bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Data Assimilation and the Relationship between ENSO and Precipitation
Authors: Injan Sittisak , Wangwongchai Angkool , Humphries Usa
Published: March 2021

Climate change in Thailand is related to the El Niño and Southern Oscillation (ENSO) phenomenon, in particular drought and heavy precipitation. The data assimilation method is used to improve the accuracy of the Ensemble Intermediate Coupled Model (EICM) that simulates the sea surface temperature (SST). The four-dimensional variational (4D-Var) and three-dimensional variational (3D-Var) schemes have been used for data assimilation purposes. The simulation was performed by the model with and without data assimilation from satellite data in 2011. The result shows that the model with data assimilation is better than the model without data assimilation. The 4D-Var scheme is the best method, with a Root Mean Square Error (RMSE) of 0.492 and a Correlation Coefficient of 0.684. The relationship between precipitation in Thailand and the ENSO area in Niño 3.4 was consistent for seven months, with a correlation coefficient of −0.882.
N-Amino-l-Proline Methyl Ester from an Australian Fish Gut-Derived Fungus: Challenging the Distinction between Natural Product and Artifact
Authors: Mohamed Osama , Khalil Zeinab , Capon Robert
Published: March 2021

Further investigation into a fish gut-derived fungus Evlachovaea sp. CMB-F563, previously reported to produce the unprecedented Schiff base prolinimines A–B (1–2), revealed a new cryptic natural product, N-amino-l-proline methyl ester (5)—only the second reported natural occurrence of an N-amino-proline, and the first from a microbial source. To enable these investigations, we developed a highly sensitive analytical derivitization methodology, using 2,4-dinitrobenzaldehyde (2,4-DNB) to cause a rapid in situ transformation of 5 to the Schiff base 9, with the latter more readily detectable by UHPLC-DAD (400 nm) and HPLC-MS analyses. Moreover, we demonstrate that during cultivation 5 is retained in fungal mycelia, and it is only when solvent extraction disrupts mycelia that 5 is released to come in contact with the furans 7–8 (which are themselves produced by thermal transformation of carbohydrates during media autoclaving prior to fungal inoculation). Significantly, on contact, 5 undergoes a spontaneous condensation with 7–8 to yield the Schiff base prolinimines 1–2, respectively. Observations made during this study prompted us to reflect on what it is to be a natural product (i.e., 5), versus an artifact (i.e., 1–2), versus a media component (i.e., 7–8).
Identification of Breast Cancer Subtype-Specific Biomarkers by Integrating Copy Number Alterations and Gene Expression Profiles
Authors: Cava Claudia , Pisati Mirko , Frasca Marco , Castiglioni Isabella
Published: March 2021

Background and Objectives: Breast cancer is a heterogeneous disease categorized into four subtypes. Previous studies have shown that copy number alterations of several genes are implicated with the development and progression of many cancers. This study evaluates the effects of DNA copy number alterations on gene expression levels in different breast cancer subtypes. Materials and Methods: We performed a computational analysis integrating copy number alterations and gene expression profiles in 1024 breast cancer samples grouped into four molecular subtypes: luminal A, luminal B, HER2, and basal. Results: Our analyses identified several genes correlated in all subtypes such as KIAA1967 and MCPH1. In addition, several subtype-specific genes that showed a significant correlation between copy number and gene expression profiles were detected: SMARCB1, AZIN1, MTDH in luminal A, PPP2R5E, APEX1, GCN5 in luminal B, TNFAIP1, PCYT2, DIABLO in HER2, and FAM175B, SENP5, SCAF1 in basal subtype. Conclusions: This study showed that computational analyses integrating copy number and gene expression can contribute to unveil the molecular mechanisms of cancer and identify new subtype-specific biomarkers.
Comprehensive Analysis of Foulants in an Ultrafiltration Membrane Used for the Treatment of Bleach Plant Effluent in a Sulfite Pulp Mill
Authors: Rudolph Gregor , Al-Rudainy Basel , Thuvander Johan , Jönsson Ann-Sofi
Published: March 2021

Fouling is a major obstacle in the introduction of membrane processes in new applications in the pulping industry. Due to the complex nature of the feed solutions, complementary analysis methods are usually needed to identify the substances involved. Four different methods were used for the comprehensive analysis of a membrane removed from an ultrafiltration plant treating alkaline bleach plant effluent in a sulfite pulp mill to identify the substances causing fouling. Magnesium was detected both on the membrane surface and in the nonwoven membrane backing and a small amount of polysaccharides was detected after acid hydrolysis of the fouled membrane. This study provides information on foulants, which can be used to improve processing conditions and cleaning protocols and thus the membrane performance in pulp mill separation processes. It also provides an overview of the usefulness of various analytical methods.
The mwtab Python Library for RESTful Access and Enhanced Quality Control, Deposition, and Curation of the Metabolomics Workbench Data Repository
Authors: Powell Christian D. , Moseley Hunter N.B.
Published: March 2021

