bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prognostic Risk Stratification Model to Identify Potential Population Benefiting From Postmastectomy Radiotherapy in T1–2 Breast Cancer With 1–3 Positive Axillary Lymph Nodes
Authors: Hou Niuniu , Zhang Juliang , Yang Lu , Wu Ying , Wang Zhe , Zhang Mingkun , Yang Li , Hou Guangdong , Wu Jianfeng , Wang Yidi , Dong Bingyao , Guo Lili , Shi Mei , Ling Rui
Published: April 2021

Background and Objectives

To establish a prognostic stratification nomogram for T1–2 breast cancer with 1–3 positive lymph nodes to determine which patients can benefit from postmastectomy radiotherapy (PMRT).

Methods

A population-based study was conducted utilizing data collected from the Surveillance, Epidemiology, and End Results database. Chi-square test or Fisher exact test was used to compare the distribution of characteristics. Cox analysis identified significant prognostic factors for survival. A prognostic stratification model was constructed by R software. Propensity score matching was applied to balance characteristics between PMRT cohort and control cohort. Kaplan-Meier method was performed to evaluate the performance of stratification and the benefits of PMRT in the total population and three risk groups.

Results

The overall performance of the nomogram was good (3-year, 5-year, 10-year AUC were 0.75, 0.72 and 0.67, respectively). The nomogram was performed to excellently distinguish low-risk, moderate-risk, and high-risk groups with 10-year overall survival (OS) of 86.9%, 73.7%, and 62.7%, respectively (P<0.001). In the high-risk group, PMRT can significantly better OS with 10-year all-cause mortality reduced by 6.7% (P = 0.027). However, there was no significant survival difference between PMRT cohort and control cohort in low-risk (P=0.49) and moderate-risk groups (P = 0.35).

Conclusion

The current study developed the first prognostic stratification nomogram for T1–2 breast cancer with 1–3 positive axillary lymph nodes and found that patients in the high-risk group may be easier to benefit from PMRT.
5-Fluorouracil: A Narrative Review on the Role of Regulatory Mechanisms in Driving Resistance to This Chemotherapeutic Agent
Authors: Ghafouri-Fard Soudeh , Abak Atefe , Tondro Anamag Farhad , Shoorei Hamed , Fattahi Faranak , Javadinia Seyed Alireza , Basiri Abbas , Taheri Mohammad
Published: April 2021

5-fluorouracil (5-FU) is among the mostly administrated chemotherapeutic agents for a wide variety of neoplasms. Non-coding RNAs have a central impact on the determination of the response of patients to 5-FU. These transcripts via modulation of cancer-related pathways, cell apoptosis, autophagy, epithelial–mesenchymal transition, and other aspects of cell behavior can affect cell response to 5-FU. Modulation of expression levels of microRNAs or long non-coding RNAs may be a suitable approach to sensitize tumor cells to 5-FU treatment via modulating multiple biological signaling pathways such as Hippo/YAP, Wnt/β-catenin, Hedgehog, NF-kB, and Notch cascades. Moreover, there is an increasing interest in targeting these transcripts in various kinds of cancers that are treated by 5-FU. In the present article, we provide a review of the function of non-coding transcripts in the modulation of response of neoplastic cells to 5-FU.
miR-4456/CCL3/CCR5 Pathway in the Pathogenesis of Tight Junction Impairment in Chronic Obstructive Pulmonary Disease
Authors: Yu Weiwei , Ye Ting , Ding Jie , Huang Yi , Peng Yang , Xia Qin , Cuntai Zhang
Published: April 2021

Background:Cigarette smoke exposure (CSE) is a major cause of chronic obstructive pulmonary disease (COPD). The smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the tight junction (TJ) proteins. Even though the inflammatory mechanism of chemokine (C-C motif) ligand 3 (CCL3) in COPD has gained increasing attention in the research community, however, the underlying signaling pathway, remains unknown.

Objectives:To identify the relationship of CCL3 in the pathogenesis of tight junction impairment in COPD and the pathway through which CSE causes damage to TJ in COPD via CCL3, bothin vivoandin vitro.

Methods:We screened the inflammatory factors in the peripheral blood mononuclear cells (PBMCs) from healthy controls and patients at each GOLD 1-4 stage of chronic obstructive pulmonary disease. RT-PCR, western blot, and ELISA were used to detect the levels of CCL3, ZO-1, and occludin after Cigarette smoke exposure. Immunofluorescence was applied to examine the impairment of the TJs in 16-HBE and A549 cells. The reverse assay was used to detect the effect of a CCR5 antagonist (DAPTA) in COPD. In the CSE-induced COPD mouse model, H&E staining and lung function tests were used to evaluate the pathological and physical states in each group. Immunofluorescence was used to assess the impairment of TJs in each group. ELISA and RT-PCR were used to examine the mRNA or protein expression of CCL3 or miR-4456 in each group.

Results:Thein vivoandin vitroresults showed that CCL3 expression was increased in COPD compared with healthy controls. CCL3 caused significant injury to TJs through its C-C chemokine receptor type 5 (CCR5), while miR-4456 could suppress the effect of CCL3 on TJs by binding to the 3′-UTR of CCL3.

