bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of ABCB1 Gene Polymorphism on Rivaroxaban Blood Concentration and Hemorrhagic Events in Patients With Atrial Fibrillation
Authors: Wang Yan , Chen Min , Chen Hui , Wang Fang
Published: April 2021

Background and Objectives: Genetic data on the pharmacokinetics of rivaroxaban and identification of factors that affect its biotransformation, distribution, and excretion will allow for generation of algorithms for personalized use of this drug in patients with atrial fibrillation (AF). Here we tested the effects of ABCB1 (ATP-binding cassette subfamily B member 1) polymorphisms on the valley rivaroxaban blood concentration and on the frequency of hemorrhagic events in patients with AF and propose a personal anticoagulation therapy management protocol.

Patients and Methods: This is a retrospective study. We enrolled Mongolian descent patients who met the criteria from May 2018 to August 2019 in Beijing and Fujian. Clinical data on gender, height, weight, liver and kidney functions, drug trough concentration, and drug dosage were collected; we recorded the bleeding events until 6 months after initiating the medication. ABCB1 single nucleotide polymorphisms including rs1128503, rs1045642, and rs4148738 were identified. After reaching the steady state of plasma concentration, the peripheral blood was collected to detect the trough rivaroxaban plasma concentrations before the next medication.

Results: We included 155 patients in this study including 81 men and 74 women, with an average age of 71.98 ± 10.72 years. The distribution of ABCB1 genotypes conformed to the Hardy–Weinberg equilibrium. Multiple comparisons between wild (TT) and mutant (CT and CC) genotypes at the rs1045642 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.586; TT vs. CC, p = 0.802; and CT vs. CC, p = 0.702). Multiple comparison between wild (TT) and mutant (CC) genotypes at the rs1128503 locus revealed a significant difference of rivaroxaban trough concentrations (TT vs. CC, p = 0.0421). But wild (TT) vs mutant (CT) genotypes and mutant CT vs mutant CC genotypes at the rs1128503 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.0651; TT vs. CT, p = 0.6127). Multiple comparisons between wild (GG) and mutant (AG and AA) genotypes at the rs4148738 locus showed no significant differences of rivaroxaban trough concentrations (GG vs. AG, p = 0.341; GG vs. AA, p = 0.612; AG vs. AA, p = 0.649). There was no significant correlation between ABCB1 gene variation loci rs1045642, rs1128503, rs4148738 and bleeding events.

Conclusion: rs1128503 locus variations are correlated with the serum concentration of rivaroxaban in patients of Mongolian descent. But no significant correlation between rs1128503 locus variations and bleeding events were obtained.
Organic Cation Transporter 1 an Intestinal Uptake Transporter: Fact or Fiction?
Authors: Wenzel Christoph , Drozdzik Marek , Oswald Stefan
Published: April 2021

Intestinal transporter proteins are known to affect the pharmacokinetics and in turn the efficacy and safety of many orally administered drugs in a clinically relevant manner. This knowledge is especially well-established for intestinal ATP-binding cassette transporters such as P-gp and BCRP. In contrast to this, information about intestinal uptake carriers is much more limited although many hydrophilic or ionic drugs are not expected to undergo passive diffusion but probably require specific uptake transporters. A transporter which is controversially discussed with respect to its expression, localization and function in the human intestine is the organic cation transporter 1 (OCT1). This review article provides an up-to-date summary on the available data from expression analysis as well as functional studies in vitro, animal findings and clinical observations. The current evidence suggests that OCT1 is expressed in the human intestine in small amounts (on gene and protein levels), while its cellular localization in the apical or basolateral membrane of the enterocytes remains to be finally defined, but functional data point to a secretory function of the transporter at the basolateral membrane. Thus, OCT1 should not be considered as a classical uptake transporter in the intestine but rather as an intestinal elimination pathway for cationic compounds from the systemic circulation.
Mechanisms of Plasma-Seed Treatments as a Potential Seed Processing Technology
Authors: Waskow Alexandra , Howling Alan , Furno Ivo
Published: April 2021

Plasma treatments are currently being assessed as a seed processing technology for agricultural purposes where seeds are typically subjected to pre-sowing treatments to improve the likelihood of timely and uniform germination. The aim of this review is to summarize the hypotheses and present the evidence to date of how plasma treatments affect seeds, considering that there is difficulty in standardizing the methodology in this interdisciplinary field given the plethora of variables in the experimental setup of the plasma device and handling of biological samples. The ever increasing interest for plasma agriculture drives the need for a review dedicated to seeds, which is understandable to an interdisciplinary audience of biologists and plasma physicists. Seeds are the first step of the agricultural cycle and at this stage, the plant can be given the highest probability of establishment, despite environmental conditions, to exploit the genetic potential of the seed. Furthermore, seedlings seem to be too sensitive to the oxidation of plasma and therefore, seeds seem to be the ideal target. This review intentionally does not include seed disinfection and sterilization due to already existing reviews. Instead, a summary of the mechanisms of how plasma may be affecting the seed and its germination and developmental properties will be provided and discussed.
Different Methods of Physical Training Applied to Women Breast Cancer Survivors: A Systematic Review
Authors: Schutz Silvia , Aidar Felipe J. , Souza Rafael Luiz Mesquita , dos Santos Jymmys Lopes , Voltarelli Fabrício Azevedo , Vieira Junior Roberto Carlos , Soares Nara Michelle Moura , Marçal Anderson Carlos
Published: April 2021

Objective: The objective of this systematic review was to identify the effects of different training methods in women who have survived breast cancer (WSBC).

