bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro cytotoxic and antiproliferative effects of usnic acid on hormone‐dependent breast and prostate cancer cells
Authors: Eryilmaz Isil Ezgi , Guney Eskiler Gamze , Egeli Unal , Yurdacan Beste , Cecener Gulsah , Tunca Berrin
Published: August 2018

The aim of the current study was first to investigate cytotoxic activity of usnic acid (UA) on hormone‐dependent breast and prostate cancer, and normal cells. Cells were treated with increasing concentrations (25 to 150 µM) of UA for 48 hours and cell viability, quantitative and morphological analysis of cell death, and cell cycle analysis were performed. UA was shown to have selective cytotoxicity on hormone‐dependent cancer cells with the IC50 levels of 71.4 and 77.5 µM for MCF7 and LNCaP cells, respectively. UA induced apoptotic cell death and G0/G1 cell cycle arrest without damaging normal cells. MCF7 cells were more sensitive to UA than LNCaP cells. Our results first revealed that UA is a promising candidate as an alternative agent for hormone‐dependent breast and prostate cancers. However, molecular mechanism underlying the UA‐mediated cell death in cancer cells should be investigated further.
Serum uric acid could be served as an independent marker for increased risk and severity of ascending aortic dilatation in Behçet's disease patients
Authors: Cai Jianfei , Zhang Yinjia , Zou Jun , Shen Yan , Luo Dan , Bao Huafang , Chen Yong , Ye Jingfen , Guan Jian‐long
Published: August 2018

Objective

This study aimed to investigate the correlation of serum uric acid (SUA) with risk and dilatation diameter of ascending aortic dilatation (AAD) in Behçet's disease (BD) patients.

Methods

Seventeen BD patients complicated with AAD and 20 BD patients without AAD were consecutively enrolled and categorized into AAD group and control group, respectively. Ascending aortic dilatation was determined by two‐dimensional doppler echocardiographic examination, and AAD was defined as a diameter of ascending aorta ≥3.8 and <4.4 cm. SUA was detected by quantitative immunoassay method.

Results

Ascending aortic dilatation patients presented with higher proportion of male patients (P = 0.003), hypertension occurrence (P = 0.036) and increased diameter of ascending aorta (P < 0.001) compared to controls. SUA was elevated in AAD patients compared to controls (P = 0.002), and receiver operating characteristic curve displayed that SUA presented with great predictive value for AAD risk in BD patients with area under curve (AUC) 0.821 (95% CI 0.675‐0.966). Pearson's analysis also disclosed that SUA was positively correlated with ascending aortic diameter in total BD patients. However, no difference of CRP (P = 0.219) or ESR (P = 0.320) between AAD patients and controls was observed, and no correlation of CRP (R = −0.150, P = 0.377) or ESR (R = 0.067, P = 0.692) with ascending aortic diameter in total BD patients was discovered either. Further multivariate logistic regression illuminated that SUA was an independent factor predicting AAD risk in BD patients (P = 0.031).

Conclusions

Serum uric acid could be served as an independent marker for increased risk and severity of AAD in BD patients.
Three validation studies of the personality assessment inventory short form
Authors: Ward Tara , Arnold Kaitlin , Cunningham Marc Clint , Liljequist Laura
Published: August 2018

Objective

We examined the psychometric properties of the Personality Assessment Inventory‐Short Form (PAI‐SF).

Method

Study 1 compared single‐session short and full form PAI profiles of 200 outpatients, Study 2 examined PAI forms of 107 nonclinical adults across two administrations, and Study 3 compared correlations between full and short form scales and extratest variables.

Results

Study 1 correlations between short and full form scales ranged from 0.85 to 0.95 (Mdn = 0.91), with lower correlations, ranging from 0.59 to 0.86 for clinical scales (Mdn = 0.82), in Study 2. In Study 3 only 4 of 34 correlations differed significantly between extratest variables and the PAI versus the PAI‐SF.

Conclusions

These results indicate favorable psychometric properties of the PAI‐SF.
Cultural adaptations and therapist multicultural competence: Two meta‐analytic reviews
Authors: Soto Alberto , Smith Timothy B. , Griner Derek , Domenech Rodríguez Melanie , Bernal Guillermo
Published: August 2018

Mental health treatments can be more effective when they align with the culture of the client and when therapists demonstrate multicultural competence. We summarize relevant research findings in two meta‐analyses. In the meta‐analysis examining culturally adapted interventions, the average effect size across 99 studies was d = 0.50 (0.35 after accounting for publication bias). In the second meta‐analysis on 15 studies of therapist cultural competence, the results differed by rating source: Client‐rated measures of therapist cultural competence correlated strongly (r = 0.38) with treatment outcomes but therapists’ self‐rated competency did not (r = 0.06). We describe patient considerations and research limitations. We conclude with research supported therapeutic practices that help clients benefit from modifications to treatment related to culture.
Childhood maltreatment and psychotic experiences: Exploring the specificity of early maladaptive schemas
Authors: Boyda David , McFeeters Danielle , Dhingra Katie , Rhoden Laura
Published: August 2018

Objective

One potential mechanism that has received limited attention in psychosis research is early maladaptive schemas (EMS). Our aim was to examine whether EMS acts as a potential mediating pathway between early trauma and psychotic symptomology.

Methods

A quantitative survey was conducted online. N = 302 participants took part. The analysis used a multiple mediation framework.

Results

Analysis demonstrated significant specificity effects. Different forms of child maltreatment were significantly associated with psychosis experiences through specific dimensions of maladaptive schemas.

