bluuebunny/crossref_metadata_2025 huggingface dataset:
Autocrine Bradykinin Release Promotes Ischemic Preconditioning-Induced Cytoprotection in Bovine Aortic Endothelial Cells
Authors: Bellis Alessandro , Sorriento Daniela , Fiordelisi Antonella , Izzo Raffaele , Sadoshima Junichi , Mauro Ciro , Cerasuolo Federica , Mancusi Costantino , Barbato Emanuele , Pilato Emanuele , Trimarco Bruno , Morisco Carmine
Published: April 2020

The aims of this study were to assess whether ischemic preconditioning (PC) induces bradykinin (Bk) synthesis in bovine aortic endothelial cells (bAECs) and, if so, to explore the molecular mechanisms by which this peptide provides cytoprotection against hypoxia. PC was induced by exposing bAECs to three cycles of 15 min of hypoxia followed by 15 min of reoxygenation. Bk synthesis peaked in correspondence to the early and late phases of PC (10−12 M and 10−11 M, respectively) and was abolished by a selective tissue kallikrein inhibitor, aprotinin. Stimulation with exogenous Bk at concentrations of 10−12 M and 10−11 M reduced the cell death induced by 12 h of hypoxia by 50%. Pretreatment with HOE−140, a Bk receptor 2 (BKR2) inhibitor, in bAECs exposed to 12 h of hypoxia, abrogated the cytoprotective effect of early and late PC, whereas des-Arg-HOE-140, a Bk receptor 1 (BKR1) inhibitor, affected only the late PC. In addition, we found that PC evoked endocytosis and the recycling of BKR2 during both the early and late phases, and that inhibition of these pathways affected PC-mediated cytoprotection. Finally, we evaluated the activation of PKA and Akt in the presence or absence of BKR2 inhibitor. HOE-140 abrogated PKA and Akt activation during both early and late PC. Consistently, BKR2 inhibition abolished cross-talk between PKA and Akt in PC. In bAECs, Bk-synthesis evoked by PC mediates the protection against both apoptotic and necrotic hypoxia-induced cell death in an autocrine manner, by both BKR2- and BKR1-dependent mechanisms.
RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer
Authors: Jonas Katharina , Calin George A. , Pichler Martin
Published: April 2020

The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments.
Sulfur Deficiency Increases Phosphate Accumulation, Uptake, and Transport in Arabidopsis thaliana
Authors: Allahham Alaa , Kanno Satomi , Zhang Liu , Maruyama-Nakashita Akiko
Published: April 2020

Recent studies have shown various metabolic and transcriptomic interactions between sulfur (S) and phosphorus (P) in plants. However, most studies have focused on the effects of phosphate (Pi) availability and P signaling pathways on S homeostasis, whereas the effects of S availability on P homeostasis remain largely unknown. In this study, we investigated the interactions between S and P from the perspective of S availability. We investigated the effects of S availability on Pi uptake, transport, and accumulation in Arabidopsis thaliana grown under sulfur sufficiency (+S) and deficiency (−S). Total P in shoots was significantly increased under −S owing to higher Pi accumulation. This accumulation was facilitated by increased Pi uptake under −S. In addition, −S increased root-to-shoot Pi transport, which was indicated by the increased Pi levels in xylem sap under −S. The −S-increased Pi level in the xylem sap was diminished in the disruption lines of PHT1;9 and PHO1, which are involved in root-to-shoot Pi transport. Our findings indicate a new aspect of the interaction between S and P by listing the increased Pi accumulation as part of −S responses and by highlighting the effects of −S on Pi uptake, transport, and homeostasis.
Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic
Authors: Vinciguerra Luisa , Lanza Giuseppe , Puglisi Valentina , Fisicaro Francesco , Pennisi Manuela , Bella Rita , Cantone Mariagiovanna
Published: April 2020

In the last years, there has been a significant growth in the literature exploring the pathophysiology of vascular cognitive impairment (VCI). As an “umbrella term” encompassing any degree of vascular-related cognitive decline, VCI is deemed to be the most common cognitive disorder in the elderly, with a significant impact on social and healthcare expenses. Interestingly, some of the molecular, biochemical, and electrophysiological abnormalities detected in VCI seem to correlate with disease process and progression, eventually promoting an adaptive plasticity in some patients and a maladaptive, dysfunctional response in others. However, the exact relationships between vascular lesion, cognition, and neuroplasticity are not completely understood. Recent findings point out also the possibility to identify a panel of markers able to predict cognitive deterioration in the so-called “brain at risk” for vascular or mixed dementia. This will be of pivotal importance when designing trials of disease-modifying drugs or non-pharmacological approaches, including non-invasive neuromodulatory techniques. Taken together, these advances could make VCI a potentially preventable cause of both vascular and degenerative dementia in late life. This review provides a timely update on the recent serological, cerebrospinal fluid, histopathological, imaging, and neurophysiological studies on this “cutting-edge” topic, including the limitations, future perspectives and translational implications in the diagnosis and management of VCI patients.
Signal Deconvolution and Noise Factor Analysis Based on a Combination of Time–Frequency Analysis and Probabilistic Sparse Matrix Factorization
Authors: Yamada Shunji , Kurotani Atsushi , Chikayama Eisuke , Kikuchi Jun
Published: April 2020

