bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a novel tissue stabilization gel to facilitate clinical sampling for translational research in surgical trials
Authors: Sutton P A , Jones R P , Morrison F , Goldring C E , Park B K , Palmer D H , Malik H Z , Vimalachandran D , Kitteringham N R
Published: January 2015

Background

The aim was to establish the feasibility of using a tissue stabilization gel (Allprotect™) as an alternative to liquid nitrogen to facilitate collection of clinical samples for translational research.

Methods

Tumour samples from patients undergoing surgery for primary or metastatic colorectal cancer were either snap-frozen in liquid nitrogen or stored in Allprotect™ under a number of different conditions. Sample integrity was compared across different storage conditions by assessing biomolecule stability and function. DNA quality was assessed spectrophotometrically and by KRas genotyping by pyrosequencing. Total RNA retrieval was determined by nanodrop indices/RNA integrity numbers, and quality assessed by reverse transcription–PCR for two representative genes (high-mobility group box 1, HMGB1; carboxylesterase 1, CES1) and two microRNAs (miR122 and let7d). Western blot analysis of HMGB1 and CES1 was used to confirm protein expression, and the metabolic conversion of irinotecan to its active metabolite, SN-38, was used to assess function.

Results

Under short-term storage conditions (up to 1 week) there was no apparent difference in quality between samples stored in Allprotect™ and those snap-frozen in liquid nitrogen. Some RNA degradation became apparent in tissue archived in Allprotect™ after 1 week, and protein degradation after 2 weeks.

Conclusion

In hospitals that do not have access to liquid nitrogen and –80°C freezers, Allprotect™ provides a suitable alternative for the acquisition and stabilization of clinical samples. Storage proved satisfactory for up to 1 week, allowing transfer of samples without the need for specialized facilities. Surgical relevanceAccess to clinical material is a fundamental component of translational research that requires significant infrastructure (research personnel, liquid nitrogen, specialized storage facilities). The aim was to evaluate a new-to-market tissue stabilization gel (Allprotect™), which offers a simple solution to tissue preservation without the need for complex infrastructure.Allprotect™ offers comparable DNA, RNA and protein stabilization to tissue snap-frozen in liquid nitrogen for up to 1 week. Degradation of biomolecules beyond this highlights its role as a short-term tissue preservative.Allprotect™ has the potential to increase surgeon participation in translational research and surgical trials requiring tissue collection.
Five-year results from the prospective European multicentre cohort study on radiofrequency segmental thermal ablation for incompetent great saphenous veins
Authors: Proebstle T M , Alm B J , Göckeritz O , Wenzel C , Noppeney T , Lebard C , Sessa C , Creton D , Pichot O
Published: January 2015

Background

This was a prospective study of radiofrequency segmental thermal ablation (RFA) for the treatment of incompetent varicose great saphenous veins (GSVs). The present report describes long-term follow-up at 5 years.

Methods

The 5-year follow-up of this multicentre European study included assessment of the Venous Clinical Severity Score (VCSS), and GSV occlusion and reflux on duplex imaging.

Results

A total of 225 patients had 295 GSVs treated by RFA, achieving an initial vein occlusion rate of 100 per cent. With 80·0 per cent compliance, Kaplan–Meier analyses showed a GSV occlusion rate of 91·9 per cent and a reflux-free rate of 94·9 per cent at 5 years. Among the 15 GSVs noted with reflux during follow-up, only three showed full recanalization of the GSV at 1 week, 6 months and 3 years. Of the 12 legs with partial recanalization, reflux originated at the saphenofemoral junction in ten, with a mean length of the patent segment of 5·8 (range 3·2–10) cm; only six patients were symptomatic. Mean(s.d.) VCSS scores improved from 3·9(2·1) at baseline to 0·6(1·2), 0·9(1·3) and 1·3(1·7) at 1, 3 and 5 years.

Conclusion

At 5 years RFA proved to be an efficient endovenous treatment for incompetent GSVs in terms of sustained clinical and anatomical success for the vast majority of treated patients.
Randomized clinical trial of autologous skin cell suspension combined with skin grafting for chronic wounds
Authors: Hu Z -C , Chen D , Guo D , Liang Y -Y , Zhang J , Zhu J -Y , Tang B
Published: January 2015

Background

Treatment of chronic wounds using traditional surgical procedures is challenging because of the low graft take rates. This study investigated the combination approach of split-thickness autografts with harvested skin cell suspension for chronic wound treatment.

Methods

This randomized clinical trial enrolled patients with chronic wounds between March 2012 and December 2013. Patients who were assigned randomly to the active treatment received a split-thickness autograft combined with harvested skin cell suspension. Control patients received the split-thickness autograft alone. The primary outcome was the rate of complete wound closure by postoperative day 28. Analysis was by intention to treat. Patients who achieved wound closure were followed up for a minimum of 6 months to evaluate the quality of healing.

Results

A total of 88 patients were included, 44 in each group. More patients achieved complete wound closure in the skin cell group than in the control group (41 versus 34 patients; P = 0·035). Complete wound closure was observed at a median of 14 (95 per cent c.i. 12·0 to 16·0) days in the skin cell group and 20 (15·7 to 24·3) days in the control group (P = 0·001). The skin cell group had significantly fewer complications (4 versus 11 patients; P = 0·047). The autografted sites displayed better physical attributes and a reduced tendency for wound recurrence in the skin cell group.

