bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Analysis of Identifying Methylation-Driven Genes Signature Predicts Prognosis in Colorectal Carcinoma
Authors: Huang Hao , Fu Jinming , Zhang Lei , Xu Jing , Li Dapeng , Onwuka Justina Ucheojor , Zhang Ding , Zhao Liyuan , Sun Simin , Zhu Lin , Zheng Ting , Jia Chenyang , Cui Binbin , Zhao Yashuang
Published: June 2021

Background

Aberrant DNA methylation is a critical regulator of gene expression and plays a crucial role in the occurrence, progression, and prognosis of colorectal cancer (CRC). We aimed to identify methylation-driven genes by integrative epigenetic and transcriptomic analysis to predict the prognosis of CRC patients.

Methods

Methylation-driven genes were selected for CRC using a MethylMix algorithm and LASSO regression screening strategy, and were further used to construct a prognostic risk-assessment model. The Cancer Genome Atlas (TCGA) database was obtained as the training set for both the screening of methylation-driven genes and the effect of genes signature on CRC prognosis. Then, the prognostic genes signature was validated in three independent expression arrays of CRC data from Gene Expression Omnibus (GEO).

Results

We identified 143 methylation-driven genes, of which the combination of BATF, PHYHIPL, RBP1, and PNPLA4 expression levels was screened as a better prognostic model with the best area under the curve (AUC) (AUC = 0.876). Compared with patients in the low-risk group, CRC patients in the high-risk group had significantly poorer overall survival in the training set (HR = 2.184, 95% CI: 1.404–3.396, P < 0.001). Similar results were observed in the validation set. Moreover, VanderWeele’s mediation analysis indicated that the effect of methylation on prognosis was mediated by the levels of their expression (HRindirect = 1.473, P = 0.001, Proportion mediated, 69.10%).

Conclusions

We identified a four-gene prognostic signature by integrative analysis and developed a risk-assessment model that is significantly associated with patients’ survival. Methylation-driven genes might be a potential prognostic signature for CRC patients.
A Pilot Study of Home-Based Exercise and Personalized Nutrition Counseling Intervention in Endometrial Cancer Survivors
Authors: Schwartz Amanda R. , Bartlett David B. , Johnson Johanna L. , Broadwater Gloria , Channell Meghan , Nolte Kimberly C. , Wilkes Patricia A. , Huffman Kim M. , Secord Angeles Alvarez
Published: June 2021

Introduction

To assess the feasibility of a home-based aerobic exercise and nutrition counseling intervention and effect on cardiorespiratory fitness, cardiovascular disease risk profile, and immune response in obese endometrial cancer survivors.

Methods

A longitudinal pilot study assessed a 12-week home-based aerobic exercise and nutrition counseling intervention in obese endometrial cancer survivors. The primary outcome was feasibility defined as 80% adherence to weekly walking sessions calculated among individuals that completed the intervention. Secondary outcomes comprised pre- and post-intervention differences in cardiorespiratory fitness, cardiovascular risk factors, and T-cell function. Descriptive statistics summarized data. Wilcoxon sign tests identified differences between and pre and post-intervention variables.

Results

Nineteen women with stage 1 endometrial cancer consented; 9 withdrew and one was a screen failure. Median adherence to weekly walking sessions was 83.3%. Body composition was significantly altered with a reduction in median fat mass from 52.5 kg to 46.9 kg (p=0.04), and BMI from 37.5 kg/m2 to 36.2 kg/m2 (p = 0.004). There was no significant difference in cardiorespiratory fitness or cardiovascular parameters. The percentage of CD4+ and CD8+ T-cells producing IFNγ towards MAGE-A4 significantly increased from and 5.9% to 7.2% (p=0.043) and 13.9% to 14.8% (p=0.046), respectively. There were 3 related adverse events: hip pain, back sprain, and abdominal pain.

Discussion

Our home-based exercise and nutrition counseling program was feasible based on 80% adherence to walking sessions and favored altered body composition. However, the discontinuation rate was high and further research is needed to overcome barriers to implementation. Improvement in cardiovascular parameters will most likely require longer and more intensive programs.
Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy
Authors: Sun Xiao-Xin , Li Yanping , Sears Rosalie C. , Dai Mu-Shui
Published: June 2021

Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated via diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation. In addition, MYC is also regulated by SUMOylation which crosstalks with the ubiquitination pathway and controls MYC protein stability and activity. In this mini-review, we will summarize current updates regarding MYC ubiquitination and provide perspectives about these MYC regulators as potential therapeutic targets in cancer.
Epidemiology and Survival of Patients With Brainstem Gliomas: A Population-Based Study Using the SEER Database
Authors: Liu Huanbing , Qin Xiaowei , Zhao Liyan , Zhao Gang , Wang Yubo
Published: June 2021

Background

Brainstem glioma is a primary glial tumor that arises from the midbrain, pons, and medulla. The objective of this study was to determine the population-based epidemiology, incidence, and outcomes of brainstem gliomas.

Methods

The data pertaining to patients with brainstem gliomas diagnosed between 2004 and 2016 were extracted from the SEER database. Descriptive analyses were conducted to evaluate the distribution and tumor-related characteristics of patients with brainstem gliomas. The possible prognostic indicators were analyzed by Kaplan-Meier curves and a Cox proportional hazards model.

