bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise Prescription to Foster Health and Well-Being: A Behavioral Approach to Transform Barriers into Opportunities
Authors: Lucini Daniela , Pagani Massimo
Published: January 2021

The current literature contains multiple examples of exercise interventions to foster health and to prevent/treat many chronic non-communicable diseases; stress and functional syndromes. On the other hand, sedentariness is increasing and to transform a sedentary subject into a regular exerciser is not only very difficult but considered by some unrealistic in current clinical practice. Ideally a physical activity intervention may be considered actually efficacious when it outgrows the research setting and becomes embedded in a system, ensuring maintenance and sustainability of its health benefits. Physicians need specific skills to improve patients’ exercise habits. These range from traditional clinical competencies, to technical competencies to correctly prescribe exercise, to competencies in behavioral medicine to motivate the subject. From a behavioral and medical point of view, an exercise prescription may be considered correct only if the subject actually performs the prescribed exercise and this results in an improvement of physiological mechanisms such as endocrine, immunological and autonomic controls. Here we describe a model of intervention intended to nurture exercise prescription in everyday clinical setting. It aims to a tailored prescription, starts from the subject’s assessment, continues defining clinical goals/possible limitations and ends when the subject is performing exercise obtaining results.
Characterization of the 2017 Summer Heat Waves and Their Effects on the Population of an Area of Southern Italy
Authors: Infusino Ernesto , Caloiero Tommaso , Fusto Francesco , Calderaro Gianfranco , Brutto Angelo , Tagarelli Giuseppe
Published: January 2021

Knowledge of bioclimatic comfort is paramount for improving people’s quality of life. To this purpose, several studies related to climatic comfort/discomfort have been recently published. These studies mainly focus on the analysis of temperature and relative humidity, i.e., the main variables influencing the environmental stress in the human body. In this context, the present work aims to analyze the number of visits to the hospital emergency department made by the inhabitants of the Crati River valley (Calabria region, southern Italy) during the heat waves that accompanied the African anticyclone in the summer of 2017. The analysis of the bioclimatic comfort was performed using the humidity index. Results showed that greater the index, the higher the number of accesses to the emergency department, in particular by the most vulnerable population groups, such as children and the elderly.
The Influence of Human–Animal Interactions on Mental and Physical Health during the First COVID-19 Lockdown Phase in the U.K.: A Qualitative Exploration
Authors: Shoesmith Emily , Shahab Lion , Kale Dimitra , Mills Daniel S. , Reeve Catherine , Toner Paul , Santos de Assis Luciana , Ratschen Elena
Published: January 2021

The coronavirus disease 2019 (COVID-19) pandemic presents an opportunity to explore the role of animals as sources of emotional and physical support during a period when most of the population is experiencing social and environmental challenges. We investigated how companion animal owners perceived the influence of human–animal interaction on their physical and mental health during the first COVID-19 lockdown phase in the U.K., and what concerns they had regarding their animals at this time. We also explored the impact of participants’ interaction with non-companion animals during this phase. A cross-sectional online survey of U.K. residents aged over 18 was conducted between April and June 2020. The final item of the survey invited open-ended free-text responses, allowing participants to describe any experiences and/or perceptions of their human–animal relationships during the COVID-19 lockdown phase. A qualitative thematic analysis of responses was undertaken. Four main themes related to the following aspects of human–animal interactions during the COVID-19 lockdown phase were identified: the positive impact of animal ownership during the COVID-19 lockdown (e.g., amelioration of wellbeing and mental health), concerns relating to animal ownership during the COVID-19 lockdown (e.g., concerns over animals carrying the COVID-19 virus), grief and loss of an animal during the COVID-19 lockdown and the impact of engaging with non-companion animals during the COVID-19 lockdown. The findings complement and extend previous insights into the impact of human–animal interaction with both companion and non-companion animals. They also highlight the challenges of caring for an animal during the lockdown phase and indicate the need to consider the development of further targeted support strategies, such as “day care” for the companion animals of key workers in this context.
CdSe/ZnS Core-Shell-Type Quantum Dot Nanoparticles Disrupt the Cellular Homeostasis in Cellular Blood–Brain Barrier Models
Authors: Kania Katarzyna Dominika , Wagner Waldemar , Pułaski Łukasz
Published: January 2021

Two immortalized brain microvascular endothelial cell lines (hCMEC/D3 and RBE4, of human and rat origin, respectively) were applied as an in vitro model of cellular elements of the blood–brain barrier in a nanotoxicological study. We evaluated the impact of CdSe/ZnS core-shell-type quantum dot nanoparticles on cellular homeostasis, using gold nanoparticles as a largely bioorthogonal control. While the investigated nanoparticles had surprisingly negligible acute cytotoxicity in the evaluated models, a multi-faceted study of barrier-related phenotypes and cell condition revealed a complex pattern of homeostasis disruption. Interestingly, some features of the paracellular barrier phenotype (transendothelial electrical resistance, tight junction protein gene expression) were improved by exposure to nanoparticles in a potential hormetic mechanism. However, mitochondrial potential and antioxidant defences largely collapsed under these conditions, paralleled by a strong pro-apoptotic shift in a significant proportion of cells (evidenced by apoptotic protein gene expression, chromosomal DNA fragmentation, and membrane phosphatidylserine exposure). Taken together, our results suggest a reactive oxygen species-mediated cellular mechanism of blood–brain barrier damage by quantum dots, which may be toxicologically significant in the face of increasing human exposure to this type of nanoparticles, both intended (in medical applications) and more often unintended (from consumer goods-derived environmental pollution).
Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer
Authors: Choi Yoon Ju , Lee Jae-Eon , Ji Hyun Dong , Lee Bo-Ra , Lee Sang Bong , Kim Kil Soo , Lee In-Kyu , Chin Jungwook , Cho Sung Jin , Lee Jaetae , Lee Sang-Woo , Ha Jeoung-Hee , Jeon Yong Hyun
Published: January 2021

