bluuebunny/crossref_metadata_2025 huggingface dataset:
Ag Surface and Bulk Segregations in Sputtered ZrCuAlNi Metallic Glass Thin Films
Authors: Steinhoff Michael K. , Holzapfel Damian M. , Karimi Aghda Soheil , Neuß Deborah , Pöllmann Peter J. , Hans Marcus , Primetzhofer Daniel , Schneider Jochen M. , Azina Clio
Published: February 2022

We report on the formation of Ag-containing ZrCuAlNi thin film metallic glass (nano)composites by a hybrid direct-current magnetron sputtering and high-power pulsed magnetron sputtering process. The effects of Ag content, substrate temperature and substrate bias potential on the phase formation and morphology of the nanocomposites were investigated. While applying a substrate bias potential did not strongly affect the morphological evolution of the films, the Ag content dictated the size and distribution of Ag surface segregations. The films deposited at low temperatures were characterized by strong surface segregations, formed by coalescence and Ostwald ripening, while the volume of the films remained featureless. At higher deposition temperature, elongated Ag segregations were observed in the bulk and a continuous Ag layer was formed at the surface as a result of thermally enhanced surface diffusion. While microstructural observations have allowed identifying both surface and bulk segregations, an indirect method for detecting the presence of Ag segregations is proposed, by measuring the electrical resistivity of the films.
Study of the Microstructure and Corrosion Properties of a Ni-Based Alloy Coating Deposited onto the Surface of Ductile Cast Iron Using High-Speed Laser Cladding
Authors: Wang Rui , Ouyang Changyao , Li Qihang , Bai Qiaofeng , Zhao Chunjiang , Liu Yingliang
Published: February 2022

To improve the surface corrosion resistance of ductile iron, Ni-based alloy coatings were prepared using a high-speed laser cladding technology with different levels of laser power. The microstructure, phases, and corrosion properties of the coatings were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), and an electrochemical workstation. Variations in laser power did not change the main phases of the coatings, which were composed of γ-Ni, Ni3B, Ni2Si, and Cr23C6. With an increase in power, the degree of segregation in the coating decreased, sufficient melting between elements was achieved, and the chemical composition became more uniform. Enhancement of the laser power resulted in more energy being injected into the cladding, which allowed adequate growth of tissue, and dendrites continued to grow in size as the power increased. The self-corrosion potentials of the coatings at laser power levels of 1.6, 2.0, and 2.4 kW were −625.7, −526.5, and −335.7 mV, respectively. The corrosion potential of the 2.4 kW coating was the highest, and the corroded surface of the cladding layer included mainly sizeable continuous structures with a light degree of corrosion and the highest corrosion resistance.
Curcumin and Graphene Oxide Incorporated into Alginate Hydrogels as Versatile Devices for the Local Treatment of Squamous Cell Carcinoma
Authors: Madeo Lorenzo Francesco , Sarogni Patrizia , Cirillo Giuseppe , Vittorio Orazio , Voliani Valerio , Curcio Manuela , Shai-Hee Tyler , Büchner Bernd , Mertig Michael , Hampel Silke
Published: February 2022

With the aim of preparing hybrid hydrogels suitable for use as patches for the local treatment of squamous cell carcinoma (SCC)-affected areas, curcumin (CUR) was loaded onto graphene oxide (GO) nanosheets, which were then blended into an alginate hydrogel that was crosslinked by means of calcium ions. The homogeneous incorporation of GO within the polymer network, which was confirmed through morphological investigations, improved the stability of the hybrid system compared to blank hydrogels. The weight loss in the 100–170 °C temperature range was reduced from 30% to 20%, and the degradation of alginate chains shifted to higher temperatures. Moreover, GO enhanced the stability in water media by counteracting the de-crosslinking process of the polymer network. Cell viability assays showed that the loading of CUR (2.5% and 5% by weight) was able to reduce the intrinsic toxicity of GO towards healthy cells, while higher amounts were ineffective due to the antioxidant/prooxidant paradox. Interestingly, the CUR-loaded systems were found to possess a strong cytotoxic effect in SCC cancer cells, and the sustained CUR release (~50% after 96 h) allowed long-term anticancer efficiency to be hypothesized.
Teaching and Practicing Humanism and Empathy through Embodied Engagement
Authors: Loue Sana
Published: February 2022

Concerns have been raised regarding medicine’s dehumanization of patients and providers and regarding the need to include, in the medical school curriculum, components that encourage the development of empathy and humanistic practice. This essay suggests that the development of humanistic practice requires attention to not only the cognitive and affective/emotive aspects of humanism, but also to the nurturing of intersubjectivity between the provider and the patient through strategies designed to promote embodied awareness. Several approaches to the development of embodied awareness are discussed, including puppetry pedagogy, drama, and virtual reality applications.
Informed Consent for Endoscopic Biliary Drainage: Time for a New Paradigm
Authors: Spadaccini Marco , Binda Cecilia , Fugazza Alessandro , Repici Alessandro , Tarantino Ilaria , Fabbri Carlo , Cugia Luigi , Anderloni Andrea ,   on behalf of the Interventional Endoscopy & Ultra Sound (I-EUS) Group
Published: February 2022

