bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversion of Perennial Biomass Crops to Conserve C and N: A Meta-Analysis
Authors: Martani Enrico , Ferrarini Andrea , Amaducci Stefano
Published: January 2022

Perennial crops have been proposed as a solution to couple the production of sustainable biomass for multiple uses with several environmental benefits such as soil C storage. Concerns exist that the C sequestered in soil could be lost in a few years after the perennial crops are reverted to arable land. In this study, the current knowledge on the effects of perennial crop reversion on soil C and N was summarized by performing a meta-analysis. One year after the reversion a significant increase of soil C and N stocks (+15% and +12% respectively) were found in the 0–30 cm layer, while in the time interval between the second to fifth year after the reversion, there were no significant increases or decreases of soil C and N. The incorporation of the belowground biomass (BGB) into the soil at reversion plays a key role in the fate of soil C and N stocks after the reversion. In fact, when reverting a multiannual biomass crop there are significant losses of soil C and N. In contrast, when reverting a perennial biomass crop (PBCs) such as rhizomatous herbaceous or SRC woody crops there are no losses of soil C and N. The BGB of perennial grass is mainly composed of root systems and not of a huge amount of belowground organs as in the case of PBCs. The shredding of the BGB and its transformation as particulate organic matter (POM) represent the major pulse C input at the reversion that can undergo further stabilization into a mineral-associated organic matter (MAOM) fraction. Introducing PBCs into crop rotation resulted in an effective carbon farming solution with a potential positive legacy for food crops in terms of achievement of both climate and soil fertility goals.
Clinical and Financial Impact of Rapid Antimicrobial Susceptibility Testing in Blood Cultures
Authors: Roth Felix , Leedahl Nathan D. , Leedahl David D. , Guerrero Dubert M.
Published: January 2022

The rapid identification of pathogens that cause bloodstream infections plays a vital role in the modern clinical microbiology laboratory. Despite demonstrating a significant reduction in turnaround time and a significant effect on clinical decisions, most methods do not provide complete antimicrobial susceptibility testing (AST) information. We employed rapid identification (ID) and AST using the Accelerate PhenoTest on positive blood cultures containing Gram-negative bacilli. The length of stay (LOS) significantly decreased from an average of 12.1 days prior to implementation to 6.6 days post-implementation (p = 0.02), representing potential total savings of USD 666,208.00. All-cause mortality did not differ significantly, 27 (19%) versus 18 (12%), p = 0.11. We also observed an associated decrease in the use of broad-spectrum antimicrobials, including meropenem and quinolones. The implementation of a rapid ID and AST method, along with a well-established antimicrobial stewardship program, has the potential to decrease LOS, broad-spectrum antibiotic use, and costs to the healthcare system, with no observable impact on mortality.
An Activity Theory-Based Approach for Context Analysis, Design and Evolution
Authors: Camargo-Henríquez Ismael , Silva Andrés
Published: January 2022

This paper presents a new interdisciplinary approach to support context modeling in context-awareness software developments. The premise of this approach relies on the idea that understanding a complex socio-technical ecology, while adapting the software to its behavior and evolution, is a primary challenge to address. Thus, the paper proposes an activity theory-based approach to aid in the conception, design, development, and evolution of emerging context-aware socio-technical ecologies. The concepts and notations used by the proposed approach are illustrated through a proof of concept that demonstrates the essential ideas and their use in real scenarios. Also, the feasibility of this approach is measured empirically through an experiment. Preliminary results show how, for a context-aware software design and development team, the proposal provides a better understanding of context than alternatives and helps to outline context models by establishing relationships and interactions between socio-technical components and by anticipating potential conflicts among them. The key ideas of the proposed approach result in the ability to analyze and model social and technological contexts around perpetually evolving system ecologies as useful representations for understanding operating environments closely tied to human actions, with software as a mediator component.
Lignocellulosic Materials Used as Biosorbents for the Capture of Nickel (II) in Aqueous Solution
Authors: Cruz-Lopes Luísa , Macena Morgana , Esteves Bruno , Santos-Vieira Isabel
Published: January 2022

Four lignocellulosic materials (walnut shell, chestnut shell, pine wood and burnt pine wood) were analyzed as biosorbents to remove nickel ions in aqueous solution. The optimal pH condition was determined. Due to this, a range of different pHs (3.0 to 7.5) was tested. The adsorption isotherms and kinetics were established. To plot Langmuir and Freundlich isotherms, batch adsorption tests were made with variable nickel concentrations (5 to 200 mg L−1). The pseudo-first order, pseudo-second order, Elovich and intraparticle diffusion models were used to describe the kinetics, batch adsorption tests were carried out with 25 mg L−1 of nickel solution and agitation time varied from 10 to 1440 min. The specific surface area of the different materials was between 3.97 and 4.85 m2g−1 with the exception for wood with 1.74 m2g−1. The pore size was 26.54 nm for wood and varied between 5.40 and 7.33 nm for the remaining materials. The diffractograms analysis showed that all the lignocellulosic materials presented some crystalline domains with the exception of burnt pine wood which was completely amorphous. The best pH was found to be around 5.0. At this pH the adsorption was higher for chestnut shells, walnut shells, burnt pine wood and wood, respectively. All samples fitted the Langmuir model well, with R2 of 0.994 to 0.998. The sorption kinetics was well described by the pseudo-second order equation with R2 between 0.996 and 1.00. No significative differences on the surface of the materials before and after adsorption could be observed by SEM. Finally, all materials tested were able to remove nickel ions in aqueous solution.
Electrically Conductive Nanocomposite Fibers for Flexible and Structural Electronics
Authors: Podsiadły Bartłomiej , Walter Piotr , Kamiński Michał , Skalski Andrzej , Słoma Marcin
Published: January 2022