Conclusion

Complementary split-thickness autologous skin grafting with autologous skin cells harvested using ReCell® (Avita Medical, Cambridge, UK) technology improved the healing rate of chronic wounds. Registration number: UMIN000011966 (http://www.umin.ac.jp/ctr).
Natural-orifice transluminal endoscopic surgery
Authors: Atallah S , Martin-Perez B , Keller D , Burke J , Hunter L
Published: January 2015

Background

Natural-orifice transluminal endoscopic surgery (NOTES) represents one of the most significant innovations in surgery to emerge since the advent of laparoscopy. A decade of progress with this approach has now been catalogued, and yet its clinical application remains controversial.

Methods

A PubMed search was carried out for articles describing NOTES in both the preclinical and the clinical setting. Public perceptions and expert opinion regarding NOTES in the published literature were analysed carefully.

Results

Two hundred relevant articles on NOTES were studied and the outcomes reviewed. A division between direct- and indirect-target NOTES was established. The areas with the most promising clinical application included direct-target NOTES, such as transanal total mesorectal excision and peroral endoscopic myotomy. The clinical experience with distant-target NOTES, such as for appendicectomy and cholecystectomy, showed feasibility; however, NOTES-specific morbidity was introduced and this represents an important limitation.

Conclusion

NOTES experimentation in the preclinical setting has increased substantially. There has also been a significant increase in the application of NOTES in humans in the past decade. Enthusiasm for NOTES should be tempered by the risk of incurring NOTES-specific morbidity. Surgeons should carefully consider patient preferences regarding this new minimally invasive option, as opinions are not unanimously supportive of NOTES. As technical limitations are overcome, the clinical application of NOTES is predicted to increase. It is paramount that, when this complex technique is performed on humans, it is applied judiciously by appropriately trained experts with outcomes recorded in a registry.
Innovation in income-poor environments
Authors: Oppong F C
Published: January 2015

Background

At the core of surgical development in any economic environment lies innovation. Innovation in high-income countries (HICs) often derives from research, whereas innovation in low- and middle-income countries (LMICs) may be spontaneous owing to a desperate drive to meet a local need. The local needs are substantial because of the unequal access to healthcare in LMICs.

Methods

The experience of the author in working in LMICs through Operation Hernia, a medical charity, provides a backdrop for this review. Other published innovative devices and models are discussed.

Results

Innovation in income-poor countries has provided cost-effective but efficient solutions to local health needs. Some innovations have been enhanced and adopted worldwide.

Conclusion

HICs can learn more from innovative strategies adopted in LMICs.
Sensitive and validated LC‐MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients
Authors: Kawanishi Misaki , Yano Ikuko , Yoshimura Kazuaki , Yamamoto Takashi , Hashi Sachiyo , Masuda Satohiro , Kondo Tadakazu , Takaori‐Kondo Akifumi , Matsubara Kazuo
Published: January 2015

Monitoring of pharmacodynamics in addition to pharmacokinetics is one of strategies to individualize mycophenolate mofetil therapy. The purpose of this study was to develop sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) methods for evaluation of the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). Concentrations of mycophenolic acid glucuronide (MPAG), mycophenolic acid acyl‐glucuronide, as well as unbound MPA and MPAG, were determined, and inosine‐5′‐monophosphate dehydrogenase activity was calculated by measuring concentrations of produced xanthosine‐5′‐monophosphate (XMP) and intracellular adenosine‐5′‐monophosphate after incubation of peripheral blood mononuclear cell (PBMC) lysates. A metal‐free MastroTM column and two gradient patterns were used to improve the quantification limit of XMP to 0.1 μm. In the clinical MPA concentration range, the linearity of the calibration curve, inter‐ and intra‐day precision and accuracy satisfied the relevant US Food and Drug Administration guidelines. The MPA concentrations in hematopoietic stem cell transplant (HSCT) patients determined by the enzyme assay and the present LC‐MS/MS method showed a good correlation (r2 = 0.95, p < 0.001). In this study, we report sensitive and validated LC‐MS/MS methods to evaluate the pharmacokinetics and pharmacodynamics of MPA, which are sufficiently sensitive to assess small quantities of PBMC lysates collected shortly after HSCT. Copyright © 2015 John Wiley & Sons, Ltd.
Temporospatial identification of language‐related cortical function by a combination of transcranial magnetic stimulation and magnetoencephalography
Authors: Shinshi Misako , Yanagisawa Takufumi , Hirata Masayuki , Goto Tetsu , Sugata Hisato , Araki Toshihiko , Okamura Yumiko , Hasegawa Yuka , Ihara Aya S. , Yorifuji Shiro
Published: January 2015

Introduction

Identification of language‐related cortical functions can be carried out noninvasively by transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), which allow for lesion‐based interrogation and global temporospatial investigation of cortices, respectively. Combining these two modalities can improve the accuracy of the identification, but the relationships between them remain unclear. We comparedTMSandMEGresponses during the same language task to elucidate their temporospatial relationships and used the results to develop a novel method to identify language‐related cortical functions.

Methods

Twelve healthy right‐handed volunteers performed a picture‐naming task duringTMSandMEG.TMSwas applied on the right or left inferior frontal gyrus (IFG) at five time points, and the reaction times (RTs) for naming the pictures were measured. The temporospatial oscillatory changes measured byMEGduring the same task were then compared with theTMSresults.

Results

Transcranial magnetic stimulation of the leftIFGsignificantly lengthenedRTs at 300 and 375 msec after picture presentation, whereasTMSof the rightIFGdid not changeRTs significantly. Interestingly, the stimulus time point at whichRTs increased significantly for each individual was correlated with when the low gamma event‐related desynchronizations (ERDs) peaked in the leftIFG. Moreover, combining the results ofTMSandMEGimproved the detection rate for identifying the laterality of language function.

