bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-Order Symmetries of a Time-Fractional Anomalous Diffusion Equation
Authors: Gazizov Rafail K. , Lukashchuk Stanislav Yu.
Published: January 2021

Higher-order symmetries are constructed for a linear anomalous diffusion equation with the Riemann–Liouville time-fractional derivative of order α∈(0,1)∪(1,2). It is proved that the equation in question has infinite sequences of nontrivial higher-order symmetries that are generated by two local recursion operators. It is also shown that some of the obtained higher-order symmetries can be rewritten as fractional-order symmetries, and corresponding fractional-order recursion operators are presented. The proposed approach for finding higher-order symmetries is applicable for a wide class of linear fractional differential equations.
Properdin Is a Modulator of Tumour Immunity in a Syngeneic Mouse Melanoma Model
Authors: Al-Rayahi Izzat A. M. , Machado Lee R. , Stover Cordula M.
Published: January 2021

Background and Objectives: Tumours are often low immunogenic. The role of complement, an innate immune defence system, in tumour control has begun to be elucidated, but findings are conflicting. A role for properdin, an amplifier of complement activation, in tumour control has recently been implicated. Materials and Methods: Properdin-deficient and congenic wildtype mice were injected subcutaneously with B16F10 melanoma cells. Tumour mass and chemokine profile were assessed. The frequencies of CD45+CD11b+ Gr-1+ cells were determined from tumours and spleens, and CD206+ F4/80+ cells were evaluated in spleens. Sera were analysed for C5a, sC5b-9, and CCL2. Results: Whilst there was no difference in tumour growth at study endpoint, properdin-deficient mice had significantly fewer myeloid-derived suppressor cells (MDSCs) in their tumours and spleens. Splenic M2 type macrophages and serum levels of C5a, sC5b-9, and CCL2 were decreased in properdin-deficient compared to wildtype mice. Conclusions: The presence of intact complement amplification sustains an environment that lessens potential anti-tumour responses.
Acknowledgment to Reviewers of Medicina in 2020
Authors:   Medicina Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Medicina maintains its standards for the high quality of its published papers [...]
The Relationship between the Timing of Sugammadex Administration and the Upper Airway Obstruction during Awakening from Anesthesia: A Retrospective Study
Authors: Kang Eunsu , Lee Byeong Cheol , Park Jae Hong , Lee Sang Eun , Kim Se Hun , Oh Daeseok , Choi Dae Yun , Ko Myoung Jin
Published: January 2021

Background and Objectives: The harmonization of recovery of consciousness and muscular function is important in emergence from anesthesia. Even if muscular function is recovered, tracheal extubation without adequate recovery of consciousness may increase the risk of respiratory complications. In particular, upper airway obstruction is one of the common respiratory complications and can sometimes be fatal. However, the association between the timing of sugammadex administration and the upper airway obstruction that can occur during awakening from anesthesia has rarely been studied. Materials and Methods: The medical records of 456 patients who had surgery under general endotracheal anesthesia (GETA) at the Haeundae Paik Hospital between October 2017 and July 2018 and who received intravenous sugammadex to reverse rocuronium-induced neuromuscular blockade were analyzed. The correlations between bispectral index (BIS) and minimum alveolar concentration (MAC) at the time of sugammadex administration, the incidence of complications, and the time to tracheal extubation were analyzed to investigate how different timings of sugammadex administration affected upper airway obstruction after tracheal extubation. Conclusions: The effect of BIS and the duration from anesthetic discontinuation to sugammadex administration on upper airway obstruction was not statistically significant. However, the odds ratio of complication rates with MAC < 0.3 compared with MAC ≥ 0.3 was 0.40 (95% confidence interval 0.20 to 0.81, p = 0.011), showing a statistically significant increase in risk with MAC ≥ 0.3 for upper airway obstruction.
Recent Advances and Implication of Bioengineered Nanomaterials in Cancer Theranostics
Authors: Rai Ayushi , Noor Saba , Ahmad Syed Ishraque , Alajmi Mohamed F. , Hussain Afzal , Abbas Hashim , Hasan Gulam Mustafa
Published: January 2021

Cancer is one of the most common causes of death and affects millions of lives every year. In addition to non-infectious carcinogens, infectious agents contribute significantly to increased incidence of several cancers. Several therapeutic techniques have been used for the treatment of such cancers. Recently, nanotechnology has emerged to advance the diagnosis, imaging, and therapeutics of various cancer types. Nanomaterials have multiple advantages over other materials due to their small size and high surface area, which allow retention and controlled drug release to improve the anti-cancer property. Most cancer therapies have been known to damage healthy cells due to poor specificity, which can be avoided by using nanosized particles. Nanomaterials can be combined with various types of biomaterials to make it less toxic and improve its biocompatibility. Based on these properties, several nanomaterials have been developed which possess excellent anti-cancer efficacy potential and improved diagnosis. This review presents the latest update on novel nanomaterials used to improve the diagnostic and therapeutic of pathogen-associated and non-pathogenic cancers. We further highlighted mechanistic insights into their mode of action, improved features, and limitations.
Quantitative Imaging and Radiomics in Multiple Myeloma: A Potential Opportunity?
Authors: Tagliafico Alberto Stefano , Dominietto Alida , Belgioia Liliana , Campi Cristina , Schenone Daniela , Piana Michele
Published: January 2021