The following paper presents a simple, low-cost, and repeatable manufacturing process for fabricating conductive, elastic carbon-elastomer nanocomposite fibers for applications in the textile industry and beyond. The presented method allows for the manufacturing of fibers with a diameter of 0.2 mm, containing up to 50 vol. % of graphite powder, 10 vol. % of CNT, and a mix of both fillers. As a result, resistivity below 0.2 Ωm for the 0.2 mm-diameter fibers was achieved. Additionally, conductive fibers are highly elastic, which makes them suitable for use in the textile industry as an element of circuits. The effect of strain on the change in resistance was also tested. Researches have shown that highly conductive fibers can withstand strain of up to 40%, with resistivity increasing nearly five times compared to the unstretched fiber. This research shows that the developed composites can also be used as strain sensors in textronic systems. Finally, functional demonstrators were made by directly sewing the developed fibers into a cotton fabric. First, the non-quantitative tests indicate the feasibility of using the composites as conductive fibers to power components in textronic systems and for bending detection.
Kinematic Relations during Double Support Phase in Parkinsonian Gait
Authors: Sitek Ondřej , Kalichová Miriam , Hedbávný Petr , Boušek Tomáš , Baláž Marek
Published: January 2022

The gait of Parkinson’s disease (PD) patients is shuffling, slow, and hesitant. We investigated peculiar gait relations during the double support phase (DSP) in PD patients and healthy controls. We used 3D motion capture (SIMI) to collect kinematic parameters of the natural gait of 11 PD patients (Hoehn and Yahr 2–3, 5 females, 6 males) tested on medication and the same-sized control sample (5 females, 6 males). The difference between groups was evaluated by the Mann-Whitney U test; for target parameters, the Spearman correlation was computed. Compared to the controls, the Parkinsonian step length index was significantly smaller (0.27 vs. 0.35, p < 0.05), step width index higher (0.12 vs. 0.09, p < 0.05), and the DSP duration was extended (0.165 s vs. 0.13 s, p < 0.05), whereas the single support phase was shortened (0.38 s vs. 0.4 s, p < 0.05). The Parkinsonians were faster during DSP initiation and slower during DSP termination (0.908 m·s−1 vs. 0.785 m·s−1, p < 0.05); the Parkinsonian speed was more constant. The patients showed significantly decreased range of motion (ROM) in the hip, ankle, and shoulder and adopted straighter posture during the gait. Understanding gait concatenations can update physiotherapy approaches to target the roots of movement problems instead of the consequences.
Optical Diffraction Tomography Using Nearly In-Line Holography with a Broadband LED Source
Authors: Ayoub Ahmed B. , Roy Abhijit , Psaltis Demetri
Published: January 2022

We present optical tomography methods for a 3D refractive index reconstruction of weakly scattering objects using LED light sources. We are able to record holograms by minimizing the optical path difference between the signal and reference beams while separating the scattered field from its twin image. We recorded multiple holograms by illuminating the LEDs sequentially and reconstructed the 3D refractive index reconstruction of the sample. The reconstructions show high signal-to-noise ratio in which the effect of speckle artifacts is highly minimized due to the partially incoherent illumination of the LEDs. Results from combining different illumination wavelengths are also described demonstrating higher acquisition speed.
Three-Dimensional Obstacle Avoidance Strategy for Fixed-Wing UAVs Based on Quaternion Method
Authors: Qu Yue , Yi Wenjun
Published: January 2022

This work provides a generalization of the three-dimensional velocity obstacle (VO) collision avoidance strategy for nonlinear second-order underactuated systems in three-dimensional dynamic uncertain environments. A hierarchical architecture is exploited to deal with conflicting multiple subtasks, which are defined as several rotations and are parameterized by quaternions. An improved VO method considering the kinodynamic constraints of a class of fixed-wing unmanned aerial vehicles (UAV) is proposed to implement the motion planning. The position error and velocity error can be mapped onto one desired axis so that, only relying on an engine, UAVs can achieve the goal of point tracking without collision. Additionally, the performance of the closed-loop system is demonstrated through a series of simulations performed in a three-dimensional manner.
Air Contaminants and Atmospheric Black Carbon Association with White Sky Albedo at Hindukush Karakorum and Himalaya Glaciers
Authors: Zainab Irfan , Ali Zulfiqar , Ahmad Usman , Raza Syed Turab , Ahmad Rida , Zona Zaidi , Sidra Safdar
Published: January 2022

