bluuebunny/crossref_metadata_2025 huggingface dataset:
Tuning the Magnetization Dynamic Properties of Nd⋅⋅⋅Fe and Nd⋅⋅⋅Co Single‐Molecular Magnets by Introducing 3 d–4 f Magnetic Interactions
Authors: Wei Rong‐Min , Liu Ting , Li Jing , Zhang Xiuling , Chen Yuting , Zhang Yi‐Quan
Published: April 2019

By using paramagnetic [Fe(CN)6]3− anions in place of diamagnetic [Co(CN)6]3− anions, two field‐induced mononuclear single‐molecular magnets, [Nd(18‐crown‐6)(H2O)4][Co(CN)6]⋅2 H2O (1) and [Nd(18‐crown‐6)(H2O)4][Fe(CN)6]⋅2 H2O (2), have been synthesized and characterized. Single‐crystal X‐ray diffraction analysis revealed that compounds 1 and 2 were ionic complexes. The NdIII ions were located inside the cavities of the 18‐crown‐6 ligands and were each bound by four water molecules on either side of the crown ether. Magnetic investigations showed that these compounds were both field‐induced single‐molecular magnets. By comparing the slow relaxation behaviors of compounds 1 and 2, we found significant differences between the direct and Raman processes for these two complexes, with a stronger direct process in compound 2 at low temperatures. Complete active space self‐consistent field (CASSCF) calculations were also performed on two [Nd(18‐crown‐6)(H2O)4]3+ fragments of compounds 1 and 2. Ab initio calculations showed that the magnetic anisotropies of the NdIII centers in complexes 1 and 2 were similar to each other, which indicated that the difference in relaxation behavior was not owing to the magnetic anisotropy of NdIII. Our analysis showed that the magnetic interaction between the NdIII ion and the low‐spin FeIII ion in complex 2 played an important role in enhancing the direct process and suppressing the Raman process of the single‐molecular magnet.
Meta-analysis of the molecular associations of mucinous colorectal cancer
Authors: Reynolds I S , Furney S J , Kay E W , McNamara D A , Prehn J H M , Burke J P
Published: April 2019

Background

Mucinous differentiation occurs in 5–15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer.

Methods

This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis.

Results

Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P < 0·001) mutation, MSI (OR 3·98, 3·30 to 4·79; P < 0·001) and CIMP (OR 3·56, 2·85 to 4·43; P < 0·001), and negatively with altered p53 expression (OR 0·46, 0·31 to 0·67; P < 0·001).

Conclusion

The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.
Novel immune–risk score of gastric cancer: A molecular prediction model combining the value of immune–risk status and chemosensitivity
Authors: Duan Shijie , Wang Pengliang , Liu Funan , Huang Hanwei , An Wen , Pan Siwei , Wang Xin
Published: April 2019

Gastric cancer is still one of the most common and deadly malignancies in the world. Not all patients could benefit from chemotherapy or chemoradiotherapy due to tumor heterogeneity. Therefore, identifying different subgroups of patients is an important trend for obtaining more effective responses. However, few molecular classifications associated with chemosensitivity are based on immune–risk status. In this study, we obtained six key immune–related genes. Using these genes, we constructed a molecular model related to immune–risk status and calculated an individual immune–risk score. The score showed great efficiency and stability in predicting prognosis and identifying different subgroups where persons could benefit from postoperative adjuvant therapy. The patients could be divided into different risk groups based on the immune–related score. For patients in the low–risk group, both postoperative chemoradiotherapy and chemotherapy could significantly improve prognosis on overall survival (OS) and disease–free survival (DFS) (DFS, P < 0.001 and P = 0.041, respectively; OS, P < 0.001, P = 0.006, respectively) and chemoradiotherapy was significantly superior than simple chemotherapy (DFS, P = 0.031; OS, P = 0.027). For patients with an intermediate–risk score, postoperative chemoradiotherapy showed a statistically significant survival advantage over no anticancer treatment (P = 0.004 and P = 0.002, respectively), while chemotherapy did not. Compared with no adjuvant treatment, neither postoperative chemoradiotherapy nor chemotherapy made significant difference for patients in the high–risk group. Combining the value of immune–risk status and chemosensitivity, the immune–risk score could not only offer us prognostic evaluation and adjuvant treatment guidance, but also improve our understanding about the binding point between chemotherapy or chemoradiotherapy and the immune system, which may be helpful for further expanding the application of immunotherapy.
Highly‐calcific carotid lesions endovascular management in symptomatic and increased‐stroke‐risk asymptomatic patients using the CGuard™ dual‐layer carotid stent system: Analysis from the PARADIGM study
Authors: Mazurek Adam , Partyka Lukasz , Trystula Mariusz , Jakala Jacek , Proniewska Klaudia , Borratynska Anna , Tomaszewski Tomasz , Slezak Magdalena , Malinowski Krzysztof P. , Drazkiewicz Tomasz , Podolec Piotr , Rosenfiled Kenneth , Musialek Piotr
Published: April 2019

Objectives

To assess feasibility, safety, angiographic, and clinical outcome of highly‐calcific carotid stenosis (HCCS) endovascular management using CGuard™ dual‐layer carotid stents.

Background

HCCS has been a challenge to carotid artery stenting (CAS) using conventional stents. CGuard combines a high‐radial‐force open‐cell frame conformability with MicroNet sealing properties.

