bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of optimum number of components in partial least squares regression from distributions of the root‐mean‐squared error obtained by Monte Carlo resampling
Authors: Kvalheim Olav Martin , Arneberg Reidar , Grung Bjørn , Rajalahti Tarja
Published: January 2018

Monte Carlo resampling is utilized to determine the number of components in partial least squares (PLS) regression. The data are randomly and repeatedly divided into calibration and validation samples. For each repetition, the root‐mean‐squared error (RMSE) is determined for the validation samples for a = 1, 2, … , A PLS components to provide a distribution of RMSE values for each number of PLS components. These distributions are used to determine the median RMSE for each number of PLS components. The component (Amin) having the lowest median RMSE is located. The fraction p of the RMSE values of Amin exceeding the median RMSE for the preceding component is determined. This fraction p represents a probability measure that can be used to decide if the RMSE for the Amin PLS component is significantly lower than the RMSE for the preceding component for a preselected threshold (pupper). If so, it defines the optimum number of PLS components. If not, the process is repeated for the previous components until significance is achieved. The pupper = 0.5 implies that the median is used for selecting the optimum number of components. The RMSE is approximately normally distributed on the smallest components. This can be utilized to relate p to a fraction of a standard deviation. For instance, p = 0.308 corresponds to half a standard deviation if RMSE is normally distributed.

The approach is demonstrated for calibration of metabolomics measurements and spectroscopic mixture data.
A frequency‐localized recursive partial least squares ensemble for soft sensing
Authors: Poerio Dominic V. , Brown Steven D.
Published: January 2018

We report the use of a frequency‐localized adaptive soft sensor ensemble using the wavelet coefficients of the responses from the physical sensors. The proposed method is based on building recursive, partial least squares soft sensor models on each of the wavelet coefficient matrices representing different frequency content of the signals from the physical sensors, combining the predictions from these models via static weights determined from an inverse‐variance weighting approach, and recursively adapting each of the soft sensor models in the ensemble when new data are received. Wavelet‐induced boundary effects are handled by using the undecimated wavelet transform with the Haar wavelet, an approach that is not subject to wavelet boundary effects that would otherwise arise on the most recent sensor data. An additional advantage of the undecimated wavelet transform is that the wavelet function is defined for a signal of arbitrary length, thus avoiding the need to either trim or pad the training signals to dyadic length, which is required with the basic discrete wavelet transform. The new method is tested against a standard recursive partial least squares soft sensor on 3 soft‐sensing applications from 2 real industrial processes. For the datasets we examined, we show that results from the new method appear to be statistically superior to those from a soft sensor based only on a recursive partial least squares model with additional advantages arising from the ability to examine performance of each localized soft sensor in the ensemble.
Tuning the Surface Composition of Ni/meso‐CeO2 with Iridium as an Efficient Catalyst for Hydrogen Generation from Hydrous Hydrazine
Authors: Qiu Yu‐Ping , Yin Hui , Dai Hao , Gan Li‐Yong , Dai Hong‐Bin , Wang Ping
Published: January 2018

Selective decomposition of hydrous hydrazine (N2H4⋅H2O) over metal catalysts provides a promising means for onboard or portable hydrogen source applications. Studies on N2H4⋅H2O decomposition catalysts mainly focus on the effects of bulk composition and structure on their performances, instead of the surface‐composition‐dependent properties. Herein, the synthesis of an Ir‐modified Ni/meso‐CeO2 catalyst is reported by using a combination of colloidal solution combustion synthesis and galvanic replacement methods. A combination of structural characterization, control experiments, and DFT calculations reveals that the Ni−Ir alloy resulting from calcination treatment exerts a profound effect on the catalytic properties. The resulting Ni@Ni−Ir/meso‐CeO2 catalyst shows excellent catalytic performance towards hydrogen generation from N2H4⋅H2O, which compares favorably with the Ni−Ir bimetallic catalysts reported to date.
Effectiveness of Biochar from Hydrothermal Carbonization of Wetland Biomass for Sorption of Ammonia
Authors: Ibrahim Bassel , Schlegel Mathias , Kanswohl Norbert
Published: January 2018

The aim of this study is twofold: firstly, to characterize the biochars resulting from the hydrothermal carbonization (HTC) of different types of wetland biomass and, secondly, to assess their potential for ammonia removal in aqueous solutions. The chars produced were carbon rich. The adsorption experiments indicated that hydrothermal treatment improved the ammonia removal efficiency rate, and loaded adsorbents were regenerable. Using an HTC char of reed as adsorbent has several advantages: it has the highest adsorption performance, the highest char yield, and the greatest affinity for regeneration.
Reclaimed Water Irrigation Effect on Agricultural Soil and Maize (Zea mays L.) in Northern China
Authors: Zhang Shichao , Yao Hong , Lu Yintao , Shan Dan , Yu Xiaohua
Published: January 2018

