bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR‐150‐5p
Authors: Cai Hongning , Zhang Peng , Xu Meng , Yan Lin , Liu Nian , Wu Xufeng
Published: December 2018

Circular RNA (circRNA) is a new class of noncoding RNA, and plays an important role in many pathological processes. Cervical cancer is the most common gynecologic malignant tumor. Recently, studies have shown that there is a variety of circRNA involved in the pathogenesis of cervical cancer. We screened out the highly expressed hsa_circ_0000263 from GSE102686 by the quantitative real‐time polymerase chain reaction assay in cervical cancer cell lines. In this study, we investigated whether hsa_circ_0000263 might affect cell proliferation, migration, cell cycle and apoptosis in cervical cancer in vitro and in vivo. The luciferase reporter assay and RNA immunoprecipitation assay confirmed the direct interaction between miR‐150‐5p and hsa_circ_0000263. By using western blot and immunohistochemistry, we confirmed that hsa_circ_0000263 can regulate the expression of murine double minute 4 (MDM4) by affecting miR‐150‐5p, and finally affect the expression of p53 gene. We found that hsa_circ_0000263 was significantly upregulated in cervical cancer cells. In addition, the knockdown of hsa_circ_0000263, would inhibit cell proliferation and migration ability. In conclusion, our current research reveals the important role of hsa_circ_0000263/miR‐150‐5p/MDM4/p53 regulatory network in cervical cancer and provides a new insight into the pathogenesis of cervical cancer.
Overexpression of cancer‐testis antigen melanoma‐associated antigen A1 in lung cancer: A novel biomarker for prognosis, and a possible target for immunotherapy
Authors: Fanipakdel Azar , Seilanian Toussi Mehdi , Rezazadeh Faezeh , Mohamadian Roshan Nema , Javadinia Seyed Alireza
Published: December 2018

Aim

We investigated melanoma‐associated antigen A1 (MAGE‐A1) expression in lung cancer tissues and its correlation with prognostic factors.

Materials and Methods

In this cross‐sectional study, samples from 101 patients with lung cancer were obtained between 2007 and 2014 and stained for MAGE‐A1 by immunohistochemistry. Correlation with prognostic factors was assessed by t test, and
χ
2, and Pearson’s tests.

Results

Eighty non‐small‐cell lung cancer (NSCLC) and 21 small‐cell lung cancer specimens were stained for MAGE‐A1. MAGE‐A1 was detected more commonly in adenocarcinomas and was expressed more frequently in male and patients >60 years.

Conclusions

MAGE‐A1 was found in several lung cancer patients. MAGE‐A1 was expressed more commonly in NSCLC, elderly, and men. Further investigations are needed to assess MAGE‐A1 as potential cancer biomarkers.
The long noncoding RNA uc.294 is upregulated in early‐onset pre‐eclampsia and inhibits proliferation, invasion of trophoblast cells (HTR‐8/SVneo)
Authors: Song Xuejing , Li Chunyan , Li Jingyun , Liu Lan , Meng Li , Ding Hongjuan , Long Wei
Published: December 2018

Recently, a large number of long noncoding RNAs (lncRNAs) have been reported in human diseases that are evolutionarily conserved and are likely to play a role in many biological events including pre‐eclampsia. In our previous research, we selected thousands of lncRNAs for their relationship with early‐onset pre‐eclampsia. Among these lncRNAs, a lncRNA named uc.294 attracted our attention, was once reported to specifically be expressed at a high level in the early‐onset of pre‐eclampsia. This study aims to investigate the function of uc.294 in early‐onset pre‐eclampsia and the possible mechanism. The uc.294 expression level in early‐onset pre‐eclampsia or in normal placenta tissues was evaluated by quantitative real‐time polymerase chain reaction. To detect the proliferation, invasion, and apoptosis capacity of the trophoblast cells, we performed the Cell Counting Kit‐8 assay, transwell assay, and flow cytometry, respectively. Here we report, for the first time, that uc.294 inhibits proliferation, invasion, and promotes apoptosis of trophoblast cells HTR‐8/SVneo by working in key aspects of biological behaviors. However, how uc.294 acts to regulate gene functions in early‐onset pre‐eclampsia needs further exploration.
Age‐related changes in the morphology and the distribution of IgA and IgG in the pharyngeal tonsils of yaks (Bos grunniens)
Authors: Xu Yuanfang , Sun Juan , Cui Yan , Yu Sijiu , He Junfeng , Liu Penggang , Zhang Qian
Published: December 2018