The silencing of thyroid-related genes presents difficulties in radioiodine therapy for anaplastic thyroid cancers (ATCs). Tunicamycin (TM), an N-linked glycosylation inhibitor, is an anticancer drug. Herein, we investigated TM-induced restoration of responsiveness to radioiodine therapy in radioiodine refractory ATCs. 125I uptake increased in TM-treated ATC cell lines, including BHT101 and CAL62, which was inhibited by KClO4, a sodium-iodide symporter (NIS) inhibitor. TM upregulated the mRNA expression of iodide-handling genes and the protein expression of NIS. TM blocked pERK1/2 phosphorylation in both cell lines, but AKT (protein kinase B) phosphorylation was only observed in CAL62 cells. The downregulation of glucose transporter 1 protein was confirmed in TM-treated cells, with a significant reduction in 18F-fluorodeoxyglucose (FDG) uptake. A significant reduction in colony-forming ability and marked tumor growth inhibition were observed in the combination group. TM was revealed to possess a novel function as a redifferentiation inducer in ATC as it induces the restoration of iodide-handling gene expression and radioiodine avidity, thereby facilitating effective radioiodine therapy.
Identification of Novel lncRNAs in Ovarian Cancer and Their Impact on Overall Survival
Authors: Cardillo Nicholas , Russo Douglas , Newtson Andreea , Reyes Henry , Lyons Yasmin , Devor Eric , Bender David , Goodheart Michael J. , Gonzalez-Bosquet Jesus
Published: January 2021

Long non-coding RNA’s (lncRNA) are RNA sequences that do not encode proteins and are greater than 200 nucleotides in length. They regulate complex cellular mechanisms and have been associated with prognosis in various types of cancer. We aimed to identify lncRNA sequences that are associated with high grade serous ovarian cancer (HGSC) and assess their impact on overall survival. RNA was extracted from 112 HGSC patients and 12 normal fallopian tube samples from our Biobank tissue repository. RNA was sequenced and the Ultrafast and Comprehensive lncRNA detection and quantification pipeline (UClncR) was used for the identification of lncRNA sequences. Univariate logistic and multivariate lasso regression analyses identified lncRNA that was associated with HGSC. Univariate and multivariate Cox proportional hazard ratios were used to evaluate independent predictors of survival. 1943 of 16,325 investigated lncRNA’s were differentially expressed in HGSC as compared to controls (p < 0.001). Nine of these demonstrated association with cancer after multivariate lasso regression. Our multivariate analysis of survival identified four lncRNA’s associated with survival in HGSC. Three out of these four were found to be independently significant after accounting for all clinical covariates. Lastly, seven lncRNAs were independently associated with initial response to chemotherapy; four portended a worse response, while three were associated with improved response. More research is needed, but there is potential for these lncRNAs to be used as biomarkers of HGSC or predictors of treatment outcome in the future.
5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction
Authors: Chang Sukkum Ngullie , Kim Se Ho , Dey Debasish Kumar , Park Seon Min , Nasif Omaima , Bajpai Vivek K. , Kang Sun Chul , Lee Jintae , Park Jae Gyu
Published: January 2021

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.
Preclinical Evaluation of Invariant Natural Killer T Cells Modified with CD38 or BCMA Chimeric Antigen Receptors for Multiple Myeloma
Authors: Poels Renée , Drent Esther , Lameris Roeland , Katsarou Afroditi , Themeli Maria , van der Vliet Hans J. , de Gruijl Tanja D. , van de Donk Niels W. C. J. , Mutis Tuna
Published: January 2021

Due to the CD1d restricted recognition of altered glycolipids, Vα24-invariant natural killer T (iNKT) cells are excellent tools for cancer immunotherapy with a significantly reduced risk for graft-versus-host disease when applied as off-the shelf-therapeutics across Human Leukocyte Antigen (HLA) barriers. To maximally harness their therapeutic potential for multiple myeloma (MM) treatment, we here armed iNKT cells with chimeric antigen receptors (CAR) directed against the MM-associated antigen CD38 and the plasma cell specific B cell maturation antigen (BCMA). We demonstrate that both CD38- and BCMA-CAR iNKT cells effectively eliminated MM cells in a CAR-dependent manner, without losing their T cell receptor (TCR)-mediated cytotoxic activity. Importantly, iNKT cells expressing either BCMA-CARs or affinity-optimized CD38-CARs spared normal hematopoietic cells and displayed a Th1-like cytokine profile, indicating their therapeutic utility. While the costimulatory domain of CD38-CARs had no influence on the cytotoxic functions of iNKT cells, CARs containing the 4-1BB domain showed a better expansion capacity. Interestingly, when stimulated only via CD1d+ dendritic cells (DCs) loaded with α-galactosylceramide (α-GalCer), both CD38- and BCMA-CAR iNKT cells expanded well, without losing their CAR- or TCR-dependent cytotoxic activities. This suggests the possibility of developing an off-the-shelf therapy with CAR iNKT cells, which might even be boostable in vivo by administration α-GalCer pulsed DCs.
In Silico Inference of Synthetic Cytotoxic Interactions from Paclitaxel Responses
Authors: Lee Jeong Hoon , Lee Kye Hwa , Kim Ju Han
Published: January 2021

