bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive genomic profiling of high‐grade serous ovarian carcinoma from Chinese patients identifies co‐occurring mutations in the Ras/Raf pathway with TP53
Authors: Zhong Fangfang , Zhu Tao , Pan Xuedong , Zhang Yanling , Yang Haikun , Wang Xiangping , Hu Jinwei , Han Hongxia , Mei Lei , Chen Donglin , Wang Kai , Zhou Xianrong , Li Xiuqin , Dong Xiaowei
Published: May 2019

High‐grade serous ovarian carcinoma (HGSOC) is a major form of ovarian epithelial tumor that is often diagnosed only at an advanced stage when it is already highly aggressive. We performed comprehensive genomic profiling using an analytically validated clinical next‐generation sequencing assay to identify genomic alterations in 450 cancer‐related genes in a cohort of 88 Chinese HGSOC patients. Overall, we detected 547 genomic alterations with an average of 6.2 alterations per tumor. Most of these HGSOC tumors had low tumor mutation burden and were microsatellite stable. Consistent with earlier studies, TP53 mutations were present in the majority (96.6%) of the tumors studied, and mutations in BRCA1/2 that affect DNA repair were also detected frequently in 20.5% of the tumors. However, we observed a 10.2% of mutated genes in the Ras/Raf pathway, all co‐occurring with TP53 mutations in the same tumor, which was unrecognized previously. Our results show that in HGSOC patients, there may be an unrecognized co‐occurrence of TP53 mutations with mutations in Ras/Raf pathway.
Poly(Ionic Liquid)‐Based Composite Gel Electrolyte for Lithium Batteries
Authors: Safa Meer , Adelowo Ebenezer , Chamaani Amir , Chawla Neha , Baboukani Amin Rabiei , Herndon Marcus , Wang Chunlei , El‐Zahab Bilal
Published: May 2019

Composite gel polymer electrolyte (cGPE) containing a poly(ionic liquid) (PIL) polymer, imidazolium cation‐based ionic liquid as a solvent, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) as salt, and glass fillers with various concentrations have been developed and tested in lithium batteries. cGPEs with 1 wt% glass filler shows the highest ionic conductivity and lithium‐ion transference number with 25 % and 18.18 % improvement compared to gel polymer electrolyte (GPE), respectively. Raman results show that the improvement is due to the improved ion‐pair dissociation of LiTFSI, which causes improvement of Li+ mobility. Cyclic charge‐discharge studies using binder‐free LiFePO4/C cathode and lithium anode for 100 cycles at various C‐rates and at a fixed rate of C/2 for 300 cycles show superior performances compared to other cGPEs and GPE. Electrochemical impedance spectroscopy and scanning electron microscopy confirm uniform deposition of reaction products on the cathode surface, which improves the charge‐transfer reactions and hence improves cyclic performances for cGPE‐1 cells with increasing cycles.
Kinetics of the dehydration of lithium dihydrogenphosphate
Authors: Yari Bahman , Sauriol Pierre , Chaouki Jamal
Published: May 2019

Phosphate‐based lithium materials, such as lithium iron phosphate (known as lithium ferrophosphate, LiFePO4, LFP), are among the safest materials for large‐scale lithium‐ion batteries due to the stability of the phosphate‐bound oxygen at elevated temperatures. LFP can be melt‐synthesized where the kinetics is faster, allowing for coarser and lower cost reactants. The most common lithium‐ and phosphate‐bearing reactants can react violently upon heat‐up and release a large volume of gaseous by‐product. Lithium metaphosphate (LiPO3, LPO) can improve the processability and safety of the operation. In this work, we investigate the thermal decomposition of lithium dihydrogenphosphate (LiH2PO4, LHP) to LPO up to 400 °C. The decomposition was analyzed by isothermal and constant rate differential thermogravimetric (DTG) experiments. Activation energy profiles were estimated by an isoconversional model‐free approach and kinetic model fitting. Li5H4P5O17 (L2.5) was determined to be the most stable reaction intermediate and can be isolated at temperatures between 200 and 240 °C. The resulting reaction is comprised of 6 reactions, where the LHP is progressively polymerized by condensation reactions leading successively to L2.5, Li3H2P3O10 (L3), Li4H2P4O13 (L4), and LPO. The first reaction step (LHP → L2.5) was fitted with 3 reactions series/parallel describing the solid surface reaction, the viscous/liquid surface reaction, and the bulk reaction. Limiting the reaction temperature to 400 °C results in a solid product that can be advantageous if LPO is to be prepared in advance and dosed for LFP synthesis.
Galvanic interaction of pyrite with Cu activated sphalerite and its effect on xanthate adsorption
Authors: Xia Liuyin , Hart Brian , Larachi Faïçal , Gravel Olivier
Published: May 2019

In the presence of Cu ions, a packed bed electrochemical reactor (PBER) was employed to deliberately avoid or induce galvanic coupling between pyrite and Cu‐activated sphalerite. The effect of galvanic interaction on Cu ions uptake and xanthate adsorption were investigated. Solution chemistry and surface chemistry studies (ethylenediaminetetraacetic acid extraction and time of flight secondary ion mass spectrometry) have observed that when sphalerite and pyrite were galvanically coupled, Cu ions migrated from the pyrite surface to the surface of the sphalerite. Along with the marked decrease in the adsorption of Cu ions on pyrite, xanthate adsorption on the minerals also dramatically dropped. The pseudo‐adsorption rate constant for the minerals in the mixed mode is only 0.0583 s‒1, much less than that in the decoupled mode, which is 0.1368 s
‒1. This testing program shows that the galvanic coupling of minerals contributes to more copper transfer and Cu ions preferentially adsorbed by sphalerite rather than pyrite. This affects the pyrite surface and causes it to become xanthate unflavoured.
BitFlow: Enabling real‐time cash‐flow evaluations through blockchain
Authors: Herskind Lasse , Giaretta Alberto , De Donno Michele , Dragoni Nicola
Published: May 2019

