bluuebunny/crossref_metadata_2025 huggingface dataset:
Physicochemical Characterization of Hyaluronic Acid and Chitosan Liposome Coatings
Authors: Bonechi Claudia , Tamasi Gabriella , Donati Alessandro , Leone Gemma , Consumi Marco , Cangeloni Lorenzo , Volpi Vanessa , Magnani Agnese , Cappelli Andrea , Rossi Claudio
Published: December 2021

Hyaluronic acid (HA) and chitosan (CH) are biopolymers that are widely used in many biomedical applications and for cosmetic purposes. Their chemical properties are fundamental to them working as drug delivery systems and improving their synergistic effects. In this work, two different protocols were used to obtain zwitterionic liposomes coated with either hyaluronic acid or chitosan. Specifically, the methodologies used to perform vesicle preparation were chosen by taking into account the specific chemical properties of these two polysaccharides. In the case of chitosan, liposomes were first synthesized and then coated, whereas the coating of hyaluronic acid was achieved through lipidic film hydration in an HA aqueous solution. The size and the zeta-potential of the polysaccharide-coated liposomes were determined by dynamic light scattering (DLS). This approach allowed coated liposomes to be obtained with hydrodynamic diameters of 264.4 ± 12.5 and 450.3 ± 16.7 nm for HA- and CH-coated liposomes, respectively. The chemical characterization of the coated liposomal systems was obtained by surface infrared (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopies. In particular, the presence of polysaccharides was confirmed by the bands assigned to amides and saccharides being in the 1500–1700 cm−1 and 800–1100 cm−1 regions, respectively. This approach allowed confirmation of the efficiency of the coating processes, evidencing the presence of HA or CH at the liposomal surface. These data were also supported by time-of-flight secondary ion mass spectrometry (ToF-SIMS), which provided specific assessments of surface (3–5 nm deep) composition and structure of the polysaccharide-coated liposomes. In this work, the synthesis and the physical chemistry characterization of coated liposomes with HA or CH represent an important step in improving the pharmacological properties of drug delivery systems.
Modular Dynamic Neural Network: A Continual Learning Architecture
Authors: Turner Daniel , Cardoso Pedro J. S. , Rodrigues João M. F.
Published: December 2021

Learning to recognize a new object after having learned to recognize other objects may be a simple task for a human, but not for machines. The present go-to approaches for teaching a machine to recognize a set of objects are based on the use of deep neural networks (DNN). So, intuitively, the solution for teaching new objects on the fly to a machine should be DNN. The problem is that the trained DNN weights used to classify the initial set of objects are extremely fragile, meaning that any change to those weights can severely damage the capacity to perform the initial recognitions; this phenomenon is known as catastrophic forgetting (CF). This paper presents a new (DNN) continual learning (CL) architecture that can deal with CF, the modular dynamic neural network (MDNN). The presented architecture consists of two main components: (a) the ResNet50-based feature extraction component as the backbone; and (b) the modular dynamic classification component, which consists of multiple sub-networks and progressively builds itself up in a tree-like structure that rearranges itself as it learns over time in such a way that each sub-network can function independently. The main contribution of the paper is a new architecture that is strongly based on its modular dynamic training feature. This modular structure allows for new classes to be added while only altering specific sub-networks in such a way that previously known classes are not forgotten. Tests on the CORe50 dataset showed results above the state of the art for CL architectures.
Gradient Boosting Machine to Assess the Public Protest Impact on Urban Air Quality
Authors: Zalakeviciute Rasa , Rybarczyk Yves , Alexandrino Katiuska , Bonilla-Bedoya Santiago , Mejia Danilo , Bastidas Marco , Diaz Valeria
Published: December 2021

Political and economic protests build-up due to the financial uncertainty and inequality spreading throughout the world. In 2019, Latin America took the main stage in a wave of protests. While the social side of protests is widely explored, the focus of this study is the evolution of gaseous urban air pollutants during and after one of these events. Changes in concentrations of NO2, CO, O3 and SO2 during and after the strike, were studied in Quito, Ecuador using two approaches: (i) inter-period observational analysis; and (ii) machine learning (ML) gradient boosting machine (GBM) developed business-as-usual (BAU) comparison to the observations. During the strike, both methods showed a large reduction in the concentrations of NO2 (31.5–32.36%) and CO (15.55–19.85%) and a slight reduction for O3 and SO2. The GBM approach showed an exclusive potential, especially for a lengthier period of predictions, to estimate strike impact on air quality even after the strike was over. This advocates for the use of machine learning techniques to estimate an extended effect of changes in human activities on urban gaseous pollution.
β-Cyclodextrin Inclusion Complexes of Budesonide with Enhanced Bioavailability for COPD Treatment
Authors: Michailidou Georgia , Papageorgiou George Z. , Bikiaris Dimitrios N.
Published: December 2021