Methods

The PARADIGM study is prospectively assessing routine CGuard use in all‐comer carotid revascularization patients; the focus of the present analysis is HCCS versus non‐HCCS lesions. Angiographic HCCS (core laboratory evaluation) required calcific segment length to lesion length ≥2/3, minimal calcification thickness ≥3 mm, circularity (≥3 quadrants), and calcification severity grade ≥3 (carotid calcification severity scoring system [CCSS]; G0‐G4).

Results

One hundred and one consecutive patients (51–86 years, 54.4% symptomatic; 106 lesions) received CAS (16 HCCS and 90 non‐HCCS); eight others (two HCCS) were treated surgically. CCSS evaluation was reproducible, with weighted kappa (95% CI) of 0.73 (0.58–0.88) and 0.83 (0.71–0.94) for inter‐ and intra‐observer reproducibility respectively. HCCS postdilatation pressures were higher than those in non‐HCCS; 22 (20–24) versus 20 (18–24) atm, p = .028; median (Q1–Q3). Angiography‐optimized HCCS‐CAS was feasible and free of contrast extravasation or clinical complications. Overall residual diameter stenosis was single‐digit but it was higher in HCCS; 9 (4–17) versus 3 (1–7) %, p = .002. At 30 days and 12 months HCCS in‐stent velocities were normal and there were no adverse clinical events.

Conclusion

CGuard HCCS endovascular management was feasible and safe. A novel algorithm to grade carotid artery calcification severity was reproducible and applicable in clinical study setting. Larger HCCS series and longer‐term follow‐up are warranted.
Bismuth Oxysulfide Photoelectrodes with Giant Incident Photon‐to‐Current Conversion Efficiency: Chemical Stability in Aqueous Solutions
Authors: Bondarenko Evgeny A. , Streltsov Eugene A. , Mazanik Alexander V. , Kulak Anatoly I.
Published: April 2019

Bismuth oxysulfide (BOS) films demonstrate giant incident photon‐to‐current conversion efficiency (IPCE≫100 %) under cathodic polarization. Their photoelectrochemical behavior and corrosion stability in aqueous solutions containing different redox systems ([Fe(CN)6]3−/[Fe(CN)6]4−, Fe3+/Fe2+, I2/I−, Sn2−/S2−) has been investigated. We established that the chemical stability of the BOS is controlled mainly by three factors: i) potentials of cathodic and anodic destruction of the BOS (Bi3+ reduction and S2− oxidation)L ii) protolytic reactions leading to the dissolution of the semiconductor in acidic solutions at pH<3; iii) presence in solutions of anions, capable to participate in ion exchange reactions with the semiconductor forming poorly soluble compounds (K[BiFe(CN)6] ⋅ 3H2O, BiOI and Bi2S3). The enrichment of the BOS surface with sulfur atoms (formation of S‐terminated surface) gives rise to the substantial increase in the electrocatalytic activity of [Fe(CN)6]3− cathodic reduction, which is accompanied by up to order increase of IPCE.
Precise Proton Mapping near Ionic Micellar Membranes with Fluorescent Photoinduced‐Electron‐Transfer Sensors
Authors: Uchiyama Seiichi , Yano Kayo , Fukatsu Eiko , de Silva A. Prasanna
Published: April 2019

One of the challenges for fluorescent sensors is to reduce their target environment size from a micrometer scale, such as biological cells, to a nanometer scale. Proton maps near membranes are of importance in bioenergetics and are the first goal in nanometer‐scale analysis with fluorescent sensors. Thirty‐three fluorescent photoinduced‐electron‐transfer pH sensors bearing an environment‐sensitive benzofurazan fluorophore and having different hydrophobicity/hydrophilicity and hydrogen‐bonding abilities were prepared. These sensors were scattered in nanospaces associated with anionic and cationic micelles as model membranes to indicate proton availability and polarity in local spaces. Gathering the data from the sensors allowed the successful drawing of proton maps near anionic and cationic micelles, in which electrostatic attraction/repulsion of protons by the charged head groups of micelles and dielectric suppression of protons were clearly observed.
When Gold Cations Meet Polyoxometalates
Authors: Blanc Aurélien , de Frémont Pierre
Published: April 2019

Merging gold(I) cations with polyoxometalate anions results in various interclusters and complexes. Herein, the synthesis of these newly emerging gold(I)/polyoxometalate materials is reviewed. The applications of these promising hybrids in organic catalysis are also summarized and evaluated in terms of the advantages and limitations of the catalysts including efficiency, synergistic effects and recyclability.
Spectroscopic Analysis of Protein‐Crowded Environments Using the Charge‐Transfer Fluorescence Probe 8‐Anilino‐1‐Naphthalenesulfonic Acid
Authors: Ota Chikashi , Takano Kazufumi
Published: April 2019

The molecular behaviors of proteins under crowding conditions are crucial for understanding the protein actions in intracellular environments. Under a crowded environment, the distance between protein molecules is almost the same size as the molecular level, thus, both the excluded volume effect and short ranged soft chemical interaction on protein surface could induce the complicated influence on the protein behavior cooperatively. Recently, various kinds of analytical approaches from macroscopic to microscopic aspects have been made to evaluate the crowding effect. The method, however, has not been established to evaluate the surface specific interactions on protein surface. In this study, the analytical method to evaluate the crowding effect has been suggested by using a charge‐transfer fluorescence probe, ANS. By employing the unique property of ANS attaching to charged residues on the surface of lysozyme, the crowding effect was focused, while the case was compared as a reference, in which ANS is confined in hydrophobic pockets of BSA. Consequently, the surface specific changes of fluorescence spectra were readily observed under the crowded environment, whereas the fluorescence spectra of ANS in protein inside did not change. This result suggests the fluorescence spectra of ANS binding to protein surface have the capability to estimate the crowding effect of proteins.
Metformin reduces maternal weight gain in obese pregnant women: A systematic review and meta‐analysis of two randomized controlled trials
Authors: D'Ambrosio Valentina , Brunelli Roberto , Vena Flaminia , Di Mascio Daniele , Marchetti Claudia , Boccherini Chiara , Piccioni Maria Grazia , Benedetti Panici Pierluigi , Giancotti Antonella
Published: April 2019

