bluuebunny/crossref_metadata_2025 huggingface dataset:
NMR Spectroscopy for Protein Higher Order Structure Similarity Assessment in Formulated Drug Products
Authors: Wang Deyun , Zhuo You , Karfunkle Mike , Patil Sharadrao M. , Smith Cameron J. , Keire David A. , Chen Kang
Published: July 2021

Peptide and protein drug molecules fold into higher order structures (HOS) in formulation and these folded structures are often critical for drug efficacy and safety. Generic or biosimilar drug products (DPs) need to show similar HOS to the reference product. The solution NMR spectroscopy is a non-invasive, chemically and structurally specific analytical method that is ideal for characterizing protein therapeutics in formulation. However, only limited NMR studies have been performed directly on marketed DPs and questions remain on how to quantitively define similarity. Here, NMR spectra were collected on marketed peptide and protein DPs, including calcitonin-salmon, liraglutide, teriparatide, exenatide, insulin glargine and rituximab. The 1D 1H spectral pattern readily revealed protein HOS heterogeneity, exchange and oligomerization in the different formulations. Principal component analysis (PCA) applied to two rituximab DPs showed consistent results with the previously demonstrated similarity metrics of Mahalanobis distance (DM) of 3.3. The 2D 1H-13C HSQC spectral comparison of insulin glargine DPs provided similarity metrics for chemical shift difference (Δδ) and methyl peak profile, i.e., 4 ppb for 1H, 15 ppb for 13C and 98% peaks with equivalent peak height. Finally, 2D 1H-15N sofast HMQC was demonstrated as a sensitive method for comparison of small protein HOS. The application of NMR procedures and chemometric analysis on therapeutic proteins offer quantitative similarity assessments of DPs with practically achievable similarity metrics.
New In Vitro-In Silico Approach for the Prediction of In Vivo Performance of Drug Combinations
Authors: Correia Cristiana , Ferreira Abigail , Santos Joana , Lapa Rui , Yliperttula Marjo , Urtti Arto , Vale Nuno
Published: July 2021

Pharmacokinetic (PK) studies improve the design of dosing regimens in preclinical and clinical settings. In complex diseases like cancer, single-agent approaches are often insufficient for an effective treatment, and drug combination therapies can be implemented. In this work, in silico PK models were developed based on in vitro assays results, with the goal of predicting the in vivo performance of drug combinations in the context of cancer therapy. Combinations of reference drugs for cancer treatment, gemcitabine and 5-fluorouracil (5-FU), and repurposed drugs itraconazole, verapamil or tacrine, were evaluated in vitro. Then, two-compartment PK models were developed based on the previous in vitro studies and on the PK profile reported in the literature for human patients. Considering the quantification parameter area under the dose-response-time curve (AUCeffect) for the combinations effect, itraconazole was the most effective in combination with either reference anticancer drugs. In addition, cell growth inhibition was itraconazole-dose dependent and an increase in effect was predicted if itraconazole administration was continued (24-h dosing interval). This work demonstrates that in silico methods and AUCeffect are powerful tools to study relationships between tissue drug concentration and the percentage of cell growth inhibition over time.
Microwave-Assisted One Pot Three-Component Synthesis of Novel Bioactive Thiazolyl-Pyridazinediones as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria
Authors: Abu-Melha Sraa , Gomha Sobhi , Abouzied Amr , Edrees Mastoura , Abo Dena Ahmed , Muhammad Zeinab
Published: July 2021

Pyridazine and thiazole derivatives have various biological activities such as antimicrobial, analgesic, anticancer, anticonvulsant, antitubercular and other anticipated biological properties. Chitosan can be used as heterogeneous phase transfer basic biocatalyst in heterocyclic syntheses. Novel 1-thiazolyl-pyridazinedione derivatives were prepared via multicomponent synthesis under microwave irradiation as ecofriendly energy source and using the eco-friendly naturally occurring chitosan basic catalyst with high/efficient yields and short reaction time. All the prepared compounds were fully characterized by spectroscopic methods, and their in vitro biological activities were investigated. The obtained results were compared with those of standard antibacterial/antifungal agents. DFT calculations and molecular docking studies were used to investigate the electronic properties and molecular interactions with specific microbial receptors.
Metabolomic Analysis of The Chemical Diversity of South Africa Leaf Litter Fungal Species Using an Epigenetic Culture-Based Approach
Authors: Serrano Rachel , González-Menéndez Víctor , Martínez Germán , Toro Clara , Martín Jesús , Genilloud Olga , Tormo  José R.
Published: July 2021

Microbial natural products are an invaluable resource for the biotechnological industry. Genome mining studies have highlighted the huge biosynthetic potential of fungi, which is underexploited by standard fermentation conditions. Epigenetic effectors and/or cultivation-based approaches have successfully been applied to activate cryptic biosynthetic pathways in order to produce the chemical diversity suggested in available fungal genomes. The addition of Suberoylanilide Hydroxamic Acid to fermentation processes was evaluated to assess its effect on the metabolomic diversity of a taxonomically diverse fungal population. Here, metabolomic methodologies were implemented to identify changes in secondary metabolite profiles to determine the best fermentation conditions. The results confirmed previously described effects of the epigenetic modifier on the metabolism of a population of 232 wide diverse South Africa fungal strains cultured in different fermentation media where the induction of differential metabolites was observed. Furthermore, one solid-state fermentation (BRFT medium), two classic successful liquid fermentation media (LSFM and YES) and two new liquid media formulations (MCKX and SMK-II) were compared to identify the most productive conditions for the different populations of taxonomic subgroups.
Process Optimization and Modeling of Phenol Adsorption onto Sludge-Based Activated Carbon Intercalated MgAlFe Ternary Layered Double Hydroxide Composite
Authors: Mu’azu Nuhu Dalhat , Zubair Mukarram , Ihsanullah Ihsanullah
Published: July 2021

