bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial solitary chondrosarcoma resulting from germline EXT2 mutation
Authors: Heddar Abdelkader , Fermey Pierre , Coutant Sophie , Angot Emilie , Sabourin Jean‐Christophe , Michelin Paul , Parodi Nathalie , Charbonnier Françoise , Vezain Myriam , Bougeard Gaëlle , Baert‐Desurmont Stéphanie , Frébourg Thierry , Tournier Isabelle
Published: September 2016

Germline mutations of EXT2, encoding Exostosin Glycosyltransferase 2, are associated with multiple osteochondromas (MO), an autosomal dominant disease characterized by the development of multiple peripheral cartilaginous benign tumors with a weak risk of malignant transformation. We report here a family with a remarkable clinical presentation characterized by the development of isolated chondrosarcomas, mostly located in ribs. Comparative analysis of exomes from two third‐degree affected relatives led us to identify a single common disruptive variation, corresponding to a stop mutation (c.237G > A, p.Trp79*; (NM_000401.3); c.138G > A, p.Trp46*; (NM_207122.1)) within exon 2 of the EXT2 gene. Interestingly, no obvious sign of MO was detected in affected members by radiological examination. This report shows that germline mutations of EXT2 can result, not only in the development of multiple benign osteochondromas, but also in the development of isolated malignant cartilaginous tumors including central tumors, and that the presence of germline EXT2 mutation should be considered in patients suspected to have an inherited predisposition to chondrosarcoma, even in the absence of MO. © 2016 Wiley Periodicals, Inc.
Serum free immunoglobulin light chain fingerprint identifies a subset of newly diagnosed multiple myeloma patients with worse outcome
Authors: Avivi Irit , Cohen Yael C. , Joffe Erel , Benyamini Noam , Held‐Kuznetsov Viki , Trestman Svetlana , Terpos Evangelos , Dimopoulos Meletios A. , Kastritis Efstathios
Published: September 2016

Multiple myeloma (MM) is a multi–subclonal malignancy with relatively high heterogeneity. Patients who initially presented with both monoclonal‐protein (MP) and free light chain (FLC) secretion but then relapsed with a light chain escape pattern have been shown to reflect disease clonal evolution and to bare a worse prognosis. We hypothesized that a discordant MP/FLC pattern at diagnosis may reflect a similar clonal evolution that had occurred prior to diagnosis of active myeloma, conferring a worse outcome. We analyzed 255 consecutive newly diagnosed MM patients who received first line bortezomib‐based therapy between 2007 and 2014, hypothesizing that their MP/FLC fingerprint at diagnosis reflects clonal heterogeneity and, therefore, affects outcome. An involved FLC level ≥ 700 mg/L and MP ≥ 2.5 g/L were used as cutoffs for low vs high FLC and MP levels, respectively. Patients were divided into 4 subgroups according to their involved FLC and MP blood levels at diagnosis: HiLC and HiMP for patients with either a predominant FLC or a predominant MP, respectively, and HiLC‐MP and LoLC‐MP when both FLC and MP were increased or decreased, respectively. There were 68 (27%) patients with HiLC, which presented more often with International Staging System‐3 stage (P < .0001). Multivariate analysis showed that HiLC was associated with a 5.1‐fold risk for mortality in a multivariate model (95% confidence interval [CI], 1.34‐19.68). Both HiLC and HiLC‐MP phenotypes were associated with shorter progression‐free survival (hazard ratio of 2.66 [95% CI, 1.33‐5.32] and 2.82 [95% CI, 1.37‐5.83], respectively), independently of other prognostic factors, including the use of autograft. Thus, we identified an LC predominant secretory fingerprint (HiLC phenotype) at diagnosis as a potential independent risk factor that may affect disease control and survival in newly diagnosed MM patients treated with bortezomib‐based induction therapy; this may represent increased subclonal heterogeneity.
Agricultural land management options after the Chernobyl and Fukushima accidents: The articulation of science, technology, and society
Authors: Vandenhove Hildegarde , Turcanu Catrinel
Published: September 2016

The options adopted for recovery of agricultural land after the Chernobyl and Fukushima accidents are compared by examining their technical and socio-economic aspects. The analysis highlights commonalities such as the implementation of tillage and other types of countermeasures and differences in approach, such as preferences for topsoil removal in Fukushima and the application of K fertilizers in Chernobyl. This analysis shows that the recovery approach needs to be context-specific to best suit the physical, social, and political environment. The complex nature of the decision problem calls for a formal process for engaging stakeholders and the development of adequate decision support tools. Integr Environ Assess Manag 2016;12:662–666. © 2016 SETAC
The importance of early investigation and publishing in an emergent health and environment crisis
Authors: Murase Kaori
Published: September 2016

To minimize the damage resulting from a long-term environmental disaster such as the 2011 Fukushima nuclear accident in Japan, early disclosure of research data by scientists and prompt decision making by government authorities are required in place of careful, time-consuming research and deliberation about the consequences and cause of the accident. A Bayesian approach with flexible statistical modeling helps scientists and encourages government authorities to make decisions based on environmental data available in the early stages of a disaster. It is evident from Fukushima and similar accidents that classical research methods involving statistical methodologies that require rigorous experimental design and complex data sets are too cumbersome and delay important actions that may be critical in the early stages of an environmental disaster. Integr Environ Assess Manag 2016;12:680–682. © 2016 SETAC.
The need to integrate laboratory- and ecosystem-level research for assessment of the ecological impact of radiation
Authors: Bréchignac François
Published: September 2016