Nuclear magnetic resonance (NMR) spectroscopy is commonly used to characterize molecular complexity because it produces informative atomic-resolution data on the chemical structure and molecular mobility of samples non-invasively by means of various acquisition parameters and pulse programs. However, analyzing the accumulated NMR data of mixtures is challenging due to noise and signal overlap. Therefore, data-cleansing steps, such as quality checking, noise reduction, and signal deconvolution, are important processes before spectrum analysis. Here, we have developed an NMR measurement informatics tool for data cleansing that combines short-time Fourier transform (STFT; a time–frequency analytical method) and probabilistic sparse matrix factorization (PSMF) for signal deconvolution and noise factor analysis. Our tool can be applied to the original free induction decay (FID) signals of a one-dimensional NMR spectrum. We show that the signal deconvolution method reduces the noise of FID signals, increasing the signal-to-noise ratio (SNR) about tenfold, and its application to diffusion-edited spectra allows signals of macromolecules and unsuppressed small molecules to be separated by the length of the T2* relaxation time. Noise factor analysis of NMR datasets identified correlations between SNR and acquisition parameters, identifying major experimental factors that can lower SNR.
LINC00312/YBX1 Axis Regulates Myofibroblast Activities in Oral Submucous Fibrosis
Authors: Yu Chuan-Hang , Fang Chih-Yuan , Yu Cheng-Chia , Hsieh Pei-Ling , Liao Yi-Wen , Tsai Lo-Lin , Chu Pei-Ming
Published: April 2020

Oral submucous fibrosis (OSF) has been recognized as a precancerous disorder in the oral cavity. Great effort has been made to inhibit the malignant progression of OSF over the past decades, but the cure of this fibrosis disease has not been discovered. In the present study, we found that a long noncoding RNA, LINC00312, was upregulated in OSF tissues, and positively associated with several fibrosis factors, such as α-SMA, type I collagen, and fibronectin. As such, we sought to investigate the role of LINC00312 in OSF progression and identify its interacting factor that mediated oral fibrogenesis. Our results showed that the inhibition of LINC00312 downregulated the myofibroblast activities, including collagen gel contractility, transwell migration, and wound healing, as well as the gene expression of myofibroblast markers. We verified that YBX1 was a downstream factor of LINC00312 and revealed that the downregulation of YBX1 repressed the gene expression of α-SMA and p-Smad2 along with the reduced myofibroblast phenotypes. Most importantly, we demonstrated that the LINC00312-induced myofibroblast activities were reverted by the knockdown of YBX1, suggesting that the LINC00312-mediated myofibroblast transdifferentiation was through YBX1. Collectively, our findings revealed that the LINC00312/ YBX1 axis may serve as a target for the development of therapies against OSF.
Regulation of Translation in the Protozoan Parasite Leishmania
Authors: Karamysheva Zemfira N. , Gutierrez Guarnizo Sneider Alexander , Karamyshev Andrey L.
Published: April 2020

Leishmaniasis represents a serious health problem worldwide and drug resistance is a growing concern. Leishmania parasites use unusual mechanisms to control their gene expression. In contrast to many other species, they do not have transcriptional regulation. The lack of transcriptional control is mainly compensated by post-transcriptional mechanisms, including tight translational control and regulation of mRNA stability/translatability by RNA-binding proteins. Modulation of translation plays a major role in parasite survival and adaptation to dramatically different environments during change of host; however, our knowledge of fine molecular mechanisms of translation in Leishmania remains limited. Here, we review the current progress in our understanding of how changes in the translational machinery promote parasite differentiation during transmission from a sand fly to a mammalian host, and discuss how translational reprogramming can contribute to the development of drug resistance.
Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness
Authors: Ciccone Valerio , Filippelli Arianna , Angeli Andrea , Supuran Claudiu T. , Morbidelli Lucia
Published: April 2020

Carbonic anhydrase IX (CA-IX) plays a pivotal role in regulation of pH in tumor milieu catalyzing carbonic acid formation by hydrating CO2. An acidification of tumor microenvironment contributes to tumor progression via multiple processes, including reduced cell-cell adhesion, increased migration and matrix invasion. We aimed to assess whether the pharmacological inhibition of CA-IX could impair tumor cell proliferation and invasion. Tumor epithelial cells from breast (MDA-MB-231) and lung (A549) cancer were used to evaluate the cytotoxic effect of sulfonamide CA-IX inhibitors. Two CA-IX enzyme blockers were tested, SLC-0111 (at present in phase Ib clinical trial) and AA-06-05. In these cells, the drugs inhibited cell proliferation, migration and invasion through shifting of the mesenchymal phenotype toward an epithelial one and by impairing matrix metalloprotease-2 (MMP-2) activity. The antitumor activity was elicited via apoptosis pathway activation. An upregulation of p53 was observed, which in turn regulated the activation of caspase-3. Inhibition of proteolytic activity was accompanied by upregulation of the endogenous tissue inhibitor TIMP-2. Collectively, these data confirm the potential use of CA-IX inhibitors, and in particular SLC-0111 and AA-06-05, as agents to be further developed, alone or in combination with other conventional anticancer drugs.
ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance
Authors: Gomes Bruno C. , Honrado Mónica , Armada Ana , Viveiros Miguel , Rueff José , Rodrigues António S.
Published: April 2020