A sewage sludge-based activated carbon (SBAC) intercalated MgAlFe ternary layered double hydroxide (SBAC-MgAlFe-LDH) composite was synthesized via the coprecipitation method. The adsorptive performance of the composite for phenol uptake from the aqueous phase was evaluated via the response surface methodology (RSM) modeling technique. The SBAC-MgAlFe-LDH phenol uptake capacity data were well-fitted to reduced RSM cubic model (R2 = 0.995, R2-adjusted = 0.993, R2-predicted = 0.959 and p-values < 0.05). The optimum phenol adsorption onto the SBAC-MgAlFe-LDH was achieved at 35 °C, 125 mg/L phenol, and pH 6. Under the optimal phenol uptake conditions, pseudo-first-order and Avrami fractional-order models provided a better representation of the phenol uptake kinetic data, while the equilibrium data models’ fitting follows the order; Liu > Langmuir > Redlich–Peterson > Freundlich > Temkin. The phenol uptake mechanism was endothermic in nature and predominantly via a physisorption process (ΔG° = −5.33 to −5.77 kJ/mol) with the involvement of π–π interactions between the phenol molecules and the functionalities on the SBAC-LDH surface. The maximum uptake capacity (216.76 mg/g) of SBAC-MgAlFe-LDH was much higher than many other SBAC-based adsorbents. The improved uptake capacity of SBAC-LDH was attributed to the effective synergetic influence of SBAC-MgAlFe-LDH, which yielded abundant functionalized surface groups that favored higher aqueous phase uptake of phenol molecules. This study showcases the potential of SBAC-MgAlFe-LDH as an effective adsorbent material for remediation of phenolic wastewater
Hydroxyapatite Obtained via the Wet Precipitation Method and PVP/PVA Matrix as Components of Polymer-Ceramic Composites for Biomedical Applications
Authors: Głąb Magdalena , Kudłacik-Kramarczyk Sonia , Drabczyk Anna , Walter Janusz , Kordyka Aleksandra , Godzierz Marcin , Bogucki Rafał , Tyliszczak Bożena , Sobczak-Kupiec Agnieszka
Published: July 2021

The aspect of drug delivery is significant in many biomedical subareas including tissue engineering. Many studies are being performed to develop composites with application potential for bone tissue regeneration which at the same provide adequate conditions for osteointegration and deliver the active substance conducive to the healing process. Hydroxyapatite shows a great potential in this field due to its osteoinductive and osteoconductive properties. In the paper, hydroxyapatite synthesis via the wet precipitation method and its further use as a ceramic phase of polymer–ceramic composites based on PVP/PVA have been presented. Firstly, the sedimentation rate of hydroxyapatite in PVP solutions has been determined, which allowed us to select a 15% PVP solution (sedimentation rate was 0.0292 mm/min) as adequate for preparation of homogenous reaction mixture treated subsequently with UV radiation. Both FT-IR spectroscopy and EDS analysis allowed us to confirm the presence of both polymer and ceramic phase in composites. Materials containing hydroxyapatite showed corrugated and well-developed surface. Composites exhibited swelling properties (hydroxyapatite reduced this property by 25%) in simulated physiological fluids, which make them useful in drug delivery (swelling proceeds parallel to the drug release). The short synthesis time, possibility of preparation of composites with desired shapes and sizes and determined physicochemical properties make the composites very promising for biomedical purposes.
Large Amplitude Motions of Pyruvic Acid (CH3-CO-COOH)
Authors: Senent María Luisa , Dalbouha Samira
Published: July 2021

Torsional and rotational spectroscopic properties of pyruvic acid are determined using highly correlated ab initio methods and combining two different theoretical approaches: Second order perturbation theory and a variational procedure in three-dimensions. Four equilibrium geometries of pyruvic acid, Tc, Tt, Ct, and CC, outcome from a search with CCSD(T)-F12. All of them can be classified in the Cs point group. The variational calculations are performed considering the three internal rotation modes responsible for the non-rigidity as independent coordinates. More than 50 torsional energy levels (including torsional subcomponents) are localized in the 406–986 cm−1 region and represent excitations of the ν24 (skeletal torsion) and the ν23 (methyl torsion) modes. The third independent variable, the OH torsion, interacts strongly with ν23. The A1/E splitting of the ground vibrational state has been evaluated to be 0.024 cm−1 as it was expected given the high of the methyl torsional barrier (338 cm−1). A very good agreement with respect to previous experimental data concerning fundamental frequencies (νCAL − νEXP ~ 1 cm−1), and rotational parameters (B0CAL − B0EXP < 5 MHz), is obtained.
The Effects of Chemical Bonding at Subatomic Resolution: A Case Study on α-Boron
Authors: Fischer Andreas , Eickerling Georg , Scherer Wolfgang
Published: July 2021