Despite the fact that the Chernobyl and Fukushima accidents have both stimulated research on the environmental impact of radiation, interpretations about the occurrence of ecological effects in the contaminated areas still do not converge. In an effort to improve the situation and progress toward better general scientific understanding of ecological impacts of radiation, reasons that may explain the disagreements and discrepancies are explored. The divergence in interpretations of the impacts from both nuclear accidents arises from differences in methodological and conceptual inference strategies (a cultural issue) more so than fundamental differences in the processes governing ecological harm. Improved integration of scientific communities that use different study approaches should be encouraged to better understand and monitor the determination of the ecological impacts of radiation. Integr Environ Assess Manag 2016;12:673–676. © 2016 SETAC.
Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study
Authors: Brunner Clair , Davies Neil M. , Martin Richard M. , Eeles Rosalind , Easton Doug , Kote‐Jarai Zsofia , Al Olama Ali Amin , Benlloch Sara , Muir Kenneth , Giles Graham , Wiklund Fredrik , Gronberg Henrik , Haiman Christopher A. , Schleutker Johanna , Nordestgaard Børge G. , Travis Ruth C. , Neal David , Donovan Jenny , Hamdy Freddie C. , Pashayan Nora , Khaw Kay‐Tee , Stanford Janet L. , Blot William J. , Thibodeau Stephen , Maier Christiane , Kibel Adam S. , Cybulski Cezary , Cannon‐Albright Lisa , Brenner Hermann , Park Jong , Kaneva Radka , Batra Jyotsna , Teixeira Manuel R. , Pandha Hardev ,   the PRACTICAL Consortium,, Zuccolo Luisa
Published: September 2016

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.
Linear Programming Application for Irrigation Network Management–Implementation in the Irrigation Network Region of Pinios (Central Greece)
Authors: Sakellariou‐Makrantonaki M. , Tzimopoulos C. , Giouvanis V.
Published: September 2016

The purpose of this study is to find the optimal economical organization of agricultural production, by minimizing the use of available water resources. This purpose can be achieved by combining operational research and hydrology for the development of the appropriate methodology. For the study, the area of the Local Organization for Land Reclamation (LOLR) of Pinios was chosen, as this is a representative part of the plain of Thessaly and the findings could contribute to the total gross value of production in the region (central Greece). The method of linear programming was used for the optimization of agricultural production. The first results obtained within the predefined constraints led us to crop restructuring, while economic profit was increased by 41.7% and water saving reached 4.2%. Copyright © 2016 John Wiley & Sons, Ltd.
Toxic effects of 4‐methylthio‐3‐butenyl isothiocyanate (Raphasatin) in the rat urinary bladder without genotoxicity
Authors: Suzuki Isamu , Cho Young‐Man , Hirata Tadashi , Toyoda Takeshi , Akagi Jun‐ichi , Nakamura Yasushi , Sasaki Azusa , Nakamura Takako , Okamoto Shigehisa , Shirota Koji , Suetome Noboru , Nishikawa Akiyoshi , Ogawa Kumiko
Published: September 2016

We recently reported that 4‐methylthio‐3‐butenyl isothiocyanate (MTBITC) exerts chemopreventive effects on the rat esophageal carcinogenesis model at a low dose of 80 ppm in a diet. In contrast, some isothiocyanates (ITCs) have been reported to cause toxic effects, promotion activity, and/or carcinogenic potential in the urinary bladder of rats. In the present study, we investigated whether MTBITC had toxic effects in the urinary bladder similar to other ITCs, such as phenethyl ITC (PEITC). First, to examine the early toxicity of MTBITC, rats were fed a diet supplemented with 100, 300 or 1000 ppm MTBITC for 14 days. Treatment with 1000 ppm MTBITC caused increased organ weights and histopathological changes in the urinary bladder, producing lesions similar to those of 1000 ppm PEITC. In contrast, rats treated with 100 or 300 ppm MTBITC showed no signs of toxicity. Additionally, we performed in vivo genotoxicity studies to clarify whether MTBITC may exhibit a carcinogenic potential through a genotoxic mechanism in rats. Rats were treated with MTBITC for 3 days at doses of 10, 30 or 90 mg kg−1 body weight by gavage, and comet assays in the urinary bladder and micronucleus assays in the bone marrow were performed. No genotoxic changes were observed after treatment with MTBITC at all doses. Overall, these results suggested that the effects of MTBITC in the rat urinary bladder are less than those of PEITC, but that MTBITC could have toxic effects through a nongenotoxic mechanism in the urinary bladder of rats at high doses. Copyright © 2016 John Wiley & Sons, Ltd.
Hydrotreating and hydrothermal treatment of alkaline lignin as technological valorization options for future biorefinery concepts: a review
Authors: Rutten Cathelijne , Ramírez Andrea , Posada Duque John
Published: September 2016