Results

The age-adjusted incidence rate was 0.311 cases per 100,000 person-years between 2004 and 2016. A total of 3387 cases of brainstem gliomas were included in our study. Most of the patients were white and diagnosed at 5-9 years of age. The most common diagnosis confirmed by histological review was ependymoma/anaplastic ependymoma. The median survival time was 24 months. Patients with tumors less than 3 cm in size had a better prognosis. Surgery was effective at improving overall survival. There was no evidence that radiotherapy and chemotherapy improved overall survival.

Conclusion

Brainstem gliomas can be diagnosed at any age. Ependymoma/anaplastic ependymoma is the most common pathological diagnosis. The prognosis is poor, and timely diagnosis and surgery are effective at improving the prognosis. We suggest that more attention should be given to the treatment of patients with brainstem gliomas.
N6-Methylandenosine-Related lncRNAs in Tumor Microenvironment Are Potential Prognostic Biomarkers in Colon Cancer
Authors: Zhang Hongliang , Zhao Lei , Li Songyan , Wang Jing , Feng Cong , Li Tanshi , Du Xiaohui
Published: June 2021

Background

LncRNA dysregulation and the tumor microenvironment (TME) have been shown to play a vital role in the progression and prognosis of colon cancer (CC). We aim to reveal the potential molecular mechanism from the perspective of lncRNA in the TME and provide the candidate biomarkers for CC prognosis.

Methods

ESTIMATE analysis was used to divide the CC patients into high and low immune or stromal score groups. The expression array of lncRNA was re-annotated by Seqmap. Microenvironment-associated lncRNAs were filtered through differential analysis. The m6A-associated lncRNAs were screened by Pearson correlation analysis. Lasso Cox regression analyses were performed to construct the m6A- and tumor microenvironment-related lncRNA prognostic model (m6A-TME-LM). Survival analysis was used to assess the prognostic efficacy of candidate lncRNAs. Enrichment analyses annotated the candidate genes’ functions.

Results

We obtained 25 common differentially expressed lncRNAs (DELs) associated with immune microenvironment and m6A-related genes for subsequent lasso analysis. Four out of these DELs were selected for the m6A-TME-LM. All the four lncRNAs were related to overall survival, and a test set testified the result. Further stratification analysis of the m6A-TME-LM retained its ability to predict OS for male and chemotherapy adjuvant patients and performed an excellent prognostic efficacy in the TNM stage III and IV subgroups. Network analysis also found the four lncRNAs mediated co-expression network was associated with tumor development.

Conclusion

We constructed the m6A-TME-LM, which could provide a better prognostic prediction of CC.
A Regression Model to Predict Augmented Renal Clearance in Critically Ill Obstetric Patients and Effects on Vancomycin Treatment
Authors: Tang Lian , Ding Xin-yuan , Duan Lu-fen , Li Lan , Lu Hao-di , Zhou Feng , Shi Lu , Lu Jian , Shen Yi , Zhuang Zhi-wei , Sun Jian-tong , Zhou Qin , Zhu Chen-qi , Li Jing-jing , Yu Yan-xia
Published: June 2021

Background: Augmented renal clearance (ARC) risk factors and effects on vancomycin (VCM) of obstetric patients were possibly different from other populations based on pathophysiological characteristics. Our study was to establish a regression model for prediction of ARC and analyze the effects of ARC on VCM treatment in critically ill obstetric patients.

Methods: We retrospectively included 427 patients, grouped into ARC and non-ARC patients. Logistic regression analysis was used to analyze the factors related to ARC. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model for ARC. Patients who received VCM therapy were collected. The published VCM population pharmacokinetic (PPK) model was used to calculate pharmacokinetic parameters. A linear regression analysis was made between the predicted and measured concentrations.

Results: Of the 427 patients, ARC was present in 201 patients (47.1%). The independent risk factors of ARC were heavier, greater gestational age, higher albumin level, fewer caesarean section, severe preeclampsia and vasoactive drug; more infection, hypertriglyceridemia and acute pancreatitis. We established the above nine-variable prediction regression model and calculated the predicted probability. ROC curve showed that the predicted probability of combined weight, albumin and gestational age had better sensitivity (70.0%) and specificity (89.8%) as well as the maximal area under the curve (AUC, AUC = 0.863). 41 cases received VCM; 21 cases (51.2%) had ARC. The initial trough concentration in ARC patients was lower than in non-ARC patients (7.9 ± 3.2 mg/L vs 9.5 ± 3.3 mg/L; p = 0.033). Comparing the predicted trough concentration of two published VCM PPK models with the measured trough concentration, correlation coefficients (r) were all more than 0.8 in the ARC group and non-ARC group. AUC was significantly decreased in the ARC group (p = 0.003; p = 0.013), and clearance (CL) increased in the ARC group (p < 0.001; p = 0.008) when compared with the non-ARC group.