Conclusion:miR-4456/CCL3/CCR5 pathway may be a potential target pathway for the treatment of COPD.
The Effects of Repeated Morphine Treatment on the Endogenous Cannabinoid System in the Ventral Tegmental Area
Authors: Zhang Hong , Lipinski Austin A. , Liktor-Busa Erika , Smith Angela F. , Moutal Aubin , Khanna Rajesh , Langlais Paul R. , Largent-Milnes Tally M. , Vanderah Todd W.
Published: April 2021

The therapeutic utility of opioids is diminished by their ability to induce rewarding behaviors that may lead to opioid use disorder. Recently, the endogenous cannabinoid system has emerged as a hot topic in the study of opioid reward but relatively little is known about how repeated opioid exposure may affect the endogenous cannabinoid system in the mesolimbic reward circuitry. In the present study, we investigated how sustained morphine may modulate the endogenous cannabinoid system in the ventral tegmental area (VTA) of Sprague Dawley rats, a critical region in the mesolimbic reward circuitry. Studies here using proteomic analysis and quantitative real-time PCR (qRT-PCR) found that the VTA expresses 32 different proteins or genes related to the endogenous cannabinoid system; three of these proteins or genes (PLCγ2, ABHD6, and CB2R) were significantly affected after repeated morphine exposure (CB2R was only detected by qRT-PCR but not proteomics). We also identified that repeated morphine treatment does not alter either anandamide (AEA) or 2-arachidonoylglycerol (2-AG) levels in the VTA compared to saline treatment; however, there may be diminished levels of anandamide (AEA) production in the VTA 4 h after a single morphine injection in both chronic saline and morphine pretreated cohorts. Treating the animals with an inhibitor of 2-AG degradation significantly decreased repeated opioid rewarding behavior. Taken together, our studies reveal a potential influence of sustained opioids on the endocannabinoid system in the VTA, suggesting that the endogenous cannabinoid system may participate in the opioid-induced reward.
Giloy Ghanvati (Tinospora cordifolia (Willd.) Hook. f. and Thomson) Reversed SARS-CoV-2 Viral Spike-Protein Induced Disease Phenotype in the Xenotransplant Model of Humanized Zebrafish
Authors: Balkrishna Acharya , Khandrika Lakshmipathi , Varshney Anurag
Published: April 2021

The current Severe Acute Respiratory Syndrome disease caused by Coronavirus-2 (SARS-CoV-2) has been a serious strain on the healthcare infrastructure mainly due to the lack of a reliable treatment option. Alternate therapies aimed at symptomatic relief are currently prescribed along with artificial ventilation to relieve distress. Traditional medicine in the form of Ayurveda has been used since ancient times as a holistic treatment option rather than targeted therapy. The practice of Ayurveda has several potent herbal alternatives for chronic cough, inflammation, and respiratory distress which are often seen in the SARS-CoV-2 infection. In this study we have used the aqueous extracts of Tinospora cordifolia (willd.) Hook. f. and Thomson in the form of Giloy Ghanvati, as a means of treatment to the SARS-CoV-2 spike-protein induced disease phenotype in a humanized zebrafish model. The introduction of spike-protein in the swim bladder transplanted with human lung epithelial cells (A549), caused an infiltration of pro-inflammatory immune cells such as granulocytes and macrophages into the swim bladder. There was also an increased systemic damage as exemplified by renal tissue damage and increased behavioral fever in the disease induction group. These features were reversed in the treatment group, fed with three different dosages of Giloy Ghanvati. The resultant changes in the disease phenotype were comparable to the group that were given the reference compound, Dexamethasone. These findings correlated well with various phyto-compounds detected in the Giloy Ghanvati and their reported roles in the viral disease phenotype amelioration.
Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway
Authors: Yang Min , Li Wen-Yun , Xie Jing , Wang Zi-Lin , Wen Yan-Long , Zhao Cun-Chao , Tao Liang , Li Ling-Fei , Tian Yang , Sheng Jun
Published: April 2021

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro. Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.
Endonasal CNS Delivery System for Blood-Brain Barrier Impermeant Therapeutic Oligonucleotides Using Heterotopic Mucosal Engrafting
Authors: Pawar Grishma , Parayath Neha N. , Sharma Aditya A. , Coito Carlos , Khorkova Olga , Hsiao Jane , Curry William T. , Amiji Mansoor M. , Bleier Benjamin S.
Published: April 2021