Conclusions

These results suggest that the low gammaERDs measured byMEGstrongly relate to the language function of picture naming in the leftIFG. Finally, we propose a novel method to identify language‐related cortical functions by combiningTMSandMEG.
Alcoholic Fermentation with Self‐Flocculating Yeast in a Tower Upflow Reactor
Authors: Pacheco Thályta F. , Galvão de Morais Júnior Wilson , Zanella Guidini Carla , Marquez Líbia Diniz S. , Cardoso Vicelma L. , Resende Miriam M. , Ribeiro Eloízio J.
Published: January 2015

Ethanol production using self‐flocculating yeast in a batch tower upflow reactor system operating with a recirculation loop was examined. Ethanol productivity, yield, and residual sucrose concentration were evaluated experimentally according to a central composite design with initial cell and sucrose concentrations and recirculation flow rate as independent variables. Yeast cell concentration strongly influenced the reactor performance. Alcoholic fermentation was conducted using this strain and reactor configuration which allowed for high productivity and high sucrose conversion. The ethanol yield was comparable with industrial yields. A kinetic study of the fermentation process under optimized conditions was performed using the experimental data and considering inhibition by sucrose and ethanol.
A numerical study of heat transfer in a turbulent pulsating impinging jet
Authors: Esmailpour Kazem , Hosseinalipour Mostafa , Bozorgmehr Behnam , Mujumdar Arun S.
Published: January 2015

Pulsating impinging jets can have significant influence on transfer processes. A number of studies have been done on heat transfer in a pulsating impinging jet but very divergent and sometimes contradictory results have been reported. In the present study, the flow and temperature field under a single confined pulsating turbulent impinging jet are determined numerically by the finite volume method. Effects of Pulsation function parameters (frequency and amplitude) and various geometries on the flow characteristics and heat transfer rate from hot surface are discussed. Results of simulation show that flow pulsation has different effects in various flow zones. Pulsation of jet improve cooling performance in the wall jet zone and simultaneously reduce heat transfer in the stagnation zone. As expected the effect of flow pulsation decays with distance from the jet nozzle. Under certain conditions flow oscillation adversely affects the heat transfer in comparison with the steady jet at the same mean Reynolds number. In pulsating jets we can introduce a critical frequency correspond to St = 0.26. The amount of heat transfer at the frequencies corresponding St = 0.26 is higher than other cases. In general, it is concluded that cooling performance of oscillating impinging jet is enhanced by increase in the frequency and amplitude of oscillation as well as decrease in nozzle to plate distance.
Pressure drop predictions for laminar pipe flow of carreau and modified power law fluids
Authors: Dosunmu Idowu T. , Shah Subhash N.
Published: January 2015

Fluids used in many chemical and petroleum industrial processes are often described as complex systems that exhibit non‐Newtonian character. Due to the complex nature of non‐Newtonian fluids, universally accepted flow equations are unavailable. This paper uses the Carreau and modified power law–Cross (MPL‐Cross) rheological models to derive pressure drop–flow rate relationships under laminar flow condition. The aim is to develop simple but effective equations that enable accurate estimation of pressure drop for flow in any pipe size using viscometric data. The new relationships compare favourably with experimental data. Furthermore, new Reynolds number and generalized Reynolds number expressions have been defined.
Impact of Hypertension on Global Cardiovascular Risk Stratification: Analysis of a Large Cohort of Outpatient Population in Italy
Authors: Tocci Giuliano , Battistoni Allegra , D'Agostino Michela , Palano Francesca , Passerini Jasmine , Francia Pietro , Ferrucci Andrea , Volpe Massimo ,   on behalf of the EFFECTUS Steering Committee
Published: January 2015

Background

Control of hypertension remains a major unmet need, worldwide.

Hypothesis

To test whether the presence of hypertension may improve global cardiovascular (CV) risk stratification and achievement of therapeutic targets for CV risk factors in adult outpatients in Italy.

Methods

Physicians were asked to submit data covering the first 10 consecutive adult outpatients. All data were centrally analyzed for global CV risk assessment and rates of control of major CV risk factors, mostly blood pressure (BP) levels, in different high‐risk subgroups of hypertensive patients.

Results

Overall, 1078 physicians collected data of 9864 outpatients (46.7% females, age 66.1 ± 10.3 years) with valuable data on BP levels, among which 7147 (72.5%) had a diagnosis of hypertension and 2717 (27.5%) were normotensive subjects. Hypertensive patients were older and had a higher prevalence of major risk factors, including smoking, obesity, dyslipidemia, and family history of cardiovascular disease, as well as comorbidities, than did normotensive subjects (P < 0.001 for all comparisons). Despite worse control of BP (66.9% vs 36.2%, P < 0.001), high‐density lipoprotein cholesterol (40.5% vs 37.4%, P < 0.005), triglycerides (72.1% vs 67.8%, P < 0.001), and fasting plasma glucose (71.2% vs 67.0%, P < 0.005), hypertension was associated with larger availability and frequency of diagnostic examinations and greater use of antihypertensive, glucose‐lowering, and lipid‐lowering drugs, as well as antiplatelet agents, compared with normotension (P < 0.001).

