bluuebunny/crossref_metadata_2025 huggingface dataset:
Correction to: Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential
Authors: Gupta Sonal , Khan Juveria , Kumari Priti , Narayana Chintam , Ayana R. , Chakrabarti Malabika , Sagar Ram , Singh Shailja
Published: March 2020

Please note, following publication of the original article [1], the authors have advised of three errors that are present in the published article.
Epigenetic modulations of noncoding RNA: a novel dimension of Cancer biology
Authors: Yang Xiao , Liu Ming , Li Mengmeng , Zhang Sen , Hiju Hong , Sun Jing , Mao Zhihai , Zheng Minhua , Feng Bo
Published: March 2020

Empowered by recent advances of sequencing techniques, transcriptome-wide studies have characterized over 150 different types of post-transcriptional chemical modifications of RNA, ranging from methylations of single base to complex installing reactions catalyzed by coordinated actions of multiple modification enzymes. These modifications have been shown to regulate the function and fate of RNAs and further affecting various cellular events. However, the current understanding of their biological functions in human diseases, especially in cancers, is still limited. Once regarded as “junk” or “noise” of the transcriptome, noncoding RNA (ncRNA) has been proved to be involved in a plethora of cellular signaling pathways especially those regulating cancer initiation and progression. Accumulating evidence has demonstrated that ncRNAs manipulate multiple phenotypes of cancer cells including proliferation, metastasis and chemoresistance and may become promising biomarkers and targets for diagnosis and treatment of cancer. Importantly, recent studies have mapped plenty of modified residues in ncRNA transcripts, indicating the existence of epigenetic modulation of ncRNAs and the potential effects of RNA modulation on cancer progression. In this review, we briefly introduced the characteristics of several main epigenetic marks on ncRNAs and summarized their consecutive effects on cancer cells. We found that ncRNAs could act both as regulators and targets of epigenetic enzymes, which indicated a cross-regulating network in cancer cells and unveil a novel dimension of cancer biology. Moreover, by epitomizing the knowledge of RNA epigenetics, our work may pave the way for the design of patient-tailored therapeutics of cancers.
Effects of endothelial progenitor cells transplantation on hyperlipidemia associated kidney damage in ApoE knockout mouse model
Authors: Gong Piyun , Zhang Zhongwen , Zhang Dongmei , Zou Zhiwei , Zhang Qian , Ma Huimei , Li Jingxiu , Liao Lin , Dong Jianjun
Published: March 2020

Background

Hyperlipidaemia causes kidney damage over the long term. We investigated the effect of the administration of endothelial progenitor cells (EPCs) on the progression of kidney damage in a mouse model of hyperlipidaemia.

Methods

Apolipoprotein E-knockout (ApoE−/−) mice were treated with a high-cholesterol diet after spleen resection. Twenty-four weeks later, the mice were divided into two groups and intravenously injected with PBS or EPCs. Six weeks later, the recruitment of EPCs to the kidney was monitored by immunofluorescence. The lipid, endothelial cell, and collagen contents in the kidney were evaluated by specific immunostaining. The protein expression levels of transforming growth factor-β (TGF-β), Smad2/3, and phospho-Smad3 (p-smad3) were detected by western blot analysis.

Results

ApoE−/−mice treated with a high-fat diet demonstrated glomerular lipid deposition, enlargement of the glomerular mesangial matrix, endothelial cell enlargement accompanied by vacuolar degeneration and an area of interstitial collagen in the kidney. Six weeks after EPC treatment, only a few EPCs were detected in the kidney tissues of ApoE−/−mice, mainly in the kidney interstitial area. No significant differences in TGF-β, p-smad3 or smad2/3 expression were found between the PBS group and the EPC treatment group (TGF-β expression, PBS group: 1.06 ± 0.09, EPC treatment group: 1.09 ± 0.17,P = 0.787; p-smad3/smad2/3 expression: PBS group: 1.11 ± 0.41, EPC treatment group: 1.05 ± 0.33,P = 0.861).

Conclusions

Our findings demonstrate that hyperlipidaemia causes basement membrane thickening, glomerulosclerosis and the vascular degeneration of endothelial cells. The long-term administration of EPCs substantially has limited effect in the progression of kidney damage in a mouse model of hyperlipidaemia.
Multivariate multilevel modeling of quality of life dynamics of HIV infected patients
Authors: Dessie Zelalem G. , Zewotir Temesgen , Mwambi Henry , North Delia
Published: March 2020

Background

Longitudinal quality of life (QoL) is an important outcome in many chronic illness studies aiming to evaluate the efficiency of care both at the patient and health system level. Although many QoL studies involve multiple correlated hierarchical outcome measures, very few of them use multivariate modeling. In this work, we modeled the long-term dynamics of QoL scores accounting for the correlation between the QoL scores in a multilevel multivariate framework and to compare the effects of covariates across the outcomes.

Methods

The data is from an ongoing prospective cohort study conducted amongst adult women who were HIV-infected and on the treatment in Kwazulu-Natal, South Africa. Independent and related QoL outcome multivariate multilevel models were presented and compared.

