bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of FACS and PCR for Detection of BCMA-CAR-T Cells
Authors: Reichman Avinoam , Kunz Alexander , Joedicke Jara J. , Höpken Uta E. , Keib Anna , Neuber Brigitte , Sedloev David , Wang Lei , Jiang Genqiao , Hückelhoven-Krauss Angela , Eberhardt Franziska , Müller-Tidow Carsten , Wermke Martin , Rehm Armin , Schmitt Michael , Schmitt Anita
Published: January 2022

Chimeric-antigen-receptor (CAR)-T-cell therapy is already widely used to treat patients who are relapsed or refractory to chemotherapy, antibodies, or stem-cell transplantation. Multiple myeloma still constitutes an incurable disease. CAR-T-cell therapy that targets BCMA (B-cell maturation antigen) is currently revolutionizing the treatment of those patients. To monitor and improve treatment outcomes, methods to detect CAR-T cells in human peripheral blood are highly desirable. In this study, three different detection reagents for staining BCMA-CAR-T cells by flow cytometry were compared. Moreover, a quantitative polymerase chain reaction (qPCR) to detect BCMA-CAR-T cells was established. By applying a cell-titration experiment of BCMA-CAR-T cells, both methods were compared head-to-head. In flow-cytometric analysis, the detection reagents used in this study could all detect BCMA-CAR-T cells at a similar level. The results of false-positive background staining differed as follows (standard deviation): the BCMA-detection reagent used on the control revealed a background staining of 0.04% (±0.02%), for the PE-labeled human BCMA peptide it was 0.25% (±0.06%) and for the polyclonal anti-human IgG antibody it was 7.2% (±9.2%). The ability to detect BCMA-CAR-T cells down to a concentration of 0.4% was similar for qPCR and flow cytometry. The qPCR could detect even lower concentrations (0.02–0.01%). In summary, BCMA-CAR-T-cell monitoring can be reliably performed by both flow cytometry and qPCR. In flow cytometry, reagents with low background staining should be preferred.
Novel Putative Transposable Element Associated with the Subtype E5 Botulinum Toxin Gene Cluster of Neurotoxigenic Clostridium butyricum Type E Strains from China
Authors: Li Tao , Ning Nianzhi , Iacobino Angelo , Zhang Liangyan , Wang Hui , Franciosa Giovanna
Published: January 2022

Previously, a whole-genome comparison of three Clostridium butyricum type E strains from Italy and the United States with different C. botulinum type E strains indicated that the bont/e gene might be transferred between the two clostridia species through transposition. However, transposable elements (TEs) have never been identified close to the bont/e gene. Herein, we report the whole genome sequences for four neurotoxigenic C. butyricum type E strains that originated in China. An analysis of the obtained genome sequences revealed the presence of a novel putative TE upstream of the bont/e gene in the genome of all four strains. Two strains of environmental origin possessed an additional copy of the putative TE in their megaplasmid. Similar putative TEs were found in the megaplasmids and, less frequently, in the chromosomes of several C. butyricum strains, of which two were neurotoxigenic C. butyricum type E strains, and in the chromosome of a single C. botulinum type E strain. We speculate that the putative TE might potentially transpose the bont/e gene at the intracellular and inter-cellular levels. However, the occasional TE occurrence in the clostridia genomes might reflect rare transposition events.
Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, cis-Dihydroxylation and Epoxidation
Authors: Boyd Derek R. , Sharma Narain D. , Stevenson Paul J. , Hoering Patrick , Allen Christopher C. R. , Dansette Patrick M.
Published: January 2022

Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic thiophenes. Thiophene oxidative dearomatization pathways involve reactive metabolites, whose detection is important in the pharmaceutical industry, and are catalyzed by monooxygenase (sulfoxidation, epoxidation) and dioxygenase (sulfoxidation, dihydroxylation) enzymes. Sulfoxide and epoxide metabolites of thiophene substrates are often unstable, and, while cis-dihydrodiol metabolites are more stable, significant challenges are presented by both types of metabolite. Prediction of the structure, relative and absolute configuration, and enantiopurity of chiral metabolites obtained from thiophene enzymatic oxidation depends on the substrate, type of oxygenase selected, and molecular docking results. The racemization and dimerization of sulfoxides, cis/trans epimerization of dihydrodiol metabolites, and aromatization of epoxides are all factors associated with the mono- and di-oxygenase-catalyzed metabolism of thiophenes and thiophene-containing drugs and their applications in chemoenzymatic synthesis and medicine.
Narrative Medicine: A Digital Diary in the Management of Bone and Soft Tissue Sarcoma Patients. Preliminary Results of a Multidisciplinary Pilot Study
Authors: Cercato Maria Cecilia , Vari Sabrina , Maggi Gabriella , Faltyn Wioletta , Onesti Concetta Elisa , Baldi Jacopo , Scotto di Uccio Alessandra , Terrenato Irene , Molinaro Claudia , Scarinci Virginia , Servoli Francesca , Cenci Cristina , Biagini Roberto , Ferraresi Virginia
Published: January 2022