Conclusions

Presence of hypertension significantly improved clinical data collection and CV risk stratification. Such an approach, however, was not paralleled by better control of major CV risk factors.
Making quantitative morphological variation from basic developmental processes: Where are we? The case of the Drosophila wing
Authors: Matamoro‐Vidal Alexis , Salazar‐Ciudad Isaac , Houle David
Published: January 2015

One of the aims of evolutionary developmental biology is to discover the developmental origins of morphological variation. The discipline has mainly focused on qualitative morphological differences (e.g., presence or absence of a structure) between species. Studies addressing subtle, quantitative variation are less common. The Drosophila wing is a model for the study of development and evolution, making it suitable to investigate the developmental mechanisms underlying the subtle quantitative morphological variation observed in nature. Previous reviews have focused on the processes involved in wing differentiation, patterning and growth. Here, we investigate what is known about how the wing achieves its final shape, and what variation in development is capable of generating the variation in wing shape observed in nature. Three major developmental stages need to be considered: larval development, pupariation, and pupal development. The major cellular processes involved in the determination of tissue size and shape are cell proliferation, cell death, oriented cell division and oriented cell intercalation. We review how variation in temporal and spatial distribution of growth and transcription factors affects these cellular mechanisms, which in turn affects wing shape. We then discuss which aspects of the wing morphological variation are predictable on the basis of these mechanisms. Developmental Dynamics 244:1058–1073, 2015. © 2015 Wiley Periodicals, Inc.
Behavioral, emotional, and situational context of purging episodes in anorexia nervosa
Authors: Goldschmidt Andrea B. , Accurso Erin C. , Schreiber‐Gregory Deanna N. , Crosby Ross D. , Cao Li , Engel Scott G. , Mitchell James E. , Crow Scott J. , Peterson Carol B. , Le Grange Daniel , Wonderlich Stephen A.
Published: January 2015

Objective

The current study examined behavioral, emotional, and situational factors involved in purging among women with anorexia nervosa (AN).

Method

Women with AN (n=118) completed a two‐week ecological momentary assessment protocol involving daily reports of eating disorder behaviors, mood, and stressful events. Generalized estimating equations examined the likelihood and context of purging following eating episodes involving both overeating and loss of control (binge eating; BE); loss of control only (LOC); overeating only (OE); and neither loss of control nor overeating (non‐pathological eating; NE).

Results

Relative to NE, purging was more likely to occur following BE, LOC, and OE (Wald chi‐square = 18.05; p < .001). BE was more strongly associated with subsequent purging than LOC but not OE; the latter two did not differ from one another. Negative affect predicted purging following NE (Wald chi‐square = 7.71; p = .005).

Discussion

Binge eating involving large amounts of food was the strongest predictor of purging in AN, which challenges the notion that loss of control is the most salient aspect of experiencing distress in bulimia nervosa and BE disorder. Parallel to findings from the BE literature, negative affect strongly predicted purging following NE. Further research should clarify the function and triggers of purging in AN. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:341–344)
Refeeding and weight restoration outcomes in anorexia nervosa: Challenging current guidelines
Authors: Redgrave Graham W. , Coughlin Janelle W. , Schreyer Colleen C. , Martin Lindsay M. , Leonpacher Anne K. , Seide Margaret , Verdi Antonia M. , Pletch Allisyn , Guarda Angela S.
Published: January 2015

Objective

Cohort study from February 2003 through May 2011 to determine weight restoration and refeeding complication outcomes for patients with anorexia nervosa (AN) treated in an integrated inpatient‐partial hospital eating disorder program designed to produce rapid weight gain and weight restoration in the majority.

Method

Consecutive admissions (females and males, adolescents and adults; N = 361 patients, 461 admissions) at least 1.8 kg below target weight with AN or subthreshold variants were included. Main outcome measures were rates of hypophosphatemia, transfer to medicine, or death; rates of weight gain and percent achieving weight restoration.

Results

Hypophosphatemia was present in 7.9% of cases at admission and in 18.5% at some point during treatment. Hypophosphatemia was mild to moderate. Lower admission body mass index (BMI), but not rate of weight gain, predicted hypophosphatemia [OR = 0.65; p < .00001 (95% CI 0.57–0.76)]. Five patients (1.1%) were transferred to medicine or surgery, none because of refeeding. There were no deaths. Mean inpatient weight gain was 1.98 kg/week; mean partial hospital weight gain was 1.36 kg/week. By program discharge, 71.8% of adults reached a BMI of 19, 58.5% a BMI of 20. For adolescents, 80.4% came within 2 kg of their target weight; 76.1% came within 1 kg.

Discussion

Refeeding patients with AN using a hospital‐based, behavioral protocol may be accomplished safely and more rapidly than generally recognized, weight restoring most patients by discharge. Helpful elements may include the program's integrated, step‐down structure; multidisciplinary team approach emphasizing group therapy to effect behavior change; and close medical monitoring for those with BMI < 15. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:866–873)
A Metalloligand Appended with Thiazole Rings: Heterometallic {Co3+–Zn2+} and {Co3+–Cd2+} Complexes and Their Heterogeneous Catalytic Applications
Authors: Bansal Deepak , Hundal Geeta , Gupta Rajeev
Published: January 2015