Results

The analysis showed that related outcome multivariate multilevel models fit better for our data used. Our analyses also revealed that higher educational levels, middle age, stable sex partners and higher weights had a significant effect on better improvements in the rate of change of QoL scores of HIV infected patients. Similarly, patients without TB co-infection, without thrombocytopenia, with lower viral load, with higher CD4 cell count levels, with higher electrolytes component score, with higher red blood cell (RBC) component score and with lower liver abnormality component score, were associated with significantly improved the rate of change of QoL, amongst HIV infected patients.

Conclusion

It is hoped that the article will help applied researchers to familiarize themselves with the models and including interpretation of results. Furthermore, three issues are highlighted: model building of multivariate multilevel outcomes, how this model can be used to assess multivariate assumptions, involving fixed effects (for example, to examine the size of the covariate effect varying across QoL domain scores) and random effects (for example, to examine the rate of change in one response variable associated to changes in the other).
Patients with stage IV epithelial ovarian cancer: understanding the determinants of survival
Authors:   For the Groupe de Recherche FRANCOGYN, Dabi Yohann , Huchon Cyrille , Ouldamer Lobna , Bendifallah Sofiane , Collinet Pierre , Bricou Alexandre , Daraï Emile , Ballester Marcos , Lavoue Vincent , Haddad Bassam , Touboul Cyril
Published: March 2020

Background

The most appropriate management for patients with stage IV ovarian cancer remains unclear. Our objective was to understand the main determinants associated with survival and to discuss best surgical management.

Methods

Data of 1038 patients with confirmed ovarian cancer treated between 1996 and 2016 were extracted from maintained databases of 7 French referral gynecologic oncology institutions. Patients with stage IV diseases were selected for further analysis. The Kaplan–Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariable analysis, was used to account for the influence of multiple variables.

Results

Two hundred and eight patients met our inclusion criteria: 65 (31.3%) never underwent debulking surgery, 52 (25%) underwent primary debulking surgery (PDS) and 91 (43.8%) neoadjuvant chemotherapy and interval debulking surgery (NACT-IDS). Patients not operated had a significantly worse overall survival than patients that underwent PDS or NACT–IDS (p < 0.001). In multivariable analysis, three factors were independent predictors of survival: upfront surgery (HR 0.32 95% CI 0.14–0.71, p = 0.005), postoperative residual disease = 0 (HR 0.37 95% CI 0.18–0.75, p = 0.006) and association of Carboplatin and Paclitaxel regimen (HR 0.45 95% CI 0.25–0.80, p = 0.007).

Conclusions

Presence of distant metastases should not refrain surgeons from performing radical procedures, whenever the patient is able to tolerate. Maximal surgical efforts should be done to minimize residual disease as it is the main determinant of survival.
Thyroid V50 is a risk factor for hypothyroidism in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a retrospective study
Authors: Zhou Ling , Chen Jia , Shen Wei , Chen Zheng-Lu , Huang Shuang , Tao Chang-Juan , Chen Ming , Yu Zhong-Hua , Chen Yuan-Yuan
Published: March 2020

Background

We investigated the risk factors of radiation-induced thyroid dysfunction, then combined the clinical factors and optimum thyroid dosimetric parameters to predict the incidence rate of hypothyroidism (HT) and to guide individualized treatment.

Methods

A total of 206 patients with histologically proven nasopharyngeal carcinoma (NPC) treated at the Cancer Hospital of the University of Chinese Academy of Sciences between January 2015 and August 2018 were included. Dose–volume histogram (DVH) data, including mean dose, absolute volume, V20, V25, V30, V35, V40, V45, V50, V55, and V60 were extracted and used as dosimetric parameters. A logistic regression analysis model was built to identify predictors related to HT occurring within 2 years.

Results

Sex, N stage, thyroid volume, mean thyroid dose, and thyroid V20 and V50 were significantly different between patients with and without HT. Logistic regression analysis showed that N stage, thyroid volume, and thyroid V50 were independent predictors of HT. The radiosensitivity of the thyroid decreased as the thyroid volume increased. Patients with N stage > 1 had significantly higher HT incidence (37.38%) than patients with N stage ≤1 (13.11%). The incidence of HT was 54.55% in patients with thyroid V50 > 24% and was 34.15% in patients with thyroid V50 ≤ 24%.

Conclusions

The incidence of HT is significantly associated with N stage, thyroid volume, and thyroid V50. More attention should be paid to patients with NPC with thyroid volume ≤ 12.82 cm3 and advanced N stage disease.
Prevention and early intervention in youth mental health: is it time for a multidisciplinary and trans-diagnostic model for care?
Authors: Colizzi Marco , Lasalvia Antonio , Ruggeri Mirella
Published: March 2020

Background

Similar to other health care sectors, mental health has moved towards the secondary prevention, with the effort to detect and treat mental disorders as early as possible. However, converging evidence sheds new light on the potential of primary preventive and promotion strategies for mental health of young people. We aimed to reappraise such evidence.

