bluuebunny/crossref_metadata_2025 huggingface dataset:
Red Spot on the European Green Map: Will the Extra Catastrophic Phenomenon Take the Polish Poaching-Pressured Ospreys to the Brink of Extinction?
Authors: Woźniak Bartłomiej , Zygmunt Michał , Porębski Łukasz , Woźniak Patrycja , Anderwald Dariusz
Published: December 2021

Poland is the only European country where the Osprey population is declining due to the mortality of adult birds from poaching, which impacts not only single breeding attempts but also the Lifetime Reproductive Success (LRS) of specimens. However, what if there came an extra mortality factor in the moment of the lowest numbers of Osprey, already vulnerable in the country? In the years 2018–2020, we installed 22 trail cameras and five digital cameras (live online video feeds) on the nests. The total failure level observed in cameras (18.5%) was high. We observed, using these cameras, the extra mortality of chicks (10.7% of potentially fledged chicks) and even adult birds by unexpected predation by Northern Goshawk and White-tailed Eagle. This phenomenon is also common in the national population, as we found a total of ten cases of total losses by predators (eight or nine of them were birds of prey), including nests not covered by camera monitoring. The extra adult-predation by Goshawks means an extra drop in LRS. Those adult and chick predations are an example of exceptional catastrophic phenomena, which have been described as the direct cause of the extinction of animal populations throughout history. Only active conservation and stop poaching of the Polish population could stop the decline and save the Polish Ospreys.
Novel Techniques for Microbiological Safety in Meat and Fish Industries
Authors: Rebezov Maksim , Farhan Jahangir Chughtai Muhammad , Mehmood Tariq , Khaliq Adnan , Tanweer Saira , Semenova Anastasia , Khayrullin Mars , Dydykin Andrey , Burlankov Stepan , Thiruvengadam Muthu , Shariati Mohammad Ali , Lorenzo José M.
Published: December 2021

The consumer tendency towards convenient, minimally processed meat items has placed extreme pressure on processors to certify the safety of meat or meat products without compromising the quality of product and to meet consumer’s demand. This has prompted difficulties in creating and carrying out novel processing advancements, as the utilization of more up-to-date innovations may influence customer decisions and assessments of meat and meat products. Novel advances received by the fish and meat industries for controlling food-borne microbes of huge potential general wellbeing concern, gaps in the advancements, and the requirement for improving technologies that have been demonstrated to be effective in research settings or at the pilot scale shall be discussed. Novel preparing advancements in the meat industries warrant microbiological approval before being named as industrially suitable alternatives and authorizing infra-structural changes. This miniature review presents the novel techniques for the microbiological safety of meat products, including both thermal and non-thermal methods. These technologies are being successfully implemented and rationalized in subsisting processing surroundings.
Optimal Tests for Combining p-Values
Authors: Chen Zhongxue
Published: December 2021

Combining information (p-values) obtained from individual studies to test whether there is an overall effect is an important task in statistical data analysis. Many classical statistical tests, such as chi-square tests, can be viewed as being a p-value combination approach. It remains challenging to find powerful methods to combine p-values obtained from various sources. In this paper, we study a class of p-value combination methods based on gamma distribution. We show that this class of tests is optimal under certain conditions and several existing popular methods are equivalent to its special cases. An asymptotically and uniformly most powerful p-value combination test based on constrained likelihood ratio test is then studied. Numeric results from simulation study and real data examples demonstrate that the proposed tests are robust and powerful under many conditions. They have potential broad applications in statistical inference.
Interpretation of Cone Penetration Test Data of an Embankment for Coupled Numerical Modeling
Authors: Islam Mohammad Nurul , Gnanendran Carthigesu T. , Sivakumar Siva T.
Published: December 2021

The Nerang Broadbeach Roadway (NBR) embankment in Australia is founded on soft clay deposits. The embankment sections were preloaded and surcharged-preloaded to limit the post-construction deformation and to avoid stability failure. In this paper, we discuss the NBR embankment’s geology, geotechnical properties of the subsurface, and long-term field monitoring data from settlement plates and piezometers. We demonstrate a comparison of cone penetration test (CPT) and piezo cone dissipation test (CPT-u) interpreted geotechnical properties and the NBR embankment’s foundation stratification with laboratory and field measured data. We also developed two elasto-viscoplastic (EVP) models for long-term performance prediction of the NBR embankment. In this regard, we considered both the associated and the non-associated flow rule in the EVP model formulation to assess the flow rule effect of soft clay. We also compared EVP model predictions with the Modified Cam Clay (MCC) model to evaluate the effect of viscous behavior of natural Estuarine clay. Both EVP models require six parameters, and five of them are similar to the MCC model. We used the secondary compression index of clay in the EVP model formulations to include the viscous response of clay. We obtained numerical models’ parameters from laboratory tests and interpretation of CPT and CPTu data. We observed that the EVP models predicted well compared with the MCC model because of the inclusion of soft clay’s viscosity in the EVP models. Moreover, the flow rule effect in the embankment’s performance predictions was noticeable. The non-associated flow rule EVP model predicted the field monitoring settlement and pore pressure better compared to the MCC model and the associated flow EVP model.
Cavernous Sinus Dural Arteriovenous Fistula in a Patient with Thyroid-Associated Ophthalmopathy: Complete Resolution after Medical Treatment
Authors: Cavasin Nicola , Presotto Fabio , Bellamio Matteo , Cagliari Enrico
Published: December 2021