Lignin has the potential to be a sustainable resource for producing biobased chemicals (e.g. phenols, aromatic hydrocarbons, vanillin) for multiple applications. However, given its heterogeneous and rigid structure, its efficient conversion to value‐added products remains one of the most important limiting factors for the successful viability of the biobased economy. Hydrotreating and hydrothermal treatment (including liquefaction, gasification and wet oxidation) are promising technologies that can convert lignin into biobased products. This review article provides a literature overview of how key process parameters of hydrotreating and hydrothermal treatment (operating conditions, catalysts, solvents, type of starting lignin) may influence the conversion of alkaline lignin into valuable chemical products. It was observed that low selectivity to products (and subsequent required separation and purification) and char formation are the main hurdles for effective conversion of alkaline lignin. However, experimental work in alternative catalytic systems, solvents and hydrogen sources has shown that promising opportunities exist to overcome these drawbacks. Certain catalysts (e.g. Ru/Al2O3) have been found to improve selectivity and the use of alcohol solvents (especially methanol or ethanol) as a hydrogen source has been found to improve product yields and reduce char formation at lower working temperatures and pressures. © 2016 Society of Chemical Industry
An Alternate Synthesis of 6H‐Indolo[2,3‐b]quinoline via One‐Pot Alkylation–Dehydration–Cyclization–Aromatization Approach
Authors: Kadam Hari K. , Tilve Santosh G.
Published: September 2016

A simple, straightforward and efficient synthesis of 6H‐indolo[2,3‐b]quinoline, a natural product isolated from leaves of Justicia betonica, is achieved through a pivalic acid‐assisted one‐pot alkylation–dehydration–cyclization–aromatization approach. This synthesis constitutes a formal approach toward a biologically important alkaloid neocryptolepine.
Highly Efficient One‐Pot Three Component Synthesis of 2H‐Indazoles by Consecutive Condensation, C–N and N–N Bond Formations Using Cu/Aminoclay/Reduced Graphene Oxide Nanohybrid
Authors: Behrouz Somayeh
Published: September 2016

A simple and straightforward one‐pot three‐component synthesis of 2H‐indazoles through copper‐catalyzed consecutive condensation, C–N and N–N bond formations of easily accessible starting materials under ligand‐free conditions is described. In this protocol, treatment of substituted 2‐bromobenzaldehydes, structurally diverse amines, and [bmim]N3 in the presence of Cu/aminoclay/reduced graphene oxide nanohybrid (Cu/AC/r‐GO nanohybrid) as an efficient heterogeneous catalyst affords the corresponding 2H‐indazoles in good to excellent yields. The influence of effective parameters on the efficient progress of the reaction was studied. The Cu/AC/r‐GO nanohybrid is a stable and inexpensive catalyst that could be simply prepared, recovered, and reused for several reaction runs with no significant decrease in its reactivity.
Oximetric angiosome imaging in diabetic feet
Authors: Zheng Jie , Muccigrosso David , Zhang Xiaodong , An Hongyu , Coggan Andrew R. , Adil Bashir , Hildebolt Charles F. , Vemuri Chandu , Geraghty Patrick , Hastings Mary K. , Mueller Michael J.
Published: September 2016

Purpose

To develop a noncontrast oximetric angiosome imaging approach to assess skeletal muscle oxygenation in diabetic feet.

Materials and Methods

In four healthy and five subjects with diabetes, the feasibility of foot oximetry was examined using a 3T clinical magnetic resonance imaging (MRI) scanner. The subjects' feet were scanned at rest and during a toe‐flexion isometric exercise. The oxygen extraction fraction of skeletal muscle was measured using a susceptibility‐based MRI method. Our newly developed MR foot oximetric angiosome model was compared with the traditional angiosome model in the assessment of the distribution of oxygen extraction fraction.

Results

Using the traditional angiosome during the toe‐flexion exercise, the oxygen extraction fraction in the medial foot of healthy subjects increased (4.9 ± 3%) and decreased (–2.7 ± 4.4%) in subjects with diabetes (difference = 7.6%; 95% confidence interval = –13.7 ± 1.4; P = 0.02). Using the oximetric angiosome, the percent difference in the areas of oxygen extraction fraction within the 0.7–1.0 range (expected oxygen extraction fraction during exercise) between rest and exercise was higher in healthy subjects (8 ± 4%) than in subjects with diabetes (4 ± 4%; P = 0.02).

Conclusion

This study demonstrates the feasibility of measuring skeletal muscle oxygen extraction fraction in the foot muscle during a toe‐flexion isometric exercise. Instead of assessing oxygen extraction fraction in a foot muscle region linked to a supplying artery (traditional angiosome), the foot oximetric angiosome model assesses oxygen extraction fraction by its different levels in all foot muscle regions and thus may be more appropriate for assessing local ischemia in ulcerated diabetic feet. J. Magn. Reson. Imaging 2016. J. MAGN. RESON. IMAGING 2016;44:1–1.
Hormesis, cellular stress response, and redox homeostasis in autism spectrum disorders
Authors: Calabrese V. , Giordano J. , Ruggieri M. , Berritta D. , Trovato A. , Ontario M.L. , Bianchini R. , Calabrese E.J.
Published: September 2016

