bluuebunny/crossref_metadata_2025 huggingface dataset:
Ni@Pd nanoparticles supported on ionic liquid‐functionalized KCC‐1 as robust and recyclable nanocatalysts for cycloaddition of propargylic amines and CO2
Authors: Sadeghzadeh Seyed Mohsen , Zhiani Rahele , Emrani Shokufe
Published: June 2017

Novel heterogeneous catalyst systems comprised of a fibrous nanosilica‐supported nano‐Ni@Pd‐based ionic liquid (KCC‐1/IL/Ni@Pd) are described for the cyclization of propargylic amines with CO2 to provide 2‐oxazolidinones. KCC‐1 with high surface area was functionalized with IL acting as a robust anchor so that the nano‐Ni@Pd was well dispersed on the fibres of the KCC‐1 microspheres, without aggregation. Because of the amplification effect of IL, high loading capacities of the nanocatalysts were achieved. The reported synthesis includes several advantages like solvent‐free conditions, operational simplicity, short reaction times, environmentally benign reaction conditions, cost effectiveness, high atom economy and excellent yields, making it a genuinely green protocol.
Analysis of the performance of polysaccharide membranes in aqueous media as a tool to assist wound‐dressing selection
Authors: Bombaldi de Souza Renata Francielle , Bombaldi de Souza Fernanda Carla , Moraes Ângela Maria
Published: June 2017

The behavior of hydrophilic matrixes in the presence of aqueous media plays a pivotal role in the selection of materials that come into contact with body fluids. Because polysaccharides have proven benefits in the treatment of skin lesions, the performance of membranes produced with chitosan combined with alginate [chitosan–alginate (Ch–A)], xanthan [chitosan–xanthan (Ch–X)], or guar gum [chitosan–guar gum (Ch–G)] after exposure to different aqueous solutions and humidity levels was analyzed with the aim of directing their applications as dressings in wounds with different exudate productions. The Ch–X membranes presented a high fluid‐uptake capacity and water‐vapor transmission rate (WVTR); this was attributed to ramifications in the xanthan structure, and the membranes were then recommended for moderately to highly exuding wounds. The Ch–G membranes showed a dense structure and presented low fluid‐uptake capacity; they were more appropriate for low‐exuding wounds or wounds in the advanced stage of cicatrization. Both the Ch–A and Ch–G membranes presented adequate mechanical properties in a wide range of relative humidity conditions and could be considered suitable for use in all body parts. However, as the Ch–A formulation showed limited WVTR, its use should be restrictedly to, at most, moderately exuding wounds. In all cases, the assessment of the wound type by a professional would be required to define the final dressing formulation. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2017,134, 45386.
Prolidase is a critical enzyme for complete gliadin digestion in Tenebrio molitor larvae
Authors: Tereshchenkova Valeriia F. , Goptar Irina A. , Zhuzhikov Dmitry P. , Belozersky Mikhail A. , Dunaevsky Yakov E. , Oppert Brenda , Filippova Irina Yu. , Elpidina Elena N.
Published: June 2017

Prolidase is a proline‐specific metallopeptidase that cleaves imidodipeptides with C‐terminal Pro residue. Prolidase was purified and characterized from the Tenebrio molitor larval midgut. The enzyme was localized in the soluble fraction of posterior midgut tissues, corresponding to a predicted cytoplasmic localization of prolidase according to the structure of the mRNA transcript. Expression of genes encoding prolidase and the major digestive proline‐specific peptidase (PSP)—dipeptidyl peptidase 4—were similar. The pH optimum of T. molitor prolidase was 7.5, and the enzyme was inhibited by Z‐Pro, indicating that it belongs to type I prolidases. In mammals, prolidase is particularly important in the catabolism of a proline‐rich protein—collagen. We propose that T. molitor larval prolidase is a critical enzyme for the final stages of digestion of dietary proline‐rich gliadins, providing hydrolysis of imidodipeptides in the cytoplasm of midgut epithelial cells. We propose that the products of hydrolysis are absorbed from the luminal contents by peptide transporters, which we have annotated in the T. molitor larval gut transcriptome. The origin of prolidase substrates in the insect midgut is discussed in the context of overall success of grain feeding insects.
Operant discrimination training to establish praise as a reinforcer
Authors: Lugo Ashley M. , Mathews Therese L. , King Melissa L. , Lamphere John C. , Damme Ana M.
Published: June 2017

Social deficits are a hallmark feature of autism spectrum disorder (ASD). Consequently, socially mediated consequences (i.e., praise) may not function as reinforcers for individuals with ASD. Given the frequency in which praise is used as a programmed consequence in empirical research and in clinical practice, it is necessary to explore procedures that could condition praise to function as reinforcers. Operant discrimination training has emerged as a potential procedure to condition stimuli to acquire reinforcing properties. This study aimed to utilize the operant discrimination training procedure to condition a praise statement to function as a reinforcer. Four children diagnosed with ASD participated in the study. A nonconcurrent multiple baseline design across participants was used to evaluate this emerging pairing procedure. Findings suggest that immediate effects were observed across all participants, but responding did not maintain, suggesting that reinforcing value of the praise statement diminished.
Design and Control Comparison of Alternative Separation Methods for n‐Heptane/Isobutanol
Authors: Luyben William L.
Published: June 2017