Thyroid-associated ophthalmopathy (TAO) is a well-known and frequent epiphenomenon of a hyperthyroid autoimmune disease that can present with proptosis, strabismus, and diplopia. Ophthalmopathy can occur in the absence of overt Graves’ disease, even in euthyroid patients. Cavernous sinus dural fistulas (CS-DAVF) are abnormal communications between the cavernous sinus (CS) and dural branches from internal carotid or external carotid arteries. They can often present with ocular symptoms that can mimic a thyroid-associated ophthalmopathy. CS-DAVF are usually successfully treated with an endovascular embolization that can be pursued both through a transvenous or transarterial approach. TAO and CS-DAVF can coexist especially when the ocular symptoms are unilateral. In those cases, an endovascular embolization is usually curative, but sometimes the procedure can fail. Our hypothesis is that some cases of CS-DAVF may be of secondary nature (i.e., caused by compression of the venous outlet by the hypertrophic ocular muscles); therefore, treating the ocular disease with medical therapy may solve the vascular problem as well. We present a case of a CS-DAVF in a patient with TAO successfully treated with sole medical therapy after the failure of a first-line endovascular treatment.
Correlation of Somatostatin Receptor 1–5 Expression, [68Ga]Ga-DOTANOC, [18F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms
Authors: Majala Susanna , Vesterinen Tiina , Seppänen Hanna , Mustonen Harri , Sundström Jari , Schalin-Jäntti Camilla , Gullichsen Risto , Schildt Jukka , Kemppainen Jukka , Arola Johanna , Kauhanen Saila
Published: December 2021

Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman’s rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (−0.353, 95% CI −0.654–0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0–3.0) and 6.38 (SD 7.25, CI 2.25–8.75) for negative tumors. Conclusion: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.
A Conceptual Framework to Improve the Symbol Implementation of 4D Printing Communication between Designers and Engineers
Authors: Azhar Faten Ezrin , Pei Eujin
Published: December 2021

This research investigates the communication barriers between designers and engineers in designing 4D Printing parts. We have proposed a conceptual design framework for 4D Printing symbols as the communication tool. Then, we have recruited sixty-fifty designers and engineers who participated in our online experiments. The focus of the online survey is to find out how designers and engineers understand reciprocal communication by using the proposed symbols. Our results showed that 85% of participants could understand the 4D Printing symbols correctly. The study concludes that using the conceptual framework can help designers and engineers communicate 4D Printing element information and stimulate design ideas effectively.
The Role of Neutrophils in the Pathogenesis of Chronic Lymphocytic Leukemia
Authors: Wachowska Malgorzata , Wojciechowska Alicja , Muchowicz Angelika
Published: December 2021

Tumor-associated neutrophils appear to be a crucial element of the tumor microenvironment that actively participates in the development and progression of cancerous diseases. The increased lifespan, plasticity in changing of phenotype, and functions of neutrophils influence the course of the disease and may significantly affect survival. In patients with chronic lymphocytic leukemia (CLL), disturbances in neutrophils functions impede the effective immune defense against pathogens. Therefore, understanding the mechanism underlying such a phenomenon in CLL seems to be of great importance. Here we discuss the recent reports analyzing the phenotype and functions of neutrophils in CLL, the most common leukemia in adults. We summarize the data concerning both the phenotype and the mechanisms by which neutrophils directly support the proliferation and survival of malignant B cells.
Pyroptosis-Mediated Periodontal Disease
Authors: Sordi Mariane Beatriz , Magini Ricardo de Souza , Panahipour Layla , Gruber Reinhard
Published: December 2021

Pyroptosis is a caspase-dependent process relevant to the understanding of beneficial host responses and medical conditions for which inflammation is central to the pathophysiology of the disease. Pyroptosis has been recently suggested as one of the pathways of exacerbated inflammation of periodontal tissues. Hence, this focused review aims to discuss pyroptosis as a pathological mechanism in the cause of periodontitis. The included articles presented similarities regarding methods, type of cells applied, and cell stimulation, as the outcomes also point to the same direction considering the cellular events. The collected data indicate that virulence factors present in the diseased periodontal tissues initiate the inflammasome route of tissue destruction with caspase activation, cleavage of gasdermin D, and secretion of interleukins IL-1β and IL-18. Consequently, removing periopathogens’ virulence factors that trigger pyroptosis is a potential strategy to combat periodontal disease and regain tissue homeostasis.
Osteocytes Influence on Bone Matrix Integrity Affects Biomechanical Competence at Bone-Implant Interface of Bioactive-Coated Titanium Implants in Rat Tibiae
Authors: Stoetzel Sabine , Malhan Deeksha , Wild Ute , Helbing Christian , Hassan Fathi , Attia Sameh , Jandt Klaus D. , Heiss Christian , El Khassawna Thaqif
Published: December 2021

Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties. Nonetheless, the need for early and immediate loading requires enhancing these properties by adding bioactive coatings. In this preclinical study, extracellular matrix properties and cellular balance at the implant/bone interface was examined. Polyelectrolyte multilayers of chitosan and gelatin or with chitosan and Hyaluronic acid fabricated on titanium alloy using a layer-by-layer self-assembly process were compared with native titanium alloy. The study aimed to histologically evaluate bone parameters that correlate to the biomechanical anchorage enhancement resulted from bioactive coatings of titanium implants in a rat animal model. Superior collagen fiber arrangements and an increased number of active osteocytes reflected a significant improvement of bone matrix quality at the bone interface of the chitosan/gelatin-coated titan implants over chitosan/hyaluronic acid-coated and native implants. Furthermore, the numbers and localization of osteoblasts and osteoclasts in the reparative and remodeling phases suggested a better cellular balance in the chitosan/Gel-coated group over the other two groups. Investigating the micro-mechanical properties of bone tissue at the interface can elucidate detailed discrepancies between different promising bioactive coatings of titanium alloys to maximize their benefit in future medical applications.
Mycobacterium chelonae Infection Identified by Metagenomic Next-Generation Sequencing as the Probable Cause of Acute Contained Rupture of a Biological Composite Graft—A Case Report
Authors: Büchler Andrea C. , Lazarevic Vladimir , Gaïa Nadia , Girard Myriam , Eckstein Friedrich , Egli Adrian , Sutter Sarah Tschudin , Schrenzel Jacques
Published: December 2021

We present the case of a 72-year-old female patient with acute contained rupture of a biological composite graft, 21 months after replacement of the aortic valve and the ascending aorta due to an aortic dissection. Auramine-rhodamine staining of intraoperative biopsies showed acid-fast bacilli, but classical culture and molecular methods failed to identify any organism. Metagenomic analysis indicated infection with Mycobacterium chelonae, which was confirmed by target-specific qPCR. The complexity of the sample required a customized bioinformatics pipeline, including cleaning steps to remove sequences of human, bovine ad pig origin. Our study underlines the importance of multiple testing to increase the likelihood of pathogen identification in highly complex samples.
Consumer Perception and Attitude toward Insects for a Sustainable Diet
Authors: Simeone Mariarosaria , Scarpato Debora
Published: December 2021

The main objective of this research paper is to understand consumer knowledge and perception of insects for food. Primary data was collected using a questionnaire conducted in Rome, and the data was analysed using a probit model in order to understand consumers’ attitudes to include insects as a sustainable solution to meat consumption in their diet. We connected the participants with a willingness to consume insects with those that are critical, informed, and concerned about the environment. This study shows that insects’ consumption and social acceptance is very low even for people who have a greater sensitivity to sustainable diets. Suggestions are included to improve the communication of this food type to raise awareness in the consumers’ minds. This research continues the debate on sustainability and global food security.
Use of Ultrasonography to Discriminate Psoriatic Arthritis from Fibromyalgia: A Post-Hoc Analysis of the ULISSE Study
Authors: Marchesoni Antonio , Macchioni Pierluigi , Gasparini Stefania , Perricone Carlo , Perrotta Fabio Massimo , Grembiale Rosa Daniela , Silvagni Ettore , Ramonda Roberta , Costa Luisa , Zabotti Alen , Curradi Giacomo , Gualberti Giuliana , Marando Francesca , Salvarani Carlo
Published: December 2021

In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray-scale (GS; B-mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS- and PD-mode changes was found in 90% and 59.3% of PsA patients (n = 140) and 62.7% and 35.3% of FMS patients (n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B- and PD-mode, respectively, 3.5 being the best cut-off GS-score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B-mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B-mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS.
Production, Mechanical Properties and Biomedical Characterization of ZrTi-Based Bulk Metallic Glasses in Comparison with 316L Stainless Steel and Ti6Al4V Alloy
Authors: Hasiak Mariusz , Sobieszczańska Beata , Łaszcz Amadeusz , Biały Michał , Chęcmanowski Jacek , Zatoński Tomasz , Bożemska Edyta , Wawrzyńska Magdalena
Published: December 2021

