bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacodynamics and Pharmacokinetics of Injectable Pimobendan and Its Metabolite, O-Desmethyl-Pimobendan, in Healthy Dogs
Authors: Pichayapaiboon Poonavit , Tantisuwat Lalida , Boonpala Pakit , Saengklub Nakkawee , Boonyarattanasoonthorn Tussapon , Khemawoot Phisit , Kijtawornrat Anusak
Published: August 2021

Objectives:This study was designed to thoroughly evaluate the effects of bolus pimobendan at a dose of 0.15 mg/kg on cardiac functions, hemodynamics, and electrocardiographic parameters together with the pharmacokinetic profile of pimobendan and its active metabolite, o-desmethyl-pimobendan (ODMP), in anesthetized dogs.

Methods:Nine beagle dogs were anesthetized and instrumented to obtain left ventricular pressures, aortic pressures, cardiac outputs, right atrial pressures, pulmonary arterial pressures, pulmonary capillary wedge pressures, electrocardiograms. After baseline data were collected, dogs were given a single bolus of pimobendan, and the pharmacodynamic parameters were obtained at 10, 20, 30, 60, and 120 min. Meanwhile, the venous blood was collected at baseline and 2, 5, 10, 20, 30, 60, 120, 180, 360, and 1,440 min after administration for the determination of pharmacokinetic parameters.

Results:Compared with baseline measurements, the left ventricular inotropic indices significantly increased in response to intravenous pimobendan, as inferred from the maximum rate of rise in the left ventricular pressure and the contractility index. Conversely, the left ventricular lusitropic parameters significantly decreased, as inferred from the maximum rate of fall in the left ventricular pressure and the left ventricular relaxation time constant. Significant increases were also noted in cardiac output and systolic blood pressure. Decreases were observed in the systemic vascular resistance, pulmonary vascular resistance, left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, right atrial pressure, and pulmonary arterial pressure. The heart rate increased, but the PQ interval decreased. There was no arrhythmia during the observed period (2 h). The mean maximum plasma concentration (in μg/L) for ODMP was 30.0 ± 8.8. Pimobendan exerted large volume of distribution ~9 L/kg.

Conclusions:Intravenous pimobendan at the recommended dose for dogs increased cardiac contraction and cardiac output, accelerated cardiac relaxation but decreased both vascular resistances. These mechanisms support the use of injectable pimobendan in acute heart failure.
Scheduling Multiprocessor Tasks with Equal Processing Times as a Mixed Graph Coloring Problem
Authors: Sotskov Yuri N. , Mihova Evangelina I.
Published: August 2021

This article extends the scheduling problem with dedicated processors, unit-time tasks, and minimizing maximal lateness Lmax for integer due dates to the scheduling problem, where along with precedence constraints given on the set V={v1,v2, …,vn} of the multiprocessor tasks, a subset of tasks must be processed simultaneously. Contrary to a classical shop-scheduling problem, several processors must fulfill a multiprocessor task. Furthermore, two types of the precedence constraints may be given on the task set V. We prove that the extended scheduling problem with integer release times ri≥0 of the jobs V to minimize schedule length Cmax may be solved as an optimal mixed graph coloring problem that consists of the assignment of a minimal number of colors (positive integers) {1,2, …,t} to the vertices {v1,v2, …,vn}=V of the mixed graph G=(V,A, E) such that, if two vertices vp and vq are joined by the edge [vp,vq]∈E, their colors have to be different. Further, if two vertices vi and vj are joined by the arc (vi,vj)∈A, the color of vertex vi has to be no greater than the color of vertex vj. We prove two theorems, which imply that most analytical results proved so far for optimal colorings of the mixed graphs G=(V,A, E), have analogous results, which are valid for the extended scheduling problems to minimize the schedule length or maximal lateness, and vice versa.
Experimental Validation of a Guaranteed Nonlinear Model Predictive Control
Authors: Fnadi Mohamed , Alexandre dit Sandretto Julien
Published: August 2021

This paper combines the interval analysis tools with the nonlinear model predictive control (NMPC). The NMPC strategy is formulated based on an uncertain dynamic model expressed as nonlinear ordinary differential equations (ODEs). All the dynamic parameters are identified in a guaranteed way considering the various uncertainties on the embedded sensors and the system’s design. The NMPC problem is solved at each time step using validated simulation and interval analysis methods to compute the optimal and safe control inputs over a finite prediction horizon. This approach considers several constraints which are crucial for the system’s safety and stability, namely the state and the control limits. The proposed controller consists of two steps: filtering and branching procedures enabling to find the input intervals that fulfill the state constraints and ensure the convergence to the reference set. Then, the optimization procedure allows for computing the optimal and punctual control input that must be sent to the system’s actuators for the pendulum stabilization. The validated NMPC capabilities are illustrated through several simulations under the DynIbex library and experiments using an inverted pendulum.
Simulation of the Influence of External Factors on the Level of Use of the Regional Tourism Potential: A Practical Aspect
Authors: Shpak Nestor , Muzychenko-Kozlovska Oksana , Gvozd Maryana , Sroka Włodzimierz
Published: August 2021