Data Sources: Studies were identified by searching SportDiscus, Web of Science, PubMed, Scopus, Scielo, and Bireme.

Study Selection: The inclusion criteria were articles that addressed only breast cancer in women, were randomized clinical trials, and interventions involving physical training with Consort ≥80.

Data Extraction: The PICO and CONSORT strategies were used for the selection of articles and quality assessment of randomized clinical trials, respectively. Two independent reviewers searched for articles among the databases. Disagreements were discussed, and in the case of an impasse, a third reviewer was consulted.

Data Synthesis: Evidence that demonstrated the beneficial effects of physical exercise programs carried out by WSBC. Moderate or high-intensity exercise sessions have been shown to benefit women survivors of breast cancer. Among the modalities, the resistance exercise showed effects from 55% of one-repetition maximum (1 RM), exclusively or associated with other training regimes, such as aerobic (from 48% of heart rate), high-intensity interval training (HIIT), or impact. The main benefits include increased muscle strength, promoted by the practice of resistance exercise in combination with other types of exercises or alone; decreased fatigue; improved quality of life; improved psychosocial effects, and increased leisure time.

Conclusions: Physical training performed at a moderate or high intensity (aerobic or anaerobic) can reduce fatigue, improve quality of life, improve sleep quality, and increase bone mineral density in women survivors of breast cancer.
Severe Acute Respiratory Syndrome Coronavirus 2 and Male Reproduction: Relationship, Explanations, and Clinical Remedies
Authors: Xu Jia , He Liting , Zhang Yuan , Hu Zhiyong , Su Yufang , Fang Yiwei , Peng Meilin , Fan Zunpan , Liu Chunyan , Zhao Kai , Zhang Huiping
Published: April 2021

Coronavirus disease 2019 (COVID-2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been an ongoing pandemic and worldwide public health emergency, having drawn a lot of attention around the world. The pathogenesis of COVID-19 is characterized by infecting angiotensin-converting enzyme 2 (ACE2)-expressing cells, including testis-specific cells, namely, Leydig, Sertoli, and spermatogenic cells, which are closely related to male reproduction. This leads to aberrant hyperactivation of the immune system generating damage to the infected organs. An impairment in testicular function through uncontrolled immune responses alerts more attention to male infertility. Meanwhile, the recent clinical data indicate that the infection of the human testis with SARS-CoV-2 may impair male germ cell development, leading to germ cell loss and higher immune cell infiltration. In this review, we investigated the evidence of male reproductive dysfunction associated with the infection with SARS-CoV-2 and its possible immunological explanations and clinical remedies.
The Role of Endoplasmic Reticulum Stress Response in Pollen Development and Heat Stress Tolerance
Authors: Singh Mohan B. , Lohani Neeta , Bhalla Prem L.
Published: April 2021

Endoplasmic reticulum (ER) stress is defined by a protracted disruption in protein folding and accumulation of unfolded or misfolded proteins in the ER. This accumulation of unfolded proteins can result from excessive demands on the protein folding machinery triggered by environmental and cellular stresses such as nutrient deficiencies, oxidative stress, pathogens, and heat. The cell responds to ER stress by activating a protective pathway termed unfolded protein response (UPR), which comprises cellular mechanisms targeted to maintain cellular homeostasis by increasing the ER’s protein folding capacity. The UPR is especially significant for plants as being sessile requires them to adapt to multiple environmental stresses. While multiple stresses trigger the UPR at the vegetative stage, it appears to be active constitutively in the anthers of unstressed plants. Transcriptome analysis reveals significant upregulation of ER stress-related transcripts in diploid meiocytes and haploid microspores. Interestingly, several ER stress-related genes are specifically upregulated in the sperm cells. The analysis of gene knockout mutants in Arabidopsis has revealed that defects in ER stress response lead to the failure of normal pollen development and enhanced susceptibility of male gametophyte to heat stress conditions. In this mini-review, we provide an overview of the role of ER stress and UPR in pollen development and its protective roles in maintaining male fertility under heat stress conditions.
The Tactile-Visual Conflict Processing and Its Modulation by Tactile-Induced Emotional States: An Event-Related Potential Study
Authors: Guo Chengyao , Dupuis-Roy Nicolas , Jiang Jun , Xu Miaomiao , Xiao Xiao
Published: April 2021