Methods

We reviewed the current state of knowledge on delivering promotion and preventive interventions addressing youth mental health.

Results

Half of all mental disorders start by 14 years and are usually preceded by non-specific psychosocial disturbances potentially evolving in any major mental disorder and accounting for 45% of the global burden of disease across the 0–25 age span. While some action has been taken to promote the implementation of services dedicated to young people, mental health needs during this critical period are still largely unmet. This urges redesigning preventive strategies in a youth-focused multidisciplinary and trans-diagnostic framework which might early modify possible psychopathological trajectories.

Conclusions

Evidence suggests that it would be unrealistic to consider promotion and prevention in mental health responsibility of mental health professionals alone. Integrated and multidisciplinary services are needed to increase the range of possible interventions and limit the risk of poor long-term outcome, with also potential benefits in terms of healthcare system costs. However, mental health professionals have the scientific, ethical, and moral responsibility to indicate the direction to all social, political, and other health care bodies involved in the process of meeting mental health needs during youth years.
Copy number variations associated with fetal congenital kidney malformations
Authors: Cai Meiying , Lin Na , Su Linjuan , Wu Xiaoqing , Xie Xiaorui , Li Ying , Chen Xuemei , Lin Yuan , Huang Hailong , Xu Liangpu
Published: March 2020

Background

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20–30% of all congenital malformations. Within the CAKUT phenotypic spectrum, renal hypodysplasia (RHD) is particularly severe. This study aimed to evaluate the applicability of single-nucleotide polymorphism (SNP) array test in prenatal diagnosis of RHD for improving prenatal genetic counseling and to search for evidence of a possible causative role of copy-number variations (CNVs) in RHD.

Results

We performed a systematic survey of CNV burden in 120 fetuses with RHD: 103 cases were isolated RHD and 17 were non-isolated RHD. Single-nucleotide polymorphism (SNP) array test was performed using the Affymetrix CytoScan HD platform. All annotated CNVs were validated by fluorescence in situ hybridization. We identified abnormal CNVs in 15 (12.5%) cases of RHD; of these CNVs, 11 were pathogenic and 4 were variants of uncertain significance. The detection rate of abnormal CNVs in non-isolated RHD was higher (29.4%, 5/17) than that in isolated RHD (9.7%, 10/103) (P = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test.

Conclusions

The variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases.
Correction to: Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer
Authors: Zheng Shaoquan , Yang Lu , Zou Yutian , Liang Jie-ying , Liu Peng , Gao Guanfeng , Yang Anli , Tang Hailin , Xie Xiaoming
Published: March 2020

The original article [1] contains an error in Fig. 5b whereby two panels have been mistakenly duplicated. The correct version of Fig. 5b can be viewed ahead alongside the rest of Fig. 5.
Monitoring Patient Respiratory Effort During Mechanical Ventilation: Lung and Diaphragm-Protective Ventilation
Authors: Bertoni Michele , Spadaro Savino , Goligher Ewan C.
Published: March 2020

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Heterogeneity of Cardiovascular Response to Standardized Sepsis Resuscitation
Authors: Guarracino Fabio , Bertini Pietro , Pinsky Michael R.
Published: March 2020

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Artificial Intelligence in the Intensive Care Unit
Authors: Gutierrez Guillermo
Published: March 2020

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
An international, Delphi consensus study to identify priorities for methodological research in behavioral trials in health research
Authors: Byrne Molly , McSharry Jenny , Meade Oonagh , Lavoie Kim L. , Bacon Simon L.
Published: March 2020

Background

Non-communicable chronic diseases are linked to behavioral risk factors (including smoking, poor diet and physical inactivity), so effective behavior change interventions are needed to improve population health. However, uptake and impact of these interventions is limited by methodological challenges. We aimed to identify and achieve consensus on priorities for methodological research in behavioral trials in health research among an international behavioral science community.

Methods

An international, Delphi consensus study was conducted. Fifteen core members of the International Behavioral Trials Network (IBTN) were invited to generate methodological items that they consider important. From these, the research team agreed a “long-list” of unique items. Two online surveys were administered to IBTN members (N = 306). Respondents rated the importance of items on a 9-point scale, and ranked their “top-five” priorities. In the second survey, respondents received feedback on others’ responses, before rerating items and re-selecting their top five.

Results

Nine experts generated 144 items, which were condensed to a long-list of 33 items. The four most highly endorsed items, in both surveys 1 (n = 77) and 2 (n = 57), came from two thematic categories:“Intervention development” (“Specifying intervention components” and “Tailoring interventions to specific populations and contexts”) and “Implementation” (“How to disseminate behavioral trial research findings to increase implementation” and “Methods for ensuring that behavioral interventions are implementable into practice and policy”). “Development of novel research designs to test behavioral interventions” also emerged as a highly ranked research priority.

