bluuebunny/crossref_metadata_2025_split huggingface dataset:
The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms
Authors: Zhang Yuanyuan , Hutterer Evelyn , Hultin Sara , Bergman Otto , Forteza Maria , Andonovic Zorana , Ketelhuth Daniel , Roy Joy , Eriksson Per , Holmgren Lars 
Published: June 2021

Abstract
Arterial endothelial cells (ECs) have the ability to respond to mechanical forces exerted by fluid shear stress. This response is of importance, as it is protective against vascular diseases such as atherosclerosis and aortic aneurysms. Mechanical forces are transmitted at the sites of adhesion to the basal membrane as well as cell-cell junctions where protein complexes connect to the cellular cytoskeleton to relay force into the cell. Here we present a novel protein complex that connects junctional VE-cadherin and radial actin filaments to the LINC complex in the nuclear membrane. We show that the scaffold protein AmotL2 is essential for the formation of radial actin filaments and the flow-induced alignment of aortic and arterial ECs. The deletion of endothelial AmotL2 alters nuclear shape as well as subcellular positioning. Molecular analysis shows that VE-cadherin is mechanically associated with the nuclear membrane via binding to AmotL2 and Actin. Furthermore, the deletion of AmotL2 in ECs provokes a pro-inflammatory response and abdominal aortic aneurysms (AAA) in the aorta of mice on a normal diet. Remarkably, transcriptome analysis of AAA samples from human patients revealed a negative correlation between AmotL2 expression and aneurysm diameters, as well as a positive correlation between AmotL2 and YAP expression. These findings provide a conceptual framework regarding how mechanotransduction in the junctions is coupled with vascular disease.
Appropriate sites for the active surveillance of carbapenemase-producing Enterobacteriaceae
Authors: Park Joung Ha , Choi Hye-Suk , Yang Hyejin , Lee Hyun-Ju , Kwak Sun Hee , Kim Eun Ok , Chong Yong Pil , Choi Sang-Ho , Lee Sang-Oh , Kim Yang Soo , Sung Heungsup , Kim Mi-Na , Kim Sung-Han , Jung Jiwon 
Published: June 2021

Abstract
Background: Active surveillance tests for carbapenemase-producing Enterobacteriaceae (CPE) are recommended in patients showing risk factors for colonization by these bacteria. There are limited data however on whether surveillance tests for anatomic sites other than the stool would be useful to detect CPE colonization, and we investigated this in our present study.Methods: Retrospective analysis was performed on cases at our tertiary care hospital during a 5-year period. Patients with CPE colonization had been admitted to our surgical intensive care unit (SICU) or sub-ICU for liver transplantation in this period and undergone surveillance tests for both the stool and other sites. Patients were grouped as stool CPE negative (but which included CPE positive cases from initial sputum and other site tests) or positive. Results: Among the total study cohort of 158 patients, 138 (87.3%) were included in the stool CPE positive group and the remaining 20 (12.7%) in the stool CPE negative group. While the sensitivity of CPE surveillance testing of the stool was 87.3% (95% CI 81.1-92.1), the sensitivity when combining stool and sputum samples was 93.7% (88.7-96.9). The transmission rates were similar for patients showing CPE positivity in the stool, sputum and other sites, at 4.8% (27/557), 4.7% (3/64), and 6.7% (1/15), respectively (p = 0.95).Conclusions: The sensitivity of CPE detection in a stool sample is suboptimal for ruling out CPE colonization and the transmission rates are similar between stool-positive or -negative cases. Thus, combining surveillance of the stool with other sites may be needed for detecting CPE.
PET Microplastics Affect Human Gut Microbiota Communities During Simulated Gastrointestinal Digestion. First Evidence of Plausible Polymer Biodegradation During Human Digestion
Authors: Tamargo Alba , Molinero Natalia , Reinosa Julián J. , Alcolea-Rodríguez Victor , Portela Raquel , Bañares Miguel A. , Fernández Jose F. , Moreno-Arribas M.Victoria 
Published: June 2021