Endoscopic retrograde cholangiopancreatography (ERCP) is considered as the first option in the management of malignant biliary obstruction. In case of ERCP failure, percutaneous transhepatic biliary drainage (PTBD) has been conventionally considered as the preferred rescue strategy. However, the use of endoscopic ultrasound (EUS) for biliary drainage (EUS-BD) has proved similarly high rates of technical success, when compared to PTBD. As a matter of fact, biliary drainage is maybe the most evident paradigm of the increasing interconnection between ERCP and EUS, and obtaining an adequate informed consent (IC) is an emerging issue. The aim of this commentary is to discuss the reciprocal roles of ERCP and EUS for malignant biliary obstruction, in order to provide a guide to help in developing an appropriate informed consent reflecting the new biliopancreatic paradigm.
First Trimester Prediction of Adverse Pregnancy Outcomes—Identifying Pregnancies at Risk from as Early as 11–13 Weeks
Authors: Bouariu Alexandra , Panaitescu Anca Maria , Nicolaides Kypros H.
Published: February 2022

There is consistent evidence that many of the pregnancy complications that occur late in the second and third trimester can be predicted from an integrated 11–13 weeks visit, where a maternal and fetal assessment are comprehensively performed. The traditional aims of the 11–13 weeks visit have been: establishing fetal viability, chorionicity and dating of the pregnancy, and performing the combined screening test for common chromosomal abnormalities. Recent studies have shown that the first trimester provides important information that may help to predict pregnancy complications, such as preeclampsia and fetal growth restriction, stillbirth, preterm birth, gestational diabetes mellitus and placenta accreta spectrum disorder. The aim of this manuscript is to review the methods available to identify pregnancies at risk for adverse outcomes after screening at 11–13 weeks. Effective screening in the first trimester improves pregnancy outcomes by allowing specific interventions such as administering aspirin and directing patients to specialist clinics for regular monitoring.
Polarization Gradient Effect of Negative Capacitance LTFET
Authors: Zhang Hao , Chen Shupeng , Liu Hongxia , Wang Shulong , Wang Dong , Fan Xiaoyang , Chong Chen , Yin Chenyu , Gao Tianzhi
Published: February 2022

In this paper, an L-shaped tunneling field effect transistor (LTFET) with ferroelectric gate oxide layer (Si: HfO2) is proposed. The electric characteristic of NC-LTFET is analyzed using Synopsys Sentaurus TCAD. Compared with the conventional LTFET, a steeper subthreshold swing (SS = 18.4 mV/dec) of NC-LTFET is obtained by the mechanism of line tunneling at low gate voltage instead of diagonal tunneling, which is caused by the non-uniform voltage across the gate oxide layer. In addition, we report the polarization gradient effect in a negative capacitance TFET for the first time. It is noted that the polarization gradient effect should not be ignored in TFET. When the polarization gradient parameter g grows larger, the dominant tunneling mechanism that affects the SS is the diagonal tunneling. The on-state current (Ion) and SS of NC-LTFET become worse.
High Temperature Magnetic Cores Based on PowderMEMS Technique for Integrated Inductors with Active Cooling
Authors: Paesler Malte , Lisec Thomas , Kapels Holger
Published: February 2022

The paper presents the realization and characterization of micro-inductors with core with active cooling capability for future integrated DC/DC converter solutions operating with wide bandgap semiconductors at high temperatures with high power densities. The cores are fabricated backend-of-line compatible by filling cavities in silicon wafers with soft magnetic iron particles and their subsequent agglomeration to rigid, porous 3D microstructures by atomic layer deposition. Wafer processing is presented as well as measurement results at up to 400 ∘C operating temperature in comparison to of-the-shelf inductors. Using a DC/DC converter operating at 25 MHz switching frequency efficiencies of 81 to 83% are demonstrated for input voltages between 5 V and 12 V. It is shown that the temperature of the novel micro-inductors decreases if an air flow through its porous core is applied. This feature could be especially helpful for the realization of resonant power converters with larger temperature stress to passive components.
Stable Carbenes as Structural Components of Partially Saturated Sulfur-Containing Heterocycles
Authors: Rozhenko Alexander B. , Horbenko Yuliia S. , Kyrylchuk Andrii A. , Zarudnitskii Evgenij V. , Mykhaylychenko Sergiy S. , Shermolovich Yuriy G. , Grafov Andriy V.
Published: February 2022

Recently, an unusual elongation of the C-S bond was observed experimentally for some sulfur-containing heterocycles. Using a superior ab initio (SCS-MP2/cc-pVTZ) level of theory, we showed that the phenomenon can be explained by a contribution of a donor–acceptor adduct of a carbene with an unsaturated ligand. One may achieve further elongation of the C-S bond, eventually turning it to a coordinate one, by increasing the stability of each part of the system as, e.g., in the utmost case of spiro adducts with Arduengo carbenes. The effect of carbene stability was quantified by employing the isodesmic reactions of carbene exchange.
Relative Stability of Boron Planar Clusters in Diatomic Molecular Model
Authors: Chkhartishvili Levan
Published: February 2022