Similar to classical asphericity shifts, aspherical deformations of the electron density in the atomic core region can result in core asphericity shifts in refinements using a Hansen-Coppens multipolar model (HCM), especially when highly precise experimental datasets with resolutions far beyond sin(θ)/λ ≤ 1.0 Å−1 are employed. These shifts are about two orders of magnitude smaller than their counterparts caused by valence shell deformations, and their underlying deformations are mainly of dipolar character for 1st row atoms. Here, we analyze the resolution dependence of core asphericity shifts in α-boron. Based on theoretical structure factors, an appropriate Extended HCM (EHCM) is developed, which is tested against experimental high-resolution (sin(θ)/λ ≤ 1.6 Å−1) single-crystal diffraction data. Bond length deviations due to core asphericity shifts of α-boron in the order of 4–6·10−4 Å are small but significant at this resolution and can be effectively compensated by an EHCM, although the correlation of the additional model parameters with positional parameters prevented a free refinement of all core model parameters. For high quality, high resolution data, a proper treatment with an EHCM or other equivalent methods is therefore highly recommended.
Effective Extraction of Limonene and Hibaene from Hinoki (Chamaecyparis obtusa) Using Ionic Liquid and Deep Eutectic Solvent
Authors: Yasutomi Rina , Anzawa Riki , Urakawa Masamitsu , Usuki Toyonobu
Published: July 2021

The essential oils of hinoki (Chamaecyparis obtusa) leaves have anti-bacterial, anti-fungal, and relaxation properties that are likely associated with the major components such as sabinene, α-terpinyl acetate, limonene, elemol, myrcene, and hibaene. The present study describes the use of a cellulose-dissolving ionic liquid (IL) [C2mim][(MeO)(H)PO2] and low-toxicity solvents called betaine-based deep eutectic solvents (DESs) for the efficient extraction of hinoki essential oils. As a control method, organic solvent extraction was performed using either hexane, ethyl acetate (EtOAc), or acetone at 30 °C for 1 h. Both the experimental and control methods were conducted under the same conditions, which relied on partial dissolution of the leaves using the IL and DESs before partitioning the hinoki oils into the organic solvent for analysis. Quantitative analysis was performed using gas chromatography–mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode. The results indicated that extraction using the [C2mim][(MeO)(H)PO2]/acetone bilayer system improved the yields of limonene and hibaene, 1.5- and 1.9-fold, respectively, when compared with the control method. In addition, extraction using betaine/l-lactic acid (molar ratio 1:1) gave the greatest yields for both limonene and hibaene, 1.3-fold and 1.5-fold greater, respectively, than when using an organic solvent. These results demonstrate the effective extraction of essential oils from plant leaves under conditions milder than those needed for the conventional method. The less toxic and environmentally begin DESs for the extraction are also applicable to the food and cosmetic industries.
Extraction of Phenolic Compounds from Fresh Apple Pomace by Different Non-Conventional Techniques
Authors: Pollini Luna , Cossignani Lina , Juan Cristina , Mañes Jordi
Published: July 2021

Red Delicious apple pomace was produced at laboratory scale with a domestic blender and different non-conventional extraction techniques were performed to isolate phenolic compounds, such as ultrasound-assisted extraction (UAE), ultraturrax extraction (UTE), accelerated solvent extraction (ASE) and pulsed electric field (PEF) extraction pre-treatment. Total phenolic content (TPC) was determined by Folin–Ciocalteu assay. Phloridzin, the main phenolic compound in apples, was determined by chromatographic analysis Q-TOF-LC/MS. The results obtained with these techniques were compared in order to identify the most efficient method to recover polyphenols. The highest value of TPC (1062.92 ± 59.80 µg GAE/g fresh apple pomace) was obtained when UAE was performed with EtOH:H2O (50:50, v/v), while ASE with EtOH:H2O (30:70, v/v) at 40 °C and 50% of flush was the most efficient technique in the recovery of phloridzin. The concentration of the main phenolic compounds ranged from 385.84 to 650.56 µg/g fresh apple pomace. The obtained results confirm that apple pomace represents an interesti-ng by-product, due to the presence of phenolic compounds. In particular, phloridzin could be considered a biomarker to determine the quality of numerous apple products. Therefore, this research could be a good starting point to develop a value-added product such as a functional food or nutraceutical.
Electrophilically Activated Nitroalkanes in Synthesis of 3,4-Dihydroquinozalines
Authors: Aksenov Alexander V. , Grishin Igor Yu. , Aksenov Nicolai A. , Malyuga Vladimir V. , Aksenov Dmitrii A. , Nobi Mezvah A. , Rubin Michael
Published: July 2021

Nitroalkanes activated with polyphosphoric acid serve as efficient electrophiles in reactions with various nucleophilic amines. Strategically placed second functionality allows for the design of annulation reactions enabling preparation of various heterocycles. This strategy was employed to develop an innovative synthetic approach towards 3,4-dihydroquinazolines from readily available 2-(aminomethyl)anilines.
Pulp Enhancement of Oil Palm Empty Fruit Bunches (OPEFBs) via Biobleaching by Using Xylano-Pectinolytic Enzymes of Bacillus amyloliquefaciens ADI2
Authors: Nawawi Muhammad Hariadi , Mohamad Rosfarizan , Tahir Paridah Md , Asa’ari Ainun Zuriyati , Saad Wan Zuhainis
Published: July 2021