This experiment used event-related potentials (ERPs) to study the tactile-visual information conflict processing in a tactile-visual pairing task and its modulation by tactile-induced emotional states. Eighteen participants were asked to indicate whether the tactile sensation on their body matched or did not match the expected tactile sensation associated with the object depicted in an image. The type of tactile-visual stimuli (matched vs. mismatched) and the valence of tactile-induced emotional states (positive vs. negative) were manipulated following a 2 × 2 factorial design. Electrophysiological analyses revealed a mismatched minus matched negative difference component between 420 and 620 ms after stimulus onset in the negative tactile-induced emotional state condition. This ND420-620 component was considered as a sign of the cross-modal conflict processing during the processing of incongruent tactile-visual information. In contrast, no significant mismatched minus matched negative difference component was found in the positive tactile-induced emotional state condition. Together, these results support the hypothesis that a positive emotional state induced by a positive tactile stimulation improves tactile-visual conflict processing abilities.
Illness Perceptions of COVID-19 in Europe: Predictors, Impacts and Temporal Evolution
Authors: Dias Neto David , Nunes da Silva Ana , Roberto Magda Sofia , Lubenko Jelena , Constantinou Marios , Nicolaou Christiana , Lamnisos Demetris , Papacostas Savvas , Höfer Stefan , Presti Giovambattista , Squatrito Valeria , Vasiliou Vasilis S. , McHugh Louise , Monestès Jean-Louis , Baban Adriana , Alvarez-Galvez Javier , Paez-Blarrina Marisa , Montesinos Francisco , Valdivia-Salas Sonsoles , Ori Dorottya , Lappalainen Raimo , Kleszcz Bartosz , Gloster Andrew , Karekla Maria , Kassianos Angelos P.
Published: April 2021

Objective: Illness perceptions (IP) are important predictors of emotional and behavioral responses in many diseases. The current study aims to investigate the COVID-19-related IP throughout Europe. The specific goals are to understand the temporal development, identify predictors (within demographics and contact with COVID-19) and examine the impacts of IP on perceived stress and preventive behaviors.

Methods: This was a time-series-cross-section study of 7,032 participants from 16 European countries using multilevel modeling from April to June 2020. IP were measured with the Brief Illness Perception Questionnaire. Temporal patterns were observed considering the date of participation and the date recoded to account the epidemiological evolution of each country. The outcomes considered were perceived stress and COVID-19 preventive behaviors.

Results: There were significant trends, over time, for several IP, suggesting a small decrease in negativity in the perception of COVID-19 in the community. Age, gender, and education level related to some, but not all, IP. Considering the self-regulation model, perceptions consistently predicted general stress and were less consistently related to preventive behaviors. Country showed no effect in the predictive model, suggesting that national differences may have little relevance for IP, in this context.

Conclusion: The present study provides a comprehensive picture of COVID-19 IP in Europe in an early stage of the pandemic. The results shed light on the process of IP formation with implications for health-related outcomes and their evolution.
The Neuroscience of the Flow State: Involvement of the Locus Coeruleus Norepinephrine System
Authors: van der Linden Dimitri , Tops Mattie , Bakker Arnold B.
Published: April 2021

Flow is a state of full task engagement that is accompanied with low-levels of self-referential thinking. Flow is considered highly relevant for human performance and well-being and has, therefore, been studied extensively. Yet, the neurocognitive processes of flow remain largely unclear. In the present mini-review we focus on how the brain's locus coeruleus-norepinephrine (LC-NE) system may be involved in a range of behavioral and subjective manifestations of flow. The LC-NE system regulates decisions regarding task engagement vs. disengagement. This is doneviadifferent modes of baseline and stimulus-evoked norepinephrine release. We emphasize the theoretical and empirical overlap between the LC-NE system and flow. For both, a match between a person's skill and task challenge is important in order to induce high levels task-related attention. Moreover, psychophysiological indicators of LC-NE system activity, such as eye pupil diameter and arousal are also sensitive to flow states. Flow is related to arousal in an inverted U-shape. Similarly, in theories on the LC-NE system, task engagement is highest with intermediate levels of arousal. We argue that knowledge about the role of the LC-NE system in establishing the flow experience may help to gain fundamental knowledge of flow and can contribute to unifying various empirical findings on this topic.
“Help! I Need Somebody”: Music as a Global Resource for Obtaining Wellbeing Goals in Times of Crisis
Authors: Granot Roni , Spitz Daniel H. , Cherki Boaz R. , Loui Psyche , Timmers Renee , Schaefer Rebecca S. , Vuoskoski Jonna K. , Cárdenas-Soler Ruth-Nayibe , Soares-Quadros João F. , Li Shen , Lega Carlotta , La Rocca Stefania , Martínez Isabel Cecilia , Tanco Matías , Marchiano María , Martínez-Castilla Pastora , Pérez-Acosta Gabriela , Martínez-Ezquerro José Darío , Gutiérrez-Blasco Isabel M. , Jiménez-Dabdoub Lily , Coers Marijn , Treider John Melvin , Greenberg David M. , Israel Salomon
Published: April 2021

