bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical inference in brain graphs using threshold‐free network‐based statistics
Authors: Baggio Hugo C. , Abos Alexandra , Segura Barbara , Campabadal Anna , Garcia‐Diaz Anna , Uribe Carme , Compta Yaroslau , Marti Maria Jose , Valldeoriola Francesc , Junque Carme
Published: February 2018

The description of brain networks as graphs where nodes represent different brain regions and edges represent a measure of connectivity between a pair of nodes is an increasingly used approach in neuroimaging research. The development of powerful methods for edge‐wise group‐level statistical inference in brain graphs while controlling for multiple‐testing associated false‐positive rates, however, remains a difficult task. In this study, we use simulated data to assess the properties of threshold‐free network‐based statistics (TFNBS). The TFNBS combines threshold‐free cluster enhancement, a method commonly used in voxel‐wise statistical inference, and network‐based statistic (NBS), which is frequently used for statistical analysis of brain graphs. Unlike the NBS, TFNBS generates edge‐wise significance values and does not require the a priori definition of a hard cluster‐defining threshold. Other test parameters, nonetheless, need to be set. We show that it is possible to find parameters that make TFNBS sensitive to strong and topologically clustered effects, while appropriately controlling false‐positive rates. Our results show that the TFNBS is an adequate technique for the statistical assessment of brain graphs.
Using quantitative tissue phenotype to assess the margins of surgical samples from a pan‐Canadian surgery study
Authors: Guillaud Martial , MacAulay Calum E. , Berean Kenneth W. , Bullock Martin , Guggisberg Kelly , Klieb Hagen , Puttagunta Lakshmi , Penner Carla , Kwan Keith , Rosin Miriam P. , Poh Catherine F.
Published: February 2018

Background

The purpose of this study was to use quantitative tissue phenotype (QTP) to assess the surgical margins to examine if a fluorescence visualization‐guided surgical approach produces a shift in the surgical field by sparing normal tissue while catching high‐risk tissue.

Methods

Using our QTP to calculate the degree of nuclear chromatin abnormalities, Nuclear Phenotypic Score (NPS), we analyzed 1290 biopsy specimens taken from surgical samples of 248 patients enrolled in the Efficacy of Optically‐guided Surgery in the Management of Early‐staged Oral Cancer (COOLS) trial. Multiple margin specimens were collected from each surgical specimen according to the presence of fluorescence visualization alterations and the distance to the surgical margins.

Results

The NPS in fluorescence visualization‐altered (fluorescence visualization‐positive) samples was significantly higher than that in fluorescence visualization‐retained (fluorescence visualization‐negative) samples. There was a constant trend of decreasing NPS of margin samples from non‐adjacent‐fluorescence visualization margins to adjacent‐fluorescence visualization margins.

Conclusion

Our results suggested that using fluorescence visualization to guide surgery has the potential to spare more normal tissue at surgical margins.
Time course and clinical characterization of cisplatin‐induced ototoxicity after treatment for nasopharyngeal carcinoma in a South East Asian population
Authors: Chan Sze Ling , Ng Li Shia , Goh Xueying , Siow Chor Hiang , Goh Han Lee , Goh Boon Cher , Cheo Timothy , Loh Kwok Seng , Brunham Liam R.
Published: February 2018

Background

The purpose of this study was to characterize the clinical course of hearing loss in patients with nasopharyngeal carcinoma (NPC) and the clinical factors affecting its severity.

Methods

The time course of hearing loss in patients with NPC was assessed using threshold shift from baseline and Common Terminology Criteria for Adverse Events (CTCAE) grade.

Results

In the chemoradiotherapy (CRT) groups, the threshold shift was significantly higher from 3 months at 4 kHz (P = 2.30 × 10−9, concurrent CRT only) but not within 2 years posttreatment in the radiotherapy (RT) group. The CRT groups had worse CTCAE grades than the RT group (percentage of latest CTCAE grade ≥1: 64.9% vs 29.0%, respectively). Cumulative cisplatin dose and cochlear RT dose significantly affects threshold shifts, especially at high frequencies.

Conclusion

Although cisplatin led to high frequency hearing impairment from about 3 months posttreatment, RT conferred no significant hearing impairment in the first 2 years.
Development of regenerative and flexible fibroin‐based wound dressings
Authors: Panico Angelica , Paladini Federica , Pollini Mauro
Published: February 2018

Skin injuries represent a health problem with consequences in terms of morbidity, disability and life quality. Numerous strategies have been developed for the treatment of wounds, including skin substitutes, biomembranes, scaffolds, and smart dressings. The excellent properties of fibroin can be exploited for the development of advanced wound dressing biomaterials, aiming at promoting the wound healing process. In this work, silk fibroin films modified through the addition of glucose were developed to enhance flexibility of medical device without affecting the biocompatibility, to promote wound healing and to improve the patient well‐being. The glucose/fibroin blend was characterized through Fourier transform infrared spectroscopy and differential scanning calorimetry to analyze the protein structure. Absorption capacity, mechanical properties, wettability and bacterial biofilm formation on silk fibroin films were also analyzed to study the effect of the addition of a plasticizer on the properties of the wound dressing. The stability of the films was analyzed through in vitro biodegradability tests. The biocompatibility and regenerative properties were demonstrated through appropriate cellular assays. The results demonstrated that the addition of glucose induced crystallization and provided good flexibility and absorption capacity of silk fibroin films. Glucose modified silk fibroin films were biocompatible and had a positive effect in promoting the wound closure. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 7–18, 2019.
Molecular dynamics study of taxadiene synthase catalysis
Authors: Escorcia Andrés M. , van Rijn Jeaphianne P. M. , Cheng Gui‐Juan , Schrepfer Patrick , Brück Thomas B. , Thiel Walter
Published: February 2018