The most significant obstacle in the treatment of neurological disorders is the blood-brain barrier (BBB), which prevents 98% of all potential neuropharmaceuticals from reaching the central nervous system (CNS). Brain derived neurotrophic factor (BDNF) is one of the most intensely studied targets in Parkinson’s disease (PD) as it can reverse disease progression. BDNF AntagoNAT’s (ATs) are synthetic oligonucleotide-like compounds capable of upregulating endogenous BDNF expression. Despite the significant promise of BDNF AT therapies for PD, they cannot cross the blood-brain barrier (BBB). Our group has developed an innovative endonasal heterotopic mucosal grafting technique to provide a permanent method of permeabilizing the BBB. This method is based on established endoscopic surgical procedures currently used in routine clinical practice. Our overall goal for the study was to investigate the distribution and efficacy of BDNF AT’s using an extra-cranial graft model in naïve rats using the innovative heterotopic mucosal engrafting technique. BDNF AT cationic liposomes (ideal size range 200–250 nm) were developed and characterized to enhance the delivery to rat brain. Uptake, distribution and transfection efficiency of BDNF AntagoNAT’s in saline and liposomes were evaluated qualitatively (microscopy) and quantitatively (ELISA and AT hybridization assays) in RT4-D6P2T rat schwannoma cells and in naïve rats. In vivo therapeutic efficacy of BDNF AT’s encapsulated in liposomes was evaluated in a 6-OHDA toxin model of PD using western blot and tyrosine hydroxylase immunohistochemistry. Using complimentary in vitro and in vivo techniques, our results demonstrate that grafts are capable of delivering therapeutic levels of BDNF ATs in liposomes and saline formulation throughout the brain resulting in significant BDNF upregulation in key end target regions relevant to PD. BDNF AT liposomes resulted in a better distribution in rat brain as compared to saline control. The delivered BDNF AT’s encapsulated in liposomes also conferred a neuroprotective effect in a rat 6-OHDA model of PD. As a platform technique, these results further suggest that this approach may be utilized to deliver other BBB impermeant oligonucleotide-based therapeutics thereby opening the door to additional treatment options for CNS disease.
Implementation of a Humanoid Robot as an Innovative Approach to Child Life Interventions in a Children’s Hospital: Lofty Goal or Tangible Reality?
Authors: Beran Tanya N. , Pearson Jacqueline Reynolds , Lashewicz Bonnie
Published: April 2021

Introduction

This study reports the findings on how Child life specialists (CLSs) implemented an innovative approach to providing therapeutic support to pediatric patients.

Methods

Part of a larger study that uncovered themes about CLSs’ experiences while working with MEDi®, this study reports the reflections that CLSs have about the process of implementation. Seven CLSs participated in semi-structured interviews. Content analysis was conducted on interview data and three themes were generated.

Results

The first was in regards to the adoption process whereby CLS challenges, successes, and surprises were revealed. Second, CLSs explained how using MEDi® aligned with the roles and responsibilities of their profession. The third area of understanding was in CLS explanation of the friendly emotional impact MEDi® seems to have on the hospital environment.

Conclusion

Child life specialists are encouraged to use the MEDi® robot to support children at the bedside.
5G and EMF Exposure: Misinformation, Open Questions, and Potential Solutions
Authors: Elzanaty Ahmed , Chiaraviglio Luca , Alouini Mohamed-Slim
Published: April 2021

The massive deployment of advanced wireless networks is essential to support broadband connectivity, low latency communication, and Internet of Things applications. Nevertheless, in the time of coronavirus disease (COVID-19) there is a massive amount of misinformation and uncertainty about the impact of fifth-generation cellular network (5G) networks on human health. In this paper, we investigate the main categories of misinformation regarding 5G, i.e., fake theories, the misconception of 5G features, and open questions that require further research. Then, we propose two novel approaches for the design of electromagnetic field (EMF)-aware cellular networks that can reduce human exposure to radio frequency radiation.
Dimensional Taxonomy of Data Visualization: A Proposal From Communication Sciences Tackling Complexity
Authors: Cavaller Victor
Published: April 2021

This article consists of a conceptual analysis—from the perspective of communication sciences—of the relevant aspects that should be considered during operational steps in data visualization. The analysis is performed taking as a reference the components that integrate the communication framework theory—the message, the form, the encoder, the context, the channel, and the decoder—which correspond to six elements in the context of data visualization: content, graphic representation, encoding setup, graphic design and approach, media, and user. The study is focused accordingly on the dimensions that these elements describe: the degrees of abstraction of the information, the functionalities of the tool for the graphical representation, the specifications for the setup of the visualization, the approach modes to the context by the graphic design, the levels of communication efficiency in the media, and the requirements of the visualization perceived as values from the user experience side. The unfolding of these dimensions is undertaken following a common pattern of six organizational layers of complexity—basic, extended, synthetic, dynamic, interactive, and integrative—according to the analytical criteria. The results of the detailed study, based on an extensive scientific literature review, allow the design of a dimensional taxonomy of data visualization built on a matrix structure where these elements act as factors of completeness and the layers act as factors of complexity. As a conclusion, an object-centered model constituted by an ordered series of phases and achievements is proposed as a guide to complete a systematic process of data visualization.
Are Social Relationships an Underestimated Resource for Mental Health in Persons Experiencing Physical Disability? Observational Evidence From 22 Countries
Authors: Fekete Christine , Tough Hannah , Arora Mohit , Hasnan Nazirah , Joseph Conran , Popa Daiana , Strom Vegard , Middleton James
Published: April 2021

Objectives: As advancing evidence on modifiable resources to support mental health in persons experiencing physical disabilities is of particular importance, we investigate whether structural and functional social relationships relate to mental health in people with spinal cord injury (SCI).

