bluuebunny/crossref_metadata_2025 huggingface dataset:
Empirical observations and numerical modelling of tides, channel morphology, and vegetative effects on accretion in a restored tidal marsh
Authors: Fleri Jesse R. , Lera Sara , Gerevini Alessandro , Staver Lorie , Nardin William
Published: May 2019

Tidal marshes form at the confluence between estuarine and marine environments where tidal movement regulates their developmental processes. Here, we investigate how the interplay between tides, channel morphology, and vegetation affect sediment dynamics in a low energy tidal marsh at the Paul S. Sarbanes Ecosystem Restoration Project at Poplar Island. Poplar Island is an active restoration site where fine‐grained material dredged from navigation channels in the upper Chesapeake Bay are being used to restore remote tidal marsh habitat toward the middle bay (Maryland, USA). Tidal currents were measured over multiple tidal cycles in the inlets and tidal creeks of one marsh at Poplar Island, Cell 1B, using Acoustic Doppler Current Profilers (ADCP) to estimate water fluxes throughout the marsh complex. Sediment fluxes were estimated using acoustic backscatter recorded by ADCPs and validated against total suspended solid measurements taken on site. A high‐resolution geomorphic survey was conducted to capture channel cross sections and tidal marsh morphology. We integrated simple numerical models built in Delft3d with empirical observations to identify which eco‐geomorphological factors influence sediment distribution in various channel configurations with differing vegetative characteristics. Channel morphology influences flood‐ebb dominance in marshes, where deep, narrow channels promote high tidal velocities and incision, increasing sediment suspension and reducing resilience in marshes at Poplar Island. Our numerical models suggest that accurately modelling plant phenology is vital for estimating sediment accretion rates. In‐situ observations indicate that Poplar Island marshes are experiencing erosion typical for many Chesapeake Bay islands. Peak periods of sediment suspension frequently coincide with the largest outflows of water during ebb tides resulting in large sediment deficits. Ebb dominance (net sediment export) in tidal marshes is likely amplified by sea‐level rise and may lower marsh resilience. We couple field observations with numerical models to understand how tidal marsh morphodynamics contribute to marsh resilience. © 2019 John Wiley & Sons, Ltd.
Volatility index and the return–volatility relation: Intraday evidence from Chinese options market
Authors: Li Jupeng , Yu Xiaoli , Luo Xingguo
Published: May 2019

We use unique intraday data to investigate the validity of the Shanghai Stock Exchange's the revised Chinese implied volatility index (iVX). We find that iVX is an effective barometer for the underlying exchange‐traded fund (ETF) market and can be used as a valid “fear index” when there is anxiety over large drops. Furthermore, we use robust quantile regressions and document the asymmetric relation between returns and iVX changes. We also show that behavioral theories offer better explanations for this asymmetric relation than do fundamental theories. More important, we examine the role of iVX in selecting trading strategies.
Which factors stimulate industrial green total factor productivity growth rate in China? An industrial aspect
Authors: Cui Herui , Wang Haoran , Zhao Qiaozhi
Published: May 2019

As an important evaluation transformation index, exploring green total factor productivity (GTFP) trend and related key factors is significant for China's economy entering into high‐quality development and green transformation. In this study, stochastic frontier analysis (SFA) and kernel density function are used to evaluate GTFP growth trend for 36 China's industrial sectors during 2000–2016, and system generalized method of moment is used to explore their key driving factors. The results are as follows: First, SFA supplies efficient estimation for GTFP growth information. The 36 industrial sectors are classified into three emission types, that is, high‐, moderate‐, and low emission. Second, GTFP growth differs significantly in three types of sectors. With kernel density results for 36 sectors, the curve of GTFP growth has shifted upward and toward the left since 2010. For high‐emission type sectors, their kernel curve has also moved upward and toward the left. The curve of moderate‐emission type sectors significantly shifted toward the left, whereas the curve of low‐emission type moved upward. Third, based on regression estimation results, environmental regulatory policy, resource input structure, foreign direct investment, and energy‐type structure significantly influence GTFP growth. Technology innovation makes insignificant impact on GTFP for industrial sectors. In conclusion, sectorial heterogeneity should be paid more focus in order to improve their growth, especially for high‐emission type sectors. Green technology innovation is the most potential factor in the future to stimulate GTFP growth in China. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Plasma soluble programmed death ligand 1 levels predict clinical response in peripheral T‐cell lymphomas
Authors: Zhang Xuhan , Liu Lu , Zhou Shiyong , Zhao Kuo , Song Zheng , Hu Ge , Zhang Tingting , Li Yang , Qiu Lihua , Li Lanfang , Qian Zhengzi , Meng Bin , Pan Yi , Ren Xiubao , Wang Xianhuo , Zhang Huilai , Fu Kai
Published: May 2019

Immune checkpoints, including PD‐1/PD‐L1, play an important role in immunosuppression in various malignancies. Elevated levels of soluble programmed death ligand 1 (sPD‐L1) are associated with worse prognosis in multiple myeloma and diffuse large B cell lymphoma. Herein, the purpose of this study is to investigate the relationships between plasma sPD‐L1 levels and clinical response in peripheral T‐cell lymphoma (PTCL) patients.

A total of 37 PTCL patients and 20 healthy volunteers were enrolled. Peripheral blood from patients was collected prior to systemic therapy. Plasma levels of sPD‐L1 and IFN‐γ were measured by enzyme‐linked immunosorbent assay (ELISA). PD‐L1 expression in tissues was detected by immunohistochemistry (IHC). Clinical response for patients was evaluated.