The present work reports the biobleaching effect on OPEFB pulp upon utilisation of extracellular xylano-pectinolytic enzymes simultaneously yielded from Bacillus amyloliquefaciens ADI2. The impacts of different doses, retention times, pH, and temperatures required for the pulp biobleaching process were delineated accordingly. Here, the OPEFB pulp was subjected to pre-treatment with xylano-pectinolytic enzymes generated from the same alkalo-thermotolerant isolate that yielded those of higher quality. Remarkable enhanced outcomes were observed across varying pulp attributes: for example, enzyme-treated pulp treated to chemical bleaching sequence generated improved brightness of 11.25%. This resulted in 11.25% of less chlorine or chemical consumption required for obtaining pulp with optical attributes identical to those generated via typical chemical bleaching processes. Ultimately, the reduced consumption of chlorine would minimise the organochlorine compounds found in an effluent, resulting in a lowered environmental effect of paper-making processes overall as a consequence. This will undoubtedly facilitate such environmentally-friendly technology incorporation in the paper pulp industry of today.
Physicochemical Properties, Cytocompatibility, and Biocompatibility of a Bioactive Glass Based Retrograde Filling Material
Authors: Murata Kazumasa , Washio Ayako , Morotomi Takahiko , Rojasawasthien Thira , Kokabu Shoichiro , Kitamura Chiaki
Published: July 2021

The ideal retrograde filling material that is easy to handle, has good physicochemical properties, and is biocompatible has not yet been developed. The current study reports the development of a novel bioactive glass based powder for use as a retrograde filling material that is capable of altering the consistency and hardening rate of mixtures when mixed with existing bioactive glass based cement. Furthermore, its physicochemical properties, in vitro effects on human cementoblast-like cells, and in vivo effects on inflammatory responses were evaluated. The surface of the hardened cement showed the formation of hydroxyapatite-like precipitates and calcium and silicate ions were eluted from the cement when the pH level was stabilized at 10.5. Additionally, the cement was found to be insoluble and exhibited favorable handling properties. No adverse effects on viability, proliferation, and expression of differentiated markers were observed in the in vitro experiment, and the cement was capable of inducing calcium deposition in the cells. Moreover, the cement demonstrated a lower number of infiltrated inflammatory cells compared to the other materials used in the in vivo mouse subcutaneous implantation experiment. These findings suggest that the retrograde filling material composed of bioactive glass and the novel bioactive glass based powder exhibits favorable physicochemical properties, cytocompatibility, and biocompatibility.
The Enhanced Hydrogen Storage Capacity of Carbon Fibers: The Effect of Hollow Porous Structure and Surface Modification
Authors: Hwang Sung-Ho , Kim Young Kwang , Seo Hye-Jin , Jeong Soon Moon , Kim Jongwon , Lim Sang Kyoo
Published: July 2021

In this study, highly porous carbon fiber was prepared for hydrogen storage. Porous carbon fiber (PCF) and activated porous carbon fiber (APCF) were derived by carbonization and chemical activation after selectively removing polyvinyl alcohol from a bi-component fiber composed of polyvinyl alcohol and polyacrylonitrile (PAN). The chemical activation created more pores on the surface of the PCF, and consequently, highly porous APCF was obtained with an improved BET surface area (3058 m2 g−1) and micropore volume (1.18 cm3 g−1) compare to those of the carbon fiber, which was prepared by calcination of monocomponent PAN. APCF was revealed to be very efficient for hydrogen storage, its hydrogen capacity of 5.14 wt% at 77 K and 10 MPa. Such hydrogen storage capacity is much higher than that of activated carbon fibers reported previously. To further enhance hydrogen storage capacity, catalytic Pd nanoparticles were deposited on the surface of the APCF. The Pd-deposited APCF exhibits a high hydrogen storage capacity of 5.45 wt% at 77 K and 10 MPa. The results demonstrate the potential of Pd-deposited APCF for efficient hydrogen storage.
One-Pot Hydrothermal Synthesis of Carbon Dots as Fluorescent Probes for the Determination of Mercuric and Hypochlorite Ions
Authors: Lee Hsin , Su Yen-Chang , Tang Hsiang-Hao , Lee Yu-Sheng , Lee Jan-Yee , Hu Cho-Chun , Chiu Tai-Chia
Published: July 2021

Nitrogen and sulfur codoped carbon dots (NSCDs) were synthesized via a one-pot hydrothermal method, and citric acid, ethylenediamine, and methyl blue were used as precursors. The obtained NSCDs were spherical with an average size of 1.86 nm. The fluorescence emission spectra of the NSCDs were excitation independent and emitted blue fluorescence at 440 nm with an excitation wavelength at 350 nm. The quantum yield of the NSCDs was calculated to be 68.0%. The NSCDs could be constructed as fluorescent probes for highly selective and sensitive sensing mercuric (Hg2+) and hypochlorite (ClO−) ions. As the addition of Hg2+ or ClO− ions to the NSCDs, the fluorescence intensity was effectively quenched due to dynamic quenching. Under the optimal conditions, the linear response of the fluorescence intensity ranged from 0.7 μM to 15 μM with a detection limit of 0.54 μM and from 0.3 μM to 5.0 μM with a limit of detection of 0.29 μM for Hg2+ and ClO− ions, respectively. Finally, the proposed method was successfully used for quantifying Hg2+ and ClO− ions in spiked tap water samples.
A High-Sensitivity Flexible Direct X-ray Detector Based on Bi2O3/PDMS Nanocomposite Thin Film
Authors: Mao Longmei , Li Yi , Chen Hu , Yu Longxin , Zhang Jianhua
Published: July 2021