To exploit negatively interacting pairs of cancer somatic mutations in chemotherapy responses or synthetic cytotoxicity (SC), we systematically determined mutational pairs that had significantly lower paclitaxel half maximal inhibitory concentration (IC50) values. We evaluated 407 cell lines with somatic mutation profiles and estimated their copy number and drug-inhibitory concentrations in Genomics of Drug Sensitivity in Cancer (GDSC) database. The SC effect of 142 mutated gene pairs on response to paclitaxel was successfully cross-validated using human cancer datasets for urogenital cancers available in The Cancer Genome Atlas (TCGA) database. We further analyzed the cumulative effect of increasing SC pair numbers on the TP53 tumor suppressor gene. Patients with TCGA bladder and urogenital cancer exhibited improved cancer survival rates as the number of disrupted SC partners (i.e., SYNE2, SON, and/or PRY) of TP53 increased. The prognostic effect of SC burden on response to paclitaxel treatment could be differentiated from response to other cytotoxic drugs. Thus, the concept of pairwise SC may aid the identification of novel therapeutic and prognostic targets.
Nanotechnology Therapy for Alzheimer′s Disease Memory Impairment Attenuation
Authors: Ribarič Samo
Published: January 2021

Currently, there is no cure for Alzheimer’s disease (AD) in humans; treatment is symptomatic only. Aging of the population, together with an unhealthy diet and lifestyle, contribute to the steady, global increase of AD patients. This increase creates significant health, societal and economical challenges even for the most developed countries. AD progresses from an asymptomatic stage to a progressively worsening cognitive impairment. The AD cognitive impairment is underpinned by progressive memory impairment, an increasing inability to recall recent events, to execute recently planned actions, and to learn. These changes prevent the AD patient from leading an independent and fulfilling life. Nanotechnology (NT) enables a new, alternative pathway for development of AD treatment interventions. At present, the NT treatments for attenuation of AD memory impairment are at the animal model stage. Over the past four years, there has been a steady increase in publications of AD animal models with a wide variety of original NT treatment interventions, able to attenuate memory impairment. NT therapy development, in animal models of AD, is faced with the twin challenges of the nature of AD, a chronic impairment, unique to human, of the tau protein and A β peptides that regulate several key physiological brain processes, and the incomplete understanding of AD′s aetiology. This paper reviews the state-of-the-art in NT based treatments for AD memory impairment in animal models and discusses the future work for translation to the successful treatment of AD cognitive impairment in human.
Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy
Authors: del Pozo-Acebo Lorena , López de las Hazas M-C , Tomé-Carneiro Joao , Gil-Cabrerizo Paula , San-Cristobal Rodrigo , Busto Rebeca , García-Ruiz Almudena , Dávalos Alberto
Published: January 2021

MicroRNAs (miRNAs) are small non-coding RNAs with a known role as mediators of gene expression in crucial biological processes, which converts them into high potential contenders in the ongoing search for effective therapeutic strategies. However, extracellular RNAs are unstable and rapidly degraded, reducing the possibility of successfully exerting a biological function in distant target cells. Strategies aimed at enhancing the therapeutic potential of miRNAs include the development of efficient, tissue-specific and nonimmunogenic delivery methods. Since miRNAs were discovered to be naturally transported within exosomes, a type of extracellular vesicle that confers protection against RNase degradation and increases miRNA stability have been proposed as ideal delivery vehicles for miRNA-based therapy. Although research in this field has grown rapidly in the last few years, a standard, reproducible and cost-effective protocol for exosome isolation and extracellular RNA delivery is lacking. We aimed to evaluate the use of milk-derived extracellular vesicles as vehicles for extracellular RNA drug delivery. With this purpose, exosomes were isolated from raw bovine milk, combining ultracentrifugation and size exclusion chromatography (SEC) methodology. Isolated exosomes were then loaded with exogenous hsa-miR148a-3p, a highly expressed miRNA in milk exosomes. The suitability of exosomes as delivery vehicles for extracellular RNAs was tested by evaluating the absorption of miR-148a-3p in hepatic (HepG2) and intestinal (Caco-2) cell lines. The potential exertion of a biological effect by miR-148a-3p was assessed by gene expression analysis, using microarrays. Results support that bovine milk is a cost-effective source of exosomes which can be used as nanocarriers of functional miRNAs with a potential use in RNA-based therapy. In addition, we show here that a combination of ultracentrifugation and SEC technics improve exosome enrichment, purity, and integrity for subsequent use.
What Is New in the Treatment of Smoldering Multiple Myeloma?
Authors: Bolli Niccolo’ , Sgherza Nicola , Curci Paola , Rizzi Rita , Strafella Vanda , Delia Mario , Gagliardi Vito Pier , Neri Antonino , Baldini Luca , Albano Francesco , Musto Pellegrino
Published: January 2021