ONCOMINE database analyses showed that PD‐L1 mRNA expression was significantly upregulated in PTCLs. The median sPD‐L1 level was 0.729 ng/mL for 20 healthy volunteers and 1.696 ng/mL for 37 PTCL patients which was significantly higher than that in healthy volunteers (0.000). The sPD‐L1 level was positively correlated with IFN‐γ level (0.000, r = 0.849) and was also positively associated with clinical staging (0.045), LDH level (0.003), and β2‐MG level (0.045). Patients with high sPD‐L1 level had lower overall response rate than those with low sPD‐L1 level (88.9% vs 50.0%, 0.022) and tended to have poorer PFS and OS. PD‐L1 expression in tissues matched very well with the sPD‐L1 level in PTCL patients. In conclusion, PTCL patients had higher sPD‐L1 level compared with healthy volunteers. High sPD‐L1 level was correlated with worse clinical response, suggesting that sPD‐L1 level was an underlying plasma biomarker to predict the prognosis for PTCL patients.
Reproductive health sequelae among women who survived Ebola virus disease in Liberia
Authors: Godwin Christine L. , Wohl David A. , Fischer 2nd William A. , Singh Kavita , Hawks Darrell A. , Devore Elizabeth E. , Brown Jerry
Published: May 2019

Objective

To estimate the incidence of failed pregnancy and menstrual irregularities among Liberian women who had survived Ebola virus disease (EVD) and to identify host‐specific and disease‐specific factors associated with these outcomes.

Methods

A cross‐sectional questionnaire‐based study was conducted between August 10, 2016, and February 7, 2017. The study population comprised 111 women aged 18–45 years who had survived EVD and were enrolled in the Longitudinal Liberian Ebola Survivor study based at the Eternal Love Winning Africa Hospital, Monrovia, Liberia. Self‐reported data on outcomes related to pregnancy and menstrual changes since recovery from EVD were collected.

Results

In all, 29 (26.1%) of the participants had become pregnant since surviving EVD. Of the 23 women whose pregnancies continued to term, 10 (43.4%) reported live birth, 11 (47.8%) reported spontaneous abortion, and two (8.7%) reported stillbirth. Of the 105 women who reported having regular menstruation before EVD, 27 (29.0%) reported experiencing irregular menstruation for unknown reasons after EVD. In bivariate logistic models, no associations were found between failed pregnancy or irregular menstruation and any of the factors of interest.

Conclusions

Adverse pregnancy outcomes and irregular menstruation were frequently reported among EVD survivors in Liberia.
Epidermal growth factor receptor genes are overexpressed within the periprosthetic soft‐tissue around percutaneous devices: A pilot study
Authors: Jeyapalina Sujee , Colombo John S. , Beck James P. , Agarwal Jayant P. , Schmidt Linda A. , Bachus Kent N.
Published: May 2019

Epidermal downgrowth around percutaneous devices produce sinus tracts, which then accumulate bacteria becoming foci of infection. This mode to failure is epidermal‐centric, and is accelerated by changes in the chemokines and cytokines of the underlying periprosthetic granulation tissue (GT). In order to more fully comprehend the mechanism of downgrowth, in this 28‐day study, percutaneous devices were placed in 10 Zucker diabetic fatty rats; 5 animals were induced with diabetes mellitus II (DM II) prior to the surgery and 5 animals served as a healthy, nondiabetic cohort. At necropsy, periprosthetic tissues were harvested, and underwent histological and polymerase chain reaction (PCR) studies. After isolating GTs from the surrounding tissue and extracting ribonucleic acids, PCR array and quantitative‐PCR (qPCR) analyses were carried‐out. The PCR array for 84 key wound‐healing associated genes showed a five‐fold or greater change in 31 genes in the GTs of healthy animals compared to uninjured healthy typical skin tissues. Eighteen genes were overexpressed and these included epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Thirteen genes were underexpressed. When GTs of DM II animals were compared to healthy animals, there were 8 genes overexpressed and 25 genes underexpressed; under expressed genes included EGF and EGFR. The qPCR and immunohistochemistry data further validated these observations. Pathway analysis of genes up‐regulated 15‐fold or more indicated two, EGFR and interleukin‐10, centric clustering effects. It was concluded that EGFR could be a key player in exacerbating the epidermal downgrowth, and might be an effective target for preventing downgrowth.
Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein
Authors: Batool Asiya , Aashaq Sabreena , Andrabi Khurshid I.
Published: May 2019

Eukaryotic initiation factor 4E (eIF4E), a fundamental effector and rate limiting element of protein synthesis, binds the 7‐methylguanosine cap at the 5′ end of eukaryotic messenger RNA (mRNA) specifically as a constituent of eIF4F translation initiation complex thus facilitating the recruitment of mRNA to the ribosomes. This review focusses on the engagement of signals contributing to growth factor originated maxim and their role in the activation of eIF4E to achieve a collective influence on cellular growth, with a key focus on conjuring vital processes like protein synthesis. The review invites considerable interest in elevating the appeal of eIF4E beyond its role in regulating translation viz a viz cancer genesis, attributed to its phosphorylation state that improves the prospect for the growth of the cancerous cell. This review highlights the latest studies that have envisioned to target these pathways and ultimately the translational machinery for therapeutic intervention. The review also brings forward the prospect of eIF4E to act as a converging juncture for signaling pathways like mTOR/PI3K and Mnk/MAPK to promote tumorigenesis.
Assessment of epigenetic alterations and in silico analysis of mutation affecting PTEN expression among Indian cervical cancer patients
Authors: Naseem Afreen , Bhat Zafar Iqbal , Kalaiarasan Ponnusamy , Kumar Bhupender , Bin Hafeez Zubair , Tiwari Raj Ranjan , Wahabi Khushnuma , Gandhi Gauri , Alam Rizvi M. Moshahid
Published: May 2019