To evaluate age‐related changes in the morphology as well as the expression and localization of IgA and IgG in yak pharyngeal tonsils, 20 healthy yaks were divided into four age groups [newborn (1–7 days old), juvenile (5–7 months old), adult (3–6 years old) and old (7–10 years old)]. Morphologic characteristics were observed by histological techniques. The expression and localization of IgA and IgG in pharyngeal tonsils were detected by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The results showed that the epithelium of the pharyngeal tonsils included nonreticular epithelium with an intact basement membrane and reticular epithelium with a discontinuous basement membrane and nonepithelial cell infiltration. In newborn yaks, only primary lymphoid follicles were observed in pharyngeal tonsils. In other age groups, both primary and secondary lymphoid follicles were observed, but some of the lymphoid follicles in the old yaks were degenerated. The number of lymphoid follicles increased from the newborn to the adult group and peaked in the adult group, but the number decreased in the old group. In addition, the age‐related trends of IgA and IgG protein expression were similar to those of the number of lymphoid follicles. The concentration of IgG was significantly higher than that of IgA in all age groups. Both IgA and IgG antibody secreting cells (ASCs) were distributed in the subepithelial region of the nonreticular epithelium, the reticular epithelium, the lymphoid follicles, the interfollicular areas and in between the salivary glands. The densities of IgA and IgG ASCs in pharyngeal tonsils were similar to the expression trend of both proteins in each age group. The results indicate that the morphology and amount of lymphoid follicles in yak pharyngeal tonsils vary with age. Pharyngeal tonsils produce more IgG than IgA, indicating that IgG could be significant component of mucosal immune responses in yaks.
Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region
Authors: Vallatos A. , Al‐Mubarak H.F.I. , Birch J.L. , Galllagher L. , Mullin J.M. , Gilmour L. , Holmes W.M. , Chalmers A.J.
Published: December 2018

Background

Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast‐enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels.

Purpose

To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration.

Study Type

Animal model.

Subjects

Mice bearing orthotopic glioblastoma xenografts generated from a patient‐derived glioblastoma cell line.

Field Strength/Sequences

7T perfusion images acquired using a high signal‐to‐noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1/T2 weighted, contrast‐enhanced T1, diffusion‐weighted, and apparent diffusion coefficient).

Assessment

Immunohistochemistry sections were stained for human leukocyte antigen (probing human‐derived tumor cells). To achieve quantitative MRI‐tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a “ground truth.”

Statistical Tests

Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two‐tailed, paired t‐test used for statistical analysis.

Results

High comparison test results (Dice 0.62–0.72, Accuracy 0.86–0.88, Sensitivity 0.51–0.7, and Specificity 0.92–0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51–0.61). MRI/histology voxel‐to‐voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004).

Data Conclusion

These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy.

Level of Evidence: 1

Technical stage: 2

J. Magn. Reson. Imaging 2019;50:529–540.
Value of Cardiac Magnetic Resonance Fractal Analysis Combined With Myocardial Strain in Discriminating Isolated Left Ventricular Noncompaction and Dilated Cardiomyopathy
Authors: Zheng Tian , Ma Xiaohai , Li Shuhao , Ueda Takuya , Wang Zheng , Lu Aijia , Zhou Wei , Zou Hongye , Zhao Lei , Gong Lianggeng
Published: December 2018

Background

Excessive trabeculation is present in isolated left ventricular noncompaction (LVNC) and dilated cardiomyopathy (DCM), which sometimes makes the differentiation between these two difficult. Fractal dimension (FD) is a unitless measure value of how completely the object fills space, which can assess the extent of myocardial trabeculae quantitatively.

Purpose

To compare the trabeculae features and myocardial strain derived from cardiac MR between LVNC and DCM.

Study Type

Respective case–control series.

Population

In all, 35 LVNC patients and 30 DCM patients were enrolled, and 20 healthy volunteers were selected as a control group.

Field Strength/Sequence

5 T with 8‐channel phased‐array cardiac receiver coil including steady‐state free precession cine imaging.

Assessment

The degree of left ventricular trabeculation was evaluated by a semiautomatic tool based on fractal analysis. Myocardial deformation was assessed by feature tracking.

Statistical Tests

Independent samples Student's t‐test, Mann–Whitney U‐test, receiver operating characteristics (ROC) curves, and Spearman's rank coefficient were conducted.

Results

Max apical FD and mean global FD were higher in the LVNC group than in the DCM group (1.433 ± 0.074 vs. 1.341 ± 0.062, P < 0.001; 1.323 ± 0.036 vs. 1.267 ± 0.041, P < 0.001, respectively). For diagnosing LVNC, max apical FD was 1.392 (area under the curve [AUC] = 0.881, 95% confidence interval [CI]: 0.804–0.957), and the cutoff value of mean global FD was 1.283 (AUC = 0.895, 95% CI: 0.828–0.961). The global peak longitudinal strain value of the left ventricle (GPLS) showed significant differences between the LVNC group and DCM group [–6.49 (–11.41, –4.90) vs. –4.61 (–5.87, –3.61), P = 0.006]. The diagnostic accuracy for LVNC is highest when using FDs in coordination with GPLS (AUC = 0.93, 95% CI: 0.86–0.98, P < 0.001).

Data Conclusion

Fractal analysis provides a quantitative measurement of myocardial trabeculation. The combination of fractal analysis with myocardial strain provides a novel biomarker in distinguishing LVNC from DCM.

Level of Evidence: 3

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2019;50:153–163.
Mixed‐cropping systems of different rice cultivars have grain yield and quality advantages over mono‐cropping systems
Authors: Li Meijuan , Zhang Jiaen , Liu Shiwei , Ashraf Umair , Zhao Benliang , Qiu Shuqing
Published: December 2018

BACKGROUND

A mixed‐cropping system that enhances farmland biodiversity has the potential to improve grain yield and quality; however, the impacts of growing different rice cultivars simultaneously has been rarely investigated. In the present study, five popular rice cultivars were selected and ten mixture combinations were made according to the growth period, plant height, grain yield and quality, and pest and disease resistance. Seedlings of the five cultivars and ten mixture combinations (mixed‐sowing of the seeds in an equal ratio, then mixed‐transplanting and finally mixed‐harvesting) were grown in plastic pots in a glasshouse during the early and late growing seasons in 2016.