In the United States, 1.1–1.5% of children have been diagnosed with autism spectrum disorders (ASD), corresponding to a 30% increase in incidence and prevalence. Social and communication impairments are the main signs and symptoms of ASD, and currently available medications have been ineffective in reducing these core deficits. Observational studies have indicated that children with ASD tend to show improved cognition and behavior after febrile illness, which is associated with alteration of metabolic pathways, leading to cellular stress responses and increased expression of heat shock proteins (Hsps). Sulforaphane and hydroxytyrosol, phytochemicals derived from cruciferous vegetables and extra virgin olive oil, respectively, can induce metabolic effects in cellular stress responses that are similar to those produced by fever. Thus, modulation of endogenous cellular defense mechanisms may be an innovative approach for therapeutic intervention in ASD and other disorders associated with neuroinflammation and neurodegeneration. This Review introduces the hormetic dose–response concept and presents possible mechanisms and applications for neuroprotection. We address the emerging role of Hsps in the neuroprotective network of redox stress‐responsive mechanisms and propose the potential therapeutic utility of the nutritional antioxidants sulforaphane and hydroxytyrosol against particular signs and symptoms of ASD. We argue that such research findings must be approached with pragmatism and prudence. It is vital to capitalize on recent and ongoing investments in brain science research and to refine neuroscientific knowledge and capability for more accurate diagnosis and safe, effective, and ethically sound treatment of ASD and other neuropsychiatric spectrum disorders. © 2016 Wiley Periodicals, Inc.
A nomogram predicting contralateral central neck lymph node metastasis for papillary thyroid carcinoma
Authors: Hei Hu , Song Yongping , Qin Jianwu
Published: September 2016

Background and Objectives

Central compartment neck dissection (CCND) is recommended for patients with papillary thyroid carcinoma (PTC). However, whether to perform contralateral CCND remains unclear. An individualized estimation of the contralateral central neck metastasis (CNM) risk would assist in the tailoring of treatment for PTC patients.

Methods

Consecutive patients who underwent bilateral CCND for unilateral PTC between 2012 and 2014 in a tertiary center were identified. The clinicopathological data of 142 patients were analyzed retrospectively. The variables that had clinical significance in the final multivariate logistic regression model were built into a nomogram to assess the risk of metastasis of the contralateral central compartment. This model was internally validated using bootstrap resampling.

Results

This nomogram demonstrated good calibration and discrimination, with a concordance index of 0.834 (bootstrap corrected, 0.824). The variables with the greatest influence on the risk of contralateral CNM in this model included tumor size, the number of positive lymph nodes, and extranodal extension in the ipsilateral central neck.

Conclusions

This nomogram integrates three variables to estimate an individualized risk of contralateral CNM in unilateral PTC patients. This model may assist in individual decision‐making regarding contralateral CCND and help avoid the over‐ and under‐treatment of PTC. J. Surg. Oncol. 2016;114:703–707. © 2016 Wiley Periodicals, Inc.
Surgical excision margin for primary acral melanoma
Authors: Lee Kyeong‐Tae , Kim Eun‐Ji , Lee Dong‐Youn , Kim Jung‐Han , Jang Kee‐Taek , Mun Goo‐Hyun
Published: September 2016

Background and Objectives

This study aimed to evaluate treatment outcomes of acral melanoma (AM) based on the excision margin.

Methods

A retrospective cohort study was conducted for patients with primary AM, analyzing recurrence rates, local and in‐transit recurrence‐free survival (LITRFS), disease‐free survival (DFS), and melanoma‐specific survival (MSS).

Results

Data from 129 patients of AM were analyzed. In 53 patients with thin AM (thickness ≤1 mm), neither recurrence nor mortality occurred regardless of whether the excision margin was >1 cm or not. Seventy‐six patients had thick AM (thickness >1 mm), including 36 treated with a <2 cm excision margin and 40 with a 2 cm margin. Multivariate analyses revealed that a 2 cm margin was associated with a reduced rate of local recurrence (HR, 0.120; P‐value = 0.023) and LITR (HR, 0.187; P‐value = 0.013) compared with a <2 cm margin. DFS and MSS did not differ between the two groups.

Conclusions

Thin AM were successfully treated with a 1 cm excision margin. For thick AM, a 2 cm excision margin provided improved local control, compared with a <2 cm margin; however, this benefit did not translate into a survival gain. J. Surg. Oncol. 2016;114:933–939. © 2016 Wiley Periodicals, Inc.
Vascular territories of the medial upper arm—an anatomic study of the vascular basis for individualized flap design
Authors: Tinhofer Ines E. , Tzou Chieh Han , Duscher Dominik , Pollhammer Michael S. , Weninger Wolfgang J. , Huemer Georg M. , Schmidt Manfred
Published: September 2016

Background

Fasciocutaneous flaps supplied by discrete perforator arteries can be raised in numerous parts of the human body and are routinely used in plastic surgery. The aim of this anatomical investigation was to provide a description of the vascular supply of the medial upper arm, to localize and measure the perforator arteries and to define potential perforator flap dimensions in pendency of individual anatomical conditions.

Material and Methods

A total of 20 upper limbs from 11 fresh cadavers were examined. The brachial arteries were exposed and the medial perforator arteries selectively injected with methylene blue and india ink in an alternating sequence. The size of the angiosomes, the diameter and length of the perforators' pedicles and distances between the arteries and the medial epicondyle and apex of the axilla respectively were measured.