Chronic obstructive pulmonary disease (COPD) is a life-threatening disease of the respiratory system, affecting many patients worldwide. Budesonide (BUD), a synthetic glucocorticosteroid applied for the treatment of COPD patients, is a hydrophobic compound with low bioavailability. The formation of inclusion complexes of hydrophobic compounds with β-cyclodextrin (CD) through the solvent evaporation technique is an appealing method for the amelioration of the compounds’ in vitro release behavior. In the present study, CD–BUD complexes were prepared through the solvent evaporation technique. The effect of the applied solvent was evaluated through FTIR, scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and in vitro release behavior measurements. It was found that the optimum complexes with the minimum degree of crystallinity and the optimum in vitro release behavior are prepared in the solvent ratio H2O/EtOH 80/20 v/v. In a further step, the formation of CD–BUD complexes containing different amounts of BUD was prepared. Through XRD measurements, the degree of crystallinity of the samples was calculated confirming the diminished crystallinity of BUD in CD complexes. The in vitro release of the samples showed the improved release behavior of BUD from the complexes in comparison to neat BUD while a direct correlation between the degree of crystallinity and in vitro release behavior was demonstrated.
Combining Parallel Computing and Biased Randomization for Solving the Team Orienteering Problem in Real-Time
Authors: Panadero Javier , Ammouriova Majsa , Juan Angel A. , Agustin Alba , Nogal Maria , Serrat Carles
Published: December 2021

In smart cities, unmanned aerial vehicles and self-driving vehicles are gaining increased concern. These vehicles might utilize ultra-reliable telecommunication systems, Internet-based technologies, and navigation satellite services to locate their customers and other team vehicles to plan their routes. Furthermore, the team of vehicles should serve their customers by specified due date efficiently. Coordination between the vehicles might be needed to be accomplished in real-time in exceptional cases, such as after a traffic accident or extreme weather conditions. This paper presents the planning of vehicle routes as a team orienteering problem. In addition, an ‘agile’ optimization algorithm is presented to plan these routes for drones and other autonomous vehicles. This algorithm combines an extremely fast biased-randomized heuristic and a parallel computing approach.
Effectiveness of Mouth Rinsing versus Ingesting Pickle Juice for Alleviating Electrically Induced Cramp in Physically Active Adults
Authors: Georgieva Julia , Brade Carly J. , Ducker Kagan J. , Davey Paul , Jacques Angela , Ohno Masato , Lavender Andrew P.
Published: December 2021

(1) Background: Stimulating oropharyngeal transient receptor potential (TRP) channels inhibits muscle cramping by triggering a supraspinal reflex to reduce α-motor neuron hyperexcitability. This study investigated whether the longer stimulation of the TRP channels via mouth rinsing with PJ is more effective than drinking PJ at inhibiting an electrically induced muscle cramp (EIMC). Both conditions were compared to the control (water). (2) Methods: The tibial nerves in 11 cramp-prone adults were percutaneously stimulated to elicit an EIMC of the flexor hallucis brevis in three trials that took place one week apart from each other. At cramp onset, the participants received mouth rinsing and expelling PJ (25 mL), ingesting PJ (1 mL∙kg−1 body-mass (BM)), or ingesting water (1 mL∙kg−1 BM). Cramp onset and offset were induced by electromyography, and the severity of discomfort was recorded using a visual analogue scale (VAS). (3) Results: The median time to cramp cessation as a percentage of water was 82.8 ± 14.63% and 68.6 ± 47.78% for PJ ingestion and PJ mouth rinsing, respectively. These results had large variability, and no statistically significant differences were observed. There were also no differences in perceived cramp discomfort between conditions, despite the hazard ratios for the time taken to reach VAS = 0, which was higher than water (control) for PJ ingestion (22%) and mouth rinsing (35%) (p = 0.66 and 0.51, respectively). (4) Conclusions: The data suggest no difference in cramp duration and perceived discomfort between PJ and water.
Fabrication of Large Area, Ordered Nanoporous Structures on Various Substrates for Potential Electro-Optic Applications
Authors: Jee Hongsub , Jeon Kiseok , Park Min-Joon , Lee Jaehyeong
Published: December 2021

Nanoporous structures have attracted great attention in electronics, sensor and storage devices, and photonics because of their large surface area, large volume to surface ratio, and potential for high-sensitivity sensor applications. Normally, electron or ion beam patterning can be used for nanopores fabrication by direct writing. However, direct writing is a rather expensive and time-consuming method due to its serial nature. Therefore, it may not translate to a preferred manufacturing process. In this research, a perfectly ordered large-area periodic pattern in an area of approximately 1 cm2 has been successfully fabricated on various substrates including glass, silicon, and polydimethylsiloxane, using a two-step process comprising visible light-based multibeam interference lithography and subsequent pattern transfer processes of reactive ion etching and nanomolding. Additionally, the multibeam interference lithography templated anodized aluminum oxide process has been described. Since the fabrication area in multibeam interference lithography can be extended by using a larger beam size, it is highly cost effective and manufacturable. Furthermore, although not described here, an electrodeposition process can be utilized as a pattern transfer process. This large-area perfectly ordered nanopore array will be very useful for high-density electronic memory and photonic bandgap and metamaterial applications.
A Novel Method for Field Measurement of Ankle Joint Stiffness in Hopping
Authors: Ghorbani Faal Sanubar , Shirzad Elham , Sharifnezhad Ali , Ashrostaghi Mojtaba , Naemi Roozbeh
Published: December 2021