Molecular dynamics (MD) simulations have been performed to study the dynamic behavior of noncovalent enzyme carbocation complexes involved in the cyclization of geranylgeranyl diphosphate to taxadiene catalyzed by taxadiene synthase (TXS). Taxadiene and the observed four side products originate from the deprotonation of carbocation intermediates. The MD simulations of the TXS carbocation complexes provide insights into potential deprotonation mechanisms of such carbocations. The MD results do not support a previous hypothesis that carbocation tumbling is a key factor in the deprotonation of the carbocations by pyrophosphate. Instead water bridges are identified which may allow the formation of side products via multiple proton transfer reactions. A novel reaction path for taxadiene formation is proposed on the basis of the simulations. © 2018 Wiley Periodicals, Inc.
Semiempirical configuration interaction calculations for ru‐centered dyes*
Authors: Fredin Lisa A. , Allison Thomas C.
Published: February 2018

Computational investigation of the photochemical properties of transition‐metal‐centered dyes typically involves optimization of the molecular structure followed by calculation of the UV/visible spectrum. At present, these steps are usually carried out using density functional theory (DFT) and time‐dependent DFT calculations. Recently, we demonstrated that semiempirical methods with appropriate parameterization could yield geometries that were in very good agreement with DFT calculations, allowing large sets of molecules to be screened quickly and efficiently. In this article, we modify a configuration interaction (CI) method based on a semiempirical PM6 Hamiltonian to determine the UV/visible absorption spectra of Ru‐centered complexes. Our modification to the CI method is based on a scaling of the two‐center, two‐electron Coulomb integrals. This modified, PM6‐based method shows a significantly better match to the experimental absorption spectra versus the default configuration interaction method (in MOPAC) on a training set of 13 molecules. In particular, the modified PM6 method blue‐shifts the location of the metal‐to‐ligand charge‐transfer (MLCT) peaks, in better agreement with experimental and DFT‐based computational results, correcting a significant deficiency of the unmodified method. Published 2018. This article is a U.S. Government work and is in the public domain in the USA
Atrial fibrillation and cryptogenic stroke. What is the current evidence? Role of electrocardiographic monitoring
Authors: Carmona‐Puerta Raimundo , Castro‐Torres Yaniel
Published: February 2018

The diagnosis of cryptogenic stroke is made by exclusion. However, current evidence supports the role of atrial fibrillation episodes as a cause of this condition. Prospective data have demonstrated the benefits of long‐term electrocardiographic monitoring to identify atrial fibrillation in association with cryptogenic stroke. This aim of this article was to analyze the contemporary evidence for the possible relationship between atrial fibrillation and cryptogenic stroke and the role of continuous electrocardiographic monitoring to clarify this hypothesis.
Clinical pharmacy in a regional Australian intensive care unit
Authors: Howle Lisa M. , Kirkpatrick Carl M. J. , Trethewy Christopher E.
Published: February 2018

Background

More than a quarter of reported incidents in hospitals are medication‐related. The critically ill population is at greater risk of medication‐related incidents due to a number of factors, including a higher number of drugs prescribed, lower physiological reserve and greater illness severity. Overseas studies have shown that the inclusion of on‐ward clinical pharmacy support may attenuate these drug‐related problems (DRPs); however, local evidence in regional Australian intensive care units (ICUs) is lacking.

Aim

To identify the frequency of DRPs and their risk to patients and the reporting of adverse drug reactions (ADRs) and incidents through the integration of a clinical pharmacist into a regional Australian ICU.

Method

A single‐centre, cohort‐controlled observational study conducted in a regional ICU over a 16‐week period. Data was collected on ADR and incident reporting, on‐call pharmacy requests and medications ordered but not administered to patients. The prospective period additionally examined the number and type of DRPs, pharmacist recommendations and acceptance by clinicians. An independent panel review assessed DRP risk and clinical significance.

Results

There were 348 DRPs requiring intervention in the prospective period with a median of two DRPs per patient. ‘Change of therapy’ was the most common recommendation (75%) and its acceptance by clinicians was 86%. Level of agreement between panel members for assigning both risk and clinical significance to DRPs was poor. Instances where medications were ordered but not administered were reduced by 62% (p = 0.0045). Requests for after‐hours pharmacy services were reduced and reporting of ADRs and incidents was marginally increased in the prospective group.

Conclusion

The addition of a clinical pharmacist to the ICU facilitated the detection and resolution of DRPs in this patient group and increased both the likelihood that intended pharmaceutical care reached the patient and that drug reactions and incidents were reported. These results provide local evidence for the inclusion of clinical pharmacists to the multidisciplinary ICU team in a regional Australian hospital.
Reducing intravenous infusion errors: an observational study of 16 866 patients over five years
Authors: Wiseman Meredith L. , Poole Susan , Ahlin Andrea , Dooley Michael J.
Published: February 2018

Background

Medication administration errors account for the largest proportion of medication errors in hospitals, impacting significantly on patient safety. Intravenous infusions carry a high risk for error due to their complex nature and use in high acuity settings. Two safety strategies for infusion safety introduced across a tertiary hospital network include the utilisation of the clinical pharmacy review and annotation of infusion orders, and the introduction of smart infusion pump technology with dose error reduction software.