Conclusions

From a wide array of identified methodological issues, intervention development, implementation and novel research designs are key themes to drive the future behavioral trials’ research agenda. Funding bodies should prioritize these issues in resource allocation.
Effects of temperature and shear on the structural, thermal and pasting properties of different potato flour
Authors: Zhang Ke , Tian Yang , Liu Chenglong , Xue Wentong
Published: March 2020

Background

The properties of potato flour will be different due to different processing parameters, which will affect their processing adaptability. In this paper, different potato flour were investigated to determine viscoelastic properties and structural transformation using thermodynamics, rheological and spectrum methods. Potato flour was prepared by drying at different temperature after soaking in citric acid, microwave and steamed respectively. The treated samples were dried by hot air and then compared with the freeze-dried potato flour. Four kinds of potato flour showed different properties after shearing at high temperature.

Results

Differential scanning calorimetry (DSC) results revealed that potato flour with low gelatinization had lower enthalpy and faster melting process than freeze-dried potato powder. RVA and texture results showed that potato flour with low gelatinization had the best retrogradation property and the stable gel. X-ray diffraction (XRD) patterns revealed that the crystalline properties of different potato flour after shearing at high temperature were the same. In addition, low gelatinization potato flour presented a crystalline structure or strong internal order. Fourier-transform infrared spectroscopy (FTIR) spectra showed that high temperature and shearing mainly caused δ-deformation of O–H in intact potato granules.

Conclusion

Freeze drying and hot air drying at low temperature made potato flour had better gel stability than microwave and steamed treatment. Hot air drying at low temperature made potato flour had good retrogradation after hot shearing, which was more conducive to the formation of hot-processed products.
Spondyloarthritis Research Consortium of Canada sacroiliac joint inflammation and structural scores: change score reliability and recalibration utility in children
Authors: Weiss Pamela F. , Maksymowych Walter P. , Xiao Rui , Biko David M. , Francavilla Michael L. , Lambert Robert G. , Jaremko Jacob L. , Heshin-Bekenstein Merav , Brandon Timothy G. , Chauvin Nancy A.
Published: March 2020

Background

The SPARCC sacroiliac joint inflammation (SIS) and structural (SSS) scores are reliable measures to quantify abnormalities in the pediatric sacroiliac joint. We aimed to evaluate the utility of online calibration modules for the SIS and SSS and the reliability of their component change scores.

Methods

Change score reliability of 6 raters was assessed by overall and pairwise intraclass correlation coefficients (ICCs) before and after the use of real-time iterative calibration (RETIC) modules for both the SIS and SSS comprised of 20 adult cases. Acceptable ICC for change scores was > 0.7 for SIS and > 0.5 for all SSS components. Sensitivity to change was assessed by the standardized response mean (SRM).

Results

In scoring exercise 1, the SIS had acceptable reliability with a change score ICC of 0.80 and sclerosis was the only SSS lesion that met the acceptability threshold with a change score ICC of 0.52. After RETIC calibration, the SIS overall (ICC = 0.83) and mean pairwise (ICC = 0.83) change scores remained reliable with a large SRM (0.90). All SSS components except sclerosis met the overall and mean pairwise change score ICC acceptability thresholds—backfill: overall = 0.54, mean pairwise = 0.50; fat metaplasia: overall = 0.65, mean pairwise = 0.57; erosion: overall = 0.60, mean pairwise = 0.58; and ankylosis: overall = 0.96, mean pairwise = 0.96. The SSS RETIC module augmented the number of SSS components surpassing the acceptability threshold from 1 to 4. Sensitivity to change, as measured by the SRM, was large for erosion (0.96), moderate for backfill (0.55) and sclerosis (0.70), and small for fat metaplasia (0.36) and ankylosis (0.28).

Conclusion

RETIC modules improved the overall reliability of SPARCC SIS and SSS change scores for previously calibrated raters. SIS recalibration was not as helpful to the most experienced raters who achieved high levels of agreement before recalibration. The SPARCC SIS and all SSS components except sclerosis are reliable measures to quantify change over time in children. A pediatric-specific RETIC tool should be developed to enhance the calibration of readers.
ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis—a EUSTAR analysis
Authors:   on behalf of EUSTAR collaborators, Bütikofer Lukas , Varisco Pierre A. , Distler O. , Kowal-Bielecka O. , Allanore Y. , Riemekasten G. , Villiger P. M. , Adler S.
Published: March 2020

Objectives

To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR).

Methods

SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC).

Results

Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29–3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32–2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC—mostly in daily dosages below 15 mg of prednisolone—did not influence the hazard for SRC.

Conclusions

ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.
AST/ALT ratio predicts the functional severity of chronic heart failure with reduced left ventricular ejection fraction
Authors: Ewid Mohammed , Sherif Hossam , Allihimy Abdulaziz S. , Alharbi Shaima A. , Aldrewesh Dawood A. , Alkuraydis Sarah A. , Abazid Rami
Published: March 2020

Objective

Despite previous research that focused on liver transaminases as predictors of cardiovascular disease, there has been limited research evaluating the predictive value of AST/ALT ratio in patients with heart failure. We aimed to investigate AST/ALT ratio as an indicator of the functional severity in chronic heart failure with reduced left ventricular ejection fraction.