Conclusion: ARC is a common state in critically ill obstetric patients. The regression model of nine variables had high predictive value for predicting ARC. The published VCM PPK models had good predictive performance for predicting trough concentrations of obstetric patients. Pharmacokinetic parameters of VCM are different in ARC obstetric patients, which results in enhanced VCM clearance and decreased trough concentration.
Considerations and Regulatory Approaches in the USA and in the EU for dsRNA-Based Externally Applied Pesticides for Plant Protection
Authors: Dietz-Pfeilstetter Antje , Mendelsohn Mike , Gathmann Achim , Klinkenbuß Dominik
Published: June 2021

Increasing pest and pathogen challenges as well as having fewer conventional pesticides to employ require innovative and sustainable solutions for plant protection. One group of pesticides that is in the pipeline and is expected to be subject to regulation and risk assessment procedures in the near future, is based on the natural gene silencing mechanism RNA interference (RNAi). These dsRNA-based products can be highly specific for a target organism due to the sequence-specific interaction between effective small interfering RNAs (siRNAs) and a complementary target RNA. General regulatory frameworks for pesticide authorization in the U.S. and in the EU are presented. In addition, production and application procedures and specific characteristics of dsRNA-based pesticides relevant for risk assessment and regulation are considered.
Identity Leadership, Social Identity Continuity, and Well-Being at Work During COVID-19
Authors: Krug Henning , Haslam S. Alexander , Otto Kathleen , Steffens Niklas K.
Published: June 2021

The COVID-19 pandemic has led to widespread remote working that has posed significant challenges for people’s sense of connection to their workplace and their mental health and well-being. In the present work, we examined how leaders’ identity leadership is associated with the well-being of employees in the context of the COVID-19 pandemic. Specifically, we examined how both leaders’ and team members’ identity leadership is associated with employees’ social identity continuity, and through this with their job satisfaction, burnout and loneliness at work. Employees (N = 363) participated in a field study during the COVID-19 pandemic, completing measures of their leader’s and team members’ identity leadership (i.e., entrepreneurship and impresarioship), social identity continuity, job satisfaction, burnout, loneliness at work. Results revealed that to the extent that employees perceived greater social identity continuity, they were more satisfied with their work and felt less lonely. Furthermore, mediation analyses revealed indirect effects of team members’ identity entrepreneurship on job satisfaction and loneliness via an increase in social identity continuity. Results suggest that to foster employees’ health and well-being in times of disruption, organizations might put in place practices that allow employees to maintain a sense of ‘we-ness’ at work by involving not only formal leaders but also other members of the organization.
It's Not That Great Anymore: The Central Role of Defense Mechanisms in Grandiose and Vulnerable Narcissism
Authors: Kampe Leonie , Bohn Johannes , Remmers Carina , Hörz-Sagstetter Susanne
Published: June 2021

Objectives: The concept of narcissism contains a yet unresolved paradox: Its grandiose facet depicts the psychopathological core but is often associated with life-satisfaction and overall functioning, whereas its vulnerable facet is associated with psychological distress, but still not included in the international classification systems. Our goal was to investigate the relationship between the two facets of narcissism expecting underlying defense mechanisms to be core elements. First, we aimed to identify defense mechanisms specific to grandiose and vulnerable narcissism. Second, we explored how both facets are differentially associated with psychological distress, assuming that grandiose narcissism would be associated with less psychological distress than vulnerable narcissism. Third, we investigated the mediating role of defense mechanisms between narcissism and psychological distress.

Methods: In a non-clinical sample of N = 254 individuals, the Pathological Narcissism Inventory was used for the assessment of grandiose and vulnerable facets of narcissism, the Defense Style Questionnaire for defense mechanisms, and the Brief Symptom Inventory for psychological distress. Structural equation modeling was employed to identify distinct factors of grandiose and vulnerable narcissism. Associations between specific defense mechanisms and both facets were calculated. Furthermore, the direct association between both facets and psychological distress was examined. We finally explored whether defense mechanisms mediate the association between distress and both grandiose and vulnerable narcissism.

Results: A distinct pattern of defense mechanisms for each facet of narcissism could be extracted: Both facets showed significant positive correlations with specific intermediate and all maladaptive defense mechanisms. Only grandiose narcissism showed significant positive correlations with adaptive defenses. Vulnerable narcissism showed negative correlations with all adaptive defenses. Specifically, grandiose narcissism was significantly related to anticipation, pseudo-altruism, rationalization, and dissociation, whereas vulnerable narcissism was negatively related to all these defense mechanisms. While grandiose narcissism was not related to psychological distress, vulnerable narcissism showed high correlations with psychological distress. Intriguingly, mediator analysis found that grandiose narcissism was related to psychological distress when mediated by maladaptive defense mechanisms.

Discussion: The role of defense mechanisms is central for a differentiated understanding of the two different faces of narcissism. The relevance of assessing defense mechanisms in clinical settings, and related empirical findings are discussed.
NEFA, BHBa, UREA and Liver Enzyme Variation in the Bloodstream of Weaned Foals up to 18 Months of Age
Authors: Cappai Maria Grazia , Taras Andrea , Biggio Giovanni Paolo , Dimauro Corrado , Gatta Domenico , Cossu Ignazio , Cherchi Raffaele , Pinna Walter
Published: June 2021