Cancer drug resistance (CDR) is a major problem in therapeutic failure. Over 90% of patients with metastatic cancer present CDR. Several mechanisms underlie CDR, including the increased expression of efflux ABC transporters and epigenetic phenomena. Nevertheless, a topic that is not usually addressed is the mechanism underlying the loss of CDR once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant, expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium. ABCB1 activity was analysed by fluorescence microscopy and flow cytometry through substrate (DiOC2) retention assays. The expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal, a decrease of ABCB1 activity and expression occurred. Moreover, we determined a signature of 23 microRNAs, 13 underexpressed and 10 overexpressed, as a tool to assess loss of resistance. Through pathway enrichment analysis, “Pathways in cancer”, “Proteoglycans in cancer” and “ECM-receptor interaction” were identified as relevant in the loss of CDR. Taken together, the data reinforce the assumption that ABCB1 plays a major role in the kinetics of CDR, and their levels of expression are in the dependence of the circuitry of cell miRNAs.
Nutrition and Genetics in NAFLD: The Perfect Binomium
Authors: Meroni Marica , Longo Miriam , Rustichelli Alice , Dongiovanni Paola
Published: April 2020

Nonalcoholic fatty liver disease (NAFLD) represents a global healthcare burden since it is epidemiologically related to obesity, type 2 diabetes (T2D) and Metabolic Syndrome (MetS). It embraces a wide spectrum of hepatic injuries, which include simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The susceptibility to develop NAFLD is highly variable and it is influenced by several cues including environmental (i.e., dietary habits and physical activity) and inherited (i.e., genetic/epigenetic) risk factors. Nonetheless, even intestinal microbiota and its by-products play a crucial role in NAFLD pathophysiology. The interaction of dietary exposure with the genome is referred to as ‘nutritional genomics,’ which encompasses both ‘nutrigenetics’ and ‘nutriepigenomics.’ It is focused on revealing the biological mechanisms that entail both the acute and persistent genome-nutrient interactions that influence health and it may represent a promising field of study to improve both clinical and health nutrition practices. Thus, the premise of this review is to discuss the relevance of personalized nutritional advices as a novel therapeutic approach in NAFLD tailored management.
Integrative Strategy of Testing Systems for Identification of Endocrine Disruptors Inducing Metabolic Disorders—An Introduction to the OBERON Project
Authors: Audouze Karine , Sarigiannis Denis , Alonso-Magdalena Paloma , Brochot Celine , Casas Maribel , Vrijheid Martine , Babin Patrick J. , Karakitsios Spyros , Coumoul Xavier , Barouki Robert
Published: April 2020

Exposure to chemical substances that can produce endocrine disrupting effects represents one of the most critical public health threats nowadays. In line with the regulatory framework implemented within the European Union (EU) to reduce the levels of endocrine disruptors (EDs) for consumers, new and effective methods for ED testing are needed. The OBERON project will build an integrated testing strategy (ITS) to detect ED-related metabolic disorders by developing, improving and validating a battery of test systems. It will be based on the concept of an integrated approach for testing and assessment (IATA). OBERON will combine (1) experimental methods (in vitro, e.g., using 2D and 3D human-derived cells and tissues, and in vivo, i.e., using zebrafish at different stages), (2) high throughput omics technologies, (3) epidemiology and human biomonitoring studies and (4) advanced computational models (in silico and systems biology) on functional endpoints related to metabolism. Such interdisciplinary framework will help in deciphering EDs based on a mechanistic understanding of toxicity by providing and making available more effective alternative test methods relevant for human health that are in line with regulatory needs. Data generated in OBERON will also allow the development of novel adverse outcome pathways (AOPs). The assays will be pre-validated in order to select the test systems that will show acceptable performance in terms of relevance for the second step of the validation process, i.e., the inter-laboratory validation as ring tests. Therefore, the aim of the OBERON project is to support the organization for economic co-operation and development (OECD) conceptual framework for testing and assessment of single and/or mixture of EDs by developing specific assays not covered by the current tests, and to propose an IATA for ED-related metabolic disorder detection, which will be submitted to the Joint Research Center (JRC) and OECD community.
3D Bioprinted Vascularized Tumour for Drug Testing
Authors: Han Seokgyu , Kim Sein , Chen Zhenzhong , Shin Hwa Kyoung , Lee Seo-Yeon , Moon Hyo Eun , Paek Sun Ha , Park Sungsu
Published: April 2020

An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.
Identification of Key Genes Related to Lung Squamous Cell Carcinoma Using Bioinformatics Analysis
Authors: Gao Miaomiao , Kong Weikaixin , Huang Zhuo , Xie Zhengwei
Published: April 2020