The characteristics of mechanical flexibility, low health risk, and simple processing of polymer nanocomposite materials make them potentially applicable as flexible X-ray detectors. In this study, we report on a high sensitivity, environmentally friendly, and flexible direct X-ray detector using polymer nanocomposite material consisting of bismuth oxide (Bi2O3) nanoparticles and polydimethylsiloxane (PDMS). This detector was realized by printing patterned Ag electrodes on the polymer nanocomposite material. The response of PDMS to X-rays was verified for the first time, and the effect of doping different contents of Bi2O3 nanoparticles on the performance of the device was tested. The optoelectronic performance of the optimized detector indicated a high sensitivity (203.58 μC Gyair−1 cm−2) to low dose rate (23.90 μGyair s−1) at a 150 V bias voltage and the X-ray current density (JX-ray) was 10,000-fold higher than the dark current density (Jdark). The flexible direct X-ray detector could be curled for 10,000 cycles with slight performance degradation. The device exhibited outstanding stability after storage for over one month in air. Finally, this device provides new guidance for the design of high-performance flexible direct X-ray detectors.
Treatment with Micafungin in a Preterm Neonate with an Invasive Candida parapsilosis Infection after a Severe Terlipressin-Induced Skin Necrosis
Authors: De Rose Domenico Umberto , Piersigilli Fiammetta , Goffredo Bianca Maria , Danhaive Olivier , Dotta Andrea , Auriti Cinzia
Published: July 2021

Candida parapsilosis infections are increasingly reported in preterm neonates, but the optimal treatment remains uncertain. We report the clinical history of an extremely preterm neonate, who developed a devastating skin necrosis due to terlipressin administration, with subsequent superinfection by Candida parapsilosis. The infant underwent multiple curettages and skin grafts to resolve skin lesions and was treated with systemic micafungin administration at a high dose (8 mg/kg/day), with resolution of the fungal infection.
A Comparison of Virulence of Three Porcine Circovirus Type 2 (PCV2) Genotypes (a, b, and d) in Pigs Singularly Inoculated with PCV2 and Dually Inoculated with PCV2 and Porcine Reproductive and Respiratory Syndrome Virus
Authors: Suh Jeongmin , Oh Taehwan , Park Keehwan , Yang Siyeon , Cho Hyejean , Chae Chanhee
Published: July 2021

The aim of this study was to compare the virulence of porcine circovirus type 2 (PCV2) genotypes in dually inoculated pigs with both three genotypes (a, b, and d) of PCV2 and porcine reproductive and respiratory syndrome virus-2 (PRRSV-2) versus pigs singularly inoculated with the same three PCV2 genotypes (a, b, and d). Differences in this comparison were found in PCV2 viremia levels, lung and lymphoid lesion severity, and the amount of PCV2 antigen within the lymphoid lesions. Regardless of PCV2 genotypes, pigs that were dually inoculated with PCV2/PRRSV had significantly higher clinical scores, less average daily weight gain, higher levels of PCV2 viremia, and more severe lug and lymphoid lesions compared to pigs singularly inoculated with PCV2. Among the dually infected pig groups, pigs infected with PCV2d/PRRSV-2 had significantly higher levels of PCV2 viremia, more severe lung and lymphoid lesions, and more PCV2-positive cells within lymphoid lesions compared to pigs dually inoculated with PCV2a/PRRSV-2 and PCV2b/PRRSV-2. The results of this study demonstrated significant differences in the virulence among dual inoculation of PCV2a/PRRSV-2, PCV2b/PRRSV-2, and PCV2d/PRRSV-2. A significant difference in the virulence among PCV2a, PCV2b, and PCV2d single-inoculated pig groups was not found with respect to the levels of PCV2 viremia and production of PCV2-associated lymphoid lesions.
The Autofluorescence Patterns of Acanthamoeba castellanii, Pseudomonas aeruginosa and Staphylococcus aureus: Effects of Antibiotics and Tetracaine
Authors: Peguda Hari Kumar , Mahbub Saabah B. , Sherpa Tashi Doma , Subedi Dinesh , Habibalahi Abbas , Anwer Ayad G. , Gu Zi , Willcox Mark D. P. , Goldys Ewa M. , Carnt Nicole A.
Published: July 2021

Acanthamoeba Keratitis (AK) can lead to substantial vision loss and morbidity among contact lens wearers. Misdiagnosis or delayed diagnosis is a major factor contributing to poor outcomes of AK. This study aimed to assess the effect of two antibiotics and one anaesthetic drug used in the diagnosis and nonspecific management of keratitis on the autofluorescence patterns of Acanthamoeba and two common bacteria that may also cause keratitis. Acanthamoeba castellanii ATCC 30868, Pseudomonas aeruginosa ATCC 9027, and Staphylococcus aureus ATCC 6538 were grown then diluted in either PBS (bacteria) or ¼ strength Ringer’s solution (Acanthamoeba) to give final concentrations of 0.1 OD at 660 nm or 104 cells/mL. Cells were then treated with ciprofloxacin, tetracycline, tetracaine, or no treatment (naïve). Excitation–emission matrices (EEMs) were collected for each sample with excitation at 270–500 nm with increments in 5 nm steps and emission at 280–700 nm at 2 nm steps using a Fluoromax-4 spectrometer. The data were analysed using MATLAB software to produce smoothed color-coded images of the samples tested. Acanthamoeba exhibited a distinctive fluorescence pattern compared to bacteria. The addition of antibiotics and anaesthetic had variable effects on autofluorescence. Tetracaine altered the fluorescence of all three microorganisms, whereas tetracycline did not show any effect on the fluorescence. Ciprofloxacin produced changes to the fluorescence pattern for the bacteria, but not Acanthamoeba. Fluorescence spectroscopy was able to differentiate Acanthamoeba from P. aeruginosa and S. aureus in vitro. There is a need for further assessment of the fluorescence pattern for different strains of Acanthamoeba and bacteria. Additionally, analysis of the effects of anti-amoebic drugs on the fluorescence pattern of Acanthamoeba and bacteria would be prudent before in vivo testing of the fluorescence diagnostic approach in the animal models.
Challenges in 3D Live Cell Imaging
Authors: Schneckenburger Herbert , Richter Verena
Published: July 2021