Today, the issue of development of the tourism industry is becoming increasingly relevant, as this industry is an important component of the economic system of each country. External factors have the most significant impact on the development of tourism: natural disasters, wars, economic crises, and pandemics have had a destabilizing effect on the development of the tourism industry around the world. To avoid or reduce the impact of negative phenomena on the tourism industry of a particular country or region, it is crucial to predict the impact of external factors, identify the most important of them, and develop strategic measures to turn threats into opportunities. In the context of solving the mentioned problem, this study aims to model the impact of external factors on the level of use of tourism potential of the region. After all, tourist services and products of each country and region are unique, as they are formed under the influence of existing special natural resources, cultural heritage, environmental, social and other factors inherent only in them; and if in one country/region the influence of a certain factor can weaken the development of tourism, in another one—it can stimulate it. A method of comparison with the reference value and a method of calculating the integral indicator were used in the study. Based on the analysis, an integral indicator of the level of use of the tourist potential of the region was calculated and the method of assessing the impact of external factors on the level of tourist potential on the example of the Carpathian region of Ukraine was tested.
Integrated Reporting Implementation and Core Activities Disclosure in UK Higher Education Institutions
Authors: Adhikariparajuli Mahalaxmi , Hassan Abeer , Fletcher Mary
Published: August 2021

Through integrated reporting (IR) and integrated thinking (IT), higher education institutions (HEIs) can engage future students, staff and other key stakeholders. This paper examines the impact of IR framework implementation on core activities disclosure within the UK HEIs. In particular, the authors explore the influence of the integrated thinking approach, intended to enhance the extent of the IR content elements, teaching and learning, internationalisation and research activities disclosure. The study is based on the annual reports of 123 UK HEIs over 3 years—2015–16, 2016–17 and 2017–18. Consistent with the predictions of legitimacy theory and the integrated thinking approach, the results show the extent that integrated reporting content elements and HEIs core activities disclosure practices have increased over the study period. The results also indicate that adoption of the IR framework, league table ranking position, key performance indicator reporting, size, research quality and graduate prospects all have significant positive influences on HEIs core activities disclosure. Based on the findings, the recommendations are that UK HEI governing and other regularity bodies, such as British Universities Finance Director Groups, Leadership Foundation in Higher Education and the Higher Education Funding Council, should consider development of voluntary integrated reporting guidelines and a core activities disclosure framework.
Tensile Properties and Fracture Mechanisms of Corn Bract for Corn Peeling Device Design
Authors: Li Zhenye , Fu Jun , Luo Xiwen
Published: August 2021

This paper describes the physical and tensile properties of corn bracts during a whole harvest period by using two corn cultivars, aiming to realize efficient peeling with minimum energy performance and decrease the incidence of ear damage. The value range and change rule of tensile properties were obtained by combining mechanical experiments and numerical statistics. Meanwhile, mathematical models were established for tensile properties depending on bract moisture content and bract thickness. The experimental results show that the tensile properties of leaf blade were affected by the orientation between pulling force and longitudinal vein, and that parallel orientation was greater than perpendicular. Further, the tensile properties of leaf sheaths depended on the angle between pulling force and natural growth direction of the bract in the following order: 0° > 90° > 180°. A larger pulling force angle can improve the probability of bract fracturing at the root of leaf sheaths, which helps reduce bract residue on the peduncle. In addition, the fracture mechanisms of leaf blades and sheaths were expressed from physiological and morphological perspectives. The experimental results are believed to be able to provide theoretical guidance by which to design and optimize corn-peeling devices.
Assessing Suitability of Sentinel-2 Bands for Monitoring of Nutrient Concentration of Pastures with a Range of Species Compositions
Authors: Punalekar Suvarna M. , Thomson Anna , Verhoef Anne , Humphries David J. , Reynolds Christopher K.
Published: August 2021

The accurate and timely assessment of pasture quantity and quality (i.e., nutritive characteristics) is vital for effective pasture management. Remotely sensed data can be used to predict pasture quantity and quality. This study investigated the ability of Sentinel-2 multispectral bands, convolved from proximal hyperspectral data, in predicting various pasture quality and quantity parameters. Field data (quantitative and spectral) were gathered for experimental plots representing four pasture types—perennial ryegrass monoculture and three mixtures of swards representing increasing species diversity. Spectral reflectance data at the canopy level were used to generate Sentinel-2 bands and calculate normalised difference indices with each possible band pair. The suitability of these indices for prediction of pasture parameters was assessed. Pasture quantity parameters (biomass and Leaf Area Index) had a stronger influence on overall reflectance than the quality parameters. Indices involving the 1610 nm band were optimal for acid detergent fibre, crude protein, organic matter and water-soluble carbohydrate concentration, while being less affected by biomass or LAI. The study emphasises the importance of accounting for the quantity parameters in the spectral data-based models for pasture quality predictions. These explorative findings inform the development of future pasture quantity and quality models, particularly focusing on diverse swards.
Effect of Sex and Reproductive Status on Inhibitory Control and Social Cognition in the Domestic Dog (Canis familiaris)
Authors: Junttila Saara , Huohvanainen Salla , Tiira Katriina
Published: August 2021