Aim

The objective of this study was to evaluate the effects of two medication safety strategies: clinical pharmacist review including medication order annotation, and introduction of smart infusion pumps on rate and severity medication administration errors.

Method

A pre‐ and post‐intervention, observational study was undertaken at four time points over a five‐year period which included the review of 16 866 patients in a large tertiary referral hospital.

Results

Pharmacist annotation independently resulted in a reduction in errors from 16.6 to 8.1%. Subsequent implementation of smart pumps with a comprehensive drug library and high user compliance resulted in a further reduction from 8.1 to 3.9%. These reductions were sustained, with an overall error rate of 5% after two years.

Conclusion

The importance of timely clinical pharmacist review of intravenous infusion medication orders, and the implementation of smart infusion pump technology, along with well‐resourced drug library development with emphasis on quality management, education and training, should be prioritised, in order to reduce medication administration errors and to maximise patient safety.
Nomogram predicting the risk of recurrence after curative‐intent resection of primary non‐metastatic gastrointestinal neuroendocrine tumors: An analysis of the U.S. Neuroendocrine Tumor Study Group
Authors: Merath Katiuscha , Bagante Fabio , Beal Eliza W. , Lopez‐Aguiar Alexandra G. , Poultsides George , Makris Eleftherios , Rocha Flavio , Kanji Zaheer , Weber Sharon , Fisher Alexander , Fields Ryan , Krasnick Bradley A. , Idrees Kamran , Smith Paula M. , Cho Cliff , Beems Megan , Schmidt Carl R. , Dillhoff Mary , Maithel Shishir K , Pawlik Timothy M.
Published: February 2018

Background

The risk of recurrence after resection of non‐metastatic gastro‐entero‐pancreatic neuroendocrine tumors (GEP‐NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative‐intent resection.

Methods

A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c‐indices.

Results

Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. On multivariable analysis, Ki‐67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki‐67 index (HR 1.08, 95% CI, 1.05‐1.10; P < 0.001). GEP‐NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03‐2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11‐2.51; P = 0.014). Patients with 1‐3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12‐2.87; P = 0.014) and 2.51 (95% CI, 1.50‐4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c‐index: training set, 0.739; test set, 0.718).

Conclusion

The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting.
Identification of preoperative factors associated with outcomes following surgical management of intra‐abdominal recurrent or metastatic GIST following neoadjuvant tyrosine kinase inhibitor therapy
Authors: Roland Christina L. , Bednarski Brian K. , Watson Kelsey , Torres Keila E. , Cormier Janice N. , Wang Wei‐Lien , Lazar Alexander J. , Somaiah Neeta , Hunt Kelly K. , Feig Barry W.
Published: February 2018

Background

The role of surgical resection in the treatment of patients with metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim of this study was to identify preoperative factors associated with oncologic outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI) therapy.

Methods

We identified 107 patients with metastatic or recurrent GIST treated with TKIs and surgical resection (2002‐2012). Patients that underwent palliative or incomplete resection were excluded. Complete resection was achieved in 87 patients which comprise the analytic cohort. Univariate and multivariate analyses were conducted to identify risk factors for GIST‐specific survival (DSS) and time‐to‐recurrence (TTR).

Results

At a median follow‐up of 51 months (91 months for survivors), median DSS was 74 months and TTR was 21 months. By univariate analysis, unifocal disease, duration of TKI < 365 days, and no evidence of radiographic progression were associated with improved TTR and DSS. Multivariate Cox regression demonstrated that evidence of radiographic progression was associated with shorter DSS (HR 2.53, 95%CI = 1.27‐5.06, P = 0.008) and increased risk of recurrence (HR 3.33, 95%CI = 1.91‐5.82, P < 0.001).

Conclusions

Patients with unifocal disease and radiographic evidence of response to TKI therapy may achieve improved oncologic outcomes when complete surgical resection is achieved following treatment with TKI.
ALBI versus Child‐Pugh grading systems for liver function in patients with hepatocellular carcinoma
Authors: Na Seong K. , Yim Sun Y. , Suh Sang J. , Jung Young K. , Kim Ji H. , Seo Yeon S. , Yim Hyung J. , Yeon Jong E. , Byun Kwan S. , Um Soon H.
Published: February 2018

Background

The prognostic performance of the albumin‐bilirubin (ALBI) grade in hepatocellular carcinoma (HCC) as an objective method of assessing liver function was investigated.

Methods

Data from 2099 patients with HCC in Korea were collected and analyzed retrospectively. The discriminative performance of ALBI grade was compared with Child‐Pugh (C‐P) grade for different stages or treatments.

Results

The median follow up duration was 16.2 months (range: 1.0‐124.9). The median survival times were 49.7 months for C‐P grade A (65.8%), 12.4 months for C‐P grade B (25.5%), and 4.2 months for C‐P grade C (8.6%) (P < 0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5 months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P < 0.001). In early UICC stages, ALBI grade showed better discriminative performance than C‐P grade. In curative treatments, ALBI grade also showed better discriminative performance than C‐P grade (Harrell's C: 0.624 (C‐P grade) vs 0.667 [ALBI grade]).