Stiffness of ankle joint has been investigated in a wide range of biomechanical studies with a focus on the improvement of performance and reduction in the risk of injury. However, measuring ankle joint stiffness (AJS) using the existing conventional methodologies requires sophisticated equipment such as force plate and motion analyses systems. This study presents a novel method for measuring AJS during a hopping task with no force or motion measurement system. Also the validity of the proposed new method was investigated by comparing the results against those obtained using conventional method in which motion capture and force plate data are used. Twelve participants performed the controlled hopping task at 2.2 Hz, on a force platform, and six high speed cameras recorded the movement. To calculate the AJS in both methods, the lower extremity was modeled as a three linked rigid segments robot with three joints. In the new method, the contact time and flight time were used to calculate ground reaction force, and inverse kinematic and inverse dynamic approaches were used to calculate the ankle kinematic and kinetic. The AJS calculated using the new method was compared against the results of conventional method as the reference. The calculated AJS using this new method (506.47 ± 177.84 N·m/rad) showed a significant correlation (r = 0.752) with the AJS calculated using conventional method (642.39 ± 185.96 N·m/rad). The validation test showed a mean difference of −24.76% using Bland–Altman plot. The presented method can be used as a valid, and low-cost tool for assessing AJS in the field in low resource settings.
Research in Sustainable Energy Systems at the Department of Management and Engineering during the First 15 Years of 2000
Authors: Bagarella Giacomo , Busato Filippo , Castellotti Francesco , D’Ascanio Andrea , Lazzarin Renato , Minchio Fabio , Nardotto Daniele , Noro Marco , Zamboni Lorenzo
Published: December 2021

At the Department of Management and Engineering (DTG) of the University of Padova (Italy), the research team led by Prof. Renato Lazzarin, formed by the authors, worked during the first fifteen years of the millennium on different topics focused on sustainable technologies for energy production and utilization in buildings. Both experimental and theoretical/modeling studies were carried out, all sharing the evaluation of energy performance and sustainability: From the life cycle assessment and life cycle cost of building insulation materials in Italy, to the measurement of energy performance of a green roof, to the experimental measurement of different photovoltaic/thermal modules, to the development of a simulation software for direct and indirect evaporative cooling techniques, to the evaluation of different energy savings techniques for refrigeration and air conditioning in supermarkets, to an extensive analysis of the urban heat island effect in the city of Padova. The paper summarizes the main theoretical and experimental approaches, providing the methods adopted in each line of research. The main results of the studies conducted during the fifteen-year period are described and commented on, some of which were a well-established reference for the following literature.
Intelligent Robotic Palletizer System
Authors: Lee Jeng-Dao , Chang Chen-Huan , Cheng En-Shuo , Kuo Chia-Chen , Hsieh Chia-Ying
Published: December 2021

In the global wave of automation, logistics and manufacturing are indispensable and important industries. Among them, the related automatic warehousing system is even more urgently needed. There are quite a few cases of using robotic arms in the current industry cargo stacking operations. Traditional operations require engineers to plan the stacking path for the robotic arm. If the size of the object changes, it will take extra time to re-plan the work path. Therefore, in recent years, quite a lot of automatic palletizing software has been developed; however, none of it has a detection mechanism for stacking correctness and personnel safety. As a result, in this research, an intelligent robotic palletizer system is developed based on a self-developed symmetrical algorithm to stack the goods in a staggered arrangement to ensure the overall structure. Innovatively, it is proposed to check the arrangement status and warnings during the visual stack inspection to ensure the correctness of the stacking process. Besides, an AI algorithm is imported to ensure that personnel cannot enter the set dangerous area during the work of the robotic arm to improve safety during stacking. In addition to uploading the relevant data to the cloud database in real time, the stacking process combined database and vision system also provide users with real-time monitoring of system information.
Comparative Assessment of Hierarchical Clustering Methods for Grouping in Singular Spectrum Analysis
Authors: Hassani Hossein , Kalantari Mahdi , Beneki Christina
Published: December 2021

Singular spectrum analysis (SSA) is a popular filtering and forecasting method that is used in a wide range of fields such as time series analysis and signal processing. A commonly used approach to identify the meaningful components of a time series in the grouping step of SSA is the utilization of the visual information of eigentriples. Another supplementary approach is that of employing an algorithm that performs clustering based on the dissimilarity matrix defined by weighted correlation between the components of a time series. The SSA literature search revealed that no investigation has compared the various clustering methods. The aim of this paper was to compare the effectiveness of different hierarchical clustering linkages to identify the appropriate groups in the grouping step of SSA. The comparison was performed based on the corrected Rand (CR) index as a comparison criterion that utilizes various simulated series. It was also demonstrated via two real-world time series how one can proceed, step-by-step, to conduct grouping in SSA using a hierarchical clustering method. This paper is supplemented with accompanying R codes.
Aligned Magnetic Field and Radiation Effects on Biomagnetic Fluid over an Unsteady Stretching Sheet with Various Slip Conditions
Authors: Gomes Anik , Alam Jahangir , Murtaza Ghulam , Sultana Tahmina , Tzirtzilakis Efstratios E. , Ferdows Mohammad
Published: December 2021