Sex differences in a variety of cognitive traits have long been reported in various species, including dogs. However, only a few canine studies have taken the possible effect of reproductive hormones into account. The aim of this study was to investigate the effects of sex and reproductive status of pet dogs (N = 1032) on two cognitive traits: inhibitory control and social cognition. Inhibitory control was assessed using the cylinder test, and the dogs’ tendency to initiate social contact with a human during a problem-solving situation was assessed using the unsolvable task. Female dogs had a significantly higher success rate in the cylinder test compared to males, and they spent significantly more time in human-directed behavior during the unsolvable task. In contrast, males spent significantly more time in independent behavior during the unsolvable task. Reproductive status had no significant effect on the results of the cylinder test or the unsolvable task. Our results showed that female dogs asked for more help/used a more cooperative strategy during a problem-solving situation and had greater inhibitory control compared to males. According to our results, it seems likely that these sex differences were not influenced to a large extent by reproductive hormones.
Metagenomics-Based Analysis of the Age-Related Cumulative Effect of Antibiotic Resistance Genes in Gut Microbiota
Authors: Wu Lei , Xie Xinqiang , Li Ying , Liang Tingting , Zhong Haojie , Ma Jun , Yang Lingshuang , Yang Juan , Li Longyan , Xi Yu , Li Haixin , Zhang Jumei , Chen Xuefeng , Ding Yu , Wu Qingping
Published: August 2021

Antibiotic resistance in bacteria has become a major global health problem. One of the main reservoirs of antibiotic resistance genes is the human gut microbiota. To characterise these genes, a metagenomic approach was used. In this study, a comprehensive antibiotic resistome catalog was established using fecal samples from 246 healthy individuals from world’s longevity township in Jiaoling, China. In total, 606 antibiotic resistance genes were detected. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate and become more complex with age as older groups harbour the highest abundance of these genes. Tetracycline resistance gene type tetQ was the most abundant group of antibiotic resistance genes in gut microbiota, and the main carrier of antibiotic resistance genes was Bacteroides. Antibiotic efflux, inactivation, and target alteration were found to be the dominant antimicrobial resistance mechanisms. This research may help to establish a comprehensive antibiotic resistance catalog that includes extremely long-lived healthy people such as centenarians, and may provide potential recommendations for controlling the use of antibiotics.
Climatic Alterations Influence Bacterial Growth, Biofilm Production and Antimicrobial Resistance Profiles in Aeromonas spp.
Authors: Grilo Miguel L. , Pereira Ana , Sousa-Santos Carla , Robalo Joana I. , Oliveira Manuela
Published: August 2021

Climate change is expected to create environmental disruptions that will impact a wide array of biota. Projections for freshwater ecosystems include severe alterations with gradients across geographical areas. Life traits in bacteria are modulated by environmental parameters, but there is still uncertainty regarding bacterial responses to changes caused by climatic alterations. In this study, we used a river water microcosm model to evaluate how Aeromonas spp., an important pathogenic and zoonotic genus ubiquitary in aquatic ecosystems, responds to environmental variations of temperature and pH as expected by future projections. Namely, we evaluated bacterial growth, biofilm production and antimicrobial resistance profiles of Aeromonas species in pure and mixed cultures. Biofilm production was significantly influenced by temperature and culture, while temperature and pH affected bacterial growth. Reversion of antimicrobial susceptibility status occurred in the majority of strains and tested antimicrobial compounds, with several combinations of temperature and pH contributing to this effect. Current results highlight the consequences that bacterial genus such as Aeromonas will experience with climatic alterations, specifically how their proliferation and virulence and phenotypic resistance expression will be modulated. Such information is fundamental to predict and prevent future outbreaks and deleterious effects that these bacterial species might have in human and animal populations.
A Fast Ubiquitination of UHRF1 Oncogene Is a Unique Feature and a Common Mechanism of Thymoquinone in Cancer Cells
Authors: Alhosin Mahmoud , Abdullah Omeima , Kayali Asaad , Omran Ziad
Published: August 2021

Downregulation of the ubiquitin-like containing PHD and ring finger 1 (UHRF1) oncogene in cancer cells in response to natural anticancer drugs, including thymoquinone (TQ), is a key event that induces apoptosis. TQ can induce UHRF1 autoubiquitination via the E3 ligase activity of its RING domain, most likely through the downregulation of herpes virus-associated ubiquitin-specific protease (HAUSP). In this study, we evaluated whether HAUSP downregulation and fast ubiquitination of UHRF1 are prerequisites for UHRF1 degradation in response to TQ in cancer cells and whether doxorubicin can mimic the effects of TQ on UHRF1 ubiquitination. RNA sequencing was performed to investigate differentially expressed genes in TQ-treated Jurkat cells. The protein expression of UHRF1, HAUSP and Bcl-2 was detected by means of Western blot analysis. The proliferation of human colon cancer (HCT-116) and Jurkat cells was analyzed via the WST-1 assay. RNA sequencing data revealed that TQ significantly decreased HAUSP expression. TQ triggered UHRF1 to undergo rapid ubiquitination as the first step in its degradation and the inhibition of its cell proliferation. TQ-induced UHRF1 ubiquitination is associated with HAUSP downregulation. Like TQ, doxorubicin induced a similar dose- and time-dependent downregulation of UHRF1 in cancer cells, but UHRF1 did not undergo ubiquitination as detected in response to TQ. Furthermore, TQ decreased Bcl-2 expression without triggering its ubiquitination. A fast UHRF1 ubiquitination is an indispensable event for its degradation in response to TQ but not for its responses to doxorubicin. TQ appears to trigger ubiquitination of UHRF1 but not of the Bcl-2 oncogene, thereby identifying UHRF1 as a specific target of TQ for cancer therapy.
Testbed for LoRaWAN Security: Design and Validation through Man-in-the-Middle Attacks Study
Authors: Pospisil Ondrej , Fujdiak Radek , Mikhaylov Konstantin , Ruotsalainen Henri , Misurec Jiri
Published: August 2021