Conclusions

ALBI grade provided better prognostic performance in survival analysis and better distribution of the grades than C‐P grade in HCC, suggesting that ALBI grade could be a good alternative grading system for liver function in patients with HCC.
Neutrophil: Lymphocyte ratio as a method of predicting complications following hepatic resection for colorectal liver metastasis
Authors: McCluney Simon J. , Giakoustidis Alexandros , Segler Angela , Bissel Juliane , Valente Roberto , Hutchins Robert R. , Abraham Ajit T. , Bhattacharya Satyajit , Kocher Hemant M.
Published: February 2018

Background and Objectives

Approximately 30‐50% of patients with colorectal cancer develop liver metastasis for which liver resection is the only hope for potential cure. However, hepatic resection is associated with considerable morbidity. The aim was to detect early complications by utilising the neutrophil: lymphocyte ratio (NLR).

Methods

We performed a retrospective cohort study of patients undergoing hepatic resection at a single institution between 2008 and 2016. Baseline demographics and complications within 30 days following surgery were recorded, with blood tests measured until day 7. Statistical analysis was performed using Mann Whitney and ROC analysis.

Results

One hundred eighty‐eight operations were included. 47.3% had an associated complication, of which 31.46% were major. The median NLR was 6.31 across the cohort, 5.44 for uncomplicated procedures, 7.0 for complications and 10.65 in major complications. Median NLR was the best parameter for detecting major complications versus minor complications (AUC 0.74) as opposed to lymphocytes (AUC 0.65), neutrophils (AUC 0.60), and CRP (AUC 0.60). The diagnostic ability of NLR increased further when predicting major complications versus an uncomplicated recovery (AUC 0.78), and it was the only significant parameter in the early post‐operative period on days 2, 3, and 4 (AUC 0.70, 0.72, and 0.75).

Conclusions

The NLR may have a role in predicting complications following hepatic resection for CLM, and with earlier detection, potentially improving outcomes.
Perioperative outcomes and survival following neoadjuvant stereotactic body radiation therapy (SBRT) versus intensity‐modulated radiation therapy (IMRT) in pancreatic adenocarcinoma
Authors: Chapman Brandon C. , Gleisner Ana , Rigg Devin , Meguid Cheryl , Goodman Karyn , Brauer Brian , Gajdos Csaba , Schulick Richard D. , Edil Barish H. , McCarter Martin D.
Published: February 2018

Background and Objectives

To compare outcomes in patients receiving neoadjuvant stereotactic body radiation therapy (SBRT) with those receiving intensity‐modulated radiation therapy (IMRT) for pancreatic adenocarcinoma.

Methods

We analyzed patients receiving neoadjuvant SBRT for borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) (2012‐2016). Differences in baseline characteristics, perioperative outcomes, progression‐free survival (PFS), and overall survival (OS) were compared.

Results

Seventy‐five (82.4%) patients received SBRT and 16 (17.6%) received IMRT. There were no differences in surgical resection rates in the SBRT (n = 38, 50.7%) and IMRT (n = 11, 68.8%) groups (P = 0.188). Among resected patients, there was no difference in postoperative outcomes or pathologic outcomes including lymph node status, margin status, lymphovascular and perineural invasion, or pathologic response to neoadjuvant treatment (P > 0.05). Among all patients, median PFS and OS were 9.9 and 23.5 months in the SBRT group, respectively, and 15.3 and 21.8 months in the IMRT group, respectively (P > 0.05). Similarly, there was no difference in PFS or OS between groups when stratified by BRPC, LAPC, and surgically resected patients (P > 0.05).

Conclusions

In the neoadjuvant setting, SBRT and IMRT appear to have similar rates of resection, perioperative outcomes, and survival outcomes, but additional studies with increased sample size and longer follow up are needed.
Macroscopic Adhesion of Thermoreversible ABC Triblock Copolymer‐Based Hydrogels Via Boronic Acid–Sugar Complexation
Authors: Tamate Ryota , Takahashi Kotomi , Ueki Takeshi , Akimoto Aya Mizutani , Yoshida Ryo
Published: February 2018

Two complementary thermoreversible ABC triblock copolymers containing either phenylboronic acids with low pKa values or galactosyl groups in the hydrophilic B blocks are synthesized by sequential reversible addition‐fragmentation chain transfer polymerization and subsequent modification of the functional groups. Both ABC triblock copolymers undergo reversible sol‐to‐gel transitions upon temperature change and form physically cross‐linked hydrogels under physiological conditions. Furthermore, the spontaneous adhesion of these thermoreversible hydrogels via the formation of boronic esters between the phenylboronic acid and galactosyl groups under physiological conditions is realized for the first time.
A Critical Evaluation of In Vitro Hesperidin 2S Bioavailability in a Model Combining Luminal (Microbial) Digestion and Caco‐2 Cell Absorption in Comparison to a Randomized Controlled Human Trial
Authors: Van Rymenant Evelien , Salden Bouke , Voorspoels Stefan , Jacobs Griet , Noten Bart , Pitart Judit , Possemiers Sam , Smagghe Guy , Grootaert Charlotte , Van Camp John
Published: February 2018

Scope

Bioavailability strongly determines polyphenol bioactivity, and is strongly influenced by food matrix, enzymatic and microbial degradation, and gastrointestinal absorption. To avoid human trials for pre‐screening of polyphenol bioavailability, studies have focused on in vitro model development. Nevertheless, their predictive value for bioavailability can be questioned.