Lung squamous cell carcinoma (LUSC) is often diagnosed at the advanced stage with poor prognosis. The mechanisms of its pathogenesis and prognosis require urgent elucidation. This study was performed to screen potential biomarkers related to the occurrence, development and prognosis of LUSC to reveal unknown physiological and pathological processes. Using bioinformatics analysis, the lung squamous cell carcinoma microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were analyzed to identify differentially expressed genes (DEGs). Furthermore, PPI and WGCNA network analysis were integrated to identify the key genes closely related to the process of LUSC development. In addition, survival analysis was performed to achieve a prognostic model that accomplished good prediction accuracy. Three hundred and thirty–seven up–regulated and 119 down-regulated genes were identified, in which four genes have been found to play vital roles in LUSC development, namely CCNA2, AURKA, AURKB, and FEN1. The prognostic model contained 5 genes, which were all detrimental to prognosis. The AUC of the established prognostic model for predicting the survival of patients at 1, 3, and 5 years was 0.692, 0.722, and 0.651 in the test data, respectively. In conclusion, this study identified several biomarkers of significant interest for additional investigation of the therapies and methods of prognosis of lung squamous cell carcinoma.
Antonyms: A Computer Game to Improve Inhibitory Control of Impulsivity in Children with Attention Deficit/Hyperactivity Disorder (ADHD)
Authors: Crepaldi Maura , Colombo Vera , Mottura Stefano , Baldassini Davide , Sacco Marco , Cancer Alice , Antonietti Alessandro
Published: April 2020

The design of a computer-supported serious game concerning inhibition skills in children with Attention Deficit/Hyperactivity Disorder (ADHD) is reported. The game consists of a series of activities, each eliciting the tendency to respond in an immediate, inadequate way. The game is based on the Dual Pathway Model of ADHD proposed by Sonuga-Barke. In the game, children must block impulsive tendencies, reflect upon the situation, inhibit irrelevant thoughts, and find the non-intuitive solution. In the game, the player personifies a superhero, who is asked to save a realm on the opposite side of the Earth (Antonyms) where things happen according to the opposite of the usual rules. The hero faces a series of challenges, in the form of mini-games, to free the planet from enemies crossing different scenarios. To succeed in the game, the player should change his/her attitude by thinking before performing any action rather than acting on impulse. The player is induced to be reflective and thoughtful as well. Results from the evaluation of a preliminary version of the serious game are reported. They support the notion that Antonyms is an adequate tool to lead children to inhibit their tendency to behave impulsively.
Smart Waste Monitoring System as an Initiative to Develop a Digital Territory in Riobamba City
Authors: Veloz-Cherrez Diego , Lozada-Yanez Raúl , Rodríguez Jesús , Mayorga Paúl , Panchi Johana
Published: April 2020

Digital territories focus on community transformation through sustainable development, saving resources in local governments, bridging the digital gap, and using technology to build smart infrastructure. This article presents the design and implementation of a smart system, called the Waste Treatment System (WTS), for controlling parameters of waste decomposition in the trash bins installed in Riobamba city (Ecuador). The prototype allows monitoring in real time both the amount of waste and the level of rottenness of garbage by means of the measurement of different parameters that indicate the characteristics of the leachates generated inside. The motivation of this work was to yield an efficient solution to urban waste treatment that optimizes resources in the collection process by providing real-time information to improve collection frequency vehicles and also reduce emissions by the decomposition of organic waste. The tests allowed assessing technical aspects such as the maximum coverage of wireless communication, the transmission channel capacity for each prototype, the data-processing requirements, and other more particular parameters such as the production of leachates due to the frequency of collection and the environmental conditions, which will be useful in future work on environmental impact.
The Effect of Ground Type on the Jump Performance of Adults of the Locust Locusta migratoria manilensis: A Preliminary Study
Authors: Wan Chao , Cao Rentian , Hao Zhixiu
Published: April 2020

The jump performance of locusts depends on several physiological and environmental factors. Few studies have examined the effects of different ground types on the jump performance of locusts. Here, mature adult locusts (Locusta migratoria manilensis) were examined using a custom-developed measuring system to test their jump performance (including postural features, kinematics, and reaction forces) on three types of ground (sand, soil, and wood). Significant differences were primarily observed in the elevation angle at take-off, the tibial angle at take-off, and the component of the mass-specific reaction force along the aft direction of the insect body between wood and the other two ground types (sand and soil). Slippage of the tarsus and insertion of the tibia were often observed when the locusts jumped on sand and soil, respectively. Nevertheless, comparisons of the different parameters of jump initiation (i.e., take-off speed and mass-specific kinetic energy) did not reveal any differences among the three types of ground, indicating that locusts were able to achieve robust jump performance on various substrates. This study provides insights into the biomechanical basis of the locust jump on different types of ground and enhances our understanding of the mechanism underlying the locust jump.
Aberrant Lymphatic Drainage in the Contralateral Axilla in Patients with Isolated Ipsilateral Breast Tumor Recurrence
Authors: Ryu Jai Min , Chae Byung Joo , Lee Jeong Eon , Yu Jonghan , Nam Seok Jin , Kim Seok Won , Lee Se Kyung
Published: April 2020