The low-power wide-area (LPWA) technologies, which enable cost and energy-efficient wireless connectivity for massive deployments of autonomous machines, have enabled and boosted the development of many new Internet of things (IoT) applications; however, the security of LPWA technologies in general, and specifically those operating in the license-free frequency bands, have received somewhat limited attention so far. This paper focuses specifically on the security and privacy aspects of one of the most popular license-free-band LPWA technologies, which is named LoRaWAN. The paper’s key contributions are the details of the design and experimental validation of a security-focused testbed, based on the combination of software-defined radio (SDR) and GNU Radio software with a standalone LoRaWAN transceiver. By implementing the two practical man-in-the-middle attacks (i.e., the replay and bit-flipping attacks through intercepting the over-the-air activation procedure by an external to the network attacker device), we demonstrate that the developed testbed enables practical experiments for on-air security in real-life conditions. This makes the designed testbed perspective for validating the novel security solutions and approaches and draws attention to some of the relevant security challenges extant in LoRaWAN.
Evaluation of Depth of Invasion in Oral Squamous Cell Carcinoma with Ultra-High Frequency Ultrasound: A Preliminary Study
Authors: Izzetti Rossana , Nisi Marco , Gennai Stefano , Oranges Teresa , Crocetti Laura , Caramella Davide , Graziani Filippo
Published: August 2021

Intraoral ultrasonography has been widely employed for the preoperative assessment of tumor margins due to its capability to evaluate depth of invasion (DOI) and tumor thickness (TT). Recently, a novel ultrasonographic technique, ultra-high frequency ultrasound (UHFUS) has been increasingly applied to the study of oral lesions. This study evaluates the potential application of intraoral UHFUS to assess DOI and TT parameters of oral squamous cell carcinoma (OSCC) lesions. Patients clinically suspected of OSCC lesions were enrolled and underwent an intraoral UHFUS examination preoperatively. The parameters of TT, DOI, echogenicity, and vascularization were assessed. The parameters of TT and DOI as evaluated by means of UHFUS were compared to histology, which was set as the benchmark. Ten patients in total were enrolled. UHFUS-based DOI and TT measurements were found to positively correlate with histology (p < 0.05), although UHFUS provided a slight overestimation of DOI. No differences were found in terms of echogenicity or vascularization depending on the site of the lesion. According to these preliminary results, UHFUS could support the preoperative assessment of TT and DOI, potentially enhancing the clinical evaluation of OSCC.
Low-Cost Air Quality Stations’ Capability to Integrate Reference Stations in Particulate Matter Dynamics Assessment
Authors: Brilli Lorenzo , Carotenuto Federico , Andreini Bianca Patrizia , Cavaliere Alice , Esposito Andrea , Gioli Beniamino , Martelli Francesca , Stefanelli Marco , Vagnoli Carolina , Venturi Stefania , Zaldei Alessandro , Gualtieri Giovanni
Published: August 2021

Low-cost air quality stations can provide useful data that can offer a complete picture of urban air quality dynamics, especially when integrated with daily measurements from reference air quality stations. However, the success of such deployment depends on the measurement accuracy and the capability of resolving spatial and temporal gradients within a spatial domain. In this work, an ensemble of three low-cost stations named “AirQino” was deployed to monitor particulate matter (PM) concentrations over three different sites in an area affected by poor air quality conditions. Data of PM2.5 and PM10 concentrations were collected for about two years following a protocol based on field calibration and validation with a reference station. Results indicated that: (i) AirQino station measurements were accurate and stable during co-location periods over time (R2 = 0.5–0.83 and RMSE = 6.4–11.2 μg m−3; valid data: 87.7–95.7%), resolving current spatial and temporal gradients; (ii) spatial variability of anthropogenic emissions was mainly due to extensive use of wood for household heating; (iii) the high temporal resolution made it possible to detect time occurrence and strength of PM10 concentration peaks; (iv) the number of episodes above the 1-h threshold of 90 μg m−3 and their persistence were higher under urban and industrial sites compared to the rural area.
Bioaerosol Emissions during Organic Waste Treatment for Biopolymer Production: A Case Study
Authors: Pascale Erica , Franchitti Elena , Caredda Chiara , Fornasero Stefania , Carletto Giulia , Pietrangeli Biancamaria , Valentino Francesco , Pavan Paolo , Gilli Giorgio , Anedda Elisa , Traversi Deborah
Published: August 2021