Genetic and epigenetic anomalies accountable for genetic dysregulation are the most common aberrations that determine the underlying heterogeneity of the tumor cells. Currently, phosphatase and tensin homolog (PTEN) incongruity has emerged as potent and persuasive malfunctioning in varied human malignancies. In this study, we have analysed the promoter hypermethylation and expression status of PTEN. We identified different mutations in the exonic region of PTEN. Functional consequences of these mutations were explored using in silico techniques. Promoter hypermethylation of PTEN was detected using methylation‐specific polymerase chain reaction (MS‐PCR), expression analysis was performed with immunohistochemistry (IHC) and mutation by direct sequencing in a total of 168 uterine cervix tumor cases. The findings were statistically correlated with the clinical parameters. In addition, the effect of nonsynonymous mutations was studied with molecular dynamics simulations. PTEN promoter hypermethylation (45.8%) was found to be significantly associated with the of PTEN loss (57.14%, P < 0.0001). Tumor stages, tumor size, lymph node (LN) were found to be significantly correlated with both PTEN promoter hypermethylation and PTEN loss. Histological grade, however, showed a significant association with only PTEN loss. In total, 11.76% of tumors exhibited mutations in exon 5 and 7, out of which E150K of exon 5 showed the highest deviations in the crystal structure of PTEN by in silico analysis. This study provides valuable insights into oncology and paves the path in the development of efficient biomarker and/or imperative therapeutic tool for cervical cancer treatment.
The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial
Authors: Ahmadi Majid , Hajialilo Mehrzad , Dolati Sanam , Eghbal‐Fard Shadi , Heydarlou Hanieh , Ghaebi Mahnaz , Ghassembaglou Arezou , Aghebati‐Maleki Leili , Samadi Kafil Hossein , Kamrani Amin , Rahnama Badrossadat , Rikhtegar Reza , Yousefi Mehdi
Published: May 2019

Aim

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients.

Methods

Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR‐27, miR‐17, and miR‐146a) and cytokines including Interleukin‐10 (IL‐10), TGF‐β, and IL‐6 were assessed by real‐time polymerase chain reaction. Furthermore, enzyme‐linked immunosorbent assay was done to determine the secretion levels of cytokines.

Results

After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT‐PCR data indicated that the expression of miR‐17 and miR‐27 were significantly decreased following nanocurcumin treatment while miR‐146a and FoxP3 were significantly increased. Moreover, nanocurcumin‐treated group had high levels of IL‐10 and TGF‐β and low levels of IL‐6 production than control group.

Conclusion

The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases.

This study is registered with IRCT.ir, number IRCT2017052927520N7.
The association between IL‐17A and IL‐23R polymorphisms and coronary artery disease risk in a Middle Eastern Chinese population
Authors: Zhao Qiang , Jiang Huaxin , Ma Teng , Qiu Hao , Guo Ming , Zhang Xinghua
Published: May 2019

Background

Polymorphisms in IL‐17A and IL‐23R may affect the expression of these genes and could contribute to a patient's susceptibility to coronary artery disease (CAD). Although this association was investigated by previous studies, the relationship remains unclear.

Method

We conducted this hospital‐based case‐control study to determine whether polymorphisms in these two genes could be associated with a risk of CAD. A total of 191 patients and 131 controls, as determined by SXscore, were enrolled in this study. The genotyping was performed with the Sequenom MassARRAY platform.

Results

The results showed that that the FPG and HbA1C levels were higher in patients with CAD than in the controls. In addition, the HDL and ApoA1 levels were significantly higher in the controls than in the cases. In contrast, the Lp(a) level was significantly lower in the controls than in the patients. The IL‐17A rs2275913 and IL‐23R rs6682925 polymorphisms were associated with an increased risk of CAD (rs2275913: AA vs GG: crude OR = 2.16, 95% CI = 1.08‐4.30; AG/AA vs GG: crude OR = 1.81, 95% CI = 1.04‐3.15; rs6682925 CC vs TT: crude OR = 1.91, 95% CI = 1.00‐3.63). The subgroup analysis by SXscore revealed that the IL‐23R rs6682925 polymorphism (CT/CC vs TT: crude OR = 3.72, 95% CI = 1.19‐11.66) was associated with an increased risk of CAD in patients with a high SXscore.

Conclusion

This study suggested that T2DM, Lp(a), HDL‐c, and ApoA1 were risk factors of CAD and that the IL‐17A rs2275913 and IL‐23R rs6682925 polymorphisms may contribute to susceptibility to CAD.
Leukocytosis in patients with favism and association with blood transfusion
Authors: Faraji‐Goodarzi Mojgan , Taee Nadereh , Bajelan Amir , Safdari Mohammad
Published: May 2019

Introduction

Leukocytosis is a condition marked by abnormal increase in leukocyte count due to an inflammatory response as a defense against most of the infections, or bone tumors; including leukemia. The aim of this study is to analyze the effect of blood transfusion in leukocytosis patients with favism as compared to patients treated with antibiotics or combination of both.