In the recently introduced phenomenological diatomic molecular model imagining the clusters as certain constructions of pair interatomic chemical bonds, there are estimated specific (per atom) binding energies of small all-boron planar clusters Bn, n = 1–15, in neutral single-anionic and single-cationic charge states. The theoretically obtained hierarchy of their relative stability/formation probability correlates not only with results of previous calculations, but also with available experimental mass-spectra of boron planar clusters generated in process of evaporation/ablation of boron-rich materials. Some overestimation in binding energies that are characteristic of the diatomic approach could be related to differences in approximations made during previous calculations, as well as measurement errors of these energies. According to the diatomic molecular model, equilibrium binding energies per B atom and B–B bond lengths are expected within ranges 0.37–6.26 eV and 1.58–1.65 Å, respectively.
Molecular Distillation of Lavender Supercritical Extracts: Physicochemical and Antimicrobial Characterization of Feedstocks and Assessment of Distillates Enriched with Oxygenated Fragrance Components
Authors: Dębczak Agnieszka , Tyśkiewicz Katarzyna , Fekner Zygmunt , Kamiński Piotr , Florkowski Grzegorz , Konkol Marcin , Rój Edward , Grzegorczyk Agnieszka , Malm Anna
Published: February 2022

Lavandula angustifolia is one of the most widely cultivated non-food crops used in the production of essential oil; it is used in perfumery, aromatherapy, pharmaceutical preparations, and food ingredients. In this study, supercritical fluid extraction (SFE) and molecular distillation (MD) were combined, primarily to enrich scCO2 extracts with lavender oxygenated monoterpenes, avoiding thermal degradation, hydrolysis, and solvent contamination, and maintaining the natural characteristics of the obtained oils. Molecular distillation was developed for the first time for the extraction of crucial lavender fragrance ingredients, i.e., from two scCO2 extracts obtained from dry flower stems of lavender cultivated in Poland and Bulgaria. The best results for high-quality distillates were obtained at 85 °C (EVT) and confirmed that linalyl acetate content increased from 51.54 mg/g (initial Bulgarian lavender extract, L-Bg-E) and 89.53 mg/g (initial Polish lavender extract, L-Pl-E) to 118.41 and 185.42 mg/g, respectively, corresponding to increases of 2.3 and 2.1 times in both distillate streams, respectively. The distillates, light oils, and extracts from lavender were also evaluated for their antimicrobial properties by determining the minimum inhibitory concentration (MIC) by the broth microdilution method. Generally, Gram-positive bacteria and Candida spp. were more sensitive to all distilled fractions and extracts than Escherichia coli (Gram-negative bacteria).
Is Genetic Engineering a Route to Enhance Microalgae-Mediated Bioremediation of Heavy Metal-Containing Effluents?
Authors: Ranjbar Saeed , Malcata Francisco Xavier
Published: February 2022

Contamination of the biosphere by heavy metals has been rising, due to accelerated anthropogenic activities, and is nowadays, a matter of serious global concern. Removal of such inorganic pollutants from aquatic environments via biological processes has earned great popularity, for its cost-effectiveness and high efficiency, compared to conventional physicochemical methods. Among candidate organisms, microalgae offer several competitive advantages; phycoremediation has even been claimed as the next generation of wastewater treatment technologies. Furthermore, integration of microalgae-mediated wastewater treatment and bioenergy production adds favorably to the economic feasibility of the former process—with energy security coming along with environmental sustainability. However, poor biomass productivity under abiotic stress conditions has hindered the large-scale deployment of microalgae. Recent advances encompassing molecular tools for genome editing, together with the advent of multiomics technologies and computational approaches, have permitted the design of tailor-made microalgal cell factories, which encompass multiple beneficial traits, while circumventing those associated with the bioaccumulation of unfavorable chemicals. Previous studies unfolded several routes through which genetic engineering-mediated improvements appear feasible (encompassing sequestration/uptake capacity and specificity for heavy metals); they can be categorized as metal transportation, chelation, or biotransformation, with regulation of metal- and oxidative stress response, as well as cell surface engineering playing a crucial role therein. This review covers the state-of-the-art metal stress mitigation mechanisms prevalent in microalgae, and discusses putative and tested metabolic engineering approaches, aimed at further improvement of those biological processes. Finally, current research gaps and future prospects arising from use of transgenic microalgae for heavy metal phycoremediation are reviewed.
Design, Synthesis, and Cytotoxic Activity of Novel Natural Arylsulfonamide-Inspired Molecules
Authors: Huang Wenbo , Shi Liqiao , Liu Manli , Zhang Zhigang , Liu Fang , Long Tong , Wen Shaohua , Huang Daye , Wang Kaimei , Zhou Ronghua , Fang Wei , Hu Hongtao , Ke Shaoyong
Published: February 2022

Primary arylsulfonamide functional groups feature prominently in diverse pharmaceuticals. However, natural arylsulfonamides are relatively infrequent. In this work, two novel arylsulfonamide natural products were first synthesized, and then a series of novel molecules derived from natural arylsulfonamides were designed and synthesized, and their in vitro cytotoxic activities against A875, HepG2, and MARC145 cell lines were systematically evaluated. The results indicate that some of these arylsulfonamide derivatives exhibit significantly good cytotoxic activity against the tested cell lines compared with the control 5-fluorouracil (5-FU), such as compounds 10l, 10p, 10q, and 10r. In particular, the potential molecule 10q, containing a carbazole moiety, exhibited the highest inhibitory activity against all tested cell lines, with IC50 values of 4.19 ± 0.78, 3.55 ± 0.63, and 2.95 ± 0.78 μg/mL, respectively. This will offer the potential to discover novel drug-like compounds from the sparsely populated area of natural products that can lead to effective anticancer agents.
Biochar Applied with Inorganic Nitrogen Improves Soil Carbon, Nitrate and Ammonium Content of a Sandy Loam Temperate Soil
Authors: Omara Peter , Aula Lawrence , Otim Fred , Obia Alfred , Souza Joao Luis Bigatao , Arnall Daryl Brain
Published: February 2022