The pattern of selected metabolites for interpreting homeostasis during the growth of foals can be used as an indicator of energy balance state and liver health. Against this background, the literature on circulating parameters of foals across growth stages is scanty. We hypothesized that circulating metabolites indicating energy distribution such as non-esterified fatty acids (NEFA), β-hydroxy-butyric acid (BHBa), UREA and liver enzyme-like γ-glutamyl-transferase (γ-GT) [interpreted in the light of circulating total bilirubin (TBIL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] may be used to monitor the energy balance of growing foals. A total of 12 Anglo-Arab (AA) foals from the same stable were enrolled in this trial. All foals were serially weighed on a digital scale and sampled for total blood at weaning, at 12 and 18 months of age. Feeding and keeping conditions were similar for all the foals involved. Animals appeared healthy and no signs of poor growth performance were pointed out. The peak of circulating NEFA mobilized from body depots was reached at one year of age but markedly dropped at 18 months, when BHBa increased (p < 0.001) alongside with liver enzyme. BHBa and γ-GT levels turned out to positively correlate (p = 0.051). However, at 6, 12 and 18 months, γ-GT dropped in the physiological reference range for the horse, thus showing no prognostic value. ALT and UREA significantly increased (p = 0.008 and p = 0.006, respectively) when NEFA also increased (p = 0.001). Liver enzyme increase could be associated with fat mobilization and ketone bodies production meanwhile amino acid transamination for energy purposes led to the increase of UREA in the bloodstream. However, no prognostic value to liver enzyme could be attributed in this trial.
Interaction of Temporin-L Analogues with the E. coli FtsZ Protein
Authors: Di Somma Angela , Canè Carolina , Moretta Antonio , Duilio Angela
Published: June 2021

The research of new therapeutic agents to fight bacterial infections has recently focused on the investigation of antimicrobial peptides (AMPs), the most common weapon that all organisms produce to prevent invasion by external pathogens. Among AMPs, the amphibian Temporins constitute a well-known family with high antibacterial properties against Gram-positive and Gram-negative bacteria. In particular, Temporin-L was shown to affect bacterial cell division by inhibiting FtsZ, a tubulin-like protein involved in the crucial step of Z-ring formation at the beginning of the division process. As FtsZ represents a leading target for new antibacterial compounds, in this paper we investigated in detail the interaction of Temporin L with Escherichia coli FtsZ and designed two TL analogues in an attempt to increase peptide-protein interactions and to better understand the structural determinants leading to FtsZ inhibition. The results demonstrated that the TL analogues improved their binding to FtsZ, originating stable protein-peptide complexes. Functional studies showed that both peptides were endowed with a high capability of inhibiting both the enzymatic and polymerization activities of the protein. Moreover, the TL analogues were able to inhibit bacterial growth at low micromolar concentrations. These observations may open up the way to the development of novel peptide or peptidomimetic drugs tailored to bind FtsZ, hampering a crucial process of bacterial life that might be proposed for future pharmaceutical applications.
Pomegranate Peel Extract Is a Potential Alternative Therapeutic for Giardiasis
Authors: El-Kady Asmaa M. , Abdel-Rahman Iman A. M. , Fouad Samer S. , Allemailem Khaled S. , Istivan Taghrid , Ahmed Sheren F. M. , Hasan Al Shaimaa , Osman Heba A. , Elshabrawy Hatem A.
Published: June 2021

Giardiasis is a major diarrheal disease affecting approximately 2.5 million children annually in developing countries. Several studies have reported the resistance of Giardia lamblia (G. lamblia) to multiple drugs. Therefore, identifying an effective drug for giardiasis is a necessity. This study examined the antiparasitic effect of Punica granatum (pomegranate) and evaluated its therapeutic efficacy in rats infected with G. lamblia. In vitro study showed high efficacy of pomegranate peel ethanolic extract in killing G. lamblia cysts as demonstrated by eosin vital staining. We showed that treating infected rats with pomegranate extract resulted in a marked reduction in the mean number of G. lamblia cysts and trophozoites in feces and intestine respectively. Interestingly, the number of G. lamblia trophozoites and cysts were significantly lower in the pomegranate extract-treated group compared to the metronidazole-positive control group. Moreover, pomegranate extract treatment significantly induced nitric oxide (NO) and reduced serum IL-6 and TNF-α, compared to infected untreated rats. Histological and scanning electron microscopy (SEM) examination of the jejunum and duodenum of pomegranate extract-treated animals confirmed the antiparasitic effect of the extract, and demonstrated the restoration of villi structure with reduction of villi atrophy, decreased infiltration of lymphocytes, and protection of intestinal cells from apoptotic cell death. In conclusion, our data show that the pomegranate peel extract is effective in controlling G. lamblia infections, which suggests that it could be a viable treatment option for giardiasis.
Anatomical Site, Typing, Virulence Gene Profiling, Antimicrobial Susceptibility and Resistance Genes of Streptococcus suis Isolates Recovered from Pigs in Spain
Authors: Petrocchi-Rilo Máximo , Martínez-Martínez Sonia , Aguarón-Turrientes Álvaro , Roca-Martínez Elisabet , García-Iglesias María-José , Pérez-Fernández Esther , González-Fernández Alba , Herencia-Lagunar Elena , Gutiérrez-Martín César-Bernardo
Published: June 2021