Disbursement registration has always been a cumbersome, opaque, and inefficient process, up to the point that most businesses perform cash‐flow evaluations only on a quarterly basis. We believe that automatic cash‐flow evaluations can actively mitigate these issues. In this paper, we present BitFlow, a blockchain‐based architecture that provides complete cash‐flow transparency and diminishes the probability of undetected frauds through the BitKrone, a non‐volatile cryptocurrency that maps to the Danish Krone (DKK). We show that confidentiality can be effectively achieved on a permissionless blockchain using Zero‐Knowledge proofs, ensuring verifiable transfers and automatic evaluations. Furthermore, we discuss several experiments to evaluate our proposal, in particular, the impact that confidential transactions have on the whole system, in terms of responsiveness and from an economical expenditure perspective.
A Fast and Reliable Method to Isolate Human Placental Macrophages
Authors: Mezouar Soraya , Ben Amara Amira , Chartier Céline , Gorvel Laurent , Mege Jean‐Louis
Published: May 2019

Macrophages are specialized cells involved in recognition, uptake, and destruction of microorganisms. Human placental macrophages are poorly investigated because of the lack of a convenient protocol for their isolation. Here, we present a straightforward and reliable method to isolate macrophages from full‐term human placentas. After enzymatic digestion of placental tissue and centrifugation of the cell suspension on a Ficoll cushion, placental macrophages are selected using magnetic beads coated with anti‐CD14 antibodies. Isolated cells are characterized by flow cytometry. Ninety eight percent of isolated CD14+ placental macrophages also express the macrophage marker CD68. Thus, this efficient and reliable method yields placental macrophages at high purity and sufficient quantity for functional studies. © 2019 by John Wiley & Sons, Inc.
Statin users have an elevated risk of dysglycemia and new‐onset‐diabetes
Authors: Zigmont Victoria A. , Shoben Abigail B. , Lu Bo , Kaye Gail L. , Clinton Steven K. , Harris Randall E. , Olivo‐Marston Susan E.
Published: May 2019

Objective

Statins are one of the most widely prescribed medications in the United States; however, there is a concern that they are associated with new‐onset‐diabetes (NOD) development. We sought to understand the risk of dysglycemia and NOD for a cohort of individuals that reflect real‐world physician prescribing patterns.

Methods

A retrospective cohort study was conducted among individuals with indications for statin use (n = 7064). To examine elevated glycosylated hemoglobin (>6.0%), logistic regression with inverse probability weighting was used to create balance between incident statin users and nonusers. To evaluate the risk of NOD development, Cox PH models with time varying statin use compared NOD diagnoses among statin users and nonusers.

Results

A higher prevalence of elevated HbA1c (PD = 0.065; 95% CI: 0.002, 0.129, P = 0.045) occurred among nondiabetic incident users of statins. Additionally, statin users had a higher risk of developing NOD (AHR = 2.20; 95% CI: 1.35, 3.58, P = 0.002). Those taking statins for 2 years or longer (AHR = 3.33; 95% CI: 1.84, 6.01, P < 0.001) were at the greatest risk of developing NOD; no differences were observed by statin class or intensity of dose.

Conclusion

As lifestyle programs like the Diabetes Prevention Program are promoted in primary care settings, we hope physicians will integrate and insurers support healthy lifestyle strategies as part of the optimal management of individuals at risk for both NOD and cardiovascular disease. The relationships between statin use and glycemic control should be evaluated in large cohort studies, medical record databases, and mechanistic investigations to inform clinical judgment and treatment.
Chemical profiling of the synthetic cannabinoid MDMB‐CHMICA: Identification, assessment, and stability study of synthesis‐related impurities in seized and synthesized samples
Authors: Münster‐Müller Sascha , Hansen Steven , Opatz Till , Zimmermann Ralf , Pütz Michael
Published: May 2019

In this work, the most discriminating synthesis‐related impurities found in samples from seizures and controlled synthesis of the synthetic cannabinoid MDMB‐CHMICA (methyl (S)‐2‐(1‐(cyclohexylmethyl)‐1H‐indole‐3‐carboxamido)‐3,3‐dimethylbutanoate) were characterized. Based on 61 available powder samples of MDMB‐CHMICA, 15 key‐impurities were assessed, isolated in larger quantities via flash chromatography and structurally elucidated and characterized via high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Apart from verifying the relation of the impurities to the major component, the interpretation of their chemical structures with distinct structural elements provided first insights into the manufacturing process and the precursor compounds used. Following liquid chromatography mass spectrometry analysis of the 15 key‐impurities, the 61 seized samples of MDMB‐CHMICA were evaluated and classified via multivariate data analysis based on the corresponding relative peak areas. In a second part of this work, stability tests and multiple controlled syntheses of MDMB‐CHMICA were carried out to better understand variations in impurity signatures and to assess the significance of variations in the impurity patterns of seized samples. The last coupling step of the amino acid with 1‐(cyclohexylmethyl)‐1H‐indole‐3‐carboxylic acid was performed using the coupling agents oxalyl chloride, thionyl chloride, and HATU. Furthermore, the impact of reaction time and temperature on the impurity profile were investigated. Overall, eight new impurities were found in the controlled syntheses and two degradation products of MDMB‐CHIMCA were found in the course of the stability tests. Replicates of a synthesis conducted on the same day showed similar impurity signatures; on different days they showed discriminable signatures. The use of different coupling reagents or conditions gave clearly distinguishable impurity signatures.
Contingency rules for pathogen competition and antagonism in a genetically based, plant defense hierarchy
Authors: Busby Posy E. , Crutsinger Gregory , Barbour Matthew , Newcombe George
Published: May 2019