Smoldering multiple myeloma (SMM), an asymptomatic plasma cell neoplasm, is currently diagnosed according to the updated IMWG criteria, which reflect an intermediate tumor mass between monoclonal gammopathy of undetermined significance (MGUS) and active MM. However, SMM is a heterogeneous entity and individual case may go from an “MGUS-like” behavior to “early MM” with rapid transformation into symptomatic disease. This wide range of clinical outcomes poses challenges for prognostication and management of individual patients. However, initial studies showed a benefit in terms of progression or even survival for early treatment of high-risk SMM patients. While outside of clinical trials the conventional approach to SMM generally remains that of close observation, these studies raised the question of whether early treatment should be offered in high-risk patients, prompting evaluation of several different therapeutic approaches with different goals. While delay of progression to MM with a non-toxic treatment is clearly achievable by early treatment, a convincing survival benefit still needs to be proven by independent studies. Furthermore, if SMM is to be considered less biologically complex than MM, early treatment may offer the chance of cure that is currently not within reach of any active MM treatment. In this paper, we present updated results of completed or ongoing clinical trials in SMM treatment, highlighting areas of uncertainty and critical issues that will need to be addressed in the near future before the “watch and wait” paradigm in SMM is abandoned in favor of early treatment.
Phacotrabeculectomy versus Phaco with Implantation of the Ex-PRESS Device: Surgical and Refractive Outcomes—A Randomized Controlled Trial
Authors: Konopińska Joanna , Byszewska Anna , Saeed Emil , Mariak Zofia , Rękas Marek
Published: January 2021

The aim of this study was to compare surgical and refractive outcomes between phacotrabeculectomy (P-Trab) and phaco with Ex-PRESS (P-Ex-PRESS) for glaucoma at a 6-month follow-up. This prospective randomized controlled trial included 81 eyes; 43 eyes (53%) and 38 eyes (47%) were assigned to the P-Ex-PRESS and P-Trab groups, respectively. Refraction, intraocular pressure (IOP), and best-corrected visual acuity were measured. Refractive change was analyzed using the cylinder’s magnitude, and polar analysis assessed the change in the trend of astigmatism [with-the-rule, against-the-rule (ATR), oblique (OBL)], evaluating mean astigmatism in centroid form. All patients showed a statistically significant postoperative decrease in IOP (P < 0.05). There were no differences between the groups in terms of postoperative IOP and visual outcomes or in astigmatism preoperatively or postoperatively (P = 0.61, P = 0.74). In both groups, the mean preoperative and postoperative astigmatism were ATR and OBL, respectively. Preoperative and postoperative centroids in the P-Ex-PRESS group were 0.44 ± 1.32 D at 177° and 0.35 ± 1 D at 8°, respectively, (P = 0.5) and in the P-Trab group were 0.16 ± 1.5 D at 141° and 0.39 ± 1.38 D at 29°, respectively (P = 0.38). Both P-Ex-PRESS and P-Trab showed comparable antihypertensive efficacy in treating open-angle glaucoma over 6 months. Preoperative and postoperative astigmatism did not differ between groups. The groups showed comparable results for final visual acuity.
GENERATOR Breast DataMart—The Novel Breast Cancer Data Discovery System for Research and Monitoring: Preliminary Results and Future Perspectives
Authors: Marazzi Fabio , Tagliaferri Luca , Masiello Valeria , Moschella Francesca , Colloca Giuseppe Ferdinando , Corvari Barbara , Sanchez Alejandro Martin , Capocchiano Nikola Dino , Pastorino Roberta , Iacomini Chiara , Lenkowicz Jacopo , Masciocchi Carlotta , Patarnello Stefano , Franceschini Gianluca , Gambacorta Maria Antonietta , Masetti Riccardo , Valentini Vincenzo
Published: January 2021

Background: Artificial Intelligence (AI) is increasingly used for process management in daily life. In the medical field AI is becoming part of computerized systems to manage information and encourage the generation of evidence. Here we present the development of the application of AI to IT systems present in the hospital, for the creation of a DataMart for the management of clinical and research processes in the field of breast cancer. Materials and methods: A multidisciplinary team of radiation oncologists, epidemiologists, medical oncologists, breast surgeons, data scientists, and data management experts worked together to identify relevant data and sources located inside the hospital system. Combinations of open-source data science packages and industry solutions were used to design the target framework. To validate the DataMart directly on real-life cases, the working team defined tumoral pathology and clinical purposes of proof of concepts (PoCs). Results: Data were classified into “Not organized, not ‘ontologized’ data”, “Organized, not ‘ontologized’ data”, and “Organized and ‘ontologized’ data”. Archives of real-world data (RWD) identified were platform based on ontology, hospital data warehouse, PDF documents, and electronic reports. Data extraction was performed by direct connection with structured data or text-mining technology. Two PoCs were performed, by which waiting time interval for radiotherapy and performance index of breast unit were tested and resulted available. Conclusions: GENERATOR Breast DataMart was created for supporting breast cancer pathways of care. An AI-based process automatically extracts data from different sources and uses them for generating trend studies and clinical evidence. Further studies and more proof of concepts are needed to exploit all the potentials of this system.
Potential Effects of Nutraceuticals in Retinopathy of Prematurity
Authors: Tsang Jessica K. W. , Wolf Susanne A. , Pompoes Inga M. , Joussen Antonia M. , Lam Wai Ching , Yang Di , Lo Amy C. Y.
Published: January 2021