A set of 207 Streptococcus suis isolates were collected from ten autonomous communities from Spain in 2019 to 2020 from pigs with meningitis, pneumonic lungs, arthritic joints or other swollen viscera, to a lesser extent. Thirteen capsular types were detected being the most prevalent serotype 2 (21.7%), followed by serotypes 1 (21.3%), 9 (19.3%) and 3 (6.3%). Serotypes 2 and 9 were recovered mainly from the central nervous system (CNS), while serotype 1 was isolated mostly from swollen joints and serotype 3 from the lungs. Twenty-five isolates (12.1%) could not be typed. The most prevalent pathotype was epf + mrp + sly + luxS (49 isolates, 23.8%), and it was related mainly to serotypes 1 and 2. Serotypes 1–3 and 9 were significantly associated with anatomical sites of isolation and virulence factors, serotype 9 (CNS) and serotypes 3 and 9 (lungs) being associated with virulence profiles without the epf gene. S. suis isolates showed globally high antimicrobial resistances, but ampicillin followed by spectinomycin and tiamulin resulted in the highest activities, while the greatest resistances were detected for sulphadimethoxine, tetracyclines, neomycin, clindamycin and macrolides. A total of 87.4% isolates were positive to the tetO gene, 62.4% to the ermB gene and 25.2% to the fexA gene, while 14.6% were positive to all three genes simultaneously. A significative association between isolate resistances to tetracyclines and macrolides and the resistance genes tested was established, except for phenicol resistance and the fexA gene. A set of 14 multiresistance patterns were obtained according to the number of antimicrobials to which the isolates were resistant, the resistances to 12 or more agents being the most prevalent ones. A remarkable amount of multiresistance profiles could be seen among the S. suis serotype 9 isolates.
The Anti-Inflammatory Effect of Aptamin C on House Dust Mite Extract-Induced Inflammation in Keratinocytes via Regulation of IL-22 and GDNF Production
Authors: Lee Dahae , Kim Yejin , Jo Hyejung , Go Cheolhyeon , Jeong Yoojin , Jang Yoojin , Kang Dongmin , Park Kwanjin , Kim Yoon-Seong , Kang Jae Seung
Published: June 2021

Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by eczemous lesions on the skin that manifest as severe itching and last a long time. AD is thought to be a response to local allergens, including house dust mites (HDMs). Aptamin C is a modified form of vitamin C comprised of aptamers (DNA fragments) that bind specifically to vitamin C and inhibit its oxidation, thereby increasing its stability and antioxidant effects. It is already known that vitamin C shows an anti-inflammatory effect on skin inflammation. Oxidative stress is one of the major causes of inflammatory diseases, including HDM-induced skin inflammation, suggesting that the antioxidant activity of Aptamin C could regulate inflammatory responses to HDMs in the skin keratinocyte cell line HaCaT and primary skin keratinocytes. Aptamin C not only inhibited HDM-induced proliferation of both type of cells, but suppressed HDM-induced increases in interleukin (IL)-1α and IL-6 production by these cells. In addition, Aptamin C suppressed the production of IL-17 and IL-22 by T cells, which are closely associated with AD pathogenesis, as well as HDM-induced IL-22Rα expression. Aptamin C also reduced the production of thymus and activation-regulated chemokine (TARC) by suppressing the interaction between IL-22 and IL-22Rα, as well as reducing T cell migration. Although HDM treatment markedly increased the expression of glial cell line-derived neurotrophic factor (GDNF), which is associated with itching in AD skin lesions, this increase was reduced by Aptamin C treatment. Taken together, these results suggest that Aptamin C can effectively regulate inflammatory lesions, such as AD, by regulating the production of inflammatory cytokines and GDNF induced by HDM.
Left Atrial Flow Stasis in Patients Undergoing Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation Using 4D-Flow Magnetic Resonance Imaging
Authors: Sheitt Hana , Kim Hansuk , Wilton Stephen , White James A , Garcia Julio
Published: June 2021

Atrial fibrillation (AF) is associated with systemic thrombo-embolism and stroke events, which do not appear significantly reduced following successful pulmonary vein (PV) ablation. Prior studies supported that thrombus formation is associated with left atrial (LA) flow alterations, particularly flow stasis. Recently, time-resolved three-dimensional phase-contrast (4D-flow) showed the ability to quantify LA stasis. This study aims to demonstrate that LA stasis, derived from 4D-flow, is a useful biomarker of LA recovery in patients with AF. Our hypothesis is that LA recovery will be associated with a reduction in LA stasis. We recruited 148 subjects with paroxysmal AF (40 following 3–4 months PV ablation and 108 pre-PV ablation) and 24 controls (CTL). All subjects underwent a cardiac magnetic resonance imaging (MRI) exam, inclusive of 4D-flow. LA was isolated within the 4D-flow dataset to constrain stasis maps. Control mean LA stasis was lower than in the pre-ablation cohort (30 ± 12% vs. 47 ± 18%, p < 0.001). In addition, mean LA stasis was reduced in the post-ablation cohort compared with pre-ablation (36 ± 15% vs. 47 ± 18%, p = 0.002). This study demonstrated that 4D flow-derived LA stasis mapping is clinically relevant and revealed stasis changes in the LA body pre- and post-pulmonary vein ablation.
Biomimicry-Gradient-Based Algorithm as Applied to Photonic Devices Design: Inverse Design of Flat Plasmonic Metalenses
Authors: Edee Kofi
Published: June 2021