Methods

A total of 97 patients with favism who were referred to the University hospital in 2016‐2017 were studied.

Key findings

These patients experienced acute hemolysis following beans meal. These patients were either treated with blood transfusion, antibiotics or combination of both.

Conclusions

This study shows that blood transfusion is an effective therapeutic option for the treatment of leukocytosis. Antibiotics are not deemed necessary for the treatment and blood transfusion alone, can decrease leukocytes to the normal level.
Comparison of computed tomography‐guided percutaneous needle biopsy and endobronchial biopsy in the diagnosis of multifocal pulmonary lesions
Authors: Li Xiao‐Feng , Zheng Li‐Li , He Yu , Wang Mao‐Shui
Published: May 2019

Background

The retrospective study aimed to compare computed tomography (CT)‐guided percutaneous needle biopsy (PNB) and endobronchial biopsy (EB) in the diagnosis of multifocal pulmonary lesions with endobronchial involvement.

Methods

Between November 2014 and June 2017, consecutive patients who had underwent both CT‐guided PNB and EB via bronchoscopy for diagnosis of pulmonary lesions were evaluated retrospectively. Tissue samples were submitted for pathological examination, acid‐fast bacilli, TB RT‐PCR, and mycobacterial culture. Sensitivities of the two methods alone or in combination were calculated and compared using Fisher's exact test.

Results

Sixty‐seven patients (46 men and 21 women) were enrolled and could be diagnosed (32 malignant, 18 TB, and 17 benign). A final diagnosis of either malignant or TB diseases was made in 34 (68.0%) patients for CT‐guided PNBs, 19 (38.0%) patients for EBs, and 42 (84.0%) patients for the combination of both methods. Further statistical analysis showed significant difference in sensitivity between CT‐guided PNBs, or the combination of both methods, and EBs (all P < 0.05), and no difference between CT‐guided PNBs and the combination (P > 0.05). However, the combination of both methods appears to have the highest sensitivity in the detection of malignancies or TB diseases.

Conclusion

Compared with EB, CT‐guided PNB has a high diagnostic yield for the detection of TB and malignancy in patients with multifocal pulmonary lesions with endobronchial involvement. When the two biopsies are combined, it appears to provide an incremental diagnostic value for the pulmonary lesions.
Rat sinus mucosa‐ and periosteum‐derived exosomes accelerate osteogenesis
Authors: Sun Ruinan , Xu Shuyu , Wang Zuolin
Published: May 2019

Guided bone regeneration (GBR) is commonly used for alveolar bone augmentation. The paracrine mechanism in the field of bone tissue engineering has been emphasized in recent years and exosomes are considered to have the potential of promoting osteogenesis. We aimed to study the influence of sinus mucosa and periosteum on bone regeneration through paracrine stimulation, especially via exosomes, and compare the differences between them. Here, we report that conditioned medium (CM) from sinus mucosa‐derived cells (SMCs) and periosteum‐derived cells (PCs) and the isolated exosomes enhanced the proliferation, migration and osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BM‐MSCs) in vitro. A rat model of femoral bone defects was used to demonstrate that the exosomes derived from SMCs (SMC‐Exos) and PCs (PC‐Exos) can accelerate bone formation in vivo. Furthermore, we present a preliminary discussion of the possible functional components involved in the effects of SMC‐Exos and PC‐Exos on bone regeneration. In conclusion, these results demonstrated that the sinus mucosa and periosteum can accelerate osteogenesis through paracrine effects and the exosomes play important roles in this process.
The cationic cell‐penetrating KT2 peptide promotes cell membrane defects and apoptosis with autophagy inhibition in human HCT 116 colon cancer cells
Authors: Maraming Pornsuda , Klaynongsruang Sompong , Boonsiri Patcharee , Peng Shu‐Fen , Daduang Sakda , Leelayuwat Chanvit , Pientong Chamsai , Chung Jing‐Gung , Daduang Jureerut
Published: May 2019

The anticancer activity of cationic antimicrobial peptides (AMPs) has become more interesting because some AMPs have selective recognition against cancer cells. However, their antitumor properties and underlying mechanisms in cancer cells have not been clearly understood. In this study, we evaluated the effects of KT2 (lysine/tryptophan‐rich AMP) on the cellular uptake and internalization mechanism, cell viability, surface charge of the cell membrane, membrane integrity, apoptotic cell death, and autophagy in human HCT 116 colon cancer cells. We found that KT2 interacted with the cell membrane of HCT 116 cells and was internalized into HCT 116 cells via clathrin‐mediated and caveolae‐mediated endocytosis mechanisms. The interaction of KT2 with cells caused cell membrane structure change, elevated membrane permeability, and KT2 also affected the lipid component. The results of atomic force microscopy showed cellular membrane defects of KT2‐treated cells. The internalized KT2 induced nuclear condensation and apoptotic cell death. It elevated the apoptotic factor levels including those of cytochrome c and apoptosis‐inducing factor. Furthermore, KT2 inhibited autophagy by the suppression of autophagy‐related 5, autophagy‐related 7, autophagy‐related 16 like 1, and Beclin‐1 proteins. In conclusion, these results revealed the cytotoxicity of cationic KT2 against HCT 116 cells and may help to clarify the interactions between cationic AMPs and cancer cells.
Micromixing efficiency in a rotating foam stirrer reactor with various reactor configurations and liquid viscosities
Authors: Yang Yu‐Cheng , Ouyang Yi , Yu Xiao‐Hui , Yu Qing‐Jie , Liu Jing‐Dong , Yang Shi‐Ying , Arowo Moses
Published: May 2019

BACKGROUND

The rotating foam stirrer reactor (RFSR) has shown its high mass transfer efficiency. Nevertheless, its micromixing efficiency, which is one of the significant parameters, still needs more comprehensive study for its better application and optimization. This work therefore employed the iodide–iodate reaction system to analyze the micromixing efficiency in an RFSR, and the effects of reactor configuration and liquid viscosity on micromixing efficiency were investigated.