Conclusions

Results indicated specificity effects in that specific types of maltreatment are associated with specific maladaptive schemas. From a practitioner’s perspective, these findings offer credence to cognitive theories of psychopathology, and support the validity of EMS identification and modification among clients with psychotic symptomology both as a fundamental component of traditional CBT and within specialized schema‐focused therapy.
Significance of hepatic resection and adjuvant hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombus in the first branch of portal vein and the main portal trunk: a project study for hepatic surgery of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery
Authors: Hatano Etsuro , Uemoto Shinji , Yamaue Hiroki , Yamamoto Masakazu ,   the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery
Published: August 2018

Background

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus in the major portal vein (PV) is extremely poor. The purpose of this study was to clarify the impact of hepatic resection for HCC with tumor thrombus in the major PV.

Patients

Four hundred patients undergoing macroscopic curative resection for HCC involving the first branch or trunk of the PV between 2001 and 2010 at the 22 institutions were enrolled. We examined the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) on prognosis and validated the prognostic index consisting of ascites, prothrombin activity, and maximal tumor diameter.

Results

Median survival time (MST) and 5‐year overall survival rate were 21.5 months and 25.7%. MST of HAIC group was longer than that of non‐HAIC group (28.1 months vs. 18.7 months, P = 0.0024). Significant prognostic factors for overall survival were PIVKA‐II, tumor diameter, and adjuvant HAIC. MST for patients with prognostic index 0, 1, 2, and 3 was 39.0, 21.1, 18.9, and 5.7 months, respectively (P = 0.005).

Conclusions

Macroscopic curative resection with adjuvant HAIC might provide better survival outcome. Furthermore, the prognostic index was useful to select adequate treatment modalities for patients with HCC with tumor thrombosis in the major PV.
Preoperative tumor texture analysis on MRI predicts high‐risk disease and reduced survival in endometrial cancer
Authors: Ytre‐Hauge Sigmund , Dybvik Julie A. , Lundervold Arvid , Salvesen Øyvind O. , Krakstad Camilla , Fasmer Kristine E. , Werner Henrica M. , Ganeshan Balaji , Høivik Erling , Bjørge Line , Trovik Jone , Haldorsen Ingfrid S.
Published: August 2018

Background

Improved methods for preoperative risk stratification in endometrial cancer are highly requested by gynecologists. Texture analysis is a method for quantification of heterogeneity in images, increasingly reported as a promising diagnostic tool in various cancer types, but largely unexplored in endometrial cancer.

Purpose

To explore whether tumor texture parameters from preoperative MRI are related to known prognostic features (deep myometrial invasion, cervical stroma invasion, lymph node metastases, and high‐risk histological subtype) and to outcome in endometrial cancer patients.

Study type

Prospective cohort study.

Population/Subjects

In all, 180 patients with endometrial carcinoma were included from April 2009 to November 2013 and studied until January 2017.

Field Strength/Sequences

Preoperative pelvic MRI including contrast‐enhanced T1‐weighted (T1c), T2‐weighted, and diffusion‐weighted imaging at 1.5T.

Assessment

Tumor regions of interest (ROIs) were manually drawn on the slice displaying the largest cross‐sectional tumor area, using the proprietary research software TexRAD for analysis. With a filtration‐histogram technique, the texture parameters standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis were calculated.

Statistical Tests

Associations between texture parameters and histological features were assessed by uni‐ and multivariable logistic regression, including models adjusting for preoperative biopsy status and conventional MRI findings. Multivariable Cox regression analysis was used for survival analysis.

Results

High tumor entropy in apparent diffusion coefficient (ADC) maps independently predicted deep myometrial invasion (odds ratio [OR] 3.2, P lt  0.001), and high MPP in T1c images independently predicted high‐risk histological subtype (OR 1.01, P = 0.004). High kurtosis in T1c images predicted reduced recurrence‐ and progression‐free survival (hazard ratio [HR] 1.5, P lt  0.001) after adjusting for MRI‐measured tumor volume and histological risk at biopsy.

Data Conclusion

MRI‐derived tumor texture parameters independently predicted deep myometrial invasion, high‐risk histological subtype, and reduced survival in endometrial carcinomas, and thus, represent promising imaging biomarkers providing a more refined preoperative risk assessment that may ultimately enable better tailored treatment strategies in endometrial cancer.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;48:1637–1647
Age‐related changes of shape and flow dynamics in healthy adult aortas: A 4D flow MRI study
Authors: Callaghan Fraser M. , Bannon Paul , Barin Edward , Celemajer David , Jeremy Richmond , Figtree Gemma , Grieve Stuart M.
Published: August 2018

Background

Abnormal flow dynamics play an early and causative role in pathologic changes of the ascending aorta.

Purpose

To identify: 1) the changes in flow, shape, and size that occur in the ascending aorta with normal human ageing and 2) the influence of these factors on aortic flow dynamics.

Study Type

Retrospective.

Subjects

In all, 247 subjects (age range 19–86 years, mean 49 ± 17.7, 169 males) free of aortic or aortic valve pathology were included in this study. Subjects were stratified by youngest (18–33 years; n = 64), highest (>60 years, n = 67), and the middle two quartiles (34–60 years, n = 116).

Field Strength/Sequence

Subjects underwent a cardiac MRI (3T) exam including 4D‐flow MRI of the aorta.