Biochar is suggested to improve soil properties. However, its combination with inorganic nitrogen (N) fertilizer in temperate soils is not well understood. This study compared the effect of fertilizer N-biochar-combinations (NBC) and fertilizer-N (FN) on total soil N (TSN), soil organic carbon (SOC), soil nitrate (NO3−–N), and ammonium (NH4+–N). Soil samples were taken from experiments at Efaw and Lake Carl Blackwell (LCB), Oklahoma, USA with ten treatments consisting of three N rates (50, 100, and 150 kg N ha−1) and three biochar rates (5, 10, and 15 t ha−1). Results at Efaw showed greater TSN and SOC under NBC compared to FN by 3 and 21%, respectively. No percentage difference was observed for NH4+–N while NO3−–N was lower by 7%. At LCB, TSN, SOC, NO3−–N, and NH4+–N were higher under NBC by 5, 18, 24, and 10%, respectively, compared to FN. Whereas application of biochar improved SOC at both sites, NO3−–N and NH4+–N were only significant at LCB site with a sandy loam soil but not at Efaw with silty clay loam. Therefore, biochar applied in combination with inorganic N can improve N availability with potential to increase crop N uptake on coarse textured soils.
Macronutrient Intake and Insulin Resistance in 5665 Randomly Selected, Non-Diabetic U.S. Adults
Authors: Tucker Larry A.
Published: February 2022

The main goal of this investigation was to evaluate the relationships between several macronutrients and insulin resistance in 5665 non-diabetic U.S. adults. A secondary objective was to determine the extent to which the associations were influenced by multiple potential confounding variables. A cross-sectional design and 8 years of data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES) were used to answer the research questions. Ten macronutrients were evaluated: total carbohydrate, starch, simple carbohydrate, dietary fiber, total protein, total fat, saturated, polyunsaturated, monounsaturated, and total unsaturated fat. The homeostatic model assessment (HOMA), based on fasting glucose and fasting insulin levels, was used to index insulin resistance. Age, sex, race, year of assessment, physical activity, cigarette smoking, alcohol use, and waist circumference were used as covariates. The relationships between total carbohydrate intake (F = 6.7, p = 0.0121), simple carbohydrate (F = 4.7, p = 0.0344) and HOMA-IR were linear and direct. The associations between fiber intake (F = 9.1, p = 0.0037), total protein (F = 4.4, p = 0.0393), total fat (F = 5.5, p = 0.0225), monounsaturated fat (F = 5.5, p = 0.0224), and total unsaturated fat (F = 6.5, p = 0.0132) were linear and inversely related to HOMA-IR, with 62 degrees of freedom. Starch, polyunsaturated fat, and saturated fat intakes were not related to HOMA-IR. In conclusion, in this nationally representative sample, several macronutrients were significant predictors of insulin resistance in U.S. adults.
Timing of Adiposity Rebound and Determinants of Early Adiposity Rebound in Korean Infants and Children Based on Data from the National Health Insurance Service
Authors: Goh Eun Kyoung , Kim Oh Yoen , Yoon So Ra , Jeon Hyo Jeong
Published: February 2022

Adiposity rebound (AR) is defined as the second rise in the body mass index (BMI) usually occurring in early childhood. This study aimed to investigate the timing of AR and the factors determining early AR (EAR) by tracking BMI patterns using large-scale longitudinal nationwide data (n = 142,668; 73,389 boys and 69,279 girls) over seven time periods (4–6, 9–12, 18–24, 30–36, 42–48, 54–60, and 66–71 months). The average BMI rebound indicating AR was found before the age of 5 years (6th time period, 54–60 months). Interestingly, children experiencing BMI rebound during the 4th to 6th time periods showed a small increase in the proportion of underweight in the 2nd time period, but a dramatically higher proportion of underweight during the corresponding time period, similar to M-shaped patterns. In contrast, overweight or obese children in the above group showed opposite W-shaped patterns. The parameters predicting the risk of EAR are diverse for each time period by sex. Adequate breastfeeding before the age of 1 year, adequate diet, and reduced sugar-sweetened beverage consumption after the age of 1 year were important for reducing EAR. This study presents for the first time, the timing of AR and the major determinants of EAR among Korean infants and children based on large-scale nationwide data.
Effects of Exercise on Nutritional Status in People with Cystic Fibrosis: A Systematic Review
Authors: Nicolson William B. , Bailey Julianna , Alotaibi Najlaa Z. , Krick Stefanie , Lowman John D.
Published: February 2022

Background: Physical exercise is an important part of regular care for people with cystic fibrosis (CF). It is unknown whether such exercise has beneficial or detrimental effects on nutritional status (body composition). Thus, the objective of this review was to evaluate the effect of exercise on measures of nutritional status in children and adults with CF. Methods: Standardized reporting guidelines for systematic reviews were followed and the protocol was prospectively registered. Multiple databases were utilized (e.g., PubMed, Scopus, and CINHAL). Two reviewers independently reviewed titles/abstracts and then the full text for selected studies. Results: In total, 924 articles were originally identified; data were extracted from 4 eligible studies. These four studies included only children; pulmonary function ranged from severe to normal, and the majority of participants were at or below their recommended weight. Exercise training did not worsen nutritional status in any study; two studies that included resistance exercise reported an increase in fat-free mass. Three of the four studies also reported increased aerobic capacity and/or muscle strength. Conclusions: Exercise training can produce positive physiologic changes in children with CF without impairing their nutritional status. In fact, resistance exercise can help improve body mass. Much less is known about how exercise may affect adults or those who are overweight.
Cognitive Performance Before and Following Habituation to Exercise-Induced Hypohydration of 2 and 4% Body Mass in Physically Active Individuals
Authors: Deshayes Thomas A. , Daigle Nicolas , Jeker David , Lamontagne-Lacasse Martin , Perreault-Briere Maxime , Claveau Pascale , Simoneau Ivan L. , Chamoux Estelle , Goulet Eric D. B.
Published: February 2022