Multiple Myeloma (MM) is the second most common type of hematological disease and, although it is rare among patients under 40 years of age, its incidence rises in elderly subjects. MM manifestations are usually identified through hyperCalcemia, Renal failure, Anaemia, and lytic Bone lesions (CRAB). In particular, the extent of the bone disease is negatively related to a decreased quality of life in patients and, in general, bone disease in MM increases both morbidity and mortality. The detection of lytic bone lesions on imaging, especially computerized tomography (CT) and Magnetic Resonance Imaging (MRI), is becoming crucial from the clinical viewpoint to separate asymptomatic from symptomatic MM patients and the detection of focal lytic lesions in these imaging data is becoming relevant even when no clinical symptoms are present. Therefore, radiology is pivotal in the staging and accurate management of patients with MM even in early phases of the disease. In this review, we describe the opportunities offered by quantitative imaging and radiomics in multiple myeloma. At the present time there is still high variability in the choice between various imaging methods to study MM patients and high variability in image interpretation with suboptimal agreement among readers even in tertiary centers. Therefore, the potential of medical imaging for patients affected by MM is still to be completely unveiled. In the coming years, new insights to study MM with medical imaging will derive from artificial intelligence (AI) and radiomics usage in different bone lesions and from the wide implementations of quantitative methods to report CT and MRI. Eventually, medical imaging data can be integrated with the patient’s outcomes with the purpose of finding radiological biomarkers for predicting the prognostic flow and therapeutic response of the disease.
Taï Forest Virus Does Not Cause Lethal Disease in Ferrets
Authors: Schiffman Zachary , Yan Feihu , He Shihua , Tierney Kevin , Zhu Wenjun , Emeterio Karla , Zhang Huajun , Banadyga Logan , Qiu Xiangguo
Published: January 2021

Filoviruses are zoonotic, negative-sense RNA viruses, most of which are capable of causing severe disease in humans and nonhuman primates, often with high case fatality rates. Among these viruses, those belonging to the Ebolavirus genus—particularly Ebola virus, Sudan virus, and Bundibugyo virus—represent some of the most pathogenic to humans. Taï Forest virus (TAFV) is thought to be among the least pathogenic ebolaviruses; however, only a single non-fatal case has been documented in humans, in 1994. With the recent success of the ferret as a lethal model for a number of ebolaviruses, we set out to evaluate its suitability as a model for TAFV. Our results demonstrate that, unlike other ebolaviruses, TAFV infection in ferrets does not result in lethal disease. None of the intramuscularly inoculated animals demonstrated any overt signs of disease, whereas the intranasally inoculated animals exhibited mild to moderate weight loss during the early stage of infection but recovered quickly. Low levels of viral RNA were detected in the blood and tissues of several animals, particularly the intranasally inoculated animals, and all animals mounted a humoral immune response, with high titers of GP-specific IgG detectable as early as 14 days post-infection. These data provide additional insight into the pathogenesis of TAFV.
Mycotoxins, Pesticide Residues, and Heavy Metals Analysis of Croatian Cereals
Authors: Kovač Marija , Bulaić Mateja , Jakovljević Jasna , Nevistić Ante , Rot Tomislav , Kovač Tihomir , Dodlek Šarkanj Ivana , Šarkanj Bojan
Published: January 2021

Cereals are still one of the most important food and feed sources, thus determining cereal’s safety, i.e., compliance with legislation, is extremely important. As systematic investigations of nowadays unavoidable secondary fungal metabolites and other common legally regulated contaminants occurrence in Croatian cereals are still lacking, this research aims to monitor the contamination levels of nation-wide crops by mycotoxins, pesticide residues, and heavy metals by employing UHPLC-MS/MS, GC-MS/MS, and atomic absorption spectrometer (AAS) validated analytical methods. The most common secondary fungal metabolites were found to be Fusarium mycotoxins, with DON being the most occurring present in 73.7% of the samples. At least one pesticide residue was found in 331.8% of the samples, and Hg and Cd were the most occurring heavy metals. A total of 8.5% of the samples was non-compliant to the European Union (EU) legislation for food regarding the found mycotoxins concentrations, 4.5% regarding pesticide residues and none regarding heavy metals. The unusual presence of certain pesticide residue and heavy metal indicates the importance of systematic control of the contaminant presence, in order to gather enough occurrence data for proper risk assessment that these contaminants represent for the consumer’s health.
Prokaryotic Diversity of the Composting Thermophilic Phase: The Case of Ground Coffee Compost
Authors: Papale Maria , Romano Ida , Finore Ilaria , Lo Giudice Angelina , Piccolo Alessandro , Cangemi Silvana , Di Meo Vincenzo , Nicolaus Barbara , Poli Annarita
Published: January 2021