RESULTS

The results show that high micromixing efficiency can be achieved when the feed location is at the outer edge of the rotor. Solid foam with low pores per linear inch (ppi) and equipping baffles on the reactor wall can also considerably improve the micromixing efficiency. The results further reveal that the micromixing efficiency decreased with increasing liquid viscosity. Micromixing times in an RFSR with various configurations, estimated based on the incorporation model, ranged from 2.1 × 10−4 to 2.0 × 10−2 s. The minimum value is smaller than that of many conventional reactors and is competitive with that of some novel reactors. In addition, a correlation to predict the micromixing time based on the average energy dissipation rate was developed, which agreed well with experimental values.

CONCLUSION

This study indicates that the RFSR has excellent micromixing efficiency and also provides fundamental information for optimization of the RFSR and its application in process industries. © 2019 Society of Chemical Industry
Chemoirradiated neutrophils and T cells differentially affect immune functions of APCs
Authors: Franklin Cindy , Bruderek Kirsten , Schilling Bastian , Brandau Sven
Published: May 2019

Extracorporeal photopheresis (ECP) is known as an immunomodulatory therapy with few side effects, which is mainly used in the treatment of cutaneous T cell lymphoma, graft-versus-host disease, and allograft rejection. During ECP, leukocytes are separated from whole blood by leukapheresis, subsequently chemoirradiated with 8-methoxypsoralen and UVA light, and re-infused into the patient. Although clinically effective, its mode of action has not been fully elucidated. In the present study, we analyzed the interaction of chemoirradiated neutrophils and CD3+ lymphocytes with APC in an in vitro model. We report that chemoirradiated CD3+ T cells induced increased expression of activation markers on dendritic cells (DC), macrophages, and monocytes. Coculture of chemoirradiated CD3+ T cells with these APC also led to significantly increased secretion of TNF-α. Although less pronounced, additional activation of APC took place when APC were stimulated with LPS or IFN-γ. In contrast, chemoirradiated neutrophils did not show activating effects on APC. The presence of chemoirradiated neutrophils during LPS and IFN-γ stimulation of DC rather diminished DC and macrophage activation. In line with these findings DC cocultured with chemoirradiated CD3+ T cells, but not neutrophils, showed significantly increased activation of CD3+ responder lymphocytes in a mixed lymphocyte reaction. With this study, we demonstrate that chemoirradiated leukocytes have differential indirect immunomodulatory effects. Whereas chemoirradiated CD3+ T cells activate APC, chemoirradiated neutrophils suppress activation of APC in the presence of other activating factors, suggesting that the composition of the ECP-treated buffy coat might be of importance for its immunomodulatory effects.
Formation of 3‐hydroxyglutaric acid in glutaric aciduria type I: in vitro participation of medium chain acyl‐CoA dehydrogenase
Authors: Peters Verena , Morath Marina , Mack Matthias , Liesert Michael , Buckel Wolfgang , Hoffmann Georg F. , Vockley Jerry , Ghisla Sandro , Zschocke Johannes
Published: May 2019

3‐Hydroxyglutaric acid (3‐OH‐GA) in urine has been identified as the most reliable diagnostic marker for glutaric aciduria type I (GA I). We showed that hydratation of glutaconyl‐CoA to 3‐hydroxyglutaryl‐CoA, which is subsequently hydrolyzed to 3‐OH‐GA, is efficiently catalyzed by 3‐methylglutaconyl‐CoA hydratase (3‐MGH). We have now investigated whether mitochondrial acyl‐CoA‐dehydrogenases can convert glutaryl‐CoA to glutaconyl‐CoA. Short‐chain acyl‐CoA dehydrogenase (SCAD), medium‐chain acyl‐CoA dehydrogenase (MCAD), and long‐chain acyl‐CoA dehydrogenase (LCAD) accepted glutaryl‐CoA as a substrate. The highest kcat of glutaryl‐CoA was found for MCAD (0.12 ± 0.01 second−1) and was about 26‐fold and 52‐fold higher than those of LCAD and SCAD, respectively. The turnover of MCAD for glutaryl‐CoA was about 1.5% of that of its natural substrate octanoyl‐CoA. Despite high Km (above 600 μM) and low turnover rate, the oxidation of glutaryl‐CoA by MCAD in combination with 3‐MGH could explain the urinary concentration of 3‐OH‐GA in GA I patients.
The genetic and biochemical basis of trimethylaminuria in an Irish cohort
Authors: Doyle Samantha , O'Byrne James J. , Nesbitt Mandy , Murphy Daniel N. , Abidin Zaza , Byrne Niall , Pastores Gregory , Kirk Richard , Treacy Eileen P.
Published: May 2019

Background

Inherited trimethylaminuria (TMAU), a rare genetic disorder of hepatic metabolism of trimethylamine (TMA) causing excessive accumulation of malodorous trimethylamine (TMA), is a socially distressing disorder. Diagnosis is made by biochemical analysis of urine, with the calculation of flavin monooxygenase trimethylamine conversion capacity. Genetic testing, sequencing the entire coding region of the FMO3 gene has been recommended for affected individuals who convert less than 90% of the total TMA load to TMAO.

