modulates outcomes of neurological diseases, although little is known about cerebrospinal fluid (CSF) UA levels in neuromyelitis optica spectrum disorders (NMOSDs).

Methods

Cerebrospinal fluid and serum UA levels were measured in samples from 68 patients, including NMOSDs during relapse (n = 38) and controls with noninflammatory and non‐neurodegenerative diseases (CTLs, n = 30). Correlation analysis was performed between CSF UA and clinical characteristics, serum UA, and blood–brain barrier integrity in NMOSDs.

Results

Cerebrospinal fluid UA levels in NMOSDs were significantly higher than in CTLs (p = .002), while serum UA differences between NMOSDs and CTLs were not statistically significant. In NMOSDs, CSF UA levels were significantly higher in patients with an impaired blood–brain barrier than in patients with an intact one (p < .001), and significantly higher in longer disease duration than in shorter disease duration patients (p = .002). CSF UA levels were also significantly higher in active patients upon MRI than in inactive patients (p < .001), and significantly higher in patients with brain lesions than without brain lesions (p = .024). CSF UA was significantly associated with the serum UA levels (r = .454, p = .002), disease duration (r = .383, p = .018), and blood–brain barrier index (r = .805, p < .001), but did not correlate with age, gender, annualized relapse rate, duration, or severity of NMOSD. Multiple regression analysis demonstrated that CSF UA was independent of the blood–brain barrier index (β = .765, p < .001) and serum UA levels (β = .01, p = .019) in NMOSDs.

Conclusions

Cerebrospinal fluid UA levels were elevated in NMOSD patients during relapse, and were likely modified by serum UA levels and blood–brain barrier integrity.
NRG1 fusion in a French cohort of invasive mucinous lung adenocarcinoma
Authors: Duruisseaux Michaël , McLeer‐Florin Anne , Antoine Martine , Alavizadeh Sanaz , Poulot Virginie , Lacave Roger , Rabbe Nathalie , Cadranel Jacques , Wislez Marie
Published: October 2016

Invasive mucinous lung adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with no effective treatment option in advanced disease. KRAS mutations occur in 28–87% of the cases. NRG1 fusions were recently discovered in KRAS‐negative IMA cases and otherwise negative for known driver oncogenes and could represent an attractive therapeutic target. Published data suggest that NRG1 fusions occur essentially in nonsmoking Asian women. From an IMA cohort of 25 French patients of known ethnicity, driver oncogenes EGFR, KRAS, BRAF, ERBB2 mutations, and ALK and ROS1 rearrangements presence were analyzed. In the IMA samples remaining negative for these driver oncogenes, an NRG1 rearrangement detection was performed by FISH. A driver oncogene was identified in 14/25 IMA, namely 12 KRAS mutations (48%), one ROS1 rearrangement (4%), and one ALK rearrangement (4%). The detection of NRG1 rearrangement by FISH was conducted in the 11 pan‐negative IMA. One sample was NRG1FISH‐positive and 100% of the tumor nuclei analyzed were positive. This NRG1‐positive patient was a 61‐year‐old nonsmoking woman of Vietnamese ethnicity and was the sole patient of Asian ethnicity of the cohort. She died 6 months after the diagnosis with a pulmonary multifocal disease. NRG1FISH detection should be considered in patients with IMA pan‐negative for known driver oncogenes. These results might suggest that NRG1 fusion is more frequent in IMA from Asian patient. Larger studies are needed.
Epidermal growth factor receptor and notch signaling in non‐small‐cell lung cancer
Authors: Pancewicz‐Wojtkiewicz Joanna
Published: October 2016