Retinopathy of prematurity (ROP), the most common cause of childhood blindness, is a hypoxia-induced eye disease characterized by retinal neovascularization. In the normal retina, a well-organized vascular network provides oxygen and nutrients as energy sources to maintain a normal visual function; however, it is disrupted when pathological angiogenesis is induced in ROP patients. Under hypoxia, inadequate oxygen and energy supply lead to oxidative stress and stimulate neovasculature formation as well as affecting the function of photoreceptors. In order to meet the metabolic needs in the developing retina, protection against abnormal vascular formation is one way to manage ROP. Although current treatments provide beneficial effects in reducing the severity of ROP, these invasive therapies may also induce life-long consequences such as systemic structural and functional complications as well as neurodevelopment disruption in the developing infants. Nutritional supplements for the newborns are a novel concept for restoring energy supply by protecting the retinal vasculature and may lead to better ROP management. Nutraceuticals are provided in a non-invasive manner without the developmental side effects associated with current treatments. These nutraceuticals have been investigated through various in vitro and in vivo methods and are indicated to protect retinal vasculature. Here, we reviewed and discussed how the use of these nutraceuticals may be beneficial in ROP prevention and management.
Process Parameters Optimization Using Taguchi-Based Grey Relational Analysis in Laser-Assisted Machining of Si3N4
Authors: Pu Yezhuang , Zhao Yugang , Meng Jianbing , Zhao Guoyong , Zhang Haiyun , Liu Qian
Published: January 2021

Despite extensive research over the past three decades proving that laser-assisted machining (LAM) is effective for machining ceramic materials, which are affected by many machining parameters, there has been no systematic study of the effects of process parameters on surface quality in LAM ceramic materials. In this paper, the effects and optimization of laser power, spindle speed, feed rate, and cutting depth on surface roughness and work hardening of LAM Si3N4 were systematically studied, using grey relational analysis coupled with the Taguchi method. The results show that the combination of machining parameters determines the material removal mode at the material removal location, and then affects the surface quality. In ductile material removal mode, both the value of surface roughness and work hardening degree are smaller. Decreased surface roughness and work hardening degree can be obtained with smaller cutting depth and higher laser power.
Multi-Stage Cold Forging Process for Manufacturing a High-Strength One-Body Input Shaft
Authors: Jo A , Jeong Myeong , Lee Sang , Moon Young , Hwang Sun
Published: January 2021

A multi-stage cold forging process was developed and complemented with finite element analysis (FEA) to manufacture a high-strength one-body input shaft with a long length body and no separate parts. FEA showed that the one-body input shaft was manufactured without any defects or fractures. Experiments, such as tensile, hardness, torsion, and fatigue tests, and microstructural characterization, were performed to compare the properties of the input shaft produced by the proposed method with those produced using the machining process. The ultimate tensile strength showed a 50% increase and the torque showed a 100 Nm increase, confirming that the input shaft manufactured using the proposed process is superior to that processed using the machining process. Thus, this study provides a proof-of-concept for the design and development of a multi-stage cold forging process to manufacture a one-body input shaft with improved mechanical properties and material recovery rate.
Raltitrexed-Modified Gold and Silver Nanoparticles for Targeted Cancer Therapy: Cytotoxicity Behavior In Vitro on A549 and HCT-116 Human Cancer Cells
Authors: Morey Jeroni , Llinás Pere , Bueno-Costa Alberto , León Alberto J. , Piña M. Nieves
Published: January 2021

Two different raltitrexed gold and silver nanoparticles for the delivery of an antitumoral drug into cancer cells were synthesized and characterized. A cysteine linker was used for the covalent bonding of raltitrexed to the surface of nanoparticles. To evaluate the efficacy of the antifolate-derivative nanoparticles, their cytotoxicity was assayed in vitro with A549 human lung adenocarcinoma and HCT-116 colorectal carcinoma human cells. Modified nanoparticles are a biocompatible material, and administration of silver raltitrexed nanoparticles strongly inhibited the viability of the cancer cells; gold raltitrexed nanoparticles do not show any type of cytotoxic effect. The results suggest that silver raltitrexed nanoparticles could be a potential delivery system for certain cancer cells.
Modifying Cellulose Acetate Mixed-Matrix Membranes for Improved Oil–Water Separation: Comparison between Sodium and Organo-Montmorillonite as Particle Additives
Authors: Ang Micah Belle Marie Yap , Devanadera Kiara Pauline O. , Duena Alyssa Nicole R. , Luo Zheng-Yen , Chiao Yu-Hsuan , Millare Jeremiah C. , Aquino Ruth R. , Huang Shu-Hsien , Lee Kueir-Rarn
Published: January 2021