RESULTS

Compared with the mono‐cropping systems in the early and late growing seasons in 2016 (paired t‐test), the mixed‐cropping systems increased the rice leaf photosynthetic rate, soil plant analysis development (SPAD) index and total aboveground dry weight. Moreover, mixed‐cropping systems improved the number of spikelets per panicle, seed‐setting rate, and grain weight per pot and harvest index by 19.52% and 5.77%, 8.53% and 4.41%, 8.31% and 4.61%, and 10.26% and 6.98% in the early and late growing seasons, respectively. In addition, mixed‐cropping systems reduced chalky rice rate and chalkiness degree by 33.12% and 43.42% and by 30.11% and 48.13% in the early and late growing seasons, respectively.

CONCLUSION

The SPAD indexes and photosynthetic rates enhanced at physiology maturity in mixed‐cropping systems may result in higher grain yield and better grain quality. In general, it was found that mixed‐cropping with different rice cultivars has the potential for increasing grain yield and improving grain quality. © 2018 Society of Chemical Industry
Levator claviculae muscle: Anatomic variation found during neck dissection
Authors: Ferreli Fabio , Mercante Giuseppe , Spriano Giuseppe
Published: December 2018

The levator claviculae muscle is a variant of the anatomy of the posterior triangle of the neck. It is reported in 2% to 3% of all humans. All previous articles described this muscle as an incidental finding during cadaveric or radiological examinations. We report here, for the first time, a case discovering this muscle variation intraoperatively during a modified radical neck dissection. The muscle was identified on the left side, originating from the transverse processes of the upper cervical vertebrae (C2‐C3), attached to the upper aspect of the middle part of the clavicle. This muscle was innervated by the supraclavicular nerve, coming from the third and fourth rami of the cervical spinal nerves. Blood supply to the muscle could not be identified clearly during the surgical procedure. Surgeons and radiologists should be aware of the presence of this rare variant muscle so as not to misinterpret the anatomy. Laryngoscope, 129:634–636, 2019
Second primary lung malignancy following head and neck squamous cell carcinoma
Authors: Crippen Meghan M. , Brady Jacob S. , Burke Lindsay A. , Eloy Jean Anderson , Baredes Soly , Park Richard Chan Woo
Published: December 2018

Objectives/Hypothesis

Analyze the characteristics of second primary lung malignancies (SPLMs) following an index head and neck squamous cell carcinoma (HNSCC).

Study Design

Retrospective cohort study.

Methods

The Surveillance, Epidemiology and End Results database was queried for all cases of HNSCC between 1973 and 2014 (N = 101,856). This population was compared to a standard population to assess relative risk for lung cancer, calculated as the standardized incidence ratio (SIR). Patients who developed SPLMs were extracted (N = 8,116) and compared to all other cases of lung cancer (N = 1,160,853) to assess histopathological differences. SPLM subpopulations divided by head and neck primary site were compared for lung cancer histology and time interval between cancer diagnoses.

Results

Overall, 8.0% of HNSCC patients developed SPLMs (SIR = 4.22, P < .001), diagnosed an average of 6.7 years later. Patients with HNSCC of the supraglottis and hypopharynx were at the highest risk relative to a standard population, with SIRs of 8.10 and 6.34, respectively. When comparing SPLMs to all other lung cancers, there was no difference in the distribution of lung lobe affected, but SPLMs were significantly more likely to be of squamous cell carcinoma histology (42.0% vs. 21.0%, P < .001). Among head and neck subsites, lung cancers following larynx tumors had a significantly higher proportion of small cell histology, and those following oropharyngeal or hypopharyngeal tumors had significantly higher proportions of squamous cell histology.

Conclusions

Patients who undergo curative treatment of HNSCC are at high risk for developing SPLMs. Subsite‐specific differences may help elucidate the degree of risk attributable to smoking, genetic susceptibility, human papillomavirus infection, or metastasis masquerading as an SPLM.

Level of Evidence

4 Laryngoscope, 129:903–909, 2019
Pott's puffy tumor in children: A review of the literature
Authors: Koltsidopoulos Petros , Papageorgiou Eleni , Skoulakis Charalampos
Published: December 2018

Objectives

Pott's puffy tumor (PTT) is a frontal subperiosteal abscess associated with underlying frontal osteomyelitis. The purpose of the present study was to assess the rate of intracranial involvement in pediatric and adolescent patients with PPT and to discuss the diagnostic workup and the therapeutic features of this pathology.

Methods

We searched Web of Science, PubMed and MEDLINE from 1998 to 2018. The search focused on papers concerning the diagnostic procedure and therapeutic management of PTT. Statistical techniques were not used.

Results

We included 53 articles that described 92 pediatric and adolescent patients with PPT. The overall rate of intracranial complications was found to be 72%. Most authors used computed tomography for the diagnosis of PTT and its complications, either alone or in combination with magnetic resonance imaging. In 50% of cases, an endoscopic endonasal approach is used for the management of the underlying acute or chronic sinusitis.

Conclusions

On the basis of the available literature, it seems that the incidence rate of intracranial involvement in patients with PPT is quite high. Early diagnosis using the appropriate imaging raise the possibility of good recovery. Concerning the therapy of PTT, endoscopic sinus surgery could be considered as a valuable technique. The vast majority of patients treated appropriately recover without long‐term neurologic complications and sequelae.