The management and implications of aberrant lymphatic drainage in the contralateral axilla during repeat sentinel lymph node biopsy (SLNB) in patients with isolated ipsilateral breast tumor recurrence (IBTR) are not well understood. We analyzed the outcomes of contralateral SLNB in cases of isolated IBTR compared to ipsilateral SLNB. We conducted a retrospective review of cases reported at Samsung Medical Center between 1995 and 2015. All patients with isolated IBTR that underwent ipsilateral and contralateral SLNB with clinically negative lymph nodes but lymphatic drainage on the ipsilateral or contralateral axilla were included. Among 233 patients with isolated IBTR, 31 patients underwent repeat SLNB, 11 underwent ipsilateral SLNB, and nine underwent contralateral SLNB. None of the patients showed contralateral axillary metastasis in cases with isolated IBTR in the absence of clinically suspicious drainage on the contralateral axilla. Contralateral drainage was associated with a longer interval to IBTR (68.4 vs.18.6 months, p = 0.001) and the overall median follow-up duration (102.6 vs. 45.4 months, p = 0.002). There was no significant difference in the recurrence after the second operation (1 of 11 vs. 1 of 9, p = 1.000). Only one patient in both groups experienced recurrence after the second operation. Two patients (22.2%) who underwent contralateral SLNB had lymphedema. We demonstrate that no patient had contralateral metastasis in patients with isolated IBTR in the absence of clinically suspicious drainage in the contralateral axilla. Further study is warranted to better understand and optimize the management of these rare and challenging cases.
The Integration of qSOFA with Clinical Variables and Serum Biomarkers Improves the Prognostic Value of qSOFA Alone in Patients with Suspected or Confirmed Sepsis at ED Admission
Authors: Mearelli Filippo , Barbati Giulia , Casarsa Chiara , Giansante Carlo , Breglia Andrea , Spica Andrea , Moras Cristina , Olivieri Gaia , Occhipinti Alessandro Agostino , De Nardo Margherita , Spagnol Francesca , Fiotti Nicola , Di Girolamo Filippo Giorgio , Ruscio Maurizio , Castello Luigi Mario , Colonetti Efrem , Marino Rossella , Ronco Claudio , Zanetti Michela , Lupia Enrico , Muiesan Maria Lorenza , Di Somma Salvatore , Avanzi Gian Carlo , Biolo Gianni
Published: April 2020

Background: The prognostic value of quick sepsis-related organ failure assessment (qSOFA) outside intensive care units has been criticized. Therefore, we aimed to improve its ability in predicting 30-day all-cause mortality, and in ruling out the cases at high risk of death among patients with suspected or confirmed sepsis at emergency department (ED) admission. Methods: This study is a secondary analysis of a prospective multicenter study. We built three predictive models combining qSOFA with the clinical variables and serum biomarkers that resulted in an independent association with 30-day mortality, in both 848 undifferentiated patients (Group 1) and in 545 patients definitively diagnosed with sepsis (Group 2). The models reaching the highest negative predictive value (NPV) with the minimum expenditure of biomarkers in Group 1 and in Group 2 were validated in two cohorts of patients initially held out due to missing data. Results: In terms of the area under the receiver-operating characteristic curve, all six models significantly exceeded qSOFA in predicting prognosis. An “extended” qSOFA (eqSOFA1) in Group 1 and an eqSOFA2 integrated with C-reactive protein and mid-regional proadrenomedullin (eqSOFA2+CRP+MR-proADM) in Group 2 reached the best NPV (0.94 and 0.93, respectively) and ease of use. eqSOFA1 and eqSOFA2+CRP+MR-proADM performed equally well in both the inception and validation cohorts. Conclusions: We have derived and validated two prognostic models that outweigh qSOFA in predicting mortality and in identifying the low risk of death among patients with suspected or confirmed sepsis at ED admission.
Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy
Authors: Lee Wen-Chin , Li Lung-Chih , Ng Hwee-Yeong , Lin Pei-Ting , Chiou Terry Ting-Yu , Kuo Wei-Hung , Lee Chien-Te
Published: April 2020

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabetes models and in patients with both diabetes and CKD. Here, we aimed to investigate pathologic miRs in diabetic nephropathy (DN) by prospectively following six nephrotic, biopsy-proven isolated DN patients (enrolled between August 2015 and July 2017) for one year. The urinary exosomes were isolated at the time of the biopsy and the contained miRs were analyzed by next-generation sequencing. The results were compared to the control group, composed of age-, gender-, and CKD stage-matched patients with proteinuric CKD who did not present diabetes. Among the 72 identified miRs, we investigated eight (miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c) exhibiting the strongest upregulation (13–15 fold) and two (miR-133a-3p and miR-153-3p) with the strongest downregulation (7–9 fold). The functional analysis of these miRs showed that they were involved in known and novel pathways of DN, supporting their pathologic roles. The bioinformatics-based prediction of the target genes of these miRs will inspire future research on the mechanisms underlying DN pathogenesis.
Synthesis of Graphene Nanoribbons–Hydroxyapatite Nanocomposite Applicable in Biomedicine and Theranostics
Authors: Nosrati Hassan , Sarraf-Mamoory Rasoul , Ahmadi Amir Hossein , Canillas Perez Maria
Published: April 2020