Waste biomass coming from a local coffee company, which supplied burnt ground coffee after an incorrect roasting process, was employed as a starting material in the composting plant of the Experimental Station of the University of Naples Federico II at Castel Volturno (CE). The direct molecular characterization of compost using 13C-NMR spectra, which was acquired through cross-polarization magic-angle spinning, showed a hydrophobicity index of 2.7% and an alkyl/hydroxyalkyl index of 0.7%. Compost samples that were collected during the early “active thermophilic phase” (when the composting temperature was 63 °C) were analyzed for the prokaryotic community composition and activities. Two complementary approaches, i.e., genomic and predictive metabolic analysis of the 16S rRNA V3–V4 amplicon and culture-dependent analysis, were combined to identify the main microbial factors that characterized the composting process. The whole microbial community was dominated by Firmicutes. The predictive analysis of the metabolic functionality of the community highlighted the potential degradation of peptidoglycan and the ability of metal chelation, with both functions being extremely useful for the revitalization and fertilization of agricultural soils. Finally, three biotechnologically relevant Firmicutes members, i.e., Geobacillus thermodenitrificans subsp. calidus, Aeribacillus pallidus, and Ureibacillus terrenus (strains CAF1, CAF2, and CAF5, respectively) were isolated from the “active thermophilic phase” of the coffee composting. All strains were thermophiles growing at the optimal temperature of 60 °C. Our findings contribute to the current knowledge on thermophilic composting microbiology and valorize burnt ground coffee as waste material with biotechnological potentialities.
Sm–Nd Isochron Age Constraints of Au and Sb Mineralization in Southwestern Guizhou Province, China
Authors: Wang Zepeng , Tan Qinping , Xia Yong , Liu Jianzhong , Yang Chengfu , Li Songtao , Li Junhai , Chen Faen , Wang Xiaoyong , Pan Qiquan , Wang Dafu
Published: January 2021

Southwestern Guizhou, China, is famous for hosting clusters of Carlin-type Au, Sb, and Hg-Tl deposits. These deposits are thought to be the products of a low-temperature hydrothermal metallogenic event. Calcite and fluorite are common and widespread gangue minerals in Au and Sb deposits, respectively. Ore-related calcite commonly coexists with stibnite, realgar, and orpiment at the periphery of high-grade orebodies in Au deposits, while ore-related fluorite is generally intergrown with stibnite in Sb deposits. In this study, ore-related calcite and fluorite samples from representative Au (Zimudang) and Sb (Dachang) deposits, respectively, were separated, and the rare earth element (REE) concentrations, Sm/Nd isotope ratios, and Sm–Nd isochron ages were analyzed. This study aims to determine the formation ages of the calcite and fluorite and to constrain the age of low-temperature metallogenic event in Southwestern Guizhou. The calcite and fluorite samples contain relatively high total concentrations of REEs (8.21–22.5 μg/g for calcite, 21.7–36.6 μg/g for fluorite), exhibit variable Sm/Nd ratios (0.51–1.01 for calcite, 0.35–0.49 for fluorite), and yield Sm–Nd isochron ages of 148.4 ± 4.8 and 141 ± 20 Ma, respectively. These ages are consistent with the age range constrained by the low-temperature thermochronology of zircon (132–160 Ma), crosscutting relationships of stratigraphy or intrusions (96–160 Ma), and previous dating results (135–150 Ma) in Southwestern Guizhou. Collectively, the ages obtained in this study add new evidence to previous geochronology studies, such that the low-temperature hydrothermal mineralization in Southwestern Guizhou can be constrained to 135–150 Ma, corresponding to the Yanshanian orogeny, which was associated with a weak extensional tectonic environment.
Environmental Evaluation of Gypsum Plasterboard Recycling
Authors: Weimann Karin , Adam Christian , Buchert Matthias , Sutter Juergen
Published: January 2021

Gypsum is widely used in the construction sector, and its worldwide consumption has been increasing for several decades. Depending on the lifetime of the used gypsum products, an increase of gypsum in construction and demolition waste follows. Especially against the background of a circular economy, the recycling of waste gypsum is of growing importance. However, the use of recycled gypsum only makes sense if it is environmentally friendly. Therefore, an evaluation of the environmental impacts of industrial-scale processing for the recycling of post-consumer gypsum waste was conducted. The evaluation was performed with an established life cycle assessment software. Original data provided by the industry and complementary data from a database for life cycle assessments were used for the calculations. Two scenarios for recycled gypsum with different transportation distances were calculated. These results were compared with the results of the environmental evaluation of gypsum derived from coal-fired power plants (FGD gypsum) and natural gypsum. The results showed that the utilization of recycled gypsum can be environmentally advantageous compared to the use of natural gypsum or FGD gypsum, especially in the impact categories of land transformation and resource consumption (abiotic depletion potential). For most environmental impact categories, the specific transportation distances have a strong influence.
Synthesis of Tetravalent Thio- and Selenogalactoside-Presenting Galactoclusters and Their Interactions with Bacterial Lectin PA-IL from Pseudomonas aeruginosa
Authors: Illyés Tünde Zita , Malinovská Lenka , Rőth Erzsébet , Tóth Boglárka , Farkas Bence , Korsák Marek , Wimmerová Michaela , Kövér Katalin E. , Csávás Magdolna
Published: January 2021

Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-β-d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis.
Genotoxicity and Immunotoxicity of Titanium Dioxide-Embedded Mesoporous Silica Nanoparticles (TiO2@MSN) in Primary Peripheral Human Blood Mononuclear Cells (PBMC)
Authors: Di Giampaolo Luca , Zaccariello Gloria , Benedetti Alvise , Vecchiotti Giulia , Caposano Francesca , Sabbioni Enrico , Groppi Flavia , Manenti Simone , Niu Qiao , Poma Anna Maria Giuseppina , Di Gioacchino Mario , Petrarca Claudia
Published: January 2021

Background: TiO2 nanoparticles (TiO2 NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO2 is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO2 NPs (TiO2@MSN) to develop a cosmetic UV filter. The aim of this study was to assess the toxicity of TiO2@MSN, compared with bare MSN and commercial TiO2 NPs, based on several biomarkers. Materials and Methods: Human peripheral blood mononuclear cells (PBMC) were exposed to TiO2@MSN, bare MSN (network) or commercial TiO2 NPs for comparison. Exposed PBMC were characterized for cell viability/apoptosis, reactive oxygen species (ROS), nuclear morphology, and cytokines secretion. Results: All the nanoparticles induced apoptosis, but only TiO2 NPs (alone or assembled into MSN) led to ROS and micronuclei. However, TiO2@MSN showed lower ROS and cytotoxicity with respect to the P25. Exposure to TiO2@MSN induced Th2-skewed and pro-fibrotic responses. Conclusions: Geno-cytotoxicity data indicate that TiO2@MSN are safer than P25 and MSN. Cytokine responses induced by TiO2@MSN are imputable to both the TiO2 NPs and MSN, and, therefore, considered of low immunotoxicological relevance. This analytical assessment might provide hints for NPs modification and deep purification to reduce the risk of health effects in the settings of their large-scale manufacturing and everyday usage by consumers.
Homogeneous and Multiphase Analysis of Nanofluids Containing Nonspherical MWCNT and GNP Nanoparticles Considering the Influence of Interfacial Layering
Authors: Ambreen Tehmina , Saleem Arslan , Park Cheol Woo
Published: January 2021

The practical implication of nanofluids is essentially dependent on their accurate modelling, particularly in comparison with the high cost of experimental investigations, yet the accuracy of different computational approaches to simulate nanofluids remains controversial to this day. Therefore, the present study is aimed at analysing the homogenous, multiphase Eulerian–Eulerian (volume of fluid, mixture, Eulerian) and Lagrangian–Eulerian approximation of nanofluids containing nonspherical nanoparticles. The heat transfer and pressure drop characteristics of the multiwalled carbon nanotubes (MWCNT)-based and multiwalled carbon nanotubes/graphene nanoplatelets (MWCNT/GNP)-based nanofluids are computed by incorporating the influence of several physical mechanisms, including interfacial nanolayering. The accuracy of tested computational approaches is evaluated by considering particle concentration and Reynolds number ranges of 0.075–0.25 wt% and 200–470, respectively. The results demonstrate that for all nanofluid combinations and operational conditions, the Lagrangian–Eulerian approximation provides the most accurate convective heat transfer coefficient values with a maximum deviation of 5.34% for 0.25 wt% of MWCNT–water nanofluid at the largest Reynolds number, while single-phase and Eulerian–Eulerian multiphase models accurately estimate the thermal fields of the diluted nanofluids at low Reynolds numbers, but overestimate the results for denser nanofluids at high Reynolds numbers.
Review of Contemporary Self-Assembled Systems for the Controlled Delivery of Therapeutics in Medicine
Authors: Osorno Laura , Brandley Alyssa , Maldonado Daniel , Yiantsos Alex , Mosley Robert , Byrne Mark
Published: January 2021

The novel and unique design of self-assembled micro and nanostructures can be tailored and controlled through the deep understanding of the self-assembly behavior of amphiphilic molecules. The most commonly known amphiphilic molecules are surfactants, phospholipids, and block copolymers. These molecules present a dual attraction in aqueous solutions that lead to the formation of structures like micelles, hydrogels, and liposomes. These structures can respond to external stimuli and can be further modified making them ideal for specific, targeted medical needs and localized drug delivery treatments. Biodegradability, biocompatibility, drug protection, drug bioavailability, and improved patient compliance are among the most important benefits of these self-assembled structures for drug delivery purposes. Furthermore, there are numerous FDA-approved biomaterials with self-assembling properties that can help shorten the approval pathway of efficient platforms, allowing them to reach the therapeutic market faster. This review focuses on providing a thorough description of the current use of self-assembled micelles, hydrogels, and vesicles (polymersomes/liposomes) for the extended and controlled release of therapeutics, with relevant medical applications. FDA-approved polymers, as well as clinically and commercially available nanoplatforms, are described throughout the paper.
Telemedicine during the Coronavirus Disease (COVID-19) Pandemic: A Multiple Sclerosis (MS) Outpatients Service Perspective
Authors: Corea Francesco , Ciotti Silvia , Cometa Antonella , De Carlo Claudia , Martini Giancarlo , Baratta Silvano , Zampolini Mauro
Published: January 2021