In this study, cellulose acetate (CA) mixed-matrix membranes were fabricated through the wet-phase inversion method. Two types of montmorillonite (MMT) nanoclay were embedded separately: sodium montmorillonite (Na-MMT) and organo-montmorillonite (O-MMT). Na-MMT was converted to O-MMT through ion exchange reaction using cationic surfactant (dialkyldimethyl ammonium chloride, DDAC). Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) compared the chemical structure and composition of the membranes. Embedding either Na-MMT and O-MMT did not change the crystallinity of the CA membrane, indicating that the nanoclays were dispersed in the CA matrix. Furthermore, nanoclays improved the membrane hydrophilicity. Compared with CANa-MMT membrane, CAO-MMT membrane had a higher separation efficiency and antifouling property. At the optimum concentration of O-MMT in the CA matrix, the pure water flux reaches up to 524.63 ± 48.96 L∙m−2∙h−1∙bar−1 with over 95% rejection for different oil-in-water emulsion (diesel, hexane, dodecane, and food-oil). Furthermore, the modified membrane delivered an excellent antifouling property.
Early Findings after Implementation of Veno-Arteriovenous ECMO: A Multicenter European Experience
Authors: Blandino Ortiz Aaron , Belliato Mirko , Broman Lars Mikael , Lheureux Olivier , Malfertheiner Maximilian Valentin , Xini Angela , Pappalardo Federico , Taccone Fabio Silvio
Published: January 2021

Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat cardiopulmonary failure in critically ill patients. Peripheral cannulation may be complicated by a persistent low cardiac output in case of veno-venous cannulation (VV-ECMO) or by differential hypoxia (e.g., lower PaO2 in the upper than in the lower body) in case of veno-arterial cannulation (VA-ECMO) and severe impairment of pulmonary function associated with cardiac recovery. The treatment of such complications remains challenging. We report the early effects of the use of veno-arterial-venous (V-AV) ECMO in this setting. Methods: Retrospective analysis including patients from five different European ECMO centers (January 2013 to December 2016) who required V-AV ECMO. We collected demographic data as well as comorbidities and ECMO characteristics, hemodynamics, and arterial blood gas values before and immediately after (i.e., within 2 h) V-AV implementation. Results: A total of 32 patients (age 53 (interquartiles, IQRs: 31–59) years) were identified: 16 were initially supported with VA-ECMO and 16 with VV-ECMO. The median time to V-AV conversion was 2 (1–5) days. After V-AV implantation, heart rate and norepinephrine dose significantly decreased, while PaO2 and SaO2 significantly increased compared to baseline values. Lactate levels significantly decreased from 3.9 (2.3–7.1) to 2.8 (1.4–4.4) mmol/L (p = 0.048). A significant increase in the overall ECMO blood flow (from 4.5 (3.8–5.0) to 4.9 (4.3–5.9) L/min; p < 0.01) was observed, with 3.0 (2.5–3.2) L/min for the arterial and 2.8 (2.1–3.6) L/min for the venous return flows. Conclusions: In ECMO patients with differential hypoxia or persistently low cardiac output syndrome, V-AV conversion was associated with improvement in some hemodynamic and respiratory parameters. A significant increase in the overall ECMO blood flow was also observed, with similar flow distributed into the arterial and venous return cannulas.
Environmentally Assisted Cracking Initiation in High-Temperature Water
Authors: Hojná Anna
Published: January 2021

Environmentally assisted cracking (EAC) is a very complex process that develops in materials that involve combining actions of environment and tensile loading. Crack initiation is the least explored stage and is not clearly defined. For this paper, current knowledge of crack initiation mechanisms was reviewed for three types of commercial structure materials exposed to high-temperature (HT) water coolants of power plants, namely ferritic low-alloy (LAS) and carbon (CS) steels, austenitic stainless (AS) steels, and nickel-based alloys. Physicochemical microprocesses engaged in the two earliest phases of the mechanism, the precursor and the incubation phases, are rather specific for each of these materials. In the latter, the slow growth phase, the crack development process passes into a sequence of repeating steps where the specific key microprocesses persist.
Effects of Manganese and Zirconium Dispersoids on Strain Localization in Aluminum Alloys
Authors: Jover Carrasco Elena , Chevy Juliette , Davo Belen , Fivel Marc
Published: January 2021

Strain localization in aluminum alloys can cause early failure of the material. Manganese and zirconium dispersoids, often present in aluminum alloys to control the grain size, have been found to be able to homogenize strain. To understand the effects of dispersoids on strain localization, a study of slip bands formed during tensile tests is carried out both experimentally and through simulations using interferometry and discrete dislocations dynamics. Simulations with various dispersoid size, volume fraction, and nature were carried out. The presence of dispersoids is proven to homogenize strain both is the experimental and numerical results.
Microstructural and Mechanical Characterization of W-CuCrZr Joints Brazed with Cu-Ti Filler Alloy
Authors: de Prado Javier , Sánchez María , Swan David , Ureña Alejandro
Published: January 2021