Level of Evidence

4 Laryngoscope, 130:225–231, 2020
Molecules targeting the androgen receptor (AR) signaling axis beyond the AR‐Ligand binding domain
Authors: Elshan N. G. R. Dayan , Rettig Matthew B. , Jung Michael E.
Published: December 2018

Prostate cancer (PCa) is the second most common cause of cancer‐related mortality in men in the United States. The androgen receptor (AR) and the physiological pathways it regulates are central to the initiation and progression of PCa. As a member of the nuclear steroid receptor family, it is a transcription factor with three distinct functional domains (ligand‐binding domain [LBD], DNA‐binding domain [DBD], and transactivation domain [TAD]) in its structure. All clinically approved drugs for PCa ultimately target the AR‐LBD. Clinically active drugs that target the DBD and TAD have not yet been developed due to multiple factors. Despite these limitations, the last several years have seen a rise in the discovery of molecules that could successfully target these domains. This review aims to present and comprehensively discuss such molecules that affect AR signaling through direct or indirect interactions with the AR‐TAD or the DBD. The compounds discussed here include hairpin polyamides, niclosamide, marine sponge–derived small molecules (eg, EPI compounds), mahanine, VPC compounds, JN compounds, and bromodomain and extraterminal domain inhibitors. We highlight the significant in vitro and in vivo data found for each compound and the apparent limitations and/or potential for further development of these agents as PCa therapies.
Technical Note: Use of commercial multilayer Faraday cup for offline daily beam range verification at the McLaren Proton Therapy Center
Authors: Tesfamicael Biniam , Athar Basit , Bejarano Buele Ana , Kozlyuk Valeri , Nichiporov Dmitri , Watts David A. , Arjomandy Bijan
Published: December 2018

Purpose

Daily verification of the proton beam range in proton radiation therapy is a vital part of the quality assurance (QA) program. The objective of this work is to study the use of a multilayer Faraday cup (MLFC) to perform a quick and precise daily range verification of proton beams produced by a synchrotron.

Methods

Proton beam depth dose measurements were performed at room iso‐center in water using PTW water tank and Bragg Peak ion chamber. The IBA Giraffe, calibrated against the water tank data, was used to measure the water equivalent thickness (WET) of the sample copper plates. The WET measurements provided the range calibration factors for the MLFC. To establish a baseline for in room measurements, range measurements for energies from 70 to 250 MeV in steps of 10 MeV were performed using the Pyramid MLFC at room iso‐center. For the daily range verification measurements, the MLFC is permanently placed at the end of the beam line, inside the accelerator vault. The daily range constancy is performed for five representative beam energies; namely 70, 100, 150, 200, and 250 MeV. Data collected over a period of more than 100 days are analyzed and presented.

Results

The measured WET values of the copper plates increased with increasing energy. The centroid channel number in the MLFC where the protons stop, was converted to depth in water and compared to the depth of the distal 80% (d80) obtained from the water tank measurements. The depths agreed to within 2 mm, with the maximum deviation of 1.97 mm observed for 250 MeV beam. The daily variation in the ranges measured by the MLFC was within ±0.5 mm. The total time to verify five proton beam ranges varies between 4 and 5 min.

Conclusion

Based on the result of our measurements, the MLFC can be used for a daily range constancy check with submillimeter accuracy. It is a quick and simple method to perform range constancy verification on a daily basis.
Scaling laws for hydraulic fractures driven by a power‐law fluid in homogeneous anisotropic rocks
Authors: Dontsov Egor V.
Published: December 2018

This study investigates parametric space of solutions for a planar hydraulic fracture propagating in a homogeneous anisotropic rock. It is assumed that the fracture has an elliptical shape and is driven by a power‐law fluid. The purpose of this study is to investigate the influence of anisotropy and power‐law fluid rheology on the parametric space of solutions. Rock anisotropy is represented by having two values of fracture toughness, one in the vertical direction and another one in the horizontal direction. Similarly, the effect of elastic anisotropy is approximated by using two different effective elastic moduli in the vertical and horizontal directions. In contrast to the isotropic case, for which there are four limiting solutions, the problem for anisotropic rocks features six different limiting cases. These cases represent competition between toughness and viscosity in the vertical and horizontal directions and competition between fluid storage inside the fracture and fluid leak‐off into formation. Approximate expressions for the limiting solutions are obtained using global volume balance and tip asymptotic solutions. Despite the developed solutions rely on a series of approximations, they precisely capture all the scaling laws associated with the problem. Zones of applicability of these limiting solutions are calculated, and their dependence on the problem parameters is investigated.
“Having the compass–drawing the map”: Exploring nurses’ management of pain and other discomforts during use of analgosedation in intensive care
Authors: Berntzen Helene , Bjørk Ida Torunn , Wøien Hilde
Published: December 2018

Aim

To explore the deliberation and enactment processes of nurses in relation to pain and other discomforts in the critically ill patients after the implementation of an analgosedation protocol.

Background

Nurses in intensive care units (ICU) face great challenges when managing pain and other discomforts and distinguishing between patients’ needs for analgesics and sedatives. An analgosedation protocol favouring pain management, light sedation and early mobilization was implemented in a university hospital ICU in Norway in 2014. Changing sedation paradigms resulting in an increasing number of awake patients during critical illness is expected to affect nursing practice.