The concentration, spatial distribution, and source of trace metals (As, Cd, Cu, Cr, Pb, and Zn) are investigated in agricultural soils and maize (Zea mays L.) subjected to two distinct types of irrigation water in Northern China. The results indicate that the concentration of trace metals in soils irrigated for approximately 30 years with reclaimed water exhibit only minor differences in comparison to that irrigated with groundwater. However, the use of reclaimed water appear to result in higher concentrations of As and Cu in the agricultural soils. Geo‐statistical and principal component analyses suggest that Cr has a lithogenic origin and Cd, Pb, and Zn are mainly influenced by other human activities (e.g., vehicle emissions in case of Pb). With regards to maize, no significant differences in metal concentrations are observed in the grains. The highest concentrations of Cd are measured in the roots, whereas elevated concentrations of Cr and Pb are found in the leaves. Cu and Zn, as necessary elements for plant growth, have higher concentrations in grains compared to the other trace metals. The observed increase of Cu and As concentrations in soils and the concentration of Pb from both areas in grains of maize exceed the safety level, indicating that continued monitoring is required to insure food safety and sustainable crop production.
Imaging‐based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy
Authors: Amer Ahmed M. , Zaid Mohamed , Chaudhury Baishali , Elganainy Dalia , Lee Yeonju , Wilke Christopher T. , Cloyd Jordan , Wang Huamin , Maitra Anirban , Wolff Robert A. , Varadhachary Gauri , Overman Michael J. , Lee Jeffery E. , Fleming Jason B. , Tzeng Ching Wei , Katz Matthew H. , Holliday Emma B. , Krishnan Sunil , Minsky Bruce D. , Herman Joseph M. , Taniguchi Cullen M. , Das Prajnan , Crane Christopher H. , Le Ott , Bhosale Priya , Tamm Eric P. , Koay Eugene J.
Published: January 2018

BACKGROUND

The assessment of pancreatic ductal adenocarcinoma (PDAC) response to therapy remains challenging. The objective of this study was to investigate whether changes in the tumor/parenchyma interface are associated with response.

METHODS

Computed tomography (CT) scans before and after therapy were reviewed in 4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received protocol‐based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients with stage I/II PDAC who received neoadjuvant chemoradiation and were prospectively followed in a registry). The tumor/parenchyma interface was visually classified as either a type I response (the interface remained or became well defined) or a type II response (the interface became poorly defined) after therapy. Consensus (cohorts 1‐3) and individual (cohort 4) visual scoring was performed. Changes in enhancement at the interface were quantified using a proprietary platform.

RESULTS

In cohort 1, type I responders had a greater probability of achieving a complete or near‐complete pathologic response (21% vs 0%; P = .01). For cohorts 1, 2, and 3, type I responders had significantly longer disease‐free and overall survival, independent of traditional covariates of outcomes and of baseline and normalized cancer antigen 19‐9 levels. In cohort 4, 2 senior radiologists achieved a κ value of 0.8, and the interface score was associated with overall survival. The quantitative method revealed high specificity and sensitivity in classifying patients as type I or type II responders (with an area under the receiver operating curve of 0.92 in cohort 1, 0.96 in cohort 2, and 0.89 in cohort 3).

CONCLUSIONS

Changes at the PDAC/parenchyma interface may serve as an early predictor of response to therapy. Cancer 2018;124:1701‐9. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Racial disparities in prostate cancer survival in a screened population: Reality versus artifact
Authors: Kaur Dhamanpreet , Ulloa‐Pérez Ernesto , Gulati Roman , Etzioni Ruth
Published: January 2018

BACKGROUND

Racial disparities in prostate cancer survival (PCS) narrowed during the prostate‐specific antigen (PSA) era, suggesting that screening may induce more equitable outcomes. However, the effects of lead time and overdiagnosis can inflate survival even without real screening benefit.

METHODS

A simulation model of PCS in the early PSA era (1991‐2000) was created. The modeled survival started with baseline survival in the pre‐PSA era (1975‐1990) and added lead times and overdiagnosis using estimates from published studies. The authors quantified 1) discrepancies between modeled and observed PCS in the PSA era and 2) residual period effects on PCS given specified values for screening benefit.

RESULTS

Lead time and overdiagnosis explained more of the improvement in PCS for older ages at diagnosis (46% [95% confidence interval (CI), 44%‐50%] for blacks and 51% [95% CI, 50%‐52%] for all races ages 50‐54 years vs 98% [95% CI, 97%‐99%] for blacks and 100% for all races ages 75‐79 years). They also explained more of the narrowing in PCS disparities for older ages (33% [95% CI, 31%‐43%] for men ages 50‐54 years vs 74% [95% CI, 71%‐81%] for men ages 75‐79 years). The period effects amounted to reductions of 27% to 40% among blacks and 26% to 38% among all races in the risk of prostate cancer death, depending on the screening benefit.