Results

On average, 4.55 ± 1.47 perforating arteries arose from the brachial artery and it's medial off branching arteries. Their mean diameter was 0.68 ± 0.27 mm and their pedicles had an average length of 3.62 ± 1.61 cm measured from suprafascial until arborisation. In 80% the first proximal perforator was present in an area of 4 cm radius at centre coordinates of (20/2). A constant distal perforator was found within a circle of 3 cm radius, of which the centre had the coordinates (8/1). The average size of the angiosomes was 121.1 ± 58.5 cm2. Direct branches of the brachial artery feed circular shaped vascular territories, whereas superior ulnar collateral arteries (SUCAs) feed oblong shaped territories.

Conclusion

This anatomical study provides valuable data of the medial arm flap in order to be applied clinically. © 2016 Wiley Periodicals, Inc.
Scoring of de novo Designed Chemical Entities by Macromolecular Target Prediction
Authors: Button Alexander L. , Hiss Jan A. , Schneider Petra , Schneider Gisbert
Published: September 2016

Computational de novo molecular design and macromolecular target prediction have become routine in applied cheminformatics. In this study, we have generated populations of drug template‐derived designs using ligand‐based building block assembly, and predicted their potential targets. The results of our analysis show that the reaction‐based de novo design generated new chemical entities with similar properties and pharmacophores as that of the template drugs as well as up to 44 % of the de novo compounds receiving the correct target predictions. Keeping in mind the probabilistic nature of the methods, such a combination of fast and meaningful computational structure generation by reaction‐based design and product scoring by target class prediction may be appropriate for prospective application in medicinal chemistry.
Human‐ and computer‐accessible 2D correlation data for a more reliable structure determination of organic compounds. Future roles of researchers, software developers, spectrometer managers, journal editors, reviewers, publisher and database managers toward artificial‐intelligence analysis of NMR spectra
Authors: Jeannerat Damien
Published: September 2016

The introduction of a universal data format to report the correlation data of 2D NMR spectra such as COSY, HSQC and HMBC spectra will have a large impact on the reliability of structure determination of small organic molecules. These lists of assigned cross peaks will bridge signals found in NMR 1D and 2D spectra and the assigned chemical structure. The record could be very compact, human and computer readable so that it can be included in the supplementary material of publications and easily transferred into databases of scientific literature and chemical compounds. The records will allow authors, reviewers and future users to test the consistency and, in favorable situations, the uniqueness of the assignment of the correlation data to the associated chemical structures. Ideally, the data format of the correlation data should include direct links to the NMR spectra to make it possible to validate their reliability and allow direct comparison of spectra. In order to take the full benefits of their potential, the correlation data and the NMR spectra should therefore follow any manuscript in the review process and be stored in open‐access database after publication. Keeping all NMR spectra, correlation data and assigned structures together at all time will allow the future development of validation tools increasing the reliability of past and future NMR data. This will facilitate the development of artificial intelligence analysis of NMR spectra by providing a source of data than can be used efficiently because they have been validated or can be validated by future users. Copyright © 2016 John Wiley & Sons, Ltd.
In Situ Use of Aqueous RAFT Prepared Poly(2‐(diethylamino)ethyl methacrylate) as a Stabilizer for Preparation of CO2 Switchable Latexes
Authors: Shirin‐Abadi Abbas Rezaee , Jessop Philip G. , Cunningham Michael F.
Published: September 2016

Poly(2‐(diethylamino)ethyl methacrylate) (PDEAEMA) macroinitiator is prepared in water by aqueous reversible addition–fragmentation chain transfer (RAFT) polymerization under CO2 atmosphere, and then used directly as a stabilizer in emulsion polymerization, without requiring further purification, to yield CO2‐switchable latexes of poly(methyl methacrylate) (PMMA) and polystyrene (PS). Chain extension of the PDEAEMA macroinitiator with styrene (S) leads to the in situ formation of poly(DEAEMA‐b‐S) diblock copolymers in a one‐pot process. The final latexes are pH and CO2‐responsive and can be coagulated by N2 bubbling and subsequently redispersed by CO2 bubbling. The effects of various parameters on the latex properties are investigated, including pH, concentration of macro‐RAFT agent, using MMA as comonomer and initiator concentration. The results show that replacing only 5 mol% MMA in emulsion polymerization of styrene eliminates the induction time and also has a significant influence on the particle size distribution.

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Leptin, acylcarnitine metabolites and development of adiposity in the Rhea mother–child cohort in Crete, Greece
Authors: Perng W. , Oken E. , Roumeliotaki T. , Sood D. , Siskos A. P. , Chalkiadaki G. , Dermitzaki E. , Vafeiadi M. , Kyrtopoulos S. , Kogevinas M. , Keun H. C. , Chatzi L.
Published: September 2016

Objective

This study aims to investigate relations of serum leptin at age 4 with development of adiposity and linear growth during 3 years of follow‐up among 75 Greek children and to identify serum metabolites associated with leptin at age 4 and to characterize their associations with adiposity gain and linear growth.

Methods

Linear regression models that accounted for maternal age, education and gestational weight gain and child's age and sex were used to examine associations of leptin and leptin‐associated metabolites measured at age 4 with indicators of adiposity and linear growth at age 7.