We investigated the effect of repeated exposures to hypohydration upon cognitive performance. In a randomized crossover design, ten physically active adults completed two 4-week training blocks, one where they maintained euhydration (EUH) and the other where they were water-restricted (DEH) during walking/running at 55% V.O2max, 40 °C. Three sessions per week were performed: (1) 1 h of exercise, (2) exercise until 2% or (3) 4% of body mass has been lost or replaced. Limited to the first and fourth training week, a 12 min walking/running time-trial was completed following the 2 and 4% exercise bouts. Trail making, the Wisconsin card sort, the Stop signal task, Simple visual reaction time and Corsi block-tapping tests were performed immediately following the time-trials. Body mass loss was maintained < 1% with EUH and reached 2.7 and 4.7% with DEH following the time-trials. Except for a lower percentage of correct responses (% accuracy) during the Wisconsin card sort test (p < 0.05) with DEH compared to EUH, no statistically significant decline in cognitive performance was induced by low and moderate levels of hypohydration. Compared to week 1, no statistical differences in cognitive responses were observed after repeated exposures to hypohydration (all p > 0.05). From a practical perspective, the gains in cognitive performance following training to DEH were mostly unclear, but under certain circumstances, were greater than when EUH was maintained. Based on the battery of cognitive tests used in the current study, we conclude that whether physically active individuals are habituated or not to its effect, exercise-induced hypohydration of 2 and 4% has, in general, no or unclear impact on cognitive performance immediately following exercise. These results encourage further research in this area.
Effects of the Mediterranean Diet on Morbidity from Inflammatory and Recurrent Diseases with Special Reference to Childhood Asthma
Authors: Calatayud-Sáez Fernando M. , Calatayud Blanca , Calatayud Ana
Published: February 2022

Objective: For 15 years, we have been working with a nutritional programme based on the traditional Mediterranean diet (TMD) to complete the treatment of inflammatory and recurrent diseases (IRD), such as childhood asthma. The objective of this study is to verify the effects of TMD in the prevention and treatment of IRD by measuring the incidence of infant morbidity over 8 years. Material and Methods: The number of patients who suffered from IRD each year (just before the pandemic) was determined, as well as the frequentation and the percentage of scheduled and on-demand consultations. Results: The incidence of infant morbidity decreased as they were incorporated into a TMD, and we observed a progressive disappearance of IRD. At the beginning of the study, 20% of the patients had been diagnosed with some type of IRD. At the study’s end, the prevalence of IRD decreased to less than 2%, and the use of drugs and surgical interventions decreased markedly. Conclusions: A diet based on the TMD reduces the incidence of infant morbidity and contributes to the disappearance of IRD, whereas some non-traditional foods with high antigenic power could be involved in the appearance of IRD.
Population Dynamics of a Two Phages–One Host Infection System Using Escherichia coli Strain ECOR57 and Phages vB_EcoP_SU10 and vB_EcoD_SU57
Authors: Koonjan Shazeeda , Cardoso Palacios Carlos , Nilsson Anders S.
Published: February 2022

In this study, we looked at the population dynamics of a two phages-one host system using phages vB_EcoP_SU10 (SU10) and vB_EcoD_SU57 (SU57) and the bacteria Escherichia coli, strain ECOR57. Phage-specific growth curves were observed where infections by SU10 resulted in a moderate production of phages and infections by SU57 resulted in a fast and extensive production of phage progeny. Sequentially adding SU10 followed by SU57 did not produce a significant change in growth rates, whereas adding SU57 followed by SU10 resulted in a decrease in SU10 titer The efficiency of the plating assays showed that ECOR57 exhibited a resistance spectrum after infection by both the single and combined phages. Phage-resistant bacteria exhibited four different morphotypes (i.e., normal, slimy, edgy, and pointy). The normal and edgy morphotypes had a high frequency of developing resistance. Bacterial growth and biofilm assays indicated that the edgy and pointy morphotypes reached a stationary phase faster and produced more biofilm compared to the wild type. These findings suggest that the dynamic structure of phage–bacteria communities dictate resistance evolution and development. Understanding when and how resistances arise and phage(s)–hosts interactions could aid in the design of phage therapy treatments.
Supramolecular Systems for Gene and Drug Delivery
Authors: Lebrón José A. , López-Cornejo Pilar , Ostos Francisco J.
Published: February 2022

Several biomaterial-based supramolecular systems (cyclodextrins [...]
Optimal Design of Novel Microemulsions-Based Two-Layered Dissolving Microneedles for Delivering Fluconazole in Treatment of Fungal Eye Infection
Authors: Suriyaamporn Phuvamin , Opanasopit Praneet , Rangsimawong Worranan , Ngawhirunpat Tanasait
Published: February 2022