Plant defense against pathogens includes a range of mechanisms, including, but not limited to, genetic resistance, pathogen‐antagonizing endophytes, and pathogen competitors. The relative importance of each mechanism can be expressed in a hierarchical view of defense. Several recent studies have shown that pathogen antagonism is inconsistently expressed within the plant defense hierarchy. Our hypothesis is that the hierarchy is governed by contingency rules that determine when and where antagonists reduce plant disease severity.

Here, we investigated whether pathogen competition influences pathogen antagonism using Populus as a model system. In three independent field experiments, we asked whether competition for leaf mesophyll cells between a Melampsora rust pathogen and a microscopic, eriophyid mite affects rust pathogen antagonism by fungal leaf endophytes. The rust pathogen has an annual, phenological disadvantage in competition with the mite because the rust pathogen must infect its secondary host in spring before infecting Populus. We varied mite–rust competition by utilizing Populus genotypes characterized by differential genetic resistance to the two organisms. We inoculated plants with endophytes and allowed mites and rust to infect plants naturally.

Two contingency rules emerged from the three field experiments: (a) Pathogen antagonism by endophytes can be preempted by host genes for resistance that suppress pathogen development, and (b) pathogen antagonism by endophytes can secondarily be preempted by competitive exclusion of the rust by the mite.

Synthesis: Our results point to a Populus defense hierarchy with resistance genes on top, followed by pathogen competition, and finally pathogen antagonism by endophytes. We expect these rules will help to explain the variation in pathogen antagonism that is currently attributed to context dependency.
Base‐Catalyzed Stereoselective 1,6‐Conjugated Addition/Aromatization of P(O)–H Compounds with para‐Quinone Methides
Authors: Xiong Biquan , Wang Gang , Zhou Congshan , Liu Yu , Xu Weifeng , Xu Wen‐Yuan , Yang Chang‐An , Tang Ke‐Wen
Published: May 2019

A versatile base‐catalyzed method for the 1,6‐conjugated addition/aromatization of para‐quinone methides with P(O)–H compounds is illustrated. Further studies on this reaction by using optically active H‐phosphinates show that the reaction takes place stereospecifically with retention or inversion of configuration at the phosphorus center. It is a simple way to produce a broad spectrum of functionalized phosphane oxides and phosphinates from basic P(O)–H starting materials. This finding also contributes significantly to the stereosynthesis in the catalysis.
On computational approaches of liver lobule function and perfusion simulation
Authors: Ricken Tim , Lambers Lena
Published: May 2019

In recent years computational models have become more important for simulating hepatic processes and investigating liver diseases in silico and so various liver models have been published. The complex behavior of biological tissue with its hierarchical structure as well as the blood perfusion through the organ have been described using different approaches and numerical techniques. This paper shows and compares numerical approaches for function and perfusion simulation recently published and compares them with a multiscale function‐perfusion model using the extended theory of porous media. We focus on the description of blood perfusion and liver tissue, but also on the simulation of liver diseases or the zonation of processes in the liver. Furthermore, the selected geometry is taken into account.
Institutional differences and arbitration mechanisms in international joint ventures
Authors: Devarakonda Shivaram , Klijn Elko , Reuer Jeffrey , Duplat Valérie
Published: May 2019

Research summary

We theoretically and empirically study the effects of legal institutions on the inclusion of arbitration provisions in international joint venture (IJV) contracts. Legal institutions offer a public trilateral forum to handle interpartner disputes. However, these institutions function differently across countries, which can impede IJV partners from resolving disputes effectively through court systems. Alternatively, partners can take advantage of private trilateral resolution mechanisms in the form of arbitration. We argue and demonstrate that differences among partners' home country legal institutions regarding the legal traditions, as well as the importance of procedures and costs imposed in these countries for enforcing contracts, increase the likelihood of choosing arbitration over litigation. We also compare results for partners' recourse to IJV boards as a private, bilateral means of addressing conflicts.