Results

Overall, 105 patients previously diagnosed with HFrEF from Buraidah-Al Qassim province, Saudi Arabia were included in this retrospective cross-sectional study. Data on study variables, including demographic data, left ventricular ejection fraction, NYHA class, and AST/ALT ratio, were collected from patients’ records. The patients were divided into two groups, namely group-1 (AST/ALT ratio < 1) and group-2 (AST/ALT ratio ≥ 1), to identify any differences in their cardiac function profiles. NYHA class and NT-proBNP were higher and LVEF was lower in group-2 than in group-1. We found a mild significant correlation between AST/ALT ratio and APRI, FIB-4 score, NYHA-class, and LVEF (r = 0.2, 0.25, 0.26, and − 0.24, respectively; P < 0.05). Multivariate linear regression analysis model and ROC curve showed that AST/ALT ratio could independently predict HFrEF functional severity with a best cut-off value of 0.9, sensitivity of 43.6%, and specificity of 81.4%.
Exosomes derived from human umbilical cord mesenchymal stem cells inhibit vein graft intimal hyperplasia and accelerate reendothelialization by enhancing endothelial function
Authors: Qu Qingxi , Pang Yingxin , Zhang Chunmei , Liu Linghong , Bi Yanwen
Published: March 2020

Background

In our previous research, we found that mesenchymal stem cell (MSC) transplantation therapy can inhibit intimal hyperplasia and enhance endothelial function in arterialized vein grafts in rats. However, whether MSC-derived exosomes (MSC-exosomes) can reduce neointimal formation and its possible mechanism is still unclear.

Methods

The primary human umbilical cord MSCs (hucMSCs) and human umbilical vein endothelial cells (HUVECs) were isolated and characterized by flow cytometry and immunofluorescence. The exosomes derived from hucMSCs (hucMSC-exosomes) were identified by transmission electron microscopy and western blots. hucMSC-exosomes were intravenously injected into a rat model of vein grafting, and its effect on vein grafts reendothelialization and intimal hyperplasia was assessed by physical, histological, immunohistochemistry, and immunofluorescence examinations. The effects of hucMSC-exosomes on endothelial cells were evaluated by integrated experiment, EdU staining, scratch assay, and Transwell assay. The expression levels of key gene and pathways associated with the biological activity of vascular endothelial cells were evaluated following the stimulation of hucMSC-exosomes.

Results

We successfully isolated and characterized primary hucMSCs and hucMSC-exosomes and primary HUVECs. We verified that the systemic administration of hucMSC-exosomes accelerates reendothelialization and decreases intimal hyperplasia of autologous vein graft in a rat model. We also identified that hucMSC-exosomes can be uptaken by endothelial cells to stimulate cell proliferative and migratory activity in vitro. Furthermore, we detected that vascular endothelial growth factor (VEGF) plays an important part in hucMSC-exosome-mediated proliferation and migration in HUVECs. In addition, we also provided evidence that the signalling pathways of PI3K/AKT and MAPK/ERK1/2 take part in hucMSC-exosome-induced VEGF regulation.

Conclusion

Our data suggest that hucMSC-exosomes exert a vasculoprotective role in the setting of vein graft disease, which may provide a new clue to protect against vein graft failure in the future.
Kinetic analysis of HER2-binding ABY-025 Affibody molecule using dynamic PET in patients with metastatic breast cancer
Authors: Alhuseinalkhudhur Ali , Lubberink Mark , Lindman Henrik , Tolmachev Vladimir , Frejd Fredrik Y. , Feldwisch Joachim , Velikyan Irina , Sörensen Jens
Published: March 2020

Background

High expression of human epidermal growth factor receptor type 2 (HER2) represents an aggressive subtype of breast cancer. Anti-HER2 treatment requires a theragnostic approach wherein sufficiently high receptor expression in biopsy material is mandatory. Heterogeneity and discordance of HER2 expression between primary tumour and metastases, as well as within a lesion, present a complication for the treatment and require multiple biopsies. Molecular imaging using the HER2-targeting Affibody peptide ABY-025 radiolabelled with68Ga-gallium for PET/CT is currently under investigation as a non-invasive tool for whole-body evaluation of metastatic HER2 expression. Initial studies demonstrated a high correlation between68Ga-ABY-025 standardized uptake values (SUVs) and histopathology. However, detecting small liver lesions might be compromised by high background uptake. This study aimed to explore the applicability of kinetic modelling and parametric image analysis for absolute quantification of68Ga-ABY-025 uptake and HER2-receptor expression and how that relates to static SUVs.

Methods

Dynamic68Ga-ABY-025 PET of the upper abdomen was performed 0-45 min post-injection in 16 patients with metastatic breast cancer. Five patients underwent two examinations to test reproducibility. Parametric images of tracer delivery (K1) and irreversible binding (Ki) were created with an irreversible two-tissue compartment model and Patlak graphical analysis using an image-derived input function from the descending aorta. A volume of interest (VOI)-based analysis was performed to validate parametric images. SUVs were calculated from 2 h and 4 h post-injection static whole-body images and compared toKi.