This work describes a Co3+‐based metalloligand containing appended thiazole rings and its reactions with secondary metal ions to produce heterometallic {Co3+–Zn2+} and {Co3+–Cd2+} complexes. Structural studies show that some of the appended thiazole rings from the metalloligand coordinate to secondary metal ions, whereas the remaining ones act as hydrogen‐bond acceptors to metal‐bound CH3OH or H2O molecules. These heterometallic complexes function as reusable heterogeneous catalysts for the ring‐opening reactions of epoxides as well as cyanation and Knoevenagel condensation reactions of aldehydes. The catalytic results illustrate that the microenvironment remains intact during the catalysis and potentially enhances the substrate interaction with the Lewis acidic secondary metal ions.
Lanthanide Complex Hybrid System for Fluorescent Sensing as Thermometer
Authors: Shen Xiang , Lu Ye , Yan Bing
Published: January 2015

A mixed lanthanide complex was synthesized hydrothermally with two kinds of organic ligands, adenine and biphenyl‐4,4′‐dicarboxylic acid, and is formulated as Ad/Tb0.999Eu0.001/BPDC (Ad = adeninate, BPDC = biphenyl‐4,4′‐dicarboxylate). The photophysical properties, especially the fluorescent sensing properties, have been studied in detail and compared to those of Tb0.999Eu0.001/BPDC, with a single ligand. It can be used as a ratiometric luminescent thermometer on the basis of the energy transfer from Tb3+ to Eu3+, whose color will change from green–yellow to red from 100 K to 300 K.
Intercalative Ion‐Exchange Route to Amino Acid Layered Double Hydroxide Nanohybrids and Their Sorption Properties
Authors: Choi Goeun , Yang Jae‐Hun , Park Ga‐Young , Vinu Ajayan , Elzatahry Ahmad , Yo Chul Hyun , Choy Jin‐Ho
Published: January 2015

A soft chemical route to amino acid layered double hydroxide (LDH) nanohybrids was demonstrated on the basis of an intercalative ion‐exchange reaction. Two different amino acids, phenylalanine and glutamic acid, were intercalated and stabilized in the interlayer space of a 2‐dimensional double hydroxide lattice by electrostatic interaction. An attempt was also made to understand the effect of the intracrystalline structure of the amino acid in the LDH on the specific surface area, porosity, and gas sorption properties of the hybrid. According to the X‐ray diffraction analysis, the basal spacings of LDH intercalated with phenylalanine and LDH intercalated with glutamic acid were expanded to 1.80 and 1.22 nm, respectively, relative to that of the pristine Mg2Al‐NO3‐LDH (0.88 nm), which indicates that amino acid molecules were successfully intercalated into the LDH. Fourier transform infrared spectra for both samples confirmed that the carboxylic acid group in the amino acid is anionic carboxylate under basic conditions and it eventually interacts with the positively charged LDH surface. From N2 adsorption/desorption analysis, the BET specific surface area of the LDH intercalated with phenylalanine was found to be twice as large as that for the LDH intercalated with glutamic acid. However, the CO2 adsorption capacity of the former was determined to be three times more enhanced than that of the latter, due to an enhanced specific surface area and effective amine sites to form carbamates.
Nucleophilic Cyclization of o‐Alkynylbenzamides Promoted by Iron(III) Chloride and Diorganyl Dichalcogenides: Synthesis of 4‐Organochalcogenyl‐1H‐isochromen‐1‐imines
Authors: Neto Jose S. S. , Back Davi F. , Zeni Gilson
Published: January 2015

We have developed a method for the preparation 4‐organochalcogenyl‐1H‐isochromen‐1‐imines from o‐alkynylbenzamides. This electrophile‐promoted nucleophilic cyclization achieved by treatment with a combination of iron salts and diorganyl dichalcogenides. FeCl3 and diorganyl dichalcogenides reacted with o‐alkynylbenzamides under aerobic conditions at room temperature and in the absence of additives to give 4‐organochalcogenyl‐1H‐isochromen‐1‐imines in good yields and with good selectivities. The reaction took place with 0.5 equiv. of the diorganyl dichalcogenides, which demonstrates that both halves of the diorganyl dichalcogenides (RYYR → 2RY) were incorporated into the final product. Mechanistic studies suggested that the regioselectivity of the cyclization is governed by a seleniranium ion, a key intermediate formed by the electrophilic addition of the organochalcogen moiety to the carbon–carbon triple bond. The utility of the 4‐organochalcogenyl‐1H‐isochromen‐1‐imines was also demonstrated by their application as starting materials in Suzuki and Sonogashira cross‐coupling reactions.
First Total Synthesis of Piperenol B and Configuration Revision of the Enantiomers Piperenol B and Uvarirufol A
Authors: Fischer Thomas C. , Cerra Bruno , Fink Michael J. , Rudroff Florian , Horkel Ernst , Mihovilovic Marko D.
Published: January 2015

We report herein the first total synthesis of piperenol B, a polyoxygenated cyclohexene derivative with reported pharmacological activity isolated from Piper cubeb. The chiral building block for this synthetic approach is derived from microbial cis‐ipso,ortho‐dihydroxylation of sodium benzoate, which was optimized to the multi‐ten‐gram scale by reaction medium engineering. Final‐stage deprotection of an acetonide was investigated in detail, leading to an efficient eight‐step protocol for the synthesis of piperenol B with a total yield of 10 %. Most importantly, the previously assigned absolute configuration of piperenol B was revised and unequivocally established by 2D NMR analysis and the Mosher's ester method.
Fmox: A Base‐Labile Aldehyde Protecting Group
Authors: Diness Frederik , Meldal Morten
Published: January 2015