Managerial summary

IJVs are powerful levers for market expansion and access to resources and capabilities. The risks of corrosive disputes caused by conflicting interests or misunderstandings among partners are nonetheless far from being negligible. Our study helps decision makers and managers increase their understanding of the options and remedies available for resolving disputes. We consider three mechanisms in particular: public courts, arbitration, and the board of directors. Findings show that considering the partners' home country legal environments but also the discrepancies between these environments is essential when it comes to giving preference to arbitration over public courts. Findings also suggest that decisions related to internal private ordering (i.e., relying on the JV board of directors) are driven by the exchange characteristics more than by institutional considerations.
Determination of Planting Time of Watermelon Under a Shallow Groundwater Table in Tidal Lowland Agriculture Areas of South Sumatra, Indonesia
Authors: Imanudin Momon Sodik , Armanto M.E. , Bakri
Published: May 2019

Watermelon cultivation is one of the appropriate alternatives in order to increase farmers' income from tidal lowland agriculture. Research into crop adaptation to wet soil conditions is required to enable farmers to decide the best planting time under various conditions within the existing land classification. The research to determine crop physiological response during the initial growth period was conducted in a greenhouse. This was combined with field treatments based on groundwater table depths at 15, 10 and 5 cm‐surface, respectively. Analysis of crop potential based on the water status conditions in the root zone was conducted by using secondary and primary data (daily records). Results of crop adaptation at shallow groundwater table depth showed that the treatments with groundwater table depth of 10 and 5 cm‐surface were not significantly different in terms of plant height, with a size of 12.6 and 12.3 cm, having three leaves. However, it had a significant effect on root length, with a length of 11.9 and 3.1 cm, respectively. Maximum plant height of 15.2 cm and four leaves were found for the treatment with a groundwater table depth of 15 cm‐surface. It may be concluded that it is best for farmers to plant at a groundwater table depth of 10 cm‐surface. © 2019 John Wiley & Sons, Ltd.
Hierarchical service providers on sliced infrastructure
Authors: Tusa Francesco , Clayman Stuart , Valocchi Dario , Galis Alex
Published: May 2019

This work presents the deployment of a hierarchical multi‐MANO environment for the instantiation and management of end‐to‐end 5G network services in a slice‐enabled infrastructure.
Optimizing detergent concentration and processing time to balance the decellularization efficiency and properties of bioprosthetic heart valves
Authors: Luo Yu , Lou Dong , Ma Lie , Gao Changyou
Published: May 2019

Decellularization treatment has been widely used to decrease the potential immunogenicity and improve the anticalcification properties of bio‐derived materials, which may be utilized as an alternative method for the preparation of bioprosthetic heart valves. However, the excessive decellularization treatments will deteriarate the properties of heart valves. Among the decellularizaton parameters, detergent concentration and processing time are considered as those of the most key factors. Therefore, it should be meaningful to balance the decellularization efficiency and properties of bioprosthetic heart valves by optimizing the detergent concentration and processing time. In this study, three groups of the decellularized heart valves treated by sodium deoxycholate (SD) with different concentration and processing time were investigated through histological, biochemical, and mechanical analysis. Similar decellularization efficiency can be concluded through histological staining, DNA and α‐Gal quantification results. Extracellular matrix contents quantification and tensile test results revealed that there is no obvious difference among the three decellularized heart valves. in vitro cytotoxicity assay showed that the remnant detergent is not enough to cause cell death, which indicated that the decellularized porcine aortic heart valves may be suitable for further in vivo research. In conclusion, Triton X‐100/SD may be a suitable protocol used for heart valves decellularization. And it is feasible to vary the detergent processing time by changing the detergent concentration without compromising the decellularization efficiency.
Retracted: Long noncoding RNA MEG3 is a tumor suppressor in choriocarcinoma by upregulation of microRNA‐211
Authors: Ji Li , Li Xue
Published: May 2019

Tumor suppressor long noncoding RNA maternally expressed gene 3 (lncRNA MEG3) exists in various cancers. Nonetheless, the functions of lncRNA MEG3 in choriocarcinoma (CC) are still not well studied. We explored the effects of lncRNA MEG3 on human CC JEG‐3 and BeWo cells. lncRNA MEG3 was overexpressed, and the effects of lncRNA MEG3 on cell viability, proliferation, apoptosis, migration, and invasion were assessed by the cell counting kit‐8 assay, western blot analysis, flow cytometry (plus western blot analysis), and transwell assay (plus western blot analysis), respectively. Then, the expression level of miR‐211 was detected by real‐time quantitative polymerase chain reaction. After that, the effects of dysregulated microRNA‐211 (miR‐211) with overexpressing lncRNA MEG3 on JEG‐3 cells and BeWo cells were testified. Western blot analysis was used to study the involvements of the signaling pathways in the lncRNA MEG3‐associated modulation. We found that lncRNA MEG3 upregulation reduced cell viability, inhibited proliferation, migration and invasion, and promoted apoptosis. Expression of miR‐211 was upregulated after lncRNA MEG3 overexpression. Effects of lncRNA MEG3 overexpression were augmented by miR‐211 overexpression, while they were declined by miR‐211 silencing. Phosphorylated levels of PI3K, AKT, and AMP‐activated protein kinase (AMPK) were decreased by lncRNA MEG3 overexpression via regulation of miR‐211. To sum up, lncRNA MEG3 could repress proliferation, migration and invasion, and promote apoptosis of JEG‐3 and BeWo cells through upregulating miR‐211. The PI3K/AKT and AMPK pathways were inhibited by lncRNA MEG3 overexpression via regulation of miR‐211.
Exosomes from human adipose‐derived stem cells promote sciatic nerve regeneration via optimizing Schwann cell function
Authors: Chen Jing , Ren Sen , Duscher Dominik , Kang Yu , Liu Yutian , Wang Cheng , Yuan Meng , Guo Guojun , Xiong Hewei , Zhan Peng , Wang Yang , Machens Hans‐Günther , Chen Zhenbing
Published: May 2019