Abstract
Microplastics are a widely recognized global problem due to their prevalence in natural environments and the food chain. However, the impacts of microplastics on human microbiota and their possible biotransformations during the gastrointestinal tract have not been well reported. To evaluate the potential risks of microplastics at the digestive level, completely passing a single dose of polyethylene terephthalate (PET) through the gastrointestinal tract was simulated by combining a harmonised static model and the dynamic gastrointestinal simgi® model, which recreates the different regions of the digestive tract in physiological conditions. PET MPs started several biotransformations in the gastrointestinal tract and appeared to expose the colon in ways that were structurally different from the original forms. We report that the feeding with microplastics alters human microbial colonic community composition, and hypothesize that some members of the colonic microbiota could adhere to MPs surface promoting the formation of biofilms. The work presented here indicates that microplastics are indeed capable of digestive-level health effects. Considering this evidence and the increasing exposure to microplastics in consumer foods and beverages, the impact of plastics on the functionality of the gut microbiome and their potential biodegradation through digestion and intestinal bacteria merits critical investigation.
Constructing MRNA, miRNA, circRNA and lncRNA Regulatory Network by Analysis of Microarray Data in Breast Cancer
Authors: Hassani Bita , Mollanoori Hasan , Pouresmaeili Farkhondeh , Asgari Yazdan , Ghafouri-Fard Soudeh 
Published: June 2021

Abstract
Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occurs to endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network. ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new field of research and therapeutic options for BC patients. Methods. In this study, BC-specific RNA expression profiles including mRNAs, miRNAs, lncRNAs, and circRNAs were retrieved from Gene Expression Omnibus (GEO) microarray datasets, and differentially expressed (DE) items were obtained. Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted. The prognostic value of hub mRNAs in patients of BC were performed using GEPIA. Subsequently, a ceRNA network was established by Cytoscape.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genes including FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined possible ncRNAs (circ0007535, circ0002727, circ0005240, circ0014130, circ0044927, circ0007001, circ0089153, NORAD, MALAT1, TUG1, ZFAS1, OPI5-AS1, miR183, miR182, miR101, miR200c, miR200b, miR149, miR342, and miR1207) which could crosstalk with each other to regulate FOXO3 and RHOA through different regulatory patterns. Conclusion. These data might improve our perception of the breast tumorigenesis and could develop new field of research and therapeutic options for BC patients.
Identification of Immunodominant Epitopes in Allelic Variants VK210 and VK247 of Pakistani based Plasmodium Vivax Circumsporozoite Immunogen
Authors: Naz Shumaila , Ahmad Sajjad , Abbasi Sumra Wajid , Ismail Saba , Waseem Shahid , Qamar Muhammad Tahir ul , Ali Zain 
Published: June 2021

Abstract
Plasmodium vivax-induced malaria is one of the leading causes of morbidity and mortality in sub-tropical and tropical regions and known to infect 2.85 billion people globally. The continual rise and propagation of resistance against anti-malarial drugs is a prerequisite to identify a possible vaccine candidate for Plasmodium vivax (P. vivax). Circumsporozoite protein (CSP) is an important immunogen of malaria parasite that has conserved the CSP structure as an immune dominant B-cell epitope. In the current study, we focused on designing multi-epitope vaccines (MEVs) using various immunoinformatics tools against Pakistani based allelic variants VK210 and VK247 of P. vivax CSP (PvCSP) gene. Antigenicity, allergic potential and physicochemical parameters of both PvCSP variants were assessed for the designed MEVs and are within acceptable range suitable for post experimental investigations. The three-dimensional structures of both MEV shave been predicted ab initio, optimized, and validated by using different online servers. Structure and from residues perspectives, the MEVs are stable and are free from aggregation-prone regions. The stability of both MEVs has been improved by a disulfide engineering approach. To estimate the binding energy and stability of the MEVs, molecular docking simulation and binding free energy calculations with TLR-4 immune receptor have been conducted. The expression of both MEVs produced in Escherichia coli K12 expression system by in silico cloning was significant. Immune simulation revealed that the proposed MEVs induce strong humoral and cellular immunological responses, in addition to significant production of interleukins and cytokines. In conclusions, we believed that the MEVs proposed in current research, using combine approach of immunoinformatics, structural biology and biophysical approaches, could induce protective and effective immune responses against P. vivax and the experimental validation of our findings could contribute to the development of potential malaria vaccine.
A Novel Determination of the Relationship Between Exposure to Industrial Toxicant HFPO-DA and pqm-1-related Aging in C. elegans
Authors: Nagam Vishruth 
Published: June 2021