The binary mixture of n‐heptane and isobutanol forms an azeotrope at atmospheric pressure, with a composition of 66.9 mol % n‐heptane and a temperature of 364 K. Several methods of separation are possible. This study compares the steady‐state economics and the dynamic controllability of three alternative separation techniques: a two‐column extractive distillation process, a two‐column pressure‐swing distillation process, and a single column with a refrigerated condenser.
Asymmetric Synthesis and Antitumor Activity of Spiro‐Oxadiazole Derivatives from 1,4:3,6‐Dianhydro‐D‐fructose
Authors: Xu Wenke , Ge Yongxun , Hou Yu , Liu Yingju , Hua Yingchun , Han Weiwei , Qin Zhiyan , Liu Fengwu
Published: June 2017

A series of spiro‐oxadiazoles were synthesized from 1,4:3,6‐dianhydro‐D‐fructose and hydrazides via a stereo‐ selective two‐step reaction sequence. The structures of newly synthesized compounds were established by spectral analysis. The absolute configuration of compound 2a was further confirmed by single crystal X‐ray analysis. All the synthesized compounds were screened for their in vitro antitumor activity, showing that these compounds have poor inhibitory activities against A549, MGC‐803 tumor cells.
Ionothermal Synthesis and Structural Characterization of a Novel Open Framework Zinc Diphosphonate with Carboxylate‐like Linker
Authors: Zhang Li , Liu Lei , Dong Jinxiang
Published: June 2017

A novel crystalline zinc diphosphonate, (CH3NH3)4Zn2(xbp)2•H2O, denoted as compound 1, was ionothermally synthesized from tetraethyl‐p‐xylylenebisphosphonate (Texbp) and Zn(OAc)2 in a protic eutectic mixture with urea/methylamine hydrochloride. Its structure was determined by single‐crystal X‐ray diffraction data and had a special three‐dimensional open framework with rhombic channels. Compound 1 belongs to the monoclinic system (space group C2/c), with lattice parameters a=22.6876(19) Å, b=8.7376(7) Å, c=8.1673(9) Å, β=108.146(2)°, V=1538.5(2) Å3, Z=2. Its structure is totally different from the typical organic pillared structure, only two oxygens of the phosphonate group are coordinated with zinc atoms, and the third oxygen exists in the terminal form, which is similar to the popular dicarboxylate linkers in MOFs. The organic cations [CH3NH3]+ of the eutectic mixture played a structure‐directing role for constructing this framework and were confined in the pore channels to balance the negative charges resulting from the zinc phosphonate inorganic chains.
Depressive symptoms predict cancer caregivers' physical health decline
Authors: Shaffer Kelly M. , Kim Youngmee , Carver Charles S. , Cannady Rachel S.
Published: June 2017

BACKGROUND

Cancer caregiving has been associated with worsening health among caregivers themselves, yet demographic and psychosocial predictors of their long‐term health decline are less known. This study examines changes in caregivers' physical health 2 to 8 years after their family members' cancer diagnosis and prospective predictors of that change.

METHODS

Caregivers (n = 664; mean age, 53.2 years) participated in a nationwide study at 2 (T1), 5 (T2), and 8 (T3) years after their family members' cancer diagnosis. Physical health (12‐item Medical Outcomes Study Short Form Health Survey Physical Component Scale) was assessed T1 through T3 as outcome. Predictors were self‐reported at T1, including caregiver demographics (age, sex, education, income, relationship to patient, and employment status), patient cancer severity (from medical records), and caregiver psychosocial factors (caregiving stress, caregiving esteem, social support, and depressive symptoms). Latent growth modeling tested predictors of caregivers' initial physical health and their physical health change across time.

RESULTS

At T1, caregivers reported slightly better physical health than the US population (M = 51.22, P = .002), which declined over the following 6 years (Mslope = −0.27, P < .001). All demographic factors, patient cancer severity, and T1 caregiving stress were related to caregivers' initial physical health (P ≤ .03). Higher depressive symptoms were unrelated to caregivers' initial physical health, but were the only significant predictor of caregivers' more rapid physical health decline (B = −0.02, P = .004).

CONCLUSION

Findings highlight the unique contribution of caregivers' depressive symptoms to their physical health decline. Assessing and addressing depressive symptoms among caregivers early in the cancer survivorship trajectory may help to prevent premature health decline among this important yet vulnerable population. Cancer 2017;123:4277–4285. © 2017 American Cancer Society.
A multicenter, phase 3, randomized trial of concurrent chemoradiotherapy plus adjuvant chemotherapy versus radiotherapy alone in patients with regionally advanced nasopharyngeal carcinoma: 10‐year outcomes for efficacy and toxicity
Authors: Lee Anne W. M. , Tung Stewart Y. , Ng Wai Tong , Lee Victor , Ngan Roger K. C. , Choi Horace C. W. , Chan Lucy L. K. , Siu Lillian L. , Ng Alice W. Y. , Leung To Wai , Yiu Harry H. Y. , O'Sullivan Brian , Chappell Rick
Published: June 2017

BACKGROUND

Concurrent‐adjuvant chemoradiotherapy (CRT) became a recommended treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) with the first report of a significant survival benefit from the Intergroup 0099 study. However, data on late toxicities are lacking. Previous reports from the current NPC‐9901 trial have raised concerns about a failure to improve overall survival (OS) because of an inadequate impact on distant control and increases in toxicities/noncancer deaths. Validation of the long‐term therapeutic ratio is needed.