Assessment

Aortic curvature, arch shape, ascending aortic angle, ascending aortic diameter, and the stroke volume normalized by the aortic volume (nSV) were measured. Velocity, vorticity, and helicity were quantified across the thoracic aorta.

Statistical Tests

Univariate and multivariate regressions were used to quantify continuous relationships between variables.

Results

Aortic diameter, ascending aortic angle, shape, and curvature all increased across age while nSV decreased (all P < 0.0001). Systolic vorticity in the mid arch decreased by 50% across the age range (P < 0.0001), while peak helicity decreased by 80% (P < 0.0001). Curvature tightly governs optimal flow in the youngest quartile, with an effect size 1.5 to 4 times larger than other parameters in the descending aorta, but had a minimal influence with advancing age. In the upper quartile of age, flow dynamics were almost completely determined by nSV, exerting an effect size on velocity and vorticity >10 times that of diameter and other shape factors.

Data Conclusion

Aortic shape influences flow dynamics in younger subjects. Flow conditions become increasingly disturbed with advancing age, and in these conditions nSV has a more dominant effect on flow patterns than shape factors.

Level of Evidence: 3

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;49:90–100.
Effect of injection barrier height on charge transport under bipolar injection
Authors: Meftali Nadia , Bouazabia Slimane , Fofana Issouf , El Maouhab Ali
Published: August 2018

In this paper, a numerical model describing the transient phenomena of electric charge in a dielectric because of a double injection at 2 electrodes is proposed. The mathematical model and the methods for its resolution are presented step by step. Thus, the Schottky equation is used to describe the injection of negative and positive charges from the cathode and anode respectively. The equations governing the conduction are the current equation and the Poisson equation coupled to the continuity equation. The adopted model uses the applied voltage instead of the applied electric field. The Poisson equation is solved by finite differences using the Thomas algorithm and the continuity equation by Euler's method. The Thomas algorithm reduces considerably the execution time compared to iterative methods. The time step is not constant; it is calculated from the speed of the charges front. The results show that the established model and the method of resolution reproduce correctly the behaviour of the system under a high voltage. It shows also that knowing the injection barrier height can be used to predict the behaviour of the dielectric under electrical stress. The developed model is a tool for describing the behaviour of the charges for a bipolar injection.
Metagenome complexity and template length are the main causes of bias in PCR‐based bacteria community analysis
Authors: Peng Wentao , Li Xiangmin , Wang Chuang , Cao Hui , Cui Zhongli
Published: August 2018

Multitemplate PCR is used widely for the study of microbial community diversity. Although such studies have established the abundance of different groups within many natural ecosystems, these reports are limited by uncertainties such as bias and artifacts in the PCR. Bias which is introduced by the simultaneous amplification of specific genes from complex mixtures of templates remains poorly understood. In this study, factors leading to the bias of the multitemplate PCR in bacterial communities were examined and optimized. Comparisons between PCR cycle parameters, DNA polymerases, PCR primer degeneracy, and 16S rRNA gene fragments GC content, revealed that annealing temperatures and DNA structure are predominant factors contributing to the observed bias. Pre‐digestion of metagenomic DNA with the restriction enzyme Sau3A I and decreased annealing temperature reduced the bias significantly. The application of these optimized conditions to the ten‐species model community in a soil sample verified the validity of these treatments.
A rapid and sensitive method for the quantitative analysis of ibuprofen and its metabolites in equine urine samples by gas chromatography with tandem mass spectrometry
Authors: Waraksa Emilia , Woźniak Mateusz Kacper , Kłodzińska Ewa , Wrzesień Robert , Bobrowska‐Korczak Barbara , Namieśnik Jacek
Published: August 2018

Ibuprofen is widely used in human and veterinary medicine for the treatment of chronic pain as well as rheumatic and musculoskeletal disorders. However, the analgesic and anti‐inflammatory properties of Ibuprofen have contributed to frequent drug abuse in equestrian sports. A sensitive and rapid gas chromatography with tandem mass spectrometry based method with a simple liquid‐liquid extraction and derivatization requiring 200 μL volume of sample and 2 mL of extraction solvent for the simultaneous determination of ibuprofen and its metabolites was developed. The proposed procedure was optimized and validated according to the principles for bioanalytical methods. The assay achieved satisfactory validation parameters, namely, recovery (92.2–105%), interday accuracy (92.5–106%), and precision (0.3–4.4%) for all investigated compounds as well as limits of quantification of 50 ng/mL for ibuprofen, 2‐hydroxyibuprofen, and carboxyibuprofen, 25 ng/mL for 1‐hydroxyibuprofen and 100 ng/mL for 3‐hydroxyibuprofen. The applicability of the method was evaluated by the analysis of five real urine samples collected from different horses after drug administration. In view of the low limits of quantification, high selectivity, repeatability, and recovery, the procedure can be utilized for laboratory applications, including the control of ibuprofen abuse in equestrian sports for anti‐doping purposes and drug/pharmaceutical mentality investigations.
Clinical efficacy of novel elastography using acoustic radiation force impulse (ARFI) for diagnosis of malignant thyroid nodules
Authors: Fukuhara Takahiro , Matsuda Eriko , Donishi Ryohei , Koyama Satoshi , Miyake Naritomo , Fujiwara Kazunori , Takeuchi Hiromi
Published: August 2018

Objective

Acoustic radiation force impulse (ARFI) imaging is a recent ultrasound elastography technique; consequently, its efficacy is not fully known. In this study, we compared ARFI imaging with conventional strain elastography (SE) and shear wave velocities (SWVs) to evaluate the utility of ARFI imaging for diagnosing thyroid nodules.