Environmental contaminants are becoming a growing issue due to their effects on the cryosphere and their impact on the ecosystem. Mountain glaciers are receding in the HKH region and are anticipated to diminish further as black carbon (BC) concentrations rise along with other pollutants in the air, increasing global warming. Air contaminants and BC concentrations were estimated (June 2017–May 2018). An inventory of different pollutants at three glaciers in Karakoram, Hindukush, and the Himalayas has been recorded with Aeroqual 500 and TSI DRX 8533, which are as follows: ozone (28.14 ± 3.58 µg/m3), carbon dioxide (208.58 ± 31.40 µg/m3), sulfur dioxide (1.73 ± 0.33 µg/m3), nitrogen dioxide (2.84 ± 0.37 µg/m3), PM2.5 (15.90 ± 3.32 µg/m3), PM10 (28.05 ± 2.88 µg/m3), total suspended particles (76.05 ± 10.19 µg/m3), BC in river water (88.74 ± 19.16 µg/m3), glaciers (17.66 ± 0.82 µg/m3), snow/rain (57.43 ± 19.66 ng/g), and air (2.80 ± 1.20 µg/m3). BC was estimated by using DRI Model 2015, Multi-Wavelength Thermal/Optical Carbon Analyzer, in conjunction with satellite-based white-sky albedo (WSA). The average BC concentrations in the Karakoram, Himalaya, and Hindukush were 2.35 ± 0.94, 4.38 ± 1.35, and 3.32 ± 1.09 (µg/m3), whereas WSA was 0.053 ± 0.024, 0.045 ± 0.015, and 0.045 ± 0.019 (µg/m3), respectively. Regression analysis revealed the inverse relationship between WSA and BC. The resulting curves provide a better understanding of the non-empirical link between BC and WSA. Increased BC will inherit ecological consequences for the region, ultimately resulting in biodiversity loss.
Mechanical Behaviour and Primary Stability of a Self-Condensing Implant: A Laboratory Critical Simulation of a Severe Maxillary Atrophy on Polyurethane Lamina
Authors: Comuzzi Luca , Iezzi Giovanna , Lucchese Alessandra , Di Pietro Natalia , Balice Pierluigi , D’Arcangelo Camillo , Piattelli Adriano , Tumedei Margherita
Published: January 2022

Background: Posterior maxillary atrophies could emerge after the loss of teeth, trauma, infections, or lesions that often require regenerative approaches. In these critical conditions, the achievement of implant primary stability represents a clinical challenge in the operative practice. Therefore, a two-stage approach is often preferred with a delay of the rehabilitation time and a consistent increasing of the biological and the operative costs. The aim of this study was to evaluate the mechanical behaviour of a self-condenser implant compared to a standard implant in a critical simulation on different thicknesses and densities of polyurethane lamina. Materials and methods: A total of two implant models were tested: a self-condensing device (test) and a standard implant (control). The study evaluated the insertion torque and the pull-out strength values of the test and control implants inserted in different sizes (1, 2, and 3 mm) and density polyurethane lamina (10, 20, and 30 pcf) for a total of 320 experimental sites. Results: In total, 320 experimental sites were produced in the polyurethane samples. A statistically significant difference of insertion and pull-out torque values between the test and control Implants was found in the different bone densities (p < 0.05). The insertion and pull-out torque values were always higher for the test implants in all experimental conditions. In all bone densities, the insertion torque values were higher than the pull-out torque values. The self-condenser dental implant design evaluated in this in vitro study showed a high level of stability in all experimental conditions. Conclusions: The test implant could represent a useful tool for a one-stage surgical approach in the presence of limited residual native bone as an alternative to a delayed technique.
Relation of Extreme Ionospheric Events with Geomagnetic and Meteorological Activity
Authors: Ratovsky Konstantin G. , Klimenko Maxim V. , Dmitriev Alexei V. , Medvedeva Irina V.
Published: January 2022

This paper studies extreme ionospheric events and their relations with geomagnetic and meteorological activity. With the long observation series at the Irkutsk (52° N, 104° E) and Kaliningrad (54° N, 20° E) ionosondes we obtained the datasets of ionospheric disturbances that were treated as relative deviations of the observed peak electron density values from their 27-day running median values. As the extreme disturbances, we considered cases when the disturbance was greater than 150%. As potential sources of extreme ionospheric disturbances, we considered sudden stratospheric warmings, geomagnetic storms by the criterion Dst ≤ −30 nT, and recurrent geomagnetic storms that did not necessarily satisfy the criterion Dst ≤ −30 nT. The morphological analysis showed that the extreme ionospheric disturbance was the nighttime phenomenon that occurs from late October to early March (mainly in December–January). Considering extreme ionospheric events as nights when disturbances were greater than 150%, we obtained 25 extreme ionospheric events (on average 1.8 events per year) from the 2003–2016 Irkutsk dataset and six extreme ionospheric events (on average 0.75 events per year) from the 2009–2016 Kaliningrad dataset. The year-by-year distribution of extreme events did not reveal a clear dependence on solar/geomagnetic activity in terms of yearly mean F10.7 and Ap values but showed a correlation between the number of events and the number of recurrent geomagnetic storms. The study of the relationship between extreme ionospheric events and manifestations of geomagnetic and meteorological activity revealed that about half of extreme ionospheric events may be related to geomagnetic storms by the criterion Dst ≤ −50 nT and/or sudden stratospheric warmings. Consideration of recurrent geomagnetic storms allowed us to find the sources of almost all extreme ionospheric events. Geomagnetic activity may be considered the main cause of extreme ionospheric events at Irkutsk (mainly associated with recurrent geomagnetic storms and partly with CME-storms); while the main cause of extreme ionospheric events at Kaliningrad is not clear (a comparable contribution of sudden stratospheric warmings and storms can be assumed).
Molecular Mechanism of Malignant Transformation of Balb/c-3T3 Cells Induced by Long-Term Exposure to 1800 MHz Radiofrequency Electromagnetic Radiation (RF-EMR)
Authors: Ding Zhen , Xiang Xiaoyong , Li Jintao , Wu Shuicai
Published: January 2022