Background. Guidelines for the implementation of narrative medicine in clinical practice exist; however, in Italy, no standard methodology is currently available for the management of oncological patients. Since 2017, at the “Regina Elena” National Cancer Institute, studies using “digital narrative diaries” (DNMLAB platform) have been carried out; this article focuses on a pilot, uncontrolled, real-life study aiming to evaluate the utility of DNM integrated with the care pathway of patients with bone and limb soft tissue sarcomas. Methods. Adult patients completed the diary during treatment or follow-up by writing their narrative guided by a set of narrative prompts. The endpoints were: (a) patients’ opinions about therapeutic alliance, awareness, and coping ability; (b) healthcare professionals’ (HCPs’) opinions about communication, therapeutic alliance, and information collection. Open- and closed-ended questions (Likert score: 1–5) were used to assess the items. Results. At the interim analysis of data from seven patients and five HCPs, DNM was shown to improve: (a) the expression of patients’ point of view, the perception of effective taking charge, disease awareness, and self-empowerment (score: 4.8/5); (b) patients’ communication, relationships, and illness knowledge (score: 4.6–4.8/5). Conclusions. The preliminary results supported the need to integrate patients’ narratives with clinical data and encourage further research.
Causal Discovery in Manufacturing: A Structured Literature Review
Authors: Vuković Matej , Thalmann Stefan
Published: January 2022

Industry 4.0 radically alters manufacturing organization and management, fostering collection and analysis of increasing amounts of data. Advanced data analytics, such as machine learning (ML), are essential for implementing Industry 4.0 and obtaining insights regarding production, better decision support, and enhanced manufacturing quality and sustainability. ML outperforms traditional approaches in many cases, but its complexity leads to unclear bases for decisions. Thus, acceptance of ML and, concomitantly, Industry 4.0, is hindered due to increasing requirements of fairness, accountability, and transparency, especially in sensitive-use cases. ML does not augment organizational knowledge, which is highly desired by manufacturing experts. Causal discovery promises a solution by providing insights on causal relationships that go beyond traditional ML’s statistical dependency. Causal discovery has a theoretical background and been successfully applied in medicine, genetics, and ecology. However, in manufacturing, only experimental and scattered applications are known; no comprehensive overview about how causal discovery can be applied in manufacturing is available. This paper investigates the state and development of research on causal discovery in manufacturing by focusing on motivations for application, common application scenarios and approaches, impacts, and implementation challenges. Based on the structured literature review, four core areas are identified, and a research agenda is proposed.
Decision-Making Strategy for Digital Transformation: A Two-Year Analytical Study and Follow-Up Concerning Innovative Improvements in University e-Services
Authors: Brdesee Hani , Alsaggaf Wafaa
Published: January 2022

Universities worldwide strive to provide the best student services possible, particularly those that support student achievements and career goals. Therefore, academic advising continues to be a significant part of the student experience, one which universities need to fully understand in terms of its objectives, application processes, and required skill. As a result of significant technological improvements since the turn of the millennium, including expanding internet applications and digital transformations, universities have established computer information systems that support academic advising and course registration services. This study examined the effects of modifications to the electronic academic advising and course registration systems at King Abdulaziz University in 2018, and then again in 2020, following a university-wide system failure in 2018 resulting from a demand overload. In 2018, a preliminary statistical analysis and student feedback survey were conducted by the authors to measure student satisfaction with the online portal On-Demand University Services (ODUS Plus). In addition to recommendations suggested by the 2018 analysis such as balancing the load distribution of the university’s network, organizational (i.e., non-technical) solutions, rules, and regulations were adjusted such as progressive course registration that prioritized those expected to graduate first. The survey and analysis were repeated by the authors in 2020 to assess improvements in student satisfaction. As a result of the changes, the investigation revealed improved student satisfaction with the performance of ODUS Plus and network access. Overall, students were significantly more satisfied in 2020 than in 2018. This research shows that some technical challenges can be resolved using re-engineered processes and organizational solutions.
Ritonavir and xk263 Binding-Unbinding with HIV-1 Protease: Pathways, Energy and Comparison
Authors: Sun Jianan , Raymundo Mark Anthony V. , Chang Chia-En A.
Published: January 2022