METHODS

In this phase 3, randomized trial, patients with nonkeratinizing NPC (stage T1‐4/N2‐3/M0) were randomly assigned to radiotherapy alone (176 patients) or to CRT (172 patients) with concurrent cisplatin followed by adjuvant cisplatin plus fluorouracil.

RESULTS

The early findings of significant improvements in tumor control were maintained: the CRT group achieved significantly higher 10‐year overall failure‐free (62% vs 50%; P = .01) and progression‐free survival rates (56% vs 42%; P = .006) because of superior locoregional control (87% vs 74%; P = .003), whereas the impact on distant control remained insignificant (68% vs 65%; P = .24). The initial differences in toxicities diminished with longer follow‐up: 52% versus 47% at 10 years for late toxicities (P = .20), 4.1% versus 2.8% for deaths due to treatment toxicity, and 15.1% versus 13.1% for deaths due to incidental/unknown causes. The OS rate for the CRT group reached statistical superiority at 10 years (62% vs 49%; P = .047).

CONCLUSIONS

Long‐term results have confirmed that CRT can significantly improve OS without excessive late toxicities for patients with regionally advanced NPC. However, more potent therapy is needed for improving distant control, especially for patients with stage IVA/B disease. Cancer 2017;123:4147–4157. © 2017 American Cancer Society.
Cost effectiveness of regorafenib as second‐line therapy for patients with advanced hepatocellular carcinoma
Authors: Parikh Neehar D. , Singal Amit G. , Hutton David W.
Published: June 2017

BACKGROUND

Regorafenib, a multikinase inhibitor, has demonstrated prolonged survival by 2.8 months as a second‐line agent in patients with hepatocellular carcinoma (HCC) who progress on sorafenib therapy. The objective of the current study was to examine the cost effectiveness of regorafenib for the treatment of HCC.

METHODS

The authors constructed a Markov simulation model of patients with unresectable HCC and Child‐Pugh A cirrhosis who received treatment with regorafenib versus best supportive care. Model inputs for regorafenib effectiveness and rates of adverse events in patients with HCC were based on published clinical trial data and literature review. Quality‐adjusted life years (QALYs) were calculated along with the incremental cost‐effectiveness ratio (ICER) of regorafenib therapy. One‐way sensitivity analyses also were conducted simultaneously on all model parameters and on various Monte‐Carlo simulation parameters, and the regorafenib cost threshold at which cost effectiveness would be achieved was determined.

RESULTS

Regorafenib provided an increase of 0.18 QALYs at a cost of $47,112. The ICER for regorafenib, compared with best supportive care, was $224,362. In 1‐way sensitivity analyses, there were no scenarios in which regorafenib was cost effective. In cost threshold analysis, regorafenib would have to be priced at or below $67 per pill to be cost effective at an ICER of $100,000.

CONCLUSIONS

Regorafenib is not cost effective as a second‐line agent in the treatment of HCC, with a marginal increase in QALYs at a high cost. Lowering the cost of regorafenib or improving the selection of patients who can achieve maximal survival benefit would improve its value as a second‐line treatment option for patients with HCC. Cancer 2017;123:3725–3731. © 2017 American Cancer Society
Green Processing of Lignocellulosic Biomass and Its Derivatives in Deep Eutectic Solvents
Authors: Tang Xing , Zuo Miao , Li Zheng , Liu Huai , Xiong Caixia , Zeng Xianhai , Sun Yong , Hu Lei , Liu Shijie , Lei Tingzhou , Lin Lu
Published: June 2017

Invited for this month′s cover is the BCCL group led by Prof. Lu Lin at Xiamen University. The image shows the fractionation of lignocellulose into its individual components (including cellulose, hemicellulose, and lignin) and the conversion of these biopolymers into their derivatives in deep eutectic solvents. The Review itself is available at 10.1002/cssc.201700457.
Reducing greenhouse gas emissions and improving air quality: Two global challenges
Authors: Erickson Larry E.
Published: June 2017

There are many good reasons to promote sustainable development and reduce greenhouse gas emissions and other combustion emissions. The air quality in many urban environments is causing many premature deaths because of asthma, cardiovascular disease, chronic obstructive pulmonary disease, lung cancer, and dementia associated with combustion emissions. The global social cost of air pollution is at least $3 trillion/year; particulates, nitrogen oxides and ozone associated with combustion emissions are very costly pollutants. Better air quality in urban environments is one of the reasons for countries to work together to reduce greenhouse gas emissions through the Paris Agreement on Climate Change. There are many potential benefits associated with limiting climate change. In the recent past, the concentrations of greenhouse gases in the atmosphere have been increasing and the number of weather and climate disasters with costs over $1 billion has been increasing. The average global temperature set new record highs in 2014, 2015, and 2016. To reduce greenhouse gas emissions, the transition to electric vehicles and electricity generation using renewable energy must take place in accord with the goals of the Paris Agreement on Climate Change. This work reviews progress and identifies some of the health benefits associated with reducing combustion emissions. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 982–988, 2017
A power balancing method of distributed generation and electric vehicle charging for minimizing operation cost of distribution systems with uncertainties
Authors: Wu Jiekang , Wu Zhishan , Wu Fan , Mao Xiaoming
Published: June 2017