The classical adjoint-based topology optimization (TO) method, based on the use of a random continuous dielectric function as design variable distribution is known to be one of the timely efficient and fast optimization methods enable a very high performance functional optical devices. It relies on the computation of the gradient of a figure of merit (FOM) with respect to the design parameters. The gradient of the figure of merit (FOM) may then be used to update the design vector element in several senarios. One of the most common use scenario consists of updating simultaneously all the design parameter vector elements. In a linear problem case involving a simply convex FOM-function shape, using the gradient information, it is a relatively easy to reach an optimal solution. In the case of constrained and non linear problems stated in an infinite and indeterminate design space, the conventional TO, a local optimizer, may require multiple restarts, with multiple initial points and multiple runs. The algorithm strongly depends on the initial conditions. In this paper, we report a global-like optimizer inspired by a wolf pack hunting, enabling efficient design of metasurfaces through their geometrical parameters. We apply the method to design a non periodic metasurface consisting of plasmonic metalenses, enabling a high energy flow focusing on a well-defined 2D focus spot. Numerical results show that the proposed inverse design method has a low sensitivity to initial conditions. In our design method of metalens, we optimize the full micro device at once, and demonstrate that the proposed method may provide both symmetric and more creative unexpected asymmetric on-axis metalenses even though under a normal illumination.
Validation of a Modal Work Approach for Forced Response Analysis of Bladed Disks
Authors: Pinelli Lorenzo , Lori Francesco , Marconcini Michele , Pacciani Roberto , Arnone Andrea
Published: June 2021

The paper describes a numerical method based on a modal work approach to evaluate the forced response of bladed disks and its validation against numerical results obtained by a commercial FEM code. Forcing functions caused by rotor–stator interactions are extracted from CFD unsteady solutions properly decomposed in time and space to separate the spinning perturbation acting on the bladed disk in a cyclic environment. The method was firstly applied on a dummy test case with cyclic symmetry where the forcing function distributions were arbitrarily selected: comparisons for resonance and out of resonance conditions revealed an excellent agreement between the two numerical methods. Finally, the validation was extended to a more realistic test case representative of a low-pressure turbine bladed rotor subjected to the wakes of two upstream rows: an IGV with low blade count and a stator row. The results show a good agreement and suggest computing the forced response problem on the finer CFD blade surface grid to achieve a better accuracy. The successful validation of the method, closely linked to the CFD environment, creates the opportunity to include the tool in an integrated multi-objective procedure able to account for aeromechanical aspects.
In-Band Pumped Thulium-Doped Tellurite Glass Microsphere Laser
Authors: Anashkina Elena A. , Dorofeev Vitaly V. , Andrianov Alexey V.
Published: June 2021

Microresonator-based lasers in the two-micron range are interesting for extensive applications. Tm3+ ions provide high gain; therefore, they are promising for laser generation in the two-micron range in various matrices. We developed a simple theoretical model to describe Tm-doped glass microlasers generating in the 1.9–2 μm range with in-band pump at 1.55 μm. Using this model, we calculated threshold pump powers, laser generation wavelengths and slope efficiencies for different parameters of Tm-doped tellurite glass microspheres such as diameters, Q-factors, and thulium ion concentration. In addition, we produced a 320-μm tellurite glass microsphere doped with thulium ions with a concentration of 5·1019 cm−3. We attained lasing at 1.9 μm experimentally in the produced sample with a Q-factor of 106 pumped by a C-band narrow line laser.
Retrofitting Masonry Walls against Out-Of-Plane Loading with Timber Based Panels
Authors: Iuorio Ornella , Dauda Jamiu A.
Published: June 2021

Unreinforced masonry walls are prone to failure when subjected to out-of-plane loading. This is due to their low performance in bending, and often the lack of appropriate connection to returning walls and floors. This paper investigates the possibility to use oriented strand boards (OSB) panels to improve the out-of-plane performance of brick masonry walls. The proposed technique considers securing OSB type-3 panels behind masonry walls with chemical and mechanical connections. The work presents finite element models to predict their behaviour. The models have been calibrated and validated through a three-phase experimental campaign, aimed at (a) characterizing the main structural components, (b) studying the out-of-plane behaviour of small-scale masonry prisms and (c) studying the behaviour of 1115 × 1115 × 215 mm masonry walls. The finite element models developed are based on a micromodel technique developed in ABAQUS and demonstrated to adequately capture the behaviour of both plain and retrofitted models to the ultimate load. The models also show an excellent correlation of the compressive damage and tensile damage with the experimental failure pattern. Generally, the model predicted the peak load and the corresponding failure and toughness to within less than 10% of the average test results.
Advances in Simulating Radiative Transfer in Complex Environments
Authors: Simon Helge , Sinsel Tim , Bruse Michael
Published: June 2021

Accurate simulation of radiative transfer is a very important aspect in climate modeling. For microclimate models in particular, it is not only important to simulate primary but also secondary radiative fluxes in great detail, i.e., emitted longwave and reflected shortwave radiation. As there are always limitations regarding computational effort and memory, these radiative fluxes are commonly implemented using simplified approaches. To overcome these simplifications and, thus, increase modeling accuracy, a new radiation scheme called indexed view sphere was introduced into the microclimate model ENVI-met. This new scheme actually accounts for radiative contributions of objects that are seen by each grid cell. In order to evaluate the advantages of the new scheme, it is compared against the formerly used averaged view factor scheme. The comparison in a complex realistic urban environment demonstrated that the indexed view sphere scheme improved the accuracy and plausibility of modeling radiative fluxes. It, however, yields an increased demand of memory to store the view facets for each cell. The higher accuracy in simulating secondary radiative fluxes should, however, overturn this shortcoming for most studies, as more detailed knowledge of local microclimatic conditions in general and eventually thermal comfort can be gained.
The Role of Plant Growth-Promoting Bacteria in Alleviating the Adverse Effects of Drought on Plants
Authors: Abdelaal Khaled , AlKahtani Muneera , Attia Kotb , Hafez Yaser , Király Lóránt , Künstler András
Published: June 2021