A base‐labile aldehyde protecting group founded upon the 3‐Fmoc‐(1,3)‐oxazinane moiety has been developed. A series of novel or previously described acid‐labile aldehyde protecting groups were proven to be fully stable under the mild basic conditions, which completely removed the new base‐labile aldehyde protecting group. The possible reaction pathways for introducing and removing the different aldehyde protecting groups have been explored and characterized.
Extraction and long‐term storage of S‐layer proteins and flagella from Lysinibacillus sphaericus NCTC 9602: Building blocks for nanotechnology
Authors: Blüher Anja , Ostermann Kai , Jäckel Petra , Clemens Andrè , Katzschner Beate , Rödel Gerhard , Mertig Michael
Published: January 2015

Self‐assembling surface layer (SL) proteins of bacteria have been widely studied, in particular their use as molecularly defined, 2D coatings of technical surfaces. An important prerequisite is the availability of a sufficient amount of protein. However, a detailed and optimized protocol for the complete SL extraction is so far not available. Here, we describe the complete purification and reassembly procedure of an SL protein of Lysinibacillus sphaericus NCTC 9602, starting from the cultivation of cells, the preparation and purification of SL proteins up to the long‐term storage and in vitro self‐assembly of the proteins. All crucial steps of the procedure are assessed by different microscopic techniques, such as light microscopy, atomic force microscopy, and scanning electron microscopy as well as by SDS‐PAGE as a biochemical method. We demonstrate that storage of the protein in the presence of sodium azide or upon lyophilization allows the preservation of the self‐assembly properties for at least 9 years. Additionally, we describe a method allowing the extraction of intact flagella with lengths in the range up to 4 μm. Flagella may have applications in bio‐nanotechnology, for example as templates for metallic nanowires.
Evaluating the impacts of climate change on diurnal wind power cycles using multiple regional climate models
Authors: Goddard Scott D. , Genton Marc G. , Hering Amanda S. , Sain Stephan R.
Published: January 2015

Electrical utility system operators must plan resources so that electricity supply matches demand throughout the day. As the proportion of wind‐generated electricity in the US grows, changes in daily wind patterns have the potential either to disrupt the utility or increase the value of wind to the system over time. Wind power projects are designed to last many years, so at this timescale, climate change may become an influential factor on wind patterns. We examine the potential effects of climate change on the average diurnal power production cycles at 12 locations in North America by analyzing averaged and individual output from nine high‐resolution regional climate models comprising historical (1971–1999) and future (2041–2069) periods. A semi‐parametric mixed model is fit using cubic B‐splines, and model diagnostics are checked. Then, a likelihood ratio test is applied to test for differences between the time periods in the seasonal daily averaged cycles, and agreement among the individual regional climate models is assessed. We investigate the significant changes by combining boxplots with a differencing approach and identify broad categories of changes in the amplitude, shape, and position of the average daily cycles. We then discuss the potential impact of these changes on wind power production. Copyright © 2015 John Wiley & Sons, Ltd.
Graph‐based hybrid hyper‐heuristic channel scheduling algorithm in multicell networks
Authors: Dong Bei , Jiao Licheng , Wu Jianshe
Published: January 2015

In this paper, we consider the scheduling problem that minimises the number of required channel without violation of traffic demand by considering the intercell interference and intracell interference simultaneously. This concerned problem is proved to be a non‐deterministic polynomial‐time hard problem. We propose a graph‐based hyper‐heuristic method composed of two level heuristics: the high level heuristic and a set of low level heuristics. A sequence of graph‐based low level heuristics is generated to guide the channel assignment process, and then searching in the heuristic space by the high level heuristic obtains the best channel scheduling scheme. The performance is tested on 20 benchmark problems, which show that the proposed graph‐based hyper‐heuristic algorithm is effective and outperforms the existing method. Copyright © 2015 John Wiley & Sons, Ltd.
Physiochemical and antioxidant properties of roselle‐mango juice blends; effects of packaging material, storage temperature and time
Authors: Mgaya‐Kilima Beatrice , Remberg Siv Fagertun , Chove Bernard Elias , Wicklund Trude
Published: January 2015

A study was conducted to determine the effects of packaging materials, seasonality, storage temperature and time on physiochemical and antioxidant properties of roselle‐mango juice blends. Roselle extract (20%, 40%, 60%, and 80%) was mixed with mango juice and stored in glass and plastic bottles at 4°C and 28°C. Total soluble solids, pH, titratable acidity, reducing sugar, color, vitamin C, total monomeric anthocyanins, total phenols, and antioxidant activity (FRAP) were evaluated in freshly prepared juice, and after, 2, 4, and 6 months of storage. The results showed that total soluble solids, reducing sugars, and pH increased with storage times under different storage time, irrespective of packaging materials. The acidity, color, total monomeric anthocyanin, vitamin C, total phenols, and antioxidant activity decreased during storage irrespective of storage temperature and packaging material. Loss of anthocyanins, total phenols, and vitamin C content were higher in blends stored at 28°C than 4°C.
DNA sensors are expressed in astrocytes and microglia in vitro and are upregulated during gliosis in neurodegenerative disease
Authors: Cox Donal J. , Field Robert H. , Williams David G. , Baran Marcin , Bowie Andrew G. , Cunningham Colm , Dunne Aisling
Published: January 2015