Design

Exploratory, single‐unit study in a mixed adult ICU.

Methods

Data collection with participant observation and semi‐structured interviews in sixteen clinical situations in 2014 and 2015. Thirteen experienced certified critical care nurses were included. Thematic content analysis was conducted.

Results

An overall theme “Having the compass–drawing the map” emerged from the analysis. The protocol or strategy of analgosedation appeared to provide a direction for treatment and care, although requiring extensive interpretation of needs and individualization of care, often in challenging situations. The overall theme was abstracted from three themes: “Interpreting a complex whole,” “Balancing conflicting goals” and “Experiencing strain from acting across ideals.”

Conclusion

Nurses seem to attend adequately to patient pain, but the approach to discomforts other than pain appears unsystematic and haphazard. More explicit goals of care and strategies to handle discomfort as distinct from pain are needed. More research is needed to identify effective comfort measures for ICU patients.
Randomized Controlled Trial of a Leucine‐Metformin‐Sildenafil Combination (NS‐0200) on Weight and Metabolic Parameters
Authors: Zemel Michael B. , Kolterman Orville , Rinella Mary , Vuppalanchi Raj , Flores Omar , Barritt A. Sidney , Siddiqui Mohammad , Chalasani Naga
Published: December 2018

Objective

Leucine was previously demonstrated to allosterically activate mammalian sirtuin 1 and synergize with other sirtuin 1/AMP‐activated protein kinase/nitric oxide pathway activators to modulate energy metabolism. The objective of this study was to evaluate the effects of a triple combination of leucine, metformin, and sildenafil (NS‐0200) on body weight and obesity comorbidities in a phase 2 randomized trial.

Methods

A total of 91 subjects with obesity were randomized to placebo, low dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil), or high dose (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) twice daily for 16 weeks. Seventy subjects completed the trial and met all a priori compliance criteria. Hypertensive (n = 35) and hypertriglyceridemic (n = 22) subcohorts were also analyzed.

Results

NS‐0200 dose‐responsively reduced weight; high dose reduced weight by 2.4 and 5.0 kg in the full and high‐triglyceride cohorts, respectively (P < 0.0001). High‐dose NS‐0200 treatment also decreased blood pressure (−5.5 mm Hg diastolic pressure; P = 0.011), with greater effects among hypertensive subjects. NS‐0200 also significantly reduced triglycerides and hemoglobin A1c. Significant improvement in ≥ 2 comorbidities was exhibited by 54% of subjects in the high‐dose arm versus 5% of placebo subjects (P = 0.0009). Treatment‐emergent adverse events did not significantly differ among groups.

Conclusions

These data support further study of NS‐0200 as a therapy for obesity and associated comorbidities.
Molecularly imprinted hydrogels for sustained release of sunitinib in breast cancer therapy
Authors: Scrivano Luca , Parisi Ortensia Ilaria , Iacopetta Domenico , Ruffo Mariarosa , Ceramella Jessica , Sinicropi Maria Stefania , Puoci Francesco
Published: December 2018

The present work reports on the synthesis of a molecularly imprinted polymer (MIP) based on methacrylic acid and ethylene glycol dimethacrylate for sunitinib delivery. Sunitinib (SUT) is a tyrosine kinase inhibitor used in many cancer diseases. Like the majority of the anticancer drugs, SUT suffers of a low bioavailability, and at the same time, it is characterized by a narrow therapeutic window. In order to reduce drug systemic toxicity, we synthesized a MIP‐based drug delivery system for SUT‐controlled release. MIP was obtained by bulk polymerization through the so‐called noncovalent approach. Rebinding experiments were performed to evaluate the success of the imprinting process and the ability of MIP to bind in a specific and selective fashion the template molecule. Resulting data showed that sunitinib rebinding percentage was 70%, while nonimprinted polymer (NIP) rebinding percentage was 46%. A not significant difference was observed between MIP and NIP in semaxanib binding experiments. Moreover, the drug release profiles were studied for both MIP and NIP. A sustained release was observed from sunitinib‐loaded MIP during 24 hours, reaching 58% after 6 hours and 76% at the end‐point. NIP, on the contrary, released almost 90% of the loaded drug within 6 hours. Furthermore, the drug carrier was tested in vitro against MCF‐7 cells, in which the cytotoxic effect of sunitinib released from MIP reached the maximum after 72 hours, while NIP completed its effect within 48 hours. These results demonstrated that molecularly imprinted polymers are suitable systems for SUT release.
Somatic mosaic monosomy 7 and UPD7q in a child with MIRAGE syndrome caused by a novel SAMD9 mutation
Authors: Csillag Bernhard , Ilencikova Denisa , Meissl Manfred , Webersinke Gerald , Laccone Franco , Narumi Satoshi , Haas Oskar , Duba Hans‐Christoph
Published: December 2018

MIRAGE syndrome caused by mutations in SAMD9 is associated with potential loss of chromosome 7 (‐7/7q‐) and an increased risk to develop myelodysplastic syndrome (MDS). We report a case of MIRAGE syndrome, caused by a novel SAMD9 mutation p.Leu641Pro, leading to characteristic clinical features as well as to the coexistence of cells with monosomy 7 (20%) and with uniparental disomy of long arm of chromosome 7 (UPD7q). In contrast to previously reported MIRAGE patients with ‐7/7q‐ developing MDS, our patient achieved complete cytogenetic remission of monosomy 7. As UPD7q remained unchanged, it seems to be a protective factor against MDS.
Peptide signaling molecules CLE5 and CLE6 affect Arabidopsis leaf shape downstream of leaf patterning transcription factors and auxin
Authors: DiGennaro Peter , Grienenberger Etienne , Dao Thai Q. , Jun Ji Hyung , Fletcher Jennifer C.
Published: December 2018