CONCLUSIONS

Real improvements in survival disparities in the PSA era are smaller than those observed and reflect similar reductions in the risk of prostate cancer death among blacks and all races. Understanding screening artifacts is necessary for valid interpretation of observed survival trends. Cancer 2018;124:1752‐9. © 2018 American Cancer Society
A Three‐Dimensional Hierarchical Dandelion‐Like HMX Architecture Formed at a Liquid‐Liquid Interface
Authors: Cheng Minmin , Li Ping , Duan Xiaohui , Pei Chonghua
Published: January 2018

A facile and mild method, liquid‐liquid interface crystallization (LLIC), is reported for the fabrication of the hierarchical structure of octahydro‐1,3,5‐tetranitro‐1,3,5,7‐tetrazocine (HMX) under ambient conditions. The morphology and structure are characterized by field emission scanning electron microscopy (FE‐SEM), dynamic light scattering (DLS), powder X‐ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy. A three‐dimensional hierarchical dandelion‐like HMX architecture is obtained through self‐assembling of the submicron particles with a main diameter range of 250–700nm at the interface of DMSO solution and CH2Cl2. Except the main polymorph β, the δ phase is found in the product. Thermal analyses are performed, and the kinetic parameter is calculated. The results indicate that hierarchical structure HMX presents much higher activation energy (280.82 KJ mol−1) than raw HMX (258.90 KJ mol−1). Similarly, the exothermic decomposition peak of HMX hierarchical structure also reaches 287.7 °C and is basically the same as raw HMX (288.4 °C). From the results of the sensitivity tests, the impact and friction sensitivities of HMX are significantly increased compared with those of raw HMX. In this work, the successful application of LLIC to energetic materials is demonstrated, thereby providing a potential method for the preparation of hierarchical structure of high‐energy ammonium nitrate explosives.
Neural crest emigration: From start to stop
Authors: Kalcheim Chaya
Published: January 2018

Within the dynamic context of a developing embryo, the multicellular patterns formed are extraordinarily precise. Through cell–cell communication, neighboring progenitors coordinate their activities, sequentially generating distinct tissues. The development of the dorsal neural tube remarkably illustrates this principle. It first generates neural crest (NC) cells, precursors of most of the peripheral nervous system, and then becomes the roof plate (RP) of the central nervous system. While the molecular network regulating emigration of NC progenitors has been extensively studied, the mechanisms by which dorsal neural tube precursors transit from an initial NC fate to a definitive RP identity remain widely open to investigation. Critical differences exist between premigratory NC and RP cells. Whereas the former extensively proliferate and undergo an epithelial‐to‐mesenchymal transition that generates cellular migrations, the latter progressively exit the cell cycle and regain epithelial traits including apico‐basal polarity and regeneration of a laminin‐containing basement membrane. To understand this transition, the nature of the cross‐talk between these two sequentially forming progenitor subsets should be unraveled, including the identity and mode of action of signals that, on the one hand, induce the arrest of NC emigration, and, on the other hand, promote formation of a definitive RP.
Recent developments and controversies in transcatheter aortic valve implantation
Authors: Ali Noman , Patel Peysh A. , Lindsay Steven J.
Published: January 2018

Interventional cardiology has been revolutionised by transcatheter aortic valve implantation (TAVI), which has become established as the benchmark treatment for severe aortic stenosis in patients at high risk for surgical aortic valve replacement (AVR). Increased procedural familiarity and progression in device technology has enabled improvements to be made in complication rates, which have led to a commensurate expansion in the use of TAVI; it is now a viable alternative to AVR in patients at intermediate surgical risk, and has been used in cohorts such as those with bicuspid aortic valves or pure, severe aortic regurgitation.

Given the rapid expansion in the use of TAVI, including cohorts of younger patients with fewer co‐morbidities, attention must be paid to further reducing remaining complications, such as cardiac tamponade or stroke. To this end, novel techniques and devices have been devised and trialled, with varying levels of success. Furthermore, significant work has gone into refining the technique with exploration of alternative imaging modalities, as well as alternative access routes to provide greater options for patients with challenging vascular anatomy.

Whilst significant progress has been made with TAVI, areas of uncertainty remain such as the management of concomitant coronary artery disease and the optimum post‐procedure antiplatelet regimen. As such, research in this field continues apace, and is likely to continue as use of TAVI becomes more widespread. This review provides a summary of the existing evidence, as well as an overview of recent developments and contentious issues in the field of TAVI.
Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain‐related working memory deficits in neuropathic pain rats
Authors: Cardoso‐Cruz H. , Dourado M. , Monteiro C. , Galhardo V.
Published: January 2018

Background

Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity.

Methods

To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food‐reinforced T‐maze sWM task. Within‐subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury (SNI) model.

Results

Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta‐oscillations. Particularly, we found a significant decrease in intrahippocampal CA1 field connectivity level.

Conclusions

Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions.

Significance

This study provides new insights into the role of D2r in the manifestation of pain‐related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta‐oscillations, and amplifies pain‐related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions.
Electrochemical Characterization of CdSe Monolayers Modified with Glycosilated Molecules
Authors: La Ferla B. , D'Orazio G. , Zotti G. , Vercelli B.
Published: January 2018

Ultrathin films of CdSe nannocrystals (CdSe‐NCs) modified with glycosilated molecules have shown interesting electrochemical properties which lead to the detection of lectin Jacalin.
Surfaces Decorated with Polymeric Nanocompartments for pH Reporting
Authors: Craciun Ioana , Denes Alexandru S. , Gunkel‐Grabole Gesine , Belluati Andrea , Palivan Cornelia G.
Published: January 2018