Results

Characterization of HER2 expression in smaller liver metastases was improved using parametric images.Kivalues from parametric images agreed very well with VOI-based gold standard (R2> 0.99,p< 0.001). SUVs of metastases at 2 h and 4 h post-injection were highly correlated withKivalues from both the two-tissue compartment model and Patlak method (R2= 0.87 and 0.95, bothp< 0.001).68Ga-ABY-025 PET yielded high test-retest reliability (relative repeatability coefficient for Patlak 30% and for the two-tissue compartment model 47%).

Conclusion

68Ga-ABY-025 binding in HER2-positive metastases was well characterized by irreversible two-tissue compartment model whereinKihighly correlated with SUVs at 2 and 4 h. Dynamic scanning with parametric image formation can be used to evaluate metastatic HER2 expression accurately.
Correction to: Does the EVA valuation model explain the market value of equity better under changing required return than constant required return?
Authors: Behera Sujata
Published: March 2020

After publication of this article [1], it is reported this article contained an error in the section ‘Risk-free return (rf)’
After the refugee crisis: public discourse and policy change in Denmark, Norway and Sweden
Authors: Hagelund Anniken
Published: March 2020

The refugee crisis of 2015 can be characterised as an exogenous shock, an immigration shock, which according to institutional theory may create a window of opportunity for path-breaking policy change. In all three Scandinavian countries a range of new policy proposals were made in order to stem the incoming migration. Although the direction of policy change pointed in a similar restrictive direction, the choice of policy instruments differed, as did the style and content of policy actors’ legitimizing and coordinating discourses.

Drawing on the analytical framework of discursive institutionalism, the three cases illustrate how a similar kind of external shock (the refugee crisis) was construed differently in different national public spheres, and generated different kinds of policy responses – in particular with respect to the social rights of refugees. The emphasis on legitimizing communicative discourse and coordinating discourse differed between the countries. In Sweden, the need to legitimize policy change normatively was acute. This mattered less in Denmark, where emphasis was on creating stable political support for a range of specific measures. Norway takes a mixed position between the two. Data includes a selection of media texts from six newspapers in 2015 as well as policy texts from 2015 and 2016.
Solubility, pH change, and calcium ion release of low solubility endodontic mineral trioxide aggregate
Authors: Galal Manar , Zaki Dalia Y. , Rabie Mohamed I. , El-Shereif Samia M. , Hamdy Tamer M.
Published: March 2020

Background

Insolubility is the main requirement for ideal root end filling material to provide perfect sealing ability. Moreover, alkalinity and bioactivity provide great chance for tissues healing and remineralization. So, the aim of this work was to evaluate the chemical composition, solubility, pH change, and calcium ion release of recently introduced commercial mineral trioxide aggregate (MTA) endodontic repair cement (Harvard, Universal HandMix MTA) compared with ProRoot MTA repair material.

Methods

Solubility was evaluated after 7- and 14-day immersion time of specimens in phosphate buffer saline solution (PBS); the mean weight loss was evaluated and solubility was calculated as a percentage of the weight loss. For assessment of pH change and calcium ion release polyethylene tubes filled with the materials were soaked in distilled water for 7 and 14 days. Measurement of pH change was done by analytical pH meter. Concentrations of calcium ion release were measured using inductively coupled plasma optical emission spectroscopy. Data were statistically analyzed by independent sample t test and paired sample t test at 5% significance level.

Results

Harvard MTA endodontic cement showed significant lower solubility and higher pH values compared with that of ProRoot MTA. ProRoot MTA exhibited significant higher calcium ion release value after 14 days (P value ≤ 0.05).

Conclusion

Harvard, Universal HandMix MTA repair cement with its different chemical composition; exhibits a low solubility with enhanced alkaline pH value compared to ProRoot MTA repair material.
Extrafloral nectary–the sleeping beauty of plant science
Authors: CHEN Xiaoya
Published: March 2020

Cotton is one of the most important cash crops, its growth season coincides with a high incidence of diverse groups of pests, leading to heavy use of pesticides. Recent identification of a signaling protein as a candidate regulator of cotton extrafloral nectary provides a new insight into the formation of sophisticated defense mechanisms in plants.
A case report of microcephaly and refractory West syndrome associated with WDR62 mutation
Authors: Zhou Ping , Ding Xin , Zeng Qi , Zou Huafang , Liao Jianxiang , Cao Dezhi
Published: March 2020