Intercellular signaling mediated by small peptides is critical to coordinate organ formation in animals, but whether extracellular polypeptides play similar roles in plants is unknown. Here we describe a role in Arabidopsis leaf development for two members of the CLAVATA3/ESR‐RELATED peptide family, CLE5 and CLE6, which lie adjacent to each other on chromosome 2. Uniquely among the CLE genes, CLE5 and CLE6 are expressed specifically at the base of developing leaves and floral organs, adjacent to the boundary with the shoot apical meristem. During vegetative development CLE5 and CLE6 transcription is regulated by the leaf patterning transcription factors BLADE‐ON‐PETIOLE1 (BOP1) and ASYMMETRIC LEAVES2 (AS2), as well as by the WUSCHEL‐RELATED HOMEOBOX (WOX) transcription factors WOX1 and PRESSED FLOWER (PRS). Moreover, CLE5 and CLE6 transcript levels are differentially regulated in various genetic backgrounds by the phytohormone auxin. Analysis of loss‐of‐function mutations generated by genome engineering reveals that CLE5 and CLE6 independently and together have subtle effects on rosette leaf shape. Our study indicates that the CLE5 and CLE6 peptides function downstream of leaf patterning factors and phytohormones to modulate the final leaf morphology.
Analysis of dose verification results for 924 intensity‐modulated radiation therapy plans
Authors: Wu Shizhang , Chen Jinhu , Li Zhenjiang , Qiu Qingtao , Wang Xingli , Li Chengqiang , Yin Yong
Published: December 2018

Objective

Intensity‐modulated radiation therapy (IMRT) plays an increasingly important role in clinical applications, and dose verification is particularly crucial for each patient. In the present study, we retrospectively analyzed the results of dose verification in 924 actual IMRT plans, including the relationship between gamma pass rates and the location of lesions, and the total number of monitor units, and the maximum area of the collected dose.

Methods

All the 924 IMRT plans implemented in a Varian Trilogy accelerator between 1 January 2014 and 31 March 2016 at Shandong Cancer Hospital were acquired. The Varian Eclipse planning system was used for all treatment planning and verification. Then, actual implemented plans were transplanted into a water phantom. Subsequently, the derived fluence was compared with the actual measured fluence by gamma analysis with the gamma criteria (3%/3 mm).

Results

A total of 924 IMRT plans were categorized into six groups, including the brain, head and neck, chest, abdomen, pelvis, and breast. The gamma pass rate average was >98% for 902 IMRT plans, whereas 22 plans did not pass the first time. A correlation was observed between the treatment site and gamma pass rate (P = 0.017). Meanwhile, a negative correlation was observed between the gamma pass rate and the total number of monitor units (P < 0.001), and the largest area of the acquisition dose (P < 0.001), respectively. Varian Trilogy accelerator IMRT QA data has a stable pass rate with a 100 confidence limit (CL) value of 95.19.

Conclusion

There was a correlation between the pass rate and the treatment site, the total number of monitor units, and the maximum area of collected dose. When using Mapcheck for patient plan dose verification, the gamma pass rate is very high, and only a few of them need to be analyzed.
Click Coupling Reactions on Flat and Nanostructured Hydrogen‐Passivated Silicon Surfaces
Authors: Henriksson Anders , Hoffmann Helmuth
Published: December 2018

Dialkynes are grafted onto hydrogen‐passivated silicon wafers, porous silicon, and silicon nanowires via thermally induced hydrosilylation followed by surface functionalization via azide alkyne cycloaddition. The surfaces are characterized with Fourier transform infrared spectroscopy (FTIR) and electrochemical measurements that indicate a correlation between the quality of the organic layer and the morphology of the substrate. After the initial hydrosilylation reaction, the amount of accessible surface bonded alkynes is observed to be substantially lower on porous, irregular surfaces compared to flat wafers and well‐defined vertically aligned silicon nanowire arrays, thus precluding an effective subsequent azide‐alkyne cycloaddition on porous silicon.
Bromophenol (5‐bromo‐3,4‐dihydroxybenzaldehyde) isolated from red alga Polysiphonia morrowii inhibits adipogenesis by regulating expression of adipogenic transcription factors and AMP‐activated protein kinase activation in 3T3‐L1 adipocytes
Authors: Ko Seok‐Chun , Ding Yuling , Kim Junseong , Ye Bo‐Ram , Kim Eun‐A , Jung Won‐Kyo , Heo Soo‐Jin , Lee Seung‐Hong
Published: December 2018

The aim of the present study was to investigate the effect of 5‐bromo‐3,4‐dihydroxybenzaldehyde (BD) isolated from Polysiphonia morrowii on adipogenesis and differentiation of 3T3‐L1 preadipocytes into mature adipocytes and its possible mechanism of action. Levels of lipid accumulation and triglyceride were significantly lower in BD treated cells than those in untreated cells. In addition, BD treatment reduced protein expression levels of peroxisome proliferator‐activated receptor‐γ, CCAAT/enhancer‐binding proteins α, and sterol regulatory element‐binding protein 1 compared with control (no treatment). It also reduced expression levels of adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. AMP‐activated protein kinase activation was found to be one specific mechanism involved in the effect of BD. These results demonstrate that BD possesses inhibitory effect on adipogenesis through activating AMP‐activated protein kinase signal pathway.
Ensemble reduction using cluster analysis
Authors: Serafin Stefano , Strauss Lukas , Dorninger Manfred
Published: December 2018