Microstructure, mechanical properties, corrosion resistance, and biocompatibility were studied for rapidly cooled 3 mm rods of Zr40Ti15Cu10Ni10Be25, Zr50Ti5Cu10Ni10Be25, and Zr40Ti15Cu10Ni5Si5Be25 (at.%) alloys, as well as for the reference 316L stainless steel and Ti-based Ti6Al4V alloy. Microstructure investigations confirm that Zr-based bulk metallic samples exhibit a glassy structure with minor fractions of crystalline phases. The nanoindentation tests carried out for all investigated composite materials allowed us to determine the mechanical parameters of individual phases observed in the samples. The instrumental hardness and elastic to total deformation energy ratio for every single phase observed in the manufactured Zr-based materials are higher than for the reference materials (316L stainless steel and Ti6Al4V alloy). A scratch tester used to determine the wear behavior of manufactured samples and reference materials revealed the effect of microstructure on mechanical parameters such as residual depth, friction force, and coefficient of friction. Electrochemical investigations in simulated body fluid performed up to 120 h show better or comparable corrosion resistance of Zr-based bulk metallic glasses in comparison with 316L stainless steel and Ti6Al4V alloy. The fibroblasts viability studies confirm the good biocompatibility of the produced materials. All obtained results show that fabricated biocompatible Zr-based materials are promising candidates for biomedical implants that require enhanced mechanical properties.
The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice
Authors: Nagao Koji , Inoue Nao , Suzuki Kunio , Shimizu Takeshi , Yanagita Teruyoshi
Published: December 2021

Dietary sterols are catabolized into various substances in the intestinal tract. Dietary 3-oxo derivatives of cholesterol and plant sterols (e.g., cholest-4-en-3-one and campest-5-en-3-one) have been shown to have anti-obesity effects. In this study, we tested whether feeding cholest-5-en-3-one (5-cholestenone), a cholesterol metabolite, to db/db mice protects them from obesity-associated metabolic disorders. In db/db mice, dietary 5-cholestenone significantly alleviated hepatomegaly and elevated serum triglyceride levels; however, the effect was not sufficient to improve hepatic steatosis and obesity. On the other hand, hyperglycemia and severe hyperinsulinemia in control db/db mice were markedly attenuated in 5-cholestenone-fed db/db mice. The production of inflammatory cytokines, such as monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-alpha (TNFα), was decreased, suggesting that the suppressive actions of 5-cholestenone were attributable to the alleviation of chronic inflammation in db/db mice. Additionally, 5-cholestenone showed an inhibitory effect on TNFα-induced nuclear factor kappa B (NFκB) activation in the NFκB luciferase gene reporter assay. These results suggest that obesity-induced abnormal glucose metabolism could be alleviated in 5-cholestenone-fed db/db mice by reducing the production of inflammatory cytokines through suppression of the NFκB signaling pathway.
Roles and Influences of Kerosene on Chalcopyrite Flotation in MgCl2 Solution: EDLVO and DFT Approaches
Authors: Li Wanqing , Li Yubiao , Xie Shaobing , Duan Wanqing , Chen Wen
Published: December 2021

Seawater has been increasingly used as an alternative to freshwater in mineral flotation. Although previous studies suggest that Mg2+ ions in seawater have the primary negative roles in chalcopyrite flotation, insufficient work has been conducted to understand the effects of kerosene as a collector in chalcopyrite flotation. In this study, the influence of kerosene emulsion on chalcopyrite floatability in a solution containing Mg2+ was systematically investigated. The results indicated that the addition of kerosene significantly reduced the adsorption of hydrophilic Mg-precipitates onto the chalcopyrite’s surface. In addition to contact angle, zeta potential, optical microscopy, and Fourier-transform infrared spectroscopy analyses, extended Derjguin–Landau–Verwey–Overbeek (EDLVO) theory and density functional theory (DFT) calculations were conducted to understand the influencing mechanisms of kerosene on chalcopyrite flotation. The adsorption energies showed an order of kerosene and Mg(OH)2 > kerosene and chalcopyrite > chalcopyrite and Mg(OH)2, indicating kerosene was preferentially adsorbed on the Mg(OH)2 surface, forming agglomerates and therefore reducing the adsorption of Mg(OH)2 precipitates onto the chalcopyrite’s surface. In addition, hydrophobic agglomerates were also formed due to the attachment of kerosene to the chalcopyrite’s surface when additional kerosene was added, further enhancing chalcopyrite floatability.
Objective Domain Boundaries Detection in New Caledonian Nickel Laterite from Spectra Using Quadrant Scan
Authors: Zaitouny Ayham , Ramanaidou Erick , Hill June , Walker David M. , Small Michael
Published: December 2021