Music can reduce stress and anxiety, enhance positive mood, and facilitate social bonding. However, little is known about the role of music and related personal or cultural (individualistic vs. collectivistic) variables in maintaining wellbeing during times of stress and social isolation as imposed by the COVID-19 crisis. In an online questionnaire, administered in 11 countries (Argentina, Brazil, China, Colombia, Italy, Mexico, the Netherlands, Norway, Spain, the UK, and USA, N = 5,619), participants rated the relevance of wellbeing goals during the pandemic, and the effectiveness of different activities in obtaining these goals. Music was found to be the most effective activity for three out of five wellbeing goals: enjoyment, venting negative emotions, and self-connection. For diversion, music was equally good as entertainment, while it was second best to create a sense of togetherness, after socialization. This result was evident across different countries and gender, with minor effects of age on specific goals, and a clear effect of the importance of music in people's lives. Cultural effects were generally small and surfaced mainly in the use of music to obtain a sense of togetherness. Interestingly, culture moderated the use of negatively valenced and nostalgic music for those higher in distress.
The Influence of Post-Traumatic Growth on College Students’ Creativity During the COVID-19 Pandemic: The Mediating Role of General Self-Efficacy and the Moderating Role of Deliberate Rumination
Authors: Zeng Wei , Zeng Yuqing , Xu Yanhua , Huang Dongtao , Shao Jinlian , Wu Jiamin , Wu Xingrou
Published: April 2021

Purpose: This study used a moderated mediation model to test the mediating effect of general self-efficacy on the relationship between post-traumatic growth (PTG) and creativity and the moderating effect of deliberate rumination in the second path of the indirect mediation path during the COVID-19 pandemic.

Methods: A sample of 881 university students from Guangdong Province, China, was surveyed with the Posttraumatic Growth Inventory, the Runco Ideational Behavior Scale, the General Self-Efficacy Scale, and the Deliberate Rumination Inventory. SPSS (23 version) and PROCESS (3.3 version) were used for correlation analyses, mediation analysis, and moderated mediation analysis.

Results: (1) PTG was positively correlated with creativity, self-efficacy, and deliberate rumination. Creativity was positively correlated with self-efficacy and deliberate rumination. Deliberate rumination was positively correlated with self-efficacy. (2) Self-efficacy mediated the relationship between PTG and creativity. (3) Deliberate rumination moderated the second half of the path of “PTG → self-efficacy → creativity.”

Conclusions: PTG affected creativity directly and also indirectly through self-efficacy. In particular, deliberate rumination moderated the relationship between self-efficacy and creativity, such that the association was stronger when the incidence of deliberate rumination was low. These results provide a more comprehensive understanding of the positive link between PTG and creativity.
The Grip Concept of Incisional Hernia Repair—Dynamic Bench Test, CT Abdomen With Valsalva and 1-Year Clinical Results
Authors: Kallinowski Friedrich , Gutjahr Dominik , Harder Felix , Sabagh Mohammad , Ludwig Yannique , Lozanovski Vladimir J. , Löffler Thorsten , Rinn Johannes , Görich Johannes , Grimm Annette , Vollmer Matthias , Nessel Regine
Published: April 2021

Incisional hernia is a frequent consequence of major surgery. Most repairs augment the abdominal wall with artificial meshes fixed to the tissues with sutures, tacks, or glue. Pain and recurrences plague at least 10–20% of the patients after repair of the abdominal defect. How should a repair of incisional hernias be constructed to achieve durability? Incisional hernia repair can be regarded as a compound technique. The biomechanical properties of a compound made of tissue, textile, and linking materials vary to a large extent. Tissues differ in age, exercise levels, and comorbidities. Textiles are currently optimized for tensile strength, but frequently fail to provide tackiness, dynamic stiction, and strain resistance to pulse impacts. Linking strength with and without fixation devices depends on the retention forces between surfaces to sustain stiction under dynamic load. Impacts such a coughing or sharp bending can easily overburden clinically applied composite structures and can lead to a breakdown of incisional hernia repair. Our group developed a bench test with tissues, fixation, and textiles using dynamic intermittent strain (DIS), which resembles coughing. Tissue elasticity, the size of the hernia under pressure, and the area of instability of the abdominal wall of the individual patient was assessed with low-dose computed tomography of the abdomen preoperatively. A surgical concept was developed based on biomechanical considerations. Observations in a clinical registry based on consecutive patients from four hospitals demonstrate low failure rates and low pain levels after 1 year. Here, results from the bench test, the application of CT abdomen with Valsalva's maneuver, considerations of the surgical concept, and the clinical application of our approach are outlined.
Three-Dimensional Imaging in Stem Cell-Based Researches
Authors: Nowzari Fariborz , Wang Huimei , Khoradmehr Arezoo , Baghban Mandana , Baghban Neda , Arandian Alireza , Muhaddesi Mahdi , Nabipour Iraj , Zibaii Mohammad I. , Najarasl Mostafa , Taheri Payam , Latifi Hamid , Tamadon Amin
Published: April 2021