The determination of the mechanical properties of a brazed joint is an important factor to reach the metallurgical level of a joint development. This paper evaluates the mechanical properties, and its correlation with the joint microstructure, of a W-CuCrZr joint brazed in a high vacuum furnace using 80Cu-20Ti flexible filler material in tape form. This joint is meant to be implemented in the divertor application in future fusion power plants. Main experimental parameters were a brazing temperature of 960 °C and a dwell time of 10 min. The microstructure of the joint was constituted by Cu solid solution and Cu4Ti phases. This last phase was distributed in the W-braze interface. Mechanical properties were evaluated by means of Vickers microhardness and mechanical tests by applying pure shear loads. The microhardness profile of the brazed joint indicated that W remained with the as-received hardness but CuCrZr base material was softened after the brazing procedure. Shear strength of 96 ± 15 MPa was obtained for the brazed joint and fracture propagated at the W-braze interface.
Pathway Tools Visualization of Organism-Scale Metabolic Networks
Authors: Paley Suzanne , Billington Richard , Herson James , Krummenacker Markus , Karp Peter D.
Published: January 2021

Metabolomics, synthetic biology, and microbiome research demand information about organism-scale metabolic networks. The convergence of genome sequencing and computational inference of metabolic networks has enabled great progress toward satisfying that demand by generating metabolic reconstructions from the genomes of thousands of sequenced organisms. Visualization of whole metabolic networks is critical for aiding researchers in understanding, analyzing, and exploiting those reconstructions. We have developed bioinformatics software tools that automatically generate a full metabolic-network diagram for an organism, and that enable searching and analyses of the network. The software generates metabolic-network diagrams for unicellular organisms, for multi-cellular organisms, and for pan-genomes and organism communities. Search tools enable users to find genes, metabolites, enzymes, reactions, and pathways within a diagram. The diagrams are zoomable to enable researchers to study local neighborhoods in detail and to see the big picture. The diagrams also serve as tools for comparison of metabolic networks and for interpreting high-throughput datasets, including transcriptomics, metabolomics, and reaction fluxes computed by metabolic models. These data can be overlaid on the metabolic charts to produce animated zoomable displays of metabolic flux and metabolite abundance. The BioCyc.org website contains whole-network diagrams for more than 18,000 sequenced organisms. The ready availability of organism-specific metabolic network diagrams and associated tools for almost any sequenced organism are useful for researchers working to better understand the metabolism of their organism and to interpret high-throughput datasets in a metabolic context.
A Transit Time-Resolved Microflow Cytometry-Based Agglutination Immunoassay for On-Site C-Reactive Protein Detection
Authors: Qu Jianxi , Zhang Yushan , Chenier Mathieu , Xu Chang-qing , Chen Lan , Wan Yonghong
Published: January 2021

An accurate and rapid microflow cytometry-based agglutination immunoassay (MCIA) suitable for on-site antibody or antigen detection was proposed. In this study, quantitative C-reactive protein (CRP) detection was chosen as a model assay in order to demonstrate the detection principle. The average transit time was employed to estimate the extent of the agglutination reaction and improve the detection accuracy as compared to the intensity-dependent methods. The detection time was less than 8 min. and only a 20 µL serum sample was needed for each test. The results showed a linear relationship between the average transit time of aggregates and CRP concentrations ranging from 0 to 1 µg/mL. The R2 of this relationship was 0.99. The detection limit of this technology was 0.12 µg/mL CRP. The system used for CRP detection can be extended to also monitor other clinically relevant molecules.
Tectonic-Related Geochemical and Hydrological Anomalies in Italy during the Last Fifty Years
Authors: Martinelli Giovanni , Ciolini Riccardo , Facca Gianluca , Fazio Francesco , Gherardi Fabrizio , Heinicke Jens , Pierotti Lisa
Published: January 2021

Seismic hazard reduction policies usually utilize earthquake catalogues and probability evaluations of occurrence. Further geophysical and geochemical parameters could contribute to hazard reduction policies as is currently the case in some countries, such as Iceland, Taiwan, China and Russian Federation. In the past four decades, intense research activity carried out by many different institutions in Italy has allowed us to recognize the most relevant sensitive sites for detecting acceleration in crustal deformation processes by means of geofluids monitoring. All scientific papers published in the period 1976–2020 concerning tectonic-related signals in geofluids have been considered. An in-depth review of previous and present-day research activities, as well as an update of two unpublished time series recorded in Central and southern Italy, has contributed to identifying areas where an instrumental array is still lacking and the most relevant priority areas for monitoring activities in geofluids. An atlas of all experimental sites utilized in recent decades has been obtained with the purpose of contributing to identifying the most suitable monitoring areas.
Effect of CO Molecule Orientation on the Reduction of Cu-Based Nanoparticles
Authors: Sarvadii Sergey Y. , Gatin Andrey K. , Kharitonov Vasiliy A. , Dokhlikova Nadezhda V. , Ozerin Sergey A. , Grishin Maxim V. , Shub Boris R.
Published: January 2021