A short overview on 3D live cell imaging is given. Relevant samples are described and various problems and challenges—including 3D imaging by optical sectioning, light scattering and phototoxicity—are addressed. Furthermore, enhanced methods of wide-field or laser scanning microscopy together with some relevant examples and applications are summarized. In the future one may profit from a continuous increase in microscopic resolution, but also from molecular sensing techniques in the nanometer range using e.g., non-radiative energy transfer (FRET).
Dynamic Speckle Illumination Digital Holographic Microscopy by Doubly Scattered System
Authors: Liu Yun , Bu Peihua , Jiao Mingxing , Xing Junhong , Kou Ke , Lian Tianhong , Wang Xian , Liu Yumeng
Published: July 2021

The coherent noise always exists in digital holographic microscopy due to the laser source, degrading the image quality. A method of speckle suppression using the dynamic speckle illumination, produced by double-moving diffusers, is presented in digital holographic microscopy. The space–time correlation functions are theoretically analyzed from the statistics distribution in the doubly and singly scattered system, respectively. The configuration of double-moving diffusers is demonstrated to have better performance in speckle suppression compared with the single diffuser and moving-static double diffusers cases. The experiment results verify the feasibility of the approach. The presented approach only requires a single shot interferogram to realize the speckle reduction, accordingly it has the potential application in real-time measurement.
An Inexpensive Portable Self-Reference Module for Digital Holographic Microscopy
Authors: Fan Xin , Tang Zhengyuan , O’Dwyer Kevin , Hennelly Bryan M.
Published: July 2021

This paper describes a novel optical system that can be integrated to the image port of an existing brightfield microscope in order to enhance the microscope with the features of digital holographic microscopy. The proposed system is modular and portable. It is relatively inexpensive and robust to vibrations due to its compact design. An additional benefit is that the system does not need to undergo path-length realignment if the sample is changed, unlike several other architectures. The module is based on a square in-line Mach–Zender architecture but achieves the off-axis condition using two sets of wedge prism pairs. This design offers a significant advantage over competing Mach–Zender nearly common-path modules in terms of path length matching of object and reference wavefields for the case of low-temporal coherence sources, which are preferable for low noise phase imaging. An additional advantage that the proposed system has when compared with similar modules is the facility to continuously vary the tilt angles of the object and reference wavefields that are incident on the sensor, which enables the module to be readily adapted to any given microscope and camera. We provide a detailed overview of the module design and construction. Experimental results are demonstrated on a micro-lens array as well as buccal epithelial cells. We also provide a detailed discussion on the relationship between the proposed self-reference module and related common-path and nearly common-path holographic modules that have previously been proposed in the literature.
Biological Activities of In-House Developed Haloxylon griffithii Plant Extract Formulations
Authors: Kamal Shagufta , Bibi Ismat , Rehman Kanwal , Zahoor Ameer Fawad , Kamal Amna , Aslam Fatima , Alasmary Fatmah Ali , Almutairi Tahani Mazyad , Alhajri Hassna Mohammed , Alissa Siham A. , Iqbal Hafiz M. N.
Published: July 2021

The therapeutic potential of whitish glaucous sub-shrub Haloxylon griffithii (H. griffithii), abundantly present in southern regions of South Asia, has been neglected. The current study aimed to assess the phytochemicals and pharmacological potential of native and gemm forms of H. griffithii. Results of antimicrobial activity revealed that all tested bacteria were susceptible at concentrations ≤50 µg/mL, while tested fungal species were susceptible at ≤25 µg/mL. The values of minimum bactericidal concentrations (MBCs) ranged between 10.75 ± 0.20 to 44.25 ± 0.42 µg/mL, 8.25 ± 0.02 to 28.20 ± 0.80 µg/mL. The value of minimum inhibitory concentration (MIC) of all microbial species was ≤100 µg/mL and the antibiotic mechanism showed that both extracts were highly bactericidal and fungicidal. Results of average log reduction of viable cell count in time kill assay indicated that Pseudomonas aeruginosa (P. aeruginosa) NCTC 1662, Candida albicans (C. albicans) IBL-01, Candidakrusei (C. krusei) ATCC 6258, and Aspergillus flavus (A. flavus) QC 6158 were the most susceptible microbial species. High performance liquid chromatography (HPLC)-based quantification confirmed the presence of gallic acid p.coumeric acid catechin, vanillin, ellagic acid, and salicylic acid, while in native extract only gallic acid. Native and gemm extracts exhibited excellent radical scavenging potential measured by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay. Significant thrombolytic activity was found in both extracts with negligible haemolytic activity. Highest percent (%) clot lysis was observed with gemm extracts (87.9 ± 0.85% clot lysis). In summary, we infer that valuable evidence congregated can be exploited for better understanding of gemm H. griffithii’s health benefits, further, to increase its utility with enriching dietary sources of health-promoting compounds.
Evolution of Plant Virus Diagnostics Used in Australian Post Entry Quarantine
Authors: Whattam Mark , Dinsdale Adrian , Elliott Candace E.
Published: July 2021