Modelling of 3D domain boundaries using information from drill holes is a standard procedure in mineral exploration and mining. Manual logging of drill holes can be difficult to exploit as the results may not be comparable between holes due to the subjective nature of geological logging. Exploration and mining companies commonly collect geochemical or mineralogical data from diamond drill core or drill chips; however, manual interpretation of multivariate data can be slow and challenging; therefore, automation of any of the steps in the interpretation process would be valuable. Hyperspectral analysis of drill chips provides a relatively inexpensive method of collecting very detailed information rapidly and consistently. However, the challenge of such data is the high dimensionality of the data’s variables in comparison to the number of samples. Hyperspectral data is usually processed to produce mineral abundances generally involving a range of assumptions. This paper presents the results of testing a new fast and objective methodology to identify the lithological boundaries from high dimensional hyperspectral data. This method applies a quadrant scan analysis to recurrence plots. The results, applied to nickel laterite deposits from New Caledonia, demonstrate that this method can identify transitions in the downhole data. These are interpreted as reflecting mineralogical changes that can be used as an aid in geological logging to improve boundary detection.
25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line
Authors: You Jae-Seek , Lim HyangI , Seo Jeong-Yeon , Kang Kyeong-Rok , Kim Do Kyung , Oh Ji-Su , Seo Yo-Seob , Lee Gyeong-Je , Kim Jin-Soo , Kim Heung-Joong , Yu Sun-Kyoung , Kim Jae-Sung
Published: December 2021

25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.
Lysinibacillus Isolate MK212927: A Natural Producer of Allylamine Antifungal ‘Terbinafine’
Authors: El-Sayed Sayed E. , Abdelaziz Neveen A. , Osman Hosam-Eldin Hussein , El-Housseiny Ghadir S. , Aleissawy Ahmed E. , Aboshanab Khaled M.
Published: December 2021

Resistance to antifungal agents represents a major clinical challenge, leading to high morbidity and mortality rates, especially in immunocompromised patients. In this study, we screened soil bacterial isolates for the capability of producing metabolites with antifungal activities via the cross-streak and agar cup-plate methods. One isolate, coded S6, showed observable antifungal activity against Candida (C.) albicans ATCC 10231 and Aspergillus (A.) niger clinical isolate. This strain was identified using a combined approach of phenotypic and molecular techniques as Lysinibacillus sp. MK212927. The purified metabolite displayed fungicidal activity, reserved its activity in a relatively wide range of temperatures (up to 60 °C) and pH values (6–7.8) and was stable in the presence of various enzymes and detergents. As compared to fluconazole, miconazole and Lamisil, the minimum inhibitory concentration of the metabolite that showed 90% inhibition of the growth (MIC90) was equivalent to that of Lamisil, half of miconazole and one fourth of fluconazole. Using different spectroscopic techniques such as FTIR, UV spectroscopy, 1D NMR and 2D NMR techniques, the purified metabolite was identified as terbinafine, an allylamine antifungal agent. It is deemed necessary to note that this is the first report of terbinafine production by Lysinibacillus sp. MK212927, a fast-growing microbial source, with relatively high yield and that is subject to potential optimization for industrial production capabilities.
Preparation of Antihypertensive Drugs in Biological Matrix with Solvent Front Position Extraction for LC–MS/MS Analysis
Authors: Jaglińska Kamila , Polak Beata , Klimek-Turek Anna , Błaszczyk Robert , Wysokiński Andrzej , Dzido Tadeusz Henryk
Published: December 2021

Solvent front position extraction procedure was used to prepare biological samples containing selected antihypertensive drugs (ramipril, lercanidipine, indapamide, valsartan, hydrochlorothiazide, perindopril, and nebivolol). Substances separated from the biological matrix components (bovine serum albumin) were quantified by means of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Sample preparation process was performed with the use of a prototype horizontal chamber with a moving pipette driven by a 3D printer mechanism enabling a controlled eluent flow velocity. Application of this device was advantageous for simultaneous preparation of several samples for further quantitative analysis, with a synchronized reduction of manual operations and solvent consumption. Quantitative results obtained for the majority of the investigated antihypertensive drugs in a complex biological matrix were satisfactory. The values of the %RSD were around 5% for six of the seven substances (with the exception of indapamide). The method exhibits a suitable accuracy (the relative error percentage was below 10% for most drugs). The values of LOD and LOQ were in the range of 1.19 µg/L–8.53 µg/L and 3.61 µg/L–25.8 µg/L, respectively.
Total Fatty Acid and Polar Lipid Species Composition of Human Milk
Authors: Ahmed Talat Bashir , Eggesbø Merete , Criswell Rachel , Uhl Olaf , Demmelmair Hans , Koletzko Berthold
Published: December 2021