Subjects and Methods

In this study we examined 233 thyroid nodules (183 benign nodules and 50 malignant nodules) isolated from human patients. The nodules were evaluated with SE and ARFI imaging, and SWVs of the nodules were simultaneously measured. ARFI images were classified using a four‐point score based on grayscale intensity of the images. The sensitivity, specificity, and diagnostic accuracy were compared between SE and ARFI imaging. Finally, SWVs for each score of SE and ARFI imaging were compared.

Results

The new scoring system for ARFI imaging can be divided into four virtual touch imaging (VTI) scores. Nodules with a VTI score of 3 or 4 as determined by ARFI imaging were determined to be malignant. The sensitivity, specificity, and diagnostic accuracy, respectively, were 63.2%, 66.3%, and 65.6% for SE, compared with 80.0%, 86.3%, and 85.0% for ARFI imaging. The median SWVs of the nodules were 1.57 m/s, 1.73 m/s, 1.88 m/s, and 2.09 m/s for VTI scores of 1, 2, 3, and 4, respectively. The SWVs of VTI scores 3 and 4 were significantly higher than those of VTI scores 1 and 2.

Conclusions

The diagnostic accuracy of ARFI imaging for differentiating malignant thyroid nodules was higher than that of SE. The VTI scores of the nodules accurately reflected their SWVs.

Level of Evidence

4
A Resuscitation Option for Upper Airway Occlusion Based on Bolus Transtracheal Lung Inflation
Authors: Villiere Sophia , Nakase Ko , Kollmar Richard , Arjomandi Hamid , Lazar Jason , Sundaram Krishnamurthi , Silverman Joshua B. , Lucchesi Michael , Wlody David , Stewart Mark
Published: August 2018

Background

Acute laryngospasm sufficient to cause obstructive apnea is a medical emergency that can be difficult to manage within the very short time available for establishing an airway. We have presented substantial evidence that laryngospasm‐based obstructive apnea is the cause of sudden death in epilepsy, and airway management is particularly challenging during seizure activity.

Objective

We sought to determine if the transtracheal delivery of a bolus of oxygen or room air below the level of an obstruction to inflate the lungs could be an effective method to prolong the time available for responders seeking to establish a stable airway, and, if so, what could be learned about optimization of delivery parameters from a rat model.

Methods

Rats were fitted with a t‐shaped tracheal tube for controlling access to air and for measuring airway pressures. After respiratory arrest from simulated laryngospasm, bolus transtracheal lung inflation with a volume of gas equivalent to half the vital capacity was delivered to the closed respiratory system as the only resuscitation step.

Results

Bolus lung inflation was sufficient for resuscitation, improving cardiac function and re‐establishing adequate oxygen status to support life. Inflation steps could be repeated and survival times were approximately 3 times that of non‐inflated lungs.

Conclusion

The properties and consequences of bolus lung inflation are described as a foundation for procedures or devices that can be useful in cases of severe laryngospasm and other cases of upper airway obstruction.

Level of Evidence

3
Hypoglossal Nerve Stimulator Implantation in a Non‐Academic Setting: Two‐Year Result
Authors: Weeks Brian , Bao Gao , Gilbert Tina M. , Emdur Larry
Published: August 2018

Objectives/Hypothesis

Upper Airway Stimulation (UAS) is an FDA approved treatment option for patients with moderate‐to‐severe obstructive sleep apnea (OSA) who could not adhere to continuous positive airway pressure (CPAP). Previous studies have shown UAS reduced apnea‐hypopnea index (AHI) in controlled clinical trials and from academic institutions. We report patient outcomes and therapy adherence of UAS in a non‐academic hospital and clinic setting.

Study Design

Case series of consecutive patients.

Methods

Consecutive implants completed at a community hospital between January 2015 to Feb 2017 are included in this report. All patients underwent baseline polysomnography (PSG) recording and drug‐induced sleep endoscopy (DISE) prior to the implant. All patients had returned for standard post‐implantation titration PSG at a community sleep clinic to validate and adjust the stimulation setting for optimal response. Results were in mean ± SD, and pre‐ and post‐implant data were compared using a paired student t‐test.

Results

A total 22 patients undergoing UAS implant were overweight (BMI of 28.9 ± 5.0 kg/m2) and middle aged (63.2 ± 11.1 years), and had severe OSA (AHI of 35.9 ± 19.1). The AHI from the entire night of the titration study was 16.0 ± 10.4 (P < .01, compared with baseline), and the treatment AHI from the sleep period when the optimal setting was programmed was 1.2 ± 1.1 (P < .001, compared with baseline), and 90% patients had titrated AHI less than 5. The lowest SpO2 increased from 81% ± 8% at baseline to 91% ± 3% at the titrated setting (P = .001). After an average follow up of 95 ± 28.5 days, the therapy use per night was 7.0 ± 1.9 hours per night. The average postoperative ESS was 6.7 ± 5.3 of 18 patients, a reduction from the baseline of 10.9 ± 4.8. A total of 13 of 18 patients with postoperative ESS < 10, a measure indicated normalization of daytime sleepiness.

Conclusion

Patients who elected to receive UAS implant surgery at a non‐academic hospital and followed at a sleep clinic showed significant reduction in OSA severity with strong adherence to treatment. These results supported that UAS as a valid treatment option for OSA can be successfully implemented in the non‐academic hospital and clinic settings.