Human adipose‐derived stem cells (ASCs) have a potential for the treatment of peripheral nerve injury. Recent studies demonstrated that stem cells can mediate therapeutic effect by secreting exosomes. We aimed to investigate the effect of human ASCs derived exosomes (ASC‐Exos) on peripheral nerve regeneration in vitro and in vivo. Our results showed after being internalized by Schwann cells (SCs), ASC‐Exos significantly promoted SC proliferation, migration, myelination, and secretion of neurotrophic factors by upregulating corresponding genes in vitro. We next evaluated the efficacy of ASC‐Exo therapy in a rat sciatic nerve transection model with a 10‐mm gap. Axon regeneration, myelination, and restoration of denervation muscle atrophy in ASC‐Exos treated group was significantly improved compared to vehicle control. This study demonstrates that ASC‐Exos effectively promote peripheral nerve regeneration via optimizing SC function and thereby represent a novel therapeutic strategy for regenerative medicine and nerve tissue engineering.
Prediction of pregnancy complications by second‐trimester uterine artery Doppler assessment in monochorionic twins
Authors: Masini Giulia , Tordini Chiara , Pietrosante Annamaria , Gaini Claudia , Di Tommaso Mariarosaria , Pasquini Lucia
Published: May 2019

Purpose

We aimed to investigate whether transabdominal uterine artery (UtA) pulsatility index (PI) differs between monochorionic (MC) diamniotic and dichorionic (DC) twins and is useful to predict pregnancy complications.

Methods

A total of 406 uncomplicated twin pregnancies (94 MC, 312 DC) were examined at 22+0‐24+6 weeks and compared for demographic characteristics, mean UtA PI, presence of notch, development of preeclampsia, fetal growth restriction (FGR), placental abruption, intrauterine fetal death and preterm delivery. Mann‐Whitney and Fisher's exact tests were performed for continuous and categorical variables, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated for mean PI >95th percentile, presence of notch, and presence of either elevated PI or notch.

Results

Median mean UtA PI was 0.68 in DC and 0.75 in MC pregnancies (P = .005). Bilateral notches were observed in one MC pregnancy; unilateral notch was seen in 8 DC (2.6%) and 5 MC diamniotic (5.3%) pregnancies. FGR occurred more frequently in DC twin pregnancies, while intrauterine fetal death in MC. Overall, the sensitivity of the parameters tested was low. Pregnancies with both PI above 95th percentile and presence of notch were all associated with complications, particularly FGR.

Conclusion

MC pregnancies have higher mean UtA PI. UtA screening in twins shows lower performances than in singletons for the detection of complications.
Observational study of the microcirculation in patients with liver cirrhosis
Authors: Wythe Stephen , Davies Thomas W , O'Beirne James , Martin Daniel , Gilbert‐Kawai Edward
Published: May 2019

Background and Aim

Liver cirrhosis is associated with widespread microcirculatory dysfunction and hemodynamic derangement, which may play a role in the pathogenesis of multiple organ failure. Little is known, however, about the progression of microvascular alterations as the severity of liver disease worsens. Therefore, our aim is to quantify the peripheral systemic microcirculatory changes associated with increasing severity of liver cirrhosis.

Methods

Forty patients with liver cirrhosis were studied and divided into groups based on Child‐Pugh classes A (n = 9), B (n = 18), and C (n = 13) for comparison. Incident dark field imaging was used to evaluate the sublingual microcirculation and near‐infrared spectroscopy at the thenar eminence to assess microvascular reactivity and function.

Results

There was no difference in microcirculatory flow index (P = 0.655), heterogeneity index (P = 0.702), or vessel density (P = 0.923) between the different Child‐Pugh groups. Microvascular reactivity did not change as the severity of liver disease worsened.

Conclusions

This study showed no association between peripheral systemic microcirculatory alterations and the severity of liver disease. Further research with larger study cohorts are needed to clarify the relationship between microcirculatory abnormalities and disease progression and to establish if the peripheral microcirculation is affected by the pathophysiology of worsening cirrhosis.
Breast Cancer Brain Metastasis Response to Radiation After Microbubble Oxygen Delivery in a Murine Model
Authors: Delaney Lauren J. , Ciraku Lorela , Oeffinger Brian E. , Wessner Corinne E. , Liu Ji‐Bin , Li Jingzhi , Nam Kibo , Forsberg Flemming , Leeper Dennis B. , O'Kane Patrick , Wheatley Margaret A. , Reginato Mauricio J. , Eisenbrey John R.
Published: May 2019

Objectives

Hypoxic cancer cells have been shown to be more resistant to radiation therapy than normoxic cells. Hence, this study investigated whether ultrasound (US)‐induced rupture of oxygen‐carrying microbubbles (MBs) would enhance the response of breast cancer metastases to radiation.

Methods

Nude mice (n = 15) received stereotactic injections of brain‐seeking MDA‐MB‐231 breast cancer cells into the right hemisphere. Animals were randomly assigned into 1 of 5 treatment groups: no intervention, 10 Gy radiation using a small‐animal radiation research platform, nitrogen‐carrying MBs combined with US‐mediated MB rupture immediately before 10 Gy radiation, oxygen‐carrying MBs immediately before 10 Gy radiation, and oxygen‐carrying MBs with US‐mediated MB rupture immediately before 10 Gy radiation. Tumor progression was monitored with 3‐dimensional US, and overall survival was noted.