Here we present a novel active surface that demonstrates pH responsiveness and can be used as a platform for designing ‘smart labels’. To generate our active surfaces, we immobilized polymer nanocompartments onto glass surfaces using thiol–ene chemistry. Prior to surface attachment, a pH responsive model dye was encapsulated within nanocompartments at two different pH values. We confirmed the attachment and distribution of dye‐loaded polymersomes and established the pH responsiveness of the active surface construct. The strategy presented here was carefully chosen to obtain small sized functional surfaces from commercially available materials that can be easily integrated into intelligent packaging systems. The ability to miniaturize such smart labels, while still being able to detect their response to the environment, is a crucial step towards developing active surfaces suitable for food packaging applications.
Case report of endometrial cancer with a microcytic, elongated, and fragmented pattern of invasion and DNA mismatch repair deficiency
Authors: Sookram Janhvi , Barroeta Julieta E. , Aikins James K.
Published: January 2018

Conflicting literature on microcytic, elongated, and fragmented patterns of tumor invasion, and mismatch repair protein expression pose a challenge in therapeutic decision making.
The association between weight gain during pregnancy and intertwin delivery weight discordance using 2011–2015 birth registration data from the USA
Authors: Xiao Yanni , Shen Minxue , Ma Shujuan , Tao Xuan , Wen Shi Wu , Tan Hongzhuan
Published: January 2018

Objective

To assess the effect of weight gain during pregnancy on intertwin delivery weight discordance.

Methods

In the present retrospective cohort study using twin delivery records, data were extracted from the 2011–2015 USA birth registration dataset created by the Centers for Disease Control and Prevention. The outcome variable was delivery weight discordance. The nonlinear association of weight gain during pregnancy with delivery weight discordance was examined using a generalized additive model, adjusting for potential confounders.

Results

A total of 255 627 twin pairs were included in this analysis. Weight gain during pregnancy showed an inverse, yet nonlinear, association with intertwin delivery weight discordance. Women with weight gain of approximately 25 kg exhibited the lowest level of discordance. When stratified by pre‐pregnancy body mass index, the association of weight gain with discordance became insignificant among obese women. When categorizing weight gain according to recommendations from the Institute of Medicine, inadequate weight gain was associated with increased risk of discordance among women of any pre‐pregnancy body mass index.

Conclusion

Twin pregnancies with maternal weight gain of approximately 25 kg demonstrated the lowest risk of developing intertwin delivery weight discordance, while inadequate weight gain was a risk factor for delivery weight discordance in all pre‐pregnancy body mass index categories.
Evaluation of autophagy induction on HEV 239 vaccine immune response in a mouse model
Authors: Khateri Mehdi , Abdoli Asghar , Motevalli Fatemeh , Fotouhi Fatemeh , Bolhassani Azam , Arashkia Arash , Jazaeri Ehsan Ollah , Shahbazi Sepideh , Mehrbod Parvaneh , Naziri Hamed , Aghasadeghi Mohammad Reza
Published: January 2018

Hepatitis E virus (HEV) infection remains a serious threat to life and productivity in developing world. Vaccine seems to be an effective, safe, and affordable approach to address HEV disease burden. The HEV genome consists of three open reading frames (ORFs). Of these, ORF2 encodes a single structural protein (pORF2) for the HEV capsid which has been studied extensively as vaccine candidates. Recently, it has been recognized that autophagy plays an important role in innate and adaptive immunity defense against intracellular pathogens. This mechanism could therefore promote a protective immune response by inducing CD4+ and CD8+ T cells. In this study, HEV 239 and Beclin1 proteins were expressed in prokaryotic host cell [Escherichia coli (BL21)]. HEV 239 protein with different formulations (+Alum, +Beclin1, and +Alum‐Beclin1) were used as candidate vaccines and administrated subcutaneously in BALB/c mice on 0, 14, and 28 days. Finally, elicited cellular and humoral immunity were evaluated. Taken together, although our results indicated that mice immunized with HEV 239 protein formulated with Alum, Beclin1, and Alum + Beclin1 displayed humoral and cellular response that was not significant in comparison with each other (P > 0.05); whereas they were significant while compared with control groups (P < 0.05). A comprehensive understanding of the intricate interplay between autophagy and immune response remains to be unraveled. Further study will clear the detailed impact of autophagy manipulation to enhance vaccine efficacy and boost the immune responses against the disease. © 2018 IUBMB Life, 70(3):207–214, 2018
Preclinical approaches to assess potential kinase inhibitor‐induced cardiac toxicity: Past, present and future
Authors: Yang Baichun , Papoian Thomas
Published: January 2018