Methods: Data from 12,330 participants of the International SCI community survey (InSCI) from 22 countries were analyzed. Structural (partnership status, living situation) and functional aspects of social relationships (belongingness, relationship satisfaction, problems with social interactions) were regressed on the SF-36 mental health index (MHI-5), stratified by countries and for the total sample using multilevel models.

Results: Functional aspects of social relationships were consistently related to clinically relevant higher MHI-5 scores and lower risk of mental health disorders (MHI-5 >56). Structural social relationships were inconsistently associated with mental health in our sample.

Conclusion: This study provides evidence that functional aspects of social relationships are important resources for mental health. Interventions to establish and maintain high quality relationships should be considered in public health interventions and rehabilitation programs to reduce long-term mental health problems in persons experiencing physical disabilities.
Assessment of Interactions between Yield Components of Common Vetch Cultivars in Both Conventional and Low-Input Cultivation Systems
Authors: Greveniotis Vasileios , Bouloumpasi Elisavet , Zotis Stylianos , Korkovelos Athanasios , Ipsilandis Constantinos
Published: April 2021

The primary purpose of this study was to explore yield stability of common vetch varieties based on the stability index, with a specific aim of exploring common vetch variety behavior regarding the yield of legumes under both conventional and low-input cultivation systems. Six varieties of common vetch (Vicia sativa L.), namely, cv. Filippos, cv. Omiros, cv. Alexandros, cv. Tempi, cv. Zefyros and cv. Pigasos, were used. The cultivation was conducted using a strip-plot design with the six varieties randomized within each plot in two farming systems (conventional and low-input). Filippos was the best variety in conventional farming for seed yield, followed by Omiros. Omiros was the best variety in the low-input farming system for seed yield. Comparisons between conventional and low-input farming systems generally did not display any effect on stability estimations, but revealed the varieties that exhibit stable performance even in low-input farming systems. Stability analysis via the AMMI1 and GxE biplot analysis for one main factor showed two groups of varieties for seed yield with similar behavior. Genotype and environment distribution were used to group varieties that showed better performance in certain environments for seed yield but with differences in comparison to other traits. Correlations between traits showed the positive relation of seed yield to the number of pods per plant, the number of seeds per pod, the pod length, the mean weight of pods and, especially, the hay weight (r = 0.771), a useful finding for indirect selection for breeders. The results provide valuable data regarding the genetic material, its adaptability and stability in varied environments and suitability for low-input cultivation systems.
Whole Blood Transcriptome Profiling Reveals Positive Effects of Olive Leaves-Supplemented Diet on Cholesterol in Goats
Authors: Ianni Andrea , Bennato Francesca , Martino Camillo , Colapietro Martina , Martino Giuseppe
Published: April 2021

Agro-industrial by-products represent an important source of compounds credited with high biotechnological potential. In the last decade, considerable interest has developed toward the use of these matrices as dietary supplements in the zootechnical field, paying particular attention to the qualitative aspects associated with animal products. However, less is known about the effect of these matrices on gene expression and thus on animal metabolism. Therefore, the aim of this study was to analyze the whole blood transcriptome of lactating goats fed a dietary supplementation with 10% olive leaves (OL), one of the main by-products deriving from the olive oil chain supply. By applying a false discovery rate (FDR) < 0.05 and a Log2 Fold change (Log2Fc) lower than −0.5 or higher than +0.5, it was possible to identify the differential regulation of gene coding for the apolipoprotein B (apoB) mRNA editing enzyme catalytic subunit 2 (APOBEC2), which showed downregulation in goats that received the dietary supplementation. An evaluation of both blood and milk cholesterol was performed, taking into account the strong association between plasma apoB and low-density lipoprotein (LDL). Results showed significantly lower concentrations of circulating cholesterol and cholesterol released into the milk through the mammary gland, demonstrating positive effects of OL feeding on animal welfare and potential health benefits for consumers.
Effects of Incorporating Dry Matter Intake and Residual Feed Intake into a Selection Index for Dairy Cattle Using Deterministic Modeling
Authors: Houlahan Kerry , Schenkel Flavio S. , Hailemariam Dagnachew , Lassen Jan , Kargo Morten , Cole John B. , Connor Erin E. , Wegmann Silvia , Junior Oliveira , Miglior Filippo , Fleming Allison , Chud Tatiane C.S. , Baes Christine F.
Published: April 2021

The inclusion of feed efficiency in the breeding goal for dairy cattle has been discussed for many years. The effects of incorporating feed efficiency into a selection index were assessed by indirect selection (dry matter intake) and direct selection (residual feed intake) using deterministic modeling. Both traits were investigated in three ways: (1) restricting the trait genetic gain to zero, (2) applying negative selection pressure, and (3) applying positive selection pressure. Changes in response to selection from economic and genetic gain perspectives were used to evaluate the impact of including feed efficiency with direct or indirect selection in an index. Improving feed efficiency through direct selection on residual feed intake was the best scenario analyzed, with the highest overall economic response including favorable responses to selection for production and feed efficiency. Over time, the response to selection is cumulative, with the potential for animals to reduce consumption by 0.16 kg to 2.7 kg of dry matter per day while maintaining production. As the selection pressure increased on residual feed intake, the response to selection for production, health, and fertility traits and body condition score became increasingly less favorable. This work provides insight into the potential long-term effects of selecting for feed efficiency as residual feed intake.
Remarkable Cryptic Diversity of Paratylenchus spp. (Nematoda: Tylenchulidae) in Spain
Authors: Clavero-Camacho Ilenia , Cantalapiedra-Navarrete Carolina , Archidona-Yuste Antonio , Castillo Pablo , Palomares-Rius Juan Emilio
Published: April 2021