Methods

Genetic analysis was undertaken for 13 Irish patients with TMAU of varying phenotypic severity (three severe, six moderate, and four mild).

Results

A genetic diagnosis was made for seven patients, including for five of the nine moderate to severely affected cases. We noted the c.913G>T;p.(Glu305*) and c.458C>T;p.(Pro153Leu) mutations in this Irish population with severe TMAU which is consistent with our earlier findings in Australian and North American families of Irish and British descent.

Three individuals were noted to be homozygous for the common variant haplotype c.472G>A;923A>G;p.(Glu158Lys);(Glu308Gly). We also identified three novel variants in this population, which are likely to be pathogenic: c.682G>A;p(Gly228Ser), c.694G>T:p(Asp232Tyr), and c.989G>A;p.(Gly330Glu).

Conclusion

Urinary biochemical analysis probably remains the first line diagnostic approach to classify the various types of TMAU. FMO3 gene analysis is likely only to be informative for certain presentations of TMAU.
A novel missense variant in SLC18A2 causes recessive brain monoamine vesicular transport disease and absent serotonin in platelets
Authors: Padmakumar Manisha , Jaeken Jaak , Ramaekers Vincent , Lagae Lieven , Greene Daniel , Thys Chantal , Van Geet Chris , BioResource NIHR , Stirrups Kathleen , Downes Kate , Turro Ernest , Freson Kathleen
Published: May 2019

Background

Brain monoamine vesicular transport disease is an infantile onset neurodevelopmental disorder caused by variants in SLC18A2, which codes for the vesicular monoamine transporter 2 (VMAT2) protein, involved in the transport of monoamines into synaptic vesicles and of serotonin into platelet dense granules.

Case presentation

The presented case is of a child, born of healthy consanguineous parents, who exhibited hypotonia, mental disability, epilepsy, uncontrolled movements, and gastrointestinal problems. A trial treatment with L‐DOPA proved unsuccessful and the exact neurological involvement could not be discerned due to normal metabolic and brain magnetic resonance imaging results.

Platelet studies and whole genome sequencing were performed. At age 4, the child's platelets showed a mild aggregation and adenosine triphosphate secretion defect that could be explained by dysmorphic dense granules observed by electron microscopy. Interestingly, the dense granules were almost completely depleted of serotonin. A novel homozygous p.P316A missense variant in VMAT2 was detected in the patient and the consanguineous parents were found to be heterozygous for this variant. Although the presence of VMAT2 on platelet dense granules has been demonstrated before, this is the first report of defective platelet dense granule function related to absent serotonin storage in a patient with VMAT2 deficiency but without obvious clinical bleeding problems.

Conclusions

This study illustrates the homology between serotonin metabolism in brain and platelets, suggesting that these blood cells can be model cells for some pathways relevant for neurological diseases. The literature on VMAT2 deficiency is reviewed.
Atmospheric heat sinks over the western Tibetan Plateau associated with snow depth in late spring
Authors: Xiao Zhixiang , Duan Anmin , Wang Ziqian
Published: May 2019

The atmospheric heat source/sink (AHS) and snow cover/depth over the Tibetan Plateau (TP) in late spring play important roles in modulating the evolution of Asian summer monsoons. However, quantitative estimation of the AHS over the TP is still a large challenge because of limited observational data. In this work, both data analyses and numerical simulations from the Weather Research and Forecasting model with an updated daily snow‐depth data set are conducted to explore the intrinsic connection between the AHS and snow depth over the TP in May. Data analyses indicate that only a weak negative relationship exists between snow depth and the AHS over the western TP. On the other hand, despite the overall consistency in the spatial pattern of the AHS between the reanalysis data sets and the Weather Research and Forecasting model, a strong cooling effect (about −14.4 W/m2) appears over the western TP (32°–40°N, 70°–78°E) and the Nyenchen Tanglha Mountains in the simulation, where the altitude is above 4,000 m with thick snow cover. This characteristic is opposite to that observed in reanalysis data sets. Further analysis indicates that the underestimated atmospheric net longwave radiative cooling effect that is associated with snow depth may exaggerate the atmospheric heat source in current reanalysis data sets. Large uncertainties in the AHS still exist in current state‐of‐the‐art reanalysis data sets, especially over the regions of the TP covered by snow.
Ultrasound prostate segmentation based on multidirectional deeply supervised V‐Net
Authors: Lei Yang , Tian Sibo , He Xiuxiu , Wang Tonghe , Wang Bo , Patel Pretesh , Jani Ashesh B. , Mao Hui , Curran Walter J. , Liu Tian , Yang Xiaofeng
Published: May 2019

Purpose

Transrectal ultrasound (TRUS) is a versatile and real‐time imaging modality that is commonly used in image‐guided prostate cancer interventions (e.g., biopsy and brachytherapy). Accurate segmentation of the prostate is key to biopsy needle placement, brachytherapy treatment planning, and motion management. Manual segmentation during these interventions is time‐consuming and subject to inter‐ and intraobserver variation. To address these drawbacks, we aimed to develop a deep learning‐based method which integrates deep supervision into a three‐dimensional (3D) patch‐based V‐Net for prostate segmentation.