Results

All groups except those treated with oxygen‐carrying MB rupture and radiation had continued rapid tumor growth after treatment. Tumors treated with radiation alone showed a mean increase in volume ± SD of 337% ± 214% during the week after treatment. Tumors treated with oxygen‐carrying MBs and radiation without MB rupture showed an increase in volume of 383% ± 226%. Tumors treated with radiation immediately after rupture of oxygen‐carrying MBs showed an increase in volume of only 41% ± 1% (P = 0.045), and this group also showed a 1 week increase in survival time.

Conclusions

Adding US‐ruptured oxygen‐carrying MBs to radiation therapy appears to delay tumor progression and improve survival in a murine model of metastatic breast cancer.
Contextual role of E2F1 in suppression of melanoma cell motility and invasiveness
Authors: Meng Peng , Bedolla Roble G. , Yun Huiyoung , Fitzpatrick James E. , Kumar Addanki P. , Ghosh Rita
Published: May 2019

The general transcription factor E2F1 reportedly functions in a protumorigenic manner in several cancer models. We show that the genetic context of cancer cells influence E2F1's role to impede the protumorigenic role. Thirty to fifty percent of melanoma patients carry mutant BRAF with about 90% of mutant BRAF melanomas being V600E mutation. Tissue microarrays from melanoma patients were used to establish an association between E2F1 and BRAFV600E. We show for the first time that low E2F1 levels in BRAFV600E melanomas are associated with lymph node metastasis. Genetic manipulation of E2F1 in BRAFV600E and BRAFwt cells were used to determine its role in malignant melanoma progression by examining effects on migration and invasion. E2F1‐mediated negative regulation of myosin light chain kinase (MYLK) increased migration and invasion in BRAFV600E cells by phosphorylating myosin light chain and increased stress fiber formation. We show that E2F1 inhibits extracellular signal‐regulated kinase (ERK) activation in BRAFV600E cells and provide evidence for a negative feedback loop between E2F1 and ERK in these cells. This study shows for the first time that E2F1 has a cancer protective role in oncogenic BRAF‐activated melanoma cells and that loss of E2F1 can allow disease progression through a novel mechanism of E2F1‐mediated MYLK regulation. This study has implications for oncogenic BRAF‐activated tumors and resistance to targeted oncogenic BRAF therapy.
Association study between matrix metalloproteinase‐3 gene (MMP3) polymorphisms and ankylosing spondylitis susceptibility
Authors: Zhu Yong , Li Shunan , Huang Zhi , Xing Wenhua , Li Feng , Da Yifeng , Xue Jianmin , Li Manglai , Sun Ke , Jia Haiyu , Yang Xuejun
Published: May 2019

Background

Ankylosing spondylitis (AS) is the second most common cause of inflammatory arthritis worldwide affecting the axial skeleton. Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase‐3 (MMP3) in the development of AS has few been investigated in Chinese population.

Methods

A total of 362 patients with AS and 362 healthy controls were enrolled in the study. Five SNPs in MMP3 genotypes were identified by Agena MassARRAY. Chi‐squared tests and genetic model were used to evaluate associations.

Results

rs522616 had a significant risk of AS development compared to those with the TT genotype (p = 0.008). By multiple logistic regression models analysis, in codominant model, rs522616 CT genotypes also had a 1.44‐fold risk (95% CI = 1.06–1.96, p = 0.008) for AS development compared to those with TT genotypes. In recessive model, the CC genotypes was a significantly reduced AS risk for individuals with TT/CT genotype (OR = 0.64; 95% CI = 0.41–0.99, p = 0.040).

Conclusion

The present study suggests that MMP3 rs522616 polymorphism is associated with AS susceptibility and MMP3 might be a potential diagnostic biomarker for AS. Further independent studies with larger cohorts are warranted to validate our findings in different populations.
Precise CCM1 gene correction and inactivation in patient‐derived endothelial cells: Modeling Knudson's two‐hit hypothesis in vitro
Authors: Spiegler Stefanie , Rath Matthias , Much Christiane D. , Sendtner Barbara S. , Felbor Ute
Published: May 2019

Background

The CRISPR/Cas9 system has opened new perspectives to study the molecular basis of cerebral cavernous malformations (CCMs) in personalized disease models. However, precise genome editing in endothelial and other hard‐to‐transfect cells remains challenging.

Methods

In a proof‐of‐principle study, we first isolated blood outgrowth endothelial cells (BOECs) from a CCM1 mutation carrier with multiple CCMs. In a CRISPR/Cas9 gene correction approach, a high‐fidelity Cas9 variant was then transfected into patient‐derived BOECs using a ribonucleoprotein complex and a single‐strand DNA oligonucleotide. In addition, patient‐specific CCM1 knockout clones were expanded after CRISPR/Cas9 gene inactivation.

Results

Deep sequencing demonstrated correction of the mutant allele in nearly 33% of all cells whereas no CRISPR/Cas9‐induced mutations in predicted off‐target loci were identified. Corrected BOECs could be cultured in cell mixtures but demonstrated impaired clonal survival. In contrast, CCM1‐deficient BOECs displayed increased resistance to stress‐induced apoptotic cell death and could be clonally expanded to high passages. When cultured together, CCM1‐deficient BOECs largely replaced corrected as well as heterozygous BOECs.