Purpose: We aimed to investigate RF-EMR-induced cell malignant transformation. Methods: We divided Balb/c-3T3 cells into sham and expo groups. The expo groups were exposed to a 1800 MHz RF continuous wave for 40 and 60 days, for 4 h per day. The sham group was sham-exposed. Cells were harvested for a cell transformation assay, transplantation in severe combined immune deficient (SCID) mice, soft agar clone formation detection, and a transwell assay. The mRNA microarray assay was used to declare key genes and pathways. Results: The exposed Balb/c-3T3 cells showed a strong increase in cell proliferation and migration. Malignant transformation was observed in expo Balb/c-3T3 cells exposed for 40 days and 60 days, which was symbolized with visible foci and clone formation. Expo Balb/c-3T3 cells that were exposed for 40 days and 60 days produced visible tumors in the SCID mice. Lipid metabolism was the key biological process and pathway involved. The mevalonate (MVA) pathway was the key metabolic pathway. The interacted miRNAs could be further research targets to examine the molecular mechanism of the carcinogenic effects of long-term exposure. Conclusion: Exposure for 40 and 60 days to 1800 MHz RF-EMR induced malignant transformation in Balb/c-3T3 cells at the SAR of 8.0 W/kg. We declared that lipid metabolism was the pivotal biological process and pathway. The MVA pathway was the key metabolic pathway.
Mammaliicoccus spp. from German Dairy Farms Exhibit a Wide Range of Antimicrobial Resistance Genes and Non-Wildtype Phenotypes to Several Antibiotic Classes
Authors: Lienen Tobias , Schnitt Arne , Hammerl Jens Andre , Maurischat Sven , Tenhagen Bernd-Alois
Published: January 2022

Mammaliicocci might play a major role in antimicrobial resistance (AMR) gene transmission between organisms of the family Staphylococcaceae, such as the potentially pathogenic species Staphylococcus aureus. The interest of this study was to analyze AMR profiles of mammaliicocci from German dairy farms to evaluate the AMR transmission potential. In total, 65 mammaliicocci isolates from 17 dairy farms with a history of MRSA detection were analyzed for AMR genotypes and phenotypes using whole genome sequencing and antimicrobial susceptibility testing against 19 antibiotics. The various genotypic and phenotypic AMR profiles of mammaliicocci from German dairy farms indicated the simultaneous occurrence of several different strains on the farms. The isolates exhibited a non-wildtype phenotype to penicillin (58/64), cefoxitin (25/64), chloramphenicol (26/64), ciprofloxacin (25/64), clindamycin (49/64), erythromycin (17/64), fusidic acid (61/64), gentamicin (8/64), kanamycin (9/64), linezolid (1/64), mupirocin (4/64), rifampicin (1/64), sulfamethoxazol (1/64), streptomycin (20/64), quinupristin/dalfopristin (26/64), tetracycline (37/64), tiamulin (59/64), and trimethoprim (30/64). Corresponding AMR genes against several antimicrobial classes were detected. Linezolid resistance was associated with the cfr gene in the respective isolate. However, discrepancies between genotypic prediction and phenotypic resistance profiles, such as for fusidic acid and tiamulin, were also observed. In conclusion, mammaliicocci from dairy farms may carry a broad variety of antimicrobial resistance genes and exhibit non-wildtype phenotypes to several antimicrobial classes; therefore, they may represent an important source for horizontal gene transfer of AMR genes to pathogenic Staphylococcaceae.
To Stick or Not to Stick: Adhesions in Orofacial Clefts
Authors: Antiguas Angelo , Paul Brian J. , Dunnwald Martine
Published: January 2022

Morphogenesis requires a tight coordination between mechanical forces and biochemical signals to inform individual cellular behavior. For these developmental processes to happen correctly the organism requires precise spatial and temporal coordination of the adhesion, migration, growth, differentiation, and apoptosis of cells originating from the three key embryonic layers, namely the ectoderm, mesoderm, and endoderm. The cytoskeleton and its remodeling are essential to organize and amplify many of the signaling pathways required for proper morphogenesis. In particular, the interaction of the cell junctions with the cytoskeleton functions to amplify the behavior of individual cells into collective events that are critical for development. In this review we summarize the key morphogenic events that occur during the formation of the face and the palate, as well as the protein complexes required for cell-to-cell adhesions. We then integrate the current knowledge into a comprehensive review of how mutations in cell-to-cell adhesion genes lead to abnormal craniofacial development, with a particular focus on cleft lip with or without cleft palate.
Calculation of Crystal-Solution Dissociation Constants
Authors: Garbuzynskiy Sergiy O. , Finkelstein Alexei V.
Published: January 2022

