bluuebunny/crossref_metadata_2025 huggingface dataset:
PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease
Authors: Lombardi Rosa , Piciotti Roberto , Dongiovanni Paola , Meroni Marica , Fargion Silvia , Fracanzani Anna Ludovica
Published: March 2022

Non-alcoholic fatty liver disease (NAFLD) is characterized by an enhanced activation of the immune system, which predispose the evolution to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Resident macrophages and leukocytes exert a key role in the pathogenesis of NAFLD. In particular, CD4+ effector T cells are activated during the early stages of liver inflammation and are followed by the increase of natural killer T cells and of CD8+ T cytotoxic lymphocytes which contribute to auto-aggressive tissue damage. To counteract T cells activation, programmed cell death 1 (PD-1) and its ligand PDL-1 are exposed respectively on lymphocytes and liver cells’ surface and can be targeted for therapy by using specific monoclonal antibodies, such as of Nivolumab, Pembrolizumab, and Atezolizumab. Despite the combination of Atezolizumab and Bevacizumab has been approved for the treatment of advanced HCC, PD-1/PD-L1 blockage treatment has not been approved for NAFLD and adjuvant immunotherapy does not seem to improve survival of patients with early-stage HCC. In this regard, different ongoing phase III trials are testing the efficacy of anti-PD-1/PD-L1 antibodies in HCC patients as first line therapy and in combination with other treatments. However, in the context of NAFLD, immune checkpoints inhibitors may not improve HCC prognosis, even worse leading to an increase of CD8+PD-1+ T cells and effector cytokines which aggravate liver damage. Here, we will describe the main pathogenetic mechanisms which characterize the immune system involvement in NAFLD discussing advantages and obstacles of anti PD-1/PDL-1 immunotherapy.
A Competition between Hydrogen, Stacking, and Halogen Bonding in N-(4-((3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)selanyl)phenyl)acetamide: Structure, Hirshfeld Surface Analysis, 3D Energy Framework Approach, and DFT Calculation
Authors: Gouda Mohamed , Ferjani Hela , Abd El-Lateef Hany M. , Khalaf Mai M. , Shaaban Saad , Yousef Tarek A.
Published: March 2022

N-(4-((3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)selanyl)phenyl)acetamide (5), C19H15NO3Se, was prepared in two steps from 4,4′-diselanediyldianiline (3) via reduction and subsequent nucleophilic reaction with 2-methyl-3-bromo-1,4-naphthalenedione, followed by acetylation with acetic anhydride. The cytotoxicity was estimated against 158N and 158JP oligodendrocytes and the redox profile was also evaluated using different in vitro assays. The technique of single-crystal X-ray diffraction is used to confirm the structure of compound 5. The enantiopure 5 crystallizes in space group P21 with Flack parameter 0.017 (8), exhibiting a chiral layered absolute structure. Molecular structural studies showed that the crystal structure is foremost stabilized by N-H···O and relatively weak C-H···O contacts between molecules, and additionally stabilized by weak C-H···π and Se···N interactions. Hirshfeld surface analysis is used to quantitatively investigate the noncovalent interactions that stabilize crystal packing. Framework energy diagrams were used to graphically represent the stabilizing interaction energies for crystal packing. The analysis of the energy framework shows that the interactions energies of and C-H···π and C-O···π are primarily dispersive and are the crystal’s main important forces. Density functional theory (DFT) calculations were used to determine the compound’s stability, chemical reactivity, and other parameters by determining the HOMO-LUMO energy differences. The determination of its optimized surface of the molecular electrostatic potential (MEP) was also carried out. This study was conducted to demonstrate both the electron-rich and electron-poor sites.
Should Degenerated Intervertebral Discs of Patients with Modic Type 1 Changes Be Treated with Mesenchymal Stem Cells?
Authors: Herger Nick , Bermudez-Lekerika Paola , Farshad Mazda , Albers Christoph E. , Distler Oliver , Gantenbein Benjamin , Dudli Stefan
Published: March 2022

Low back pain (LBP) has been among the leading causes of disability for the past 30 years. This highlights the need for improvement in LBP management. Many clinical trials focus on developing treatments against degenerative disc disease (DDD). The multifactorial etiology of DDD and associated risk factors lead to a heterogeneous patient population. It comes as no surprise that the outcomes of clinical trials on intradiscal mesenchymal stem cell (MSC) injections for patients with DDD are inconsistent. Intradiscal MSC injections have demonstrated substantial pain relief and significant disability-related improvements, yet they have failed to regenerate the intervertebral disc (IVD). Increasing evidence suggests that the positive outcomes in clinical trials might be attributed to the immunomodulatory potential of MSCs rather than to their regenerative properties. Therefore, patient stratification for inflammatory DDD phenotypes may (i) better serve the mechanisms of action of MSCs and (ii) increase the treatment effect. Modic type 1 changes—pathologic inflammatory, fibrotic changes in the vertebral bone marrow—are frequently observed adjacent to degenerated IVDs in chronic LBP patients and represent a clinically distinct subpopulation of patients with DDD. This review discusses whether degenerated IVDs of patients with Modic type 1 changes should be treated with an intradiscal MSC injection.
Dynamics of Reactive Carbonyl Species in Pea Root Nodules in Response to Polyethylene Glycol (PEG)-Induced Osmotic Stress
Authors: Soboleva Alena , Frolova Nadezhda , Bureiko Kseniia , Shumilina Julia , Balcke Gerd U. , Zhukov Vladimir A. , Tikhonovich Igor A. , Frolov Andrej
Published: March 2022