A power balancing method of distributed generation (DG) and electric vehicle charging is presented for minimizing operation costs of distribution systems with uncertainties, which includes the uncertainties in output power of DG and the randomness of charging power of electric vehicles (EV). A probability model is established for the uncertain characteristics of DG and electric vehicle charging. A multi‐state optimization coordination method for DG of renewable energy systems and electric vehicle charging in distribution systems based on quadratic rotation cone programming is presented to minimize the expected generation cost of generators in the main power grid, the expected operation cost of DG systems in distribution systems, and the expected social outage loss. An objective function maximizing the operation efficiency of distribution systems with DGs and EVs is proposed. Using quadratic rotated conic programming, the nonlinear objective function and constraint functions are transformed into a linear form. An IEEE 14‐node distribution system is used as a study example to illustrate adaptability of the proposed model and the feasibility of the proposed method. The simulation results show that the proposed method simplifies the original problem of the optimization problem and makes its solution faster, more stable, and better.
Mineral composition of Tamarindus indica LINN (tamarind) pulp and seeds from different agro‐ecological zones of Uganda
Authors: Okello Jaspher , Okullo John B. L. , Eilu Gerald , Nyeko Philip , Obua Joseph
Published: June 2017

Mineral composition of dry Tamarindus indica LINN pulp and seeds was evaluated on samples collected from three different agro‐ecological zones of Uganda (Lake Victoria Crescent, and Eastern and West Nile). The objective of the study was to evaluate the mineral composition of T. indica pulp and seed samples from across Uganda's different agro‐ecological zones and land use types. Separately grounded samples of T. indica pulp and seeds were analyzed for Zn, Fe, Mg, P, Na, K, and Ca. The univariate analysis of variance in the General Linear Model was used to compare differences in mineral composition. Treatment means were separated using Least Significant Difference (LSD) in Post Hoc Tests. The results showed that there were significant differences (p ≤ 0.005) in mineral composition levels of T. indica pulp and seed samples between the different agro‐ecological zones with the exception of P and Na (for pulp). The T. indica pulp and seeds samples from the Lake Victoria Crescent zone and wild land use type had generally higher mineral levels than T. indica samples from other agro‐ecological zones and different land use types. As mineral composition levels were generally higher in the seed than the pulp samples, consumption of T. indica seeds should be promoted. There is also need to conserve individual species both on‐farm and in the wild population, but T. indica mineral concentrations (both pulp and seeds) were higher in the samples from the wild population, making them good for human and animal diets.
Sensory processes modulate differences in multi‐component behavior and cognitive control between childhood and adulthood
Authors: Gohil Krutika , Bluschke Annet , Roessner Veit , Stock Ann‐Kathrin , Beste Christian
Published: June 2017

Many everyday tasks require executive functions to achieve a certain goal. Quite often, this requires the integration of information derived from different sensory modalities. Children are less likely to integrate information from different modalities and, at the same time, also do not command fully developed executive functions, as compared to adults. Yet still, the role of developmental age‐related effects on multisensory integration processes has not been examined within the context of multicomponent behavior until now (i.e., the concatenation of different executive subprocesses). This is problematic because differences in multisensory integration might actually explain a significant amount of the developmental effects that have traditionally been attributed to changes in executive functioning. In a system, neurophysiological approach combining electroencephaloram (EEG) recordings and source localization analyses, we therefore examined this question. The results show that differences in how children and adults accomplish multicomponent behavior do not solely depend on developmental differences in executive functioning. Instead, the observed developmental differences in response selection processes (reflected by the P3 ERP) were largely dependent on the complexity of integrating temporally separated stimuli from different modalities. This effect was related to activation differences in medial frontal and inferior parietal cortices. Primary perceptual gating or attentional selection processes (P1 and N1 ERPs) were not affected. The results show that differences in multisensory integration explain parts of transformations in cognitive processes between childhood and adulthood that have traditionally been attributed to changes in executive functioning, especially when these require the integration of multiple modalities during response selection. Hum Brain Mapp 38:4933–4945, 2017. © 2017 Wiley Periodicals, Inc.
Thyroid neoplasia risk is increased nearly 30 years after the Chernobyl accident
Authors: Tronko Mykola , Brenner Alina V. , Bogdanova Tetiana , Shpak Victor , Oliynyk Valeriy , Cahoon Elizabeth K. , Drozdovitch Vladimir , Little Mark P. , Tereshchenko Valeriy , Zamotayeva Galyna , Terekhova Galyna , Zurnadzhi Lyudmila , Hatch Maureen , Mabuchi Kiyohiko
Published: June 2017

To evaluate risk of thyroid neoplasia nearly 30 years following exposure to radioactive iodine (I‐131) from the 1986 Chernobyl nuclear accident, we conducted a fifth cycle of thyroid screening of the Ukrainian‐American cohort during 2012–2015, following four previous screening cycles started in 1998. We identified 47 thyroid cancers (TC) and 33 follicular adenomas (FA) among 10,073 individuals who were <18 years at the time of the accident and had a mean I‐131 dose of 0.62 Gy. We found a significant I‐131 dose response for both TC and FA, with an excess odd ratio per Gy of 1.36 (95% CI: 0.39–4.15) and 2.03 (95% CI: 0.55–6.69), respectively. The excess risk of malignant and benign thyroid neoplasia persists nearly three decades after exposure and underscores the importance of continued follow‐up of this cohort to characterize long‐term pattern of I‐131 risk.
Impact of extending screening mammography to older women Information to support informed choices
Authors: Jacklyn Gemma , Howard Kirsten , Irwig Les , Houssami Nehmat , Hersch Jolyn , Barratt Alexandra
Published: June 2017