Over a decade ago, use of tyrosine kinase inhibitors (TKIs) for the treatment of malignancies was found to cause left ventricular dysfunction, a finding that was unexpected and not well predicted by standard preclinical studies. Subsequently, several preclinical approaches were proposed to address this issue. Over the last 5 years, several approaches for preclinical evaluation of cardiac function using isolated perfused hearts, engineered heart tissue and human‐induced pluripotent stem cell‐derived cardiac myocytes have been shown to be relatively predictive of the cardiotoxic potential of TKIs. Further, preclinical studies submitted for regulatory review for recently approved KIs have demonstrated various forms of KI‐induced cardiotoxicity. Thus, early identification and assessment of cardiotoxicity in the preclinical setting is now possible. Given that kinases are involved in diverse cellular processes common to both normal and tumor cells, KI‐induced toxicity, particularly in the heart, appears difficult to avoid. To develop drugs with fewer adverse effects, better efficacy and safety assessments, such as pharmacological separation of targets for cancer from heart, and/or wider separation of the drug concentrations for antitumor activity from cardiac toxicity, may be helpful. Additional preclinical approaches for assessing drug efficacy and toxicity in parallel may include use of animal cancer models and a 3D integrated in vitro model of perfused tumor and heart tissues. Minimizing and predicting potential KI‐induced cardiotoxicity is still an important regulatory challenge, and better preclinical approaches may help achieve this goal.
Retracted: Protective effects of microRNA‐330 on amyloid β‐protein production, oxidative stress, and mitochondrial dysfunction in Alzheimer's disease by targeting VAV1 via the MAPK signaling pathway
Authors: Zhou Ying , Wang Zhou‐Fan , Li Wei , Hong Hui , Chen Juan , Tian Yi , Liu Zhao‐Yun
Published: January 2018

This study aims to explore the effect of miR‐330 targeting VAV1 on amyloid β‐protein (Aβ) production, oxidative stress (OS), and mitochondrial dysfunction in Alzheimer's disease (AD) mice through the MAPK signaling pathway. Putative targeted gene of miR‐330 was performed by a miRNA target prediction website and dual‐luciferase reporter gene assay. AD mouse model was successfully established. Fourteen C57 mice were randomized into AD and control groups. The positive protein expression rate of VAV1 was measured by immunohistochemistry. Neuron cells were assigned into control, blank, negative control (NC), miR‐330 mimics, miR‐330 inhibitors, siRNA‐VAV1, and miR‐330 inhibitors + siRNA‐VAV1 groups. Expression of miR‐330, VAV1, ERK1, JNK1, P38MAPK, Aβ, COX, and lipoprotein receptor‐related protein‐1 (LRP‐1) were determined using RT‐qPCR and Western blotting. Colorimetry was applied to measure the levels of OS parameters of superoxide dismutase (SOD) and malondialdehyde (MDA). Aβ production in brain tissue was detected using ELISA, while that in neuron cell was measured by radioimmunoassay. MiR‐330 was down‐regulated in neuron cells of AD mice and VAV1 was negatively regulated by miR‐330. Compared with the control group, the positive protein expression rate of VAV1 was significantly elevated in the AD group. Overexpression of miR‐330 decreased the expression of VAV1, ERK1, JNK1, P38MAPK, and Aβ, but increased the expression of COX and LRP‐1. AD mice revealed elevated Aβ production and MDA with decreased SOD level. The result indicates that overexpressed miR‐330 targeting VAV1 through the MAPK signaling pathway reduces Aβ production and alleviates OS and mitochondrial dysfunction in AD.
Exploring the functional impact of mutational drift in LRRK2 gene and identification of specific inhibitors for the treatment of Parkinson disease
Authors: Nagarajan Nagasundaram , Chellam Jaynthy , Kannan Rajaretinam Rajesh
Published: January 2018

Parkinson's disease (PD) is a disorder of the central nervous system that is caused due to the death of the dopaminergic neurons in the region of the brain called substantia nigra. Mutations in LRRK2 genes are associated with disease condition and it's been reported as crucial factor for drug resistance. Identification of deleterious mutations and studying the structural and functional impact of such mutations may lead to the identification of potential selective inhibitors. In this study, we analyzed 52 PD associated mutations, among that 20 were identified as highly deleterious. The deleterious mutations G2019S and I2020T in the kinase domain were playing a key role in causing resistance to drug levedopa. Molecular docking analyses have been performed to understand the binding affinity of levodapa with LRRK2 in wild and mutant condition. Molecular docking results show that levedopa binds differentially and obtained less number of hydrogen bonds in compared with wild type LRRK2. In addition, molecular dynamics simulations were performed to study the efficacy of docked complexes and it was observed that the efficacy of the mutant complexes (G2019S‐Levodopa and I2020T‐Levodopa) affected in the presence of mutation. Finally, through virtual screening approach specific inhibitors SCHEMBL6473053 and SCHEMBL1278779 have been identified that could potentially inhibit LLRK2 mutants G2019S and I2020T respectively. Over all this computational investigation correlates the impact of genotypic modulation in structure and function of drug target which enhanced in the identification of precision medicine to treat PD.
The association between serum testosterone and mortality among elderly men on hemodialysis
Authors: Wu Hung‐Chieh , Lee Lin‐Chien , Wang Wei‐Jie
Published: January 2018

Objectives

This study examines the associations between total testosterone levels and dialysis mortality.

Methods

Elderly men who initiate hemodialysis in Taoyuan General Hospital from January 2012 to June 2017 were enrolled. We reviewed clinical characteristics and biochemical data from start of dialysis and followed over a 5‐year period after dialysis. Body composition parameters were assessed 3‐6 months after dialysis. Skeletal muscle mass index (SMMI) was defined by skeletal muscle mass divided by squared height. We defined those with lowest tertile of testosterone values as low testosterone group. Adjusted hazard ratios (aHRs) and 95% confidence interval (95% CI) for mortality and cumulative survival curves were evaluated by Cox hazards model and Kaplan‐Meier method. The discriminative power of SMMI and testosterone levels was calculated according to the area under the curve and the receiver operating characteristic curve (AUROC).