Level of Evidence

4
Injectable and Cell‐Adhesive Polyethylene Glycol Cryogel Scaffolds: Independent Control of Cryogel Microstructure and Composition
Authors: Bruns Joseph , McBride‐Gagyi Sarah , Zustiak Silviya Petrova
Published: August 2018

Polyethylene glycol (PEG) cryogels are promising alternatives to hydrogels due to their macroporosity. PEG is bioinert and modifications with adhesive ligands enable independent control of cryogel physical, mechanical, and biochemical properties. Pre‐functionalization of PEG cryogels with ligands is crucial, as cryogel formation consumes all functional groups. Here, injectable ligand pre‐functionalized PEG cryogels are fabricated and characterized. Cryogel pore size (54–163 µm), porosity (40–80%), and Young's modulus (1–40 kPa) are modulated through controlling the rate of freezing, ice crystal formation, and polymer concentration. Ligand pre‐functionalization does not affect cryogel properties. NIH 3T3 cell viability and infiltration are governed by ligand concentration and cryogel porosity.
Integrated Functional High‐Strength Hydrogels with Metal‐Coordination Complexes and H‐Bonding Dual Physically Cross‐linked Networks
Authors: Li Xuefeng , Li Rongzhe , Liu Zuifang , Gao Xiang , Long Shijun , Zhang Gaowen
Published: August 2018

With the deepening of research on high‐strength hydrogels, the multi‐functional study of hydrogels has become a hot spot. In this paper, a dual cross‐linked physical high‐strength hydrogels is prepared by a relatively simple method. 2‐Vinyl‐ 4,6‐Diamino‐2‐vinyl‐1,3,5‐triazine (VDT) induces the formation of the first cross‐linking points through the interaction of hydrogen bonds with poly(acrylamide‐co‐acrylic acid) (PAm‐co‐Ac) chains, then the secondary physical cross‐linkers Fe3+ that introduce ionic coordinates between Fe3+ and –COO− groups. Due to the synergistic effect of hydrogen bonding and ionic coordination, hydrogels possess high tensile strength (approx. 4.34 MPa), large elongation (approx. 17.64 times), and good healing properties under alkali solution after cutting into two pieces. Meanwhile, VDT contains diaminotriazine functional groups that easily form hydrogen bonds so that the polymer of hydrogels could absorb 5‐fluorouridine. In addition, the contribution of ionic polymer segments enables pH to be sensitive to hydrogels and facilitates the adsorption of a large number of ionic monomers to form ionic conductive networks, the prepared hydrogel capacitor device has very high sensitivity to pressure and deformation, and can detect the movement behavior of the human body. The dual‐physical cross‐linked hydrogels had a selective adsorption to biological small molecules and could be assembled into a flexible wearable device with high sensitivity.
Soluble Hyperbranched Porous Organic Polymers
Authors: Yang Yuwan , Feng Lingyun , Ren Jun , Liu Yunfei , Jin Shangbin , Su Li , Wood Colin , Tan Bien
Published: August 2018

Soluble porous organic polymers (SPOPs) are currently the subject of extensive investigation due to the enhanced processability compared to insoluble counterparts. Here, a new concept for the construction of SPOPs is presented, which combines the unique topological structure of hyperbranched polymers with rigid building blocks. By using this facile, one‐step strategy, a class of novel SPOPs which possess surface areas up to 646 m2 g−1 have been synthesized. The extended π‐conjugated backbone affords the polymers bright fluorescence under UV irradiation. Interestingly, after dissolution in a suitable solvent that was slowly evaporated, the polymers retain a large extent of porosity. The SPOPs are potential candidates for gas storage and separation, photovoltaic, and biological applications. In particular, due to the presence of an internal porous structure and open conformations, they show high drug loading efficiency (1.91 g of ibuprofen per gram), which is considerably higher than conventional porous organic polymers.
Targeting EGFRL858R/T790M and EGFRL858R/T790M/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry
Authors: Lu Xiaoyun , Yu Lei , Zhang Zhang , Ren Xiaomei , Smaill Jeff B. , Ding Ke
Published: August 2018

Both the first‐generation reversible epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib and the second‐generation covalent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) afatinib have significantly improved the survival of non‐small‐cell lung cancer (NSCLC) patients with activating EGFR mutations. However, a secondary EGFRT790M mutation leads to the clinically acquired resistance to the first‐ and second‐generation EGFR‐TKIs drugs. A number of the third‐generation wild‐type sparing EGFR inhibitors, for example, WZ4002, CO1686, AZD9291, HM61713, EGF816, ASP8173, and PF0674775, have been developed, among which AZD9291 has been approved by US FDA for the treatment of NSCLC patients with EGFRT790M. More recently, a tertiary EGFRC797S mutation was reported as the dominant resistance mechanism to the third‐generation irreversible inhibitors. It is highly desirable to develop the fourth‐generation EGFR inhibitors. This review summarizes the mechanisms of acquired resistance and the latest medicinal chemistry advances on the third‐ and fourth‐generation EGFR inhibitors, with special attention being paid to the allosteric and reversible inhibitors combating the tertiary EGFRC797S mutation.
A non‐iterative method for approximation of the exact solution to the point‐to‐plane variational problem for orthogonal transformations
Authors: Makovetskii Artyom , Voronin Sergei , Kober Vitaly , Voronin Aleksei
Published: August 2018