The aim of the present study is to analyze the effects of aligned magnetic field and radiation on biomagnetic fluid flow and heat transfer over an unsteady stretching sheet with various slip conditions. The magnetic field is assumed to be sufficiently strong enough to saturate the ferrofluid, and the variation of magnetization is approximated by a linear function of temperature difference. The governing boundary layer equations with boundary conditions are simplified by suitable transformations. Numerical solution is obtained by using the bvp4c function technique in MATLAB software. The numerical results are derived for the velocity, temperature, the skin friction coefficient, and the rate of heat transfer. The evaluated results are compared with analytical study documented in scientific literature. The present investigation illustrates that the fluid velocity is decreased with the increasing values of radiation parameter, magnetic parameter, and ferromagnetic interaction parameter, though is increased as the Prandtl number, Grashof number, permeable parameter and thermal slip parameter are increased. In this investigation, the suction/injection parameter had a good impact on the skin friction coefficient and the rate of heat transfer.
Clustering Algorithm to Measure Student Assessment Accuracy: A Double Study
Authors: Sobral Sónia Rolland , de Oliveira Catarina Félix
Published: December 2021

Self-assessment is one of the strategies used in active teaching to engage students in the entire learning process, in the form of self-regulated academic learning. This study aims to assess the possibility of including self-evaluation in the student’s final grade, not just as a self-assessment that allows students to predict the grade obtained but also as something to weigh on the final grade. Two different curricular units are used, both from the first year of graduation, one from the international relations course (N = 29) and the other from the computer science and computer engineering courses (N = 50). Students were asked to self-assess at each of the two evaluation moments of each unit, after submitting their work/test and after knowing the correct answers. This study uses statistical analysis as well as a clustering algorithm (K-means) on the data to try to gain deeper knowledge and visual insights into the data and the patterns among them. It was verified that there are no differences between the obtained grade and the thought grade by gender and age variables, but a direct correlation was found between the thought grade averages and the grade level. The difference is less accentuated at the second moment of evaluation—which suggests that an improvement in the self-assessment skill occurs from the first to the second evaluation moment.
Consumer Perception of Milk and Plant-Based Alternatives Added to Coffee
Authors: Gorman Mackenzie , Knowles Sophie , Falkeisen Anika , Barker Sophie , Moss Rachael , McSweeney Matthew B.
Published: December 2021

Consumers have begun to use plant-based alternatives (PBAs) in their coffee instead of dairy products. PBAs can include soy milk, rice milk, coconut milk, almond milk, oat milk, and hemp milk. The objective of this study was to investigate consumer acceptability and sensory perception of coffee with added dairy milk and added oat, soy, and almond PBAs. Consumers (n = 116) that frequently add milk to their coffee (n= 58) and consumers that usually use PBAs (n = 58) were recruited to participate in the study. They evaluated four different coffee samples with the addition of dairy milk as well as soy, almond, and oat PBAs. Overall, the consumers liking increased when they perceived sweetness in their coffee. The plant consumers (usually added PBAs to their coffee) liked the milk addition significantly less than the dairy consumers (usually added dairy to their coffee). In addition, the plant consumers were able to differentiate between the almond and soy PBAs, while the dairy consumers grouped them together. More studies need to be completed to investigate a wider range of PBAs, dairy products, and varieties of coffee.
Can We Identify Subgroups of Patients with Chronic Low Back Pain Based on Motor Variability? A Systematic Scoping Review
Authors: Dijk Lars , Leving Marika T. , Reneman Michiel F. , Lamoth Claudine J. C.
Published: December 2021

The identification of homogeneous subgroups of patients with chronic low back pain (CLBP), based on distinct patterns of motor control, could support the tailoring of therapy and improve the effectiveness of rehabilitation. The purpose of this review was (1) to assess if there are differences in motor variability between patients with CLBP and pain-free controls, as well as inter-individually among patients with CLBP, during the performance of functional tasks; and (2) to examine the relationship between motor variability and CLBP across time. A literature search was conducted on the electronic databases Pubmed, EMBASE, and Web of Science, including papers published any time up to September 2021. Two reviewers independently screened the search results, assessed the risk of bias, and extracted the data. Twenty-two cross-sectional and three longitudinal studies investigating motor variability during functional tasks were examined. There are differences in motor variability between patients with CLBP and pain-free controls during the performance of functional tasks, albeit with discrepant results between tasks and among studies. The longitudinal studies revealed the persistence of motor control changes following interventions, but the relationship between changes in motor variability and reduction in pain intensity was inconclusive. Based on the reviewed literature, no stratification of homogeneous subgroups into distinct patterns of motor variability in the CLBP population could be made. Studies diverged in methodologies and theoretical frameworks and in metrics used to assess and interpret motor variability. In the future, more large-sample studies, including longitudinal designs, are needed, with standardized metrics that quantify motor variability to fill the identified evidence gaps.
Towards Personalized Antioxidant Use in Female Infertility: Need for More Molecular and Clinical Studies
Authors: Tesarik Jan
Published: December 2021