Results

From a total of 137 elderly hemodialysis patients, the range of lowest, middle, and highest tertile of testosterone values was <6.25 nmol/L, 6.25‐10.5 nmol/L, and >10.5 nmol/L. After multivariate adjustment other than SMMI, total testosterone levels at baseline were a significant predictor for mortality aHR(95% CI): 0.79 (0.70‐0.91). The unadjusted and adjusted c‐statistics of SMMI vs testosterone values to predict overall were 770 (0.688‐0.852) vs 0.779 (0.691‐0.866) and 855 (0.812‐0.886) vs 0.812 (0.744‐0.856) (Ps < .05), whereas the capacity of c‐statistics was similar (χ2 = 0.143 and 2.709, Ps > .05).

Conclusions

Total testosterone value was a predictor for mortality. It was noninferior to SMMI in predicting dialysis mortality.
An update on cell intrinsic negative regulators of the NLRP3 inflammasome
Authors: Poudel Barun , Gurung Prajwal
Published: January 2018

Inflammasomes are multimeric protein complexes that promote inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. The central role of inflammasomes in combating infection and maintaining homeostasis has been studied extensively. Although inflammasome-mediated inflammation and cell death are vital to limit pathogenic insults and to promote wound healing/tissue regeneration, unchecked/uncontrolled inflammation, and cell death can cause cytokine storm, tissue damage, autoinflammatory and autoimmune diseases, and even death in the afflicted individuals. NLRP3 is one of the major cytosolic sensors that assemble an inflammasome. Given the adverse consequences of uncontrolled inflammasome activation, our immune system has developed tiered mechanisms to inhibit NLRP3 inflammasome activation. In this review, we highlight and discuss recent advances and our current understanding of mechanisms by which NLRP3 inflammasome can be negatively regulated.
In‐line monitoring of component content of polypropylene/polystyrene blends during melt extrusion using Raman spectroscopy
Authors: Huang Xi , Lei Yu , Wang Mengmeng , Jin Gang
Published: January 2018

At present, the component content measured by off‐line methods, which are hysteresis, destructive, and unrepresentative for the whole sample, makes it hard for real‐time monitoring of the performance of products in the process of polymer blending and modification. Therefore, in this paper, Raman spectroscopy as a real‐time measurement technology is applied for in‐line monitoring of component content of polypropylene/polystyrene (PS) blends during melt extrusion. Prior to performing an analysis of PS content in polypropylene/PS blends, the signal to noise ratio and relative standard deviation are evaluated with respect to the effects of screw speed, sampling distance of laser spot to melt surface, and single scan time in order to optimize sampling conditions. Owing to this, for quantitative analysis of PS content, different wavenumber ranges and pretreatment methods are used to develop the optimal partial least squares model, which is compared with the optimal partial least squares model of PS content based on off‐line infrared spectroscopy. It is concluded that in‐line Raman spectroscopy determination of PS content shows comparative accuracy and predicting ability, which is achieved exhibiting calibration results that coefficient of determination (R2) and root mean square error of cross‐validation are 0.9998 and 0.438 wt.% and prediction results that R2 and root mean square error of prediction are 0.9993 and 0.725 wt.%. What is more, in‐line monitoring system of Raman spectroscopy is successfully applied to measure PS content variation process from 80 to 50 wt.% then to 20 wt.%.
Recent advances in postharvest technology of the wine grape to improve the wine aroma
Authors: Mencarelli Fabio , Bellincontro Andrea
Published: January 2018

Postharvest techniques are widely used for the handling and storage of fresh horticultural crops. Some of these techniques are interesting for use with wine grapes to improve the quality of wine. In this review, we consider the postharvest techniques that are already commercially used in the wine sector and others that may be significant in inducing or extracting the aroma from grapes to produce high‐quality wines. Precooling consists of rapidly lowering the grape temperature, which allows the preservation/increase of volatile organic compounds (VOCs). We also discuss sustainability. Partial dehydration consists of the partial removal of water from grapes, and if a suitable environment is adopted it can be used to produce and extract berry VOCs. As a solid, carbon dioxide is used in wine processing for the rapid cooling of grapes and, as a gas, it is used for carbonic maceration. Ozone has been used for sanitation purposes in wineries for a long time, but more recently it has been used to produce wine without sulfite addition and to increase the aromatic quality of wine grapes. Ethylene application is not used commercially for wine grapes, but promising results in terms of phenolic extraction and aromatic changes in grapes are discussed. A comparison among the proposed techniques is reported in terms of grape aromatic quality and process features. The proposed techniques could help a winemaker to maintain or induce aromatic compounds in grape berries before the vinification process. The choice depends on the desired wine and economic consistency. © 2018 Society of Chemical Industry
Fabrication of an ionic‐liquid‐based polymer monolithic column and its application in the fractionation of proteins from complex biosamples
Authors: Zhang Doudou , Zhang Qian , Bai Ligai , Han Dandan , Liu Haiyan , Yan Hongyuan
Published: January 2018