Plant growth-promoting bacteria play an essential role in enhancing the physical, chemical and biological characters of soils by facilitating nutrient uptake and water flow, especially under abiotic stress conditions, which are major constrains to agricultural development and production. Drought is one of the most harmful abiotic stress and perhaps the most severe problem facing agricultural sustainability, leading to a severe shortage in crop productivity. Drought affects plant growth by causing hormonal and membrane stability perturbations, nutrient imbalance and physiological disorders. Furthermore, drought causes a remarkable decrease in leaf numbers, relative water content, sugar yield, root yield, chlorophyll a and b and ascorbic acid concentrations. However, the concentrations of total phenolic compounds, electrolyte leakage, lipid peroxidation, amounts of proline, and reactive oxygen species are considerably increased because of drought stress. This negative impact of drought can be eliminated by using plant growth-promoting bacteria (PGPB). Under drought conditions, application of PGPB can improve plant growth by adjusting hormonal balance, maintaining nutrient status and producing plant growth regulators. This role of PGPB positively affects physiological and biochemical characteristics, resulting in increased leaf numbers, sugar yield, relative water content, amounts of photosynthetic pigments and ascorbic acid. Conversely, lipid peroxidation, electrolyte leakage and amounts of proline, total phenolic compounds and reactive oxygen species are decreased under drought in the presence of PGPB. The current review gives an overview on the impact of drought on plants and the pivotal role of PGPB in mitigating the negative effects of drought by enhancing antioxidant defense systems and increasing plant growth and yield to improve sustainable agriculture.
Nuclear Syndecan-1 Regulates Epithelial-Mesenchymal Plasticity in Tumor Cells
Authors: Kumar-Singh Ashish , Parniewska Malgorzata Maria , Giotopoulou Nikolina , Javadi Joman , Sun Wenwen , Szatmári Tünde , Dobra Katalin , Hjerpe Anders , Fuxe Jonas
Published: June 2021

Tumor cells undergoing epithelial-mesenchymal transition (EMT) lose cell surface adhesion molecules and gain invasive and metastatic properties. EMT is a plastic process and tumor cells may shift between different epithelial-mesenchymal states during metastasis. However, how this is regulated is not fully understood. Syndecan-1 (SDC1) is the major cell surface proteoglycan in epithelial cells and has been shown to regulate carcinoma progression and EMT. Recently, it was discovered that SDC1 translocates into the cell nucleus in certain tumor cells. Nuclear SDC1 inhibits cell proliferation, but whether nuclear SDC1 contributes to the regulation of EMT is not clear. Here, we report that loss of nuclear SDC1 is associated with cellular elongation and an E-cadherin-to-N-cadherin switch during TGF-β1-induced EMT in human A549 lung adenocarcinoma cells. Further studies showed that nuclear translocation of SDC1 contributed to the repression of mesenchymal and invasive properties of human B6FS fibrosarcoma cells. The results demonstrate that nuclear translocation contributes to the capacity of SDC1 to regulate epithelial-mesenchymal plasticity in human tumor cells and opens up to mechanistic studies to elucidate the mechanisms involved.
Contributions to Management Strategies in the NE Atlantic Regarding the Life History and Population Structure of a Key Deep-Sea Fish (Mora Moro)
Authors: Santos Régis , Medeiros-Leal Wendell , Crespo Osman , Novoa-Pabon Ana , Pinho Mário
Published: June 2021

With the commercial fishery expansion to deeper waters, some vulnerable deep-sea species have been increasingly captured. To reduce the fishing impacts on these species, exploitation and management must be based on detailed and precise information about their biology. The common mora Mora moro has become the main deep-sea species caught by longliners in the Northeast Atlantic at depths between 600 and 1200 m. In the Azores, landings have more than doubled from the early 2000s to recent years. Despite its growing importance, its life history and population structure are poorly understood, and the current stock status has not been assessed. To better determine its distribution, biology, and long-term changes in abundance and size composition, this study analyzed a fishery-dependent and survey time series from the Azores. M. moro was found on mud and rock bottoms at depths below 300 m. A larger–deeper trend was observed, and females were larger and more abundant than males. The reproductive season took place from August to February. Abundance indices and mean sizes in the catch were marked by changes in fishing fleet operational behavior. M. moro is considered vulnerable to overfishing because it exhibits a long life span, a large size, slow growth, and a low natural mortality.
MDCAN-Lys: A Model for Predicting Succinylation Sites Based on Multilane Dense Convolutional Attention Network
Authors: Wang Huiqing , Zhao Hong , Yan Zhiliang , Zhao Jian , Han Jiale
Published: June 2021