Obese pregnant women are likely to face several gestational and neonatal complications. Metformin is an effective oral antihyperglycaemic agent that is considered to be effective during pregnancy. The aim of our study was to evaluate the effect of metformin on obstetric and perinatal outcomes in obese pregnant women. Electronic databases were searched (MEDLINE, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, OVID, and Cochrane Library). The selection criteria included only randomized clinical trials (RCTs) of obese pregnant women randomized to a daily metformin regimen or to a placebo condition. The type of participants included women with a body mass index (BMI) ≥ 30 kg/m2 who did not have diabetes mellitus, any other disease, or a contraindication to metformin use. The summary measures were reported as relative risk (RR) with 95% confidence intervals (CIs). The primary outcome was the effect on maternal weight gain (MWG). Two double‐blind RCTs, including 849 obese pregnant women, were included in the meta‐analysis: 428 (50.4%) were randomized to the metformin group, and 421 (49.6%) were randomized to the placebo group. The use of metformin was significantly associated with lower MWG. Metformin was also associated with a significantly lower incidence of preeclampsia (PE) and admission to the neonatal intensive care unit (NICU). Metformin could be considered a useful drug for the treatment of obese, nondiabetic pregnant women because it can significantly decrease weight gain in pregnant women and improve perinatal outcomes by reducing the incidence of PE and NICU admission. However, women should be aware of the uncertainties concerning the long‐term effects of metformin transplacental passage on metabolic outcomes.
One‐Step Synthesis of MoS2 Nanosheet Arrays on 3D Carbon Fiber Felts as a Highly Efficient Catalyst for the Hydrogen Evolution Reaction
Authors: Zang Xiaobei , Zhou Chaofan , Shao Qingguo , Yu Sirong , Qin Yijiang , Lin Xueqiang , Cao Ning
Published: April 2019

Many efforts have been made to pursue low‐cost and efficient electrocatalysts for the hydrogen evolution reaction (HER), which is important for real water splitting applications. Herein, a 3D hydrogen evolution cathode is designed and synthesized by in situ grafting MoS2 nanosheets on a 3D carbon fiber felt (CFF) framework. As a low‐cost HER catalyst, MoS2 nanosheets have effective hydrogen atom adsorption activity due to their uniform distribution in the 3D CFF framework. Meanwhile, the 3D CFF framework facilitates the electrolyte to penetrate into the inner space and accelerate the electron transfer, which leads to a drastic increase in the HER activity. Electrochemical measurements show that the MoS2/CFF composite exhibit an excellent electrocatalytic activity with 101 mV overpotential, affording a current density of 10 mA cm−2 and a high exchange current density of 3.3 × 10−2 mA cm−2. Therefore, this 3D material, which has splendid catalytic performance and stability, exhibits great potential in the electrocatalytic hydrogen production for water splitting.
Seasonal, tidal, and geomorphic controls on sediment export to Amazon River tidal floodplains
Authors: Nowacki Daniel J. , Ogston Andrea S. , Nittrouer Charles A. , Fricke Aaron T. , Asp Nils E. , Souza Filho Pedro Walfir M.
Published: April 2019

Mainstem–floodplain material exchange in the tidal freshwater reach of major rivers may lead to significant sequestration of riverine sediment, but this zone remains understudied compared to adjacent fluvial and marine environments. This knowledge gap prompts investigation of floodplain‐incising tidal channels found along the banks of tidal rivers and their role in facilitating water and suspended‐sediment fluxes between mainstem and floodplain. To evaluate this role, and how it evolves along the tidal river and with time, we measured water level, flow velocity, temperature, and suspended‐sediment concentration (SSC) in four tidal channels along the tidal Amazon River, Brazil. Eleven deployments were made during low, rising, high, and falling seasonal Amazon discharge. Generally, channels export high‐SSC water from the mainstem to the tidal floodplain on flood tides and transfer low‐SSC water back to the mainstem on ebbs. Along the length of the tidal river, the interaction between tidal and seasonal water‐level variations and channel–floodplain morphology is a primary control on tidal‐channel sediment dynamics. Close to the river mouth, where tides are large, this interaction produces transient flow features and current‐induced sediment resuspension, but the importance of these processes decreases with distance upstream. Although the magnitude of the exchange of water and sediment between mainstem and floodplain via tidal channels is a small percentage of the total mainstem discharge in this large tidal‐river system, tidal channels are important conduits for material flux between these two environments. This flux is critical to resisting floodplain submergence during times of rising sea level. © 2019 John Wiley & Sons, Ltd.
Quantifying flow resistance in mountain streams using computational fluid dynamics modeling over structure‐from‐motion photogrammetry‐derived microtopography
Authors: Chen Yunxiang , DiBiase Roman A. , McCarroll Nicholas , Liu Xiaofeng
Published: April 2019