The Metabolomics Workbench (MW) is a public scientific data repository consisting of experimental data and metadata from metabolomics studies collected with mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. MW has been constantly evolving; updating its ‘mwTab’ text file format, adding a JavaScript Object Notation (JSON) file format, implementing a REpresentational State Transfer (REST) interface, and nearly quadrupling the number of datasets hosted on the repository within the last three years. In order to keep up with the quickly evolving state of the MW repository, the ‘mwtab’ Python library and package have been continuously updated to mirror the changes in the ‘mwTab’ and JSONized formats and contain many new enhancements including methods for interacting with the MW REST interface, enhanced format validation features, and advanced features for parsing and searching for specific metabolite data and metadata. We used the enhanced format validation features to evaluate all available datasets in MW to facilitate improved curation and FAIRness of the repository. The ‘mwtab’ Python package is now officially released as version 1.0.1 and is freely available on GitHub and the Python Package Index (PyPI) under a Clear Berkeley Software Distribution (BSD) license with documentation available on ReadTheDocs.
Comparing Levels of Metabolic Predictors of Coronary Heart Disease between Healthy Lean and Overweight Females
Authors: Abu-El-Ruz Rasha , Abdel-Rahman Manar E. , Atkin Stephen L. , Elrayess Mohamed A.
Published: March 2021

Screening for the metabolomic signature of coronary heart disease (CHD) before disease onset could help in early diagnosis and potentially disease prevention. In this study, the levels of 17 CHD metabolic biomarkers in apparently healthy overweight females were compared to lean counterparts, and their associations with conventional clinical risk factors were determined. Clinical and metabolic data from 200 apparently healthy non-obese Qatari females were collected from Qatar Biobank (discovery cohort). Logistic regression was used to assess the association between body mass index (BMI) groups and 17 CHD metabolic biomarkers, and receiver operating characteristic (ROC) analysis was used to evaluate the prognostic value of CHD metabolic biomarkers in overweight. Stepwise linear regression was performed to identify the classical risk factors associated with CHD metabolites differentiating the two BMI groups. Validation of the association of CHD metabolic biomarkers with BMI groups was performed in 107 subjects (replication cohort). Out of the tested CHD metabolic biomarkers, five were significantly different between lean and overweight females in the discovery cohort (AUC = 0.73). Among these, the association of mannose, asparagine, and linoleate with BMI groups was confirmed in the replication cohort (AUC = 0.97). Significant correlations between predictors of CHD in overweight healthy women and classical risk factors were observed, including serum levels of cholesterol, testosterone, triiodothyronine, thyroxine, creatinine, albumin, bilirubin, glucose, c-peptide, uric acid, calcium and chloride. Apparently, healthy overweight females exhibit significantly different levels of specific CHD metabolites compared to their lean counterparts, offering a prognostic potential with preventative value.
Generation of Complex Transverse Energy Flow Distributions with Autofocusing Optical Vortex Beams
Authors: Khonina Svetlana N. , Porfirev Alexey P. , Ustinov Andrey V. , Butt Muhammad Ali
Published: March 2021

Optical vortex (OV) beams are widely used for the generation of light fields with transverse energy flow inducing orbital motion of the nano- and microparticles in the transverse plane. Here, we present some new modifications of OV beams with autofocusing properties for shaping complex transverse energy flow distributions varying in space. The angular component of the complex amplitude of these beams is defined by the superpositions of OV beams with different topological charges. The proposed approach provides a convenient method to control the three-dimensional structure of the generated autofocusing OV beams. The control of the transverse distribution of an autofocusing beam provides a wide variety of generated fields with both rotating and periodic properties, which can be used in the field of laser manipulation and laser material processing. Thus, the obtained numerical results predict different types of motion of the trapped particles for the designed OV autofocusing beams. The experimental results agree with modeling results and demonstrate the principal possibility to shape such laser beams using spatial light modulators.
The Micro Topology and Statistical Analysis of the Forces of Walking and Failure of an ITAP in a Femur
Authors: Langford Euan , Griffiths Christian Andrew , Rees Andrew , Bird Josh
Published: March 2021