The adsorption of CO on the surface of Cu-based nanoparticles was studied in the presence of an external electric field by means of scanning tunneling microscopy (STM) and spectroscopy (STS). Nanoparticles were synthesized on the surface of a graphite support by the impregnation–precipitation method. The chemical composition of the surface of the nanoparticles was determined as a mixture of Cu2O, Cu4O3 and CuO oxides. CO was adsorbed from the gas phase onto the surface of the nanoparticles. During the adsorption process, the potential differences ΔV = +1 or −1 V were applied to the vacuum gap between the sample and the grounded tip. Thus, the system of the STM tip and sample surface formed an asymmetric capacitor, inside which an inhomogeneous electric field existed. The CO adsorption process is accompanied by the partial reduction of nanoparticles. Due to the orientation of the CO molecule in the electric field, the reduction was weak in the case of a positive potential difference, while in the case of a negative potential difference, the reduction rate increased significantly. The ability to control the adsorption process of CO by means of an external electric field was demonstrated. The size of the nanoparticle was shown to be the key factor affecting the adsorption process, and particularly, the strength of the local electric field close to the nanoparticle surface.
Numerical Study on Enhanced Line Focusing via Buried Metallic Nanowire Assisted Binary Plate
Authors: Kim Hyuntai
Published: January 2021

Line focusing, which collects light into a line rather than a single point, has an advantage on variable fields such as machining and imaging. The 1-dimensional metallic zone plate is one of the candidates for line focusing, which is ultra-thin and simple to fabricate. Metallic nano-slits can replace the metal blocked region to increase the efficiency, however, the efficiency and stability are still low. Therefore, this paper proposes a structure with an additional dielectric layer to protect the metallic nano-slit layer—a buried metallic wire structure—and verify the idea based on numerical simulations. Two structures are proposed. In terms of stability, a flat surface structure is proposed and a corrugated surface structure with a consistent thickness with the nano-slit is proposed which has low fabrication difficulty. The optimization of the buried wire structure and performance after applying the buried wire structure to the dual-line focusing plate is calculated by numerical simulation. Finally, it was shown that the electric field intensity was 2.13 times greater.
Engineering Red-Enhanced and Biocompatible Upconversion Nanoparticles
Authors: Alkahtani Masfer , Alsofyani Najla , Alfahd Anfal , Almuqhim Anas A. , Almughem Fahad A. , Alshehri Abdullah A. , Qasem Hussam , Hemmer Philip R.
Published: January 2021

The exceptional optical properties of lanthanide-doped upconversion nanoparticles (UCNPs) make them among the best fluorescent markers for many promising bioapplications. To fully utilize the unique advantages of the UCNPs for bioapplications, recent significant efforts have been put into improving the brightness of small UCNPs crystals by optimizing dopant concentrations and utilizing the addition of inert shells to avoid surface quenching effects. In this work, we engineered bright and small size upconversion nanoparticles in a core–shell–shell (CSS) structure. The emission of the synthesized CSS UCNPs is enhanced in the biological transparency window under biocompatible excitation wavelength by optimizing dopant ion concentrations. We also investigated the biosafety of the synthesized CSS UCNP particles in living cell models to ensure bright and non-toxic fluorescent probes for promising bioapplications.
Evidence for Establishing the Clinical Breakpoint of Cefquinome against Haemophilus Parasuis in China
Authors: Mi Kun , Sun Da , Li Mei , Hao Haihong , Zhou Kaixiang , Liu Zhenli , Yuan Zonghui , Huang Lingli
Published: January 2021

Haemophilus parasuis can cause high morbidity and mortality in swine. Cefquinome possesses excellent antibacterial activity against pathogens causing diseases of the respiratory tract. This study aimed to establish the clinical breakpoint (CBP) of cefquinome against H. parasuis and to monitor the resistance change. Referring to the minimum inhibitory concentration (MIC) distribution of cefquinome against 131 H. parasuis isolates, the MIC50 and MIC90 were determined to be 0.125 and 1 μg/mL, respectively. And the epidemiological cutoff (ECOFF) value was 1 μg/mL. HPS42 was selected as a representative strain for the pharmacodynamic (PD) experiment, pharmacokinetic (PK) experiment and clinical experiments. The PK/PD index values, area under concentration-time curve (AUC)/MIC, of the bacteriostatic, bactericidal, and bacterial elimination effects were 23, 41, and 51 h, respectively. The PK/PD cutoff was calculated as 0.125 μg/mL by Monte Carlo simulation (MCS), and the clinical cutoff was 0.25−4 μg/mL by WindoW. Combing these three values, the CBP of cefquinome against H. parasuis was found to be 1 μg/mL. In conclusion, this was the first study to integrate various cutoffs to establish the CBP in the laboratory. It is helpful to distinguish wild type H. parasuis and reduce the probability of treatment failure.
Severe Concomitant Physaloptera sp., Dirofilaria immitis, Toxocara cati, Dipylidium caninum, Ancylostoma sp. and Taenia taeniaeformis Infection in a Cat
Authors: Menk P. Lima Jose Cesar , Del Piero Fabio
Published: January 2021

Here we describe an unusual and severe mixed parasitic infection in a cat that died during routine surgery. Gastric Physaloptera sp., cardiac Dirofilaria immitis, and intestinal Toxocara cati, Dipylidium caninum, Ancylostoma sp. and Taenia taeniaeformis were observed. Histologic lesions included chronic proliferative pulmonary endarteritis, mild increase of mucosal intestinal white cells, and terminal aspiration of gastric content. The severe dirofilariasis may have contributed to this patient death during anesthesia.