Treatment with antioxidants is increasingly used to slow down aging processes in different organs of the human body, including those implicated in female fertility. There is a plethora of different natural, synthetic or semi-synthetic medicines available on the market; most of them can be purchased without medical prescription. Even though the use of antioxidants, even under conditions of auto-medication, was shown to improve many functions related to female infertility related to oxidative stress, the lack of medical control and supervision can lead to an overmedication resulting in an opposite extreme, reductive stress, which can be counterproductive with regard to reproductive function and produce various adverse health effects in general. This paper reviews the current knowledge relative to the effects of different antioxidants on female reproductive function. The persisting gaps in this knowledge are also highlighted, and the need for medical supervision and personalization of antioxidant prescription is underscored.
Epigenetic Dysregulation of Trophoblastic Gene Expression in Gestational Trophoblastic Disease
Authors: Szabolcsi Zoltan , Demeter Amanda , Kiraly Peter , Balogh Andrea , Wilson Melissa L. , King Jennifer R. , Hetey Szabolcs , Gelencser Zsolt , Matsuo Koji , Hargitai Beata , Mhawech-Fauceglia Paulette , Hupuczi Petronella , Szilagyi Andras , Papp Zoltan , Roman Lynda D. , Cortessis Victoria K. , Than Nandor Gabor
Published: December 2021

Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks and consequent transcriptomic changes. Here, we analyzed genome-wide DNA methylation and transcriptome data to reveal the epigenetic basis of disease pathways that may lead to benign or malignant GTDs. RNA-Seq, mRNA microarray, and Human Methylation 450 BeadChip data from complete moles and choriocarcinoma cells were bioinformatically analyzed. Paraffin-embedded tissues from complete moles and control placentas were used for tissue microarray construction, DNMT3B immunostaining and immunoscoring. We found that DNA methylation increases with disease severity in GTDs. Differentially expressed genes are mainly upregulated in moles while predominantly downregulated in choriocarcinoma. DNA methylation principally influences the gene expression of villous trophoblast differentiation-related or predominantly placenta-expressed genes in moles and choriocarcinoma cells. Affected genes in these subsets shared focal adhesion and actin cytoskeleton pathways in moles and choriocarcinoma. In moles, cell cycle and differentiation regulatory pathways, essential for trophoblast/placental development, were enriched. In choriocarcinoma cells, hormone biosynthetic, extracellular matrix-related, hypoxic gene regulatory, and differentiation-related signaling pathways were enriched. In moles, we found slight upregulation of DNMT3B protein, a developmentally important de novo DNA methylase, which is strongly overexpressed in choriocarcinoma cells that may partly be responsible for the large DNA methylation differences. Our findings provide new insights into the shared and disparate molecular pathways of disease in GTDs and may help in designing new diagnostic and therapeutic tools.
Analytical Techniques for the Characterization of Bioactive Coatings for Orthopaedic Implants
Authors: Kravanja Katja Andrina , Finšgar Matjaž
Published: December 2021

The development of bioactive coatings for orthopedic implants has been of great interest in recent years in order to achieve both early- and long-term osseointegration. Numerous bioactive materials have been investigated for this purpose, along with loading coatings with therapeutic agents (active compounds) that are released into the surrounding media in a controlled manner after surgery. This review initially focuses on the importance and usefulness of characterization techniques for bioactive coatings, allowing the detailed evaluation of coating properties and further improvements. Various advanced analytical techniques that have been used to characterize the structure, interactions, and morphology of the designed bioactive coatings are comprehensively described by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), 3D tomography, quartz crystal microbalance (QCM), coating adhesion, and contact angle (CA) measurements. Secondly, the design of controlled-release systems, the determination of drug release kinetics, and recent advances in drug release from bioactive coatings are addressed as the evaluation thereof is crucial for improving the synthesis parameters in designing optimal bioactive coatings.
Antimicrobial and Prebiotic Activity of Lactoferrin in the Female Reproductive Tract: A Comprehensive Review
Authors: Artym Jolanta , Zimecki Michał
Published: December 2021