Flow resistance in mountain streams is important for assessing flooding hazard and quantifying sediment transport and bedrock incision in upland landscapes. In such settings, flow resistance is sensitive to grain‐scale roughness, which has traditionally been characterized by particle size distributions derived from laborious point counts of streambed sediment. Developing a general framework for rapid quantification of resistance in mountain streams is still a challenge. Here we present a semi‐automated workflow that combines millimeter‐ to centimeter‐scale structure‐from‐motion (SfM) photogrammetry surveys of bed topography and computational fluid dynamics (CFD) simulations to better evaluate surface roughness and rapidly quantify flow resistance in mountain streams. The workflow was applied to three field sites of gravel, cobble, and boulder‐bedded channels with a wide range of grain size, sorting, and shape. Large‐eddy simulations with body‐fitted meshes generated from SfM photogrammetry‐derived surfaces were performed to quantify flow resistance. The analysis of bed microtopography using a second‐order structure function identified three scaling regimes that corresponded to important roughness length scales and surface complexity contributing to flow resistance. The standard deviation σz of detrended streambed elevation normalized by water depth, as a proxy for the vertical roughness length scale, emerges as the primary control on flow resistance and is furthermore tied to the characteristic length scale of rough surface‐generated vortices. Horizontal length scales and surface complexity are secondary controls on flow resistance. A new resistance predictor linking water depth and vertical roughness scale, i.e.  H/σz, is proposed based on the comparison between σz and the characteristic length scale of vortex shedding. In addition, representing streambeds using digital elevation models (DEM) is appropriate for well‐sorted streambeds, but not for poorly sorted ones under shallow and medium flow depth conditions due to the missing local overhanging features captured by fully 3D meshes which modulate local pressure gradient and thus bulk flow separation and pressure distribution. An appraisal of the mesh resolution effect on flow resistance shows that the SfM photogrammetry data resolution and the optimal CFD mesh size should be about 1/7 to 1/14 of the standard deviation of bed elevation. © 2019 John Wiley & Sons, Ltd.
Neuropsychiatric symptoms in severe dementia: Associations with specific cognitive domains the Cache County Dementia Progression Study
Authors: Rozum William J. , Cooley Bryce , Vernon Elizabeth , Matyi Joshua , Tschanz JoAnn T.
Published: April 2019

Objectives

To examine the prevalence of neuropsychiatric symptoms (NPS) and cognitive correlates in severe dementia.

Methods

A population‐based sample of 56 individuals with severe dementia (85.7% Alzheimer's type; 67.9% female) were assessed with the Severe Cognitive Impairment Profile (SCIP) and the Neuropsychiatric Inventory (NPI). Descriptive statistics displayed the frequency of NPS and bivariate and multiple regression analyses examined the associations between cognitive domains on the SCIP and NPS total, domain, and cluster scores.

Results

NPS were common in severe dementia with 98% of the sample exhibiting at least one symptom. Most common were delusions, apathy, agitation/aggression, and aberrant motor behavior, affecting 50% or more of participants. SCIP comportment was significantly associated with NPI total score and apathy (r = −.350 and −.292, respectively). All SCIP domains except for arithmetic, visuospatial, comportment, and motor behavior were significantly associated with agitation/aggression (r = −.285 to −.350). These associations remained in individual multiple regression models.

Conclusion

In severe dementia, impairment in specific cognitive domains was associated with more severe NPS. Environmental manipulations to reduce processing demands in persons with severe dementia may be a useful strategy to target agitation and aggressive behaviors.
Role of sternomastoid muscle interposition in concomitant transoral oncologic resection and neck dissection
Authors: Panda Smriti , Thakar Alok , Sikka Kapil , Sharma Suresh C.
Published: April 2019

Background

To report the experience with sternomastoid (SM) myofascial flap for reconstruction/buttressing of lateral pharyngeal wall and floor of mouth defects following transoral onco‐surgery.

Methods

Prospectively collected data from February 2012‐January 2018. SM flap harvested as a superiorly based flap supplied by the occipital artery and consisting of only the anterior SM head.

Results

A total of 42 patients were included (TORS, n = 40; TOUSS, n = 2). Three of 42 patients developed transient pharyngo‐cervical communications with subsequent spontaneous healing. Flap loss was not noted in any patient. Forty‐one of 42 patients resumed normal swallowing and one patient was PEG dependent. Fifteen of 42 patients had pretreatment metastatic neck nodes. No patient however developed nodal recurrence over a median follow‐up of 30 months.

Conclusion

The modified SM flap as reported here is a simple locally available reconstructive option when undertaking transoral surgery. Oncological concerns may however limit its use in situations with large nodal metastasis or extracapsular spread.
Perceptions, attitudes, and expectation of baccalaureate nurses toward position of nursing in Bosnia and Herzegovina
Authors: Racic Maja , Pavlovic Jelena , Hadzivukovic Natalija , Ivkovic Nedeljka
Published: April 2019

Introduction

Numerous challenges and barriers have emerged since changing the minimum requirement for those interested in pursuing employment as a nurse in Europe to a baccalaureate degree. To analyze the perceptions of baccalaureate nurses regarding the current status of their profession and the issues involved in implementing the prerequisite of earning a baccalaureate degree in order to practice as nurses in Bosnia and Herzegovina.

Methods

A series of six focus groups were undertaken with 49 baccalaureate nurses employed in primary health care centers and regional hospitals. The focus groups were recorded and transcribed verbatim. Data collected were analyzed using conventional content analysis approach.

Results

Baccalaureate nurses report dissatisfaction with their level of autonomy and anxiety over their limited career opportunities. They expressed concern over difficult working conditions, inadequate financial compensation, and ongoing resistance by physicians as the primary barriers to implementing advanced nursing education and professional reform. The global image of the nursing profession is negative.