The calculation of dissociation constants is an important problem in molecular biophysics. For such a calculation, it is important to correctly calculate both terms of the binding free energy; that is, the enthalpy and entropy of binding. Both these terms can be computed using molecular dynamics simulations, but this approach is very computationally expensive, and entropy calculations are especially slow. We develop an alternative very fast method of calculating the binding entropy and dissociation constants. The main part of our approach is based on the evaluation of movement ranges of molecules in the bound state. Then, the range of molecular movements in the bound state (here, in molecular crystals) is used for the calculation of the binding entropies and, then (using, in addition, the experimentally measured sublimation enthalpies), the crystal-to-vapor dissociation constants. Previously, we considered the process of the reversible sublimation of small organic molecules from crystals to vapor. In this work, we extend our approach by considering the dissolution of molecules, in addition to their sublimation. Similar to the sublimation case, our method shows a good correlation with experimentally measured dissociation constants at the dissolution of crystals.
Sulfurtransferases and Cystathionine Beta-Synthase Expression in Different Human Leukemia Cell Lines
Authors: Jurkowska Halina , Wróbel Maria , Jasek-Gajda Ewa , Rydz Leszek
Published: January 2022

The studies concerned the expression of sulfurtransferases and cystathionine beta-synthase in six human leukemia cell lines: B cell acute lymphoblastic leukemia-B-ALL (REH cells), T cell acute lymphoblastic leukemia-T-ALL (DND-41 and MOLT-4 cells), acute myeloid leukemia—AML (MV4-11 and MOLM-14 cells), and chronic myeloid leukemia—CML (K562 cells). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were performed to determine the expression of thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, gamma-cystathionase, and cystathionine beta-synthase on the mRNA and protein level. Interestingly, we found significant differences in the mRNA and protein levels of sulfurtransferases and cystathionine beta-synthase in the studied leukemia cells. The obtained results may contribute to elucidating the significance of the differences between the studied cells in the field of sulfur compound metabolism and finding new promising ways to inhibit the proliferation of various types of leukemic cells by modulating the activity of sulfurtransferases, cystathionine beta-synthase, and, consequently, the change of intracellular level of sulfane sulfur as well as H2S and reactive oxygen species production.
Aqueous Integrated Process for the Recovery of Oil Bodies or Fatty Acid Emulsions from Sunflower Seeds
Authors: Cassen Audrey , Fabre Jean-François , Lacroux Eric , Cerny Muriel , Vaca-Medina Guadalupe , Mouloungui Zéphirin , Merah Othmane , Valentin Romain
Published: January 2022

An aqueous integrated process was developed to obtain several valuable products from sunflower seeds. With a high-shear rate crusher, high-pressure homogenization and centrifugation, it is possible to process 600× g of seeds in 1400× g of water to obtain a concentrated cream phase with a dry matter (dm) content of 46%, consisting of 74 (w/w dm) lipids in the form of an oil-body dispersion (droplet size d(0.5): 2.0 µm) rich in proteins (13% w/w dm, with membranous and extraneous proteins). The inclusion of an enzymatic step mediated by a lipase made possible the total hydrolysis of trigylcerides into fatty acids. The resulting cream had a slightly higher lipid concentration, a ratio lipid/water closer to 1, with a dry matter content of 57% consisting of 69% (w/w) lipids, a more complex structure, as observed on Cryo-SEM, with a droplet size slightly greater (d(0.5): 2.5 µm) than that of native oil bodies and a conserved protein concentration (12% w/w dm) but an almost vanished phospholipid content (17.1 ± 4.4 mg/g lipids compared to 144.6 ± 6 mg/g lipids in the oil-body dispersion and 1811.2 ± 122.2 mg/g lipids in the seed). The aqueous phases and pellets were also characterized, and their mineral, lipid and protein contents provide new possibilities for valorization in food or technical applications.
Advancements in Fabrication and Application of Chitosan Composites in Implants and Dentistry: A Review
Authors: Sharifianjazi Fariborz , Khaksar Samad , Esmaeilkhanian Amirhossein , Bazli Leila , Eskandarinezhad Sara , Salahshour Peyman , Sadeghi Farnaz , Rostamnia Sadegh , Vahdat Seyed Mohammad
Published: January 2022

Chitosan is a biopolymer that is found in nature and is produced from chitin deacetylation. Chitosan has been studied thoroughly for multiple applications with an interdisciplinary approach. Antifungal antibacterial activities, mucoadhesion, non-toxicity, biodegradability, and biocompatibility are some of the unique characteristics of chitosan-based biomaterials. Moreover, chitosan is the only widely-used natural polysaccharide, and it is possible to chemically modify it for different applications and functions. In various fields, chitosan composite and compound manufacturing has acquired much interest in developing several promising products. Chitosan and its derivatives have gained attention universally in biomedical and pharmaceutical industries as a result of their desired characteristics. In the present mini-review, novel methods for preparing chitosan-containing materials for dental and implant engineering applications along with challenges and future perspectives are discussed.
VEGF-Trap Modulates Retinal Inflammation in the Murine Oxygen-Induced Retinopathy (OIR) Model
Authors: Rojo Arias Jesús Eduardo , Englmaier Vanessa Elisabeth , Jászai József
Published: January 2022