Method and results

We used the orange flavonoid hesperidin 2S to validate a model combining digestion in the simulator of the human intestinal microbial ecosystem (SHIME) and Caco‐2 cell transport, with a human intervention study. In vitro, hesperidin was resistant to degradation in the stomach and small intestine, but was rapidly deconjugated on reaching the proximal colon. Extensive and colon‐region‐specific degradation to smaller phenolics was observed. Hydrocaffeic and dihydroisoferulic acid accumulated in proximal, and hydroferulic acid in distal colon. Caco‐2 transport was the highest for dihydroisoferulic acid. In humans, plasma and urine hesperetin‐glucuronide levels increased significantly, whereas the impact on small phenolics was limited.

Conclusions

In the combined in vitro model, smaller phenolics strongly accumulated, whereas in humans, hesperetin conjugates were the main bioavailable compounds. Future in vitro model development should focus on simulating faster polyphenol absorption and elimination of smaller phenolics to improve their predictive value of in vivo polyphenol bioavailability.
Theoretical and experimental determination of scaling factors in electron dosimetry for 3D‐printed polylactic acid
Authors: Diamantopoulos Stefanos , Kantemiris Ioannis , Patatoukas Georgios , Dilvoi Maria , Efstathopoulos Efstathios , Kouloulias Vassilis , Platoni Kalliopi
Published: February 2018

Purpose

Plastic phantoms are commonly used in daily routine for dosimetric tasks in radiation therapy. Although water is the reference medium according to the dosimetric protocols, measurements with nonwater phantoms are easier to be performed. To succeed absorbed dose determination, certain scaling factors have to be applied to the acquired measurements. Taking into account the increased availability of three‐dimensional (3D) printing, we attempted to obtain scaling factors for polylactic acid (PLA), a commonly used thermoplastic material for 3D printing.

Methods

Measurements were performed with a custom‐made phantom from PLA material, which was designed and constructed using 3D printing technology. Depth and fluence scaling factors were obtained within the range of 6 to 20 MeV. Moreover, Monte Carlo simulations were performed to verify the measured results.

Results

Experimental and Monte Carlo (MC) values showed a good agreement, especially in lower energies. Mean value of depth scaling factor (cpl) over the whole range of energies was 0.946, while mean fluence scaling factor (hpl) was found to be 1.050. For energies below 10 MeV, the corresponding mean values for cpl and hpl were 0.946 and 1.054, respectively.

Conclusions

PLA phantoms could be constructed and used for electron beam nonreference measurements, reproducing even more complex geometries, from simple quality assurance devices to geometrically complicated anthropomorphic phantoms.
Triple Helicene Cage: Three‐Dimensional π‐Conjugated Chiral Cage with Six [5]Helicene Units
Authors: Matsushima Tomoya , Kikkawa Shoko , Azumaya Isao , Watanabe Soichiro
Published: February 2018

A three‐dimensional π‐conjugated chiral cage with six [5]helicene units (a triple helicene cage) was synthesized for the first time. Taking advantage of the Yamamoto coupling reaction, the triflate‐substituted triple [5]helicene, a strained and preorganized precursor, was dimerized to afford the target compound. Single‐crystal X‐ray diffraction analysis revealed the unique structural features of the triple helicene cage: a cage‐shaped rigid structure with outer helical grooves and an inner chiral cavity. All‐P and all‐M enantiomers were separated successfully by HPLC over a chiral column and their chiroptical properties were characterized by circular dichroism spectra.
The effect of alkylated graphene oxide on the crystal structure of poly(4‐methyl‐1‐pentene) during uniaxial deformation at high temperature
Authors: Xu Li‐Yang , Ma Ai‐Ping , Yin Bo , Yang Ming‐Bo
Published: February 2018

This work discussed the deformation‐induced structure changes of poly(4‐methyl‐1‐pentene)/alkylated graphene oxide (TPX/GO‐ODA) nanocomposites during uniaxial stretching at a certain temperature (80°C). Based on crystalline behaviors of samples during deformation, the strain range could be divided into two regions. Within Region I, the melting temperature of TPX rose with strain; and the figures for TPX/GO‐ODA were volatile; the crystallinity of these two samples showed a similar trend. Within Region II, melting points of two samples did not experience any remarkable changes; the figure for TPX/GO‐ODA was higher than TPX. However, the crystallinity of two samples had a similar pattern; and the figures for nanocomposites showed a moderate increase and reached the plateau region at a greater strain. Wide‐angle X‐ray scattering demonstrated that crystal structure of samples could be destroyed during deformation. Small‐angle X‐ray scattering showed that the spherulitic structure of samples would transform into fibrillar structure. And the fibrillar structure size of TPX/GO‐ODA was smaller than that of TPX according to Guinier approximation. All data revealed that GO‐ODA not only prevented crystal structures from being destroyed within Region I, but also it might restrict rearrangements of molecular chains and crystal fragment within Region II. POLYM. COMPOS., 40:E493–E500, 2019. © 2018 Society of Plastics Engineers
Thermal and combustion features of rigid polyurethane biofoams filled with four forest‐based wastes
Authors: Delucis Rafael de Avila , Magalhães Washington Luiz Esteves , Petzhold Cesar Liberato , Amico Sandro Campos
Published: February 2018