The detection of nucleic acids by the innate immune system is an essential host response during viral infection. In recent years, a number of immune sensors capable of recognizing cytosolic DNA have been identified and include the PYHIN family members AIM2, IFI16, and p204 as well as the enzyme, cGAS. Activation of these receptors leads to the induction of antiviral genes including Type‐1 interferons and chemokines such as CCL5. We have carried out extensive expression profiling of these DNA sensors and other members of the PYHIN family in highly purified primary astrocytes and microglia and have demonstrated that both cell types express the majority of these proteins at the mRNA level. In microglia, several family members are highly upregulated in response to IFN‐β treatment while both cell types induce robust proinflammatory and antiviral cytokine production (e.g., IL‐6, CCL5, IFN‐β) in the presence of immune stimulatory DNA and RNA. The production of IL‐6 is partially dependent on the interferon receptor as is IFN‐β itself. Furthermore, we have found that p204 and AIM2 are upregulated in a Type I IFN dependent fashion in vivo, in a murine model of chronic neurodegeneration. Given the propensity of inflammatory responses to cause neuronal damage, increased expression and activation of these receptors, not only during viral infection but also during sterile inflammatory responses, has the potential to exacerbate existing neuroinflammation leading to further damage and impaired neurogenesis. GLIA 2015;63:812–825
The thrombin receptor is a critical extracellular switch controlling myelination
Authors: Yoon Hyesook , Radulovic Maja , Drucker Kristen L. , Wu Jianmin , Scarisbrick Isobel A.
Published: January 2015

Hemorrhagic white matter injuries in the perinatal period are a growing cause of cerebral palsy yet no neuroprotective strategies exist to prevent the devastating motor and cognitive deficits that ensue. We demonstrate that the thrombin receptor (protease‐activated receptor 1, PAR1) exhibits peak expression levels in the spinal cord at term and is a critical regulator of the myelination continuum from initiation to the final levels achieved. Specifically, PAR1 gene deletion resulted in earlier onset of spinal cord myelination, including substantially more Olig2‐positive oligodendrocytes, more myelinated axons, and higher proteolipid protein (PLP) levels at birth. In vitro, the highest levels of PAR1 were observed in oligodendrocyte progenitor cells (OPCs), being reduced with differentiation. In parallel, the expression of PLP and myelin basic protein (MBP), in addition to Olig2, were all significantly higher in cultures of PAR1−/− oligodendroglia. Moreover, application of a small molecule inhibitor of PAR1 (SCH79797) to OPCs in vitro increased PLP and MBP expression. Enhancements in myelination associated with PAR1 genetic deletion were also observed in adulthood as evidenced by higher amounts of MBP and thickened myelin sheaths across large, medium, and small diameter axons. Enriched spinal cord myelination in PAR1−/− mice was coupled to increases in extracellular‐signal‐regulated kinase 1/2 and AKT signaling developmentally. Nocturnal ambulation and rearing activity were also elevated in PAR1−/− mice. These studies identify the thrombin receptor as a powerful extracellular regulatory switch that could be readily targeted to improve myelin production in the face of white matter injury and disease. GLIA 2015;63:846–859
Apolipoprotein E ε4 modulates functional brain connectome in Alzheimer's disease
Authors: Wang Jinhui , Wang Xiao , He Yi , Yu Xin , Wang Huali , He Yong
Published: January 2015

The apolipoprotein E (APOE) ɛ4 allele is a well‐established genetic risk factor for Alzheimer's disease (AD). Recent research has demonstrated an APOE ɛ4‐mediated modulation of intrinsic functional brain networks in cognitively normal individuals. However, it remains largely unknown whether and how APOE ɛ4 affects the brain's functional network architecture in patients with AD. Using resting‐state functional MRI and graph‐theory approaches, we systematically investigated the topological organization of whole‐brain functional networks in 16 APOE ɛ4 carriers and 26 matched noncarriers with AD at three levels: global whole‐brain, intermediate module, and regional node/connection. Neuropsychological analysis showed that the APOE ɛ4 carriers performed worse on delayed memory but better on a late item generation of a verbal fluency task (associated with executive function) than noncarriers. Whole‐brain graph analyses revealed that APOE ɛ4 significantly disrupted whole‐brain topological organization as characterized by (i) reduced parallel information transformation efficiency; (ii) decreased intramodular connectivity within the posterior default mode network (pDMN) and intermodular connectivity of the pDMN and executive control network (ECN) with other neuroanatomical systems; and (iii) impaired functional hubs and their rich‐club connectivities that primarily involve the pDMN, ECN, and sensorimotor systems. Further simulation analysis indicated that these altered connectivity profiles of the pDMN and ECN largely accounted for the abnormal global network topology. Finally, the changes in network topology exhibited significant correlations with the patients' cognitive performances. Together, our findings suggest that the APOE genotype modulates large‐scale brain networks in AD and shed new light on the gene‐connectome interaction in this disease. Hum Brain Mapp 36:1828–1846, 2015. © 2015 Wiley Periodicals, Inc.
View‐centralized multi‐atlas classification for Alzheimer's disease diagnosis
Authors: Liu Mingxia , Zhang Daoqiang , Shen Dinggang ,   the Alzheimer's Disease Neuroimaging Initiative
Published: January 2015