Ensemble reduction is the task of selecting a subset of the members of a global ensemble prediction system (EPS) to specify the initial and boundary conditions for the integration of a limited‐area EPS. Cluster analysis is often used for this purpose, even if random member selection would be a legitimate approach as well. Clustering algorithms organize forecasts from different ensemble members into groups, based on the degree of similarity between selected forecast fields. Reduction is performed by choosing one representative member from each cluster. Ensemble reduction degrades forecast accuracy, measured by the continuous rank probability score. The degree of degradation depends primarily on the size of the reduced ensemble and becomes larger as the ensemble gets smaller. We estimate the loss of forecast accuracy caused by different ensemble reduction methods by comparing the probabilistic forecasts obtained from the 51‐member EPS run by ECMWF with those from several reduced ensembles. We show that different ensemble reduction methods cause marginally different loss of accuracy and that, generally, clustering methods are not significantly better at ensemble reduction than random sampling. Clustering typically results in reduced ensembles with significantly lower spread than both the parent ensemble and randomly defined subsets. The effectiveness of clustering depends on the forecast range and on the variables used to cluster the global ensemble members; not all meteorological parameters are equally good clustering variables. Clustering is most effective at ensemble reduction when it detects meaningful differences between the ensemble members. This is only possible at forecast ranges beyond about 3 days and when variables with a low degree of small‐scale spatial variability are used as object descriptors.
Nonbonding pairs in cyclic thioethers: Electrostatic modeling and ab initio calculations for complexes of 2,5‐dihydrothiophene, thietane, and thiirane with hydrogen fluoride
Authors: Hill J. Grant , Legon Anthony C.
Published: December 2018

Electrostatic potential energies V(ϕ) of a non‐perturbing, protonic charge at fixed distances r from the S atom in three cyclic thioethers were examined as functions of the angles ϕ made by the r‐vector with the C2 axis (thiirane and 2,5‐dihydrothiophene) or the local C2 axis (thietane). The electrostatic PE VHF(ϕ) of HF (HF modelled as an extended electric dipole) was also calculated and the results compared with geometries of the thioether⋯HF complexes calculated at the CCSD(T)‐F12c/cc‐pVTZ‐F12 level. The latter reveal angular deviations θ ∼10‐20° of the S⋯HF nuclei from collinearity in directions suggesting secondary interactions of F with H atom(s) of the rings. Angles ϕ made by the S⋯H hydrogen bond with the C2 (or local C2) axes in the complexes are systematically larger (∼4‐9°) than indicated by the VHF(ϕ) functions. Minima in the simple V(ϕ) versus ϕ functions occur at values smaller (∼5‐10°) than those in the VHF(ϕ) curves.
Defect‐Based Single‐Atom Electrocatalysts
Authors: Zhang Yiqiong , Guo Lan , Tao Li , Lu Yanbing , Wang Shuangyin
Published: December 2018

Single‐atom catalysts (SACs) have attracted great attention owing to their maximum atomic utilization and high catalytic performance in electrochemical reactions. But the synthesis of SACs is not easy due to large surface energies of single atomic metal sites which often lead to their aggregation. The defects on supports can serve as anchor sites to stabilize single metal atoms and prevent them from aggregation, which has become an effective method to fabricate SACs. This review summarizes the meaningful findings about the defects on supports stabilizing single metal atoms, and their applications in electrocatalytic reaction. Various defects, including the intrinsic defects or heteroatom doping of carbon‐based materials, cation or anion vacancies of metal compound supports, and other defects (step edges, lattice defects, and caves), are comprehensively summarized, and the effects of defects on designing SACs are discussed. Although there are still many challenges to fully explore the SACs, it is believed that the newly established defect sites stabilized single atoms mechanism will be helpful for designing and fabricating highly powerful single atomic electrocatalysts for practical applications.
A new test specimen to investigate the bond behavior of post‐installed reinforcing bars
Authors: Rex Justus , Sharma Akanshu , Hofmann Jan
Published: December 2018

Recent developments in the field of adhesives have led to the availability of post‐installed reinforcing bar (rebar) systems with high strength mortar. The bond strength of these mortar‐rebar systems can reach significantly higher values than the bond strength of cast‐in rebar systems in normal strength concrete. However, based on the boundary conditions of concrete cover, concrete strength, transverse reinforcement, etc., the usable bond strength of post‐installed rebar system could be limited by concrete splitting prior to attainment of the bond strength. In order to study the influence of above‐stated boundary conditions on the usable bond strength of post‐installed rebar, a new test specimen is designed on the basis of the beam‐end specimen. The specimen allows for testing of the post‐installed rebar system under realistic boundary conditions and clearly defined bonded zone while measuring unloaded‐end slip and the width of splitting cracks.
One-Person Moral Twin Earth Cases
Authors: Sinhababu Neil ,   Philosophy Documentation Center
Published: December 2018