In previous studies, fifteen species of Paratylenchus, commonly known as pin nematodes, have been reported in Spain. These plant-parasitic nematodes are ectoparasites with a wide host range and global distribution. In this research, 27 populations from twelve Paratylenchus species from 18 municipalities in Spain were studied using morphological, morphometrical and molecular data. This integrative taxonomic approach allowed the identification of twelve species, four of them were considered new undescribed species and eight were already known described. The new species described here are P. caravaquenus sp. nov., P. indalus sp. nov., P. pedrami sp. nov. and P. zurgenerus sp. nov. As for the already known described species, five were considered as first reports for the country, specifically P.enigmaticus, P. hamatus, P. holdemani, P. israelensis, and P. veruculatus, while P. baldaccii, P. goodeyi and P. tenuicaudatus had already been recorded in Spain. This study provides detail morphological and molecular data, including the D2-D3 expansion segments of 28S rRNA, ITS rRNA, and partial mitochondrial COI regions for the identification of different Paratylenchus species found in Spain. These results confirm the extraordinary cryptic diversity in Spain and with examples of morphostatic speciation within the genus Paratylenchus.
Considerations for the Nonclinical Safety Evaluation of Antibody–Drug Conjugates
Authors: Fisher J. Edward
Published: April 2021

The targeted delivery of drugs by means of linking them to antibodies (Abs) to form antibody–drug conjugates (ADCs) has become an important approach in oncology and could potentially be used in other therapeutic areas. Targeted therapy is aimed at improving clinical efficacy while minimizing adverse reactions. The nonclinical safety assessment of ADCs presents several unique challenges involving the need to examine a complex molecule, each component of which can contribute to the effects observed, in appropriate animal models. Some considerations for the nonclinical safety evaluation of ADCs based on a literature review of ADCs in clinical development (currently or previously) are discussed.
Oxidative Stress and Rare Diseases: From Molecular Crossroads to Therapeutic Avenues
Authors: Romá-Mateo Carlos , García-Giménez José Luis
Published: April 2021

Writing an editorial about rare diseases can become a messy subject from the biological perspective [...]
Antioxidant Effects of Schisandra chinensis Fruits and Their Active Constituents
Authors: Kopustinskiene Dalia M. , Bernatoniene Jurga
Published: April 2021

Schisandra chinensis Turcz. (Baill.) fruits, their extracts, and bioactive compounds are used in alternative medicine as adaptogens and ergogens protecting against numerous neurological, cardiovascular, gastrointestinal, liver, and skin disorders. S. chinensis fruit extracts and their active compounds are potent antioxidants and mitoprotectors exerting anti-inflammatory, antiviral, anticancer, and anti-aging effects. S. chinensis polyphenolic compounds—flavonoids, phenolic acids and the major constituents dibenzocyclooctadiene lignans are responsible for the S. chinensis antioxidant activities. This review will focus on the direct and indirect antioxidant effects of S. chinensis fruit extract and its bioactive compounds in the cells during normal and pathological conditions.
Numerical Modelling of Flow-Debris Interaction during Extreme Hydrodynamic Events with DualSPHysics-CHRONO
Authors: Ruffini Gioele , Briganti Riccardo , De Girolamo Paolo , Stolle Jacob , Ghiassi Bahman , Castellino Myrta
Published: April 2021

Floods can transport debris of a very wide range of dimensions, from cohesive sediments to large floating debris, such as trees and cars. The latter increases the risk associated with floods by, for example, obstructing the flow or damaging structures due to impact. The transport of this type of debris and their interaction with structures are often studied experimentally in the context of tsunamis and flash floods. Numerical studies on this problem are rare, therefore the present study focuses on the numerical modelling of the flow-debris interaction. This is achieved by simulating multiple laboratory experiments, available in the literature, of a single buoyant container transported by a dam-break flow in order to validate the chosen numerical approach. The numerical simulations are carried using the open source DualSPHysics model based on the smoothed particle hydrodynamics method coupled with the multi-physics engine CHRONO, which handles the container–bottom interactions. The trajectory, as well as the velocity of the centroid of the container, were tracked throughout the simulation and compared with the same quantities measured in the laboratory. The agreement between the model and the experiment results is quantitatively assessed using the normalised root mean squared error and it is shown that the model is accurate in reproducing the floating container trajectory and velocity.
Technical Specification of the Small-Angle Neutron Scattering Instrument SKADI at the European Spallation Source
Authors: Jaksch Sebastian , Chennevière Alexis , Désert Sylvain , Kozielewski Tadeusz , Feilbach Herbert , Lavie Pascal , Hanslik Romuald , Gussen Achim , Butterweck Stephan , Engels Ralf , Frielinghaus Henrich , Förster Stephan , Müller-Buschbaum Peter
Published: April 2021