The most popular algorithm for aligning of three‐dimensional point data is the iterative closest point (ICP). In this paper, a new algorithm for orthogonal registration of point clouds based on the point‐to‐plane ICP algorithm is proposed. The algorithm consists of three steps: first, a matrix of affine transformation between two given point clouds are calculated; second, the affine transformation matrix is projected onto the manifold SO(3) of orthonormal matrices; finally, a translation vector is reestimated. The proposed algorithm does not require an approximate initial estimate. At each iterative step of the ICP algorithm, an approximated closed‐form solution for the orthogonal transformation is derived. The performance of the proposed algorithm is compared with that of common algorithms for the geometrical transformations estimation.
Stability of an adaptive immunity pathogen dynamics model with latency and multiple delays
Authors: Elaiw Ahmed M. , AlShamrani Noura H.
Published: August 2018

We incorporate three distributed time delays into the model of pathogen dynamics with antibody and Cytotoxic T Lymphocyte (CTL) immune responses. We consider both actively and latently infected cells. The pathogen‐target incidence rate, production/proliferation, and removal rates of the cells and pathogens are represented by general nonlinear functions. We show that the solutions of the proposed model are nonnegative and ultimately bounded. We derive four threshold parameters that fully determine the existence and stability of the five steady states of the model. Using Lyapunov functionals, we established the global stability of the steady states of the model. The theoretical results are confirmed by numerical simulations.
Fractional matrix and inverse matrix projective synchronization methods for synchronizing the disturbed fractional‐order hyperchaotic system
Authors: He Jinman , Chen Fangqi , Lei Tengfei
Published: August 2018

In this paper, for synchronizing two actual nonidentical fractional‐order hyperchaotic systems disturbed by model uncertainty and external disturbance, the fractional matrix and inverse matrix projective synchronization methods are presented and the methods' correctness and effectiveness are proved. Especially, under certain degenerative conditions, the methods are reduced to study the complete synchronization, antisynchronization, projective (or inverse projective) synchronization, modified (or modified inverse) projective synchronization, and stabilization problem for the disturbed (or undisturbed) fractional‐order hyperchaotic systems. In addition, as the fractional matrix and inverse matrix projective synchronization methods' applications, the fractional‐order hyperchaotic Chen and Rabinovich systems disturbed by model uncertainty and external disturbance are constructed, and the matrix and inverse matrix projective synchronizations between the two disturbed systems are achieved, respectively. This work constructs a basic theoretical framework of fractional matrix and inverse matrix projective synchronization methods and provides a general method for synchronizing the actual disturbed fractional‐order hyperchaotic systems that are related to science and engineering.
Diverse Excretion Pathways of Benzyl Glucosinolate in Humans after Consumption of Nasturtium (Tropaeolum majus L.)—A Pilot Study
Authors: Kühn Carla , Kupke Franziska , Baldermann Susanne , Klopsch Rebecca , Lamy Evelyn , Hornemann Silke , Pfeiffer Andreas F. H. , Schreiner Monika , Hanschen Franziska S. , Rohn Sascha
Published: August 2018

Scope

Different metabolic and excretion pathways of the benzyl glucosinolate breakdown products benzyl isothiocyanate and benzyl cyanide are investigated to obtain information about their multiple fate after ingestion. Detailed focus is on the so far underestimated transformation/excretion pathways—protein conjugation and exhalation.

Methods and results

Metabolites, protein conjugates, and non‐conjugated isothiocyanates are determined in plasma, urine, and breath of seven volunteers after consuming freeze‐dried nasturtium or bread enriched with nasturtium. Samples are collected up to 48 h at selected time points. The metabolites of the mercapturic acid pathway are detectable in plasma up to 24 h after consumption. Additionally, mercapturic acid is the main metabolite in urine, but non‐conjugated benzyl isothiocyanate is detectable as well. Protein conjugates show high amounts in plasma even 48 h after consumption. In breath, benzyl isothiocyanate and benzyl cyanide are detectable up to 48 h after consumption.

Conclusion

Isothiocyanates are not only metabolized via the mercapturic acid pathway, but also form protein conjugates in blood and are exhaled. To balance intake and excretion, it is necessary to investigate all potential metabolites and excretion routes. This has important implications for the understanding of physiological and pharmacological effects of isothiocyanate‐containing products.
Cromolyn/gelatin mixtures as aqueous alignment media and utilization of their mechanical stability for a layering technique
Authors: Niklas Thomas , Schulze Philipp , Farès Christophe
Published: August 2018

In this study, aqueous blends of cromolyn and gelatin (“cromogels”) are introduced as anisotropic media. The addition of gelatin enables an advantageous adjustability of the strength, the homogeneity, and the stability of the cromolyn alignment. The mechanical stability of these polymer‐dispersed liquid crystals is further utilized by stacking layers of D2O/cromolyn/gelatin with varying component ratio. The resulting distinct phases with correspondingly different degrees of alignment can be targeted by spatially resolved NMR techniques. As a case study, we investigated sucrose in a two‐phase system with neat D2O and analyte layered over the anisotropic medium. A recently presented spatially selective coupled‐type HSQC experiment allows the determination of one‐bond C‐H splitting in both phases.
Assessing recrudescence of photoregressed Siberian hamster ovaries using in vitro whole ovary culture
Authors: Shahed Asha , Young Kelly A.
Published: August 2018