From 2013 through 2017, the Australian national breast cancer screening programme is gradually inviting women aged 70–74 years to attend screening, following a policy decision to extend invitations to older women. We estimate the benefits and harms of the new package of biennial screening from age 50–74 compared with the previous programme of screening from age 50–69. Using a Markov model, we applied estimates of the relative risk reduction for breast cancer mortality and the risk of overdiagnosis from the Independent UK Panel on Breast Cancer Screening review to Australian breast cancer incidence and mortality data. We estimated screening specific outcomes (recalls for further imaging, biopsies, false positives, and interval cancer rates) from data published by BreastScreen Australia. When compared with stopping at age 69, screening 1,000 women to age 74 is likely to avert one more breast cancer death, with an additional 78 women receiving a false positive result and another 28 women diagnosed with breast cancer, of whom eight will be overdiagnosed and overtreated. The extra 5 years of screening results in approximately 7 more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. Supporting informed decision making for this age group should be a public health priority.
Atypical uterine cervix metastases from invasive lobular carcinoma of the breast
Authors: Parrilla Carmen , Barco Israel , Pedrerol Ares , Pessarrodona Antoni , Giménez Nuria , García‐Fernández Antonio
Published: June 2017

Invasive lobular carcinoma exhibits considerable differences from invasive ductal carcinoma; its potential to spread to uncommon locations should be born in mind.
Spectroscopic investigation of the effects of aqueous‐phase prepared CdTe quantum dots on protein hemoglobin at the molecular level
Authors: Guo Dandan , Liu Rutao
Published: June 2017

3‐Mercaptopropionic Acid‐modified CdTe quantum dots (QDs) were synthesized and characterized by infrared, fluorescence, and ultraviolet–visible absorption spectra and Nano‐ZetaSizer measurements. Then the interaction between QDs and hemoglobin was studied to investigate the effects of QDs on the structure and function of hemoglobin by using a variety of spectroscopy methods and isothermal titration calorimetry. The results showed van der Waals forces and hydrogen bonding predominantly played major roles in the binding. The intrinsic fluorescence of hemoglobin was quenched with changes to the microenvironment of tyrosine and tryptophan residues and complex conformational changes of hemoglobin were induced with the loosening and unfolding skeleton. However, the heme in hemoglobin was still stable, indicating that the main physiological function of hemoglobin might not be significantly inhibited. This study will provide a new strategy to study the biological toxicity of QDs at the molecular level.
N‐linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H+‐ATPase (V‐ATPase) biosynthesis
Authors: Esmail Sally , Kartner Norbert , Yao Yeqi , Kim Joo Wan , Reithmeier Reinhart A.F. , Manolson Morris F.
Published: June 2017

The a subunit of the V0 membrane‐integrated sector of human V‐ATPase has four isoforms, a1‐a4, with diverse and crucial functions in health and disease. They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N‐glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N‐glycosylated. Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope‐tagged human a1‐a3 subunits, with or without mutations that convert Asn to Gln at putative N‐glycosylation sites. Expression and N‐glycosylation were characterized by immunoblotting and mobility shifts after enzymatic deglycosylation, and intracellular localization was determined using immunofluorescence microscopy. All unglycosylated mutants, where predicted N‐glycosylation sites had been eliminated by sequon mutagenesis, showed increased relative mobility on immunoblots, identical to what was seen for wild‐type a subunits after enzymatic deglycosylation. Cycloheximide‐chase experiments showed that unglycosylated subunits were turned over at a higher rate than N‐glycosylated forms by degradation in the proteasomal pathway. Immunofluorescence colocalization analysis showed that unglycosylated a subunits were retained in the ER, and co‐immunoprecipitation studies showed that they were unable to associate with the V‐ATPase assembly chaperone, VMA21. Taken together with our previous a4 subunit studies, these observations show that N‐glycosylation is crucial in all four human V‐ATPase a subunit isoforms for protein stability and ultimately for functional incorporation into V‐ATPase complexes.
Therapeutic potentials of adenosine receptors agonists and antagonists in colitis; Current status and perspectives
Authors: Bahreyni Amirhossein , Samani Seyed S. , Khazaei Majid , Ryzhikov Mikhail , Avan Amir , Hassanian Seyed M.
Published: June 2017

Increasing evidence suggests that adenosine is dysregulated in ulcerative colitis (UC), potentially affecting UC pathogenesis, diagnosis, and therapy. Dysregulation of the activity of adenosine generating enzymes including adenosine deaminase in serum of patients with acute colitis supports the role of this omnipresent metabolite in the pathogenesis of colitis. Adenosine regulates inflammatory responses including epithelial barrier hyper‐permeability, myeloperoxidase activity, and neuromuscular motility in colitis, supporting the therapeutic potency of adenosine receptors agonists and antagonists in this disease. Depending upon the adenosine receptor subtype, activation or suppression of the receptor with pharmacological agonists or antagonists attenuates colitis pathological symptoms in colitis model. This review summarizes the role of adenosine receptors agonists and antagonists in the pathogenesis of colitis for a better understanding and hence a better management of this disease.
Endogenous bioelectric currents promote differentiation of the mammalian lens
Authors: Cao Lin , Liu Jie , Pu Jin , Collinson J. Martin , Forrester John V. , McCaig Colin D.
Published: June 2017