The autosomal recessive form of primary microcephaly (MCPH) is a rare disorder characterized by microcephaly with variable degree of intellectual disability. WDR62 has been reported as the second causative gene of MCPH2. West syndrome is a severe epilepsy syndrome composed of the triad of spasms, hypsarrhythmia, and mental retardation. There are limited clinical reports regarding WDR62 mutation and West syndrome. Here we report a boy who was identified with WDR62 mutation and was followed up from age 3 months to 5 months and 14 days. He had the first seizure as the classic epileptic spasm at the age of 3 months. Psychomotor retardation was noted before the seizure occurred. The head circumference was 38.5 cm (SD 2.6) when he was 4 months old, no dysmorphic facial features were observed. He couldn’t support his head steadily or turn over. He was able to laugh when tricked by the parents, but couldn’t track the sound and light. At the early stage, the electroencephalogram showed multifocal discharges, which evolved into hypsarrhythmia one month later, and brain MRI showed developmental malformation of cerebral gyrus. Two heterozygous mutations were identified in WDR62 by whole exome sequencing c.1535G > A, p.R512Q and c.2618dupT, p.K874Qfs*40. The patient was administrated with oral sodium valproate, nitrazepam, intramuscular adrenocorticotropic hormone for 2 weeks, and followed by prednisone, levetiracetam, topiramate and vigabatrin. However, there was no significant improvement on the seizure control after these treatments. According to the genetic report and clinical manifestation, we speculated that the WDR62 compound heterozygous mutation is responsible for the serious clinical phenotype.
Denatured proteins as a novel template for the synthesis of well-defined, ultra-stable and water-soluble metal nanostructures for catalytic applications
Authors: Chen Chaojian , Ng David Yuen Wah , Weil Tanja
Published: March 2020

The templated synthesis of noble metal nanoparticles using biomass, such as proteins and polysaccharides, has generated great interest in recent years. In this work, we report on denatured proteins as a novel template for the preparation of water-soluble metal nanoparticles with excellent stability even after high speed centrifugation or storage at room temperature for one year. Different noble metal nanoparticles including spherical gold and platinum nanoparticles as well as gold nanoflowers are obtained using sodium borohydride or ascorbic acid as the reducing agent. The particle size can be controlled by the concentration of the template. These metal nanoparticles are further used as catalysts for the hydrogenation reaction of p-nitrophenol to p-aminophenol. Especially, spherical gold nanoparticles with an average size of 2 nm show remarkable catalytic performance with a rate constant of 1.026 × 10− 2 L s− 1 mg− 1. These metal nanoparticles with tunable size and shape have great potential for various applications such as catalysis, energy, sensing, and biomedicine.

Graphical abstract
The reliability of the computed tomography perfusion parameters as a predictor of colorectal cancer grade: influence of tumor region of interest position
Authors: Khalaf Lamiaa M. R. , Megal Peter E. , El-Sharkawy Mostafa , Elkader Afaf Abd , Sayed Mona M. , Hussien Marwa T. , Eltyb Hanan A.
Published: March 2020

Background

The aim of this study is to prospectively determine whether the computed tomography perfusion (CTP) can predict the tumor grade in colorectal cancer (CRC), and investigation of the best position of the tumor region of interest (ROI) could improve the tumor grade differentiation.

Results

The mean blood flow (mBF) at the tumor edge was significantly different among different tumor grades with the highest value noted in moderately differentiated and the lowest value in poorly differentiated CRC (111.67 ± 38.91 vs. 52.25 ± 21.97 ml/min/100 g, respectively, P = 0.03). At the tumor center, the BF and blood volume (BV) showed highest value in moderately differentiated and the lowest value in poorly differentiated CRC (P < 0.001, 0.02 respectively). The ROC curve revealed that the BF at the tumor edge showed its best results as regard its sensitivity 73.9% and specificity 82.1% in the characterization of moderately differentiated CRC from the other subtypes at > 92.2 ml/100 g/min cut off point and their AUC and P value were (0.82 and < 0.001 respectively), while the AUC of the BF at the tumor center was 0.81 and its P value was 0.03. In the characterization of poorly differentiated CRC from the other subtypes, BF cut off value at < 67.32 ml/100 g/min at the tumor edge showed the best performance of its sensitivity 88% and specificity 88% with 0.92 AUC and P value was < 0.001, while the AUC of the BF at the tumor center was 0.89. BF was higher at the edge than at the center of the tumor (88.53 ± 22.45 vs. 78.79 ± 28.98 ml/min/100 g; P < 0.001 respectively).

Conclusions

PCT could help in prediction of the poorly and the moderately differentiated CRC and the mBF was the most reliable parameter in prediction of the grade. The variation in ROI position has no substantial difference in the prediction of the tumor grade; however, this variation has a significant impact on the measurements of the PCT parameters especially the BF.
Characterization of vulnerability of road networks to fluvial flooding using SIS network diffusion model
Authors: Abdulla Bahrulla , Kiaghadi Amin , Rifai Hanadi S. , Birgisson Bjorn
Published: March 2020