Lysine succinylation is an important post-translational modification, whose abnormalities are closely related to the occurrence and development of many diseases. Therefore, exploring effective methods to identify succinylation sites is helpful for disease treatment and research of related drugs. However, most existing computational methods for the prediction of succinylation sites are still based on machine learning. With the increasing volume of data and complexity of feature representations, it is necessary to explore effective deep learning methods to recognize succinylation sites. In this paper, we propose a multilane dense convolutional attention network, MDCAN-Lys. MDCAN-Lys extracts sequence information, physicochemical properties of amino acids, and structural properties of proteins using a three-way network, and it constructs feature space. For each sub-network, MDCAN-Lys uses the cascading model of dense convolutional block and convolutional block attention module to capture feature information at different levels and improve the abstraction ability of the network. The experimental results of 10-fold cross-validation and independent testing show that MDCAN-Lys can recognize more succinylation sites, which is consistent with the conclusion of the case study. Thus, it is worthwhile to explore deep learning-based methods for the recognition of succinylation sites.
Characterization of an Immobilized Amino Acid Racemase for Potential Application in Enantioselective Chromatographic Resolution Processes
Authors: Harriehausen Isabel , Bollmann Jonas , Carneiro Thiane , Bettenbrock Katja , Seidel-Morgenstern Andreas
Published: June 2021

Enantioselective resolution processes can be improved by integration of racemization. Applying environmentally friendly enzymatic racemization under mild conditions is in particular attractive. Owing to the variety of enzymes and the progress in enzyme engineering, suitable racemases can be found for many chiral systems. An amino acid racemase (AAR) from P. putida KT2440 is capable of processing a broad spectrum of amino acids at fast conversion rates. The focus of this study is the evaluation of the potential of integrating AAR immobilized on Purolite ECR 8309 to racemize L- or D-methionine (Met) within an enantioselective chromatographic resolution process. Racemization rates were studied for different temperatures, pH values, and fractions of organic co-solvents. The long-term stability of the immobilized enzyme at operating and storage conditions was found to be excellent and recyclability using water with up to 5 vol% ethanol at 20 °C could be demonstrated. Packed as an enzymatic fixed bed reactor, the immobilized AAR can be coupled with different resolution processes; for instance, with chromatography or with preferential crystallization. The performance of coupling it with enantioselective chromatography is estimated quantitatively, exploiting parametrized sub-models. To indicate the large potential of the AAR, racemization rates are finally given for lysine, arginine, serine, glutamine, and asparagine.
Fetal Gene Reactivation in Pulmonary Arterial Hypertension: GOOD, BAD, or BOTH?
Authors: Lemay Sarah-Eve , Awada Charifa , Shimauchi Tsukasa , Wu Wen-Hui , Bonnet Sébastien , Provencher Steeve , Boucherat Olivier
Published: June 2021

Pulmonary arterial hypertension is a debilitating chronic disorder marked by the progressive obliteration of the pre-capillary arterioles. This imposes a pressure overload on the right ventricle (RV) pushing the latter to undergo structural and mechanical adaptations that inexorably culminate in RV failure and death. Thanks to the advances in molecular biology, it has been proposed that some aspects of the RV and pulmonary vascular remodeling processes are orchestrated by a subversion of developmental regulatory mechanisms with an upregulation of a suite of genes responsible for the embryo’s early growth and normally repressed in adults. In this review, we present relevant background regarding the close relationship between overactivation of fetal genes and cardiopulmonary remodeling, exploring whether the reawakening of developmental factors plays a causative role or constitutes a protective mechanism in the setting of PAH.
Characterization of GAGG Doped with Extremely Low Levels of Chromium and Exhibiting Exceptional Intensity of Emission in NIR Region
Authors: Inkrataite Greta , Laurinavicius Gerardas , Enseling David , Zarkov Aleksej , Jüstel Thomas , Skaudzius Ramunas
Published: June 2021

Cerium and chromium co-doped gadolinium aluminum gallium garnets were prepared using sol-gel technique. These compounds potentially can be applied for NIR-LED construction, horticulture and theranostics. Additionally, magnesium and calcium ions were also incorporated into the structure. X-ray diffraction data analysis confirmed the all-cubic symmetry with an Ia-3d space group, which is appropriate for garnet-type materials. From the characterization of the luminescence properties, it was confirmed that both chromium and cerium emissions could be incorporated. Cerium luminescence was detected under 450 nm excitation, while for chromium emission, 270 nm excitation was used. The emission of chromium ions was exceptionally intense, although it was determined that these compounds are doped only by parts per million of Cr3+ ions. Typically, the emission maxima of chromium ions are located around 650–750 nm in garnet systems. However, in this case, the emission maximum for chromium is measured to be around 790 nm, caused by re-absorption of Cr3+ ions. The main observation of this study is that the switchable emission wavelength in a compound of single phase was obtained, despite the fact that doping with Cr ions was performed in ppm level, causing an intense emission in NIR region.
TransET: Knowledge Graph Embedding with Entity Types
Authors: Wang Peng , Zhou Jing , Liu Yuzhang , Zhou Xingchen
Published: June 2021

Knowledge graph embedding aims to embed entities and relations into low-dimensional vector spaces. Most existing methods only focus on triple facts in knowledge graphs. In addition, models based on translation or distance measurement cannot fully represent complex relations. As well-constructed prior knowledge, entity types can be employed to learn the representations of entities and relations. In this paper, we propose a novel knowledge graph embedding model named TransET, which takes advantage of entity types to learn more semantic features. More specifically, circle convolution based on the embeddings of entity and entity types is utilized to map head entity and tail entity to type-specific representations, then translation-based score function is used to learn the presentation triples. We evaluated our model on real-world datasets with two benchmark tasks of link prediction and triple classification. Experimental results demonstrate that it outperforms state-of-the-art models in most cases.