In vitro culture has been used to study different aspects of ovarian function; however, this technique has not been applied to study recrudescence, or the return of ovarian function in seasonally breeding species. In Siberian hamsters, exposure to inhibitory photoperiods induces declines in ovarian function, which are restored with photostimulation. Because these changes are mediated by changes in systemic gonadotropin (GT) secretion, we hypothesized that culturing photoregressed ovaries with GT would restore aspects of function and induce expression of key folliculogenic factors. Adult female Siberian hamsters were exposed to either long‐day (LD; 16L:8D) or short‐day (SD; 8L:16D) photoperiods for 14 weeks to maintain in vivo cyclicity or induce gonadal regression, respectively. Isolated ovaries were then cultured for 10 days with or without GT. Ovarian mass and messenger RNA (mRNA) expression of mitotic marker Pcna were increased in cultured SD ovaries (cSD) ovaries with GT as compared to without GT, with no changes noted among cultured LD (cLD) ovaries. Media estradiol and progesterone concentrations increased in both cLD and cSD ovaries cultured with GT as compared to without GT. No differences in follicle numbers or incidence of apoptosis were noted across groups. In addition, differential mRNA expression of folliculogenic growth factors (
Bmp‐4,
Ntf‐3,
Inh‐α,
Gdf‐9, Igf‐1, Has‐2, and Cox‐2) was observed in cSD treated with or without GT. Together, these results suggest that this in vitro model could be a useful tool to (a) study the return of function in photoregressed ovaries, and (b) to identify the specific roles folliculogenic factors play in ovarian recrudescence.
Mathematical Disease Progression Modeling in Type 2/3 Spinal Muscular Atrophy
Authors: Jacqmin Philippe , Gieschke Ronald , Delor Isabelle , Snoeck Eric , Vianna Eduardo , Vuillerot Carole , Sanwald Ducray Patricia
Published: August 2018

Introduction: We propose a mathematical model to empirically describe spinal muscular atrophy (SMA) progression assessed by the 3 domains of the motor function measure (MFM) scale. The model implements development and deterioration of muscle function. Methods: Nonlinear mixed‐effects modeling was applied to data from 2 observational studies and 1 prospective clinical efficacy study comprising 190 healthy participants and 277 patients with type 2/3 SMA. Results: The model evidenced correlations between parameter estimates for different MFM domains. Slower development in MFM domain D1 (standing and transfers) was associated with faster deterioration for MFM domains D2 (proximal and axial motricity) and D3 (distal motor function). Discussion: The model describes all individual data well, although sparseness and variability of observational data prevented numerically stable estimation of parameters. Treatment duration in clinical studies was too limited to determine a proper drug‐effect model that could differentiate between symptomatic and disease modifying effects. Muscle Nerve 58: 528–535, 2018
Targeting PDGF‐mediated recruitment of pericytes blocks vascular mimicry and tumor growth
Authors: Thijssen Victor LJL , Paulis Yvette WJ , Nowak‐Sliwinska Patrycja , Deumelandt Katrin L , Hosaka Kayoko , Soetekouw Patricia MMB , Cimpean Anca M , Raica Marius , Pauwels Patrick , van den Oord Joost J , Tjan‐Heijnen Vivianne CG , Hendrix Mary J , Heldin Carl‐Henrik , Cao Yihai , Griffioen Arjan W
Published: August 2018

Aggressive tumor cells can adopt an endothelial cell‐like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry‐positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular‐like networks. The pericyte recruitment is mediated through platelet‐derived growth factor (PDGF)‐B. Consequently, preventing PDGF‐B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular‐like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry‐positive cancer types. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Hybridization of a thermoplastic natural rubber composite with multi‐walled carbon nanotubes/silicon carbide nanoparticles and the effects on morphological, thermal, and mechanical properties
Authors: Tarawneh Mou'ad A. , Chen Ruey Shan , Hj Ahmad Sahrim , Al‐Tarawni Musab A. M. , Saraireh S.A.
Published: August 2018

The thermal conductivity and mechanical performance of a hybrid multi‐walled carbon nanotubes/silicon carbide (MWCNTs/SiC)‐reinforced thermoplastic natural rubber (TPNR) nanocomposite were investigated. TPNR was fabricated from polypropylene, natural rubber (NR) and liquid NR at a volume ratio of 70:20:10, respectively. The Young's modulus, the tensile strength, and the storage and loss modulus of the nanocomposites with a single filler of MWCNTs or SiC were enhanced compared with those of neat TPNR. The greatest improvements in these properties were achieved at a composition of 1.5 wt% SiC‐1.5 wt% MWCNTs‐reinforced nanocomposite. In addition, the thermal conductivity and specific heat capacity of the nanocomposites, determined using a laser flash technique, were improved in the 3 wt% SiC‐reinforced nanocomposite sample relative to those of the pure sample and the other reinforced nanocomposites. Based on these findings, MWCNTs and SiC could serve as suitable percolated networks of hybrid reinforcement fillers to achieve optimal thermal and mechanical properties in the TPNR matrix. POLYM. COMPOS., 40:E695–E703, 2019. © 2018 Society of Plastics Engineers
Optical and dielectric properties of PMMA (poly(methyl methacrylate))/carbon dots composites
Authors: Bouknaitir Ilham , Panniello Annamaria , Teixeira Silvia Soreto , Kreit Lamyaa , Corricelli Michela , Striccoli Marinella , Costa Luis Cadillon , Achour Mohamed Essaid
Published: August 2018