Anti-Vascular Endothelial Growth Factor (VEGF) agents are the first-line treatment for retinal neovascular diseases, which represent the most prevalent causes of acquired vision loss world-wide. VEGF-Trap (Aflibercept, AFL), a recombinant decoy receptor recognizing ligands of both VEGFR-1 and -2, was recently reported to be highly efficient in improving visual acuity and preserving retinal anatomy in individuals affected by diabetic macular edema. However, the precise molecular and cell biological mechanisms underlying the beneficial effects of this novel tool have yet to be elucidated. Using the mouse oxygen-induced retinopathy (OIR) model as a surrogate of retinopathies with sterile post-ischemic inflammation, such as late proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and diabetic macular edema (DME), we provide evidence that AFL modulates inflammation in response to hypoxia by regulating the morphology of microglial cells, a parameter commonly used as a proxy for changes in their activation state. We show that AFL administration during the hypoxic period of OIR leads to an increased number of ramified Iba1+ microglial cells/macrophages while subsequently limiting the accumulation of these cells in particular retinal layers. Our results suggest that, beyond its well-documented beneficial effects on microvascular regeneration, AFL might exert important modulatory effects on post-ischemic retinal inflammation.
Inhibition of SGLT2 Preserves Function and Promotes Proliferation of Human Islets Cells In Vivo in Diabetic Mice
Authors: Karlsson Daniel , Ahnmark Andrea , Sabirsh Alan , Andréasson Anne-Christine , Gennemark Peter , Sandinge Ann-Sofie , Chen Lihua , Tyrberg Björn , Lindén Daniel , Sörhede Winzell Maria
Published: January 2022

Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of diabetes. This study examines the effects of dapagliflozin on human islets, focusing on alpha and beta cell composition in relation to function in vivo, following treatment of xeno-transplanted diabetic mice. Mouse beta cells were ablated by alloxan, and dapagliflozin was provided in the drinking water while controls received tap water. Body weight, food and water intake, plasma glucose, and human C-peptide levels were monitored, and intravenous arginine/glucose tolerance tests (IVarg GTT) were performed to evaluate islet function. The grafted human islets were isolated at termination and stained for insulin, glucagon, Ki67, caspase 3, and PDX-1 immunoreactivity in dual and triple combinations. In addition, human islets were treated in vitro with dapagliflozin at different glucose concentrations, followed by insulin and glucagon secretion measurements. SGLT2 inhibition increased the animal survival rate and reduced plasma glucose, accompanied by sustained human C-peptide levels and improved islet response to glucose/arginine. SGLT2 inhibition increased both alpha and beta cell proliferation (Ki67+glucagon+ and Ki67+insulin+) while apoptosis was reduced (caspase3+glucagon+ and caspase3+insulin+). Alpha cells were fewer following inhibition of SGLT2 with increased glucagon/PDX-1 double-positive cells, a marker of alpha to beta cell transdifferentiation. In vitro treatment of human islets with dapagliflozin had no apparent impact on islet function. In summary, SGLT2 inhibition supported human islet function in vivo in the hyperglycemic milieu and potentially promoted alpha to beta cell transdifferentiation, most likely through an indirect mechanism.
Predictive Factors for Neutralizing Antibody Levels Nine Months after Full Vaccination with BNT162b2: Results of a Machine Learning Analysis
Authors: Papadopoulos Dimitris , Ntanasis-Stathopoulos Ioannis , Gavriatopoulou Maria , Evangelakou Zoi , Malandrakis Panagiotis , Manola Maria S. , Gianniou Despoina D. , Kastritis Efstathios , Trougakos Ioannis P. , Dimopoulos Meletios A. , Karalis Vangelis , Terpos Evangelos
Published: January 2022

Vaccination against SARS-CoV-2 with BNT162b2 mRNA vaccine plays a critical role in COVID-19 prevention. Although BNT162b2 is highly effective against COVID-19, a time-dependent decrease in neutralizing antibodies (NAbs) is observed. The aim of this study was to identify the individual features that may predict NAbs levels after vaccination. Machine learning techniques were applied to data from 302 subjects. Principal component analysis (PCA), factor analysis of mixed data (FAMD), k-means clustering, and random forest were used. PCA and FAMD showed that younger subjects had higher levels of neutralizing antibodies than older subjects. The effect of age is strongest near the vaccination date and appears to decrease with time. Obesity was associated with lower antibody response. Gender had no effect on NAbs at nine months, but there was a modest association at earlier time points. Participants with autoimmune disease had lower inhibitory levels than participants without autoimmune disease. K-Means clustering showed the natural grouping of subjects into five categories in which the characteristics of some individuals predominated. Random forest allowed the characteristics to be ordered by importance. Older age, higher body mass index, and the presence of autoimmune diseases had negative effects on the development of NAbs against SARS-CoV-2, nine months after full vaccination.
L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction
Authors: Erens Céline , Van Broeckhoven Jana , Hoeks Cindy , Schabbauer Gernot , Cheng Paul N. , Chen Li , Hellings Niels , Broux Bieke , Lemmens Stefanie , Hendrix Sven
Published: January 2022

Background: Spinal cord injury (SCI) elicits robust neuroinflammation that eventually exacerbates the initial damage to the spinal cord. L-arginine is critical for the responsiveness of T cells, which are important contributors to neuroinflammation after SCI. Furthermore, L-arginine is the substrate for nitric oxide (NO) production, which is a known inducer of secondary damage. Methods: To accomplish systemic L-arginine depletion, repetitive injections of recombinant arginase-1 (rArg-I) were performed. Functional recovery and histopathological parameters were analyzed. Splenic immune responses were evaluated by flow cytometry. Pro-inflammatory gene expression and nitrite concentrations were measured. Results: We show for the first time that systemic L-arginine depletion improves locomotor recovery. Flow cytometry and immunohistological analysis showed that intraspinal T-cell infiltration was reduced by 65%, and peripheral numbers of Th1 and Th17 cells were suppressed. Moreover, rArg-I treatment reduced the intraspinal NO production by 40%. Histopathological analyses revealed a 37% and 36% decrease in the number of apoptotic neurons and neuron-macrophage/microglia contacts in the spinal cord, respectively. Conclusions: Targeting detrimental T-cell responses and NO-production via rArg-I led to a reduced neuronal cell death and an improved functional recovery. These findings indicate that L-arginine depletion holds promise as a therapeutic strategy after SCI.
The Clinical Features of In-Hospital Recurrence in Acute Ischaemic Stroke Patients over Time: A Real-World Observation at a Single Center
Authors: Zhang Gaoqi , Yang Qiong , Zhang Huagang , Huang Xiao , Fu Yu , Fan Dongsheng
Published: January 2022