Understanding non-covalent biomolecular recognition, which includes drug–protein bound states and their binding/unbinding processes, is of fundamental importance in chemistry, biology, and medicine. Fully revealing the factors that govern the binding/unbinding processes can further assist in designing drugs with desired binding kinetics. HIV protease (HIVp) plays an integral role in the HIV life cycle, so it is a prime target for drug therapy. HIVp has flexible flaps, and the binding pocket can be accessible by a ligand via various pathways. Comparing ligand association and dissociation pathways can help elucidate the ligand–protein interactions such as key residues directly involved in the interaction or specific protein conformations that determine the binding of a ligand under certain pathway(s). Here, we investigated the ligand unbinding process for a slow binder, ritonavir, and a fast binder, xk263, by using unbiased all-atom accelerated molecular dynamics (aMD) simulation with a re-seeding approach and an explicit solvent model. Using ritonavir-HIVp and xk263-HIVp ligand–protein systems as cases, we sampled multiple unbinding pathways for each ligand and observed that the two ligands preferred the same unbinding route. However, ritonavir required a greater HIVp motion to dissociate as compared with xk263, which can leave the binding pocket with little conformational change of HIVp. We also observed that ritonavir unbinding pathways involved residues which are associated with drug resistance and are distal from catalytic site. Analyzing HIVp conformations sampled during both ligand–protein binding and unbinding processes revealed significantly more overlapping HIVp conformations for ritonavir-HIVp rather than xk263-HIVp. However, many HIVp conformations are unique in xk263-HIVp unbinding processes. The findings are consistent with previous findings that xk263 prefers an induced-fit model for binding and unbinding, whereas ritonavir favors a conformation selection model. This study deepens our understanding of the dynamic process of ligand unbinding and provides insights into ligand–protein recognition mechanisms and drug discovery.
Tissue Engineering and Regeneration of the Human Hair Follicle in Androgenetic Alopecia: Literature Review
Authors: Llamas-Molina José María , Carrero-Castaño Alejandro , Ruiz-Villaverde Ricardo , Campos Antonio
Published: January 2022

Androgenetic alopecia (AGA) is an androgen-dependent process and represents the most frequent non-scarring alopecia. Treatments for AGA do not always achieve a satisfactory result for the patient, and sometimes cause side effects that lead to discontinuation of treatment. AGA therapeutics currently includes topical and oral drugs, as well as follicular unit micro-transplantation techniques. Tissue engineering (TE) is postulated as one of the possible future solutions to the problem and aims to develop fully functional hair follicles that maintain their cyclic rhythm in a physiological manner. However, despite its great potential, reconstitution of fully functional hair follicles is still a challenge to overcome and the knowledge gained of the key processes in hair follicle morphogenesis and biology has not yet been translated into effective replacement therapies in clinical practice. To achieve this, it is necessary to research and develop new approaches, techniques and biomaterials. In this review, present and emerging hair follicle bioengineering strategies are evaluated. The current problems of these bioengineering techniques are discussed, as well as the advantages and disadvantages, and the future prospects for the field of TE and successful hair follicle regeneration.
Neurological Complications of Biological Treatment of Psoriasis
Authors: Ożóg Mateusz , Grabarek Beniamin , Wierzbik-Strońska Magdalena , Świder Magdalena
Published: January 2022

In the available literature, little attention has been paid to the assessment of psoriasis and the biological therapy used for it and the nervous system. The purpose of this article is to discuss the relationship between psoriasis and the nervous system as well as to analyze the mechanisms that lead to neurological complications during anticytokine therapies in psoriasis. However, this connection requires further analysis. The use of biological drugs in psoriasis, although it yields positive therapeutic results, is not without numerous side effects. Serious neurological side effects of the therapy are most often visible with the use of anti-TNF-alpha, which is why patients should be monitored for their potential occurrence. Early detection of complications and rapid discontinuation of treatment with the drug may potentially increase the patient’s chances of a full recovery or improvement of his/her neurological condition. It also seems reasonable that, in the case of complications occurring during anti-TNF-alpha therapy, some of the drugs from other groups should be included in the therapy.
Zinc Oxide Synthesis from Extreme Ratios of Zinc Acetate and Zinc Nitrate: Synergistic Morphology
Authors: Kaenphakdee Sujittra , Putthithanas Pimpaka , Yodyingyong Supan , Leelawattanachai Jeerapond , Triampo Wannapong , Sanpo Noppakun , Jitputti Jaturong , Triampo Darapond
Published: January 2022

The synthesis of ZnO comprising different ratios of zinc acetate (ZA) and zinc nitrate (ZN) from the respective zinc precursor solutions was successfully completed via a simple precipitation method. Zinc oxide powders with different mole ratios of ZA/ZN were produced—80/1, 40/1, and 20/1. The crystallinity, microstructure, and optical properties of all produced ZnO powders were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV-Vis-NIR spectrophotometry. The average agglomerated particle sizes of ZnO-80/1, ZnO-40/1, and ZnO-20/1 were measured at 655, 640, and 620 nm, respectively, using dynamic light scattering (DLS). The optical properties of ZnO were significantly affected by the extreme ratio differences in the zinc precursors. ZnO-80/1 was found to have a unique coral-sheet structure morphology, which resulted in its superior ability to reflect near-infrared (NIR) radiation compared to ZnO-40/1 and ZnO-20/1. The NIR-shielding performances of ZnO were assessed using a thermal insulation test, where coating with ZnO-80/1 could lower the inner temperature by 5.2 °C compared with the neat glass substrate. Due to the synergistic effects on morphology, ZnO-80/1 exhibited the property of enhanced NIR shielding in curtailing the internal building temperature, which allows for its utilization as an NIR-reflective pigment coating in the construction of building envelopes.
Printed Nanocarbon Heaters for Stretchable Sport and Leisure Garments
Authors: Claypole Andrew , Claypole James , Bezodis Neil , Kilduff Liam , Gethin David , Claypole Tim
Published: January 2022