Methods and materials

We developed a multidirectional deep‐learning‐based method to automatically segment the prostate for ultrasound‐guided radiation therapy. A 3D supervision mechanism is integrated into the V‐Net stages to deal with the optimization difficulties when training a deep network with limited training data. We combine a binary cross‐entropy (BCE) loss and a batch‐based Dice loss into the stage‐wise hybrid loss function for a deep supervision training. During the segmentation stage, the patches are extracted from the newly acquired ultrasound image as the input of the well‐trained network and the well‐trained network adaptively labels the prostate tissue. The final segmented prostate volume is reconstructed using patch fusion and further refined through a contour refinement processing.

Results

Forty‐four patients' TRUS images were used to test our segmentation method. Our segmentation results were compared with the manually segmented contours (ground truth). The mean prostate volume Dice similarity coefficient (DSC), Hausdorff distance (HD), mean surface distance (MSD), and residual mean surface distance (RMSD) were 0.92 ± 0.03, 3.94 ± 1.55, 0.60 ± 0.23, and 0.90 ± 0.38 mm, respectively.

Conclusion

We developed a novel deeply supervised deep learning‐based approach with reliable contour refinement to automatically segment the TRUS prostate, demonstrated its clinical feasibility, and validated its accuracy compared to manual segmentation. The proposed technique could be a useful tool for diagnostic and therapeutic applications in prostate cancer.
Comparison of planned dose on different CT image sets to four‐dimensional Monte Carlo dose recalculation using the patient's actual breathing trace for lung stereotactic body radiation therapy
Authors: Freislederer Philipp , von Münchow Asmus , Kamp Florian , Heinz Christian , Gerum Sabine , Corradini Stefanie , Söhn Matthias , Reiner Michael , Roeder Falk , Floca Ralf , Alber Markus , Belka Claus , Parodi Katia
Published: May 2019

Purpose

The need for four‐dimensional (4D) treatment planning becomes indispensable when it comes to radiation therapy for moving tumors in the thoracic and abdominal regions. The primary purpose of this study is to combine the actual breathing trace during each individual treatment fraction with the Linac's log file information and Monte Carlo 4D dose calculations. We investigated this workflow on multiple computed tomography (CT) datasets in a clinical environment for stereotactic body radiation therapy (SBRT) treatment planning.

Methods

We have developed a workflow, which allows us to recalculate absorbed dose to a 4DCT dataset using Monte Carlo calculation methods and accumulate all 4D doses in order to compare them to the planned dose using the Linac's log file, a 4DCT dataset, and the patient's actual breathing curve for each individual fraction. For five lung patients, three‐dimensional‐conformal radiation therapy (3D‐CRT) and volumetric modulated arc treatment (VMAT) treatment plans were generated on four different CT image datasets: a native free‐breathing 3DCT, an average intensity projection (AIP) and a maximum intensity projection (MIP) CT both obtained from a 4DCT, and a 3DCT with density overrides based on the 3DCT (DO). The Monte Carlo 4D dose has been calculated on each 4DCT phase using the Linac's log file and the patient's breathing trace as a surrogate for tumor motion and dose was accumulated to the gross tumor volume (GTV) at the 50% breathing phase (end of exhale) using deformable image registration.

Results

and between 4D dose and planned dose differed largely for 3DCT‐based planning and also for DO in three patients. Least dose differences between planned and recalculated dose have been found for AIP and MIP treatment planning which both tend to be superior to DO, but the results indicate a dependency on the breathing variability, tumor motion, and size. An interplay effect has not been observed in the small patient cohort.

Conclusions

We have developed a workflow which, to our best knowledge, is the first incorporation of the patient breathing trace over the course of all individual treatment fractions with the Linac's log file information and 4D Monte Carlo recalculations of the actual treated dose. Due to the small patient cohort, no clear recommendation on which CT can be used for SBRT treatment planning can be given, but the developed workflow, after adaption for clinical use, could be used to enhance a priori 4D Monte Carlo treatment planning in the future and help with the decision on which CT dataset treatment planning should be carried out.
Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition Consensus Malnutrition Characteristics: Usability and Association With Outcomes
Authors: Mogensen Kris M. , Malone Ainsley , Becker Patricia , Cutrell Stephanie , Frank Laura , Gonzales Kelly , Hudson Lauren , Miller Sarah , Guenter Peggi ,   Malnutrition Committee of the American Society for Parenteral and Enteral Nutrition (ASPEN)
Published: May 2019

Malnutrition has been documented in approximately one‐third of patients in developed countries on hospital admission and is associated with negative clinical outcomes. The need to identify and intervene in at‐risk patients is critical to minimize these negative outcomes. A consensus approach for diagnosing and documenting malnutrition in hospitalized adult and pediatric patients was published jointly by the Academy of Nutrition and Dietetics (Academy) and the American Society for Parenteral and Enteral Nutrition (ASPEN) in 2012 and 2014, respectively. The purpose of this paper is to review the available literature on the usability, feasibility, validity, and reliability of both the adult and pediatric consensus malnutrition diagnostic approaches, as well as to evaluate their use in studying clinical outcomes. In adults, abstracts and published studies have shown the diagnostic tool is a usable, feasible, and reliable method for the identification of severe and non‐severe or moderate malnutrition. In pediatrics, only 1 published study to date used the pediatric malnutrition indicators, indicating the need to demonstrate that the tool is feasible, valid, and reliable. Both the adult and pediatric tools have shown significant correlation with negative clinical outcomes in malnourished patients, including increased mortality, increased hospital length of stay (adults), increased complications (pediatrics), and increased hospital readmissions. Further large‐scale studies are needed to evaluate the feasibility, usability, validity, and reliability of both the adult and pediatric malnutrition diagnostic approaches.
Spontaneous Restoration of Nutrition Autonomy in a Case of Intestinal Failure Secondary to a Gastrointestinal Neuromuscular Disease
Authors: McCulloch Adam , Malhi Hardip , Parkinson Sharmalie , Martin Joanne E. , Cooper Sheldon C.
Published: May 2019