Conclusion

The perception is that revising the legal framework regarding nursing qualifications, duties, and standards will result in reform necessary to positively affect the during profession. Progress toward implementing reform of the nursing profession is negligible. Addressing barriers such as work environment, lack of job classification, fair payment, autonomy, and interdisciplinary collaboration toward the competences of baccalaureate nurse is essential if successful reform is to occur.
Claudin7‐dependent exosome‐promoted reprogramming of nonmetastasizing tumor cells
Authors: Kyuno Daisuke , Zhao Kun , Schnölzer Martina , Provaznik Jan , Hackert Thilo , Zöller Margot
Published: April 2019

Claudin7 (cld7) is a cancer‐initiating cell (CIC) marker in gastrointestinal tumors, a cld7‐knockdown (kd) being accompanied by loss of tumor progression. Tumor exosomes (TEX) restoring CIC activities, we explored the contribution of cld7. This became particularly interesting, as tight junction (TJ)‐ and glycolipid‐enriched membrane domain (GEM)‐derived cld7 is recruited into distinct TEX. TEXs were derived from CIC or cld7kd cells of a rat pancreatic and a human colon cancer line. TEX derived from pancreatic cancer cld7kd cells rescued with palmitoylation site‐deficient cld7 (cld7mP) allowed selectively evaluating the contribution of GEM‐derived TEX, only palmitoylated cld7 being integrated into GEM. Cld7 CIC‐TEX promoted tumor cell dissemination and metastatic growth without a major impact on proliferation, apoptosis resistance and epithelial–mesenchymal transition. Instead, migration, invasion and (lymph)angiogenesis were strongly supported, only migration being selectively fostered by GEM‐derived cld7 TEX. CIC‐TEX coculture of cld7kd cells uncovered significant changes in the cld7kd cell protein and miRNA profiles. However, changes did not correspond to the CIC‐TEX profile, CIC‐TEX rather initiating integrin, protease and RTK, particularly lymphangiogenic receptor activation. CIC‐TEX preferentially rescuing cld7kd‐associated defects in signal transduction was backed up by an RTK inhibitor neutralizing the impact of CIC‐TEX on tumor progression. In conclusion, cld7 contributes to selective steps of the metastatic cascade. Defects of cld7kd and cld7mP cells in migration, invasion and (lymph)angiogenesis are effaced by CIC‐TEX that act by signaling cascade activation. Accordingly, RTK inhibitors are an efficient therapeutic defeating CIC‐TEX.
Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF‐β‐induced EMT
Authors: Zhang Yan , Li Jun‐Hui , Yuan Qing‐Gong , Cao Gang , Yang Wen‐Bin
Published: April 2019

LASP2 (LIM and SH3 protein 2), a member of the LIM‐protein subfamily of the nebulin group, was first identified as a splice variant of the nebulin gene. In the past, investigators mainly focused on the impact of LASP2 on cardiac diseases because of its identification in the myocardium. Recently, several studies have reported that LASP2 is associated with the progression of various cancers. However, there have been no investigations on the expression and function of LASP2 in pancreatic cancer (PC). In this study, we performed the quantitative real‐time polymerase chain reaction and Western blot analysis to detect the expression of LASP2 in PC tissues and cell lines. PC cells were transfected with LASP2 overexpression plasmid or the negative control in the presence or absence of tumor growth factor‐β (TGF‐β). The transwell assays were used to measure the effects of LASP2 on PC cell migration and invasion. The protein expression of epithelial‐mesenchymal transition (EMT) markers was detected using Western blot assay. Our results demonstrated that LASP2 was downregulated in PC tissues and cell lines. In addition, upregulation of LASP2 inhibited the PC cell migration and invasion. We also found that LASP2 upregulation reversed TGF‐β‐induced EMT in PC cells. Taken together, we provided novel evidence supporting the tumor‐suppressor role of LASP2 in PC and suggested it as a potential therapeutic target in PC treatment.
Institutional betrayal following military sexual trauma is associated with more severe depression and specific posttraumatic stress disorder symptom clusters
Authors: Andresen Felicia J. , Monteith Lindsey L. , Kugler Jordan , Cruz Rick A. , Blais Rebecca K.
Published: April 2019

Objective

Preliminary research suggests that perceptions of institutional betrayal are associated with more severe symptoms of posttraumatic stress disorder (PTSD) and depression, as well as suicide attempts in military sexual trauma (MST) survivors. However, results have not been replicated. Additionally, associations of institutional betrayal with specific PTSD symptom clusters or sexual function are understudied.

Method

Female service members/veterans who reported experiencing MST (N = 679) completed self‐report measures of PTSD and depression symptom severity, suicidal ideation, and sexual function. Institutional betrayal was assessed from free‐text descriptions of self‐reported index traumas.

Results

Institutional betrayal was significantly associated with more severe depression and PTSD symptoms, including avoidance, negative alterations in cognitions and mood, re‐experiencing, and dysphoric arousal.