Results

Each 1‐unit increment in natural log‐(ln)‐transformed leptin corresponded with 0.33 (95% CI: 0.10, 0.55) units greater body mass index‐for‐age z‐score gain during follow‐up. Likewise, higher levels of the leptin‐associated metabolites methylmalonyl‐carnitine and glutaconyl‐carnitine corresponded with 0.14 (95% CI: 0.01, 0.27) and 0.07 (95% CI: −0.01, 0.16) units higher body mass index‐for‐age z‐score gain, respectively. These relationships did not differ by sex or baseline weight status and were independent of linear growth.

Conclusions

These findings suggest that leptin, methylmalonyl‐carnitine and possibly glutaconyl‐carnitine are associated with weight gain during early childhood. Future studies are warranted to confirm these findings in other populations.
Selective and sensitive quantification of the cytochrome P450 3A4 protein in human liver homogenates through multiple reaction monitoring mass spectrometry
Authors: Cieślak Anna , Kelly Isabelle , Trottier Jocelyn , Verreault Mélanie , Wunsch Ewa , Milkiewicz Piotr , Poirier Guy , Droit Arnaud , Barbier Olivier
Published: September 2016

This study aimed at establishing a sensitive multiple reaction monitoring‐mass spectrometry (MRM‐MS) method for the quantification of the drug metabolizing cytochrome P450 (CYP)3A4 enzyme in human liver homogenates. Liver samples were subjected to trypsin digestion. MRM‐MS analyses were performed using three transitions optimized on one purified synthetic peptide unique to CYP3A4 and the standardizing protein, calnexin. Coefficient of variations for the precision and reproducibility of the MRM‐MS measurement were also determined. The method was applied to liver samples from ten non‐cholestatic donors and 34 cholestatic patients with primary biliary cholangitis (n = 12; PBC), primary sclerosing cholangitis (n = 10; PSC) or alcoholic liver disease (n = 12; ALD). The established method presented high sensitivity with limit of detection lower than 5 fmol, and was successfully applied for the absolute and relative quantification of CYP3A4 in both whole liver homogenate and microsomal fractions. When all groups were analyzed together, a significant correlation was observed for the MRM‐based CYP3A4 protein quantification in homogenates and microsomes (r = 0.49, p < 0.001). No statistically significant difference was detected between CYP3A4 levels in PSC, PBC, ALD and control samples. Finally, the MRM‐MS quantification of CYP3A4 in homogenates also correlated (r = 0.44; p < 0.05) with the level of enzyme activity in the same samples, as determined by measuring the chenodeoxycholic to hyocholic acid conversion. The established method provides a sensitive tool to evaluate the CYP3A4 protein in human liver homogenates from patients with normal or chronic/severe hepatic injury.
Highly concentrated polycarbonate‐based solid polymer electrolytes having extraordinary electrochemical stability
Authors: Kimura Kento , Motomatsu Joh , Tominaga Yoichi
Published: September 2016

Solid polymer electrolytes (SPEs) are compounds of great interest as safe and flexible alternative ionics materials, particularly suitable for energy storage devices. We study an unusual dependence on the salt concentration of the ionic conductivity in an SPE system based on poly(ethylene carbonate) (PEC). Dielectric relaxation spectroscopy reveals that the ionic conductivity of PEC/lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) electrolyte continues to increase with increasing salt concentration because the segmental motion of the polymer chains is enhanced by the plasticizing effect of the imide anion. Fourier transfer‐infrared (FTIR) spectroscopy suggests that this unusual phenomenon arises because of a relatively loose coordination structure having moderately aggregated ions, in contrast to polyether‐based systems. Comparative FTIR study against PEC/lithium perchlorate (LiClO4) electrolytes suggests that weak ionic interaction between Li and TFSI ions is also important. Highly concentrated electrolytes with both reasonable conductivity and high lithium transference number (t+) can be obtained in the PEC/LiTFSI system as a result of the unusual salt concentration dependence of the conductivity and the ionic solvation structure. The resulting concentrated PEC/LiTFSI electrolytes have extraordinary oxidation stability and prevent any Al corrosion reaction in a cyclic voltammetry. These are inherent effects of the highly concentrated salt. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 2442–2447
What do people fear about cancer? A systematic review and meta‐synthesis of cancer fears in the general population
Authors: Vrinten Charlotte , McGregor Lesley M. , Heinrich Małgorzata , von Wagner Christian , Waller Jo , Wardle Jane , Black Georgia B.
Published: September 2016

Background

Cancer has long inspired fear, but the effect of fear is not well understood; it seems both to facilitate and to deter early diagnosis behaviours. To elucidate fear's behavioural effects, we systematically reviewed and synthesised qualitative literature to explore what people fear about cancer.

Methods

We searched Medline, Embase, PsycInfo, Web of Science, AnthroSource, and Anthrobase for studies on cancer fear in breast, cervical, and colorectal cancer screening and analysed 102 studies from 26 countries using thematic synthesis.

Results

Fears of cancer emanated from a core view of cancer as a vicious, unpredictable, and indestructible enemy, evoking fears about its proximity, the (lack of) strategies to keep it at bay, the personal and social implications of succumbing, and fear of dying from cancer.