This paper studies the forces acting upon the Intraosseous Transcutaneous Amputation Prosthesis, ITAP, that has been designed for use in a quarter amputated femur. To design in a failure feature, utilising a safety notch, which would stop excessive stress, σ, permeating the bone causing damage to the user. To achieve this, the topology of the ITAP was studied using MATLAB and ANSYS models with a wide range of component volumes. The topology analysis identified critical materials and local maximum stresses when modelling the applied loads. This together with additive layer manufacture allows for bespoke prosthetics that can improve patient outcomes. Further research is needed to design a fully functional, failure feature that is operational when extreme loads are applied from any direction. Physical testing is needed for validation of this study. Further research is also recommended on the design so that the σ within the ITAP is less than the yield stress, σs, of bone when other loads are applied from running and other activities.
Design and Application of MEMS-Based Hall Sensor Array for Magnetic Field Mapping
Authors: Lee Chia-Yen , Lin Yu-Ying , Kuo Chung-Kang , Fu Lung-Ming
Published: March 2021

A magnetic field measurement system based on an array of Hall sensors is proposed. The sensors are fabricated using conventional microelectromechanical systems (MEMS) techniques and consist of a P-type silicon substrate, a silicon dioxide isolation layer, a phosphide-doped cross-shaped detection zone, and gold signal leads. When placed within a magnetic field, the interaction between the local magnetic field produced by the working current and the external magnetic field generates a measurable Hall voltage from which the strength of the external magnetic field is then derived. Four Hall sensors are fabricated incorporating cross-shaped detection zones with an identical aspect ratio (2.625) but different sizes (S, M, L, and XL). For a given working current, the sensitivities and response times of the four devices are found to be almost the same. However, the offset voltage increases with the increasing size of the detection zone. A 3 × 3 array of sensors is assembled into a 3D-printed frame and used to determine the magnetic field distributions of a single magnet and a group of three magnets, respectively. The results show that the constructed 2D magnetic field contour maps accurately reproduce both the locations of the individual magnets and the distributions of the magnetic fields around them.
On the Performance Evaluation of Commercial SAW Resonators by Means of a Direct and Reliable Equivalent-Circuit Extraction
Authors: Gugliandolo Giovanni , Marinković Zlatica , Campobello Giuseppe , Crupi Giovanni , Donato Nicola
Published: March 2021

Nowadays, surface acoustic wave (SAW) resonators are attracting growing attention, owing to their widespread applications in various engineering fields, such as electronic, telecommunication, automotive, chemical, and biomedical engineering. A thorough assessment of SAW performance is a key task for bridging the gap between commercial SAW devices and practical applications. To contribute to the accomplishment of this crucial task, the present paper reports the findings of a new comparative study that is based on the performance evaluation of different commercial SAW resonators by using scattering (S-) parameter measurements coupled with a Lorentzian fitting and an accurate modelling technique for the straightforward extraction of a lumped-element equivalent-circuit representation. The developed investigation thus provides ease and reliability when choosing the appropriate commercial device, depending on the requirements and constraints of the given sensing application. This paper deals with the performance evaluation of commercial surface acoustic wave (SAW) resonators by means of scattering (S-) parameter measurements and an equivalent-circuit model extracted using a reliable modeling procedure. The studied devices are four TO-39 packaged two-port resonators with different nominal operating frequencies: 418.05, 423.22, 433.92, and 915 MHz. The S-parameter characterization was performed locally around the resonant frequencies of the tested SAW resonators by using an 8753ES Agilent vector network analyzer (VNA) and a home-made calibration kit. The reported measurement-based study has allowed for the development of a comprehensive and detailed comparative analysis of the performance of the investigated SAW devices. The characterization and modelling procedures are fully automated with a user-friendly graphical user interface (GUI) developed in the Python environment, thereby making the experimental analysis faster and more efficient.
Design of Customize Interbody Fusion Cages of Ti64ELI with Gradient Porosity by Selective Laser Melting Process
Authors: Pan Cheng-Tang , Lin Che-Hsin , Huang Ya-Kang , Jang Jason S. C. , Lin Hsuan-Kai , Kuo Che-Nan , Lin De-Yao , Huang Jacob C.
Published: March 2021