Lung cancer is the most common reason of cancer deaths and about 85% of these are non‐small‐cell lung cancer. Currently, lung cancer therapy is mainly based on the tumor node metastasis (TNM) disease staging and tumor histological classification. Despite therapeutic innovations, the prognosis for lung cancer patients has not significantly changed in the last years. Therefore, a proper understanding of cell signaling pathways involved in cancer pathogenesis seems to be essential for improvement in cancer therapy field. The knowledge of crosstalk between epidermal growth factor receptor (EGFR) and Notch pathway can lead to enhanced screening for the expression of these genes allowing patients to optimize treatment options and predict potential treatment resistance. This review focuses on recent advances related to the mechanisms of EGFR and Notch signaling in non‐small‐cell lung cancer and the effectiveness of current Notch‐ and EGFR‐targeted therapies.
Developing a model of working with worry in emotion‐focused therapy: A discovery‐phase task analytic study
Authors: Murphy Jennifer , Rowell Lucy , McQuaid Anne , Timulak Ladislav , O'Flynn Rosie , McElvaney James
Published: October 2016

Background

Generalised anxiety disorder (GAD) is an anxiety disorder characterised by excessive anxiety and worry. Worry is seen as a key‐defining feature of GAD. Several cognitive‐behavioural models of working with worry in GAD exist. More recently, there have been efforts to adapt emotion‐focused therapy (EFT) for GAD. This study focused on task analysis, observing therapist and client processes (using qualitative observations as well as observer‐used measures) in the clinically developed, two‐chair dialogue for worry (an intervention inspired by a similar EFT task of working with self‐criticism in depression).

Method

A task analysis methodological approach was applied to 34 worry dialogues from eight clients. The worry dialogues were qualitatively analysed, focusing on therapist and client processes in the task and also using observer‐based measures such as Classification of Affective‐Meaning States, Client Emotion Arousal Scale and Client Emotion Productivity Scale.

Results

A tentative model of worry transformation using the two‐chair dialogue for worry is presented. The model consists of marker identification, enactment of the worry, deepening the toll of the worry, articulation of the need towards the worry and the worry softening or the client's standing up to the worry. The results also focus on the progression in the dialogues across the series of dialogues.

Implications

The model has an immediate practical application as it can inform therapists' actions when working with worry processes in GAD clients. Implications for future research are also discussed.
Biocidal Compounds from Mentha sp. Essential Oils and Their Structure–Activity Relationships
Authors: Kimbaris Athanasios C. , González‐Coloma Azucena , Andrés Maria Fe , Vidali Veroniki P. , Polissiou Moschos G. , Santana‐Méridas Omar
Published: October 2016

Essential oils from Greek Mentha species showed different chemical compositions for two populations of M. pulegium, characterized by piperitone and pulegone. Mentha spicata essential oil was characterized by endocyclic piperitenone epoxide, piperitone epoxide, and carvone. The bioactivities of these essential oils and their components have been tested against insect pests (Leptinotarsa decemlineata, Spodoptera littoralis and Myzus persicae), root‐knot nematodes (Meloydogine javanica) and plants (Lactuca sativa, Lolium perenne, Solanum lycopersicum). The structure–activity relationships of these compounds have been studied including semi‐synthetic endocyclic trans‐carvone epoxide, exocyclic carvone epoxide, a new exocyclic piperitenone epoxide and trans‐pulegone epoxide. Leptinotarsa decemlineata feeding was affected by piperitenone and piperitone epoxide. Spodoptera littoralis was affected by piperitone epoxide and pulegone. The strongest nematicidal agent was piperitenone epoxide, followed by piperitone epoxide, piperitenone and carvone. Germination of S. lycopersicum and L. perenne was significantly affected by piperitenone epoxide. This compound and carvone epoxide inhibited L. perenne root and leaf growth. Piperitenone epoxide also inhibited the root growth of S. lycopersicum. The presence of a C(1) epoxide resulted in strong antifeedant, nematicidal and phytotoxic compounds regardless of the C(4) substituent. New natural crop protectants could be developed through appropriate structural modifications in the p‐menthane skeleton.
Mosaic partial pericentromeric trisomy 8 and maternal uniparental disomy in a male patient with autism spectrum disorder
Authors: Ahram Dina F. , Stambouli Danae , Syrogianni Aleksandra , Al‐Sarraj Yasser , Gerou Spyridon , El‐Shanti Hatem , Kambouris Marios
Published: October 2016