In this study, four fillers from forest‐based wastes were studied using thermogravimetry and contact angle measurements, and their compatibility with polyurethane were investigated by infrared spectroscopy performed in induced reaction mixtures, wherein the fillers were tested in the presence of excess isocyanate and catalyst. The fillers were then incorporated into rigid bio‐based polyurethane foams (RPUFs), which were characterized using thermal and combustion analyses. Wood presented higher compatibility with the polyurethane system, leading to a copolymer formation comprised by urethane groups during its polymerization. Filled RPUF reached increased thermal and dimensional stabilities, and similar thermal conductivities and flammabilities compared with the neat RPUF. POLYM. COMPOS., 39:E1770–E1777, 2018. © 2018 Society of Plastics Engineers
Prenatal diagnosis of anomalous origin of pulmonary artery
Authors: Li Xuelei , Mu Zhongping , Li Xu , Weng Zongjie
Published: February 2018

Background

Anomalous origin of the pulmonary arteries is a rare congenital pulmonary vascular malformation that includes unilateral absence of the pulmonary artery (UAPA), anomalous origin of unilateral pulmonary artery (AOPA), and left pulmonary artery sling (LPAS).

Methods

We analyze 15 cases of fetal pulmonary artery abnormalities from 2011 to 2017, detected via prenatal ultrasound at our center.

Results

The 15 cases include UAPA (5), AOPA (6), and LPAS (4). Of the UAPA cases, 2 had pulmonary atresia and 3 had pulmonary artery stenosis. In 5 cases, the descending aorta issued collateral vessels to the left lung. Of the AOPA cases, 2 had left pulmonary artery abnormalities originating in the ascending aorta and 4 showed right pulmonary artery abnormalities originating in the ascending aorta. Of the LPAS cases, 2 were type IA, 1 was type IIA, and 1 was type IIB. Two of the LPAS were associated with right lung dysplasia.

Conclusion

Abnormal origin of the pulmonary artery has a characteristic ultrasonographic appearance. The branch of the pulmonary artery cross section can provide important clues to the diagnosis of abnormal pulmonary artery origin. Pulmonary artery abnormalities are often associated with pulmonary atresia or stenosis.
Soluble polybenzimidazoles with intrinsic porosity: Synthesis, structure, properties and processability
Authors: Kumar Vikas , Chatterjee Shyambo , Sharma Pragati , Chakrabarty Suman , Avadhani Chilukuri V. , Sivaram Swaminathan
Published: February 2018

We have explored two novel comonomers, namely, 4,16‐dicarboxyl[2.2]paracyclophane and 5,5′,6,6′‐tetraamino‐3,3,3′,3′‐tetramethyl‐1,1′‐spirobi[indane], for the synthesis of co‐polybenzimidazoles (co‐PBIs) with intrinsic porosity. Both these monomers possess twisted structures that can lead to “awkward” macromolecular shapes that cannot pack efficiently. The consequences of introducing these two monomers on the structure and properties of PBIs are reported. The random copolymers synthesized are amorphous and possess glass transition temperatures (Tgs) greater than 400 °C.Tgdecreases with increasing comonomer content indicating an increase in fractional free volume. The copolymers have low surface area. TEM and BET measurements show evidence of mesopore formation. The copolymers show significant carbon dioxide adsorption. Single chain molecular dynamics simulation of 24‐mer repeat units shows intramolecular void spaces arising as a result of distorted polymer chain with reduced conformational mobility. These studies define a new synthetic strategy for “bottoms‐up” synthesis of PBIs with intrinsic porosity. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2018,56, 1046–1057
A TRAMP‐derived orthotopic prostate syngeneic (TOPS) cancer model for investigating anti‐tumor treatments
Authors: Lardizabal Justin , Ding Jun , Delwar Zahid , Rennie Paul S. , Jia William
Published: February 2018

Background

Patients with advanced prostate cancer have limited curative options, therefore new treatments are needed. Mouse models play a pivotal role in the discovery and development of new treatments. In the present study, a TRAMP‐derived Orthotopic Prostate Syngeneic (TOPS) mouse model was developed and found to provide a consistent means of monitoring tumor and metastatic responses to novel treatments.

Methods

The mouse TOPS model was generated using luciferase transduced TRAMP‐C2 prostate cancer cells that were orthotopically injected into Bl6 mice by ultrasound guidance. Tumor growth and development was monitored using ultrasound and bioluminescence imaging.

Results

Tumors and metastases were consistently established and increases in tumor size correlated with increases in bioluminescence. In addition, when mice with an established tumor were castrated, tumor progression mirrored clinical progression. We further treated the TOPS model with an oncolytic Herpes Simplex virus and showed that we were able to monitor the therapeutic effect of the orthotopic tumor after virus treatment through IVIS imaging system.