In order to investigate the effect of graphene nanoribbons on the final properties of hydroxyapatite-based nanocomposites, a solvothermal method was used at 180 °C and 5 h for the synthesis of graphene nanoribbons–hydroxyapatite nanopowders by employing hydrogen gas injection. Calcium nitrate tetrahydrate and diammonium hydrogenphosphate were used as calcium and phosphate precursors, respectively. To synthesize the powders, a solvent containing diethylene glycol, anhydrous ethanol, dimethylformamide, and water was used. Graphene oxide nanoribbons were synthesized by chemical unzipping of carbon nanotubes under oxidative conditions. The synthesized powders were consolidated by spark plasma sintering methodat 950 °C and a pressure of 50 MPa. The powders and sintered samples were then evaluated using X-ray diffraction, Raman spectroscopy, high-resolution transmission electron microscopy, Vickers microindentation techniques, and biocompatibility assay. The findings of this study showed that the final powders synthesized by the solvothermal method had calcium to phosphate ratio of about 1.67. By adding a small amount of graphene nanoribbon (0.5%W), elastic modulus and hardness of hydroxyapatite increased dramatically. In biological experiments, the difference of hydroxyapatite effect in comparison with the nanocomposite was not significant. The findings of this study showed that graphene nanoribbons have a positive effect on the properties of hydroxyapatite, and these findings would be useful for the medical and theranostic application of this type of nanocomposites.
Molar Ratio Effect of Sodium to Chloride Ions on the Electrochemical Corrosion of Alloy 600 and SA508 in HCl + NaOH Mixtures
Authors: Hur Do Haeng , Han Jeoh , Choi Jun
Published: April 2020

This study aims to investigate the molar ratio effect of sodium to chloride ions on the corrosion of an Alloy 600 steam generator tube and an SA508 tubesheet material. The corrosion behavior was evaluated in solutions with three different molar ratios of sodium to chloride ions using a potentiodynamic polarization method. The corrosion potentials and corrosion rates of both the two materials were significantly decreased as the molar ratio increased from 0.1 to 10. Therefore, it is recommended that the molar ratio control to a value of 1 is beneficial only when the crevice chemistry has a low molar ratio with an acidic pH. The corrosion potentials and corrosion rates were little affected by the total sodium and chloride ion concentrations. SA508 acted as an anode and its corrosion rate was accelerated by galvanic coupling with Alloy 600.
Hierarchical Composite Meshes of Electrospun PS Microfibers with PA6 Nanofibers for Regenerative Medicine
Authors: Krysiak Zuzanna J. , Gawlik Małgorzata Z. , Knapczyk-Korczak Joanna , Kaniuk Łukasz , Stachewicz Urszula
Published: April 2020

One of the most frequently applied polymers in regenerative medicine is polystyrene (PS), which is commonly used as a flat surface and requires surface modifications for cell culture study. Here, hierarchical composite meshes were fabricated via electrospinning PS with nylon 6 (PA6) to obtain enhanced cell proliferation, development, and integration with nondegradable polymer fibers. The biomimetic approach of designed meshes was verified with a scanning electron microscope (SEM) and MTS assay up to 7 days of cell culture. In particular, adding PA6 nanofibers changes the fibroblast attachment to meshes and their development, which can be observed by cell flattening, filopodia formation, and spreading. The proposed single-step manufacturing of meshes controlled the surface properties and roughness of produced composites, allowing governing cell behavior. Within this study, we show the alternative engineering of nondegradable meshes without post-treatment steps, which can be used in various applications in regenerative medicine.
Near-Duplicate Image Detection System Using Coarse-to-Fine Matching Scheme Based on Global and Local CNN Features
Authors: Zhou Zhili , Lin Kunde , Cao Yi , Yang Ching-Nung , Liu Yuling
Published: April 2020

Due to the great success of convolutional neural networks (CNNs) in the area of computer vision, the existing methods tend to match the global or local CNN features between images for near-duplicate image detection. However, global CNN features are not robust enough to combat background clutter and partial occlusion, while local CNN features lead to high computational complexity in the step of feature matching. To achieve high efficiency while maintaining good accuracy, we propose a coarse-to-fine feature matching scheme using both global and local CNN features for real-time near-duplicate image detection. In the coarse matching stage, we implement the sum-pooling operation on convolutional feature maps (CFMs) to generate the global CNN features, and match these global CNN features between a given query image and database images to efficiently filter most of irrelevant images of the query. In the fine matching stage, the local CNN features are extracted by using maximum values of the CFMs and the saliency map generated by the graph-based visual saliency detection (GBVS) algorithm. These local CNN features are then matched between images to detect the near-duplicate versions of the query. Experimental results demonstrate that our proposed method not only achieves a real-time detection, but also provides higher accuracy than the state-of-the-art methods.
On Wong Type Contractions
Authors: Karapınar Erdal , Fulga Andreea
Published: April 2020