The optimal design of novel microneedles (MNs) for the ocular delivery system is necessary and useful for improving the effectiveness of medication. The objective of this study was to design and develop the optimal fluconazole (FLUZ)-microemulsions (MEs)-loaded two-layered dissolving MNs as a potential treatment for fungal eye infection. The experimental designs using the simplex-lattice design were used to select the optimal formulation. The two-layered dissolving MNs were fabricated from 3% chitosan and 20% polyvinyl alcohol (PVA) in a weight ratio of 1:4 as an outer layer and FLUZ-loaded MEs containing eugenol, tween 80, PEG400, and water as an inner layer. The physical appearance, mechanical properties, penetration ability, dissolution time, in vitro/ex vivo ocular drug delivery, and antifungal activity were evaluated. From the results, the optimal two-layered dissolving MNs exhibited good physical properties, complete insertion, minimally invasive ocular tissue, and high stability at 4 °C and 25 °C for 3 months. Moreover, the optimal two-layered dissolving MNs showed significantly higher FLUZ permeation into the ocular tissue than other formulations, while providing highly potential antifungal activity. In conclusion, the optimal MEs-loaded two-layered MNs’ formulation had appropriate properties for ocular delivery of FLUZ, resulting in an improvement of fungal keratitis treatment.
Assessing the Appropriateness of Formulations on the WHO Model List of Essential Medicines for Children: Development of a Paediatric Quality Target Product Profile Tool
Authors: Walsh Jennifer , Masini Tiziana , Huttner Benedikt , Moja Lorenzo , Penazzato Martina , Cappello Bernadette
Published: February 2022

The World Health Organization’s Model List of Essential Medicines for Children (EMLc) presents a list of the most efficacious, safe, and cost-effective medicines for priority conditions, intended for use in children up to 12 years of age. However, gaps in global availability and use of age-appropriate formulations of medicines for children still exist. To address these shortcomings, a comprehensive analysis of the appropriateness of formulations of essential medicines for children is being undertaken through the Global Accelerator for Paediatric Formulations (GAP-f) network, a WHO network launched in 2020 to respond to the paediatric treatment gap. This article describes the development and application of a paediatric Quality Target Product Profile (pQTPP) tool by WHO, to retrospectively evaluate the paediatric age-appropriateness of formulations on the EMLc and identify potential formulation gaps, to inform the review of the EMLc in 2023. A combination of paediatric-centric and global health-focused attributes and targets were defined, taking into consideration regulatory agency paediatric development guidelines and literature sources, and a qualitative scoring system was developed and tested. Example evaluations of paracetamol and clofazimine are provided, illustrating the tool’s use. The assessment of EMLc formulations is ongoing and shortcomings and gaps in EMLc formulations have already been identified. The pQTTP tool may also be applied to national lists and prospectively when designing new paediatric formulations.
A Dual-Reporter Platform for Screening Tumor-Targeted Extracellular Vesicles
Authors: Kanada Masamitsu , Linenfelser Lauren , Cox Elyssa , Gilad Assaf A.
Published: February 2022

Extracellular vesicle (EV)-mediated transfer of biomolecules plays an essential role in intercellular communication and may improve targeted drug delivery. In the past decade, various approaches to EV surface modification for targeting specific cells or tissues have been proposed, including genetic engineering of parental cells or postproduction EV engineering. However, due to technical limitations, targeting moieties of engineered EVs have not been thoroughly characterized. Here, we report the bioluminescence resonance energy transfer (BRET) EV reporter, PalmReNL-based dual-reporter platform for characterizing the cellular uptake of tumor-homing peptide (THP)-engineered EVs, targeting PDL1, uPAR, or EGFR proteins expressed in MDA-MB-231 breast cancer cells, simultaneously by bioluminescence measurement and fluorescence microscopy. Bioluminescence analysis of cellular EV uptake revealed the highest binding efficiency of uPAR-targeted EVs, whereas PDL1-targeted EVs showed slower cellular uptake. EVs engineered with two known EGFR-binding peptides via lipid nanoprobes did not increase cellular uptake, indicating that designs of EGFR-binding peptide conjugation to the EV surface are critical for functional EV engineering. Fluorescence analysis of cellular EV uptake allowed us to track individual PalmReNL-EVs bearing THPs in recipient cells. These results demonstrate that the PalmReNL-based EV assay platform can be a foundation for high-throughput screening of tumor-targeted EVs.
Synthesis of Polyethylene Glycol Diacrylate/Acrylic Acid Nanoparticles as Nanocarriers for the Controlled Delivery of Doxorubicin to Colorectal Cancer Cells
Authors: Myat Yin Yin , Ngawhirunpat Tanasait , Rojanarata Theerasak , Opanasopit Praneet , Bradley Mark , Patrojanasophon Prasopchai , Pornpitchanarong Chaiyakarn
Published: February 2022