Environmentally sustainable methods of waste disposal are a strategic priority. For organic waste management and innovative biological treatments present advantageous opportunities, although organic waste treatment also includes environmental drawbacks, such as bioaerosol production. This study aims to evaluate bioaerosol spread during an innovative experimental treatment. The process consists of two anaerobic steps: acidogenesis, which includes polyhydroxyalkanoate accumulation, followed by methanogenesis. Bioaerosol, PM10, and endotoxin concentrations were measured at three sampling points during different campaigns to evaluate: (1) the background levels, (2) the contamination produced in the pre-treatment stage, and (3) the residual contamination of the outgoing digested sludge. Environmental PM10 seemed to be generally quite contained, while the endotoxin determination was close to 90 EU/m3. Significant microbial concentrations were detected during the loading of the organic fraction of municipal solid waste (fungi > 1300 CFU/m3, Bacillus genus (≈103 CFU/m3), higher Clostridium spp. and opportunistic human pathogens such as Pseudomonas aeruginosa and Klebsiella pneumoniae), suggesting a significant contamination level. Such results are useful for hazard identification in the risk assessment of innovative processes, as they reveal contaminants potentially harmful to both workers’ health and the environment.
In Vitro Anticancer Drug Sensitivity Sensing through Single-Cell Raman Spectroscopy
Authors: Wang Jingkai , Lin Kaicheng , Hu Huijie , Qie Xingwang , Huang Wei E. , Cui Zhisong , Gong Yan , Song Yizhi
Published: August 2021

Traditional in vitro anticancer drug sensitivity testing at the population level suffers from lengthy procedures and high false positive rates. To overcome these defects, we built a confocal Raman microscopy sensing system and proposed a single-cell approach via Raman-deuterium isotope probing (Raman-DIP) as a rapid and reliable in vitro drug efficacy evaluation method. Raman-DIP detected the incorporation of deuterium into the cell, which correlated with the metabolic activity of the cell. The human non-small cell lung cancer cell line HCC827 and human breast cancer cell line MCF-7 were tested against eight different anticancer drugs. The metabolic activity of cancer cells could be detected as early as 12 h, independent of cell growth. Incubation of cells in 30% heavy water (D2O) did not show any negative effect on cell viability. Compared with traditional methods, Raman-DIP could accurately determine the drug effect, meanwhile, it could reduce the testing period from 72–144 h to 48 h. Moreover, the heterogeneity of cells responding to anticancer drugs was observed at the single-cell level. This proof-of-concept study demonstrated the potential of Raman-DIP to be a reliable tool for cancer drug discovery and drug susceptibility testing.
Reduction of Sniff Nasal Inspiratory Pressure (SNIP) as an Early Indicator of the Need of Enteral Nutrition in Patients with Amyotrophic Lateral Sclerosis
Authors: Zoccolella Stefano , Capozzo Rosa , Quaranta Vitaliano N. , Castellana Giorgio , Marra Lorenzo , Liotino Vito , Giorgio Vincenza , Simone Isabella L. , Resta Onofrio , Piccininni Marco , Tortelli Rosanna , Logroscino Giancarlo
Published: August 2021

Percutaneous endoscopic gastrostomy (PEG) is the standard procedure for feeding severely dysphagic patients with amyotrophic lateral sclerosis (ALS). It is associated with prolonged survival and improvement in quality of life. Nasal inspiratory pressure during a sniff (SNIP) is a respiratory test used extensively in ALS for the assessment of inspiratory muscle strength. In this study, we aimed to investigate the role of SNIP at baseline to predict PEG placement in ALS. Data from a clinical incident cohort of 179 ALS cases attending the multidisciplinary ALS unit of the University of Bari between April 2006 and December 2012 were retrospectively analysed. At baseline, patients underwent detailed neurological, nutritional and respiratory assessments, including measurements of SNIP and forced vital capacity (FVC). Patients were therefore followed up approximately every three to six months until they were able to attend the centre. The censoring date for the survival analysis was 15 April 2014, with PEG placement as the main outcome. Cox proportional hazard regression models were used to examine the association between SNIP and PEG placement, adjusted for possible confounders. During the follow-up period, 75 participants (42%) received PEG implant. PEG placement was more frequent (57% vs. 31%; p = 0.001) and earlier (after 11.6 ± 14.0 months from the first visit, vs. 23.3 ± 15.5 months; p < 0.0001) in the group of patients with baseline SNIP ≤ 40 cm H2O. Baseline SNIP was a predictor of PEG placement even after correction for multiple potential confounders (HR 0.98; 95% CI: 0.96–0.99; p = 0.02). To conclude, the present study showed that SNIP at baseline is an early indicator of disease progression and therefore of the need for enteral nutrition in ALS.
Ovarian Cancer and Cancer Stem Cells—Cellular and Molecular Characteristics, Signaling Pathways, and Usefulness as a Diagnostic Tool in Medicine and Oncology
Authors: Nowicki Andrzej , Kulus Magdalena , Wieczorkiewicz Maria , Pieńkowski Wojciech , Stefańska Katarzyna , Skupin-Mrugalska Paulina , Bryl Rut , Mozdziak Paul , Kempisty Bartosz , Piotrowska-Kempisty Hanna
Published: August 2021