Conclusions

Targeting specific PTSD and depressive symptoms through evidence‐based treatment may be important for managing institutional betrayal sequelae. Future research should identify specific strategies to help support survivors in their recovery following institutional betrayal.
The potential utility of melatonin in the treatment of childhood cancer
Authors: Chao Yu‐Hua , Wu Kang‐Hsi , Yeh Chia‐Ming , Su Shih‐Chi , Reiter Russel J. , Yang Shun‐Fa
Published: April 2019

Childhood cancer management has improved considerably, with the overall objective of preventing early‐life cancers completely. However, cancer remains a major cause of death in children, with the survivors developing anticancer treatment‐specific health problems. Therefore, the anticancer treatment needs further improvement. Melatonin is a effective antioxidant and circadian pacemaker. Through multiple mechanisms, melatonin has significant positive effects on multitude adult cancers by increasing survival and treatment response rates, and slowing disease progression. In addition, melatonin appears to be safe for children. As an appealing therapeutic agent, we herein address several key concerns regarding melatonin's potential for treating children with cancer.
Phosphoinositide 3‐kinase/protein kinase B inhibition restores regulatory T cell's function in pulmonary sarcoidosis
Authors: Zhang Bin , Dai Qianqian , Jin Xuguang , Liang Dongmei , Li Xiaojie , Lu Haiyan , Liu Yu , Ding Jingjing , Gao Qian , Wen Yanting
Published: April 2019

Sarcoidosis is a systemic granulomatous disease associated with Th1/ regulatory T cells (Treg) paradigm. PI3K/Akt signaling, critical for maintaining Treg's homeostasis, is aberrantly activated in sarcoidosis patients. Here we tested the role of the PI3K inhibitors, LY294002 and BKM120, in immune modulation in experimental pulmonary sarcoidosis, concerning Th1/Th17/Treg immune profile detected by fluorescence‐activated cell sorting analysis or quantitative polymerase chain reaction, as well as the effect on Treg's suppressive functions. Our investigation showed abnormal activation of PI3K/Akt signaling both in lung and Treg in pulmonary sarcoidosis, along with decreased frequency and damaged function of Treg. Blockage of PI3K suppressed this signaling in Treg, rebalanced Th1/Treg, inhibited the production of inflammatory cytokines, and enhanced Treg's function. These results demonstrate the key role of the PI3K/Akt signaling in regulating Th1/Th2 rebalances and indicates that PI3K/Akt signaling is critical for the optimal Treg responses in pulmonary sarcoidosis. Thus, PI3K inhibitors have potential for therapeutic translation, and can be candidate for add‐on drugs to treat pulmonary sarcoidosis.
G Protein γ subunit 7 loss contributes to progression of clear cell renal cell carcinoma
Authors: Xu Shan , Zhang Haibao , Liu Tianjie , Chen Yule , He Dalin , Li Lei
Published: April 2019

Clear cell renal cell carcinoma (ccRCC) is a common urinary neoplasm, looking for useful candidates to establish scientific foundation for the therapy of ccRCC is urgent. We downloaded genomic profiles of GSE781, GSE6244, GSE53757, and GSE66271 from the Gene Expression Omnibus (GEO) database. GEO2R was used to analyze the derivative genes, while hub genes were screened by protein‐protein interactions and cytoscape. Further, overall survival, gene methylation, gene mutation, and gene expression were all analyzed using bioinformatics tools. Colony formation and cell‐cycle assay were used to detect the biological function of GNG7 in vitro. We found that GNG7 was downregulated in ccRCC tissues and negatively associated with overall survival in ccRCC patients. We also found that promoter methylation and frequent gene mutation were responsible for GNG7 gene suppression. GNG7 low expression was related to upregulation of enhancer of zeste homolog 2 and downregulation of disabled homolog 2‐interacting protein. Further, Gene Set Enrichment Analysis results showed that mTOR1, E2F, G2M, and MYC pathways were all significantly altered in response to GNG7 low expression. In vitro, A498 and 786‐O cells in which GNG7 expression was silenced, exhibited a lower G1 phase when compared to the negative control cells. Taken together, our findings suggest that
GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment.
Small intestinal bacterial overgrowth in children with intestinal failure on home parenteral nutrition
Authors: McGrath Kathleen H , Pitt James , Bines Julie E
Published: April 2019

Background and Aim

Children with intestinal failure (IF) have abnormal intestinal anatomy, secretion, or motility, which impairs homeostatic mechanisms and can lead to small intestinal bacterial overgrowth (SIBO). We sought to describe clinical features at the time of clinically suspected SIBO by experienced clinicians in children with IF on home parenteral nutrition (PN), review specific challenges of diagnostic testing in this population, and describe potential new diagnostic surrogate markers.

Methods

A descriptive single‐center retrospective chart review was performed during all episodes of clinically suspected SIBO over 33 months. Information was recorded on clinical symptoms, and diagnostic tests performed.

Results

Of all patients on home PN, 71% (12/17) had at least one episode of clinically suspected SIBO (mean 1 episode/year, range 1–7); 50% of patients had short bowel syndrome (SBS), and 50% had non‐SBS IF. The average reported symptoms per episode were 1.9 (range 1–5). Children with SBS reported fewer symptoms per episode (1.5) than children with non‐SBS IF (2.3). Diarrhea was the most commonly reported symptom, particularly in children with SBS.

Conclusions

Children with IF on home PN are a high‐risk group for SIBO. Clinical features of SIBO vary depending on the cause of IF and may mimic symptoms of the underlying condition. Diagnostic tests have innate challenges in this group, and a strong index of clinical suspicion is paramount. Further research is recommended into potential new surrogate markers (urinary metabolite screen, gastric aspirate) for this diagnostically challenging population.
MRI characteristics of supraclavicular brown adipose tissue in relation to cold‐induced thermogenesis in healthy human adults
Authors: Gashi Gani , Madoerin Philipp , Maushart Claudia I. , Michel Regina , Senn Jaël‐Rut , Bieri Oliver , Betz Matthias J.
Published: April 2019

Background

Brown adipose tissue (BAT) has been proposed as a target to treat obesity and metabolic disease. Currently, 18F‐Fluordeoxyglucose positron emission tomography (FDG‐PET) is the standard for BAT‐imaging. MRI might be a promising alternative, as it is not associated with ionizing radiation, offers a high resolution, and allows to discriminate different types of soft tissue.