Women’s intimate health depends on several factors, such as age, diet, coexisting metabolic disorders, hormonal equilibrium, sexual activity, drug intake, contraception, surgery, and personal hygiene. These factors may affect the homeostasis of the internal environment of the genital tract: the vulva, vagina and cervix. This equilibrium is dependent on strict and complex mutual interactions between epithelial cells, immunocompetent cells and microorganisms residing in this environment. The microbiota of the genital tract in healthy women is dominated by several species of symbiotic bacteria of the Lactobacillus genus. The bacteria inhibit the growth of pathogenic microorganisms and inflammatory processes by virtue of direct and multidirectional antimicrobial action and, indirectly, by the modulation of immune system activity. For the homeostasis of the genital tract ecosystem, antimicrobial and anti-inflammatory peptides, as well as proteins secreted by mucus cells into the cervicovaginal fluid, have a fundamental significance. Of these, a multifunctional protein known as lactoferrin (LF) is one of the most important since it bridges innate and acquired immunity. Among its numerous properties, particular attention should be paid to prebiotic activity, i.e., exerting a beneficial action on symbiotic microbiota of the gastrointestinal and genital tract. Such activity of LF is associated with the inhibition of bacterial and fungal infections in the genital tract and their consequences, such as endometritis, pelvic inflammation, urinary tract infections, miscarriage, premature delivery, and infection of the fetus and newborns. The aim of this article is to review the results of laboratory as well as clinical trials, confirming the prebiotic action of LF on the microbiota of the lower genital tract.
An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab
Authors: Anesi Andrea , Di Minno Alessandro , Calcaterra Ilenia , Cavalca Viviana , Tripaldella Maria , Porro Benedetta , Di Minno Matteo Nicola Dario
Published: December 2021

Rationale: Familial hypercholesterolemia (FH) is caused by mutations in genes involved in low-density lipoprotein cholesterol (LDL-C) metabolism, including those for pro-protein convertase subtilisin/kexin type 9 (PCSK-9). The effect of PCSK-9 inhibition on the plasma lipidome has been poorly explored. Objective: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, the plasma lipidome of FH subjects before and at different time intervals during treatment with the PCSK-9 inhibitor Evolocumab was explored. Methods and Results: In 25 FH subjects, heterozygotes or compound heterozygotes for different LDL receptor mutations, untargeted lipidomic revealed significant reductions in 26 lipid classes belonging to phosphatidylcholine (PC), sphingomyelin (SM), ceramide (CER), cholesteryl ester (CE), triacylglycerol (TG) and phosphatidylinositol (PI). Lipid changes were graded between baseline and 4- and 12-week treatment. At 12-week treatment, five polyunsaturated diacyl PC, accounting for 38.6 to 49.2% of total PC at baseline; two ether/vinyl ether forms; seven SM; five CER and glucosyl/galactosyl-ceramide (HEX-CER) were reduced, as was the unsaturation index of HEX-CER and lactosyl—CER (LAC-CER). Although non quantitative modifications were observed in phosphatidylethanolamine (PE) during treatment with Evolocumab, shorter and more saturated fatty acyl chains were documented. Conclusions: Depletion of several phospholipid classes occurs in plasma of FH patients during treatment with the PCSK-9 inhibitor Evolocumab. The mechanism underlying these changes likely involves the de novo synthesis of SM and CER through the activation of the key enzyme sphingomyelin synthase by oxidized LDL and argues for a multifaceted system leading to vascular improvement in users of PCSK-9 inhibitors.
Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path
Authors: Iessi Elisabetta , Vona Rosa , Cittadini Camilla , Matarrese Paola
Published: December 2021

In cancer cells, metabolic adaptations are often observed in terms of nutrient absorption, biosynthesis of macromolecules, and production of energy necessary to meet the needs of the tumor cell such as uncontrolled proliferation, dissemination, and acquisition of resistance to death processes induced by both unfavorable environmental conditions and therapeutic drugs. Many oncogenes and tumor suppressor genes have a significant effect on cellular metabolism, as there is a close relationship between the pathways activated by these genes and the various metabolic options. The metabolic adaptations observed in cancer cells not only promote their proliferation and invasion, but also their survival by inducing intrinsic and acquired resistance to various anticancer agents and to various forms of cell death, such as apoptosis, necroptosis, autophagy, and ferroptosis. In this review we analyze the main metabolic differences between cancer and non-cancer cells and how these can affect the various cell death pathways, effectively determining the susceptibility of cancer cells to therapy-induced death. Targeting the metabolic peculiarities of cancer could represent in the near future an innovative therapeutic strategy for the treatment of those tumors whose metabolic characteristics are known.
Azadirachtin Attenuates Lipopolysaccharide-Induced ROS Production, DNA Damage, and Apoptosis by Regulating JNK/Akt and AMPK/mTOR-Dependent Pathways in Rin-5F Pancreatic Beta Cells
Authors: John Annie , Raza Haider
Published: December 2021

Pancreatic inflammation and the resulting cellular responses have been implicated in pancreatitis, diabetes, and pancreatic cancer. Inflammatory responses due to the bacterial endotoxin, lipopolysaccharide (LPS), have been demonstrated to alter cellular metabolism, autophagy, apoptosis, and cell proliferation in different cell populations, and hence increases the risks for organ toxicity including cancer. The exact molecular mechanism is however not clear. In the present study, we investigated the role and mechanism of an antioxidant, azadirachtin (AZD), a limonoid extracted from the neem tree (Azadirachta indica), against LPS-induced oxidative stress in the pancreatic β-cell line, Rin-5F. We demonstrated that cells treated with LPS (1 µg/mL for 24 h) showed increased reactive oxygen species (ROS) production, DNA damage, cell cycle arrest, and apoptosis. Our results also showed that LPS induced alterations in the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways, suppressing autophagy and augmenting apoptosis. Treatment with Azadirachtin (25 µM for 24 h), on the other hand, rendered some degree of protection to the pancreatic cells from apoptosis by inducing the autophagy signals required for cell survival. These results may have significance in elucidating the mechanisms of pancreatic β-cell survival and death by balancing the molecular communication between autophagy and apoptosis under inflammatory and pathological conditions.
Altered Metabolic Profiles of the Plasma of Patients with Amyotrophic Lateral Sclerosis
Authors: Chang Kuo-Hsuan , Lin Chia-Ni , Chen Chiung-Mei , Lyu Rong-Kuo , Chu Chun-Che , Liao Ming-Feng , Huang Chin-Chang , Chang Hong-Shiu , Ro Long-Sun , Kuo Hung-Chou
Published: December 2021