Acute ischaemic stroke (AIS) has a high risk of recurrence, particularly in the early stage. Our study aimed to assess the clinical characteristics and risk factors of in-hospital ischaemic recurrence in AIS patients in different periods. This study was a retrospective, single-center analysis. The patients were divided into two stages based on their admission time. The primary endpoint was recurrent stroke during hospitalization. In total, 978 patients in Stage 1 and 1047 patients in Stage 2 were included in this study. The in-hospital recurrence rate in Stage 1 was 5.9%, while that in Stage 2 was 4.0% (p = 0.046). A recurrence rate reduction mainly occurred in the minor stroke and large-artery atherosclerosis (LAA) stroke patients. Infection was an independent risk factor despite amelioration by antiplatelet therapy (p < 0.001). Diabetes patients also had a higher risk of in-hospital ischaemic recurrence among the minor stroke and large-artery atherosclerosis patients. A positive attitude towards antiplatelet therapy failed to completely halt recurrence of the disease. In conclusion, the rate of in-hospital ischaemic recurrence in AIS patients showed a decreasing trend over time, especially in the minor stroke and large-artery atherosclerosis stroke patients. Infection and diabetes were associated with a higher risk of stroke recurrence.
HELLS Is Negatively Regulated by Wild-Type P53 in Liver Cancer by a Mechanism Involving P21 and FOXM1
Authors: Schuller Stefanie , Sieker Jan , Riemenschneider Philip , Köhler Bianca , Drucker Elisabeth , Weiler Sofia M. E. , Dauch Daniel , Sticht Carsten , Goeppert Benjamin , Roessler Stephanie , Ribback Silvia , Breuhahn Kai , Fend Falko , Dombrowski Frank , Singer Kerstin , Singer Stephan
Published: January 2022

The major tumor suppressor P53 (TP53) acts primarily as a transcription factor by activating or repressing subsets of its numerous target genes, resulting in different cellular outcomes (e.g., cell cycle arrest, apoptosis and senescence). P53-dependent gene regulation is linked to several aspects of chromatin remodeling; however, regulation of chromatin-modifying enzymes by P53 is poorly understood in hepatocarcinogenesis. Herein, we identified Helicase, lymphoid specific (HELLS), a major epigenetic regulator in liver cancer, as a strong and selective P53 repression target within the SNF2-like helicase family. The underlying regulatory mechanism involved P53-dependent induction of P21 (CDKN1A), leading to repression of Forkhead Box Protein M1 (FOXM1) that in turn resulted in downregulation of HELLS expression. Supporting our in vitro data, we found higher expression of HELLS in murine HCCs arising in a Trp53−/− background compared to Trp53+/+ HCCs as well as a strong and highly significant correlation between HELLS and FOXM1 expression in different HCC patient cohorts. Our data suggest that functional or mutational inactivation of P53 substantially contributes to overexpression of HELLS in HCC patients and indicates a previously unstudied aspect of P53′s ability to suppress liver cancer formation.
Evaluating Iodine-125 DNA Damage Benchmarks of Monte Carlo DNA Damage Models
Authors: Thompson Shannon J. , Rooney Aoife , Prise Kevin M. , McMahon Stephen J.
Published: January 2022

A wide range of Monte Carlo models have been applied to predict yields of DNA damage based on nanoscale track structure calculations. While often similar on the macroscopic scale, these models frequently employ different assumptions which lead to significant differences in nanoscale dose deposition. However, the impact of these differences on key biological readouts remains unclear. A major challenge in this area is the lack of robust datasets which can be used to benchmark models, due to a lack of resolution at the base pair level required to deeply test nanoscale dose deposition. Studies investigating the distribution of strand breakage in short DNA strands following the decay of incorporated 125I offer one of the few benchmarks for model predictions on this scale. In this work, we have used TOPAS-nBio to evaluate the performance of three Geant4-DNA physics models at predicting the distribution and yield of strand breaks in this irradiation scenario. For each model, energy and OH radical distributions were simulated and used to generate predictions of strand breakage, varying energy thresholds for strand breakage and OH interaction rates to fit to the experimental data. All three models could fit well to the observed data, although the best-fitting strand break energy thresholds ranged from 29.5 to 32.5 eV, significantly higher than previous studies. However, despite well describing the resulting DNA fragment distribution, these fit models differed significantly with other endpoints, such as the total yield of breaks, which varied by 70%. Limitations in the underlying data due to inherent normalisation mean it is not possible to distinguish clearly between the models in terms of total yield. This suggests that, while these physics models can effectively fit some biological data, they may not always generalise in the same way to other endpoints, requiring caution in their extrapolation to new systems and the use of multiple different data sources for robust model benchmarking.
Untapped Neuroimaging Tools for Neuro-Oncology: Connectomics and Spatial Transcriptomics
Authors: Germann Jurgen , Zadeh Gelareh , Mansouri Alireza , Kucharczyk Walter , Lozano Andres M. , Boutet Alexandre
Published: January 2022