Stem cells have an important role in regenerative therapies, developmental biology studies and drug screening. Basic and translational research in stem cell technology needs more detailed imaging techniques. The possibility of cell-based therapeutic strategies has been validated in the stem cell field over recent years, a more detailed characterization of the properties of stem cells is needed for connectomics of large assemblies and structural analyses of these cells. The aim of stem cell imaging is the characterization of differentiation state, cellular function, purity and cell location. Recent progress in stem cell imaging field has included ultrasound-based technique to study living stem cells and florescence microscopy-based technique to investigate stem cell three-dimensional (3D) structures. Here, we summarized the fundamental characteristics of stem cells via 3D imaging methods and also discussed the emerging literatures on 3D imaging in stem cell research and the applications of both classical 2D imaging techniques and 3D methods on stem cells biology.
Health-Related Quality of Life Profiles in Dialyzed Patients With Varying Health Literacy. A Cross-Sectional Study on Slovak Haemodialyzed Population
Authors: Skoumalova Ivana , Madarasova Geckova Andrea , Rosenberger Jaroslav , Majernikova Maria , Kolarcik Peter , Klein Daniel , de Winter Andrea F. , van Dijk Jitse P. , Reijneveld Sijmen A.
Published: April 2021

Objectives: Chronic kidney disease (CKD) strongly affects patients’ health-related quality of life (HRQoL), mostly in the advanced stages of CKD. Health literacy (HL) may affect this association, in particular for some aspects of HRQoL. The aim of this study is to compare the profiles of HRQoL in dialyzed patients with varying HL.

Methods: We obtained data on HL using the Health Literacy Questionnaire (HLQ) and on HRQoL using the Kidney Disease Quality of Life – Short Form (KDQoL-SF 1.3) in a multicentre cross-sectional study in 20 dialysis clinics in Slovakia (n = 542; mean age = 63.6 years; males: 60.7%). We compared HRQoL for three HL groups using ANOVA and the Kruskal-Wallis test.

Results: Patients with low HL reported worse HRQoL than patients with moderate and high HL. The greatest differences between HL groups were found in the scales Effect of kidney disease, Cognitive function, Quality of social interaction, Social support, Dialysis staff encouragement, Patient satisfaction, Physical functioning, Pain, Emotional well-being and Social function. p-values in all cases were <0.001.

Conclusion: Patients with low HL have a worse HRQoL in several domains than patients with a higher HL. Increasing HL capacities and better supporting patients with low HL should thus be given priority to support their HRQoL and at least maintain its level.
Interaction of Air Pollution with Snow and Seasonality Effects
Authors: Nazarenko Yevgen , Ariya Parisa A.
Published: April 2021

Interactions with environmental surfaces significantly affect the abundance and distribution of air pollutants [...]
Understanding the Role of Mean and Eddy Momentum Transport in the Rapid Intensification of Hurricane Irma (2017) and Hurricane Michael (2018)
Authors: Green Alrick , Gopalakrishnan Sundararaman G. , Alaka Ghassan J. , Chiao Sen
Published: April 2021

The prediction of rapid intensification (RI) in tropical cyclones (TCs) is a challenging problem. In this study, the RI process and factors contributing to it are compared for two TCs: an axis-symmetric case (Hurricane Irma, 2017) and an asymmetric case (Hurricane Michael, 2018). Both Irma and Michael became major hurricanes that made significant impacts in the United States. The Hurricane Weather Research and Forecasting (HWRF) Model was used to examine the connection between RI with forcing from the large-scale environment and the subsequent evolution of TC structure and convection. The observed large-scale environment was reasonably reproduced by HWRF forecasts. Hurricane Irma rapidly intensified in an environment with weak-to-moderate vertical wind shear (VWS), typically favorable for RI, leading to the symmetric development of vortical convective clouds in the cyclonic, vorticity-rich environment. Conversely, Hurricane Michael rapidly intensified in an environment of strong VWS, typically unfavorable for RI, leading to major asymmetries in the development of vortical convective clouds. The tangential wind momentum budget was analyzed for these two hurricanes to identify similarities and differences in the pathways to RI. Results suggest that eddy transport terms associated with convective processes positively contributed to vortex spin up in the early stages of RI and inhibited spin up in the later stages of RI in both TCs. In the early stages of RI, the mean transport terms exhibited notable differences in these TCs; they dominated the spin-up process in Irma and were of secondary importance to the spin-up process in Michael. Favorable aspects of the environment surrounding Michael appeared to aid in the RI process despite hostile VWS.
Node Centrality Measures Identify Relevant Structural MRI Features of Subjects with Autism
Authors: Zanghieri Marcello , Menichetti Giulia , Retico Alessandra , Calderoni Sara , Castellani Gastone , Remondini Daniel
Published: April 2021

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental conditions characterized by impairments in social interaction and communication and restricted patterns of behavior, interests, and activities. Although the etiopathogenesis of idiopathic ASD has not been fully elucidated, compelling evidence suggests an interaction between genetic liability and environmental factors in producing early alterations of structural and functional brain development that are detectable by magnetic resonance imaging (MRI) at the group level. This work shows the results of a network-based approach to characterize not only variations in the values of the extracted features but also in their mutual relationships that might reflect underlying brain structural differences between autistic subjects and healthy controls. We applied a network-based analysis on sMRI data from the Autism Brain Imaging Data Exchange I (ABIDE-I) database, containing 419 features extracted with FreeSurfer software. Two networks were generated: one from subjects with autistic disorder (AUT) (DSM-IV-TR), and one from typically developing controls (TD), adopting a subsampling strategy to overcome class imbalance (235 AUT, 418 TD). We compared the distribution of several node centrality measures and observed significant inter-class differences in averaged centralities. Moreover, a single-node analysis allowed us to identify the most relevant features that distinguished the groups.
Capacity Assessment of Existing RC Columns
Authors: Vecchi Francesca , Belletti Beatrice
Published: April 2021