As part of a special edition for MDPI on plant virology in Australia, this review provides a brief high-level overview on the evolution of diagnostic techniques used in Australian government Post-Entry Quarantine (PEQ) facilities for testing imported plants for viruses. A comprehensive range of traditional and modern diagnostic approaches have historically been employed in PEQ facilities using bioassays, serological, and molecular techniques. Whilst these techniques have been effective, they are time consuming, resource intensive and expensive. The review highlights the importance of ensuring the best available science and diagnostic developments are constantly tested, evaluated, and implemented by regulators to ensure primary producers have rapid and safe access to new genetics to remain productive, sustainable and competitive.
Interactions between Sterically Stabilized Nanoparticles: The Effects of Brush Bidispersity and Chain Stiffness
Authors: Egorov Sergei A.
Published: July 2021

Density Functional Theory is employed to study structural properties and interactions between solvent-free polymer-grafted nanoparticles. Both monodisperse and bidisperse polymer brushes with variable chain stiffness are considered. The three major control parameters are the grafting density, the grafted chain length, and its stiffness. The effect of these parameters on the brush-brush overlap and attractive interaction strength is analyzed. The Density Functional Theory results are compared with the available simulation data, and good quantitative agreement is found.
Physical and Mechanical Characterization of Fibrin-Based Bioprinted Constructs Containing Drug-Releasing Microspheres for Neural Tissue Engineering Applications
Authors: Sharma Ruchi , Kirsch Rebecca , Valente Karolina Papera , Perez Milena Restan , Willerth Stephanie Michelle
Published: July 2021

Three-dimensional bioprinting can fabricate precisely controlled 3D tissue constructs. This process uses bioinks—specially tailored materials that support the survival of incorporated cells—to produce tissue constructs. The properties of bioinks, such as stiffness and porosity, should mimic those found in desired tissues to support specialized cell types. Previous studies by our group validated soft substrates for neuronal cultures using neural cells derived from human-induced pluripotent stem cells (hiPSCs). It is important to confirm that these bioprinted tissues possess mechanical properties similar to native neural tissues. Here, we assessed the physical and mechanical properties of bioprinted constructs generated from our novel microsphere containing bioink. We measured the elastic moduli of bioprinted constructs with and without microspheres using a modified Hertz model. The storage and loss modulus, viscosity, and shear rates were also measured. Physical properties such as microstructure, porosity, swelling, and biodegradability were also analyzed. Our results showed that the elastic modulus of constructs with microspheres was 1032 ± 59.7 Pascal (Pa), and without microspheres was 728 ± 47.6 Pa. Mechanical strength and printability were significantly enhanced with the addition of microspheres. Thus, incorporating microspheres provides mechanical reinforcement, which indicates their suitability for future applications in neural tissue engineering.
A Basic Study on Establishing the Automatic Sewing Process According to Textile Properties
Authors: Lee Suhyun , Rho Soohyeon , Lim Daeyoung , Jeong Wonyoung
Published: July 2021

This study aimed to establish an automatic sewing process for garment production according to textile properties. An automatic feeding system and a self-made template were introduced to an industrial sewing machine. Two types of stitches were performed on fabrics with various physical properties and surface roughness using this automatic sewing machine. The appearance, stitch length and width, seam strength, and seam efficiency were evaluated according to the sewing conditions, such as presser height and sewing speed. In addition, the correlation between textile properties, sewing conditions, and sewability was analyzed to derive a regression equation for sewability. The evaluation showed no difference in the lock stitch condition. On the other hand, under the zigzag stitch condition, the stitch width differed according to the presser height, which also affected the seam structure. The optimal presser height for each fabric was derived from the experimental results. In terms of the sewing speed, however, the seam strength was the best at 200 RPM in the lock stitch and 400 RPM in the zigzag stitch. The moderating effect of the presser height between textile properties and sewability in the lock stitch condition was confirmed. This result can be used as basic data for establishing an automatic sewing process for smart factories.
Two Decades of Experience with the Granular Sludge-Based ANAMMOX® Process Treating Municipal and Industrial Effluents
Authors: Driessen Willie , Hendrickx Tim
Published: July 2021

This paper is a review of 20 years of full-scale experience with the granular sludge-based ANAMMOX process. The ANAMMOX process is a biological deammonification process for energy-efficient removal of ammoniacal nitrogen, which has been successfully applied on dewatering reject liquors from biosolids sludge digesters (e.g., mesophilic anaerobic digestions, codigestion, thermal sludge hydrolysis process (THP)) and nutrient-rich anaerobically treated industrial effluents (e.g., fermentation industry, food industry). The ANAMMOX process is a continuously operated biological process using granular biomass. The highly active concentrated granular biomass allows for compact reactor systems and a fast start-up. Long term operations of various case studies show stable process performance of full-scale reactors treating municipal and industrial effluents, achieving ammoniacal nitrogen (NH4-N) removal in excess of 90% at low and high loading rates up to 2.5 kgNH4-N/(m3·d). Some special aspects (e.g., micro-nutrients, inhibition, alkalinity consumption) of treating various wastewaters are discussed in detail. The ANAMMOX process is demonstrated to be resilient in handling process upsets and off-spec wastewater composition.
Formulation, In Vitro and In Vivo Evaluation of Gefitinib Solid Dispersions Prepared Using Different Techniques
Authors: Alshehri Sultan , Alanazi Abdullah , Elzayat Ehab M. , Altamimi Mohammad A. , Imam Syed S. , Hussain Afzal , Alqahtani Faleh , Shakeel Faiyaz
Published: July 2021