Intervertebral fusion surgery for spinal trauma, degeneration, and deformity correction is a major vertebral reconstruction operation. For most cages, the stiffness of the cage is high enough to cause stress concentration, leading to a stress shielding effect between the vertebral bones and the cages. The stress shielding effect affects the outcome after the reconstruction surgery, easily causing damage and leading to a higher risk of reoperation. A porous structure for the spinal fusion cage can effectively reduce the stiffness to obtain more comparative strength for the surrounding tissue. In this study, an intervertebral cage with a porous gradation structure was designed for Ti64ELI alloy powders bonded by the selective laser melting (SLM) process. The medical imaging software InVesalius and 3D surface reconstruction software Geomagic Studio 12 (Raindrop Geomagic Inc., Morrisville, NC, USA) were utilized to establish the vertebra model, and ANSYS Workbench 16 (Ansys Inc., Canonsburg, PA, USA) simulation software was used to simulate the stress and strain of the motions including vertical body-weighted compression, flexion, extension, lateral bending, and rotation. The intervertebral cage with a hollow cylinder had porosity values of 80–70–60–70–80% (from center to both top side and bottom side) and had porosity values of 60–70–80 (from outside to inside). In addition, according to the contact areas between the vertebras and cages, the shape of the cages can be custom-designed. The cages underwent fatigue tests by following ASTM F2077-17. Then, mechanical property simulations of the cages were conducted for a comparison with the commercially available cages from three companies: Zimmer (Zimmer Biomet Holdings, Inc., Warsaw, IN, USA), Ulrich (Germany), and B. Braun (Germany). The results show that the stress and strain distribution of the cages are consistent with the ones of human bone, and show a uniform stress distribution, which can reduce stress concentration.
Preparation of Cobalt Oxide–Reduced Graphitic Oxide Supercapacitor Electrode by Photothermal Processing
Authors: Gaire Madhu , Khatoon Najma , Chrisey Douglas
Published: March 2021

We report a photonic technique to instantaneously synthesize cobalt oxide reduced graphitic oxide (CoOx-rGO) supercapacitor electrodes. The electrode processing is achieved through rapidly heating the precursor material by irradiation of high-energy pulsed mostly visible light from a xenon lamp. Due to the short duration of the light pulse, we prepared the electrodes at room temperature instantaneously (ms), thus eliminating the several hours of processing times of the conventional techniques. The as-prepared electrodes exhibited a highly porous morphology, allowing for enhanced ionic transport during electrochemical interactions. The electrochemical properties of the CoOx-rGO electrodes were studied in 1 M KOH aqueous electrolyte. The non-rectangular cyclic voltammetry (CV) curves with characteristic redox peaks indicated the pseudocapacitive charge storage mechanism of the electrodes. From the discharge curves at 0.4 mA/cm2 and 1.6 A/g constant current densities, the electrode showed areal specific capacitance of 17 mF/cm2 and specific capacitance of 69 F/g, respectively. Cyclic stability was tested by performing 30,000 galvanostatic charge–discharge (GCD) cycles and the electrode exhibited 65% capacitance retention, showing its excellent electrochemical performance and ultra-long cycle life. The excellent electrochemical electrode properties are attributed to the unique processing technique, optimum processing parameters, improved conductivity due to the presence of rGO, and highly porous morphology which offers a high specific surface area. The novel photonic processing we report allows for high-temperature heating of the precursor films achieved via non-radiative recombination of photogenerated electron holes pairs during irradiation. Such extremely quick (ms) heating followed by instantaneous cooling results in the formation of a dense and robust bottom layer of the electrode, resulting in a long cycle life.
Optical Polymer Waveguides Fabricated by Roll-to-Plate Nanoimprinting Technique
Authors: Prajzler Vaclav , Chlupaty Vaclav , Kulha Pavel , Neruda Milos , Kopp Sonja , Mühlberger Michael
Published: March 2021

The paper reports on the properties of UV-curable inorganic-organic hybrid polymer multimode optical channel waveguides fabricated by roll-to-plate (R2P) nanoimprinting. We measured transmission spectra, refractive indices of the applied polymer materials, and optimized the R2P fabrication process. Optical losses of the waveguides were measured by the cut-back method at wavelengths of 532, 650, 850, 1310, and 1550 nm. The lowest optical losses were measured at 850 nm and the lowest average value was 0.19 dB/cm, and optical losses at 1310 nm were 0.42 dB/cm and 0.25 dB/cm at 650 nm respectively. The study has demonstrated that nanoimprinting has great potential for the implementation of optical polymer waveguides not only for optical interconnection applications.
Joining Caffeic Acid and Hydrothermal Treatment to Produce Environmentally Benign Highly Reduced Graphene Oxide
Authors: Barra Ana , Lazăr Oana , Pantazi Aida , Hortigüela María J. , Otero-Irurueta Gonzalo , Enăchescu Marius , Ruiz-Hitzky Eduardo , Nunes Cláudia , Ferreira Paula
Published: March 2021