Background: During the COVID-19 pandemic, the need for a broader implementation of telemedicine for many diseases has become apparent. Televisits are one type of telemedicine in which clinical visits are conducted remotely using an audio-visual connection with the patient at home. The use of televisits is more established in Stroke care but was also recently formally evaluated for Multiple Sclerosis (MS). This retrospective case series describes patient characteristics and reasons for televisits in persons with MS during the COVID-19 pandemic outbreak in Italy, which was declared in February 2020. Methods: Recruitment occurred in a general hospital based MS clinic during Italy’s lockdown months period (9 March–18 May). Each subject completed at least one televisit. The baseline data included were demographics and MS history; reasons for the remote house calls were analyzed focusing on COVID-19 related needs. Results: Forty-six participants completed at least one study visit. The patients enrolled were more often females suffering from Relapsing Remitting Multiple Sclerosis (RRMS). Half of the patients had an intermediate level of education and lived within a 60 min drive from the clinic. These patients predominately had a short disease duration and were mostly involved in oral treatment. The main reasons for the call were drug use and counseling on social distancing. In 5 cases, COVID-19 infection was reported. Conclusions: Televisits during the COVID-19 outbreak demonstrated their utility as a care delivery method for MS. Hence, it is vital to facilitate the implementation of this technology in common practice to both face infectious threats and increase accessibility of the health care system.
Nutrition and Muscle Recovery
Authors: Mielgo-Ayuso Juan , Fernández-Lázaro Diego
Published: January 2021

Exercise-induced muscle damage (EIMD) is characterized by histopathological muscle tissue changes that originate skeletal muscle damage [...]
Investigation of Iron and Zinc Concentrations in Human Milk in Correlation to Maternal Factors: An Observational Pilot Study in Poland
Authors: Bzikowska-Jura Agnieszka , Sobieraj Piotr , Michalska-Kacymirow Magdalena , Wesołowska Aleksandra
Published: January 2021

The aim of this study was to evaluate iron and zinc concentrations in the mature human milk (HM) and to investigate the relationship between these concentrations and maternal factors. HM samples were collected between 4–6 weeks postpartum from 32 healthy, exclusively breastfeeding mothers. The assessment of dietary intake during breastfeeding was based on a food frequency questionnaire and three-day dietary records. Nutritional status of participants was assessed with body mass index and body composition analysis, measured with bioelectrical impedance. HM intake was assessed with infants’ weighting, whereas iron and zinc contents in HM were determined by inductively coupled plasma mass spectrometer. The median intake of HM was 492.5 mL (466–528.5) and the concentrations of HM iron and zinc were 0.33 mg/L (0.26–0.46) and 2.12 mg/L (1.97–2.45), respectively. Maternal total zinc and iron intake (diet + supplementation) was positively correlated with their concentrations in HM. Consumption frequency of meat, vegetables and legumes was revealed to be a significant factor influencing zinc concentration in HM. Regarding iron, it was the consumption frequency of meat, fish and seafood, vegetables and legumes, nuts and seeds. The intake of iron from HM was low, and after assuming a mean fractional iron absorption, it was only 0.038 mg/d. Our results show that maternal diet influences iron and zinc content in HM, suggesting that adequate intake of food rich in investigated minerals may be a positive factor for their concentrations in HM.
Towards New Horizons: Climate Trends in Europe Increase the Environmental Suitability for Permanent Populations of Hyalomma marginatum (Ixodidae)
Authors: Fernández-Ruiz Natalia , Estrada-Peña Agustín
Published: January 2021

Ticks and tick-borne pathogens are changing their current distribution, presumably due to the impact of the climate trends. On a large scale, these trends are changing the environmental suitability of Hyalomma marginatum, the main vector of several pathogens affecting human health. We generated annual models of environmental suitability for the tick in the period 1970–2018, using harmonic regression-derived data of the daily maximum and minimum temperature, soil moisture and water vapor deficit. The results demonstrate an expansion of the suitable area in Mediterranean countries, southeast central Europe and south of the Balkans. Also, the models allowed us to interpret the impact of the ecological variables on these changes. We deduced that (i) maximum temperature was significant for all of the biogeographical categories, (ii) soil humidity has an influence in the Mediterranean climate areas, and (iii) the minimum temperature and deficit water vapor did not influence the environmental suitability of the species. The conclusions clearly show that climate change could create new areas in Europe with suitable climates for H. marginatum, while keeping its “historical” distribution in the Mediterranean. Therefore, it is necessary to further explore possible risk areas for H. marginatum and its associated pathogens.
Characterization of Enterococci- and ESBL-Producing Escherichia coli Isolated from Milk of Bovides with Mastitis in Egypt
Authors: Ahmed Wedad , Neubauer Heinrich , Tomaso Herbert , El Hofy Fatma Ibrahim , Monecke Stefan , Abd El-Tawab Ashraf Awad , Hotzel Helmut
Published: January 2021