Conclusion

We here demonstrate that a non‐viral CRISPR/Cas9 approach can not only be used for gene knockout but also for precise gene correction in hard‐to‐transfect endothelial cells (ECs). Comparing patient‐derived isogenic CCM1+/+, CCM1+/−, and CCM1−/− ECs, we show that the inactivation of the second allele results in clonal evolution of ECs lacking CCM1 which likely reflects the initiation phase of CCM genesis.
Structural neuroimaging in mild traumatic brain injury: A chronic effects of neurotrauma consortium study
Authors: Bigler Erin D. , Abildskov Tracy J. , Eggleston Barry , Taylor Brian A. , Tate David F. , Petrie Jo Ann , Newsome Mary R. , Scheibel Randall S. , Levin Harvey , Walker William C. , Goodrich‐Hunsaker Naomi , Tustison Nicholas J. , Stone James R. , Mayer Andrew R. , Duncan Timothy D. , York Gerry E. , Wilde Elisabeth A.
Published: May 2019

Objectives

The chronic effects of neurotrauma consortium (CENC) observational study is a multisite investigation designed to examine the long‐term longitudinal effects of mild traumatic brain injury (mTBI). All participants in this initial CENC cohort had a history of deployment in Operation Enduring Freedom (Afghanistan), Operation Iraqi Freedom (Iraq), and/or their follow‐on conflicts (Operation Freedom's Sentinel). All participants undergo extensive medical, neuropsychological, and neuroimaging assessments and either meet criteria for any lifetime mTBI or not. These assessments are integrated into six CENC core studies—Biorepository, Biostatistics, Data and Study Management, Neuroimaging, and Neuropathology.

Methods

The current study outlines the quantitative neuroimaging methods managed by the Neuroimaging Core using FreeSurfer automated software for image quantification.

Results

At this writing, 319 participants from the CENC observational study have completed all baseline assessments including the imaging protocol and tertiary data quality assurance procedures.

Conclusions/Discussion

The preliminary findings of this initial cohort are reported to describe how the Neuroimaging Core manages neuroimaging quantification for CENC studies.
The belonging model of trust
Authors: Knapp Joshua R. , Sprinkle Therese A. , Urick Michael J. , Delaney‐Klinger Kelly A.
Published: May 2019

Although we know that high‐quality employee–organization relationships are beneficial, these relationships are complex and not fully understood, especially among employees of nonprofit organizations. In particular, we know little about how these employees perceive trust, which may overlook an important contributor to effective management. We begin to address this issue by testing a new theoretical model that conceptualizes perceived insider status, psychological ownership, and organizational identification as foundations for the perception of justice and subsequent trust. Our results indicate that psychological ownership and perceived insider status relate to trust through procedural and interpersonal justice. These results contrast those typically found in for‐profit contexts in that organizational identification did not predict justice and that distributive and informational justice did not predict trust.
Getting the Best out of Your Fiber
Authors: Pozo Jose
Published: May 2019

Prof. Fetah Benabid, director of research at CNRS, honorary professor of two universities and CTO / CSO of GLOphotonics, talks to Jose Pozo, CTO at EPIC, about the challenges of introducing disruptive specialty fibers and gas photonics to the photonics market.
Proteomics Analysis of Avian Eggshell Matrix Proteins: Toward New Advances on Biomineralization
Authors: Gautron Joël
Published: May 2019

Eggs are widely consumed all over the world. The eggshell is its protective barrier whose original function is to protect the embryo during development. Avian eggshells are made of calcium carbonate with a small amount of organic matrix (proteins and proteoglycans). During eggshell formation, the mineral precursors interact with matrix proteins to regulate the calcification of this highly resistant biomineral. In order to better characterize the functions of matrix proteins in eggshell biominerals, many proteomics studies have been performed during the last 15 years. The chicken eggshell is the main model studied in birds, but there is a need for comparative approaches in order to determine whether there is a general protein toolkits associated with calcitic biomineralization, and to determine its components. The study by Zhu et al., reported in article number 1900011, volume 19, issue 11, is a major step forward as it is the first shell proteomics survey performed on duck. Thus, it will contribute to improved knowledge of the eggshell mineralization process and will provide new insight for shell quality improvement and to guide biomimetic efforts in material sciences.
Controlled processing of polymer nanoribbons: Enabling microhelix transformations
Authors: Choudhary Satyan , Crosby Alfred J.
Published: May 2019

Flow‐coated, two‐dimensional polymer ribbon structures undergo a shape‐transformation into a three‐dimensional helix upon their release into a solution. Driven by surface forces and due to geometric asymmetry, the helix radius and spring constant depend upon the ribbon cross‐section dimensions, surface energy, and material elastic modulus. Such spring‐like microhelices offer multiple functionalities combined with mechanical stretching and shape recovery. Fabricating such microhelices requires a sequence of processing steps, beginning with flow‐coating of ribbons on a substrate, followed by etching of a “scum layer” to allow for an independent release into a solution, upon which shape‐transformation occurs. During the deposition‐etch‐release sequence, various control parameters influence the nanoribbon size and geometry, hence the helix properties. The experimental study presented here focuses on the influence of meniscus height, substrate velocity, substrate surface energy, and etch time on nanoribbon size (height and width), scum layer thickness, and helix radius. The results show that meniscus height and contact angle dictate flux toward the meniscus edge and volume available for spatial assembly, allowing control over the aspect ratio of ribbons. We vary the aspect ratio by two orders of magnitude, while maintaining geometric asymmetry needed for helix shape‐transformation. We provide robust scaling for the nanoribbon size and geometry and report the advantages and disadvantages of different parameters, in the control of polymer nanoribbon and helix fabrication. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 1270–1278
l‐α‐Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK‐dependent pathway
Authors: Robertson‐Gray Olivia J. , Walsh Sarah K. , Ryberg Erik , Jönsson‐Rylander Ann‐Cathrine , Lipina Christopher , Wainwright Cherry L.
Published: May 2019