Reduced graphene oxide (rGO) is a promising graphene-based material, with transversal applicability to a wide range of technological fields. Nevertheless, the common use of efficient—but hazardous to environment and toxic—reducing agents prevents its application in biological and other fields. Consequently, the development of green reducing strategies is a requirement to overcome this issue. Herein, a green, simple, and cost-effective one-step reduction methodology is presented. Graphene oxide (GO) was hydrothermally reduced in the presence of caffeic acid (CA), a natural occurring phenolic compound. The improvement of the hydrothermal reduction through the presence of CA is confirmed by XRD, Raman, XPS and TGA analysis. Moreover, CA polymerizes under hydrothermal conditions with the formation of spherical and non-spherical carbon particles, which can be useful for further rGO functionalization. FTIR and XPS confirm the oxygen removal in the reduced samples. The high-resolution scanning transmission electron microscopy (HRSTEM) images also support the reduction, showing rGO samples with an ordered graphitic layered structure. The promising rGO synthesized by this eco-friendly methodology can be explored for many applications.
Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Markun Stefan , Gravestock Isaac , Jäger Levy , Rosemann Thomas , Pichierri Giuseppe , Burgstaller Jakob M.
Published: March 2021

Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.
Polydatin Prevents Calcium Pyrophosphate Crystal-Induced Arthritis in Mice
Authors: Oliviero Francesca , Galozzi Paola , Scanu Anna , Galuppini Francesca , Lazzarin Vanni , Brocco Silvia , Ravagnan Giampietro , Sfriso Paolo , Ramonda Roberta , Spinella Paolo , Punzi Leonardo , Pennelli Gianmaria , Luisetto Roberto
Published: March 2021

Background: Polydatin is a stilbenoid with important antioxidant, anti-inflammatory, and immunomodulating properties. The aim of this study was to assess the anti-inflammatory preventive effect of polydatin in the mouse model of acute arthritis induced by calcium pyrophosphate (CPP) crystals. Methods: Acute arthritis was induced by the injection of a suspension of sterile CPP crystals into the ankle joint of Balb/c mice. Animals were randomized to receive polydatin or colchicine (the control drug) according to a prophylactic and a therapeutic protocol. The primary outcome was the variation of ankle swelling obtained after crystal injection and treatment, while histological parameters such as leukocyte infiltration, IL-1ß and CXCL1 levels and tissue expression were considered as secondary outcomes. Results: Prophylactic treatment with PD significantly diminished ankle swelling after 48 h from crystal injection. Secondary outcomes such as leukocyte infiltration, necrosis, edema, and synovitis were also decreased. PD caused a reduction in circulating levels of IL-1ß and CXCL1, as well as their tissue expression. By contrast, the therapeutic administration of PD did not have any beneficial effect. Conclusions: PD can effectively prevent acute inflammatory response to crystals in the mouse model of CPP crystal-induced arthritis. These results suggest that this bioactive compound might be used in the prevention of crystal-induced acute attacks in humans.
Enteral Nutrition in Term Infants with Congenital Heart Disease: Knowledge Gaps and Future Directions to Improve Clinical Practice
Authors: Martini Silvia , Beghetti Isadora , Annunziata Mariarosaria , Aceti Arianna , Galletti Silvia , Ragni Luca , Donti Andrea , Corvaglia Luigi
Published: March 2021

Optimal nutrition is essential to improve short- and long-term outcomes in newborns with congenital heart disease (CHD). Nevertheless, several issues on nutritional management and concerns about the potential risk of complications related to enteral feeding exist. This narrative review aims to summarize and discuss the available literature on enteral feeding in term infants with CHD. A wide variability in feeding management exists worldwide. Emerging approaches to improve nutritional status and outcomes in infants with CHD include: implementation of a standardized enteral feeding protocol, both preoperative and postoperative, clearly defining time of initiation and advancement of enteral feeds, reasons to withhold, and definitions of feeding intolerance; early minimal enteral feeding; enteral feeding in stable term infants on hemodynamic support; evaluation of enteral feeding in term infants with umbilical arterial catheters and during prostaglandin infusion; assessment and support of oro-motor skills; and promotion and support of breastfeeding and provision of mother’s own milk or donor milk when mother’s own milk is not available. As evidence from term infants is scarce, available observations and recommendations partially rely on studies in preterm infants. Thus, well-designed studies assessing standardized clinically relevant outcomes are needed to provide robust evidence and shared recommendations and practices.
Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice
Authors: Wu Li , Han Yuqiu , Zheng Zhipeng , Zhu Shuai , Chen Jun , Yao Yuanyuan , Yue Siqing , Teufel Andreas , Weng Honglei , Li Lanjuan , Wang Baohong
Published: March 2021

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.
New Methodologies for Conducting Maternal, Infant, and Child Nutrition Research in the Era of COVID-19
Authors: Gould Jacqueline F. , Best Karen , Netting Merryn J. , Gibson Robert A. , Makrides Maria
Published: March 2021