Doxorubicin (Dox) is known for its potential to deliver desirable anticancer effects against various types of cancer including colorectal cancer. However, the adverse effects are serious. This study aimed to synthesize polyethylene glycol diacrylate (PEGDA)/acrylic acid (AA)-based nanoparticles (PEGDA/AA NPs) for Dox delivery to colorectal cancer cells. The NPs were synthesized using free-radical polymerization reaction using the monomers PEGDA and AA with their physical properties, drug loading and release, biocompatibility, and anticancer effect evaluated. The NPs were spherical with a size of around 230 nm, with a 48% Dox loading efficiency and with loading capacity of 150 µg/mg. Intriguingly, the NPs had the ability to prolong the release of Dox in vitro over 24 h and were non-toxic to intestinal epithelial cells. Dox-loaded PEGDA/AA NPs (Dox-NPs) were able to effectively kill the colorectal cancer cell line (HT-29) with the Dox-NPs accumulating inside the cell and killing the cell through the apoptosis pathway. Overall, the synthesized PEGDA/AA NPs exhibit considerable potential as a drug delivery carrier for colon cancer-directed, staged-release therapy.
Enhancement of the Solubility and Bioavailability of Pitavastatin through a Self-Nanoemulsifying Drug Delivery System (SNEDDS)
Authors: Ashfaq Mehran , Shah Shahid , Rasul Akhtar , Hanif Muhammad , Khan Hafeez Ullah , Khames Ahmed , Abdelgawad Mohamed A. , Ghoneim Mohammed M. , Ali Muhammad Yasir , Abourehab Mohammad A. S. , Maheen Safirah , Iqbal Omeira , Abbas Ghulam , El Sisi Amani M.
Published: February 2022

The purpose of the study was to develop an SNEDDS to improve the solubility and bioavailability of pitavastatin. The solubility of pitavastatin in different oils, surfactants, and co-surfactants was determined and a pseudo-ternary phase diagram was constructed. The SNEDDS was characterized by zeta-sizer, zeta-potential, FTIR, DSC, and TGA. Release and permeation of pitavastatin from the SNEDDS was studied for 12 and 24 h, respectively. The lipolysis test, RBC lysis, effect on lipid profile, and pharmacokinetics were studied. The SPC3 formulation showed a 104 ± 1.50 nm particle size, a 0.198 polydispersity index (PDI), and a –29 zeta potential. FTIR, DSC, and TGA showed the chemical compatibility and thermal stability. The release and permeation of pitavastatin from SPC3 was 88.5 ± 2.5% and 96%, respectively. In the lipolysis test, the digestion of SPC3 yielded a high amount of pitavastatin and showed little RBC lysis. The lipid profile suggested that after 35 days of administration of the SNEDDS, there was a marked decrease in TC, LDL, and triglyceride levels. The SNEDDS of SPC3 showed an 86% viability of Caco-2 cells. Pharmacokinetics of SPC3 showed improved values of Cmax, Tmax, half-life, MRT, AUC, and AUMC compared to the reference formulation. Our study demonstrated that the SNEDDS effectively enhanced the solubility and bioavailability of a BCS class II drug.
Hadron Therapy Achievements and Challenges: The CNAO Experience
Authors: Rossi Sandro
Published: February 2022

Protons and carbon ions (hadrons) have useful properties for the treatments of patients affected by oncological pathologies. They are more precise than conventional X-rays and possess radiobiological characteristics suited for treating radio-resistant or inoperable tumours. This paper gives an overview of the status of hadron therapy around the world. It focusses on the Italian National Centre for Oncological Hadron therapy (CNAO), introducing operation procedures, system performance, expansion projects, methodologies and modelling to build individualized treatments. There is growing evidence that supports safety and effectiveness of hadron therapy for a variety of clinical situations. However, there is still a lack of high-level evidence directly comparing hadron therapy with modern conventional radiotherapy techniques. The results give an overview of pre-clinical and clinical research studies and of the treatments of 3700 patients performed at CNAO. The success and development of hadron therapy is strongly associated with the creation of networks among hadron therapy facilities, clinics, universities and research institutions. These networks guarantee the growth of cultural knowledge on hadron therapy, favour the efficient recruitment of patients and present available competences for R&D (Research and Development) programmes.
A Temperature-Independent Methodology for Polymer Bitumen Modification Evaluation Based on DSR Measurement
Authors: Wu Jiantao , Wang Haoan , Liu Quan , Gao Yangming , Liu Shengjie
Published: February 2022

Owing to the continuous increase of traffic loads, bitumen modification has been manifested as an efficient methodology to enhance asphaltic pavement performance. Currently, the modification index, defined as the ratio of mechanical properties (e.g., complex modulus) before and after bitumen modification, is extensively adopted to evaluate the modification degree. However, bituminous materials behave as temperature-dependent, which indicates that the mechanical property varies with measured temperatures. As a result, the calculated modification index also shows temperature-dependent property, which inhibits the use of modification index. For this reason, this study introduced a method to eliminate the temperature-dependency of the modification index. In specific, a mathematical model considering the properties of modifiers was firstly established to predict the modification index-temperature curve (MI-T curve). In what follows, the temperature-dependency of modification index was analyzed to verify the proposed model on three types of modifiers, which were graphene, Styrene-Butadiene-Styrene (SBS), and Ethyl-Vinyl-Acetate (EVA), respectively. The results indicated that the developed model could efficiently predict the MI-T curves. Besides, the effective modification area (EMA) and optimal modification index (OMI) were two reasonable indicators that evaluate the bitumen modification without considering the temperature-dependency.
Research Progress of Light Wavelength Conversion Materials and Their Applications in Functional Agricultural Films
Authors: Liu Yi , Gui Zhiguo , Liu Jialei
Published: February 2022