This paper presents two cases demonstrating that theories allowing the environment to partially determine the content of moral concepts (such as the causal theory of reference) that provide incorrect truth-conditions for moral terms. While typical Moral Twin Earth cases seek to establish that these theories fail to account formoral disagreement, neither case here essentially involves interpersonal disagreement. Both involve a single person retaining moral beliefs despite recognizing actual or potential mismatches with the purportedly content-determining facts. This lets opponents of such theories grant objections that standard Moral Twin Earth cases fail to demonstrate disagreement, and argue more straightforwardly that they generate implausible truth-conditions for moral claims.
Perceptual learning
Authors: Prettyman Adrienne
Published: December 2018

Perceptual learning involves long‐term changes to perception due to practice or experience. While perceptual learning has been studied for over a century in philosophy and psychology, research into the cognitive and neural mechanisms underlying perceptual learning remains an area of ongoing development. This review explores what perceptual learning is and how it occurs, with a focus on areas of controversy. It then turns to several current debates. First, it explores the debate as to whether such learning involves genuine perceptual change at all, rather than a change in action, attention, or decision‐making. Second, it questions the role that higher‐cognitive mechanisms, like attention, might play in perceptual learning. Does perceptual learning require attention, or can it occur through mere exposure in the absence of attention? Third, it examines a debate about what perceptual learning means for the perception–cognition divide. Does it blur the divide or preserve it?

This article is categorized under:

Philosophy > Psychological Capacities

Psychology > Perception and Psychophysics

Psychology > Learning
The Development Aid Situation in Malawi
Authors: Page Samantha
Published: December 2018

In this chapter, I demonstrate the powerful and influential role that international donors (bilateral and multilateral agencies and INGOs) play in constructing AIDS policies and programmes. Additionally, this chapter emphasises that aid conditionality can fail to respond effectively to the AIDS epidemic by demonstrating how funding is often donor led. For example, if donors disagree with policies being implemented in the country to which they are supplying aid, whether it is the way money is being spent or the type of policies the government implements, then they will withdraw funds. I provide an example of the British Government suspending aid because it was unhappy with the President of Malawi’s autocratic management style. The paradox of such policies in practice is that they reduce the ability of nation states to be self-sufficient and instead put them in a dependency relationship with international donors. In this chapter, I also show how the AIDS epidemic was considered to be exceptional, thus requiring exceptional efforts at prevention and mitigation. That HIV requires a response above ‘normal’ health interventions began as a Western response to the virus. I also look at the influence the national elite in Malawi have in shaping international perceptions of sexual cultural practices and AIDS.
Obesity, Biopower, and Embodiment of Caring: Foodwork and Maternal Ambivalences in Ho Chi Minh City
Authors: Ehlert Judith
Published: December 2018

Child obesity is increasingly addressed as a public health problem in Vietnam and framed as one of the most severe food-related risks globally. By drawing on theories of the body and from the perspective of mothers feeding their children, this chapter stresses the ambivalences women face in their capacity of caring through food. It puts eating and feeding as subjective embodied experience in context by retracing how different authorities of biopower such as the public health sector, the food industry, and the family work on the bodies of mothers and children, admonishing and regulating food in concert with conflicting body ideals in children. Rather than obesity as supposed food-related risk number one, it is the complex struggle of ‘good motherhood’ that essentially drives women’s food-related anxiety.
Trust and Food Modernity in Vietnam
Authors: Figuié Muriel , Moustier Paule , Bricas Nicolas , Nguyen Thi Tan Loc
Published: December 2018

The authors detail the deep transformation of the Vietnamese food system during the last decades, in relation with the industrialization of food production and the extension of the food market chains. The consequences are a growing food anxiety among consumers and an evolution in the process of trust building: the urban consumers still rely on their own know-how to keep their home as a safe place to eat as well as on their day-to-day personal relations with their usual retailers. But trust building has also evolved to include the trust in some stakeholders such as supermarkets rather than in public control. This diversity in the ways of building trust in food can be seen as a characteristic of modernity in emerging Asian economies.
When Food Crosses Borders: Paradigm Shifts in China’s Food Sectors and Implications for Vietnam
Authors: Zhang Hongzhou
Published: December 2018

This chapter aims to provide a preliminary overview of the macro trends that are emerging in regard to Chinese food security strategy at the national level and the food preferences at the household level and its implications for Vietnam. Moving away from the traditional micro-perspective analysis which focuses on the economic, social, and environmental impacts of various forms of Chinese agro-capitalism, this chapter adopts a macro-perspective: examining how Vietnam fits into China’s new food security strategy as well as the shifting dietary preferences of Chinese consumers and its potential implications for Vietnam’s food sectors.
Assessing perturbativity and vacuum stability in high-scale leptogenesis
Authors: Ipek Seyda , Plascencia Alexis D. , Turner Jessica
Published: December 2018

Abstract

We consider the requirements that all coupling constants remain perturbative and the electroweak vacuum metastable up to the Planck scale in high-scale thermal leptogenesis, in the context of a type-I seesaw mechanism. We find a large region of the model parameter space that satisfies these conditions in combination with producing the baryon asymmetry of the Universe. We demonstrate these conditions require Tr[Y

N

†
Y

N
] ≲ 0.66 on the neutrino Yukawa matrix. We also investigate this scenario in the presence of a large number N

F
of coloured Majorana octet fermions in order to make quantum chromodynamics asymptotically safe in the ultraviolet.