The ability to maintain body temperature has been shown to bring about improvements in sporting performance. However, current solutions are limited with regards to flexibility, heating uniformity and robustness. An innovative screen-printed Nanocarbon heater is demonstrated which is robust to bending, folding, tensile extensions of up to 20% and machine washing. This combination of ink and substrate enables the heated garments to safely flex without impeding the wearer. It is capable of producing uniform heating over a 15 × 4 cm area using a conductive ink based on a blend of Graphite Nanoplatelets and Carbon Black. This can be attributed to the low roughness of the conductive carbon coating, the uniform distribution and good interconnection of the carbon particles. The heaters have a low thermal inertia, producing a rapid temperature response at low voltages, reaching equilibrium temperatures within 120 s of being switched on. The heaters reached the 40 °C required for wearable heating applications within 20 s at 12 Volts. Screen printing was demonstrated to be an effective method of controlling the printed layer thickness with good interlayer adhesion and contact for multiple printed layers. This can be used to regulate their electrical properties and hence adjust the heater performance.
Symmetry Analysis of Magnetoelectric Effects in Perovskite-Based Multiferroics
Authors: Gareeva Zukhra , Zvezdin Anatoly , Zvezdin Konstantin , Chen Xiangming
Published: January 2022

In this article, we performed symmetry analysis of perovskite-based multiferroics: bismuth ferrite (BiFeO3)-like, orthochromites (RCrO3), and Ruddlesden–Popper perovskites (Ca3Mn2O7-like), being the typical representatives of multiferroics of the trigonal, orthorhombic, and tetragonal crystal families, and we explored the effect of crystallographic distortions on magnetoelectric properties. We determined the principal order parameters for each of the considered structures and obtained their invariant combinations consistent with the particular symmetry. This approach allowed us to analyze the features of the magnetoelectric effect observed during structural phase transitions in BixR1−xFeO3 compounds and to show that the rare-earth sublattice has an impact on the linear magnetoelectric effect allowed by the symmetry of the new structure. It was shown that the magnetoelectric properties of orthochromites are attributed to the couplings between the magnetic and electric dipole moments arising near Cr3+ ions due to distortions linked with rotations and deformations of the CrO6 octahedra. For the first time, such a symmetry consideration was implemented in the analysis of the Ruddlesden–Popper structures, which demonstrates the possibility of realizing the magnetoelectric effect in the Ruddlesden–Popper phases containing magnetically active cations, and allows the estimation of the conditions required for its optimization.
Biomechanical Analyses of Porous Designs of 3D-Printed Titanium Implant for Mandibular Segmental Osteotomy Defects
Authors: Shen Yen-Wen , Tsai Yuen-Shan , Hsu Jui-Ting , Shie Ming-You , Huang Heng-Li , Fuh Lih-Jyh
Published: January 2022

Clinically, a reconstruction plate can be used for the facial repair of patients with mandibular segmental defects, but it cannot restore their chewing function. The main purpose of this research is to design a new three-dimensionally (3D) printed porous titanium mandibular implant with both facial restoration and oral chewing function reconstruction. Its biomechanical properties were examined using both finite element analysis (FEA) and in vitro experiments. Cone beam computed tomography images of the mandible of a patient with oral cancer were selected as a reference to create 3D computational models of the bone and of the 3D-printed porous implant. The pores of the porous implant were circles or hexagons of 1 or 2 mm in size. A nonporous implant was fabricated as a control model. For the FEA, two chewing modes, namely right unilateral molar clench and right group function, were set as loading conditions. Regarding the boundary condition, the displacement of both condyles was fixed in all directions. For the in vitro experiments, an occlusal force (100 N) was applied to the abutment of the 3D-printed mandibular implants with and without porous designs as the loading condition. The porous mandibular implants withstood higher stress and strain than the nonporous mandibular implant, but all stress values were lower than the yield strength of Ti-6Al-4V (800 MPa). The strain value of the bone surrounding the mandibular implant was affected not only by the shape and size of the pores but also by the chewing mode. According to Frost’s mechanostat theory of bone, higher bone strain under the porous implants might help maintain or improve bone quality and bone strength. The findings of this study serve as a biomechanical reference for the design of 3D-printed titanium mandibular implants and require confirmation through clinical investigations.
The Effect of Coatings on Cutting Force in Turning of C45 Steel
Authors: Kovalčík Jaroslav , Mašek Petr , Malý Jan , Kožmín Pavel , Syrovátka Jiří
Published: January 2022