This study aimed to investigate the prevalence and antimicrobial resistance of enterococci- and ESBL-producing E. coli isolated from milk of bovine mastitis cases in Egypt. Fifty milk samples of dairy animals were collected from localities in the Nile Delta region of Egypt. Isolates were identified using MALDI-TOF MS, and antibiotic susceptibility testing was performed by the broth microdilution method. PCR amplifications were carried out, targeting resistance-associated genes. Seventeen Enterococcus isolates and eight coliform isolates could be cultivated. Vancomycin resistance rate was high in Ent. faecalis. The VITEK 2 system confirmed all E. coli isolates as ESBL-producing. All Ent. faecalis isolates harbored erm(B), tetL and aac-aphD genes. The vanA gene was detected in Ent. faecalis isolate, vanB was found in other Enterococcus, while one isolate of E. casseliflavus exhibited the vanA gene. E. coli isolates exhibited high prevalence of erm(B) and tetL. E. coli isolates were analyzed by DNA microarray analysis. Four isolates were determined by O-serotyping as O8 (n = 1), O86 (n = 2) and O157 (n = 1). H-serotyping resulted in H11, H12, H21 (two isolates each) and one was of H16 type. Different virulence-associated genes were detected in E. coli isolates including lpfA, astA, celB, cmahemL, intI1 and intI2, and the iroN gene was identified by DNA microarray analysis.
Community Parameters and Genome-Wide RAD-Seq Loci of Ceratothoa oestroides Imply Its Transfer between Farmed European Sea Bass and Wild Farm-Aggregating Fish
Authors: Mladineo Ivona , Hrabar Jerko , Trumbić Željka , Manousaki Tereza , Tsakogiannis Alexandros , Taggart John B. , Tsigenopoulos Costas S.
Published: January 2021

Wild fish assemblages that aggregate within commercial marine aquaculture sites for feeding and shelter have been considered as a primary source of pathogenic parasites vectored to farmed fish maintained in net pens at an elevated density. In order to evaluate whether Ceratothoa oestroides (Isopoda, Cymothoidae), a generalist and pestilent isopod that is frequently found in Adriatic and Greek stocks of farmed European sea bass (Dicentrarchus labrax), transfers between wild and farmed fish, a RAD-Seq (restriction-site-associated DNA sequencing)-mediated genetic screening approach was employed. The double-digest RAD-Seq of 310 C. oestroides specimens collected from farmed European sea bass (138) and different wild farm-aggregating fish (172) identified 313 robust SNPs that evidenced a close genetic relatedness between the “wild” and “farmed” genotypes. ddRAD-Seq proved to be an effective method for detecting the discrete genetic structuring of C. oestroides and genotype intermixing between two populations. The parasite prevalence in the farmed sea bass was 1.02%, with a mean intensity of 2.0 and mean abundance of 0.02, while in the wild fish, the prevalence was 8.1%; the mean intensity, 1.81; and the mean abundance, 0.15. Such differences are likely a consequence of human interventions during the farmed fish’s rearing cycle that, nevertheless, did not affect the transfer of C. oestroides.
Coenzyme Q10 and Silymarin Reduce CCl4-Induced Oxidative Stress and Liver and Kidney Injury in Ovariectomized Rats—Implications for Protective Therapy in Chronic Liver and Kidney Diseases
Authors: Lamia Samanta Sifat , Emran Tushar , Rikta Jubaida Khatun , Chowdhury Nowreen Islam , Sarker Manoneeta , Jain Preeti , Islam Tabinda , Gias Zarin Tasnim , Shill Manik Chandra , Reza Hasan Mahmud
Published: January 2021

Oxidative stress is one of the key factors in the pathophysiology of liver disease. The present study aimed to evaluate the potential impact of two antioxidants, namely coenzyme Q10 (CoQ10) and silymarin, on carbon tetrachloride (CCl4)-induced oxidative stress and hepatic damage in ovariectomized rats. Female Long Evans rats were divided into six groups (n = 6): control, CCl4, CCl4 + CoQ10 (200 mg/kg), CCl4 + silymarin (140 mg/kg), Control + CoQ10, and Control + silymarin. Plasma and tissues from liver and kidney were analyzed for oxidative stress parameters and antioxidant enzyme activities using biochemical assays. Infiltration of inflammatory cells and fibrosis were assessed by histological staining of tissue sections. Both CoQ10 and silymarin significantly lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels that were detected to be higher in CCl4 rats compared to controls. Significant reduction in CCl4-induced elevated levels of oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was observed with both antioxidants. However, in control rats, CoQ10 and silymarin did not produce a significant effect. Histological analysis revealed that CCl4 markedly increased the level of inflammatory cells infiltration and fibrosis in liver and kidney tissues, but this was significantly reduced in CCl4 + CoQ10 and CCl4 + silymarin groups. Taken together, our results suggest that CoQ10 and silymarin can protect the liver against oxidative damage through improved antioxidant enzyme activities and reduced lipid peroxidation. Thus, supplementation of the aforementioned antioxidants may be useful as a therapeutic intervention to protect liver health in chronic liver diseases.
Mapping of Absolute Host Concentration and Exchange Kinetics of Xenon Hyper-CEST MRI Agents
Authors: Kunth Martin , Witte Christopher , Schröder Leif
Published: January 2021