In this paper, by using admissible mapping, Wong type contraction mappings are extended and investigated in the framework of quasi-metric spaces to guarantee the existence of fixed points. We consider examples to illustrate the main results. We also demonstrate that the main results of the paper cover several existing results in the literature.
The Role of VEGFA, COX2, HUR and CUGBP2 in Predicting the Response to Neoadjuvant Therapy in Rectal Cancer Patients
Authors: Pauzas Henrikas , Gyvyte Ugne , Latkauskas Tadas , Kairevice Laura , Lizdenis Paulius , Svagzdys Saulius , Birgiolaite Erika , Kuliaviene Irma , Kupcinskas Juozas , Tamelis Algimantas
Published: April 2020

Background and objectives: The effectiveness of neoadjuvant therapy, which is commonly used for stage II-III rectal cancer (RC) treatment, is limited. Genes associated with the pathogenesis of RC could determine response to this treatment. Therefore, the aim of this study was to investigate the potential predictive value of VEGFA, COX2, HUR and CUGBP2 genes and the associations between post-treatment changes in gene expression and the efficacy of neoadjuvant therapy. Materials and Methods: Biopsies from RC and healthy rectal tissue of 28 RC patients were collected before neoadjuvant therapy and 6-8 weeks after neoadjuvant therapy. The expression levels of VEGFA, COX2, HUR, CUGBP2 genes were evaluated using a quantitative real-time polymerase chain reaction. Results: The results reveal a significantly higher expression of VEGFA, COX2 and HUR mRNA in RC tissue compared to healthy rectal tissue (p < 0.05), and elevated VEGFA gene expression in pre-treatment tissues was associated with a better response to neoadjuvant therapy based on T-stage downstaging (p < 0.05). The expression of VEGFA, HUR and CUGBP2 genes significantly decreased after neoadjuvant therapy (p < 0.05). Responders to treatment demonstrated a significantly stronger decrease of VEGFA and COX2 expression after neoadjuvant therapy than non-responders (p < 0.05). Conclusions: The findings of this study suggest that the pre-treatment VEGFA gene expression might have predictive value for the response to neoadjuvant therapy, while the post-treatment decrease in VEGFA and COX2 gene expression could indicate the effectiveness of neoadjuvant therapy in RC patients.
Subspecialty Second-Opinion in Multiple Myeloma CT: Emphasis on Clinically Significant Lytic Lesions
Authors: Tagliafico Alberto Stefano , Belgioia Liliana , Bonsignore Alessandro , Rossi Federica , Succio Giulia , Bignotti Bianca , Dominietto Alida
Published: April 2020

Background and objectives: In order to increase the accuracy of lytic lesion detection in multiple myeloma, a dedicated second-opinion interpretation of medical images performed by subspecialty musculoskeletal radiologists could increase accuracy. Therefore, the purpose of this study is to evaluate the added value (increased accuracy) of subspecialty second-opinion (SSO) consultations for Computed Tomography (CT) examinations in Multiple Myeloma (MM) patients undergoing stem cell transplantation on standard computed tomography with a focus on focal lesion detection. Materials and Methods: Approval from the institutional review board was obtained. This retrospective study included 70 MM consecutive patients (mean age, 62 years ± 11.3 (standard deviation); range, 35–88 years) admitted in the last six years. Pre-transplant total-body CT (reported by general radiologists) was the only inclusion criteria. Each of these CT examinations had a second-opinion interpretation by two experienced subspecialty musculoskeletal (MSK) radiologists (13 years of experience and 6 years of experience, mean: 9.5 years), experts in musculoskeletal radiology and bone image interpretation with a focus on lytic lesions. Results: Per lesion intra- and inter-observer agreement between the two radiologists was calculated with K statistics and the results were good (K = 0.67: Confidence Inteval (CI) 95%: 0.61–0.78). When the initial CT reports were compared with the re-interpretation reports, 46 (65%) of the 70 cases (95% CI: 37–75%) had no discrepancy. There was a discrepancy in detecting a clinically unimportant abnormality in 10/70 (14%) patients (95% CI: 7–25%) unlikely to alter patient care or irrelevant to further clinical management. A discrepancy in interpreting a clinically important abnormality was registered in 14/70 (21%) patients for focal lesions. The mean diameter of focal lesions was: 23 mm (95% CI: 5–57 mm). The mean number of focal lesions per patient was 3.4 (95% CI). Conclusions: subspecialty second-opinion consultations in multiple myeloma CT is more accurate to identify lesions, especially lytic lesions, amenable to influence patients’ care.
Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation
Authors: Byrne Alexandra , Bush Rachel , Johns Felicia , Upadhyay Kiran
Published: April 2020