This article focuses on the development of a mathematical model of a cutting force that is applicable for coated and uncoated cutting tool inserts and aims to enable more accurate calculation of the cutting force. Two common PVD coatings, AlTiN and TiAlCrN, were used. Firstly, a mathematical model of the cutting force based on the specific cutting force and cutting area is proposed. This mathematical model considers the cutting speed and coating correction factor as well as the real cutting edge geometry, i.e., it includes both the straight and rounded parts of the cutting edge. For this proposed model, material constants for C45 steel, which was machined with uncoated inserts, were obtained. Before determining an equation for a coating correction factor and implementing it into the model, experimental cutting force data for coated and uncoated inserts were compared using a paired t-test. The result was that the difference between them was statistically significant. Their percentage difference was found to be up to 4%. The correction factor equation that was obtained and implemented into the mathematical model was applied to compare the calculated and experimental data of the coated inserts, also using a paired t-test. The result was that the difference between them was insignificant. Moreover, their percentage difference was found to be up to 0.6%.
Role of Cyclic Thermal Shocks on the Physical and Mechanical Responses of White Marble
Authors: Feng Yujie , Su Haijian , Nie Yinjiang , Zhao Honghui
Published: January 2022

Marble is a common rock used in many buildings for structural or ornamental purposes and is widely distributed in underground engineering projects. The rocks are exposed to high temperatures when a tunnel fire occurs, and they will be rapidly cooled during the rescue process, which has a great impact on the rock performance and the underground engineering stability. Therefore, the role of cyclic thermal shocks on the physical and mechanical properties of marble specimens was systematically investigated. Different cyclic thermal shock treatments (T = 25, 200, 400, 600, 800 °C; N = 1, 3, 5, 7, 9) were applied to marble specimens and the changes in mass, volume, density and P-wave velocity were recorded in turn. Then, the thermal conductivity, optical microscopy and uniaxial compression tests were carried out. The results showed that both the cyclic thermal shock numbers (N) and the temperature level (T) weaken the rock properties. When the temperature of a thermal shock exceeds 600 °C, the mass loss coefficient and porosity of the marble will increase significantly. The most noticeable change in P-wave velocity occurs between 200 and 400 °C, with a 52.98% attenuation. After three thermal shocks, the cyclic thermal shock numbers have little influence on the uniaxial compressive strength and Young’s modulus of marble specimens. Shear failure is the principal failure mode in marble specimens that have experienced severe thermal damage (high N or T). The optical microscopic pictures are beneficial for illustrating the thermal cracking mechanism of marble specimens after cyclic thermal shocks.
Multiagent Control of Airplane Wing Stability with “Feathers” under the Flexural Torsional Flutter
Authors: Shalymov Dmitry , Granichin Oleg , Ivanskiy Yury , Volkovich Zeev
Published: January 2022

This paper proposes a novel method for the unbounded oscillation prevention of an aircraft wing under the flexural torsional flutter, an innovative multiagent attitude to control an aircraft wing with a surface consisting of managed rotating “feathers” (agents). Theoretical evaluation of the method demonstrates its high aptitude to avoid an aircraft wing’s flexural-torsional vibrations via expansion of the model’s ability to dampen the wing oscillations. It potentially allows increasing an aircraft’s speed without misgiving of the flutter. A new way to control an aircraft wing based on the Speed-Gradient methodology is suggested to increase the maximal possible flight speed without a flutter occurrence. Provided experiments demonstrate the theoretical advantage of the multiagent approach to the “feathers” rotation control.
Precorrected-FFT Accelerated Singular Boundary Method for High-Frequency Acoustic Radiation and Scattering
Authors: Li Weiwei , Wang Fajie
Published: January 2022

This paper presents a precorrected-FFT (pFFT) accelerated singular boundary method (SBM) for acoustic radiation and scattering in the high-frequency regime. The SBM is a boundary-type collocation method, which is truly free of mesh and integration and easy to program. However, due to the expensive CPU time and memory requirement in solving a fully-populated interpolation matrix equation, this method is usually limited to low-frequency acoustic problems. A new pFFT scheme is introduced to overcome this drawback. Since the models with lots of collocation points can be calculated by the new pFFT accelerated SBM (pFFT-SBM), high-frequency acoustic problems can be simulated. The results of numerical examples show that the new pFFT-SBM possesses an obvious advantage for high-frequency acoustic problems.
Characterizing Base in Warped Product Submanifolds of Complex Projective Spaces by Differential Equations
Authors: Alkhaldi Ali H. , Laurian-Ioan Pişcoran , Ahmad Izhar , Ali Akram
Published: January 2022

In this study, a link between the squared norm of the second fundamental form and the Laplacian of the warping function for a warped product pointwise semi-slant submanifold Mn in a complex projective space is presented. Some characterizations of the base NT of Mn are offered as applications. We also look at whether the base NT is isometric to the Euclidean space Rp or the Euclidean sphere Sp, subject to some constraints on the second fundamental form and warping function.
Lipid Indexes and Quality Evaluation of Omega-3 Rich Oil from the Waste of Japanese Spanish Mackerel Extracted by Supercritical CO2
Authors: Roy Vikash Chandra , Park Jin-Seok , Ho Truc Cong , Chun Byung-Soo
Published: January 2022