Conclusion

We have developed a powerful animal model to advance the current selection of effective treatments for patients with advanced prostate cancer.
On the Possible Roles of the Zn Cation in the Carbon Dioxide Hydration Reaction: An Ab Initio RHF‐SCF MO Study of Transition Structures on the [OH2 + CO2] [ZnOH2CO2]2+ and [Zn(NH3)3OH2CO2]2+ Reactive Hypersurfaces
Authors: JACOB O. , TAPIA O.
Published: February 2018

Transition structures and related minima on the reactive energy hypersurfaces for the hydration of carbon dioxide in the presence of a bare zinc ion and with the cation liganded with three ammonia molecules are determined in the RHF MO SCF framework at a relatively high level of basis‐set representation. For the sake of comparison, the standard intramolecular proton transfer model in absence of zinc is revisited and the corresponding transition structure (TS) located. In the coordination sphere of zinc, the standard mechanism of hydration in vacuo is modified: a nucleophilic attack of water onto zinc‐activated carbon dioxide. The reactive path goes via TS signaling synchronous movements in the coordination sphere of zinc: Water goes away from and carbon dioxide toward the metal. For the model systems [ZnOH2CO2]2+, this TS connects with a valley having a geminal carbonic acid (gCA) as product; the carbon–oxygen interaction of the in vacuo complex H2O···CO2 is transformed into a covalent bond by its binding to zinc: H2O—CO2‐Zn is a minimum on this energy hypersurface. The standard path for intramolecular proton transfer, namely, H2O—CO2—Zn changing into (HO)2—CO—Zn, is not catalyzed by the metal. For the ammonia‐ligand model system, the carbon dioxide hydration follows the same pathway as in the bare‐zinc case. A possible irreversible mechanism of carbon dioxide hydration catalyzed by carbonic anhydrases at pH lower than 6 can be suggested based on the present study; here, a central role is played by an intermolecular deprotonation of gCA by water found at the active‐site cleft around the metal center. This zinc–water mechanism is extrapolated to include a general acid catalysis of bicarbonate/carbon dioxide interconversion in water. Results obtained with a hydronium ion replacing zinc and an ancillary water acting as a proton acceptor for the gCA strongly suggest that, in water at pHs lower than 7, direct deprotonation of gCA offers a low‐activation channel to produce carbonic acid; in the reverse direction, protonation of the hydroxyl oxygen in bicarbonate leading to gCA offers a reasonable answer to the instability of this anion in solution at low pH. This picture agrees with the one reported by Paneth and O'Leary. [J. Am. Chem. Soc. 107, 7381 (1985)] based on experimental kinetic information.
The ability of Ex2Box4+ to interact with guests containing π‐electron‐rich and π‐electron‐poor moieties
Authors: Nagurniak Glaucio R. , Caramori Giovanni F. , Muñoz‐Castro Alvaro , Parreira Renato L. T. , da Silva Éder H.
Published: February 2018

The ability of ExBox4+ as a host, able to trap guests containing both π‐electron rich (polycyclic aromatic hydrocarbons‐PAHs) and π‐electron poor (quinoid‐ and nitro‐PAHs) moieties was investigated to shed light on the main factors that control the host–guest (HG) interaction. The nature of the HG interactions was elucidated by energy decomposition (EDA‐NOCV), noncovalent interaction (NCI), and magnetic response analyses. EDA‐NOCV reveals that dispersion contributions are the most significant to sustain the HG interaction, while electrostatic and orbital contributions are very tiny. In fact, no significant covalent character in the HG interactions was observed. The obtained results point strictly to NCIs, modulated by dispersion contributions. Regardless of whether the guests contain π‐electron‐rich or π‐electron‐poor moieties, and no significant charge‐transfer was observed. All in all, HG interactions between guests 3‐14 and host 2 are predominantly modulated by π‐π stacking.
Direct Imaging of Space‐Charge Accumulation and Work Function Characteristics of Functional Organic Interfaces
Authors: Siles Pablo F. , Devarajulu Mirunalini , Zhu Feng , Schmidt Oliver G.
Published: February 2018

The tailoring of organic systems is crucial to further extend the efficiency of charge transfer mechanisms and represents a cornerstone for molecular device technologies. However, this demands control of electrical properties and understanding of the physics behind organic interfaces. Here, a quantitative spatial overview of work function characteristics for phthalocyanine architectures on Au substrates is provided via kelvin probe microscopy. While macroscopic investigations are very informative, the current approach offers a nanoscale spatial rendering of electrical characteristics which is not possible to attain via conventional techniques. Interface dipole is observed due to the formation of charge accumulation layers in thin F16CuPc, F16CoPc, and MnPc films, displaying work functions of 5.7, 6.1, and 5.0 eV, respectively. The imaging and quantification of interface locations with significant surface potential and work function response (<0.33 eV for material thickness <1 nm) show also a dependency on the crystalline state of the organic systems. The work function mapping suggests space‐charge carrier regions of about 4 nm at the organic interface. This reveals rich spatial electric parameters and ambipolar characteristics that may drive electrical performance at device scales, opening a realm of possibilities toward the development of functional organic architectures and its applications.
Layer‐by‐Layer Decoupling of Twisted Graphene Sheets Epitaxially Grown on a Metal Substrate
Authors: Simon Sabina , Voloshina Elena , Tesch Julia , Förschner Felix , Enenkel Vivien , Herbig Charlotte , Knispel Timo , Tries Alexander , Kröger Jörg , Dedkov Yuriy , Fonin Mikhail
Published: February 2018