Background: Epstein–Barr virus (EBV) infection is associated with significant morbidity and mortality in renal transplant (RT) recipients. The spectrum of illness ranges from infectious mononucleosis (IM) to post-transplant lymphoproliferative disorder (PTLD). In association with clinical signs and symptoms, virus-specific serology and heterophile antibody tests are widely used in confirming the diagnosis of IM in the general population. However, these tests may have a limited role in immunosuppressed RT recipients from seropositive donor, especially in children who were EBV-seronegative prior to the transplant. The aim of this study is to evaluate the utility of these tests in the early diagnosis of IM in this subset of patients. Methods: This is a case study with a review of literature. Results: Here, we present a 14-year-old male with hemophilia B who presented with fever, fatigue, sore throat, palatal petechial rash, exudative tonsillitis and cervical lymphadenopathy 3 months post-RT. He was EBV seronegative prior to RT and received a deceased donor kidney transplant from a seropositive donor. Induction was done with Thymoglobulin and maintenance immunosuppression consisted of tacrolimus and mycophenolate. Initial heterophile antibody test (monospot) was negative, but became positive at 5 months and remained positive at 9 months follow-up post-RT. EBV viral capsid antigens (VCA) IgM and IgG, early antigen (EA) and nuclear antigen (EBNA) were all negative at the time of presentation. VCA IgM and IgG both became positive at 5 months and peaked at 9 months follow-up, however the EA and EBNA remained negative. EBV viral load as measured by polymerase chain reaction (PCR) was negative for the first 3 months post-RT but became positive at presentation, peaked at 6 months and started declining thereafter. Peripheral blood smear examination showed no absolute and atypical lymphocytosis. Cytomegalovirus PCR in the blood and throat culture for streptococcus were negative. There was no splenomegaly. He was managed conservatively with intravenous fluids, bed rest, antipyretics and reduction of immunosuppression. Conclusions: EBV serological markers have a limited role in the early diagnosis of EBV-IM following RT in prior seronegative children. Initial heterophile antibody test may also be negative, and hence a repeat test may be necessary. Once becoming positive, the VCA IgM may remain persistently elevated for prolonged duration. In addition to the suppressed cellular immunity secondary to immunosuppression, humoral response to viral infections is also delayed in transplant recipients, especially in the early transplant period. Hence, routine monitoring with PCR is superior to serology in diagnosing IM early and monitoring the EBV infection post-RT for timely evaluation and management.
Titanium Nitride (TiN) Germination and Growth during Vacuum Arc Remelting of a Maraging Steel
Authors: Descotes Vincent , Quatravaux Thibault , Bellot Jean-Pierre , Witzke Sylvain , Jardy Alain
Published: April 2020

During the processing of maraging steels, Titanium easily combines with Nitrogen to form nitride inclusions, known to be deleterious for fatigue properties of the alloy. According to thermodynamic calculations, the precipitation occurs during solidification of the vacuum arc remelted (VAR) ingot. A coupled model of titanium nitride (TiN) inclusion precipitation and vacuum remelting has been set-up to study the inclusion cleanliness of the ingot. The nitrogen content, nuclei numeral density and solidification time appear as the key factors which control the inclusion size.
Solvent Extraction of Ni and Co from the Phosphoric Acid Leaching Solution of Laterite Ore by P204 and P507
Authors: Rao Mingjun , Zhang Tao , Li Guanghui , Zhou Qun , Luo Jun , Zhang Xin , Zhu Zhongping , Peng Zhiwei , Jiang Tao
Published: April 2020

An alternative process of pre-roasting, phosphoric acid leaching followed by solvent extraction of a limonitic laterite ore was described in this work, with emphasis on the solvent extraction of Ni and Co from the phosphoric acid leaching solution by P204 and P507. First, the pH value of the leaching solution was adjusted using ammonia to reduce the content of Al3+ and Fe3+ by precipitation, then the content of Al3+, Fe3+ and Mn2+ were further decreased by extraction using P204. At last, Ni2+ and Co2+ were separated by three-stage extraction using P507. After extraction, the extraction ratio of Co2+ was 96.61%, while that of Ni2+ was 12.32%, and the selective extraction of Ni2+ and Co2+ could be realized.
A Data Set of 255,000 Randomly Selected and Manually Classified Extracted Ion Chromatograms for Evaluation of Peak Detection Methods
Authors: Müller Erik , Huber Carolin , Beckers Liza-Marie , Brack Werner , Krauss Martin , Schulze Tobias
Published: April 2020

Non-targeted mass spectrometry (MS) has become an important method over recent years in the fields of metabolomics and environmental research. While more and more algorithms and workflows become available to process a large number of non-targeted data sets, there still exist few manually evaluated universal test data sets for refining and evaluating these methods. The first step of non-targeted screening, peak detection and refinement of it is arguably the most important step for non-targeted screening. However, the absence of a model data set makes it harder for researchers to evaluate peak detection methods. In this Data Descriptor, we provide a manually checked data set consisting of 255,000 EICs (5000 peaks randomly sampled from across 51 samples) for the evaluation on peak detection and gap-filling algorithms. The data set was created from a previous real-world study, of which a subset was used to extract and manually classify ion chromatograms by three mass spectrometry experts. The data set consists of the converted mass spectrometry files, intermediate processing files and the central file containing a table with all important information for the classified peaks.