Key Clinical Message

Various chromosomal anomalies including small supernumerary marker chromosome (sSMC) and Uniparental disomy (UPD) have been described in association with intellectual disability and autism spectrum disorder. Based on our reported findings, we recommend that patients with sSMC(8) be evaluated for autism spectrum disorder (ASD) for early institution of therapy. In the presence of an identifiable sSMC, exploration of UPD is also recommended to further investigate the role of chromosome 8 UPD in ASD.
Access to Isoquinolin‐1(2 H)‐ones and Pyridones by Cobalt‐Catalyzed Oxidative Annulation of Amides with Allenes
Authors: Boobalan Ramadoss , Kuppusamy Ramajayam , Santhoshkumar Rajagopal , Gandeepan Parthasarathy , Cheng Chien‐Hong
Published: October 2016

A cobalt‐catalyzed oxidative annulation of amides with allenes to provide isoquinolin‐1(2 H)‐ones and pyridones was explored. The new catalytic reaction proceeded through aminoquinoline‐directed C−H activation followed by unusual regioselective insertion, annulation, and isomerization. A variety of functionalized amides and allenes were converted into the corresponding products under mild reaction conditions.
Promotional Effects of Nanodiamond‐Derived Onion‐Like Carbons on the Electrocatalytic Properties of Pd‐MnO2 for the Oxidation of Glycerol in Alkaline Medium
Authors: Ejikeme Paul M. , Makgopa Katlego , Raju Kumar , Ozoemena Kenneth I.
Published: October 2016

The potential of onion‐like carbon (OLC) as an efficient alternative carbon support for palladium‐decorated manganese dioxide (Pd‐MnO2) catalyst for the electro‐oxidation of glycerol in alkaline medium is reported. Pd‐MnO2/OLC and Pd‐MnO2/C (where C denotes activated carbon or Vulcan carbon XC‐72) catalysts and their corresponding reference monometallic catalysts (Pd/OLC and Pd/C) are synthesized by a microwave‐assisted solvothermal procedure. Electrochemical measurements clearly prove that OLC, contrary to the state‐of‐the‐art Vulcan carbon XC‐72, is able to promote the electrocatalytic performance of Pd and Pd‐MnO2 towards the oxidation of glycerol in alkaline medium (in terms of decreased onset potential, large current density, and fast electron transport). Incredibly, the current density of the OLC‐based system is more than 150 % greater than their corresponding activated carbon‐based counterparts. These highly insightful results of Pd‐based catalyst are correlated with the synergistic effects of the ternary nanohybrid materials promoted by the unique intrinsic physico‐chemical properties of OLC.
Theory and Simulations for the Electron‐Transfer/Ion‐Transfer Mode of Scanning Electrochemical Microscopy in the Presence or Absence of Homogenous Kinetics
Authors: Oleinick Alexander , Yu Yun , Svir Irina , Mirkin Michael V. , Amatore Christian
Published: October 2016

The electron‐transfer/ion‐transfer (ET/IT) mode of scanning electrochemical microscopy (SECM) was developed recently and applied to studies of heterogeneous reactions at the substrate surface. The charged products or intermediates are detected by measuring the ion‐transfer current of the species across the liquid/liquid interface supported at the tip of a nanopipette. In this article, we develop the theory for this technique and explore its potential advantages and limitations. By using the COMSOL Multiphysics package, the approach curves were simulated for three commonly encountered experimental situations, that is, the surface‐generated ionic species is either chemically stable or participates in a first‐ or second‐order homogeneous reaction. The simulation results are generalized in the form of analytical approximations derived under limiting conditions.
Iridium‐Catalyzed Asymmetric Hydrogenation of Unfunctionalized Exocyclic C=C Bonds
Authors: Xia Jingzhao , Yang Guoqiang , Zhuge Ruijing , Liu Yangang , Zhang Wanbin
Published: October 2016

An iridium‐catalyzed asymmetric hydrogenation of unfunctionalized exocyclic C=C bonds was performed by using an axially flexible chiral phosphine–oxazoline ligand, providing the desired chiral 1‐benzyl‐2,3‐dihydro‐1H‐indene products with up to 98 % ee (enantiomeric excess). This represents the first general hydrogenation of unfunctionalized exocyclic olefins with high selectivity reported thus far. The additive acetate ion plays an important role in the reaction's high enantioselectivity. The chiral product can be further transformed into key intermediates required for the synthesis of an important insecticide and a drug compound.
Continuous bioproduction of 1,3‐propanediol from biodiesel raw glycerol: Operation with free and immobilized cells of Clostridium butyricum DSM 10702
Authors: Loureiro‐Pinto Marina , Coca Mónica , González‐Benito Gerardo , Lucas Susana , García‐Cubero M. Teresa
Published: October 2016