As new fluorescent materials, light wavelength conversion materials (light conversion agents) have attracted increasing attention from scientific researchers and agricultural materials companies due to their potential advantages in efficiently utilizing solar energy and increasing crop yield. According to the material properties, the light conversion agents can be divided into fluorescent dyes, organic rare-earth complexes, and inorganic rare-earth complexes. The current researches indicates that the fluorescent dyes have relatively high production costs, poor light stability, difficult degradation processes, and easily cause pollution to the ecological environment. The organic rare-earth complexes have short luminescence times, high production costs, and suffer from rapid decreases in luminescence intensity. Compared with fluorescent dyes and organic rare-earth complexes, although rare-earth inorganic complexes have high luminous efficiency, stable chemical properties, and better spectral matching performance, the existing inorganic light conversion agents have relatively poor dispersibility in agricultural films. According to the research on light conversion agents at home and abroad in recent years, this paper first introduces the three common light conversion agents, namely fluorescent dyes, organic rare-earth complexes, and inorganic rare-earth complexes, as well as their uses in agricultural films and their mechanisms of light conversion. At the same time, the preparation methods, advantages, disadvantages, and existing problems of various light conversion agents are classified and explained. Finally, we predict the development trends for light conversion agents in the future by considering six aspects, namely efficiency, cost, compatibility with greenhouse films, light matching, and light transmittance, in order to provide a reference for the preparation of stable and efficient light conversion agent materials.
Geopolymers—Design, Preparation, and Applications
Authors: Blanco Ignazio , Catauro Michelina
Published: February 2022

Concrete is the most commonly used construction material worldwide, and many efforts have been carried out in recent years to improve its functional properties while also trying to increase its sustainability [...]
Sensory and Biological Potential of Encapsulated Common Bean Protein Hydrolysates Incorporated in a Greek-Style Yogurt Matrix
Authors: Free-Manjarrez Samantha , Mojica Luis , Espinosa-Andrews Hugo , Morales-Hernández Norma
Published: February 2022

The work aimed to develop a gel as a protective barrier of common bean protein hydrolysates to be incorporated into a Greek-style yogurt and evaluate the sensory perception and biological potential. The gel was formed by complex coacervation and induced heat at a pH 3.5 and 3:1 biopolymer ratio (whey protein and gum arabic). The gel presented a 39.33% yield, low syneresis (0.37%), and a gel strength of 100 gf. The rheological properties showed an elastic behavior (G′ > G″). The gel with the most stable characteristics favored the incorporation of 2.3 g of hydrolysates to be added into the Greek-style yogurt. Nutritionally, the Greek-style yogurt with the encapsulated hydrolysates presented 9.96% protein, 2.27% fat, and 1.76% carbohydrate. Syneresis (4.64%), titratable acidity (1.39%), and viscoelastic behavior presented similar characteristics to the Greek-style control yogurt. The bitterness and astringency in yogurt with encapsulated hydrolysates decreased 44% and 52%, respectively, compared to the yogurt control with the unencapsulated hydrolysates. The Greek-style yogurt with the encapsulated hydrolysates showed the ability to inhibit enzymes related to carbohydrate metabolism (α-amylase (92.47%) and dipeptidyl peptidase-4 (75.24%) after simulated gastrointestinal digestion). The use of gels could be an alternative to transporting, delivering, and masking off-flavors of common bean protein hydrolysates in food matrices to decrease glucose absorption for type 2 diabetes patients.
Anomalous Dynamics in Macromolecular Liquids
Authors: Guenza Marina G.
Published: February 2022

Macromolecular liquids display short-time anomalous behaviors in disagreement with conventional single-molecule mean-field theories. In this study, we analyze the behavior of the simplest but most realistic macromolecular system that displays anomalous dynamics, i.e., a melt of short homopolymer chains, starting from molecular dynamics simulation trajectories. Our study sheds some light on the microscopic molecular mechanisms responsible for the observed anomalous behavior. The relevance of the correlation hole, a unique property of polymer liquids, in relation to the observed subdiffusive dynamics, naturally emerges from the analysis of the van Hove distribution functions and other properties.
3D Printed Scaffold Based on Type I Collagen/PLGA_TGF-β1 Nanoparticles Mimicking the Growth Factor Footprint of Human Bone Tissue
Authors: Banche-Niclot Federica , Licini Caterina , Montalbano Giorgia , Fiorilli Sonia , Mattioli-Belmonte Monica , Vitale-Brovarone Chiara
Published: February 2022

In bone regenerative strategies, the controlled release of growth factors is one of the main aspects for successful tissue regeneration. Recent trends in the drug delivery field increased the interest in the development of biodegradable systems able to protect and transport active agents. In the present study, we designed degradable poly(lactic-co-glycolic)acid (PLGA) nanocarriers suitable for the release of Transforming Growth Factor-beta 1 (TGF-β1), a key molecule in the management of bone cells behaviour. Spherical TGF-β1-containing PLGA (PLGA_TGF-β1) nanoparticles (ca.250 nm) exhibiting high encapsulation efficiency (ca.64%) were successfully synthesized. The TGF-β1 nanocarriers were subsequently combined with type I collagen for the fabrication of nanostructured 3D printed scaffolds able to mimic the TGF-β1 presence in the human bone extracellular matrix (ECM). The homogeneous hybrid formulation underwent a comprehensive rheological characterisation in view of 3D printing. The 3D printed collagen-based scaffolds (10 mm × 10 mm × 1 mm) successfully mimicked the TGF-β1 presence in human bone ECM as assessed by immunohistochemical TGF-β1 staining, covering ca.3.4% of the whole scaffold area. Moreover, the collagenous matrix was able to reduce the initial burst release observed in the first 24 h from about 38% for the PLGA_TGF-β1 alone to 14.5%, proving that the nanocarriers incorporation into collagen allows achieving sustained release kinetics.