Currently, there is no objective biomarker to indicate disease progression and monitor therapeutic effects for amyotrophic lateral sclerosis (ALS). This study aimed to identify plasma biomarkers for ALS using a targeted metabolomics approach. Plasma levels of 185 metabolites in 36 ALS patients and 36 age- and sex-matched normal controls (NCs) were quantified using an assay combining liquid chromatography with tandem mass spectrometry and direct flow injection. Identified candidates were correlated with the scores of the revised ALS Functional Rating Scale (ALSFRS-r). Support vector machine (SVM) learning applied to selected metabolites was used to differentiate ALS and NC subjects. Forty-four metabolites differed significantly between ALS and NC subjects. Significant correlations with ALSFRS-r score were seen in 23 metabolites. Six of them showing potential to distinguish ALS from NC—asymmetric dimethylarginine (area under the curve (AUC): 0.829), creatinine (AUC: 0.803), methionine (AUC: 0.767), PC-acyl-alkyl C34:2 (AUC: 0.808), C34:2 (AUC: 0.763), and PC-acyl-acyl C42:2 (AUC: 0.751)—were selected for machine learning. The SVM algorithm using selected metabolites achieved good performance, with an AUC of 0.945. In conclusion, our findings indicate that a panel of metabolites were correlated with disease severity of ALS, which could be potential biomarkers for monitoring ALS progression and therapeutic effects.
Neutrophils and Platelets: Immune Soldiers Fighting Together in Stroke Pathophysiology
Authors: Ansari Junaid , Gavins Felicity N. E.
Published: December 2021

Neutrophils and platelets exhibit a diverse repertoire of functions in thromboinflammatory conditions such as stroke. Most cerebral ischemic events result from longstanding chronic inflammation secondary to underlying pathogenic conditions, e.g., hypertension, diabetes mellitus, obstructive sleep apnea, coronary artery disease, atrial fibrillation, morbid obesity, dyslipidemia, and sickle cell disease. Neutrophils can enable, as well as resolve, cerebrovascular inflammation via many effector functions including neutrophil extracellular traps, serine proteases and reactive oxygen species, and pro-resolving endogenous molecules such as Annexin A1. Like neutrophils, platelets also engage in pro- as well as anti-inflammatory roles in regulating cerebrovascular inflammation. These anucleated cells are at the core of stroke pathogenesis and can trigger an ischemic event via adherence to the hypoxic cerebral endothelial cells culminating in aggregation and clot formation. In this article, we review and highlight the evolving role of neutrophils and platelets in ischemic stroke and discuss ongoing preclinical and clinical strategies that may produce viable therapeutics for prevention and management of stroke.
Peripheral Infection after Traumatic Brain Injury Augments Excitability in the Perilesional Cortex and Dentate Gyrus
Authors: Wang Ying , Andrade Pedro , Pitkänen Asla
Published: December 2021

Peripheral infections occur in up to 28% of patients with traumatic brain injury (TBI), which is a major etiology for structural epilepsies. We hypothesized that infection occurring after TBI acts as a “second hit” and facilitates post-traumatic epileptogenesis. Adult male Sprague–Dawley rats were subjected to lateral fluid-percussion injury or sham-operation. At 8 weeks post-injury, rats were treated with lipopolysaccharide (LPS, 5 mg/kg) to mimic Gram-negative peripheral infection. T2-weighted magnetic resonance imaging was used to detect the cortical lesion type (small focal inflammatory [TBIFI] vs. large cavity-forming [TBICF]). Spontaneous seizures were detected with video-electroencephalography, and seizure susceptibility was determined by the pentylenetetrazole (PTZ) test. Post-PTZ neuronal activation was assessed using c-Fos immunohistochemistry. LPS treatment increased the percentage of rats with PTZ-induced seizures among animals with TBIFI lesions (p < 0.05). It also increased the cumulative duration of PTZ-induced seizures (p < 0.01), particularly in the TBIFI group (p < 0.05). The number of c-Fos immunopositive cells was higher in the perilesional cortex of injured animals compared with sham-operated animals (p < 0.05), particularly in the TBI-LPS group (p < 0.05). LPS treatment increased the percentage of injured rats with bilateral c-Fos staining in the dentate gyrus (p < 0.05), particularly in the TBIFI group (p < 0.05). Our findings demonstrate that peripheral infection after TBI increases PTZ-induced seizure susceptibility and neuronal activation in the perilesional cortex and bilaterally in the dentate gyrus, particularly in animals with prolonged perilesional T2 enhancement. Our data suggest that treatment of infections and reduction of post-injury neuro-inflammation are important components of the treatment regimen aiming at preventing epileptogenesis after TBI.
The Effect of a Multimodal Occupational Therapy Program with Cognition-Oriented Approach on Cognitive Function and Activities of Daily Living in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Ham Min-Joo , Kim Sujin , Jo Ye-Ji , Park Chisoo , Nam Yunkwon , Yoo Doo-Han , Moon Minho
Published: December 2021