Neuro-oncology research is broad and includes several branches, one of which is neuroimaging. Magnetic resonance imaging (MRI) is instrumental for the diagnosis and treatment monitoring of patients with brain tumors. Most commonly, structural and perfusion MRI sequences are acquired to characterize tumors and understand their behaviors. Thanks to technological advances, structural brain MRI can now be transformed into a so-called average brain accounting for individual morphological differences, which enables retrospective group analysis. These normative analyses are uncommonly used in neuro-oncology research. Once the data have been normalized, voxel-wise analyses and spatial mapping can be performed. Additionally, investigations of underlying connectomics can be performed using functional and structural templates. Additionally, a recently available template of spatial transcriptomics has enabled the assessment of associated gene expression. The few published normative analyses have shown relationships between tumor characteristics and spatial localization, as well as insights into the circuitry associated with epileptogenic tumors and depression after cingulate tumor resection. The wide breadth of possibilities with normative analyses remain largely unexplored, specifically in terms of connectomics and imaging transcriptomics. We provide a framework for performing normative analyses in oncology while also highlighting their limitations. Normative analyses are an opportunity to address neuro-oncology questions from a different perspective.
Intracranial Hemorrhage in Patients with Anticoagulant Therapy Undergoing Stereotactic Radiosurgery for Brain Metastases: A Bi-Institutional Analysis
Authors: Ehret Felix , Kaul David , Mose Lucas , Budach Volker , Vajkoczy Peter , Fürweger Christoph , Haidenberger Alfred , Muacevic Alexander , Mehrhof Felix , Kufeld Markus
Published: January 2022

Background: Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body, affected patients have an increased risk of comorbidities, such as atrial fibrillation (AF) and venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT). These may require therapeutic anticoagulant therapy (ACT). Limited data are available on the risk of intracranial hemorrhage (ICH) after SRS for patients with BM who are receiving ACT. This bi-institutional analysis aimed to describe the bleeding risk for this patient subgroup. Methods: Patients with ACT at the time of single-fraction SRS for BM from two institutions were eligible for analysis. The cumulative incidence of ICH with death as a competing event was assessed during follow-up with magnetic resonance imaging or computed tomography. Results: Forty-one patients with 97 BM were included in the analyses. The median follow-up was 8.2 months (range: 1.7–77.5 months). The median and mean BM volumes were 0.47 and 1.19 cubic centimeters, respectively. The most common reasons for ACT were PE (41%), AF (34%), and DVT (7%). The ACT was mostly performed utilizing phenprocoumon (37%), novel oral anticoagulants (32%), or low-molecular-weight heparin (20%). Nine BM from a group of five patients with ICH after SRS were identified: none of them caused neurological or any other deficits. The 6-, 12-, and 18-month cumulative bleeding incidences per metastasis were 2.1%, 12.4%, and 12.4%, respectively. The metastases with previous bleeding events and those originating from malignant melanomas were found to more frequently demonstrate ICH after SRS (p = 0.02, p = 0.01). No surgical or medical intervention was necessary for ICH management, and no observed death was associated with an ICH. Conclusion: Patients receiving an ACT and single-fraction SRS for small- to medium-sized BM did not seem to have a clinically relevant risk of ICH. Previous bleeding and metastases originating from a malignant melanoma may favor bleeding events after SRS. Further studies are needed to validate our reported findings.
Endocrine and Neuroendocrine Tumors Special Issue—Checkpoint Inhibitors for Adrenocortical Carcinoma and Metastatic Pheochromocytoma and Paraganglioma: Do They Work?
Authors: Jimenez Camilo , Armaiz-Pena Gustavo , Dahia Patricia L. M. , Lu Yang , Toledo Rodrigo A. , Varghese Jeena , Habra Mouhammed Amir
Published: January 2022

Adrenocortical cancers and metastatic pheochromocytomas are the most common malignancies originating in the adrenal glands. Metastatic paragangliomas are extra-adrenal tumors that share similar genetic and molecular profiles with metastatic pheochromocytomas and, subsequently, these tumors are studied together. Adrenocortical cancers and metastatic pheochromocytomas and paragangliomas are orphan diseases with limited therapeutic options worldwide. As in any other cancers, adrenocortical cancers and metastatic pheochromocytomas and paragangliomas avoid the immune system. Hypoxia-pseudohypoxia, activation of the PD-1/PD-L1 pathway, and/or microsatellite instability suggest that immunotherapy with checkpoint inhibitors could be a therapeutic option for patients with these tumors. The results of clinical trials with checkpoint inhibitors for adrenocortical carcinoma or metastatic pheochromocytoma or paraganglioma demonstrate limited benefits; nevertheless, these results also suggest interesting mechanisms that might enhance clinical responses to checkpoint inhibitors. These mechanisms include the normalization of tumor vasculature, modification of the hormonal environment, and vaccination with specific tumor antigens. Combinations of checkpoint inhibitors with classical therapies, such as chemotherapy, tyrosine kinase inhibitors, radiopharmaceuticals, and/or novel therapies, such as vaccines, should be evaluated in clinical trials.