This study aims to characterize the vulnerability of road networks to fluvial flooding using a network diffusion-based method. Various network diffusion models have been applied widely for modeling the spreading of contagious diseases or capturing opinion dynamics in social networks. By comparison, their application in the context of physical infrastructure networks has just started to gain some momentum, although physical infrastructure networks also exhibit diffusion-like phenomena under certain stressors. This study applies a susceptible-impacted-susceptible (SIS) diffusion model to capture the impact of flooding on the road network connectivity. To that end, this paper undertook the following four steps. First, the road network was modeled as primal graphs and nodes that were flood-prone (or the origins of the fluvial flood) were identified. Second, temporal changes in the flood depth within the road network during a flooding event were obtained using a data-driven geospatial model. Third, based on the relationship between vehicle speed and flood depth on road networks, at each time step, the nodes in the road network were divided into two discrete categories, namely functional and closed, standing for Susceptible and Impacted in the SIS diffusion model, respectively. Then, two parameters of the SIS model, average transition probabilities between states, were estimated using the results of the hydraulic simulation. Fourth, the robustness of the road network under various SIS diffusion scenarios was estimated, which was used to test the statistical significance of the difference between the robustness of the road network against diffusions started from the randomly chosen nodes and nodes with different high centrality measures. The methodology was demonstrated using the road network in the Memorial super neighborhood in Houston. The results show that diffusive disruptions that start from nodes with high centrality values do not necessarily cause a more significant loss to the connectivity of the road network. The proposed method has important implications for applying link predictions on road networks, and it casts significant insights into the mechanism by which cascading disruptions spread from flood control infrastructure to road networks, as well as the diffusion process in the road networks.
Fatigue life prediction of pipeline with equivalent initial flaw size using Bayesian inference method
Authors: Salemi Milad , Wang Hao
Published: March 2020

Majority of pipeline infrastructure are old and susceptible to possible catastrophic failures due to fatigue. Timely maintenance is the key to keep pipeline in serviceable and safe condition. This paper proposed a Bayesian inference methodology based on the observed crack growth measurements and cycle data that predicts the probability density of failure after initially estimating the equivalent initial flaw size (EIFS). The model was first developed based on one-dimensional crack growth problem in plate with edge crack. Then the model was expanded to two-dimensional crack growth problem in pipe wall. Stress intensity factors (SIF) at the crack tip in pipe model were calculated using finite element (FE) analysis for different crack lengths and depths. Polynomial function and Gaussian process were used to develop surrogate models of SIF. The analysis demonstrated that the proposed Bayesian inference method with hyperparameters generated accurate inferred results for probability density function (PDF) of both EIFS and the number of cycles to failure.
Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes
Authors: Beebe-Dimmer Jennifer L. , Kapron Ashley L. , Fraser Alison M. , Smith Ken R. , Cooney Kathleen A.
Published: March 2020

PURPOSE

Recently developed clinical guidelines suggest that men in families with specific cancer syndromes, such as hereditary breast and ovarian cancer (HBOC), consider genetic testing, especially in the setting of aggressive disease. However, although a family history (FH) of the same disease among close relatives is an established risk factor for prostate cancer (PC), a direct comparison of PC risk for men with each syndrome in a single population is needed.

METHODS

The Utah Population Database was used to identify 619,630 men, age ≥ 40 years, who were members of a pedigree that included at least 3 consecutive generations. Each man was evaluated for FH of hereditary PC (HPC), HBOC, and Lynch syndrome (LS) and for his own PC status. PC occurrences (N = 36,360) were classified into one or more subtypes: early onset (EO), lethal, and/or clinically significant. Relative risks (RRs) associated with each subtype, adjusted for important covariables, were calculated in STATA using a modified Poisson regression with robust error variances to obtain corresponding RR CIs for each FH definition.

RESULTS

An FH of HPC conveyed the greatest relative risk for all PC subtypes combined (RR, 2.30; 95% CI, 2.22 to 2.40), followed by HBOC and LS (both with 1 < RR < 2 and statistically significant). The strongest risks associated with FH were observed for EO disease in all pedigree types, consistent with the contribution of genetic factors to disease occurrence.

CONCLUSION

In this large, population-based, family database, the risk of PC varied by cancer FH and was most strongly associated with EO disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.
Photoinduced Electron Transfer in a MoS2/Anthracene Mixed-Dimensional Heterojunction in Aqueous Media
Authors: Tajima Tomoyuki , Okabe Shogo , Takaguchi Yutaka
Published: March 2020

Mixed-dimensional (0D/2D) van der Waals heterojunctions were constructed by physical adsorption of anthracene (Anth) onto few-layer MoS2 nanosheets. The physical modification of few-layer MoS2 nanosheets using anthryl dendron 1, i.e., a poly(amidoamine) dendrimer having an anthracene core, via a simple yet efficient exfoliation approach afforded MoS2/1 hybrids, which are stable for at least one month. The emission quenching typical for anthracene is also observed in the MoS2/anthracene mixed-dimensional heterojunctions. Transient absorption measurements on MoS2/1 hybrids proved that photoinduced electron transfer occurs at the MoS2/anthracene interface. The lifetime of the singlet excited state (τS1(1Anth*)) for MoS2/1 was evaluated to be 4.1 ns, which is shorter than that of anthryl dendron 1 (13 ns). Interestingly, a remarkably long lifetime was observed for the anthracene cation radical (6.1 µs). Relatively long lifetimes of charge-separate states of MoS2/1 hybrids would be beneficial design features for efficient photovoltaics, photocatalysts, and related optoelectronic applications.