Xenon magnetic resonance imaging (MRI) provides excellent sensitivity through the combination of spin hyperpolarization and chemical exchange saturation transfer (CEST). To this end, molecular hosts such as cryptophane-A or cucurbit[n]urils provide unique opportunities to design switchable MRI reporters. The concentration determination of such xenon binding sites in samples of unknown dilution remains, however, challenging. Contrary to 1H CEST agents, an internal reference of a certain host (in this case, cryptophane-A) at micromolar concentration is already sufficient to resolve the entire exchange kinetics information, including an unknown host concentration and the xenon spin exchange rate. Fast echo planar imaging (EPI)-based Hyper-CEST MRI in combination with Bloch–McConnell analysis thus allows quantitative insights to compare the performance of different emerging ultra-sensitive MRI reporters.
Model-Based Prediction to Evaluate Residence Time of Hyaluronic Acid Based Dermal Fillers
Authors: Ryu Hyo-jeong , Kwak Seong-sung , Rhee Chang-hoon , Yang Gi-hyeok , Yun Hwi-yeol , Kang Won-ho
Published: January 2021

Dermal fillers are gel-type substances for nonsurgical medical-device use to achieve facial rejuvenation. Currently, the most widely used skin fillers are hyaluronic-acid-based dermal fillers. This study aimed to explain the change in the volume of injected dermal fillers by developing a mathematical kinetic model for various dermal fillers. The kinetics of the injected fillers were separated by a biphasic phenomenon. We attributed an increase in filler volume to the hydration of hyaluronic acid molecules and injection-site reaction and a decrease in volume to enzyme-mediated degradation. To explain these in vivo characteristics of dermal fillers, we proposed a two-compartment model, divided into a depot compartment (where the filler was injected) and a subcutaneous compartment (an observation compartment where the fillers swell and degrade), assuming that the swelling and degradation occurred in accordance with the swelling and degradation rate constants, respectively. The model was developed using five hyaluronic-acid-based dermal fillers and NONMEM. We determined that the rate-limiting step for the complete degradation of the dermal fillers in vivo was the swelling phase, as described by the swelling rate constant (Kswell). This study could enable scientists developing novel dermal fillers to predict the in vivo behavior of fillers.
Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats
Authors: Costa Angelica , Erustes Adolfo , Sinigaglia Rita , Girardi Carlos , Pereira Gustavo , Ureshino Rodrigo , Smaili Soraya
Published: January 2021

The pharmacological modulation of autophagy is considered a promising neuroprotective strategy. While it has been postulated that lithium regulates this cellular process, the age-related effects have not been fully elucidated. Here, we evaluated lithium-mediated neuroprotective effects in young and aged striatum. After determining the optimal experimental conditions for inducing autophagy in loco with lithium carbonate (Li2CO3), we measured cell viability, reactive oxygen species (ROS) generation and oxygen consumption with rat brain striatal slices from young and aged animals. In the young striatum, Li2CO3 increased tissue viability and decreased ROS generation. These positive effects were accompanied by enhanced levels of LC3-II, LAMP 1, Ambra 1 and Beclin-1 expression. In the aged striatum, Li2CO3 reduced the autophagic flux and increased the basal oxygen consumption rate. Ultrastructural changes in the striatum of aged rats that consumed Li2CO3 for 30 days included electrondense mitochondria with disarranged cristae and reduced normal mitochondria and lysosomes area. Our data show that the striatum from younger animals benefits from lithium-mediated neuroprotection, while the striatum of older rats does not. These findings should be considered when developing neuroprotective strategies involving the induction of autophagy in aging.
Novel Polymorph of Favipiravir—An Antiviral Medication
Authors: Goloveshkin Alexander S. , Korlyukov Alexander A. , Vologzhanina Anna V.
Published: January 2021

Various solid forms of pharmaceutically important compounds exhibit different physical properties and bioactivity; thus, knowledge of the structural landscape and prediction of spontaneous polymorph transformations for an active pharmaceutical ingredient is of practical value for the pharmaceutical industry. By recrystallization from ethyl acetate, a novel polymorph of 6-fluoro-3-hydroxypyrazine-2-carboxamide (trademark favipiravir, RNA polymerase inhibitor) was obtained and characterized using differential scanning calorimetry (DSC), infra-red spectroscopy and powder X-ray diffraction (XRD) analysis. The favipiravir molecule in two polymorphs realizes similar H-bonding motifs, but the overall H-bonded networks differ. Based on periodic density functional theory calculations, the novel tetragonal polymorph with two interpenetrated H-bonded networks is slightly less stable than the orthorhombic one with the zst topology of the underlying H-bonded net that is in accord with experimentally observed powder XRD patterns of slow conversion of the tetragonal phase to the orthorhombic one. However, topological analysis of net relations revealed that no transformations can be applied to convert H-bonded networks in the experimental unit cells, and DSC data indicate no solid-state reactions at heating.
Patients’ Use and Perceptions of a Drug-Drug Interaction Database: A Survey of Janusmed Interactions
Authors: Justad Hanna , Askfors Ylva , Shemeikka Tero , Andersson Marine L. , Hammar Tora
Published: January 2021