Human milk lipids are essential for infant health. However, little is known about the relationship between total milk fatty acid (FA) composition and polar lipid species composition. Therefore, we aimed to characterize the relationship between the FA and polar lipid species composition in human milk, with a focus on differences between milk with higher or lower milk fat content. From the Norwegian Human Milk Study (HUMIS, 2002–2009), a subset of 664 milk samples were analyzed for FA and polar lipid composition. Milk samples did not differ in major FA, phosphatidylcholine, or sphingomyelin species percentages between the highest and lowest quartiles of total FA concentration. However, milk in the highest FA quartile had a lower phospholipid-to-total-FA ratio and a lower sphingomyelin-to-phosphatidylcholine ratio than the lowest quartile. The only FAs associated with total phosphatidylcholine or sphingomyelin were behenic and tridecanoic acids, respectively. Milk FA and phosphatidylcholine and sphingomyelin species containing these FAs showed modest correlations. Associations of arachidonic and docosahexaenoic acids with percentages of phosphatidylcholine species carrying these FAs support the conclusion that the availability of these FAs limits the synthesis of phospholipid species containing them.
Seasonality of Coxiella burnetii among Wild Rabbits (Oryctolagus cuniculus) and the Hyalomma lusitanicum (Acari: Ixodidae) in a Meso-Mediterranean Ecosystem
Authors: Sánchez María , Valcárcel Félix , González Julia , González Marta G. , Martín-Hernández Raquel , Tercero José M. , González-Jara Pablo , Olmeda A. Sonia
Published: December 2021

(1) Background: Q fever is a worldwide zoonosis caused by Coxiella burnetii that have cases reported in humans and animals almost everywhere. The aim of this study was to describe the seasonality of Coxiella burnetii in the wild rabbit (Oryctolagus cuniculus) and the tick Hyalomma lusitanicum in a meso-Mediterranean ecosystem. (2) Methods: two populations of wild rabbits that differ in whether or not they share habitat with ungulates, mainly red deer (Cervus elaphus) were sampled for a year to collect ticks, blood and vaginal or anal swabs. Presence of C. burnetii DNA in swabs and the tick H. lusitanicum was determined by PCR and serum antibodies by ELISA. (3) Results: C. burnetii DNA was detected in 47.2% of 583 rabbits, in 65.5% of sera, and in more than half of the H. lusitanicum. There were small variations according to sex and age of the rabbits but significant according to the habitat (4) Conclusions: The results indicate that C. burnetii circulates freely between wild rabbits and H. lusitanicum and the sylvatic cycle in meso-Mediterranean environments relies in the presence of wild rabbits and H. lusitanicum above all if sharing habitat with red deer.
High-Precision Digital Surface Model Extraction from Satellite Stereo Images Fused with ICESat-2 Data
Authors: Ye Jiang , Qiang Yuxuan , Zhang Rui , Liu Xinguo , Deng Yixin , Zhang Jiawei
Published: December 2021

The lack of ground control points (GCPs) affects the elevation accuracy of digital surface models (DSMs) generated by optical satellite stereo images and limits the application of high-resolution DSMs. It is a feasible idea to use ICESat-2 (Ice, Cloud, and land Elevation Satellite-2) laser altimetry data to improve the elevation accuracy of optical stereo images, but it is necessary to accurately match the two types of data. This paper proposes a DSM registration strategy based on terrain similarity (BOTS), which integrates ICESat-2 laser altimetry data without GCPs and improves the DSM elevation accuracy generation from optical satellite stereo pairs. Under different terrain conditions, Worldview-2, SV-1, GF-7, and ZY-3 stereo pairs were used to verify the effectiveness of this method. The experimental results show that the BOTS method proposed in this paper is more robust when there are a large number of abnormal points in the ICESat-2 data or there is a large elevation gap between DSMs. After fusion of ICESat-2 data, the DSM elevation accuracy extracted from the satellite stereo pair is improved by 73~92%, and the root mean square error (RMSE) of Worldview-2 DSM reaches 0.71 m.
Atopic Status in Children with Asthma and Respiratory Allergies—Comparative Analysis of Total IgE, ImmunoCAP Phadiatop/fx5 and Euroimmun Pediatric Immunoblot
Authors: Lazova Snezhina , Baleva Marta , Priftis Stamatios , Naseva Emilia , Velikova Tsvetelina
Published: December 2021

Introduction: An atopic status assessment (skin prick test or specific immunoglobulin (sIgE)) in asthmatic children is considered a milestone in identifying potential risk factors and triggers provoking loss of asthma control and asthma exacerbation. Objective: The study aims to perform a comparative analysis of different laboratory methods for a serological assessment of an atopic status in asthma and respiratory allergies in children. Material and methods: A total of 86 children were included, all of whom were diagnosed with bronchial asthma, aged from 5 to 17 years and screened for total IgE level using enzyme-linked immunosorbent assay (ELISA). In 48 randomly selected children, we performed a semi-quantitative serological in vitro assessment of the specific IgE antibodies against food and aeroallergen, using two different laboratory methods—Euroimmun Immunoblot and ImmunoCAP (Phadiatop/fx5). Results: In 70% of the children with a history of allergies, and 65.3% without clinically manifested allergies, multiscreen test ImmunoCAP Phadiatop/fx5 showed positivity and confirmed atopy. Our results showed a significant moderate to strong correlation between multiscreen ImmunoCAP Phadiatop/fx5, and Euroimmun specific IgE titers against aero-allergens—cats, mites, tree mix and food allergens—soy, wheat (р = 0.006), rice, р = 0.090), apple р = 0.007) and peanut. A sensitivity of 63% and specificity of 73.5% was observed for EUROIMMUN Pediatric (food allergens, IgE titer > 1) compared with the gold standard ImmunoCap/fx5. The mean value of total IgE is significantly higher in children with asthma and concomitant with allergic rhinitis compared to those without allergic rhinitis (mean 202.52 U/mL, IQR 102.50 (24.20–363.95) vs. 316.68, IQR 261.00 (109.20–552.50), p = 0.005). Conclusion: Establishing the spectrum of the most common respiratory and food allergens is an essential factor for maintaining asthma control, both through a strategy to avoid allergen exposure and by developing a recommendation plan. The immunoblotting technique is easily applicable in daily clinical and laboratory practice. It is also a cost-effective and reliable alternative to the “gold standard” ImmunoCAP Phadiatop/fx5 in diagnosing atopy in children.
SIV Evolutionary Dynamics in Cynomolgus Macaques during SIV-Mycobacterium tuberculosis Co-Infection
Authors: Tisthammer Kaho H. , Kline Christopher , Rutledge Tara , Diedrich Collin R. , Ita Sergio , Lin Philana Ling , Ambrose Zandrea , Pennings Pleuni S.
Published: December 2021