Small-K Advanced DIffractometer (SKADI is a Small-Angle Neutron Scattering (SANS) instrument to be constructed at the European Spallation Source (ESS). SANS instruments allow investigations of the structure of materials in the size regime between Angstroms up to micrometers. As very versatile instruments, they usually cater to the scientific needs of communities, such as chemists, biologists, and physicists, ranging from material and food sciences to archeology. They can offer analysis of the micro- and mesoscopic structure of the samples, as well as an analysis of the spin states in the samples, for example, for magnetic samples. SKADI, as a broad range instrument, thus offers features, such as an extremely flexible space for the sample environment, to accommodate a wide range of experiments, high-flux, and optimized detector-collimation system to allow for an excellent resolution of the sample structure, short measurement times to be able to record the internal kinetics during a transition in the sample, as well as polarized neutron scattering. In this manuscript, we describe the final design for the construction of SKADI. All of the features and capabilities presented here are projected to be included into the final instrument when going into operation phase.
Microcrack Detection Using Spectral Response Data Alone
Authors: Lee Gee-Soo , Kim Chan-Jung
Published: April 2021

Microcracks of depth less than 200 μm in mechanical components are difficult to detect because conventional methods such as X-ray or eddy current measurements are less sensitive to such depths. Nonetheless, an efficient microcrack detection method is required urgently in the mechanical industry because microcracks are produced frequently during cold-forming. The frequency response function (FRF) is known to be highly sensitive even to microcracks, and it can be obtained using both the input data of an impact hammer and the response data of an accelerometer. Under the assumption of an impulse force with a similar spectral impulse pattern, spectral response data alone could be used as a crack indicator because the dynamic characteristics of a microcrack may be dependent solely on these measured data. This study investigates the feasibility of microcrack detection using the response data alone through impact tests with a simple rectangular specimen. A simple rectangular specimen with a 200 μm microcrack at one face was prepared. The experimental modal analysis was conducted for the normal (uncracked) specimen and found-first bending mode about 1090 Hz at the X-Y plane (in-plane). Response accelerations were obtained in both at in-plane locations as well as X-Z plane (out-of-plane), and the crack was detected using the coherence function between a normal and a cracked specimen. A comparison of the crack inspection results obtained using the response data and the FRF data indicated the validity of the proposed method.
Transparent Substance in a Transnational Existence: Materiality, Migration, Memory, and Gender—The Case of Israeli Artist Alina Rom Cohen
Authors: Dekel Tal
Published: April 2021

This article discusses the art of Alina Rome Cohen, a woman artist from the former Soviet Union who immigrated to Israel. Her glass sculptures highlight her hyphenated, multilayered, and dynamic identity, illustrating identity construction processes of migrant women under conditions of uprooting and re-grounding in the globalized era of transnationalism. The discussion feeds from theories influenced by “the material turn”, suggesting that artifacts “speak”. I will therefore argue that the material—glass—is involved in the active discussion and negotiation of power relations within society. Framed through Alfred Gell’s anthropological theory of art, first introduced in his book titled Art and Agency from 1998, this approach proposes a horizon of agency for the artworks themselves, which function in the world alongside other actants operating in the field, such as human beings. This article will analyze Rom Chohen’s artworks and will be informed by cultural theories from migration studies and gender studies, in order to ask new questions about the dynamics of the exclusion and inclusion of migrants under the ethno-national state of Israel, while offering alternative ways by which to think of concepts such as memory and time, as past and present are brought to a simultaneity.
Multiscale Modeling of Convection and Pollutant Transport Associated with Volcanic Eruption and Lava Flow: Application to the April 2007 Eruption of the Piton de la Fournaise (Reunion Island)
Authors: Filippi Jean-Baptiste , Durand Jonathan , Tulet Pierre , Bielli Soline
Published: April 2021

Volcanic eruptions can cause damage to land and people living nearby, generate high concentrations of toxic gases, and also create large plumes that limit observations and the performance of forecasting models that rely on these observations. This study investigates the use of micro- to meso-scale simulation to represent and predict the convection, transport, and deposit of volcanic pollutants. The case under study is the 2007 eruption of the Piton de la Fournaise, simulated using a high-resolution, coupled lava/atmospheric approach (derived from wildfire/atmosphere coupled code) to account for the strong, localized heat and gaseous fluxes occurring near the vent, over the lava flow, and at the lava–sea interface. Higher resolution requires fluxes over the lava flow to be explicitly simulated to account for the induced convection over the flow, local mixing, and dilution. Comparisons with air quality values at local stations show that the simulation is in good agreement with observations in terms of sulfur concentration and dynamics, and performs better than lower resolution simulation with parameterized surface fluxes. In particular, the explicit representation of the thermal flows associated with lava allows the associated thermal breezes to be represented. This local modification of the wind flow strongly impacts the organization of the volcanic convection (injection height) and the regional transport of the sulfur dioxide emitted at the vent. These results show that explicitly solving volcanic activity/atmosphere complex interactions provides realistic forecasts of induced pollution.
Impact of SARS-CoV-2 on Ambient Air Quality in Northwest China (NWC)
Authors: Zaib Shah , Lu Jianjiang , Shahid Muhammad Zeeshaan , Ahmar Sunny , Shahid Imran
Published: April 2021