Despite the increasing development of medicine, ovarian cancer is still a high-risk, metastatic disease that is often diagnosed at a late stage. In addition, difficulties in its treatment are associated with high resistance to chemotherapy and frequent relapse. Cancer stem cells (CSCs), recently attracting significant scientific interest, are considered to be responsible for the malignant features of tumors. CSCs, as the driving force behind tumor development, generate new cells by modifying different signaling pathways. Moreover, investigations on different types of tumors have shown that signaling pathways are key to epithelial-mesenchymal transition (EMT) regulation, metastasis, and self-renewal of CSCs. Based on these established issues, new therapies are being investigated based on the use of inhibitors to block CSC growth and proliferation signals. Many reports indicate that CSC markers play a key role in cancer metastasis, with hopes placed in their targeting to block this process and eliminate relapses. Current histological classification of ovarian tumors, their epidemiology, and the most recent knowledge of ovarian CSCs, with particular emphasis on their molecular background, are important aspects for consideration. Furthermore, the importance of signaling pathways involved in tumor growth, development, and metastasis, is also presented.
Insights into the Evolving Roles of Circular RNAs in Cancer
Authors: Harper Katherine Louise , Mottram Timothy James , Whitehouse Adrian
Published: August 2021

The majority of RNAs transcribed from the human genome have no coding capacity and are termed non-coding RNAs (ncRNAs). It is now widely accepted that ncRNAs play key roles in cell regulation and disease. Circular RNAs (circRNAs) are a form of ncRNA, characterised by a closed loop structure with roles as competing endogenous RNAs (ceRNAs), protein interactors and transcriptional regulators. Functioning as key cellular regulators, dysregulated circRNAs have a significant impact on disease progression, particularly in cancer. Evidence is emerging of specific circRNAs having oncogenic or tumour suppressive properties. The multifaceted nature of circRNA function may additionally have merit as a novel therapeutic target, either in treatment or as a novel biomarker, due to their cell-and disease-state specific expression and long-term stability. This review aims to summarise current findings on how circRNAs are dysregulated in cancer, the effects this has on disease progression, and how circRNAs may be targeted or utilised as future potential therapeutic options.
Developing an Agnostic Risk Prediction Model for Early AKI Detection in Cancer Patients
Authors: Scanlon Lauren A. , O’Hara Catherine , Garbett Alexander , Barker-Hewitt Matthew , Barriuso Jorge
Published: August 2021

Acute kidney injury (AKI) is a common complication among oncology patients associated with lower remission rates and higher mortality. To reduce the impact of this condition, we aimed to predict AKI earlier than existing tools, to allow clinical intervention before occurrence. We trained a random forest model on 597,403 routinely collected blood test results from 48,865 patients undergoing cancer treatment at The Christie NHS Foundation Trust between January 2017 and May 2020, to identify AKI events upcoming in the next 30 days. AKI risk levels were assigned to upcoming AKI events and tested through a prospective analysis between June and August 2020. The trained model gave an AUROC of 0.881 (95% CI 0.878–0.883), when assessing predictions per blood test for AKI occurrences within 30 days. Assigning risk levels and testing the model through prospective validation from the 1st June to the 31st August identified 73.8% of patients with an AKI event before at least one AKI occurrence, 61.2% of AKI occurrences. Our results suggest that around 60% of AKI occurrences experienced by patients undergoing cancer treatment could be identified using routinely collected blood results, allowing clinical remedial action to be taken and disruption to treatment by AKI to be minimised.
Mechanisms Regulating Abnormal Circular RNA Biogenesis in Cancer
Authors: Huang Ying , Zhu Qubo
Published: August 2021

Circular RNAs (circRNAs), which are a class of endogenous RNA with covalently closed loops, play important roles in epigenetic regulation of gene expression at both the transcriptional and post-transcriptional level. Accumulating evidence demonstrated that numerous circRNAs were abnormally expressed in tumors and their dysregulation was involved in the tumorigenesis and metastasis of cancer. Although the functional mechanisms of many circRNAs have been revealed, how circRNAs are dysregulated in cancer remains elusive. CircRNAs are generated by a “back-splicing” process, which is regulated by different cis-regulatory elements and trans-acting proteins. Therefore, how these cis and trans elements change during tumorigenesis and how they regulate the biogenesis of circRNAs in cancer are two questions that interest us. In this review, we summarized the pathways for the biogenesis of circRNAs; and then illustrated how circRNAs dysregulated in cancer by discussing the changes of cis-regulatory elements and trans-acting proteins that related to circRNA splicing and maturation in cancer.
DUOX2, a New Biomarker for Disseminated Gastric Cancer’s Response to Low Dose Radiation in Mice
Authors: Parekh Palak R. , Solano-Gonzalez Eduardo , Martins Mariana B. , Ma Xinrong , Tighe Kayla , Casildo Andrea , Zodda Andrew , Johnstone Christopher , Poirier Yannick , Mahmood Javed , Bhalla Kavita , Li Sheri , Lapidus Rena G. , Carrier France
Published: August 2021

Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, Dual Oxidase 2 (DUOX2). Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or reduced levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; modified regimen of docetaxel, cisplatin and 5′-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 0.15 Gy in three days), 4; mDCF and LD-WART. The combined regimen increased the odds of preventing cancer dissemination (mDCF + LD-WART OR = 4.16; 80% CI = 1.0, 17.29) in the DUOX2 positive tumors, while tumors expressing lower DUOX2 levels were more responsive to mDCF alone with no added benefit from LD-WART. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-κB upregulation. These data are particularly important since our study indicates that about 33% of human stomach adenocarcinoma do not express DUOX2. DUOX2 thus seems a likely biomarker for potential clinical application of chemopotentiation by LD-WART.
Cladribine Combined with Low-Dose Cytarabine as Frontline Treatment for Unfit Elderly Acute Myeloid Leukemia Patients: Results from a Prospective Multicenter Study of Polish Adult Leukemia Group (PALG)
Authors: Budziszewska Bożena Katarzyna , Salomon-Perzyński Aleksander , Pruszczyk Katarzyna , Barankiewicz Joanna , Pluta Agnieszka , Helbig Grzegorz , Janowska Anna , Kuydowicz Marta , Bołkun Łukasz , Piszcz Jarosław , Patkowska Elżbieta , Wątek Marzena , Małecki Piotr , Kościołek-Zgódka Sylwia , Cichocka Edyta , Charliński Grzegorz , Irga-Staniukiewicz Anna , Zaucha Jan Maciej , Piekarska Agnieszka , Gromek Tomasz , Hus Marek , Wójcik Karol , Raźny Małgorzata , Sędzimirska Mariola , Puła Bartosz , Giebel Sebastian , Grosicki Sebastian , Wierzbowska Agnieszka , Lech-Marańda Ewa
Published: August 2021

Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not eligible for intensive chemotherapy (IC) who had either the Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 or the hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥3. The induction phase included two cycles of LD-AC+cladribine. Patients who achieved at least partial remission (PR) received maintenance treatment with LD-AC alone. Overall, 117 patients with a median age of 70 years were enrolled. Adverse cytogenetics, ECOG PS ≥2 and HCT-CI score ≥3 was observed in 43.5%, 60%, and 58% of patients, respectively. The response rate (≥PR) was 54% (complete remission [CR], 32%; CR with incomplete hematologic recovery [CRi], 5%). A median overall survival (OS) was 21 and 8.8 months in CR/CRi and PR group, respectively. Advanced age (≥75 years) and adverse cytogenetics had a negative impact on OS. The 56-day mortality rate was 20.5%. In conclusion, LD-AC+cladribine is a beneficial therapeutic option with a predictable safety profile in elderly AML patients not eligible for IC.
Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing
Authors: Lee Chul Seung , Kim Hoon Seok , Schageman Jeoffrey , Lee In Kyu , Kim Myungshin , Kim Yonggoo
Published: August 2021

The objective of this study was to characterize circulating tumor DNA (ctDNA) mutations in colorectal cancer (CRC) patients and evaluate their prognostic values during treatment. Forty-nine patients with CRC planned for operation were enrolled. A total of 115 plasma samples were collected pre-operation, post-operation, and post-chemotherapy. ctDNA analysis was performed using next-generation sequencing (NGS) including 14 genes. In 22 (44.9%) out of 49 patients, at least one mutation (40 total mutations) was detected in the initial plasma sample. The median sum of variant allele frequency was 0.74% (range: 0.10–29.57%). TP53 mutations were the most frequent (17 of 49 patients, 34.7%), followed by APC (18.4%), KRAS (12.2%), FBXW7 (8.2%), NRAS (2.0%), PIK3CA (2.0%), and SMAD4 (2.0%). After surgery, five (14.3%) out of 35 patients harbored ctDNA mutation. All five patients experienced relapse or metastasis during follow-up. It was noteworthy that all three patients with persistent ctDNA relapsed after R0 resection. After chemotherapy, ctDNA analysis was performed for 31 patients, all of which were ctDNA-negative. Analytical and clinical performances of NGS to utilize ctDNA in CRC were determined. Results revealed that postoperative ctDNA might serve as a marker for identifying risk of recurrence, thus contributing to patient-oriented treatment strategies.
Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside
Authors: Bērziņa Santa , Harrison Alexandra , Taly Valérie , Xiao Wenjin
Published: August 2021

Tumor-on-chip technology has cemented its importance as an in vitro tumor model for cancer research. Its ability to recapitulate different elements of the in vivo tumor microenvironment makes it promising for translational medicine, with potential application in enabling personalized anti-cancer therapies. Here, we provide an overview of the current technological advances for tumor-on-chip generation. To further elevate the functionalities of the technology, these approaches need to be coupled with effective analysis tools. This aspect of tumor-on-chip technology is often neglected in the current literature. We address this shortcoming by reviewing state-of-the-art on-chip analysis tools for microfluidic tumor models. Lastly, we focus on the current progress in tumor-on-chip devices using patient-derived samples and evaluate their potential for clinical research and personalized medicine applications.
Anti-Coking and Anti-Sintering Ni/Al2O3 Catalysts in the Dry Reforming of Methane: Recent Progress and Prospects
Authors: Gao Xingyuan , Ge Zhiyong , Zhu Guofeng , Wang Ziyi , Ashok Jangam , Kawi Sibudjing
Published: August 2021