Purpose

We sought to evaluate whether supraclavicular BAT (scBAT) volume, fat‐fraction (FF), and relaxation rate (R2*) determined by MRI can predict its metabolic activity, which was assessed by measurement of cold‐induced thermogenesis (CIT).

Study Type

Prospective cohort study.

Subjects

Twenty healthy volunteers (9 female, 11 male), aged 18–47 years, with a body mass index (BMI) of 18–30 kg/m2.

Field Strength/Sequence

Multiecho gradient MRI for water–fat separation was used on a 3T device to measure the FF and T2* of BAT.

Assessment

Prior to imaging, CIT was determined by measuring the difference in energy expenditure (EE) during warm conditions and after cold exposure. Volume, FF, and R2* of scBAT was assessed and compared with CIT. In 11 participants, two MRI sessions with and without cold exposure were performed and the dynamic changes in FF and R2* assessed.

Statistical Tests

Linear regression was used to evaluate the relation of MRI measurements and CIT. P‐values below 0.05 were considered significant; data are given as mean ± SD.

Results

R2* correlated positively with CIT (r = 0.64, R2 = 0.41 P = 0.0041). Volume and FF did not correlate significantly with CIT. After mild cold exposure EE increased significantly (P = 0.0002), with a mean CIT of 147 kcal/day. The mean volume of scBAT was 72.4 ± 38.4 ml, mean FF was 74.3 ± 5.8%, and the mean R2* (1/T2*) was 33.5 ± 12.7 s‐1.

Data Conclusion

R2* of human scBAT can be used to estimate CIT. FF of scBAT was not associated with CIT.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1160–1168.
Deep convolutional neural networks with multiplane consensus labeling for lung function quantification using UTE proton MRI
Authors: Zha Wei , Fain Sean B. , Schiebler Mark L. , Evans Michael D. , Nagle Scott K. , Liu Fang
Published: April 2019

Background

Ultrashort echo time (UTE) proton MRI has gained popularity for assessing lung structure and function in pulmonary imaging; however, the development of rapid biomarker extraction and regional quantification has lagged behind due to labor‐intensive lung segmentation.

Purpose

To evaluate a deep learning (DL) approach for automated lung segmentation to extract image‐based biomarkers from functional lung imaging using 3D radial UTE oxygen‐enhanced (OE) MRI.

Study Type

Retrospective study aimed to evaluate a technical development.

Population

Forty‐five human subjects, including 16 healthy volunteers, 5 asthma, and 24 patients with cystic fibrosis.

Field Strength/Sequence

1.5T MRI, 3D radial UTE (TE = 0.08 msec) sequence.

Assessment

Two 3D radial UTE volumes were acquired sequentially under normoxic (21% O2) and hyperoxic (100% O2) conditions. Automated segmentation of the lungs using 2D convolutional encoder‐decoder based DL method, and the subsequent functional quantification via adaptive K‐means were compared with the results obtained from the reference method, supervised region growing.

Statistical Tests

Relative to the reference method, the performance of DL on volumetric quantification was assessed using Dice coefficient with 95% confidence interval (CI) for accuracy, two‐sided Wilcoxon signed‐rank test for computation time, and Bland–Altman analysis on the functional measure derived from the OE images.

Results

The DL method produced strong agreement with supervised region growing for the right (Dice: 0.97; 95% CI = [0.96, 0.97]; P < 0.001) and left lungs (Dice: 0.96; 95% CI = [0.96, 0.97]; P < 0.001). The DL method averaged 46 seconds to generate the automatic segmentations in contrast to 1.93 hours using the reference method (P < 0.001). Bland–Altman analysis showed nonsignificant intermethod differences of volumetric (P ≥ 0.12) and functional measurements (P ≥ 0.34) in the left and right lungs.

Data Conclusion

DL provides rapid, automated, and robust lung segmentation for quantification of regional lung function using UTE proton MRI.

Level of Evidence: 2

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;50:1169–1181.
Three‐dimensional pixel configurations for optical outcoupling of OLED displays—optical simulation
Authors: Lee Wei‐Kai , Chen Yi‐Ting , Wen Sheng‐Wen , Liao Po‐Hsiang , Lee Min‐Chia , Hsu Ting‐Sheng , Chen Yi‐Jiun , Su Guo‐Dong , Lin Hoang Yan , Chen Chung‐Chia , Lin Wan‐Yu , Xu Lisong , Yu Gang , Kwak B. Leo , Visser Robert Jan , Wu Chung‐Chih
Published: April 2019

Because of considerations on image quality and fabrication/integration compatibility, current active‐matrix OLED displays (AMOLEDs) hardly adopt any effective light outcoupling techniques/structures, and it remains an unsolved critical technical issue. Recently, through optical simulation, we proposed a three‐dimensional (3D) pixel configuration as a potential and promising way to boost light outcoupling of OLED display pixels. By extending the bottom reflective electrode to bank slope of the pixel definition layer (PDL) and selectively filling the bank opening (concave area) with high‐index filler to form the optically reflective concave structure, it is possible to give several‐fold light extraction enhancement. In this paper, we further extend the simulation work by evaluating effects of more realistic graded bank slopes vs straight bank slope, less challenging nonpatterned (blanket) high‐index filler vs patterned filler, and real OLED layer stacks and properties. The optical simulation clearly reveals that light extraction enhancement can be mostly kept with more realistic graded bank profiles and even less ideal (but also less challenging) nonpatterned filler can provide substantial extraction enhancement. The graded bank structure also provides beneficial effects on viewing characteristics.
Microextraction by packed sorbent followed by ultra high performance liquid chromatography for the fast extraction and determination of six antidepressants in urine
Authors: Fuentes Ana María Ares , Fernández Purificación , Fernández Ana Maria , Carro Antonia M , Lorenzo Rosa Antonia
Published: April 2019