The severe acute respiratory syndrome coronavirus disease 2019 (COVID-19) outbreak rapidly became a worldwide pandemic in early 2020. In Australia, government-mandated restrictions on non-essential face-to-face contact in the healthcare setting have been crucial for limiting opportunities for COVID-19 transmission, but they have severely limited, and even halted, many research activities. Our institute’s research practices in the vulnerable populations of pregnant women and young infants needed to adapt in order to continue without exposing participants, or staff, to an increased risk of exposure to COVID-19. Here, we discuss our pre-and-post COVID-19 methods for conducting research regarding nutrition during pregnancy, infancy, and early childhood. We discuss modifications to study methods implemented to avoid face-to-face contact when identifying and recruiting potential participants, gaining informed consent, conducting appointments, and collecting outcome data, and the implications of these changes. The COVID-19 pandemic has required numerous changes to the conduct of research activities, but many of those modifications will be useful in post-COVID-19 research settings.
Nutrition in the First Week after Stroke Is Associated with Discharge to Home
Authors: Sato Yoichi , Yoshimura Yoshihiro , Abe Takafumi
Published: March 2021

Malnutrition is associated with poor clinical outcomes in stroke patients. The effect of early nutritional intake after admission on home discharge is unclear. We evaluated the impact of energy intake in the first week of hospitalization of acute stroke patients on home discharge and activities of daily living (ADL). A retrospective cohort study was conducted with 201 stroke patients admitted to an acute care hospital in Japan. The energy and protein intake during the first week were evaluated. Multivariate models were used to estimate variables related to discharge destination and ADL at discharge. The cut-off point of nutritional intake for determining the discharge destination was evaluated using the receiver operating characteristic curve. Out of 163 patients included in the analysis, 89 (54.6%) and 74 (45.4%) were discharged home and elsewhere, respectively. Those discharged home had higher energy and protein intake than those discharged elsewhere. In multiple regression analysis, energy intake was independently associated with ADL at discharge and home discharge (odds ratio 1.146). Those with energy intake >20.7 kcal/kg/day had higher ADL at discharge and more patients discharged home than those with energy intake <20.7 kcal/kg/day. Energy intake during the first week affected home discharge in acute stroke patients.
The Joint Effects of Diet and Dietary Supplements in Relation to Obesity and Cardiovascular Disease over a 10-Year Follow-Up: A Longitudinal Study of 69,990 Participants in Australia
Authors: Xu Xiaoyue , Shi Zumin , Liu Gang , Chang Dennis , Inglis Sally C. , Hall John J. , Schutte Aletta E. , Byles Julie E. , Parker Deborah
Published: March 2021

It is unknown whether a healthy diet or unhealthy diet combined with specific supplements may jointly contribute to incidence of obesity and cardiovascular disease (CVD). We included 69,990 participants from the 45 and Up Study who completed both baseline (2006–2009) and follow-up (2012–2015) surveys. We found that compared to participants with a long-term healthy diet and no supplement consumption, those with a long-term healthy diet combined with multivitamins and minerals (MVM) or fish oil consumption were associated with a lower incidence of CVD (p < 0.001); whilst those with an unhealthy diet and no MVM or fish oil consumption were associated with a higher risk of obesity (p < 0.05). Compared to participants with a long-term healthy diet and no calcium consumption, the combination of a long-term healthy diet and calcium consumption was linked to a lower risk of CVD (IRR = 0.87, 95% CI: 0.78; 0.96). In conclusion, a long-term healthy diet combined with MVM or fish oil was associated with a lower incidence of CVD. Participants who maintained a healthy diet and used calcium supplements were associated with a lower incidence of obesity. However, these associations were not found among those with an unhealthy diet, despite taking similar supplements.
Delayed Speech Perception and Production after Cochlear Implantation in Bilingual Children from Non-Native Families
Authors: Nassif Nader , Barezzani Maria Grazia , Redaelli de Zinis Luca Oscar
Published: March 2021