The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lens equator are poorly understood. We detected that mature, denucleated lens fibers expressed high levels of the α1 and β1 subunits of Na+/K+‐ATPase (ATP1A1 and ATP1B1 of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem). In contrast, differentiating, nucleated lens fiber cells had little ATP1A1 and ATP1B1 and a depolarized Vmem. Mimicking the natural equatorial ES with an applied electrical field (EF) induced a striking reorientation of lens epithelial cells to lie perpendicular to the direction of the EF. An EF also promoted the expression of β‐crystallin, aquaporin‐0 (AQP0) and the Beaded Filament Structural Protein 2 (BFSP2) in lens epithelial cells (LECs), all of which are hallmarks of differentiation. In addition, applied EF activated the AKT and CDC2 and inhibition of AKT reduced the activation of CDC2. Our results indicate that the endogenous bioelectrical signal at the lens equator promotes differentiation of LECs into denucleated lens fiber cells via depolarization of Vmem. Development of methods and devices of EF application or amplification in vivo may supply a novel treatment for lens diseases and even promote regeneration of a complete new lens following cataract surgery.
Recovery and primary purification of bacteriophage M13 using aqueous two‐phase systems
Authors: González‐Mora Alejandro , Ruiz‐Ruiz Federico , Benavides Jorge , Willson Richard C , Rito‐Palomares Marco
Published: June 2017

BACKGROUND

Bacteriophage M13 is an Escherichia coli‐specific non‐lytic filamentous virus commonly used in applications ranging from antibody screening and nanomaterial construction to drug delivery, among others. In this tenor, alternative methods for the fractionation, recovery and partial purification of phage particles are desired. In this work, the use of aqueous two‐phase systems (ATPS) was evaluated as an alternative method for the recovery of phage particles.

RESULTS

The partition behavior of M13 in PEG–salt and ionic liquid (IL)–salt ATPS was characterized using a pre‐purified feedstock. In PEG‐salt ATPS, M13 was preferentially partitioned to the interface. In IL ATPS, however, M13 showed a high‐top phase preference with recovery yields above 65%. Selected systems were tested for the extraction of M13 from a crude fermentation broth. From crude broth, a PEG 400‐potassium phosphate system with volume ratio (VR) of 1 and 25% w/w tie line length (TLL) gave the best M13 top phase recovery (83%) and purification fold (18.2) in terms of total protein concentration.

CONCLUSIONS

The results presented here demonstrate the practical application of ATPS as an efficient process for the primary recovery and partial purification of M13 and represent the first study of the extraction of viral particles directly from a crude broth as well as the use of IL‐Salt ATPS. © 2017 Society of Chemical Industry
Proposed new staging system for ampulla of Vater cancer with greater discriminatory ability: multinational study from eastern and western centers
Authors: He Jin , Kim Jae Ri , Lee Seung Yeoun , Oh Jinseok , Park Taesung , Kang Mee Joo , Kwon Wooil , Kim Hongbeom , Kim Sun‐Whe , Cameron John L. , Wolfgang Christopher L. , Jang Jin‐Young
Published: June 2017

Background

We built a multinational retrospective database of patients with ampulla of Vater cancer to develop a reliable new staging system.

Method

This study included 841 patients with ampulla of Vater cancer after curative surgery at Seoul National University Hospital (n = 440) and Johns Hopkins University medical institutions (n = 401) between 1985 and 2013.

Results

The 5‐year overall survival (OS) rates of patients staged according to the 7th American Joint Committee on Cancer staging system were 80.3%, 60.9%, 58.1%, 36.6%, 17.9%, and 25.0% for Stages IA (n = 140), IB (n = 194), IIA (n = 115), IIB (n = 348), III (n = 33), and IV (n = 4), respectively. Five‐year OS rates were similar in patients with Stage IB (T2N0M0) and IIA (T3N0M0) tumors (P = 0.556), but differed significantly between other pairs of groups. The number of positive lymph nodes (PLN) enhanced prognosis when stratified as 0, 1–2 and ≥3 (P < 0.001). The revised staging system consisted of Stages I (T1, PLN 0), IIA (T2–T3, PLN 0), IIB (T1–T3, PLN 1–2), III (PLN ≥3 or any T4), and IV (any M1), with 5‐year OS rates differing significantly in each pair of groups, including Stages I and IIA (P < 0.001).

Conclusion

This new staging system has better discriminatory ability in stratifying 5‐year OS rates based on a large multinational database.
Intracavitary vaginal brachytherapy using a custom balloon applicator
Authors: Paterson Dean B. , Pearson Shelley M. , Wilson Andrew N.
Published: June 2017

A custom balloon applicator was created to deliver intracavitary high‐dose‐rate brachytherapy to a patient with a superficial vaginal cancer. The patient was unable to be treated conventionally due to an extremely narrow introitus that prevented the introduction of a conventional cylinder applicator. The custom applicator was constructed by inserting a straight titanium tandem applicator through the drainage lumen of a Foley catheter. The applicator was inserted and the catheter balloon was inflated when positioned at the vaginal apex. Three brachytherapy treatments were performed using this technique. Individual balloon eccentricities resulted in small radial tandem offsets within the balloon. This phenomenon was exploited by orientating the tandem offset in the direction of the target volume. Acceptable dosimetry was achieved for all fractions and the procedure was very well tolerated. The custom applicator was a viable solution that was safely developed in a short time frame using equipment readily available in our department.
Prevalence of human papillomavirus infection in women in the Autonomous Region of Inner Mongolia: A population‐based study of a Chinese ethnic minority
Authors: Wang Xiaohua , Ji Yunpeng , Li Juan , Dong Hong , Zhu Bo , Zhou Yan , Wang Jie , Zhou Xueyuan , Wang Yan , Peppelenbosch Maikel P. , Pan Qiuwei , Ji Xiaoping , Liu Dongjun
Published: June 2017