The phospholipid l‐α‐lysophosphatidylinositol (LPI), an endogenous ligand for GPR55, is elevated in patients with acute coronary syndrome, and a GPR55 antagonist cannabidiol (CBD) reduces experimental ischemia/reperfusion (I/R) injury. While LPI activates multiple signaling pathways, little is known about which ones are important in cardiomyocytes. In this study we explored whether activation of the Rho kinase/ROCK/p38 MAPK pathway is responsible for LPI‐induced extension of I/R injury. Using a high‐throughput screening method (dynamic mass redistribution; DMR), mouse‐ and human‐induced pluripotent stem cell (iPSC) cardiomyocytes exposed to LPI were shown to exhibit a rapid, sustained, and concentration‐dependent (1 nmol L−1‐30 μmol L−1) cellular response. Y‐27632 (ROCK inhibitor; 10 & 50 μmol L−1) and CBD (1 μmol L−1) both abolished the DMR response to LPI (10 μmol L−1). In murine iPSC cardiomyocytes, LPI‐induced ROCK and p38 MAPK phosphorylation, both of which were prevented by Y‐27632 and CBD, but did not induce JNK activation or cleavage of caspase‐3. In hearts isolated from wild type (WT) mice subjected to 30 minutes global I/R, LPI (10 μmol L−1) administered via the coronary circulation increased infarct size when applied prior to ischemia onset, but not when given at the time of reperfusion. The exacerbation of tissue injury by LPI was not seen in hearts from GPR55−/− mice or in the presence of Y‐27632, confirming that injury is mediated via the GPR55/ROCK/p38 MAPK pathway. These findings suggest that raised levels of LPI in the vicinity of a developing infarct may worsen the outcome of AMI.
Lifestyle migration from the Global South to the Global North: Individualism, social class, and freedom in a centre of “superdiversity”
Authors: Robins Daniel
Published: May 2019

Lifestyle migration is a growing field of interest. Traditionally, research into lifestyle migration has focused on either “North to North” or “North to South” migration. This article analyses middle‐class Brazilian migration to London together with examples from the lifestyle migration literature to argue that there are instances of movement from the Global South to the Global North, which should be classified as lifestyle migration according to how the term is used in the literature. This is important because there is a tendency in migration studies to implicitly classify all voluntary migration from South to North as “economic.” The article compares the similarities in terms of motivations to migrate and identity as a migrant, between “lifestyle migrants” as characterised in the literature and many Brazilian middle‐class migrants to London. Rather than economic gain, individualist ideals of anonymity and mobility are often central in the discourse. Mobility is conceived not only as mobility across space but also in terms of mobility of identity, specifically as a disavowal of a transnational identity in favour of a more individualistic ideological stance. The article goes on to examine how the dichotomy between lifestyle and economic migrants is operationalised within the discourse of middle‐class Brazilian migrants to demarcate their situation from their “transnational” compatriots who they view as “other.” This act of distancing themselves from the “typical migrant” and often from Brazilian “culture” more generally is often stratified by class and race. Distancing becomes especially important in cases when differences may not be so apparent to an outside observer. The article ultimately argues for an understanding of lifestyle migration that incorporates movements from South to North and thus for a greater emphasis on social class, which, in the context of Brazil, is bound up with issues of racial and ethnic identity.
The effect of atmosphere–ocean coupling on the prediction of 2016 western North Pacific tropical cyclones
Authors: Feng Xiangbo , Klingaman Nicholas P. , Hodges Kevin I.
Published: May 2019

We examine the merit of atmosphere–ocean coupled models for tropical cyclone (TC) predictions in the western North Pacific (WNP), where accurate TC predictions remain challenging. The UK Met Office operational atmospheric global numerical weather prediction (NWP) model is compared with two trial coupled configurations, in which the operational atmospheric model is coupled to a one‐dimensional mixed‐layer ocean model and a three‐dimensional dynamical ocean model. Reforecasts for the 2016 TC season show that the coupled models outperform the NWP model for TC location predictions, with a systematic improvement of 50–100 km over the seven‐day forecasts, but the coupled models amplify the underestimation of TC intensity in the NWP model. Nearly identical TC predictions (for both location and intensity) are found in the two coupled models, indicating the dominance of thermodynamic processes at the air–sea interface for TC predictions on these timescales. The improved prediction of the TC position in the coupled models is associated with an enhanced Western North Pacific Subtropical High (WNPSH), which introduces an anticyclonic steering flow anomaly that shifts TC tracks further west in the southern part of the region and further east in the northern part. Based on sensitivity experiments, we show that these improvements in the coupled models are due mainly to colder initial sea‐surface temperatures (SSTs). Air–sea feedbacks do not change the WNPSH or TC tracks noticeably. Apart from the effect of the initial SSTs, tropical ocean warming due to air–sea interaction in the coupled forecasts can also reduce the predicted TC intensity, presumably due to a stronger regional Hadley circulation with increased subtropical subsidence.