Existing reinforced concrete (RC) members, designed in accordance with obsolete codes, are often characterized by high stirrup spacing. The collapse mechanisms generated by high stirrup spacing are typically related to the buckling of longitudinal reinforcement and can be accentuated when corrosion takes place. In this paper, new refined material constitutive laws for steel, including inelastic buckling and corrosion of reinforcement, are implemented in a fixed crack model suitable for RC elements subjected to cyclic loadings called the PARC_CL 2.1 crack model. The effectiveness of the proposed model is validated through comparison with available experimental data and analytical predictions. Finally, the proposed model is used to calibrate correction coefficients to be applied to current codes formulation for the ultimate rotational capacity prediction of non-conforming elements subjected to buckling phenomena and characterized by corrosion of reinforcing bars.
Reverse Engineering of Ewing Sarcoma Regulatory Network Uncovers PAX7 and RUNX3 as Master Regulators Associated with Good Prognosis
Authors: Ribeiro-Dantas Marcel da Câmara , Oliveira Imparato Danilo Oliveira , Dalmolin Matheus Gibeke Siqueira , de Farias Caroline Brunetto , Brunetto André Tesainer , da Cunha Jaeger Mariane , Roesler Rafael , Sinigaglia Marialva , Siqueira Dalmolin Rodrigo Juliani
Published: April 2021

Ewing Sarcoma (ES) is a rare malignant tumor occurring most frequently in adolescents and young adults. The ES hallmark is a chromosomal translocation between the chromosomes 11 and 22 that results in an aberrant transcription factor (TF) through the fusion of genes from the FET and ETS families, commonly EWSR1 and FLI1. The regulatory mechanisms behind the ES transcriptional alterations remain poorly understood. Here, we reconstruct the ES regulatory network using public available transcriptional data. Seven TFs were identified as potential MRs and clustered into two groups: one composed by PAX7 and RUNX3, and another composed by ARNT2, CREB3L1, GLI3, MEF2C, and PBX3. The MRs within each cluster act as reciprocal agonists regarding the regulation of shared genes, regulon activity, and implications in clinical outcome, while the clusters counteract each other. The regulons of all the seven MRs were differentially methylated. PAX7 and RUNX3 regulon activity were associated with good prognosis while ARNT2, CREB3L1, GLI3, and PBX3 were associated with bad prognosis. PAX7 and RUNX3 appear as highly expressed in ES biopsies and ES cell lines. This work contributes to the understanding of the ES regulome, identifying candidate MRs, analyzing their methilome and pointing to potential prognostic factors.
Gene Amplification-Associated Overexpression of the Selenoprotein tRNA Enzyme TRIT1 Confers Sensitivity to Arsenic Trioxide in Small-Cell Lung Cancer
Authors: Coll-SanMartin Laia , Davalos Veronica , Piñeyro David , Rosselló-Tortella Margalida , Bueno-Costa Alberto , Setien Fernando , Villanueva Alberto , Granada Isabel , Ruiz-Xiviller Neus , Kotter Annika , Helm Mark , Yokota Jun , Kawabata-Iwakawa Reika , Kohno Takashi , Esteller Manel
Published: April 2021

The alteration of RNA modification patterns is emerging as a common feature of human malignancies. If these changes affect key RNA molecules for mRNA translation, such as transfer RNA, they can have important consequences for cell transformation. TRIT1 is the enzyme responsible for the hypermodification of adenosine 37 in the anticodon region of human tRNAs containing serine and selenocysteine. Herein, we show that TRIT1 undergoes gene amplification-associated overexpression in cancer cell lines and primary samples of small-cell lung cancer. From growth and functional standpoints, the induced depletion of TRIT1 expression in amplified cells reduces their tumorigenic potential and downregulates the selenoprotein transcripts. We observed that TRIT1-amplified cells are sensitive to arsenic trioxide, a compound that regulates selenoproteins, whereas reduction of TRIT1 levels confers loss of sensitivity to the drug. Overall, our results indicate a role for TRIT1 as a small-cell lung cancer-relevant gene that, when undergoing gene amplification-associated activation, can be targeted with the differentiation agent arsenic trioxide.
Development of Machine Learning Models to Predict Platinum Sensitivity of High-Grade Serous Ovarian Carcinoma
Authors: Hwangbo Suhyun , Kim Se Ik , Kim Ju-Hyun , Eoh Kyung Jin , Lee Chanhee , Kim Young Tae , Suh Dae-Shik , Park Taesung , Song Yong Sang
Published: April 2021