Co-infection with Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) is a worldwide public health concern, leading to worse clinical outcomes caused by both pathogens. We used a non-human primate model of simian immunodeficiency virus (SIV)-Mtb co-infection, in which latent Mtb infection was established prior to SIVmac251 infection. The evolutionary dynamics of SIV env was evaluated from samples in plasma, lymph nodes, and lungs (including granulomas) of SIV-Mtb co-infected and SIV only control animals. While the diversity of the challenge virus was low and overall viral diversity remained relatively low over 6–9 weeks, changes in viral diversity and divergence were observed, including evidence for tissue compartmentalization. Overall, viral diversity was highest in SIV-Mtb animals that did not develop clinical Mtb reactivation compared to animals with Mtb reactivation. Among lung granulomas, viral diversity was positively correlated with the frequency of CD4+ T cells and negatively correlated with the frequency of CD8+ T cells. SIV diversity was highest in the thoracic lymph nodes compared to other sites, suggesting that lymphatic drainage from the lungs in co-infected animals provides an advantageous environment for SIV replication. This is the first assessment of SIV diversity across tissue compartments during SIV-Mtb co-infection after established Mtb latency.
Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells
Authors: Yang Xiao , Wan Mingming , Cai Linjun , Hou Ali , Sun Bo , Zhou Yan , Gao Feng , Su Weiheng , Jiang Chunlai
Published: December 2021

Inactivated vaccines based on cell culture are very useful in the prevention and control of many diseases. The most popular strategy for the production of inactivated vaccines is based on monkey-derived Vero cells, which results in high productivity of the virus but has a certain carcinogenic risk due to non-human DNA contamination. Since human diploid cells, such as MRC-5 cells, can produce a safer vaccine, efforts to develop a strategy for inactivated vaccine production using these cells have been investigated using MRC-5 cells. However, most viruses do not replicate efficiently in MRC-5 cells. In this study, we found that rabies virus (RABV) infection activated a robust interferon (IFN)-β response in MRC-5 cells but almost none in Vero cells, suggesting that the IFN response could be a key limiting factor for virus production. Treatment of the MRC-5 cells with IFN inhibitors increased RABV titers by 10-fold. Additionally, the RABV titer yield was improved five-fold when using IFN receptor 1 (IFNAR1) antibodies. As such, we established a stable IFNAR1-deficient MRC-5 cell line (MRC-5IFNAR1−), which increased RABV production by 6.5-fold compared to normal MRC-5 cells. Furthermore, in a pilot-scale production in 1500 square centimeter spinner flasks, utilization of the MRC-5IFNAR1− cell line or the addition of IFN inhibitors to MRC cells increased RABV production by 10-fold or four-fold, respectively. Thus, we successfully established a human diploid cell-based pilot scale virus production platform via inhibition of IFN response for rabies vaccines, which could also be used for other inactivated virus vaccine production.
BCG Substrains Change Their Outermost Surface as a Function of Growth Media
Authors: Guallar-Garrido Sandra , Almiñana-Rapún Farners , Campo-Pérez Víctor , Torrents Eduard , Luquin Marina , Julián Esther
Published: December 2021

Mycobacterium bovis bacillus Calmette-Guérin (BCG) efficacy as an immunotherapy tool can be influenced by the genetic background or immune status of the treated population and by the BCG substrain used. BCG comprises several substrains with genetic differences that elicit diverse phenotypic characteristics. Moreover, modifications of phenotypic characteristics can be influenced by culture conditions. However, several culture media formulations are used worldwide to produce BCG. To elucidate the influence of growth conditions on BCG characteristics, five different substrains were grown on two culture media, and the lipidic profile and physico-chemical properties were evaluated. Our results show that each BCG substrain displays a variety of lipidic profiles on the outermost surface depending on the growth conditions. These modifications lead to a breadth of hydrophobicity patterns and a different ability to reduce neutral red dye within the same BCG substrain, suggesting the influence of BCG growth conditions on the interaction between BCG cells and host cells.
International Efforts and Next Steps to Advance COVID-19 Vaccines Research and Production in Low- and Middle-Income Countries
Authors: Du Li , Wang Meng , Raposo Vera Lúcia
Published: December 2021