Conclusions

This view of cancer as ‘an enemy’ reprises the media's ‘war on cancer’ theme and may affect the acceptance of cancer early detection and prevention messages, since cancer's characteristics influenced whether ‘fight’ or ‘flight’ was considered appropriate.
Activation of bacterial lytic polysaccharide monooxygenases with cellobiose dehydrogenase
Authors: Loose Jennifer S. M. , Forsberg Zarah , Kracher Daniel , Scheiblbrandner Stefan , Ludwig Roland , Eijsink Vincent G. H. , Vaaje‐Kolstad Gustav
Published: September 2016

Lytic polysaccharide monooxygenases (LPMOs) represent a recent addition to the carbohydrate‐active enzymes and are classified as auxiliary activity (AA) families 9, 10, 11, and 13. LPMOs are crucial for effective degradation of recalcitrant polysaccharides like cellulose or chitin. These enzymes are copper‐dependent and utilize a redox mechanism to cleave glycosidic bonds that is dependent on molecular oxygen and an external electron donor. The electrons can be provided by various sources, such as chemical compounds (e.g., ascorbate) or by enzymes (e.g., cellobiose dehydrogenases, CDHs, from fungi). Here, we demonstrate that a fungal CDH from Myriococcum thermophilum (MtCDH), can act as an electron donor for bacterial family AA10 LPMOs. We show that employing an enzyme as electron donor is advantageous since this enables a kinetically controlled supply of electrons to the LPMO. The rate of chitin oxidation by CBP21 was equal to that of cosubstrate (lactose) oxidation by MtCDH, verifying the usage of two electrons in the LPMO catalytic mechanism. Furthermore, since lactose oxidation correlates directly with the rate of LPMO catalysis, a method for indirect determination of LPMO activity is implicated. Finally, the one electron reduction of the CBP21 active site copper by MtCDH was determined to be substantially faster than chitin oxidation by the LPMO. Overall, MtCDH seems to be a universal electron donor for both bacterial and fungal LPMOs, indicating that their electron transfer mechanisms are similar.
Applying bimolecular fluorescence complementation to screen and purify aquaporin protein:protein complexes
Authors: Sjöhamn Jennie , Båth Petra , Neutze Richard , Hedfalk Kristina
Published: September 2016

Protein:protein interactions play key functional roles in the molecular machinery of the cell. A major challenge for structural biology is to gain high‐resolution structural insight into how membrane protein function is regulated by protein:protein interactions. To this end we present a method to express, detect, and purify stable membrane protein complexes that are suitable for further structural characterization. Our approach utilizes bimolecular fluorescence complementation (BiFC), whereby each protein of an interaction pair is fused to nonfluorescent fragments of yellow fluorescent protein (YFP) that combine and mature as the complex is formed. YFP thus facilitates the visualization of protein:protein interactions in vivo, stabilizes the assembled complex, and provides a fluorescent marker during purification. This technique is validated by observing the formation of stable homotetramers of human aquaporin 0 (AQP0). The method's broader applicability is demonstrated by visualizing the interactions of AQP0 and human aquaporin 1 (AQP1) with the cytoplasmic regulatory protein calmodulin (CaM). The dependence of the AQP0‐CaM complex on the AQP0 C‐terminus is also demonstrated since the C‐terminal truncated construct provides a negative control. This screening approach may therefore facilitate the production and purification of membrane protein:protein complexes for later structural studies by X‐ray crystallography or single particle electron microscopy.
Characterisation of Ramularia collo‐cygni laboratory mutants resistant to succinate dehydrogenase inhibitors
Authors: Piotrowska Marta J , Fountaine James M , Ennos Richard A , Kaczmarek Maciej , Burnett Fiona J
Published: September 2016

BACKGROUND

Ramularia collo‐cygni (Rcc) is responsible for Ramularia leaf spot (RLS), a foliar disease of barley contributing to serious economic losses. Protection against the disease has been almost exclusively based on fungicide applications, including succinate dehydrogenase inhibitors (SDHIs). In 2015, the first field isolates of Rcc with reduced sensitivity to SDHIs were recorded in some European countries. In this study we established baseline sensitivity of Rcc to SDHIs in the United Kingdom and characterised mutations correlating with resistance to SDHIs in UV‐generated mutants.

RESULTS

Five SDHI‐resistant isolates were generated by UV mutagenesis. In four of these mutants a single amino acid change in a target succinate dehydrogenase (Sdh) protein was associated with decrease in sensitivity to SDHIs. Three of these mutations were stably inherited in the absence of SDHI fungicide, and resistant isolates did not demonstrate a fitness penalty. There were no detectable declines in sensitivity in field populations in the years 2010–2012 in the United Kingdom.

CONCLUSIONS

SDHIs remained effective in controlling Rcc in the United Kingdom in the years 2010–2012. However, given that the first isolates of Rcc with reduced sensitivity appeared in other European countries in 2015, robust antiresistance strategies need to be continuously implemented to maintain effective disease control. © 2016 Society of Chemical Industry
Electrodeposited n‐type cuprous oxide cubic nanostructures for liquefied petroleum gas sensing
Authors: Jayasingha J. L. K. , Jayathilaka K. M. D. C. , Gunewardene M. S. , Dissanayake D. P. , Jayanetti J. K. D. S.
Published: September 2016