This work investigates the bioproduction of 1,3‐propanediol (1,3‐PD) from biodiesel derived raw glycerol with free and immobilized cells of Clostridium butyricum DSMZ 10702. The cultures were carried out under continuous conditions in a stirred tank bioreactor with suspended cells and a fluidized‐bed bioreactor with immobilized cells. The microorganisms were immobilized by entrapment in calcium alginate gel beads. The effect of dilution rate and glycerol concentration in the feed on 1,3‐PD production was investigated for both bioreactor configurations. Results showed that 1,3‐PD concentration and glycerol uptake decreased when dilution rate increased. Maximum product concentration was similar in both bioreactors, 24.3 g/L and 20.5 g/L for suspended cells and Ca‐alginate immobilized cells, respectively, for a glycerol feed concentration of 50 g/L and a dilution rate of 0.05 h−1. The higher productivities were observed for a dilution rate of 0.15 h−1 for the suspended culture bioreactor and 0.2 h−1 for the immobilized cell bioreactor. Although maximum productivity was similar in both systems, 2.8 g 1,3‐PD/(L · h), cell immobilization was shown to be more resistant to washout at higher dilution rates.
INF2‐ and FHOD‐related formins promote ovulation in the somatic gonad of C. elegans
Authors: Hegsted Anna , Wright Forrest A. , Votra SarahBeth , Pruyne David
Published: October 2016

Formins are regulators of actin filament dynamics. We demonstrate here that two formins, FHOD‐1 and EXC‐6, are important in the nematode Caenorhabditis elegans for ovulation, during which actomyosin contractions push a maturing oocyte from the gonad arm into a distensible bag‐like organ, the spermatheca. EXC‐6, a homolog of the disease‐associated mammalian formin INF2, is highly expressed in the spermatheca, where it localizes to cell‐cell junctions and to circumferential actin filament bundles. Loss of EXC‐6 does not noticeably affect the organization the actin filament bundles, and causes only a very modest increase in the population of junction‐associated actin filaments. Despite absence of a strong cytoskeletal phenotype, approximately half of ovulations in exc‐6 mutants exhibit extreme defects, including failure of the oocyte to enter the spermatheca, or breakage of the oocyte as the distal spermatheca entrance constricts during ovulation. Loss of FHOD‐1 alone has little effect, and we cannot detect FHOD‐1 in the spermatheca. However, combined loss of these formins in double fhod‐1;exc‐6 mutants results in profound ovulation defects, with significant slowing of the entry of oocytes into the spermatheca, and failure of nearly 80% of ovulations. We suggest that EXC‐6 plays a role directly in the spermatheca, perhaps by modulating the ability of the spermatheca wall to rapidly accommodate an incoming oocyte, while FHOD‐1 may play an indirect role relating to its known importance in the growth and function of the egg‐laying muscles. © 2016 The Authors. Cytoskeleton Published by Wiley Periodicals, Inc.
Heterogeneous cloudlet deployment and user‐cloudlet association toward cost effective fog computing
Authors: Yao Hong , Bai Changmin , Xiong Muzhou , Zeng Deze , Fu Zhangjie
Published: October 2016

Both mobile computing and cloud computing have experienced rapid development in recent years. Although centralized cloud computing exhibits abundant resources for computation‐intensive tasks, the unpredictable and unstable communication latency between the mobile users and the cloud makes it challenging to handle latency‐sensitive mobile computing tasks. To address this issue, fog computing recently was proposed by pushing the cloud computing to the network edge closer to the users. To realize such vision, we can augment existing access points in wireless networks with cloudlet servers for hosting various mobile computing tasks. In this paper, we investigate how to deploy the servers in a cost‐effective manner without violating the predetermined quality of service. In particular, we practically consider that the available cloudlet servers are heterogeneous, ie, with different cost and resource capacities. The problem is formulated into an integer linear programming form, and a low‐complexity heuristic algorithm is invented to address it. Extensive simulation studies validate the efficiency of our algorithm by it performs much close to the optimal solution.
Robust human detection and localization in security applications
Authors: Chowdhury Mozammel , Gao Junbin , Islam Rafiqul
Published: October 2016