The electronic properties of graphene can be efficiently altered upon interaction with the underlying substrate resulting in a dramatic change of charge carrier behavior. Here, the evolution of the local electronic properties of epitaxial graphene on a metal upon the controlled formation of multilayers, which are produced by intercalation of atomic carbon in graphene/Ir(111), is investigated. Using scanning tunneling microscopy and Landau‐level spectroscopy, it is shown that for a monolayer and bilayers with small‐angle rotations, Landau levels are fully suppressed, indicating that the metal–graphene interaction is largely confined to the first graphene layer. Bilayers with large twist angles as well as twisted trilayers demonstrate a sequence of pronounced Landau levels characteristic for a free‐standing graphene monolayer pointing toward an effective decoupling of the top layer from the metal substrate. These findings give evidence for the controlled preparation of epitaxial graphene multilayers with a different degree of decoupling, which represent an ideal platform for future electronic and spintronic applications.
Self‐Template‐Directed Metal–Organic Frameworks Network and the Derived Honeycomb‐Like Carbon Flakes via Confinement Pyrolysis
Authors: Wang Jie , Tang Jing , Ding Bing , Chang Zhi , Hao Xiaodong , Takei Toshiaki , Kobayashi Naoya , Bando Yoshio , Zhang Xiaogang , Yamauchi Yusuke
Published: February 2018

Metal–organic frameworks (MOFs) have become a research hotspot since they have been explored as convenient precursors for preparing various multifunctional nanomaterials. However, the preparation of MOF networks with controllable flake morphology in large scale is not realized yet. Herein, a self‐template strategy is developed to prepare MOF networks. In this work, layered double‐metal hydroxide (LDH) and other layered metal hydroxides are used not only as a scaffold but also as a self‐sacrificed metal source. After capturing the abundant metal cations identically from the LDH by the organic linkers, MOF networks are in situ formed. It is interesting that the MOF network‐derived carbon materials retain the flake morphology and exhibit a unique honeycomb‐like macroporous structure due to the confined shrinkage of the polyhedral facets. The overall properties of the carbon networks are adjustable according to the tailored metal compositions in LDH and the derived MOFs, which are desirable for target‐oriented applications as exemplified by the electrochemical application in supercapacitors.
An Indispensable Role of Androgen Receptor in Wnt Responsive Cells During Prostate Development, Maturation, and Regeneration
Authors: He Yongfeng , Hooker Erika , Yu Eun-Jeong , Wu Huiqing , Cunha Gerald R. , Sun Zijie
Published: February 2018

Androgen signaling is essential for prostate development, morphogenesis, and regeneration. Emerging evidence indicates that Wnt/β-catenin signaling also contributes to prostate development specifically through regulation of cell fate determination. Prostatic Axin2-expressing cells are able to respond to Wnt signals and possess the progenitor properties to regenerate prostatic epithelium. Despite critical roles of both signaling pathways, the biological significance of androgen receptor (AR) in Axin2-expressing/Wnt-responsive cells remains largely unexplored. In this study, we investigated this important question using a series of newly generated mouse models. Deletion of Ar in embryonic Axin2-expressing cells impaired early prostate development in both ex vivo and tissue implantation experiments. When Ar expression was deleted in prostatic Axin2-expressing cells at pre-puberty stages, it results in smaller and underdeveloped prostates. A subpopulation of Axin2 expressing cells in prostate epithelium is resistant to castration and, following androgen supplementation, is capable to expand to prostatic luminal cells. Deletion of Ar in these Axin2-expressing cells reduces their regenerative ability. These lines of evidence demonstrate an indispensable role for the Ar in Wnt-responsive cells during the course of prostate development, morphogenesis, and regeneration, which also imply an underlying interaction between the androgen and Wnt signaling pathways in the mouse prostate.
Delphinidin induces apoptosis and inhibits epithelial‐to‐mesenchymal transition via the ERK/p38 MAPK‐signaling pathway in human osteosarcoma cell lines
Authors: Kang Hae‐Mi , Park Bong‐Soo , Kang Hyun‐Kyung , Park Hae‐Ryoun , Yu Su‐Bin , Kim In‐Ryoung
Published: February 2018

Delphinidin is major anthocyanidin that is extracted from many pigmented fruits and vegetables. This substance has anti‐oxidant, anti‐inflammatory, anti‐angiogenic, and anti‐cancer properties. In addition, delphinidin strongly suppresses the migration and invasion of various cancer cells during tumorigenesis. Although delphinidin has anti‐cancer effects, little is known about its functional roles in osteosarcoma (OS). For these reasons, we have demonstrated the effects of delphinidin on OS cell lines. The effects of delphinidin on cell viability and growth of OS cells were assessed using the MTT assay and colony formation assays. Hoechst staining indicated that the delphinidin‐treated OS cells were undergoing apoptosis. Flow cytometry, confocal microscopy, and a western blot analysis also indicated evidence of apoptosis. Inhibition of cell migration and invasion was found to be associated with epithelial‐to‐mesenchymal transition (EMT), observed by using a wound healing assay, an invasion assay, and a western blot analysis. Furthermore, delphinidin treatment resulted in a profound reduction of phosphorylated forms of ERK and p38. These findings demonstrate that delphinidin treatment suppressed EMT through the mitogen‐activated protein kinase (MAPK) signaling pathway in OS cell lines. Taken together, our results suggest that delphinidin strongly inhibits cell proliferation and induces apoptosis. Delphinidin treatment also suppresses cell migration and prevents EMT via the MAPK‐signaling pathway in OS cell lines. For these reasons, delphinidin has anti‐cancer effects and can suppress metastasis in OS cell lines, and it might be worth using as an OS therapeutic agent.