The optical and the dielectric properties of an original nanocomposite based on the incorporation of carbon dots (C‐dots) in poly(methyl methacrylate) (PMMA) at several filler loading were studied. The optical characterization demonstrated the preservation of the excitation dependent intense emission of the C‐dots in the polymer, ascribed to the presence of organic fluorophores formed during the nanoparticle synthesis. The composite PMMA/C‐dots dielectric properties were investigated in the frequency range from 40 Hz to 1 MHz and over the temperature range from 200 to 400 K. The dielectric response was obtained using the complex permittivity or the modulus formalisms, depending on the concentration of filler in the polymer matrix. A relaxation phenomenon was induced by the incorporation of the C‐dots in the PMMA matrix. In addition, both the real and imaginary parts of the dielectric permittivity and electric modulus changed with the volume fraction of the C‐dots, suggesting that the presence of the fillers greatly affect the dielectric properties of the polymer matrix because of polarization phenomenon induced by the nanoparticles. POLYM. COMPOS., 40:E1312–E1319, 2019. © 2018 Society of Plastics Engineers
Production and characterization of ureaurethane elastomers with rapeseed‐based polyol
Authors: Mizera Kamila , Ryszkowska Joanna , Kurańska Maria , Prociak Aleksander
Published: August 2018

The purpose of this study was to evaluate the effect of rapeseed‐oil‐based (RO) polyol on the thermal and mechanical properties of tested ureaurethane elastomers (EPUUs). The chemical structure and degree of phase separation connected to the value of hydrogen bonds were tested by infrared spectroscopy. Thermal degradation was examined by TGA. The glass transition temperature and the enthalpy of heat effects were analysed by DSC. The mechanical properties were tested by dynamic mechanical thermal analysis and static tensile strength. The physicomechanical properties were also examined, including wear resistance and hardness of the tested materials. The use of RO polyol in 10–40 wt% concentration in polyol premixes changed the chemical structure of the EPUUs indicating a change in the quantity of hydrogen bonds and the degree of phase separation. DSC analysis showed that addition of the RO polyol causes an increase in the glass transition temperature of the soft phase in the EPUUs. © 2018 Society of Chemical Industry
Structure and dynamics of polypyrrole/chitosan nanocomposites
Authors: Ali Asmaa A , Elmahdy Mahdy M , Sarhan Afaf , Abdel Hamid Maysa I , Ahmed Moustafa T
Published: August 2018

Polypyrrole/chitosan (PPy/Cs) nanocomposites with various amounts of polypyrrole nanoparticles (PPy‐NPs) have been synthesized and afterwards exposed to UV irradiation for 240 min. Structure, dynamics and antibacterial activity of pure compounds and the corresponding nanocomposites were investigated by means of wide‐angle X‐ray scattering, Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, broadband dielectric spectroscopy and antibacterial activity assay. The occurrence of a pronounced interaction between PPy‐NPs and Cs has been verified. Broadband dielectric spectroscopy measurements revealed two relaxation processes at low and high frequencies. The low‐frequencyα‐relaxation associated with the glass–rubber transition is attributed to the presence of hydrogen‐bonded water (plasticizing effect) appearing at low temperature (<373 K). The high‐frequencyσ‐relaxation is related to water molecules which become desorbed upon heating atT > 373 K and demonstrates Arrhenius temperature dependence with activation energy in the range 70–90 kJ mol−1in good agreement with previous reports. On the contrary, PPy‐NPs do not show any structural relaxation process and the charge transport mechanism follows the correlated barrier hopping model. All PPy/Cs nanocomposites exhibit an improved antibacterial activity against bothStaphylococcus aureusandEscherichia colibacteria as compared with pure Cs and PPy‐NPs. © 2018 Society of Chemical Industry
Efficient organic photovoltaic cells based on thiazolothiazole and benzodithiophene copolymers with π‐conjugated bridges
Authors: Park Junhoo , Park Jong Baek , Ha Jong‐Woon , Park Hea Jung , Kang In‐Nam , Hwang Do‐Hoon
Published: August 2018

New donor–π–acceptor (D–π–A) type conjugated copolymers, poly[(4,8‐bis((2‐hexyldecyl)oxy)benzo[1,2‐b:4,5‐b′]dithiophene)‐alt‐(2,5‐bis(4‐octylthiophen‐2‐yl)thiazolo[5,4‐d]thiazole)] (PBDT‐tTz), and poly[(4,8‐bis((2‐hexyldecyl)oxy)benzo[1,2‐b:4,5‐b′]dithiophene)‐alt‐(2,5‐bis(6‐octylthieno[3,2‐b]thiophen‐2‐yl)thiazolo[5,4‐d]thiazole)] (PBDT‐ttTz) were synthesized and characterized with the aim of investigating their potential applicability to organic photovoltaic active materials. While copolymer PBDT‐tTz showed a zigzagged non‐linear structure by thiophene π‐bridges, PBDT‐ttTz had a linear molecular structure with thieno[3,2‐b]thiophene π‐bridges. The optical, electrochemical, morphological, and photovoltaic properties of PBDT‐tTz and PBDT‐ttTz were systematically investigated. Furthermore, bulk heterojunction photovoltaic devices were fabricated by using the synthesized polymers as p‐type donors and [6,6]‐phenyl‐C71‐butyric acid methyl ester as an n‐type acceptor. PBDT‐ttTz showed a high power conversion efficiency (PCE) of 5.21% as a result of the extended conjugation arising from the thienothiophene π‐bridges and enhanced molecular ordering in the film state, while PBDT‐tTz showed a relatively lower PCE of 2.92% under AM 1.5 G illumination (100 mW/cm2). © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1978–1988