Human detection and localization has attracted much attention in security applications because of the increasing demand of safety and security in different environments, including surveillance systems, secure access control, person recognition, border monitoring, preventing criminal acts, intrusion detection, alarm monitoring, and so on. This article proposes a robust approach for human detection and localization by analyzing and matching corresponding facial features extracted from video sequences. The proposed technique captures the video scenes using a stereo system consisting of two cameras: left and right cameras with similar intrinsic parameters. The system first tracks the human by detecting the face area from the video scenes using an efficient fuzzy face detection algorithm. To localize the human position, the depth information is computed from the extracted face images by using a robust stereo matching algorithm. A neural network is used to match the correspondence pixels between the left and the right face images. Experimental evaluation demonstrates the competence and robustness of the proposed method. The low computation time required for the detection and localization of human objects compared with other methods raises its suitability toward its use in real‐time applications. Copyright © 2016 John Wiley & Sons, Ltd.
Physiologically based pharmacokinetic modeling in regulatory decision‐making at the European Medicines Agency
Authors: Luzon E , Blake K , Cole S , Nordmark A , Versantvoort C , Berglund E Gil
Published: October 2016

Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision‐making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA.
Polymorphic Variation in TPMT Is the Principal Determinant of TPMT Phenotype: A Meta‐Analysis of Three Genome‐Wide Association Studies
Authors: Tamm R , Mägi R , Tremmel R , Winter S , Mihailov E , Smid A , Möricke A , Klein K , Schrappe M , Stanulla M , Houlston R , Weinshilboum R , Mlinarič Raščan Irena , Metspalu A , Milani L , Schwab M , Schaeffeler E
Published: October 2016

Thiopurine‐related hematotoxicity in pediatric acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases has been linked to genetically defined variability in thiopurine S‐methyltransferase (TPMT) activity. While gene testing of TPMT is being clinically implemented, it is unclear if additional genetic variation influences TPMT activity with consequences for thiopurine‐related toxicity. To examine this possibility, we performed a genome‐wide association study (GWAS) of red blood cell TPMT activity in 844 Estonian individuals and 245 pediatric ALL cases. Additionally, we correlated genome‐wide genotypes to human hepatic TPMT activity in 123 samples. Only genetic variants mapping to chromosome 6, including the TPMT gene region, were significantly associated with TPMT activity (P < 5.0 × 10‐8) in each of the three GWAS and a joint meta‐analysis of 1,212 cases (top hit P = 1.2 × 10‐72). This finding is consistent with TPMT genotype being the primary determinant of TPMT activity, reinforcing the rationale for genetic testing of TPMT alleles in routine clinical practice to individualize mercaptopurine dosage.
Circulating acetaminophen metabolites are toxicokinetic biomarkers of acute liver injury
Authors: Vliegenthart ADB , Kimmitt RA , Seymour JH , Homer NZ , Clarke JI , Eddleston M , Gray A , Wood DM , Dargan PI , Cooper JG , Antoine DJ , Webb DJ , Lewis SC , Bateman DN , Dear JW
Published: October 2016

Acetaminophen (paracetamol‐APAP) is the most common cause of drug‐induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP‐metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analyzed from discovery (n = 116) and validation (n = 150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP‐metabolites than those without ALI. Receiver operator curve (ROC) analysis demonstrated that at hospital presentation CYP‐metabolites were more sensitive/specific for ALI than alanine aminotransferase (ALT) activity and APAP concentration (optimal CYP‐metabolite receiver operating characteristic area under the curve (ROC‐AUC): 0.91 (95% confidence interval (CI) 0.83–0.98); ALT ROC‐AUC: 0.67 (0.50–0.84); APAP ROC‐AUC: 0.50 (0.33–0.67)). This enhanced sensitivity/specificity was replicated in the validation cohort. Circulating CYP‐metabolites stratify patients by risk of liver injury prior to starting NAC. With development, APAP metabolites have potential utility in stratified trials and for refinement of clinical decision‐making.
Cytology diagnosis of metastatic clear cell renal cell carcinoma, synchronous to pancreas, and metachronous to thyroid and contralateral adrenal: Report of a case and literature review
Authors: Bokhari Aqiba , Tiscornia‐Wasserman Patricia G.
Published: October 2016