A surfactant free template assisted electrodeposition method was used to fabricate thick n‐type Cu2O films having cubic nanostructures for the detection of liquefied petroleum (LP) gas at low concentrations. Templates were fabricated by initially electrodepositing a p‐type Cu2O thin film on a Ti substrate followed by annealing that changed conductivity type of the film, as confirmed by Mott–Schottky and spectral response measurements. SEM measurements of resulting films showed nano‐cubic crystals having sizes of 150–300 nm. When exposed to a mixture of LP gas and dry air, the resistance of these films increased and the maximum response was recorded when films were maintained at 180 °C for all concentrations and it was independent of the surface morphology. At 180 °C, at the lowest tested LP gas concentration of 2 vol.%, a twofold increase in response was observed in the nano‐cubic films compared to the micro‐crystalline n‐type Cu2O films. This improvement in gas response is attributed to increased effective surface area of these nanostructured films. Compared to other LP gas sensing materials, Cu2O films showed very good response times and recovery times of ∼120 and ∼90 s, respectively.
Optimal sequential enrichment designs for phase II clinical trials
Authors: Zang Yong , Yuan Ying
Published: September 2016

In the early phase development of molecularly targeted agents (MTAs), a commonly encountered situation is that the MTA is expected to be more effective for a certain biomarker subgroup, say marker‐positive patients, but there is no adequate evidence to show that the MTA does not work for the other subgroup, that is, marker‐negative patients. After establishing that marker‐positive patients benefit from the treatment, it is often of great clinical interest to determine whether the treatment benefit extends to marker‐negative patients. The authors propose optimal sequential enrichment (OSE) designs to address this practical issue in the context of phase II clinical trials. The OSE designs evaluate the treatment effect first in marker‐positive patients and then in marker‐negative patients if needed. The designs are optimal in the sense that they minimize the expected sample size or the maximum sample size under the null hypothesis that the MTA is futile. An efficient, accurate optimization algorithm is proposed to find the optimal design parameters. One important advantage of the OSE design is that the go/no‐go interim decision rules are specified prior to the trial conduct, which makes the design particularly easy to use in practice. A simulation study shows that the OSE designs perform well and are ethically more desirable than the commonly used marker‐stratified design. The OSE design is applied to an endometrial carcinoma trial. Copyright © 2016 John Wiley & Sons, Ltd.
Synthesis of 1‐Deoxy‐8,8a–di–epi–castanospermine, 1‐Deoxy‐6,7,8a–tri–epi–castanospermine and Formal Synthesis of Pumilotoxin 251D
Authors: Chacko Shibin , Ramapanicker Ramesh
Published: September 2016

An efficient synthesis of 1‐deoxy‐8,8a‐di‐epi‐castanospermine and 1‐deoxy‐6,7,8a‐tri‐epi‐castanospermine through the use of proline‐catalyzed asymmetric α‐aminoxylation of an N‐Boc derivative of L‐homoprolinal is reported. The configuration of the proline catalyst used for the asymmetric aminoxylation step ultimately controls the absolute configuration of three adjacent stereogenic centers in the final products. The method is also used to achieve a formal synthesis of Pumilotoxin 251D.
Overdiagnosis and rising rate of obstetric anal sphincter injuries (OASIS): time for reappraisal
Authors: Sioutis D. , Thakar R. , Sultan A. H.
Published: September 2016

Objectives

To determine the accuracy of clinical diagnosis of obstetric anal sphincter injuries (OASIS) using three‐dimensional (3D) endoanal ultrasound (EA‐US) and to compare symptoms and anal manometry measurements between women with anal sphincters adequately repaired and those with persistent anal sphincter defects.

Methods

The EA‐US images of women with clinically diagnosed and repaired OASIS, defined as third‐ or fourth‐degree perineal tear, who attended the perineal clinic at Croydon University Hospital over a 10‐year period (2003–2013) were reanalyzed by a single expert blind to symptoms and the results of clinical examination. St Mark's Incontinence Scores (SMIS) and anal manometry measurements were obtained and compared between women with an intact anal sphincter and those with an anal sphincter scar and between those with an intact anal sphincter and those with a defect. Anal manometry measurements were compared between women with an external anal sphincter (EAS) defect and those with an internal anal sphincter (IAS) defect.

Results

The images of 908 women were reanalyzed. No evidence of OASIS was found in 64 (7.0%) women, an EAS scar alone was detected in 520 (57.3%) and an anal sphincter defect in 324 (35.7%). Of the 324 women with a defect, 112 had an EAS defect, 90 had an IAS defect and 122 had a combined IAS and EAS defect. SMIS results were significantly higher in women with an anal sphincter defect compared with those with no evidence of OASIS (P = 0.018), but there was no significant difference in scores between women with an intact sphincter and those with an EAS scar only. Women with a defect had a significantly lower maximum resting pressure (median (range), 44 (8–106)vs55 (29–86) mmHg;P < 0.001) and maximum squeeze pressure (median (range), 74 (23–180)vs103 (44–185) mmHg;P < 0.001) compared with those in the intact group. Similar, but less marked, differences were observed in women with an EAS scar compared with those who had an intact anal sphincter. The anal length was significantly shorter in women with a defect compared with those in the intact group (median (range), 20 (10–40)vs25 (10–40) mm;P = 0.003).

Conclusions

Seven percent of women with a clinical diagnosis of OASIS were wrongly diagnosed. We believe that this rate may differ from that of other units but training methods and competency assessment tools for the diagnosis and repair of OASIS need urgent reappraisal. The role of EA‐US in the immediate postpartum period needs further evaluation as the accurate interpretation of the images is dependent on the expertise of the staff involved. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.