Japanese Spanish mackerel (JSM) (Scomberomorus niphonius) is a marine fish species containing health-beneficial polyunsaturated fatty acids (PUFAs). In the present study, the quality of JSM by-products oils extracted by supercritical CO2 (SC-CO2) and organic solvent extraction was compared in terms of physico-chemical properties of the oils. Eicosapentaenoic acid (EPA) is one of the important polyunsaturated fatty acids present in SC-CO2-extracted skin and muscle oil 5.81 ± 0.69% and 4.93 ± 0.06%, respectively. The amount of docosahexaenoic acid (DHA) in SC-CO2-extracted skin and muscle oil was 12.56 ± 0.38% and 15.01 ± 0.28%, respectively. EPA and DHA are considered as important PUFAs for the development of brain function and the prevention of coronary heart diseases. Extracted oils showed considerable antioxidant activity. In the obtained oils, atherogenic index (AI) values varied from 0.72 to 0.93 and thrombogenic index (TI) ranged from 0.75 to 0.92, which is considered an acceptable level. Fatty acid composition, bio potentiality, thermogravimetric, and vitamin D analysis showed that oils extracted from JSM by-products can be a good source of oil for application in food, pharmaceutical and cosmetic industries. Therefore, the present research revealed the potentiality of green valorisation of S. niphonius by-products as a possible sustainable approach for targeting the era of zero waste.
Prevention of Secondary Lymphedema after Complete Lymph Node Dissection in Melanoma Patients: The Role of Preventive Multiple Lymphatic–Venous Anastomosis in Observational Era
Authors: Nacchiero Eleonora , Maruccia Michele , Robusto Fabio , Elia Rossella , De Cosmo Alessio , Giudice Giuseppe
Published: January 2022

Background and Objectives: Current guidelines have limited the performance of complete lymph node dissection (CLND) for patients with clinically detectable lymphatic metastases. Despite the limitations of this surgical procedure, secondary lymphedema (SL) is an unsolved problem that affects approximately 20% of patients undergoing CLND. Preventive lymphatic–venous micro-anastomoses (PMLVA) has already demonstrated its efficacy in the prevention of SL in melanoma patients with a positive sentinel lymph node biopsy (SLNB), but the efficacy of this procedure is not demonstrated in patients with clinically detectable lymphatic metastases. Materials and Methods: This retrospective cohort study, was performed in two observation periods. Until March 2018, CLND was proposed to all subjects with positive-SLNB andPMLVA was performed in a subgroup of patients with risk factors for SL (Group 1). From April 2018, according to the modification of melanoma guidelines, all patients with detectable metastatic lymph nodes underwent PMLVA during CLND (Group 2). The frequency of lymphedema in subjects undergoing PMLVA was compared with the control group. Results: Database evaluation revealed 172 patients with melanoma of the trunk with follow-up information for at least 6 mounts. Twenty-three patients underwent PMLVA during CLND until March 2018, 29 from April 2018, and 120 subjects underwent CLND without any preventive surgery (control Group). The frequency of SL was significantly lower in both Group 1 (4.3% vs. 24.2%, p = 0.03) and Group 2 (3.5%, p = 0.01). Patients undergoing PMLVA showed a similar recurrence-free periods and overall survival when compared to the control group. Conclusions: PMLVA significantly reduces the frequency of SL both in immediate and delayed CLND. This procedure is safe and does not lead to an increase in length of hospitalization.
Difficult Biliary Stones: A Comprehensive Review of New and Old Lithotripsy Techniques
Authors: Troncone Edoardo , Mossa Michelangela , De Vico Pasquale , Monteleone Giovanni , Del Vecchio Blanco Giovanna
Published: January 2022

Biliary stones represent the most common indication for therapeutic endoscopic retrograde cholangiopancreatography. Many cases are successfully managed with biliary sphincterotomy and stone extraction with balloon or basket catheters. However, more complex conditions secondary to the specific features of stones, the biliary tract, or patient’s needs could make the stone extraction with the standard techniques difficult. Traditionally, mechanical lithotripsy with baskets has been reported as a safe and effective technique to achieve stone clearance. More recently, the increasing use of endoscopic papillary large balloon dilation and the diffusion of single-operator cholangioscopy with laser or electrohydraulic lithotripsy have brought new, safe, and effective therapeutic possibilities to the management of such challenging cases. We here summarize the available evidence about the endoscopic management of difficult common bile duct stones and discuss current indications of different lithotripsy techniques.
Cellulose Membranes in the Treatment of Spent Deep Eutectic Solvent Used in the Recovery of Lignin from Lignocellulosic Biomass
Authors: Ippolitov Vadim , Anugwom Ikenna , van Deun Robin , Mänttäri Mika , Kallioinen-Mänttäri Mari
Published: January 2022

Ultrafiltration was employed in the purification of spent Deep Eutectic Solvent (DES, a mixture of choline chloride and lactic acid, 1:10, respectively) used in the extraction of lignin from lignocellulosic biomass. The aim of this was to recover different lignin fractions and to purify spent solvent. The results revealed that the commercial regenerated cellulose membranes—RC70PP and Ultracel 5 kDa UF membranes—could be used in the treatment of the spent DES. The addition of cosolvent (ethanol) to the spent DES decreased solvent’s viscosity, which enabled filtration. With two-pass ultrafiltration process with 10 kDa and 5 kDa membranes about 95% of the dissolved polymeric compounds (lignin and hemicelluloses) were removed from the spent DES. The utilized membranes also showed the capability to fractionate polymeric compounds into two fractions—above and under 10,000 Da. Moreover, the 10 kDa cellulose-based membrane showed good stability during a continuous period of three weeks exposure to the solution of DES and ethanol. Its pure water permeability decreased only by 3%. The results presented here demonstrate the possibility to utilize cellulose membranes in the treatment of spent DES to purify the solvent and recover the interesting compounds.
Hydrophobic Mismatch Controls the Mode of Membrane-Mediated Interactions of Transmembrane Peptides
Authors: Kondrashov Oleg V. , Kuzmin Peter I. , Akimov Sergey A.
Published: January 2022