Renal cell carcinoma metastases to pancreas, thyroid, and contralateral adrenal gland are decidedly uncommon. Clear cell renal cell carcinoma (CCRCC) is the most frequent subtype. Cytology diagnosis may be challenging. A 74‐year‐old male with remote history of vocal cord malignancy and hypertension presented with abdominal pain. Computed tomography (CT) revealed 8.4 cm left renal mass highly suspicious for renal cell carcinoma, a 1.8 cm mass within vessels near left adrenal and a 2.5 cm mass in pancreatic tail. Right pulmonary middle lobe showed two small nodules. Metastatic CCRCC was diagnosed on preoperative transgastric, endoscopic ultrasound guided fine‐needle aspiration cytology of pancreatic tail mass. Left radical nephrectomy and distal pancreatectomy and splenectomy confirmed CCRCC (pT3bNxM1), with metastases in adrenal and pancreatic tail. The 3p deletion identification in pancreatic tumor suggested CCRCC origin. Follow‐up positron emission tomography‐CT (PET‐CT) scan revealed left thyroid lower pole mass. Thyroid ultrasound showed three clustered 6 mm nodules in left mid pole. Ultrasound‐guided fine needle aspiration (US‐FNA) biopsies, 4‐month post‐nephrectomy, were consistent with metastatic renal cell carcinoma in lower, and atypia of undetermined significance in mid poles respectively. Left lobectomy and isthmus and pyramidal lobe resections confirmed metastatic renal cell carcinoma. One year post‐radical nephrectomy, contralateral adrenal lesion noted on PET‐CT was interpreted as metastatic CCRCC on CT‐guided core biopsy with touch imprints. Rapid on‐site evaluation was implemented, and immunoprofile typical of CCRCC substantiated cytomorphology at all three sites. Previously reported cases of renal cell carcinoma metastases to organs as in the described case are reviewed as well. Diagn. Cytopathol. 2017;45:161–167. © 2016 Wiley Periodicals, Inc.
Isomeric discrimination of synthetic cannabinoids by GC‐EI‐MS: 1‐adamantyl and 2‐adamantyl isomers of N‐adamantyl carboxamides
Authors: Asada Akiko , Doi Takahiro , Tagami Takaomi , Takeda Akihiro , Sawabe Yoshiyuki
Published: October 2016

N‐(1‐adamantyl)‐1‐pentyl‐1H‐indazole‐3‐carboxamide (APINACA) and N‐(1‐adamantyl)‐1‐pentyl‐1H‐indole‐3‐carboxamide (APICA) are carboxamide‐type synthetic cannabinoids comprising indazole/indole‐3‐carboxylic acid and adamantan‐1‐amine moieties. However, in the case of compounds like APINACA or APICA, adamantyl positional isomers exist, wherein either adamantan‐1‐amine or adamantan‐2‐amine is present. These adamantyl positional isomers have not been reported in previous studies, and no analytical data are available. To avoid misidentification of adamantyl carboxamide‐type synthetic cannabinoids, it is important to develop methods to discriminate these adamantyl positional isomers. In this study, we report the analytical characterization by gas chromatography‐electron ionization‐mass spectrometry (GC‐EI‐MS). For providing analytical standards, we synthesized eight carboxamide‐type synthetic cannabinoids (APINACA 2‐adamantyl isomer, APICA 2‐adamantyl isomer, 5 F‐APINACA 2‐adamantyl isomer, 5 F‐APICA 2‐adamantyl isomer, 5Cl‐APINACA, 5Cl‐APINACA 2‐adamantyl isomer, adamantyl‐THPINACA, 2‐adamantyl‐THPINACA) and purchased four 1‐adamantyl derivatives (APINACA, APICA, 5 F‐APINACA, 5 F‐APICA). Although the retention times of the isomers are similar, 1‐adamantyl carboxamides can be clearly discriminated from their 2‐adamantyl isomers based on their different fragmentation patterns in the EI‐MS spectra. Specifically, EI‐MS spectra for adamantylindazole carboxamides showed remarkable differences between the 1‐adamantyl and 2‐adamantyl isomers. On the other hand, EI‐MS spectra for adamantylindole carboxamides were similar, but the diagnostic ions of the 2‐adamantyl isomers were observed. The method described herein was applicable to all compounds tested in this study and is expected to be of use for isomeric differentiation between other untested adamantyl carboxamide‐type synthetic cannabinoids. Copyright © 2016 John Wiley & Sons, Ltd.
Brazil's worst mining disaster: Corporations must be compelled to pay the actual environmental costs
Authors: Garcia Letícia Couto , Ribeiro Danilo Bandini , de Oliveira Roque Fabio , Ochoa‐Quintero Jose Manuel , Laurance William F.
Published: October 2016