To support the implementation of individualized disease management, we aimed to develop machine learning models predicting platinum sensitivity in patients with high-grade serous ovarian carcinoma (HGSOC). We reviewed the medical records of 1002 eligible patients. Patients’ clinicopathologic characteristics, surgical findings, details of chemotherapy, treatment response, and survival outcomes were collected. Using the stepwise selection method, based on the area under the receiver operating characteristic curve (AUC) values, six variables associated with platinum sensitivity were selected: age, initial serum CA-125 levels, neoadjuvant chemotherapy, pelvic lymph node status, involvement of pelvic tissue other than the uterus and tubes, and involvement of the small bowel and mesentery. Based on these variables, predictive models were constructed using four machine learning algorithms, logistic regression (LR), random forest, support vector machine, and deep neural network; the model performance was evaluated with the five-fold cross-validation method. The LR-based model performed best at identifying platinum-resistant cases with an AUC of 0.741. Adding the FIGO stage and residual tumor size after debulking surgery did not improve model performance. Based on the six-variable LR model, we also developed a web-based nomogram. The presented models may be useful in clinical practice and research.
Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions
Authors: Lalmanach Gilles , Kasabova-Arjomand Mariana , Lecaille Fabien , Saidi Ahlame
Published: April 2021

Alongside its contribution in maintaining skin homeostasis and its probable involvement in fetal and placental development, cystatin M/E (also known as cystatin 6) was first described as a tumor suppressor of breast cancer. This review aims to provide an update on cystatin M/E with particular attention paid to its role during tumorigenesis. Cystatin M/E, which is related to type 2 cystatins, displays the unique property of being a dual tight-binding inhibitor of both legumain (also known as asparagine endopeptidase) and cysteine cathepsins L, V and B, while its expression level is epigenetically regulated via the methylation of the CST6 promoter region. The tumor-suppressing role of cystatin M/E was further reported in melanoma, cervical, brain, prostate, gastric and renal cancers, and cystatin M/E was proposed as a biomarker of prognostic significance. Contrariwise, cystatin M/E could have an antagonistic function, acting as a tumor promoter (e.g., oral, pancreatic cancer, thyroid and hepatocellular carcinoma). Taking into account these apparently divergent functions, there is an urgent need to decipher the molecular and cellular regulatory mechanisms of the expression and activity of cystatin M/E associated with the safeguarding homeostasis of the proteolytic balance as well as its imbalance in cancer.
Epigenetic Drift Association with Cancer Risk and Survival, and Modification by Sex
Authors: Yu Chenglong , Wong Ee Ming , Joo Jihoon Eric , Hodge Allison M. , Makalic Enes , Schmidt Daniel , Buchanan Daniel D. , Severi Gianluca , Hopper John L. , English Dallas R. , Giles Graham G. , Southey Melissa C. , Dugué Pierre-Antoine
Published: April 2021

To investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case–control studies of colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869) and urothelial (n = 428) cancers, and mature B-cell lymphoma (n = 438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls)-replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios (HR)), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates for these CpGs using GS summary data were 94%, 86% and 91%, respectively. Significant associations for cancer risk and survival were identified at some individual age-related CpGs. Opposite to previous findings using epigenetic clocks, there was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Methylation at two CpGs overlapping TMEM49 and ARX genes was associated with survival of overall (HR = 0.91, p = 7.7 × 10−4) and colorectal (HR = 1.52, p = 1.8 × 10−4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.
Clinicopathological and Molecular Features of Patients with Early and Late Recurrence after Curative Surgery for Colorectal Cancer
Authors: Lan Yuan-Tzu , Chang Shih-Ching , Lin Pei-Ching , Lin Chun-Chi , Lin Hung-Hsin , Huang Sheng-Chieh , Lin Chien-Hsing , Liang Wen-Yi , Chen Wei-Shone , Jiang Jeng-Kai , Yang Shung-Haur , Lin Jen-Kou
Published: April 2021

Background: Few reports have investigated genetic alterations between patients with early and late recurrence following curative surgery for colorectal cancer (CRC). Methods: A total of 1227 stage I–III CRC patients who underwent curative resection were included retrospectively. Among them, 236 patients had tumor recurrence: 139 had early (<2 years after surgery) and 97 had late (≥2 years after surgery) recurrence. Clinicopathological features and genetic alterations were compared between the two groups. Results: Compared to those with late recurrence, patients with early recurrence were more likely to have advanced pathological node (N) categories; tumor, node, metastasis (TNM) stages; adjuvant chemotherapy treatment; liver metastases; APC mutations; and worse five-year overall survival rates. Patients with right-sided colon cancer were more likely to develop early recurrence than were those with left-sided colon cancer or rectal cancer. Regarding rectal cancer, patients with early recurrence were more likely to be at advanced pathological N categories and TNM stages than those with late recurrence. Multivariate analysis revealed old age, early recurrence, multiple-site recurrence, and BRAF and NRAS mutations to be independent prognostic factors. Conclusion: CRC patients with early recurrence have a worse OS rate and more APC mutations than those with late recurrence.
Tumor Biological Feature and Its Association with Positive Surgical Margins and Apical Margins after Radical Prostatectomy in Non-Metastasis Prostate Cancer
Authors: Wang Shuo , Du Peng , Cao Yudong , Yang Xiao , Yang Yong
Published: April 2021