The growing use of antidepressants in recent years has led to their increasing presence in forensic analyses. In this work, microextraction by packed sorbent followed by ultra‐performance liquid chromatography with photodiode array detection provided a fast method for determining the antidepressants mirtazapine, venlafaxine, escitalopram, fluoxetine, fluvoxamine, and sertraline in human urine. The microextraction conditions (viz., type of sorbent, number of draw–eject extraction cycles or strokes, sample volume and pH, and type and volume of washing solution and eluent) were optimized by using an experimental design. The ensuing analytical method was validated in terms of linearity (25–1000 ng/mL urine), limit of detection (lower than 7.1 ng/mL), limit of quantification (25 ng/mL), precision (4.7–15.1% as relative standard deviation), and accuracy (80.4–126.1% as mean recovery for four replicate determinations). The proposed method allowed the six target antidepressants to be determined at concentrations from therapeutic to toxic levels. The application to small volumes (300 μL) of urine afforded fast extraction of the analytes and provided results on a par with those of existing clinical and forensic alternatives.
A strategy for screening trypsin inhibitors from traditional Chinese medicine based on a monolithic capillary immobilized enzyme reactor coupled with offline liquid chromatography and mass spectrometry
Authors: Lin Hang , Zhang Changfa , Lin Yuanjing , Chang Yiqun , Crommen Jacques , Wang Qiqin , Jiang Zhengjin , Guo Jialiang
Published: April 2019

A novel strategy was successfully developed for screening trypsin inhibitors in traditional Chinese medicines based on monolithic capillary immobilized enzyme reactors combined with liquid chromatography‐tandem mass spectrometry. Organic polymer based monolithic enzyme reactors were firstly prepared by covalently bonding trypsin to a poly(glycidyl methacrylate‐co‐poly (ethylene glycol) diacrylate) monolith by the ring‐opening reaction of epoxy groups. The activity and kinetic parameters of the obtained monolithic trypsin reactors were systematically evaluated using micro‐liquid chromatography. Fourier transform infrared spectroscopy and scanning electron microscopy were also used to characterize the monolithic trypsin reactors. The resulting functional and denatured monolithic trypsin reactors were applied as affinity solid‐phase extraction columns, and offline coupled with a liquid chromatography‐tandem mass spectrometry system to construct a binding affinity screening platform. Subsequently, the proposed platform was applied for screening trypsin binders in a Scutellaria baicalensis Georgi extract. Three compounds, namely scutellarin, baicalin, and wogonoside were identified, and their inhibitory activities were further confirmed via an in vitro enzymatic inhibition assay. Additionally, molecular docking was also performed to study the interactions between trypsin and these three compounds.
Rate constants of the reactions of O(3P) atoms with Br2 and NO2 over the temperature range 220‐950 K
Authors: Bedjanian Yuri , Kalyan Chaitanya
Published: April 2019

The kinetics of the reactions of Br2 and NO2 with ground state oxygen atoms have been studied over a wide temperature range, T = 220‐950 K, using a low‐pressure flow tube reactor coupled with a quadrupole mass spectrometer: O + NO2 → NO + O2 (1) and O + Br2 → Br + BrO (2). The rate constant of reaction (1) was determined under pseudo–first‐order conditions, either monitoring the kinetics of O‐atom or NO2 consumption in excess of NO2 or of the oxygen atoms, respectively: k1 = (6.1 ± 0.4) × 10−12 exp((155 ± 18)/T) cm3 molecule−1 s−1 (where the uncertainties represent precision at the 2σ level, the estimated total uncertainty on k1 being 15% at all temperatures). The temperature dependence of k1, found to be in excellent agreement with multiple previous low‐temperature data, was extended to 950 K. The rate constant of reaction (2) determined under pseudo–first‐order conditions, monitoring the kinetics of Br2 consumption in excess of O‐atoms, showed upward curvature at low and high temperatures of the study and was fitted with the following three‐parameter expression: k2 = 9.85 × 10−16 T1.41 exp(543/T) cm3 molecule−1 s−1 at T = (220‐950) K, which is recommended from the present study with an independent of temperature conservative uncertainty of 15% on k2.
A promising methyl ester of pectic acid polysaccharide in biomedicine and pharmaceutics applications: Oxidation of methyl ester of pectic acid by alkaline hexacyanoferrate(III). A kinetic and mechanistic orientation
Authors: Hassan Refat , Ibrahim Samia
Published: April 2019

The oxidation of methyl ester of pectic acid (pectin) (PEC) by a hexacyanoferrate(III) ion at a constant ionic strength of 0.1 mol dm−3 has been investigated spectrophotometrically. The oxidation rates were found to increase with increasing the alkali concentration, indicating that the nature of reaction was base catalyzed. The agreement of [pectin] dependence of the rate constants to the Michaelis‐Menten kinetics proves the formation of 1:1 intermediate complex prior to the rate‐determining step. The deviation of the pseudo–first‐order curves from linearity after 65‐70% of reaction completion indicates the interference of some oxidation products during the reaction progression. The oxidation process was proceeding via a free‐radical intervention mechanism. The activation parameters have been evaluated, and a suitable reaction mechanism is suggested and discussed.