Coking and metal sintering are limitations of large-scale applications of Ni/Al2O3 catalysts in DRM reactions. In this review, several modification strategies to enhance the anti-deactivation property of Ni/Al2O3 are proposed and discussed with the recently developed catalyst systems, including structure and morphology control, surface acidity/basicity, interfacial engineering and oxygen defects. In addition, the structure–performance relationship and deactivation/anti-deactivation mechanisms are illustrated in depth, followed by prospects for future work.
Erythropoietin (EPO) as a Key Regulator of Erythropoiesis, Bone Remodeling and Endothelial Transdifferentiation of Multipotent Mesenchymal Stem Cells (MSCs): Implications in Regenerative Medicine
Authors: Tsiftsoglou Asterios S.
Published: August 2021

Human erythropoietin (EPO) is an N-linked glycoprotein consisting of 166 aa that is produced in the kidney during the adult life and acts both as a peptide hormone and hematopoietic growth factor (HGF), stimulating bone marrow erythropoiesis. EPO production is activated by hypoxia and is regulated via an oxygen-sensitive feedback loop. EPO acts via its homodimeric erythropoietin receptor (EPO-R) that increases cell survival and drives the terminal erythroid maturation of progenitors BFU-Es and CFU-Es to billions of mature RBCs. This pathway involves the activation of multiple erythroid transcription factors, such as GATA1, FOG1, TAL-1, EKLF and BCL11A, and leads to the overexpression of genes encoding enzymes involved in heme biosynthesis and the production of hemoglobin. The detection of a heterodimeric complex of EPO-R (consisting of one EPO-R chain and the CSF2RB β-chain, CD131) in several tissues (brain, heart, skeletal muscle) explains the EPO pleotropic action as a protection factor for several cells, including the multipotent MSCs as well as cells modulating the innate and adaptive immunity arms. EPO induces the osteogenic and endothelial transdifferentiation of the multipotent MSCs via the activation of EPO-R signaling pathways, leading to bone remodeling, induction of angiogenesis and secretion of a large number of trophic factors (secretome). These diversely unique properties of EPO, taken together with its clinical use to treat anemias associated with chronic renal failure and other blood disorders, make it a valuable biologic agent in regenerative medicine for the treatment/cure of tissue de-regeneration disorders.
Ion and Radical Characteristics (Mass/Energy Distribution) of a Capacitively Coupled Plasma Source Using Plasma Process Gases (CxFy)
Authors: Kim Yong-Hyun , Kim Jong-Sik , Kim Dae-Chul , Kim Young-Woo , Park Jong-Bae , Han Duk-Sun , Song Mi-Young
Published: August 2021

We constructed a capacitively coupled plasma (CCP) source and installed various diagnostic tools to perform process diagnosis using a plasma process gas (CxFy). We obtained the energy and mass distributions of the ions and radicals from Ar, C4F8/Ar, and C4F6/Ar plasmas. The energy distribution of the ions incident on the substrate was controlled using the self-bias voltage, and the ion energy was found to be inversely proportional to the mass. The measured species and density of the ions and radicals can help understand plasma process results as they provide information about the ions and radicals incident on the substrate.
Grain Rotation Accommodated GBS Mechanism for the Ti-6Al-4V Alloy during Superplastic Deformation
Authors: Yang Junzhou , Wu Jianjun
Published: August 2021

An investigation of flow behavior and the deformation mechanism for Ti-6Al-4V alloy during the superplastic deformation process is presented in this paper. Constant strain rate tensile tests were performed at 890–950 °C and strain rates of 10−2, 10−3, and 10−4/s. Then, surface observation by Optical Microscope (OM), Scanning Electron Microscopy (SEM), and Electron Back-scattered Diffraction (EBSD) was applied to obtain the microstructure mechanism. With pole figure maps (PF) for α-phase, obvious texture gradually changed in the main deformation direction. For the titanium alloy, the evolution of texture in deformed samples was attributed to grain rotation (GR). Significant grain rearrangement occurred between grains after deformation. A complete grain rotation accommodated grain boundary sliding (GBS) deformation mechanism is proposed, which can explain texture evolution without grain deformation.
Application of COI Primers 30F/885R in Rotifers to Regional Species Diversity in (Sub)Tropical China
Authors: Zhang Ya-Nan , Xu Shao-Lin , Huang Qi , Liu Ping , Han Bo-Ping
Published: August 2021

Rotifers are the most diverse group in freshwater zooplankton and play an important role in food webs and ecosystems. DNA barcoding has become a useful approach to investigate species diversity at local and regional scales, but its application is still limited by efficient primers for the group. To test a pair of primers 30F/885R recently designed for rotifers, we applied them to investigating regional species diversity in the freshwater of South China. We sequenced the cytochrome c oxidase subunit I (COI) gene of rotifers collected from the investigated 23 reservoirs in a large river basin and obtained 145 COI sequences from 33 species in 14 genera. The mean PCR success rate for all tested species was 50%. The 145 sequenced mtCOI in this study covered 33 of 64 identified morphological taxa, including most of the common species in the basin. The intraspecific genetic distance was calculated with a K2P model for 24 rotifer species occurring in the quantitative samples, in which 15 rotifers, such as Keratella cochlearis and Brachionus calyciflorus, had a genetic distance higher than 5%. The high intraspecific genetic differentiation indicates that cryptic species are probably common in (sub)tropical China.