Various cellular processes require the concerted cooperative action of proteins. The possibility for such synchronization implies the occurrence of specific long-range interactions between the involved protein participants. Bilayer lipid membranes can mediate protein–protein interactions via relatively long-range elastic deformations induced by the incorporated proteins. We considered the interactions between transmembrane peptides mediated by elastic deformations using the framework of the theory of elasticity of lipid membranes. An effective peptide shape was assumed to be cylindrical, hourglass-like, or barrel-like. The interaction potentials were obtained for membranes of different thicknesses and elastic rigidities. Cylindrically shaped peptides manifest almost neutral average interactions—they attract each other at short distances and repel at large ones, independently of membrane thickness or rigidity. The hourglass-like peptides repel each other in thin bilayers and strongly attract each other in thicker bilayers. On the contrary, the barrel-like peptides repel each other in thick bilayers and attract each other in thinner membranes. These results potentially provide possible mechanisms of control for the mode of protein–protein interactions in membrane domains with different bilayer thicknesses.
Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities
Authors: Lao-Martil David , Verhagen Koen , Schmitz Joep , Teusink Bas , Wahl S. , van Riel Natal
Published: January 2022

Central carbon metabolism comprises the metabolic pathways in the cell that process nutrients into energy, building blocks and byproducts. To unravel the regulation of this network upon glucose perturbation, several metabolic models have been developed for the microorganism Saccharomyces cerevisiae. These dynamic representations have focused on glycolysis and answered multiple research questions, but no commonly applicable model has been presented. This review systematically evaluates the literature to describe the current advances, limitations, and opportunities. Different kinetic models have unraveled key kinetic glycolytic mechanisms. Nevertheless, some uncertainties regarding model topology and parameter values still limit the application to specific cases. Progressive improvements in experimental measurement technologies as well as advances in computational tools create new opportunities to further extend the model scale. Notably, models need to be made more complex to consider the multiple layers of glycolytic regulation and external physiological variables regulating the bioprocess, opening new possibilities for extrapolation and validation. Finally, the onset of new data representative of individual cells will cause these models to evolve from depicting an average cell in an industrial fermenter, to characterizing the heterogeneity of the population, opening new and unseen possibilities for industrial fermentation improvement.
Plethora of Resistance Genes in Carbapenem-Resistant Gram-Negative Bacteria in Greece: No End to a Continuous Genetic Evolution
Authors: Tsilipounidaki Katerina , Athanasakopoulou Zoi , Müller Elke , Burgold-Voigt Sindy , Florou Zoi , Braun Sascha D. , Monecke Stefan , Gatselis Nikolaos K. , Zachou Kalliopi , Stefos Aggelos , Tsagalas Ilias , Sofia Marina , Spyrou Vassiliki , Billinis Charalambos , Dalekos George N. , Ehricht Ralf , Petinaki Efthymia
Published: January 2022

Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four K. pneumoniae ST258, seven different profiles among the eight K. pneumoniae ST11, four profiles among the six A. baumannii ST409 and two among the three K. oxytoca. This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.
Antimicrobial Susceptibility of Persister Biofilm Cells of Bacillus cereus and Pseudomonas fluorescens
Authors: Fernandes Susana , Gomes Inês B. , Sousa Sérgio F. , Simões Manuel
Published: January 2022

The present study evaluates the antimicrobial susceptibility of persister cells of Bacillus cereus and Pseudomonas fluorescens after their regrowth in suspension and as biofilms. Two conventional (benzalkonium chloride—BAC and peracetic acid—PAA) and two emerging biocides (glycolic acid—GA and glyoxal—GO) were selected for this study. Persister cells resulted from biofilms subjected to a critical treatment using the selected biocides. All biocide treatments developed B. cereus persister cells, except PAA that effectively reduced the levels of vegetative cells and endospores. P. fluorescens persister cells comprise viable and viable but non-culturable cells. Afterwards, persister cells were regrown in suspension and in biofilms and were subjected to a second biocide treatment. In general, planktonic cultures of regrown persister cells in suspension lost their antimicrobial tolerance, for both bacteria. Regrown biofilms of persister cells had antimicrobial susceptibility close to those regrown biofilms of biocide-untreated cells, except for regrown biofilms of persister P. fluorescens after BAC treatment, which demonstrated increased antimicrobial tolerance. The most active biocide against persister cells was PAA, which did not promote changes in susceptibility after their regrowth. In conclusion, persister cells are ubiquitous within biofilms and survive after critical biocide treatment. The descendant planktonic and biofilms populations showed similar properties as the original ones.
Highly Distinct Microbial Communities in Elevated Strings and Submerged Flarks in the Boreal Aapa-Type Mire
Authors: Rakitin Andrey L. , Begmatov Shahjahon , Beletsky Alexey V. , Philippov Dmitriy A. , Kadnikov Vitaly V. , Mardanov Andrey V. , Dedysh Svetlana N. , Ravin Nikolai V.
Published: January 2022