Equitable and efficient distribution of COVID-19 vaccines continues to be a key issue in global health, and a targeted approach is needed to meet the World Health Organization’s world vaccination targets. Although some low- and middle-income countries (LMICs) are developing their own vaccines to address the distribution problem, legal and technical challenges have had a negative impact on productivity. This article explores relevant international legal instruments that can enable faster research and development of COVID-19 vaccines in LMICs, focusing on the role of biosafety standards, biological materials transfer, and key knowledge sharing. Our analysis has established that the potential of existing global health legal instruments has yet to be realized in order to close the productivity gap in LMICs and strengthen their vaccine manufacturing capacity. Additionally, mutual recognition of vaccine efficacy has become a new challenge for achieving global vaccination targets. We argue that the World Health Organization should continue its leading position by developing a more practical and targeted framework to help LMICs overcome challenges arising from technology transfer, knowledge sharing, and politics.
Publicly Available Data-Based Flood Risk Assessment Methodology: A Case Study for a Floodplain in Poland
Authors: Bralewski Adrian , Bralewska Karolina
Published: December 2021

Flood risk assessment is used to estimate the expected consequences and probability of a flood. It leads to the strengthening of resilience through appropriate preparation for an event of a specific scale. The methodology described in this paper was developed by the authors for the purposes of flood risk assessment in Poland, introduced to and applied on an actual example. It is based on simple calculations and a comparison of the results with a template. All of the data required for calculation came from freely available sources. Therefore, it is essential to evaluate the effectiveness of the flood risk assessment methodology in improving construction safety and identifying the factors that influence its implementation. The approach presented in this article is based on implementation of the parameters of floods, describing the characteristics of the exposed area and human vulnerability, among other factors, to the national risk assessment methodology, and then using it to determine the directions of activities aimed at reducing the risk of flooding. Simultaneously, assessment of these parameters might not be related directly to flood threats, but rather to the broader approach to risk assessment, including other threats. As a result of the application of the described methodology, it was estimated that the flood risk in the studied area is catastrophic, which requires immediate decisions of people responsible for safety.
Drug-Induced Liver Injuries as a Complication of Therapy Gestagens for Miscarriage
Authors:   Smolensk State Medical University, Argunova I.A. ,   Perinatal Center of the Clinical Hospital № 1, Smolensk,   Center of IVF, Smolensk
Published: December 2021

An increase of liver function scores may be related to rarely diagnosed drug-induced liver injuries. Their frequency of pregnant women is increasing against the background of therapy of miscarriage with gestagens, which have potential heptotoxicity. The clinical case with the progression of acute hepatitis caused by the use of dydrogesterone and micronized progesterone was analyzed according to the criteria of the European Association for the Study of the Liver and the RUCAM scale, taking into account the physiological growth of alkaline phosphatase activity during gestation. The probability of drug damage to the liver, risk factors, variant, severity were determined. Typical mistakes in diagnosis and treatment are shown, recommendations are given on the use of hepatoprotectors in women with this pathology. An opinion about the genetic relationship of gestagen-induced liver damage and intrahepatic cholestasis of pregnancy and the need to create clinical guidelines for the management of pregnant women with drug-induced liver injuries was expressed
Some Approaches to the Therapy of Changes in Intestinal Microbiocenosis in Non-Alcoholic Steatohepatitis
Authors:   Saratov State Medical University named after V.I. Razumovsky, Kozlova I.V. , Lapteva E.A. , Bykova A.P. , Pakhomova A.L. ,   Penza State University
Published: December 2021

The aim is to evaluate the effectiveness of complex therapy with the inclusion of the drug Saccharomyces boulardii in patients with non-alcoholic steatohepatitis (NASH) and intestinal dysfunction. Material and methods. An open prospective comparative study of the effectiveness of complex therapy of intestinal dysfunction in patients with non-alcoholic steatohepatitis was carried out. The study included two groups of 36 patients with NASH with symptoms of intestinal dysfunction, established intestinal dysbiosis, structural changes in the mucous membrane of the colon. Results and discussion. It was found that the complex therapy of intestinal dysfunction with the inclusion of the drug Saccharomyces boulardii against the background of NASH reduces the frequency of abdominal pain associated with the intestines, normalizes stool, reduces the degree of dysbiosis, promotes epithelialization of microerosions, and reduces the frequency of neutrophilic infiltration of the colon mucosa. Conclusion. The results of the study indicate the effectiveness of complex therapy with the addition of Saccharomyces boulardii in patients with NASH and intestinal dysfunction