Human papillomavirus (HPV) is one of the most common sexually transmitted infectious pathogens. Persistent infection has been linked to cancer development, in particular to cervical cancer. This study aims to investigate the epidemiology of HPV infection in women in Inner Mongolia of China and to dissect the disparities between the Han and Mongolian ethnic populations. Cervical cell samples from 5655 women (17‐68 years old) were collected during routine gynecologic examination. HPV infection was established using the HPV GenoArray kit detecting 21 HPV genotypes. The overall HPV prevalence was 14.5%. HPV16 (5.0%), HPV58 (2.2%), and HPV52 (1.5%) are the most common genotypes. Of the 21 genotypes investigated, high‐risk HPV genotypes dominate in all age groups. HPV16 and HPV58 are the most common genotypes in patients with cervical lesions. HPV prevalence among Han women is 11.5% and the most common genotypes are HPV16 (4%) and HPV58 (2.1%). HPV prevalence is significantly higher in Mongolian women (32.6%), with the most common genotypes being HPV16 (10.7%), HPV31 (7.1%), and HPV52 (4.3%). The multiple infection rate in Mongolian participants (14.9%) is also higher than that of Han participants (4.3%). Urbanization, the number of sex partners, and PAP history appear as risk factors for HPV infection in Han, but not in Mongolian participants. HPV infection is highly prevalent in women in Inner Mongolia, China. HPV16 remains the most common genotype in this area. However, there are clear ethnical disparities in respect to the HPV epidemiology between the Han and Mongolian population.
Text mining for search term development in systematic reviewing: A discussion of some methods and challenges
Authors: Stansfield Claire , O'Mara‐Eves Alison , Thomas James
Published: June 2017

Using text mining to aid the development of database search strings for topics described by diverse terminology has potential benefits for systematic reviews; however, methods and tools for accomplishing this are poorly covered in the research methods literature. We briefly review the literature on applications of text mining for search term development for systematic reviewing. We found that the tools can be used in 5 overarching ways: improving the precision of searches; identifying search terms to improve search sensitivity; aiding the translation of search strategies across databases; searching and screening within an integrated system; and developing objectively derived search strategies. Using a case study and selected examples, we then reflect on the utility of certain technologies (term frequency–inverse document frequency and Termine, term frequency, and clustering) in improving the precision and sensitivity of searches. Challenges in using these tools are discussed. The utility of these tools is influenced by the different capabilities of the tools, the way the tools are used, and the text that is analysed. Increased awareness of how the tools perform facilitates the further development of methods for their use in systematic reviews.
Comprehensive Network Map of ADME‐Tox Databases
Authors: Canault Baptiste , Bourg Stéphane , Vayer Philippe , Bonnet Pascal
Published: June 2017

In the last decade, many statistical‐based approaches have been developed to improve poor pharmacokinetics (PK) and to reduce toxicity of lead compounds, which are one of the main causes of high failure rate in drug development. Predictive QSAR models are not always very efficient due to the low number of available biological data and the differences in the experimental protocols. Fortunately, the number of available databases continues to grow every year. However, it remains a challenge to determine the source and the quality of the original data. The main goal is to identify the relevant databases required to generate the most robust predictive models. In this study, an interactive network of databases was proposed to easily find online data sources related to ADME‐Tox parameters data. In this map, relevant information regarding scope of application, data availability and data redundancy can be obtained for each data source. To illustrate the usage of data mining from the network, a dataset on plasma protein binding is selected based on various sources such as DrugBank, PubChem and ChEMBL databases. A total of 2,606 unique molecules with experimental values of PPB were extracted and can constitute a consistent dataset for QSAR modeling.
Prolonged first‐line PEG‐asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol—Pharmacokinetics and antibody formation
Authors: Tram Henriksen Louise , Gottschalk Højfeldt Sofie , Schmiegelow Kjeld , Frandsen Thomas Leth , Skov Wehner Peder , Schrøder Henrik , Klug Albertsen Birgitte ,   on behalf of the Nordic Society of Pediatric Hematology and Oncology, NOPHO Group
Published: June 2017

Background

As pegylated asparaginase is becoming the preferred first‐line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment.

Methods

The aim of this study was to evaluate the pharmacokinetics of prolonged upfront biweekly PEG‐asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l‐asparaginase activity and formation of anti‐PEG‐asparaginase antibodies. A total of 97 evaluable patients (1–17 years), diagnosed with ALL, and treated according to the NOPHO ALL2008 protocol (where NOPHO is Nordic Society of Paediatric Haematology and Oncology) were included. In the NOPHO ALL2008 protocol, patients are randomized to 8 or 15 doses of intramuscular PEG‐asparaginase (Oncaspar®) 1,000 IU/m²/dose, at 2‐week or 6‐week intervals with a total of 30‐week treatment (Clinical trials.gov. no.: NCT00819351).