Purpose: We assessed clinical and tumor biological features and evaluated their association with positive surgical margins (PSMs) and positive apical margins (PAMs) variability after radical prostatectomy (RP) in men with non-metastasis prostate cancer (nmPCa) in our institute. Patients and methods: During the period from January 2013 to December 2017, clinical and pathological data were collected in 200 patients with nmPCa undergoing RP in the Urological department of Peking University Cancer Hospital & Institute. Surgical and apical margins were stated negative and positive, separately. A dichotomous logistic regression model was used to assess clinical and tumor biological features including age, total prostate volume (TPV), biopsy positive cores (BPC), D’Amico risk grade, tumor clinical stage, International Society of Urologic Pathology (ISUP) grade, tPSA, f/t and pelvic lymph nodes (PLN) invasion, and their association with PSMs and PAMs was evaluated. Results: Overall, men with nmPCa in this study had a high ISUP grade (58.5% grade 3–5), high risk grade (89.4%) and high clinical T stage (56% cT3-4). PSMs were detected in 106 patients; the rate of PSMs was 53%. Among patients with PSMs, 83% were PAMs; the overall rate of PAMs was 44%. Among patients with PSMs, high risk (OR, 1.439; p = 0.023), cT3a (OR, 1.737; p = 0.045), cT3b (OR, 5.286; p < 0.001), cT4 (OR, 6.12; p < 0.001), ISUP Grade 4 (OR, 2; p = 0.034) and Grade 5 (OR, 6.167; p < 0.001) and PLN invasion (OR, 6; p = 0.019) were strongly associated with PSMs using a dichotomous logistic regression univariable model, and high risk (OR, 6; p = 0.019), cT3a (OR, 5.116; p = 0.048), cT3b (OR, 9.194; p = 0.008), cT4 (OR, 4.58; p = 0.01), ISUP Grade 4 (OR, 7.04; p = 0.035), Grade 5 (OR, 16.514; p = 0.002) and PLN invasion (OR, 5.516; p = 0.03) were independently associated with PSMs by using multivariable analysis. Among patients with PAMs, cT3b (OR, 2.667; p = 0.004), cT4 (OR, 3; p = 0.034) and proportion of BPC (OR, 4.594; p = 0.027) were strongly associated with PAMs by using a dichotomous logistic regression univariable model, and cT3b (OR, 3.899; p = 0.02), cT4 (OR, 2.8; p = 0.041) and proportion of BPC (OR, 5.247; p = 0.04) were independently associated with PSMs by using multivariable analysis. Conclusions: Patients with nmPCa in our institute had high risk, high ISUP grade and high clinical stage. Tumor biological factors were strongly associated with PSMs and PAMs, and PLN invasion was independently associated with PSMs. The risk factors influenced the status of surgical margins, and apical margins were different.
Trapping of Electrons around Nanoscale Metallic Wires Embedded in a Semiconductor Medium
Authors: Huynh Chi Cuong , Evrard Roger , Nguyen Ngoc Duy
Published: April 2021

We predict that conduction electrons in a semiconductor film containing a centered square array of metal nanowires normal to its plane are bound in quantum states around the central wires, if a positive bias voltage is applied between the wires at the square vertices and the latter. We obtain and discuss the eigenenergies and eigenfunctions of two models with different dimensions. The results show that the eigenstates can be grouped into different shells. The energy differences between the shells is typically a few tens of meV, which corresponds to frequencies of emitted or absorbed photons in a range of 3THz to 20THz approximately. These energy differences strongly depend on the bias voltage. We calculate the linear response of individual electrons on the ground level of our models to large-wavelength electromagnetic waves whose electric field is in the plane of the semiconductor film. The computed oscillator strengths are dominated by the transitions to the states in each shell whose wave function has a single radial node line normal to the wave electric field. We include the effect of the image charge induced on the central metal wires and show that it modifies the oscillator strengths so that their sum deviates from the value given by the Thomas-Reiche-Kuhn rule. We report the linear response, or polarizability, versus photon energy, of the studied models and their absorption spectra. The latter show well-defined peaks as expected from the study of the oscillator strengths. We show that the position of these absorption peaks is strongly dependent on the bias voltage so that the frequency of photon absorption or emission in the systems described here is easily tunable. This makes them good candidates for the development of novel infrared devices.
Multiple-Load Forecasting for Integrated Energy System Based on Copula-DBiLSTM
Authors: Zheng Jieyun , Zhang Linyao , Chen Jinpeng , Wu Guilian , Ni Shiyuan , Hu Zhijian , Weng Changhong , Chen Zhi
Published: April 2021

With the tight coupling of multi-energy systems, accurate multiple-load forecasting will be the primary premise for the optimal operation of integrated energy systems. Therefore, this paper proposes a Copula correlation analysis combined with deep bidirectional long and short-term memory neural network forecasting model. First, Copula correlation analysis is used to conduct correlation analysis on multiple loads and various influencing factors. The influencing factors that have a great correlation with multiple loads were screened out as the input feature set of the model to eliminate the influence of interfering factors. Then, a deep bidirectional long and short-term memory neural network was constructed. Combined with the input feature set screened by the Copula correlation analysis method, the useful information contained in the historical data was more comprehensively learned from the forward and backward directions for training and forecasting. Through the actual calculation example analysis and comparison with other models, the forecasting accuracy of the method presented in this paper was improved to a certain extent.