Abstract
Hexafluoropropylene oxide dimer acid (HFPO-DA, ammonium salt with trade name “GenX”) is an industrial toxicant that has recently been detected in the environment [1]. However, HFPO-DA’s potential aging-related effects on organisms of higher trophic levels, including worms and humans, have not been extensively explored. The purpose of this study is to quantify influences on C. elegans (free-living nematode) lifespan by HFPO-DA exposure, specifically via ingestion of food to simulate the mechanisms of toxicant exposure, through lower trophic-level organisms, commonly found in nature. C. elegans N2 (wild-type) samples were prepared with a uracil-based medium and E. coli OP50 (food source) at room temperature; C. elegans in the experimental, treated sample was fed E. coli OP50 incubated with 280 ng/L HFPO-DA. The target gene pqm-1 was selected due to its role in an evolutionarily conserved insulin signaling pathway and in promoting development. Molecular biology laboratory techniques (RNA extraction, qRT-PCR, fluorescence tagging, etc.) were used to quantify pqm-1 expression to yield four technical replicates for each sample. The data was analyzed through null hypothesis t-tests, heatmaps, protein interactions, and gene homology tools. HFPO-DA exposure through E. coli caused a statistically insignificant (0.811-fold) change in pqm-1-related aging in C. elegans. Future work includes investigating the effects of different levels of HFPO-DA exposure on C. elegans aging.
Do clinical practice guidelines consider evidence about test consequences? A critical document analysis
Authors: Tuut Mariska , Burgers Jako , Weijden Trudy van der , Langendam Miranda 
Published: June 2021

Abstract
Background

Supporting evidence for medical test recommendations in clinical practice guidelines (CPGs) should not only include diagnostic accuracy, but also the downstream consequences of the test result on patient relevant outcomes. The aim of this study is to assess the methodology of developing of evidence-based CPGs about medical tests, and to explore determinants of best CPGs.
Methods

We performed a systematic document analysis and quality assessment of publicly accessible CPGs about three common diagnostic topics: C-reactive protein (CRP), colonoscopy and fractional exhaled nitric oxide (FeNO). Evaluation of the complete test-treatment pathway (diagnostic accuracy as well as downstream consequences on patient relevant outcomes (i.e. burden of the test, natural course, treatment effectiveness, and link between test result and administration of treatment)) was considered best practice for developing medical test recommendations.
Results

We retrieved 15 recommendations in 15 CPGs. The methodological quality of the CPGs varied from poor to excellent. Seven CPGs reported the use of the GRADE approach. In three CPGs, however, we could not find elements of that approach in the guideline documents. Ten recommendations considered diagnostic accuracy. Four of these were supported with a systematic review of the literature and rating of the certainty in the evidence. None of the CPGs evaluated all steps of the test-treatment pathway. Burden of the test was considered in three CPGs, but not with a systematic review of the evidence. Natural course was considered in two CPGs, and also not with a systematic review of the evidence. In three recommendations, treatment effectiveness was considered, which was supported with a systematic review and rating of the certainty in the evidence in one CPG. The link between test result and administration of treatment was not considered in any CPG.
Conclusions

CPGs with recommendations about medical tests do not seem to consider evidence about test consequences on patient relevant outcomes. This might be explained by reporting issues and challenging methodology. Future research is needed to investigate how to facilitate guideline developers in explicitly and reliably considering all steps of a test-treatment pathway when developing medical test recommendations.
Mediation role of alexithymia, sensory processing sensitivity and emotional-mental processes between childhood trauma and adult psychopathology: a self-report study
Authors: DİNÇ Pelin KARACA , OKTAY Seda , BATIGÜN Ayşegül DURAK 
Published: June 2021