An ionic‐liquid‐based polymer monolithic column was synthesized by free radical polymerization within the confines of a stainless‐steel column (50 mm × 4.6 mm id). In the processes, ionic liquid and stearyl methacrylate were used as dual monomers, ethylene glycol dimethacrylate as the cross‐linking agent, and polyethylene glycol 200 and isopropanol as co‐porogens. Effects of the prepolymerization solution components on the properties of the resulting monoliths were studied in detail. Scanning electron microscopy, nitrogen adsorption–desorption measurements, and mercury intrusion porosimetry were used to investigate the morphology and pore size distribution of the prepared monoliths, which showed that the homemade ionic‐liquid‐based monolith column possessed a relatively uniform macropore structure with a total macropore specific surface area of 44.72 m2/g. Compared to a non‐ionic‐liquid‐based monolith prepared under the same conditions, the ionic‐liquid‐based monolith exhibited excellent selectivity and high performance for separating proteins from complex biosamples, such as egg white, snailase, bovine serum albumin digest solution, human plasma, etc., indicating promising applications in the fractionation and analysis of proteins from the complex biosamples in proteomics research.
Chitosan‐Based Thermo/pH Double Sensitive Hydrogel for Controlled Drug Delivery
Authors: Bai Xiaoyu , Bao Zixian , Bi Shichao , Li Yang , Yu Xiaoping , Hu Shihao , Tian Meiping , Zhang Xin , Cheng Xiaojie , Chen Xiguang
Published: January 2018

A series of thermo/pH sensitive N‐succinyl hydroxybutyl chitosan (NSHBC) hydrogels with different substitution degrees of succinyl are prepared for drug delivery. Rheology analysis shows that the gelation temperature of NSHBC hydrogels is 3.8 °C higher than that of hydroxybutyl chitosan (HBC) hydrogels. A model drug bovine serum albumin (BSA) is successfully loaded and released. NSHBC hydrogels show excellent pH sensitivity drug release behaviors. After incubation for 24 h, 93.7% of BSA is released from NSHBC hydrogels in phosphate buffer saline (PBS) (pH 7.4), which is significantly greater than that of 24.6% at pH 3.0. In contrast, the release rate of BSA from HBC is about 70.0% at pH 3.0 and 7.4. Thus, these novel hydrogels have the prominent merits of high adaptability to soluble drugs and pH sensitivity triggered release, indicating that NSHBC hydrogels have promising applications in oral drug delivery.
Biological Activity of an Injectable Biphasic Calcium Phosphate/PMMA Bone Cement for Induced Osteogensis in Rabbit Model
Authors: Zhang Xiashiyao , Kang Ting , Liang Peiqing , Tang Yong , Quan Changyun
Published: January 2018

Polymethylmethacrylate (PMMA) bone cement is widely used in repair of vertebral fracture because of its good biomechanical properties and fast curing. However, the bioinertness of PMMA cement may cause interfacial loosening, fatigue, fracture, and ultimate failure. In this study, biphasic calcium phosphate (BCP) is introduced into PMMA cement to prepare an injectable composite bone cement (BCPx/PMMA) and the content of BCP is optimized to achieve appropriate rate of absorption that matches the bone regeneration. The compressive strength of BCPx/PMMA bone cement is found to comply with the International Standardization Organization standard 5833, and can promote biomineralization as well as adhesion, proliferation, and osteogenic differentiation of Sprague‐Dawley rat bone marrow mesenchymal stem cells in vitro. Furthermore, in vivo test performed on a rabbit radius defect model demonstrates that the presence of BCP can significantly improve the osteogenic efficacy of PMMA cement. Therefore, it is anticipated that BCPx/PMMA bone cement, as a promising injectable biomaterial, is of great potential in bone tissue regeneration.
The Tunable Porous Structure of Gelatin–Bioglass Nanocomposite Scaffolds for Bone Tissue Engineering Applications: Physicochemical, Mechanical, and In Vitro Properties
Authors: Arabi Neda , Zamanian Ali , Rashvand Sarvenaz N. , Ghorbani Farnaz
Published: January 2018