Janusmed interactions is a drug-drug interactions (DDI) database available online for healthcare professionals (HCP) at all levels of the healthcare system including pharmacies. The database is aimed at HCP but is also open to the public for free, for those individuals who register for a personal account. The aim of this study was to investigate why and how patients use the database Janusmed interactions, how they perceive content and usability, and how they would react if they found an interaction. A web-based questionnaire was sent by email to all users who had registered for Janusmed interactions as a “patient” (n = 3219). A total of 406 patients completed the survey (response rate 12.6%). The study shows that there is an interest among patients to use a DDI database to check their own or a relative’s medication. The respondents found the database easy to use and perceive they understand the information aimed at HCP. Most patients stated they would talk to their HCP if they found an interaction and not adjust their treatment by themselves. However, the respondents in this study are actively searching for information and seem to have high health literacy. Thus, the findings are not generalizable for the general population.
Experiences of the Medication Use Process by People with Intellectual Disabilities. What a Pharmacist Should Know!
Authors: Flood Bernadette , Henman Martin C.
Published: January 2021

There is a scarcity of information about the experience of people with intellectual disabilities in the medication use process. Six people with intellectual disabilities consented to be interviewed by a pharmacist to determine their knowledge and views of medication use. Data from semi-structured interviews were analysed using a grounded theory approach. Self-determination and risk to the quality of the medication use process were identified as theories. Literature review provided two explanations—vulnerabilities of people with intellectual disabilities in healthcare and pharmacists have a role to play in ensuring a quality medication use process for people with intellectual disabilities. People with intellectual disabilities may be ‘expert patients’ and can provide valuable insights into their experience of medication use. They may be ‘high risk’ patients but may not be recognized as such by pharmacists.
Agency, Responsibility, Selves, and the Mechanical Mind
Authors: Battaglia Fiorella
Published: January 2021

Moral issues arise not only when neural technology directly influences and affects people’s lives, but also when the impact of its interventions indirectly conceptualizes the mind in new, and unexpected ways. It is the case that theories of consciousness, theories of subjectivity, and third person perspective on the brain provide rival perspectives addressing the mind. Through a review of these three main approaches to the mind, and particularly as applied to an “extended mind”, the paper identifies a major area of transformation in philosophy of action, which is understood in terms of additional epistemic devices—including a legal perspective of regulating the human–machine interaction and a personality theory of the symbiotic connection between human and machine. I argue this is a new area of concern within philosophy, which will be characterized in terms of self-objectification, which becomes “alienation” following Ernst Kapp’s philosophy of technology. The paper argues that intervening in the brain can affect how we conceptualize the mind and modify its predicaments.
Arbitrary-Order Photonic Hilbert Transformers Based on Phase-Modulated Fiber Bragg Gratings in Transmission
Authors: Li Yanxin , Liu Xin , Shu Xuewen , Zhang Lin
Published: January 2021

Photonic Hilbert transformers are fundamental components for optical computing and signal processing. Here, for the first time we propose all-optical arbitrary-order Hilbert transformers using phase-modulated fiber Bragg gratings (PM-FBGs) in transmission to our best knowledge. The PM-FBG is a kind of fiber grating, whose coupling strength remains almost uniform and period varies along the fiber length. For demonstration, we have designed and numerically simulated 0.5th-order, first-order, and 1.5th-order photonic Hilbert transformers, respectively. The profiles of those PM-FBGs are obtained employing quasi-Newton optimization algorithm. Simulation results show that the designed three Hilbert transformers are all in good agreement with the ideal results in bandwidths up to 500 GHz and can tolerate a large range of input pulse width.
Tolerance Mechanisms of the Aromatic and Medicinal Plant Salvia sclarea L. to Excess Zinc
Authors: Dobrikova Anelia , Apostolova Emilia , Hanć Anetta , Yotsova Ekaterina , Borisova Preslava , Sperdouli Ilektra , Adamakis Ioannis-Dimosthenis S. , Moustakas Michael
Published: January 2021

In recent years, due to the development of industrial and agricultural production, heavy metal contamination has attracted increasing attention. Aromatic and medicinal plant Salvia sclarea L. (clary sage) is classified to zinc (Zn) accumulators and considered as a potential plant for the phytoremediation of heavy metal polluted soils. In this study, an adaptation of clary sage to 900 µM (excess) Zn exposure for eight days in a hydroponic culture was investigated. The tolerance mechanisms under excess Zn exposure were assessed by evaluating changes in the nutrient uptake, leaf pigment and phenolic content, photosynthetic activity and leaf structural characteristics. The uptake and the distribution of Zn, as well as some essential elements such as: Ca, Mg, Fe, Mn and Cu, were examined by inductively coupled plasma mass spectrometry. The results revealed that Salvia sclarea is a Zn-accumulator plant that tolerates significantly high toxic levels of Zn in the leaves by increasing the leaf contents of Fe, Ca and Mn ions to protect the photosynthetic function and to stimulate the photosystem I (PSI) and photosystem II (PSII) activities. The exposure of clary sage to excess Zn significantly increased the synthesis of total phenolics and anthocyanins in the leaves; these play an important role in Zn detoxification and protection against oxidative stress. The lipid peroxidation and electrolyte leakage in leaves, used as clear indicators for heavy metal damage, were slightly increased. All these data highlight that Salvia sclarea is an economically interesting plant for the phytoextraction and/or phytostabilization of Zn-contaminated soils.