Abstract
Background
There is overwhelming evidence for a strong association between childhood trauma and adult psychopathology. This study aims to investigate the mediation roles of alexithymia, sensory processing sensitivity, and emotional-mental processes in the relationship between childhood traumas and adult psychopathology.
Methods
337 people (78.9% female, 21.1% male) between the ages of 20–64 participated in this study. Participants filled the scales online via google form. Reading Mind in the Eyes (EYES), Sensory Processing Sensitivity Scale (SPS), Toronto Alexithymia Scale (TAS-26), Childhood Trauma Questionnaire (CTQ), and the Brief Symptom Inventory (BSI) were used. SPSS Process (Model 4) was used to examine the mediating role of sensory processing sensitivity, alexithymia and the eyes test results in the relationship between childhood trauma and psychopathology.
Results
Sensory processing sensitivity and alexithymia have been found to mediate the relationship between childhood trauma and adult psychopathology. The eyes test (mentalization) was not found to have a mediating effect on this relationship.
Conclusion
This study shows that childhood traumas may relate more psychopathology in individuals with high sensory processing sensitivity and alexithymia. Our study may contribute to the understanding of what may lead to a person's vulnerability to experiencing psychopathology after childhood trauma. It may be important that future treatment and intervention programs should include sensory sensitivity and alexithymia. Sensory processing sensitivity and alexithymic characteristics of individuals can be examined in the treatment of psychological problems of individuals who have experienced childhood trauma.
Inhibitory Effects of Redroot Pigweed and Crabgrass on Germination and Growth----From Lab To Field
Authors: Hou Xincun , Hu Xu , Yue Yuesen , Guo Qiang , Zhao Chunqiao , Fan Xifeng , Wu Juying 
Published: June 2021

Abstract
Interactions between weeds and crops often occur by resource competition or allelopathy. However, it is still unknown how local weed species influence artificially introduced switchgrass. In this study, four experiments were conducted to evaluate the inhibitory effects of redroot pigweed (Amaranthus retroflexus) and crabgrass (Digitaria sanguinalis) on germination and growth of switchgrass, the lowland tetraploid cultivar ‘Alamo’ (Panicum virgatum cv. Alamo). Switchgrass germination was inhibited significantly in Petri dishes, with 48.1% and 33.9% inhibition on germination rate by redroot pigweed and crabgrass root aqueous extracts at 0.1 g·mL− 1 concentration, respectively. Significant inhibitory effects on switchgrass seedling biomass were observed at 5:5 proportion with redroot pigweed and crabgrass in glass jars, with 61.6% and 53.4% inhibition on plant biomass, respectively. Under the same root segregation, redroot pigweed had a stronger inhibitory effect on switchgrass seedling growth than crabgrass. Growth of transplanted switchgrass seedlings was inhibited significantly by local weeds in the field, with 46.2% and 11.7% inhibition on shoot biomass during the first and second growing seasons, respectively. However, no significant growth reduction in switchgrass was detected in the third growing season.
Integrated High-Throughput Small RNA and Transcriptome Sequencing Unveil The Shape-Dependent Toxicity of Nano-Alumina in Rat Astrocytes
Authors: Chen Yuanyuan , Dong Li , Deng Fuchang , Cao Yaqiang , Fu Yuanzheng , Zhu Mu , Qin Guangqiu , Schultz Dayna , Shekh Kamran , Tang Song 
Published: June 2021