Multi‐atlas based methods have been recently used for classification of Alzheimer's disease (AD) and its prodromal stage, that is, mild cognitive impairment (MCI). Compared with traditional single‐atlas based methods, multiatlas based methods adopt multiple predefined atlases and thus are less biased by a certain atlas. However, most existing multiatlas based methods simply average or concatenate the features from multiple atlases, which may ignore the potentially important diagnosis information related to the anatomical differences among different atlases. In this paper, we propose a novel view (i.e., atlas) centralized multi‐atlas classification method, which can better exploit useful information in multiple feature representations from different atlases. Specifically, all brain images are registered onto multiple atlases individually, to extract feature representations in each atlas space. Then, the proposed view‐centralized multi‐atlas feature selection method is used to select the most discriminative features from each atlas with extra guidance from other atlases. Next, we design a support vector machine (SVM) classifier using the selected features in each atlas space. Finally, we combine multiple SVM classifiers for multiple atlases through a classifier ensemble strategy for making a final decision. We have evaluated our method on 459 subjects [including 97 AD, 117 progressive MCI (p‐MCI), 117 stable MCI (s‐MCI), and 128 normal controls (NC)] from the Alzheimer's Disease Neuroimaging Initiative database, and achieved an accuracy of 92.51% for AD versus NC classification and an accuracy of 78.88% for p‐MCI versus s‐MCI classification. These results demonstrate that the proposed method can significantly outperform the previous multi‐atlas based classification methods.Hum Brain Mapp 36:1847–1865, 2015. ©2015 Wiley Periodicals, Inc.
The role of the salience network in processing lexical and nonlexical stimuli in cochlear implant users
Authors: Song Jae‐Jin , Vanneste Sven , Lazard Diane S. , Van de Heyning Paul , Park Joo Hyun , Oh Seung Ha , De Ridder Dirk
Published: January 2015

Previous positron emission tomography (PET) studies have shown that various cortical areas are activated to process speech signal in cochlear implant (CI) users. Nonetheless, differences in task dimension among studies and low statistical power preclude from understanding sound processing mechanism in CI users. Hence, we performed activation likelihood estimation meta‐analysis of PET studies in CI users and normal hearing (NH) controls to compare the two groups. Eight studies (58 CI subjects/92 peak coordinates; 45 NH subjects/40 peak coordinates) were included and analyzed, retrieving areas significantly activated by lexical and nonlexical stimuli. For lexical and nonlexical stimuli, both groups showed activations in the components of the dual‐stream model such as bilateral superior temporal gyrus/sulcus, middle temporal gyrus, left posterior inferior frontal gyrus, and left insula. However, CI users displayed additional unique activation patterns by lexical and nonlexical stimuli. That is, for the lexical stimuli, significant activations were observed in areas comprising salience network (SN), also known as the intrinsic alertness network, such as the left dorsal anterior cingulate cortex (dACC), left insula, and right supplementary motor area in the CI user group. Also, for the nonlexical stimuli, CI users activated areas comprising SN such as the right insula and left dACC. Previous episodic observations on lexical stimuli processing using the dual auditory stream in CI users were reconfirmed in this study. However, this study also suggests that dual‐stream auditory processing in CI users may need supports from the SN. In other words, CI users need to pay extra attention to cope with degraded auditory signal provided by the implant. Hum Brain Mapp 36:1982–1994, 2015. © 2015 Wiley Periodicals, Inc.
Interaction of tetraspan(in) TM4SF5 with CD44 promotes self‐renewal and circulating capacities of hepatocarcinoma cells
Authors: Lee Doohyung , Na Juri , Ryu Jihye , Kim Hye‐Jin , Nam Seo Hee , Kang Minkyung , Jung Jae Woo , Lee Mi‐Sook , Song Haeng Eun , Choi Jungeun , Lee Gyu‐Ho , Kim Tai Young , Chung June‐Key , Park Ki Hun , Kim Sung‐Hak , Kim Hyunggee , Seo Howon , Kim Pilhan , Youn Hyewon , Lee Jung Weon
Published: January 2015

Tumor metastasis involves circulating and tumor‐initiating capacities of metastatic cancer cells. Epithelial‐mesenchymal transition (EMT) is related to self‐renewal capacity and circulating tumor cell (CTC) characteristics for tumor metastasis. Although tumor metastasis is a life‐threatening, complicated process that occurs through circulation of tumor cells, mechanistic aspects of self‐renewal and circulating capacities have been largely unknown. Hepatic transmembrane 4 L six family member 5 (TM4SF5) promotes EMT for malignant growth and migration, so it was rationalized that TM4SF5, as a hepatocellular carcinoma (HCC) biomarker, might be important for metastatic potential. Here, self‐renewal capacity by TM4SF5 was mechanistically explored using hepatocarcinoma cells with or without TM4SF5 expression, and we explored whether they became CTCs using mouse liver‐orthotopic model systems. We found that TM4SF5‐dependent sphere growth correlated with CD24−, aldehyde dehydrogenase (ALDH) activity, as well as a physical association between CD44 and TM4SF5. Interaction between TM4SF5 and CD44 was through their extracellular domains with N‐glycosylation modifications. TM4SF5/CD44 interaction activated proto‐oncogene tyrosine‐protein kinase Src (c‐Src)/signal transducer and activator of transcription 3 (STAT3)/Twist‐related protein 1 (Twist1)/B‐cell‐specific Moloney murine leukemia virus integration site 1 (Bmi1) signaling for spheroid formation, whereas disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts using 200∼5,000 cells per injection, TM4SF5‐positive tumors exhibited subpopulations with locally increased CD44 expressions, supporting for tumor cell differentiation. TM4SF5‐positive, but not TM4SF5‐ or CD44‐knocked‐down, cells were identified circulating in blood 4‐6 weeks after orthotopic liver injection using in vivo laser scanning endomicroscopy. Anti‐TM4SF5 reagent blocked their metastasis to distal intestinal organs. Conclusion: TM4SF5 promotes self‐renewal and CTC properties supported by TM4SF5+/CD44+(TM4SF5‐bound)/ALDH+/CD24− markers during HCC metastasis. (Hepatology 2015;61:1978‐1997)