Polyglucosan inclusion body myopathy (PIBM) is a recently described gastrointestinal neuromuscular disease. Given its rarity, very little is known of its natural history and prognosis. In this case report, we present the first case of PIBM and resultant intestinal failure in which, following 7 years of home parenteral nutrition, gastrointestinal symptoms subsided and nutrition autonomy was restored.
Using a vibratory source at Mt. Etna (Italy) to investigate the wavefield polarization at Pernicana Fault
Authors: Di Giulio Giuseppe , Punzo Michele , Bruno Pier Paolo , Cara Fabrizio , Rovelli Antonio
Published: May 2019

The paper presents the results of a controlled‐source seismic experiment performed using a vibratory source capable of producing harmonic vibrations. The survey aimed at investigating the horizontal directional amplification mechanism observed at the Pernicana Fault (Mt. Etna in Sicily, Italy) along an N150°/N330° orientation. With the vibratory source (a shaker truck) working in shear‐wave mode in the frequency range 5–40 Hz, we recorded seismic data using both three‐component velocimeters and 4.5 Hz geophones. These two types of receivers were arranged in linear configuration along two orthogonal orientations: radial and transverse to the direction of the main polarization observed within the fault zone. The two lines of seismic stations allowed us to investigate the polarization evolution as a function of the distance from the source. Results show that when the shear excitation induced by the source is parallel to the direction of observed polarization of the ground motion, the seismic signal propagates efficiently, maintaining the same horizontal polarization induced by the active source. This polarization is well recorded up to distances as large as 300 m from the source. On the contrary, when the shear excitation is orthogonal to the predominant site polarization, the ground excitation loses its initial polarization in less than 50 m away from the source position. At larger distances, the transmitted energy propagates with the natural site polarization independently from the original source polarization. The observations in terms of polarization were combined with surface‐wave analysis, aimed at investigating the dispersion characteristics of the wavefield on the geophone lines. The data suggest that the experimental Rayleigh‐wave dispersion spectra show a more coherent signal over the frequency range along the same orientation of the observed site polarization, supporting a preferential direction in the propagation of surface waves. From inversion of the Rayleigh dispersion curves, we inferred the shear‐wave velocity (Vs) to be in the range of 120–450 m/s in the first 30 m deep of Quaternary volcanic sediments. The dispersion curves are not constant along transverse and radial directions, suggesting the presence of fracture‐induced seismic anisotropy in the near surface.
Policy entrepreneurship in developing countries: A systematic review of the literature
Authors: Frisch Aviram Neomi , Cohen Nissim , Beeri Itai
Published: May 2019

What can be learned from two decades of studies on policy entrepreneurship in developing countries? Policy entrepreneurship is a rapidly evolving analytical concept. A growing number of studies exploring public policy in developing countries use policy entrepreneurship as an explanatory theoretical concept. However, a substantial part of this research relies on qualitative case study analysis, lacking a comprehensive overview of the concept of policy entrepreneurship. This paper conducts a systematic review of the literature on policy entrepreneurship in developing countries. A total of 47 papers addressing policy entrepreneurship in the developing world, published between 1993 and 2017, have been analysed. The purpose and contribution of this paper are to offer a clearer picture of policy entrepreneurship in the developing world by concentrating on two aspects. First, we describe the characteristics of the studies on policy entrepreneurship in the developing world. Second, we analyse such studies, identifying the lessons that can be drawn on the phenomenon of policy entrepreneurship in the developing world. We conclude with an agenda for future studies, examining new theoretical, methodological, and empirical opportunities to advance the understanding of policy entrepreneurship in developing countries.
Microcellular antibacterial polylactide‐based systems prepared by additive extrusion with ALUM
Authors: Amini Moghaddam Maliheh , Stloukal Petr , Kucharczyk Pavel , Tow‐Swiatek Aneta , Garbacz Tomasz , Pummerova Martina , Klepka Tomasz , Sedlařík Vladimír
Published: May 2019

This work investigates preparation by extrusion of microcellular antimicrobial polylactide (PLA) with an additive, the latter comprising 1% potassium aluminum sulfate dodecahydrate (ALUM), and 3% or 5% of a mixture of sodium hydrogen carbonate and sodium dihydrogen phosphate (1:1). Study was made as to the properties of the materials, their hydrolysis, release profiles, and antimicrobial properties in comparison with the pure polymer. Measuring the molecular weight of samples by gel permeation chromatography revealed that, during thermal processing, the molecular weight of the PLA prepared with additives mentiond above had reduced by approximately 43%. A mechanical test confirmed a decline in mechanical properties after processing as compared with the pure PLA. Release of the antimicrobial compound and the subsequent antimicrobial activity against Staphylococcus aureus and Escherichia coli was evaluated according to ISO 22196:2007. The release of ALUM from the microcellular specimens took place in two steps. During the first 10 days, the rate of release was extremely high in contrast with the remaining period. However, the release rate of the nonporous sample was seen to equal less than 1% in the first 10 days, a phenomenon probably arising through its less active surface.