Non-pharmacological intervention, which includes a broad range of approaches, may be an alternative treatment for Alzheimer’s disease (AD). Multimodal non-pharmacological intervention alleviates cognitive dysfunction and the impairment of activities of daily living (ADL) in AD patients. However, it is still unclear which combination of non-pharmacological interventions is preferred. We selected a non-pharmacological intervention combined with occupational therapy (OT). We investigated the effect of a multimodal OT program with cognition-oriented approach on cognitive dysfunction and impairments of ADL in patients with AD. Four electronic databases were searched from January 2000 to August 2020. The studies were assessed for heterogeneity, quality assessment, effect size and publication bias. A total of seven randomized controlled trials examining multimodal OT programs with cognition-oriented approach in AD patients were included in the meta-analysis. Compared with the control group, the multimodal OT program with cognition-oriented approach group was statistically beneficial for cognitive dysfunction (95% CI: 0.25–0.91). However, compared with the control group, the multimodal OT program with cognition-oriented approach group tended to be beneficial for basic ADL, and instrumental ADL. These results suggest that the multimodal OT program with cognition-oriented approach might be the optimal multimodal non-pharmacological intervention for improving cognitive dysfunction in AD patients.
T-Cell Receptor Repertoire Analysis with Computational Tools—An Immunologist’s Perspective
Authors: Arunkumar Mahima , Zielinski Christina E.
Published: December 2021

Over the last few years, there has been a rapid expansion in the application of information technology to biological data. Particularly the field of immunology has seen great strides in recent years. The development of next-generation sequencing (NGS) and single-cell technologies also brought forth a revolution in the characterization of immune repertoires. T-cell receptor (TCR) repertoires carry comprehensive information on the history of an individual’s antigen exposure. They serve as correlates of host protection and tolerance, as well as biomarkers of immunological perturbation by natural infections, vaccines or immunotherapies. Their interrogation yields large amounts of data. This requires a suite of highly sophisticated bioinformatics tools to leverage the meaning and complexity of the large datasets. Many different tools and methods, specifically designed for various aspects of immunological research, have recently emerged. Thus, researchers are now confronted with the issue of having to choose the right kind of approach to analyze, visualize and ultimately solve their task at hand. In order to help immunologists to choose from the vastness of available tools for their data analysis, this review addresses and compares commonly used bioinformatics tools for TCR repertoire analysis and illustrates the advantages and limitations of these tools from an immunologist’s perspective.
Electrodes for Paracetamol Sensing Modified with Bismuth Oxide and Oxynitrate Heterostructures: An Experimental and Computational Study
Authors: Franceschini Filippo , Bartoli Mattia , Tagliaferro Alberto , Carrara Sandro
Published: December 2021

In this work, novel platforms for paracetamol sensing were developed by the deposition of Bi2O3, Bi5O7NO3 and their heterostructures onto screen-printed carbon-paste electrodes. An easy and scalable solid state synthesis route was employed, and by setting the calcination temperatures at 500 °C and 525 °C we induced the formation of heterostructures of Bi2O3 and Bi5O7NO3. Cyclic voltammetry measurements highlighted that the heterostructure produced at 500 °C provided a significant enhancement in performance compared to the monophases of Bi2O and Bi5O7NO3, respectively. That heterostructure showed a mean peak-to-peak separation Ep of 411 mV and a sensitivity increment of up to 70% compared to bare electrodes. A computational study was also performed in order to evaluate the geometrical and kinetic parameters of representative clusters of bismuth oxide and subnitrate when they interact with paracetamol.
Recent Progress in the Correlative Structured Illumination Microscopy
Authors: Wang Meiting , Chen Jiajie , Wang Lei , Zheng Xiaomin , Zhou Jie , Zeng Youjun , Qu Junle , Shao Yonghong , Gao Bruce Zhi
Published: December 2021

The super-resolution imaging technique of structured illumination microscopy (SIM) enables the mixing of high-frequency information into the optical transmission domain via light-source modulation, thus breaking the optical diffraction limit. Correlative SIM, which combines other techniques with SIM, offers more versatility or higher imaging resolution than traditional SIM. In this review, we first briefly introduce the imaging mechanism and development trends of conventional SIM. Then, the principles and recent developments of correlative SIM techniques are reviewed. Finally, the future development directions of SIM and its correlative microscopies are presented.