The aim of the study was to evaluate the outcomes of cochlear implantation (CI) in a group of immigrant deaf children living in a foreign language family, following up to 3 years of a personalized habilitation program compared to age-matched Italian CI recipients. Tests of speech perception ability such as the IT-MAIS, the LiP, the CAP, and speech production such as the MUSS have been used before CI and then after 6 months, 1 year, 2 years, and 3 years. Nonparametrical tests were chosen for comparison. Eight bilingual CI recipients were included in the study and matched to 11 Italian CI recipients. The difference between chronological age at implantation, age at diagnosis, hearing age, and verbal age in the two groups of children was not significant. Comparison of the auditory perceptive and linguistic abilities between the two groups showed significant differences only in preoperative MAIS and postoperative CAP (1 to 3 years). In agreement with other studies, we achieved good performances from bilingual children with CI and our personal experience confirm the attitude of promoting bilingualism throughout the rehabilitation process.
Prevalence of blaKPC-2, blaKPC-3 and blaKPC-30—Carrying Plasmids in Klebsiella pneumoniae Isolated in a Brazilian Hospital
Authors: Migliorini Letícia B. , de Sales Romário O. , Koga Paula C. M. , Doi Andre M. , Poehlein Anja , Toniolo Alexandra R. , Menezes Fernando G. , Martino Marines D. V. , Gales Ana C. , Brüggemann Holger , Severino Patricia
Published: March 2021

Klebsiella pneumoniae carbapenemase (KPC) actively hydrolyzes carbapenems, antibiotics often used a last-line treatment for multidrug-resistant bacteria. KPC clinical relevance resides in its widespread dissemination. In this work, we report the genomic context of KPC coding genes blaKPC-2, blaKPC-3 and blaKPC-30 in multidrug-resistant Klebsiellapneumoniae isolates from Brazil. Plasmids harboring blaKPC-3 and blaKPC-30 were identified. Fifteen additional carbapenem-resistant K. pneumoniae isolates were selected from the same tertiary hospital, collected over a period of 8 years. Their genomes were sequenced in order to evaluate the prevalence and dissemination of blaKPC–harboring plasmids. We found that blaKPC genes were mostly carried by one of two isoforms of transposon Tn4401 (Tn4401a or Tn4401b) that were predominantly located on plasmids highly similar to the previously described plasmid pKPC_FCF3SP (IncN). The identified pKPC_FCF3SP-like plasmids carried either blaKPC-2 or blaKPC-30. Two K. pneumoniae isolates harbored pKpQIL-like (IncFII) plasmids, only recently identified in Brazil; one of them harbored blaKPC-3 in a Tn4401a transposon. Underlining the risk of horizontal spread of KPC coding genes, this study reports the prevalence of blaKPC-2 and the recent spread of blaKPC-3, and blaKPC-30, in association with different isoforms of Tn4401, together with high synteny of plasmid backbones among isolates studied here and in comparison with previous reports.
Safflower Seed Extract Attenuates the Development of Osteoarthritis by Blocking NF-κB Signaling
Authors: Han Seong Jae , Lim Min Ju , Lee Kwang Min , Oh Eunjeong , Shin Yu Su , Kim Seokho , Kim Joong Sun , Yun Seung Pil , Kang Li-Jung
Published: March 2021

Although safflower seed extract exhibits pharmacological activity against various diseases, the effects of its individual compounds on osteoarthritis (OA) have not been elucidated. Here, we evaluated the effects of these extracts and their single compounds on OA. N-(p-Coumaroyl) serotonin and N-feruloyl serotonin, main components of safflower seed extract, were isolated by high-performance liquid chromatography. Under in vitro OA mimic conditions, the expression of the matrix metalloproteinases (MMPs) MMP3/13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) ADAMTS5 were reduced in mouse chondrocytes treated with safflower seed extract. Furthermore, the oral administration of safflower seed extract attenuated cartilage destruction in a mouse OA model induced by destabilization of the medial meniscus. N-(p-Coumaroyl) serotonin and N-feruloyl serotonin, but not serotonin, reduced MMP3, MMP13, and ADAMTS5 expression in IL-1β-treated chondrocytes. Additionally, they significantly blocked the nuclear factor-κB (NF-κB) pathway by inhibiting IκB degradation and p65 phosphorylation. Our results suggest that safflower seed extract and its single compounds can attenuate cartilage destruction by suppressing MMP and ADMATS5 expression. The anti-arthritic effects are mediated by NF-κB signaling and involve the inhibition of IκB degradation and p65 phosphorylation. These results indicate that safflower seed extract may serve as a novel therapeutic agent against OA.
Safety and Tolerability of Mass Diethylcarbamazine and Albendazole Administration for the Elimination of Lymphatic Filariasis in Kenya: An Active Surveillance Study
Authors: Khaemba Christabel , Barry Abbie , Omondi Wyckliff P. , Bota Kefa , Matendechero Sultani , Wandera Cecilia , Siyoi Fred , Kirui Elvis , Oluka Margaret , Nambwa Pamela , Gurumurthy Parthasarathi , Njenga Sammy M. , Guantai Anastacia , Aklillu Eleni
Published: March 2021