Large areas in the northern hemisphere are covered by extensive wetlands, which represent a complex mosaic of raised bogs, eutrophic fens, and aapa mires all in proximity to each other. Aapa mires differ from other types of wetlands by their concave surface, heavily watered by the central part, as well as by the presence of large-patterned string-flark complexes. In this paper, we characterized microbial diversity patterns in the surface peat layers of the neighboring string and flark structures located within the mire site in the Vologda region of European North Russia, using 16S rRNA gene sequencing. The microbial communities in raised strings were clearly distinct from those in submerged flarks. Strings were dominated by the Alpha- and Gammaproteobacteria. Other abundant groups were the Acidobacteriota, Bacteroidota, Verrucomicrobiota, Actinobacteriota, and Planctomycetota. Archaea accounted for only 0.4% of 16S rRNA gene sequences retrieved from strings. By contrast, they comprised about 22% of all sequences in submerged flarks and mostly belonged to methanogenic lineages. Methanotrophs were nearly absent. Other flark-specific microorganisms included the phyla Chloroflexi, Spirochaetota, Desulfobacterota, Beijerinckiaceae- and Rhodomicrobiaceae-affiliated Alphaproteobacteria, and uncultivated groups env.OPS_17 and vadinHA17 of the Bacteroidota. Such pattern probably reflects local anaerobic conditions in the submerged peat layers in flarks.
In Silico Prediction and Design of Uropathogenic Escherichia coli Alpha-Hemolysin Generate a Soluble and Hemolytic Recombinant Toxin
Authors: Caetano Bruna De Lucca , Domingos Marta de Oliveira , da Silva Miriam Aparecida , da Silva Jessika Cristina Alves , Polatto Juliana Moutinho , Montoni Fabio , Iwai Leo Kei , Pimenta Daniel Carvalho , Vigerelli Hugo , Vieira Paulo Cesar Gomes , Ruiz Rita de Cassia , Patané José Salvatore , Piazza Roxane Maria Fontes
Published: January 2022

The secretion of α-hemolysin by uropathogenic Escherichia coli (UPEC) is commonly associated with the severity of urinary tract infections, which makes it a predictor of poor prognosis among patients. Accordingly, this toxin has become a target for diagnostic tests and therapeutic interventions. However, there are several obstacles associated with the process of α-hemolysin purification, therefore limiting its utilization in scientific investigations. In order to overcome the problems associated with α-hemolysin expression, after in silico prediction, a 20.48 kDa soluble α-hemolysin recombinant denoted rHlyA was constructed. This recombinant is composed by a 182 amino acid sequence localized in the aa542–723 region of the toxin molecule. The antigenic determinants of the rHlyA were estimated by bioinformatics analysis taking into consideration the tertiary form of the toxin, epitope analysis tools, and solubility inference. The results indicated that rHlyA has three antigenic domains localized in the aa555–565, aa600–610, and aa674–717 regions. Functional investigation of rHlyA demonstrated that it has hemolytic activity against sheep red cells, but no cytotoxic effect against epithelial bladder cells. In summary, the results obtained in this study indicate that rHlyA is a soluble recombinant protein that can be used as a tool in studies that aim to understand the mechanisms involved in the hemolytic and cytotoxic activities of α-hemolysin produced by UPEC. In addition, rHlyA can be applied to generate monoclonal and/or polyclonal antibodies that can be utilized in the development of diagnostic tests and therapeutic interventions.
Integrated Parametric Graph Closure and Branch-and-Cut Algorithm for Open Pit Mine Scheduling under Uncertainty
Authors: Joshi Devendra , Paithankar Amol , Chatterjee Snehamoy , Equeenuddin Sk Md
Published: January 2022

Open pit mine production scheduling is a computationally expensive large-scale mixed-integer linear programming problem. This research develops a computationally efficient algorithm to solve open pit production scheduling problems under uncertain geological parameters. The proposed solution approach for production scheduling is a two-stage process. The stochastic production scheduling problem is iteratively solved in the first stage after relaxing resource constraints using a parametric graph closure algorithm. Finally, the branch-and-cut algorithm is applied to respect the resource constraints, which might be violated during the first stage of the algorithm. Six small-scale production scheduling problems from iron and copper mines were used to validate the proposed stochastic production scheduling model. The results demonstrated that the proposed method could significantly improve the computational time with a reasonable optimality gap (the maximum gap is 4%). In addition, the proposed stochastic method is tested using industrial-scale copper data and compared with its deterministic model. The results show that the net present value for the stochastic model improved by 6% compared to the deterministic model.