Abstract
Background
The large-scale applications of alumina nanoparticles (Al2O3-NPs), one of the most important NPs in the global market, is causing severe damages to the environment and human health. Our previous research has revealed a critical role of nanoparticle morphology (e.g., flake and rod) in determining the toxic potencies of Al2O3-NPs, where nanorods demonstrated a significantly stronger toxic response than that of nanoflakes. However, their underlying mechanisms have not been completely elucidated yet. In the present study, we evaluated and compared the potential toxicological mechanisms of two shapes of γ-Al2O3-NPs (flake versus rod) by measuring miRNAs and mRNAs profiles of astrocytes in rat cerebral cortex, ex vivo.
Results
Totals of 269 mRNAs and 122 miRNAs, 180 mRNAs and 116 miRNAs were differentially expressed after nanoflakes or nanorods exposure, respectively. Among them, 55 miRNAs (e.g., miR-760-5p, miR-326-3p, and miR-35) and 105 mRNAs (e.g., Kdm4d, Wdr62, and Rps6) showed the same trend between the two shapes. These miRNAs and mRNAs were mainly involved in apoptosis, inflammatory pathways (e.g., NF-kappa B), carcinogenic pathways (e.g., MAPK, p53, Notch, Rap1, and Ras), and cellular lipid metabolisms (e.g., glycerolipid metabolism, sphingolipid, and ether lipid metabolism). However, the remaining miRNAs and mRNAs either showed an opposite trend or only changed by a particular shape. Nanorods could specifically alter the changes of PI3K/Akt, AMPK and TNF pathways, cell cycle, and cellular senescence, while nanoflakes caused the changes of Toll and lmd signaling pathways.
Conclusions
In this study, we demonstrate that the toxicity of nanorods might be stronger than that of nanoflakes. And this study also demonstrates the critical role of morphology in nanotoxicity of nano-alumina and reveals its potential biomolecular mechanisms.
Titania Nanosheets Generates Peroxynitrite for S-Nitrosylation and Enhanced p53 Function in Lung Cancer Cells
Authors: Soonnarong Rapeepun , Tungsukruthai Sucharat , Nutho Bodee , Rungrotmongkol Thanyada , Vinayanuwattikun Chanida , Maluangnont Tosapol , chanvorachote pithi 
Published: June 2021

Abstract
Background: Metal oxide nanomaterials are increasingly being exploited in cancer therapy thanks to their unique properties, which can enhance the efficacy of current cancer therapies. However, the nanotoxicity and mechanism of Ti0.8O2 nanosheets for specific site-targeting strategies in NSCLC have not yet been investigated.Methods: The effects of Ti0.8O2 nanosheets on cytotoxicity in NSCLC cells and normal cells were examined. The apoptosis characteristics, including condensed and fragmented nuclei, as assessed by positive staining with annexin V. The cellular uptake of the nanosheets and the induction of stress fiber were assessed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses, respectively. We also evaluated the expression of protein in death mechanism to identify the molecular mechanisms behind the toxicity of these cells. We investigated the relationship between S-nitrosylation and the increase in p53 stability by molecular dynamics.Results: Ti0.8O2 nanosheets caused cytotoxicity in several lung cancer cells, but not in normal cells. The nanosheets could enter lung cancer cells and exert an apoptosis induction. Results for protein analysis further indicated the activation of p53, increased Bax, decreased Bcl-2 and Mcl-1, and activation of caspase-3. The nanosheets also exhibited a substantial apoptosis effect in drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than that of cisplatin and etoposide. In terms of their mechanism of action, we found that the mode of apoptosis induction was through the generation of cellular ONOO− mediated the S-nitrosylation of p53 at C182. Molecular dynamics analysis further showed that the S-nitrosylation of one C182 stabilized the p53 dimer. Consequently, this nitrosylation of the protein led to an upregulation of p53 through its stabilization.Conclusions: Taking all the evidence together, we provided information on the apoptosis induction effect of the nanosheets through a molecular mechanism involving reactive nitrogen species, which affects the protein stability; thus emphasizing the novel mechanism of action of nanomaterials for cancer therapy.
An Exceptional Dark Matter from Cayley–Dickson Algebras
Authors: Masi Nicolo' 
Published: June 2021

Abstract
In this article I propose a new criterion to individuate the origin and the properties of the dark matter particle sector. The emerging candidates come from a straightforward algebraic conjecture: the symmetries of physical microscopic forces originate from the automorphism groups of main Cayley–Dickson algebras, from complex numbers to octonions and sedenions. This correspondence leads to a natural enlargement of the Standard Model color sector, from a SU(3) gauge group to an exceptional Higgs-broken G(2) group, following the octonionic automorphism relation guideline. In this picture, dark matter is a relic heavy G(2)-gluons ensemble, separated from the particle dynamics of the Standard Model due to the high mass scale of its constituents.