Preventive chemotherapy with diethylcarbamazine citrate (DEC) and albendazole (ALB) is the core intervention strategy to eliminate lymphatic filariasis (LF). We conducted a large-scale prospective active safety surveillance study to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass drug administration (MDA) of single-dose DEC and ALB in 10,010 participants from Kilifi County, Kenya. AEs were actively monitored and graded at 24 h, 48 h, and on day 7 Post-MDA. Out of 10,010 enrolled study participants, 1621 participants reported a total of 3102 AEs during a seven-day follow-up. The cumulative incidence of AEs was 16.2% (95% CI, 15.5–16.9%). The proportion of participants who experienced one, two, or ≥three types of AEs was 9.2%, 4.6%, 2.4%, respectively. AEs were mild (87.3%), moderate (12.4%), and severe (0.3%) and resolved within 72 h. The five most common AEs were dizziness (5.9%), headache (5.6%), loss of appetite (3.3%), fever (2.9%), and drowsiness (2.6%). Older age, taking concurrent medications, ≥three tablets of DEC, and type of meal taken before MDA were significant predictors of AEs. One in six participants experienced systemic mild-to-moderate severity grading and transient AEs. DEC and ALB co-administration for the elimination of LF is generally safe and well-tolerated.
Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit
Authors: Deguchi Saori , Ogata Fumihiko , Isaka Takumi , Otake Hiroko , Nakazawa Yosuke , Kawasaki Naohito , Nagai Noriaki
Published: March 2021

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy.
Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia
Authors: Scuteri Damiana , Cassano Roberta , Trombino Sonia , Russo Rossella , Mizoguchi Hirokazu , Watanabe Chizuko , Hamamura Kengo , Katsuyama Soh , Komatsu Takaaki , Morrone Luigi Antonio , Rombolà Laura , Adornetto Annagrazia , Laganà Annarita S. , Corasaniti Maria Tiziana , Tonin Paolo , Sakurada Shinobu , Sakurada Tsukasa , Nicotera Pierluigi , Bagetta Giacinto
Published: March 2021

Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia. Therefore, the aim of this study was to engineer a nanotechnology delivery system based on solid lipid nanoparticles loaded with bergamot essential oil (BEO) and devised in the pharmaceutical form of an odorless cream (NanoBEO) to confirm its analgesic efficacy for further development and application to control agitation in dementia. BEO has proven strong antinociceptive and anti-allodynic properties and, in its bergapten-free form, it is completely devoid of phototoxicity. NanoBEO has been studied in vivo confirming the previously reported analgesic activity of BEO to which is now added its anti-itching properties. Due to the nanotechnology delivery system, the stability of titrated BEO components is guaranteed. Finally, the latter invention, currently under patent consideration, is smell-devoid allowing efficacy and safety to be established in double-blind clinical trials; until now the latter studies have been impeded in aromatherapy by the strong odor of essential oils. A clinical trial NCT04321889 has been designed to provide information about the efficacy and safety of NanoBEO on agitation and pain in patients suffering from severe dementia.
Study of the l-Phenylalanine Ammonia-Lyase Penetration Kinetics and the Efficacy of Phenylalanine Catabolism Correction Using In Vitro Model Systems
Authors: Dyshlyuk Lyubov , Sukhikh Stanislav , Noskova Svetlana , Ivanova Svetlana , Prosekov Alexander , Babich Olga
Published: March 2021

The kinetics of l-phenylalanine ammonia-lyase (PAL) penetration into the monolayer of liver cells after its release from capsules was studied. The studies showed the absence of the effect of the capsule shell based on plant hydrocolloids on the absorption of l-phenylalanine ammonia-lyase in systems simulating the liver surface. After 120 min of incubation, in all variants of the experiment, from 87.0 to 96.8% of the enzyme penetrates the monolayer of liver cells. The combined analysis of the results concludes that the developed encapsulated form of l-phenylalanine ammonia-lyase is characterized by high efficiency in correcting the disturbed catabolism of phenylalanine in phenylketonuria, which is confirmed by the results of experiments carried out on in vitro model systems. PAL is approved for the treatment of adult patients with phenylketonuria. The encapsulated l-phenylalanine ammonia-lyase form can find therapeutic application in the phenylketonuria treatment after additional in vitro and in vivo studies, in particular, the study of preparation safety indicators. Furthermore, it demonstrated high efficacy in tumor regression and the treatment of tyrosine-related metabolic disorders such as tyrosinemia. Several therapeutically valuable metabolites biosynthesized by PAL via its catalytic action are included in food supplements, antimicrobial peptides, drugs, amino acids, and their derivatives. PAL, with improved pharmacodynamic and pharmacokinetic properties, is a highly effective medical drug.