SARS-CoV-2 was discovered in Wuhan (Hubei) in late 2019 and covered the globe by March 2020. To prevent the spread of the SARS-CoV-2 outbreak, China imposed a countrywide lockdown that significantly improved the air quality. To investigate the collective effect of SARS-CoV-2 on air quality, we analyzed the ambient air quality in five provinces of northwest China (NWC): Shaanxi (SN), Xinjiang (XJ), Gansu (GS), Ningxia (NX) and Qinghai (QH), from January 2019 to December 2020. For this purpose, fine particulate matter (PM2.5), coarse particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were obtained from the China National Environmental Monitoring Center (CNEMC). In 2020, PM2.5, PM10, SO2, NO2, CO, and O3 improved by 2.72%, 5.31%, 7.93%, 8.40%, 8.47%, and 2.15%, respectively, as compared with 2019. The PM2.5 failed to comply in SN and XJ; PM10 failed to comply in SN, XJ, and NX with CAAQS Grade II standards (35 µg/m3, 70 µg/m3, annual mean). In a seasonal variation, all the pollutants experienced significant spatial and temporal distribution, e.g., highest in winter and lowest in summer, except O3. Moreover, the average air quality index (AQI) improved by 4.70%, with the highest improvement in SN followed by QH, GS, XJ, and NX. AQI improved in all seasons; significant improvement occurred in winter (December to February) and spring (March to May) when lockdowns, industrial closure etc. were at their peak. The proportion of air quality Class I improved by 32.14%, and the number of days with PM2.5, SO2, and NO2 as primary pollutants decreased while they increased for PM10, CO, and O3 in 2020. This study indicates a significant association between air quality improvement and the prevalence of SARS-CoV-2 in 2020.
Antitumor Activity of Pulvomycin via Targeting Activated-STAT3 Signaling in Docetaxel-Resistant Triple-Negative Breast Cancer Cells
Authors: Byun Woong Sub , Bae Eun Seo , Cui Jinsheng , Park Hyen Joo , Oh Dong-Chan , Lee Sang Kook
Published: April 2021

Although docetaxel-based regimens are common and effective for early-stage triple-negative breast cancer (TNBC) treatment, acquired drug resistance frequently occurs. Therefore, a novel therapeutic strategy for docetaxel-resistant TNBC is urgently required. Signal transducer and activator of transcription 3 (STAT3) plays a pivotal role in the tumorigenesis and metastasis of numerous cancers, and STAT3 signaling is aberrantly activated in TNBC cells. In this study, a docetaxel-resistant TNBC cell line (MDA-MB-231-DTR) was established, and mechanisms for the antitumor activity of pulvomycin, a novel STAT3 inhibitor isolated from marine-derived actinomycete, were investigated. Levels of activated STAT3 (p-STAT3 (Y705)) increased in docetaxel-resistant cells, and knockdown of STAT3 recovered the sensitivity to docetaxel in MDA-MB-231-DTR cells. Pulvomycin effectively inhibited the proliferation of both cell lines. In addition, pulvomycin suppressed the activation of STAT3 and subsequently induced G0/G1 cell cycle arrest and apoptosis. Pulvomycin also significantly inhibited the invasion and migration of MDA-MB-231-DTR cells through the modulation of epithelial-mesenchymal transition markers. In an MDA-MB-231-DTR-bearing xenograft mouse model, the combination of pulvomycin and docetaxel effectively inhibited tumor growth through STAT3 regulation. Thus, our findings demonstrate that the combination of docetaxel and STAT3 inhibitors is an effective strategy for overcoming docetaxel resistance in TNBC.
Nutritional Intervention Facilitates Food Intake after Epilepsy Surgery
Authors: Suzumura Rika , Fujimoto Ayataka , Sato Keishiro , Baba Shimpei , Kubota Satoko , Itoh Sayuri , Shibamoto Isamu , Enoki Hideo , Okanishi Tohru
Published: April 2021

Background: We investigated whether nutritional intervention affected food intake after epilepsy surgery and if intravenous infusions were required in patients with epilepsy. We hypothesized that postoperative food intake would be increased by nutritional intervention. The purpose of this study was to compare postoperative food intake in the periods before and after nutritional intervention. Methods: Between September 2015 and October 2020, 124 epilepsy surgeries were performed. Of these, 65 patients who underwent subdural electrode placement followed by open cranial epilepsy surgery were studied. Postoperative total food intake, rate of maintenance of food intake, and total intravenous infusion were compared in the periods before and after nutritional intervention. Results: A total of 26 females and 39 males (age range 3–60, mean 27.1, standard deviation (SD) 14.3, median 26 years) were enrolled. Of these, 18 females and 23 males (3–60, mean 28.2, SD 15.1, median 26 years) were in the pre-nutritional intervention period group, and eight females and 16 males (5–51, mean 25.2, SD 12.9, median 26.5 years) were in the post-nutritional intervention period group. The post-nutritional intervention period group showed significantly higher food intake (p = 0.015) and lower total infusion (p = 0.006) than the pre-nutritional intervention period group. Conclusion: The nutritional intervention increased food intake and also reduced the total amount of intravenous infusion. To identify the cut-off day to cease the intervention and to evaluate whether the intervention can reduce the complication rate, a multicenter study with a large number of patients is warranted.
EEG—Single-Channel Envelope Synchronisation and Classification for Seizure Detection and Prediction
Authors: Romaine James , Pereira Martín Mario , Salvador Ortiz José , Manzano Crespo José
Published: April 2021