In November 2015, a large mine‐tailing dam owned by Samarco Corporation collapsed in Brazil, generating a massive wave of toxic mud that spread down the Doce River, killing 20 people and affecting biodiversity across hundreds of kilometers of river, riparian lands, and Atlantic coast. Besides the disaster's serious human and socioeconomic tolls, we estimate the regional loss of environmental services to be ~US$521 million per year. Although our estimate is conservative, it is still six times higher than the fine imposed on Samarco by Brazilian environmental authorities. To reduce such disparities between estimated damages and levied fines, we advocate for an environmental bond policy that considers potential risks and environmental services that could possibly be impacted by irresponsible mining activity. Environmental bonds and insurance are commonly used policy instruments in many countries, but there are no clear environmental bond policies in Brazil. Environmental bonds are likely to be more effective at securing environmental restitution than post‐disaster fines, which generally are inadequate and often unpaid. We estimate that at least 126 mining dams in Brazil are vulnerable to failure in the forthcoming years. Any such event could have severe social‐environmental consequences, underscoring the need for effective disaster‐management strategies for large‐scale mining operations.
Cropping history trumps fallow duration in long‐term soil and vegetation dynamics of shifting cultivation systems
Authors: Wood Sylvia L. R. , Rhemtulla Jeanine M. , Coomes Oliver T.
Published: October 2016

In the study of shifting cultivation systems, fallow duration is seen as the key determinant of vegetation and soil dynamics: long fallows renew soil fertility, biomass, and biodiversity. However, long fallow systems are increasingly replaced around the world with short–medium fallow systems, and awareness is growing of the need to look across multiple (not just single) crop‐fallow cycles to accurately understand observed soil and vegetation patterns. In a study from Peru that builds on 50+ years of field‐level land‐use histories, we found that, over multiple crop–fallow cycles, farmers' cropping practices mattered more than fallow duration for biodiversity and soil fertility. After initial clearing of primary forest, a precipitous decline occurred in tree species richness of fallows (>50%) with gradual but continued loss thereafter (~0.5 species/yr), which resulted in shifts in species composition over time. For soils, the decline in fertility was more gradual with each additional cycle of cropping resulting in lowered soil organic matter, available phosphorus, and exchangeable sodium levels, even in fields with long fallow durations. In the most intensively used sites, soils experienced a 16% decline of soil organic matter over 4+ cycles. In contrast to previous studies, biomass accumulation and carbon stocks were not related to cropping history or to the number and duration of cycles observed. This suggests that biodiversity–soils–biomass dynamics may not necessarily “move together” in these systems. These results point to the importance of the number of crop–fallow cycles over fallow duration in driving soil fertility and vegetation dynamics under shifting cultivation in the Peruvian Amazon. Overtime shifting cultivation may erode soil fertility and biodiversity levels even if long fallows persist. As the decline in soils appears slow, it may be possible to address this effect with the use of amendments, however biodiversity declines and species compositional changes may be much harder to reverse.