Results

The pharmacological target of treatment (l‐asparaginase activity above 100 IU/l) was reached in 612 of 652 (94%) samples obtained 14 ± 2 days after PEG‐asparaginase administration. Mean l‐asparaginase activity was 338 IU/l. Six patients had l‐asparaginase activity below 50 IU/l in all samples. A total of 25 patients (26%) developed Immunoglobulin G (IgG) anti‐PEG‐asparaginase antibodies, but there was no correlation between anti‐PEG‐asparaginase antibodies and low levels of asparaginase activity.

Conclusion

We conclude that prolonged first‐line biweekly PEG‐asparaginase therapy, 1,000 IU/m²/dose was above the pharmacological target in the vast majority of patients. Presence of anti‐PEG‐asparaginase antibodies was not a predictor of l‐asparaginase activity.
Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management
Authors: Ghanem Khaled M. , Dhayni Raghida M. , Al‐Aridi Carol , Tarek Nidale , Tamim Hani , Chan Anthony K. C. , Saab Raya , Abboud Miguel R. , El‐Solh Hassan , Muwakkit Samar A.
Published: June 2017

Background

Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No available consensus exists regarding its risk factors and appropriate management due to the rarity of cases.

Procedures

Out of 209 ALL patients aged 1–21 years treated at the Children's Cancer Center of Lebanon between May 2002 and May 2015, 13 developed CSVT during therapy. Patient characteristics, clinical management, and outcomes were studied.

Results

The incidence of CSVT was 6.2% (95% confidence interval [CI]: 3.4–10.4). Using univariate analysis, increased risk of CSVT was observed with age >10 years (odds ratio [OR]: 3.56, 95% CI: 1.13–11.2), T‐cell immunophenotype (OR: 4.14, 95% CI: 1.16–14.7), and intermediate/high risk disease (OR: 3.4, 95% CI: 1.03–11.7). The only statistically significant risk factor by multivariate analysis was the treatment as per the intermediate‐/high‐risk protocol (HR: 15.6, 95% CI: 1.43–171.3). Most cases (77%) occurred in the postinduction phases of treatment while receiving a combination of asparaginase and dexamethasone rather than prednisone. Treatment with low molecular weight heparin (LMWH) for a minimum of 3 months and until significant radiological improvement is observed resulted in 100% survival rate. All but one patient had complete neurological recovery.

Conclusions

CSVT is an important complication of childhood ALL therapy. Postinduction combined asparaginase and dexamethasone intensive treatment for intermediate‐/high‐risk patients was the most important risk factor. Treatment with LMWH for a minimum of 3 months, and until asparginase therapy is over, with major radiological improvement seems to be effective and feasible.
EVIDENCE AND FALLIBILITY
Authors: DiPaolo Joshua
Published: June 2017

The “Evidentialist Dictum” says we must believe what our evidence supports, and the “Fallibility Norm” says we must take our fallibility into account when managing our beliefs. This paper presents a problem for the Evidentialist Dictum based in the Fallibility Norm and a particular conception of evidential support. It then addresses two novel Evidentialist responses to this problem. The first response solves the problem by claiming that fallibility information causes “evidence-loss.” In addition to solving the problem, this response appears to explain what's wrong with certain illegitimate dismissals of misleading evidence. However, this explanation opens it up to objections. Next, I consider and pose challenges to an Evidentialist strategy that attempts to solve the problem by converting accounts of fallibility's epistemic significance for rational belief into principles of evidential support. I conclude by sketching a solution that allows us to capture what's true in the Evidentialist Dictum and the Fallibility Norm.
Global Shifts and the Limits of the EU’s Transformative Power in the European Periphery: Comparative Perspectives from Hungary and Turkey
Authors: Öniş Ziya , Kutlay Mustafa
Published: June 2017

This article highlights the weakening of the EU’s transformative capacity in the broader European periphery in a rapidly shifting global order, with reference to Hungary and Turkey. Although Hungary is an ‘insider’ and Turkey a relative ‘outsider’, their recent experiences display strikingly similar patterns, raising important concerns about the EU’s leverage. Under the influence of strong nationalist-populist leaders backed by powerful majorities, both countries have been moving in an increasingly illiberal direction, away from well-established EU norms. The article proposes an analytical framework based on a combination of push and pull factors that are driven by changing global political economy dynamics, which explains the EU’s declining appeal in its periphery, not only in reference to the internal dynamics of European integration and its multiple crises, but also the appeal of illiberal versions of strategic capitalism employed by rising powers, which serve as reference points for the elites of several states in diverse geographic settings.
Exploring novel target structures for manipulating relativistic laser–plasma interaction
Authors: Ji Liangliang , Jiang Sheng , Pukhov Alexander , Freeman Richard , Akli Kramer
Published: June 2017

The improved laser-to-pedestal contrast ratio enabled by current high-power laser pulse cleaning techniques allows the fine features of the target survive before the main laser pulse arrives. We propose to introduce the nano-fabrication technologies into laser–plasma interaction to explore the novel effects of micro-structures. We found out that not only laser-driven particle sources but also the laser pulse itself can be manipulated by specifically designed micro-cylinder and -tube targets, respectively. The proposal was supported by full-3D particle-in-cell simulations and successful proof-of-principle experiments for the first time. We believe this would open a way to manipulate relativistic laser–plasma interaction at the micro-size level.