Unidirectional freeze‐casting method is used to fabricate gelatin–bioglass nanoparticles (BGNPs) scaffolds. Transmission electron microscopy (TEM) images show that sol–gel prepared BGNPs are distributed throughout the scaffold with diameters of less than 10 nm. Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetric are used to evaluate the physicochemical properties of BGNPs. Scanning electron microscopy (SEM) micrographs present an oriented porous structure and a homogeneous distribution of BGNPs in the gelatin matrix. The lamellar‐type structure indicates an improvement of mechanical strength and absorption capacity of the scaffolds. Increasing the concentration of BGNPs from 0 to 50 wt% have no noticeable effect on pore orientation, but decreases porosity and pore size distribution. Increase in BGNPs content improves the compressive strength. The absorption and biodegradation rate reduces with augmentation in BGNPs concentration. Bioactivity is evaluated through apatite formation after immersion of the nanocomposites in simulated body fluid and is verified by SEM–energy‐dispersive X‐ray spectroscopy (EDS), an element map analysis, X‐ray powder diffractometer, and FTIR spectrum. SEM images and methyl thiazolyl tetrazolium assay confirm the biocompatibility of scaffolds and the supportive behavior of nanocomposites in cellular spreading. The results show that gelatin–(30 wt%)bioglass nanocomposites have incipient physicochemical and biological properties.
Clinical and Vitamin Response to a Short‐Term Multi‐Micronutrient Intervention in Brazilian Children and Teens: From Population Data to Interindividual Responses
Authors: Mathias Mariana Giaretta , Coelho‐Landell Carolina de Almeida , Scott‐Boyer Marie‐Pier , Lacroix Sébastien , Morine Melissa J. , Salomão Roberta Garcia , Toffano Roseli Borges Donegá , Almada Maria Olímpia Ribeiro do Vale , Camarneiro Joyce Moraes , Hillesheim Elaine , de Barros Tamiris Trevisan , Camelo‐Junior José Simon , Campos Giménez Esther , Redeuil Karine , Goyon Alexandre , Bertschy Emmanuelle , Lévêques Antoine , Oberson Jean‐Marie , Giménez Catherine , Carayol Jerome , Kussmann Martin , Descombes Patrick , Métairon Slyviane , Draper Colleen Fogarty , Conus Nelly , Mottaz Sara Colombo , Corsini Giovanna Zambianchi , Myoshi Stephanie Kazu Brandão , Muniz Mariana Mendes , Hernandes Lívia Cristina , Venâncio Vinícius Paula , Antunes Lusania Maria Greggi , da Silva Rosana Queiroz , Laurito Taís Fontellas , Rossi Isabela Ribeiro , Ricci Raquel , Jorge Jéssica Ré , Fagá Mayara Leite , Quinhoneiro Driele Cristina Gomes , Reche Mariana Chinarelli , Silva Paula Vitória Sozza , Falquetti Letícia Lima , da Cunha Thaís Helena Alves , Deminice Thalia Manfrin Martins , Tambellini Tâmara Hambúrguer , de Souza Gabriela Cristina Arces , de Oliveira Mariana Moraes , Nogueira‐Pileggi Vicky , Matsumoto Marina Takemoto , Priami Corrado , Kaput Jim , Monteiro Jacqueline Pontes
Published: January 2018

Scope

Micronutrients are in small amounts in foods, act in concert, and require variable amounts of time to see changes in health and risk for disease. These first principles are incorporated into an intervention study designed to develop new experimental strategies for setting target recommendations for food bioactives for populations and individuals.

Methods and results

A 6‐week multivitamin/mineral intervention is conducted in 9–13 year olds. Participants (136) are (i) their own control (n‐of‐1); (ii) monitored for compliance; (iii) measured for 36 circulating vitamin forms, 30 clinical, anthropometric, and food intake parameters at baseline, post intervention, and following a 6‐week washout; and (iv) had their ancestry accounted for as modifier of vitamin baseline or response. The same intervention is repeated the following year (135 participants). Most vitamins respond positively and many clinical parameters change in directions consistent with improved metabolic health to the intervention. Baseline levels of any metabolite predict its own response to the intervention. Elastic net penalized regression models are identified, and significantly predict response to intervention on the basis of multiple vitamin/clinical baseline measures.

Conclusions

The study design, computational methods, and results are a step toward developing recommendations for optimizing vitamin levels and health parameters for individuals.
Cross‐vendor harmonization of T2‐relaxation‐under‐spin‐tagging (TRUST) MRI for the assessment of cerebral venous oxygenation
Authors: Jiang Dengrong , Liu Peiying , Li Yang , Mao Deng , Xu Cuimei , Lu Hanzhang
Published: January 2018

Purpose

Cerebral venous oxygenation (Yv) is an important physiological parameter and has potential clinical application in many brain diseases. T2‐relaxation‐under‐spin‐tagging (TRUST) is a commonly used MRI method to measure Yv. Harmonization of this technique across MRI vendors is important for dissemination and multicenter studies of brain oxygenation and metabolism as a disease biomarker.

Methods

TRUST pulse sequence components and imaging parameters were carefully matched between two major MRI vendors, Philips and Siemens. Each subject (N = 10) was scanned on both scanners within a 2.5‐h period. On each scanner, the subject was scanned in two sessions to assess intersession reproducibility. A hyperoxia challenge was also included in both sessions and on both scanners to evaluate the sensitivity of the technique to Yv changes. Measured Yv values, confidence interval of Yv estimates (
), as well as intrasession and intersession coefficient of variation (CoV) of Yv, were compared between the two scanners.

Results

Yv measured on the two vendors were highly compatible and strongly correlated (R2 = 0.957). Yv changes associated with hyperoxia challenge were significant on both scanners (P < 0.001) and were also correlated across scanners (P = 0.007). Intrasession and intersession CoV of measured Yv were less than 3% and showed no difference between scanners.
were less than 1% on both scanners and showed no difference between scanners when echo times were matched on the two scanners.

Conclusion

This work suggests that harmonized TRUST MRI can yield highly compatible Yv measurements across different vendors. Magn Reson Med 80:1125–1131, 2018. © 2018 International Society for Magnetic Resonance in Medicine.