This paper tackles the complex issue of detecting and classifying epileptic seizures whilst maintaining the total calculations at a minimum. Where many systems depend on the coupling between multiple sources, leading to hundreds of combinations of electrodes, our method calculates the instantaneous phase between non-identical upper and lower envelopes of a single-electroencephalography channel reducing the workload to the total number of electrode points. From over 600 h of simulations, our method shows a sensitivity and specificity of 100% for high false-positive rates and 83% and 75%, respectively, for moderate to low false positive rates, which compares well to both single- and multi-channel-based methods. Furthermore, pre-ictal variations in synchronisation were detected in over 90% of patients implying a possible prediction system.
Morphological and Hemodynamic Changes during Cerebral Aneurysm Growth
Authors: Nordahl Emily R. , Uthamaraj Susheil , Dennis Kendall D. , Sejkorová Alena , Hejčl Aleš , Hron Jaroslav , Švihlová Helena , Carlson Kent D. , Suzen Yildirim Bora , Dragomir-Daescu Dan
Published: April 2021

Computational fluid dynamics (CFD) has grown as a tool to help understand the hemodynamic properties related to the rupture of cerebral aneurysms. Few of these studies deal specifically with aneurysm growth and most only use a single time instance within the aneurysm growth history. The present retrospective study investigated four patient-specific aneurysms, once at initial diagnosis and then at follow-up, to analyze hemodynamic and morphological changes. Aneurysm geometries were segmented via the medical image processing software Mimics. The geometries were meshed and a computational fluid dynamics (CFD) analysis was performed using ANSYS. Results showed that major geometry bulk growth occurred in areas of low wall shear stress (WSS). Wall shape remodeling near neck impingement regions occurred in areas with large gradients of WSS and oscillatory shear index. This study found that growth occurred in areas where low WSS was accompanied by high velocity gradients between the aneurysm wall and large swirling flow structures. A new finding was that all cases showed an increase in kinetic energy from the first time point to the second, and this change in kinetic energy seems correlated to the change in aneurysm volume.
Future Perspectives on the TNM Staging for Lung Cancer
Authors: Rami-Porta Ramón
Published: April 2021

Since its conception by Pierre Denoix in the mid-20th century, the tumor, node, and metastasis (TNM) classification has undergone seven revisions. The North American database managed by Clifton Mountain was used to inform the 2nd to the 6th editions, and an international database collected by the International Association for the Study of Lung Cancer, promoted by Peter Goldstraw, was used to inform the 7th and the 8th editions. In these two latest editions, it was evident that the impact of tumor size was much greater than it was suggested in previous editions; that the amount of nodal disease had prognostic relevance; and that the number and location of the distant metastases had prognostic implications. However, the TNM classification is not the only prognostic factor. Data are being collected now to inform the 9th edition of the TNM classification, scheduled for publication in 2024. Patient-, environment-, and tumor-related factors, including biomarkers (genetic biomarkers, copy number alterations, and protein alterations) are being collected to combine them in prognostic groups to enhance the prognosis provided by the mere anatomic extent of the tumor, and to offer a more personalized prognosis to an individual patient. International collaboration is essential to build a large and detailed database to achieve these objectives.
Biomarker-Guided Anti-EGFR Rechallenge Therapy in Metastatic Colorectal Cancer
Authors: Ciardiello Davide , Martini Giulia , Famiglietti Vincenzo , Napolitano Stefania , De Falco Vincenzo , Troiani Teresa , Latiano Tiziana , Ros Javier , Elez Fernandez Elena , Vitiello Pietro , Maiello Evaristo , Ciardiello Fortunato , Martinelli Erika
Published: April 2021

The prognosis of patients with metastatic colorectal cancer (mCRC) who progressed to the first and the second lines of treatment is poor. Thus, new therapeutic strategies are needed. During the last years, emerging evidence suggests that retreatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAbs) in the third line of mCRC patients, that have previously obtained clinical benefit by first-line therapy with anti-EGFR MAbs plus chemotherapy, could lead to prolonged survival. The rationale beyond this “rechallenge” strategy is that, after disease progression to first line EGFR-based therapy, a treatment break from anti-EGFR drugs results in RAS mutant cancer cell decay, restoring the sensitivity of cancer cells to cetuximab and panitumumab. In fact, rechallenge treatment with anti-EGFR drugs has shown promising clinical activity, particularly in patients with plasma RAS and BRAF wild type circulating tumor DNA, as defined by liquid biopsy analysis at baseline treatment. The aim of this review is to analyze the current knowledge on rechallenge and to investigate the role of novel biomarkers that can guide the appropriate selection of patients that could benefit from this therapeutic strategy. Finally, we discuss on-going trials and future perspectives.