Gefitinib (Gef) is a poorly water-soluble antitumor drug, which shows poor absorption/bioavailability after oral administration. Therefore, this study was carried out to develop Gef solid dispersions (SDs) using different carriers and different techniques in order to enhance its dissolution and oral absorption/bioavailability. Various SD formulations of Gef were established using fusion and microwave methods utilizing Soluplus, Kollidone VA64, and polyethylene glycol 4000 (PEG 4000) as the carriers. Developed SDs of Gef were characterized physicochemically and evaluated for in vitro dissolution and in vivo pharmacokinetic studies. The physicochemical evaluation revealed the formation of Gef SDs using fusion and microwave methods. In vitro dissolution studies indicated significant release of Gef from all SDs compared to the pure Gef. Optimized SD of Gef (S2-MW) presented significant release of Gef (82.10%) compared with pure Gef (21.23%). The optimized Gef SD (S2) was subjected to in vivo pharmacokinetic evaluation in comparison with pure Gef in rats. The results indicated significant enhancement in various pharmacokinetic parameters of Gef from an optimized SD S2 compared to the pure Gef. In addition, Gef-SD S2 resulted in remarkable improvement in bioavailability compared to the pure Gef. Overall, this study suggested that the prepared Gef-SD by microwave method showed marked enhancement in dissolution and bioavailability.
A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease
Authors: Catanese Lorenzo , Siwy Justyna , Mavrogeorgis Emmanouil , Amann Kerstin , Mischak Harald , Beige Joachim , Rupprecht Harald
Published: July 2021

Non-invasive urinary peptide biomarkers are able to detect and predict chronic kidney disease (CKD). Moreover, specific urinary peptides enable discrimination of different CKD etiologies and offer an interesting alternative to invasive kidney biopsy, which cannot always be performed. The aim of this study was to define a urinary peptide classifier using mass spectrometry technology to predict the degree of renal interstitial fibrosis and tubular atrophy (IFTA) in CKD patients. The urinary peptide profiles of 435 patients enrolled in this study were analyzed using capillary electrophoresis coupled with mass spectrometry (CE-MS). Urine samples were collected on the day of the diagnostic kidney biopsy. The proteomics data were divided into a training (n = 200) and a test (n = 235) cohort. The fibrosis group was defined as IFTA ≥ 15% and no fibrosis as IFTA < 10%. Statistical comparison of the mass spectrometry data enabled identification of 29 urinary peptides with differential occurrence in samples with and without fibrosis. Several collagen fragments and peptide fragments of fetuin-A and others were combined into a peptidomic classifier. The classifier separated fibrosis from non-fibrosis patients in an independent test set (n = 186) with area under the curve (AUC) of 0.84 (95% CI: 0.779 to 0.889). A significant correlation of IFTA and FPP_BH29 scores could be observed Rho = 0.5, p < 0.0001. We identified a peptidomic classifier for renal fibrosis containing 29 peptide fragments corresponding to 13 different proteins. Urinary proteomics analysis can serve as a non-invasive tool to evaluate the degree of renal fibrosis, in contrast to kidney biopsy, which allows repeated measurements during the disease course.
Scoring Models and Credit Risk: The Case of Cooperative Banks in Poland
Authors: Kil Krzysztof , Ciukaj Radosław , Chrzanowska Justyna
Published: July 2021

The aim of the research presented in the article was to analyse the legitimacy of the use of scoring models in banking activities, together with the assessment of the effectiveness of this tool in reducing the high value of the NPL ratio in Polish cooperative banks on the example of banks belonging to the BPS S.A. association in the period between 2004 and 2020. We used a variety of research methods for this purpose including a depth review of the literature, analysis of statistical data regarding the sector of Polish cooperative banks, analysis of financial data of cooperative banks, construction of an econometric panel model, and the designing a questionnaire (which was later sent to the management board of selected cooperative banks). Our research confirmed the significant impact of the use of scoring models in lending activities on the value of the NPL ratio in cooperative banks. The analysed cooperative banks, which used the scoring models proposed by BIK in their lending activity, showed significantly lower values of the NPL ratio in each analysed year than banks that used other scoring models. Our study also confirmed the different direction of the impact of the models offered by BIK and individual scoring models on the value of the NPL ratio. We have also shown that the scoring models proposed by BIK have a statistically significant negative impact on the level of the NPL ratio, and the banks’ own scoring models have a statistically significant positive impact on the level of the NPL ratio.
Unsupervised Assessment of Balance and Falls Risk Using a Smartphone and Machine Learning
Authors: Greene Barry R. , McManus Killian , Ader Lilian Genaro Motti , Caulfield Brian
Published: July 2021

Assessment of health and physical function using smartphones (mHealth) has enormous potential due to the ubiquity of smartphones and their potential to provide low cost, scalable access to care as well as frequent, objective measurements, outside of clinical environments. Validation of the algorithms and outcome measures used by mHealth apps is of paramount importance, as poorly validated apps have been found to be harmful to patients. Falls are a complex, common and costly problem in the older adult population. Deficits in balance and postural control are strongly associated with falls risk. Assessment of balance and falls risk using a validated smartphone app may lessen the need for clinical assessments which can be expensive, requiring non-portable equipment and specialist expertise. This study reports results for the real-world deployment of a smartphone app for self-directed, unsupervised assessment of balance and falls risk. The app relies on a previously validated algorithm for assessment of balance and falls risk; the outcome measures employed were trained prior to deployment on an independent data set. Results for a sample of 594 smartphone assessments from 147 unique phones show a strong association between self-reported falls history and the falls risk and balance impairment scores produced by the app, suggesting they may be clinically useful outcome measures. In addition, analysis of the quantitative balance features produced seems to suggest that unsupervised, self-directed assessment of balance in the home is feasible.