Drought dramatically affects crop productivity worldwide. For legumes this effect is especially pronounced, as their symbiotic association with rhizobia is highly-sensitive to dehydration. This might be attributed to the oxidative stress, which ultimately accompanies plants’ response to water deficit. Indeed, enhanced formation of reactive oxygen species in root nodules might result in up-regulation of lipid peroxidation and overproduction of reactive carbonyl compounds (RCCs), which readily modify biomolecules and disrupt cell functions. Thus, the knowledge of the nodule carbonyl metabolome dynamics is critically important for understanding the drought-related losses of nitrogen fixation efficiency and plant productivity. Therefore, here we provide, to the best of our knowledge, for the first time a comprehensive overview of the pea root nodule carbonyl metabolome and address its alterations in response to polyethylene glycol-induced osmotic stress as the first step to examine the changes of RCC patterns in drought treated plants. RCCs were extracted from the nodules and derivatized with 7-(diethylamino)coumarin-3-carbohydrazide (CHH). The relative quantification of CHH-derivatives by liquid chromatography-high resolution mass spectrometry with a post-run correction for derivative stability revealed in total 194 features with intensities above 1 × 105 counts, 19 of which were down- and three were upregulated. The upregulation of glyceraldehyde could accompany non-enzymatic conversion of glyceraldehyde-3-phosphate to methylglyoxal. The accumulation of 4,5-dioxovaleric acid could be the reason for down-regulation of porphyrin metabolism, suppression of leghemoglobin synthesis, inhibition of nitrogenase and degradation of legume-rhizobial symbiosis in response to polyethylene glycol (PEG)-induced osmotic stress effect. This effect needs to be confirmed with soil-based drought models.
Current Advances in RNA Therapeutics for Human Diseases
Authors: Zogg Hannah , Singh Rajan , Ro Seungil
Published: March 2022

Following the discovery of nucleic acids by Friedrich Miescher in 1868, DNA and RNA were recognized as the genetic code containing the necessary information for proper cell functioning. In the years following these discoveries, vast knowledge of the seemingly endless roles of RNA have become better understood. Additionally, many new types of RNAs were discovered that seemed to have no coding properties (non-coding RNAs), such as microRNAs (miRNAs). The discovery of these new RNAs created a new avenue for treating various human diseases. However, RNA is relatively unstable and is degraded fairly rapidly once administered; this has led to the development of novel delivery mechanisms, such as nanoparticles to increase stability as well as to prevent off-target effects of these molecules. Current advances in RNA-based therapies have substantial promise in treating and preventing many human diseases and disorders through fixing the pathology instead of merely treating the symptomology similarly to traditional therapeutics. Although many RNA therapeutics have made it to clinical trials, only a few have been FDA approved thus far. Additionally, the results of clinical trials for RNA therapeutics have been ambivalent to date, with some studies demonstrating potent efficacy, whereas others have limited effectiveness and/or toxicity. Momentum is building in the clinic for RNA therapeutics; future clinical care of human diseases will likely comprise promising RNA therapeutics. This review focuses on the current advances of RNA therapeutics and addresses current challenges with their development.
A Novel Method of Generating Geospatial Intelligence from Social Media Posts of Political Leaders
Authors: Sufi Fahim , Alsulami Musleh
Published: March 2022

Social media platforms such as Twitter have been used by political leaders, heads of states, political parties, and their supporters to strategically influence public opinions. Leaders can post about a location, a state, a country, or even a region in their social media accounts, and the posts can immediately be viewed and reacted to by millions of their followers. The effect of social media posts by political leaders could be automatically measured by extracting, analyzing, and producing real-time geospatial intelligence for social scientists and researchers. This paper proposed a novel approach in automatically processing real-time social media messages of political leaders with artificial intelligence (AI)-based language detection, translation, sentiment analysis, and named entity recognition (NER). This method automatically generates geospatial and location intelligence on both ESRI ArcGIS Maps and Microsoft Bing Maps. The proposed system was deployed from 1 January 2020 to 6 February 2022 to analyze 1.5 million tweets. During this 25-month period, 95K locations were successfully identified and mapped using data of 271,885 Twitter handles. With an overall 90% precision, recall, and F1score, along with 97% accuracy, the proposed system reports the most accurate system to produce geospatial intelligence directly from live Twitter feeds of political leaders with AI.
Discrete Event Modeling and Simulation for Reinforcement Learning System Design
Authors: Capocchi Laurent , Santucci Jean-François
Published: March 2022

Discrete event modeling and simulation and reinforcement learning are two frameworks suited for cyberphysical system design, which, when combined, can give powerful tools for system optimization or decision making process for example. This paper describes how discrete event modeling and simulation could be integrated into reinforcement learning concepts and tools in order to assist in the realization of reinforcement learning systems, more specially considering the temporal, hierarchical, and multi-agent aspects. An overview of these different improvements are given based on the implementation of the Q-Learning reinforcement learning algorithm in the framework of the Discrete Event system Specification (DEVS) and System Entity Structure (SES) formalisms.
Mass Trapping Drosophila suzukii, What Would It Take? A Two-Year Field Study on Trap Interference
Authors: Clymans Rik , Van Kerckvoorde Vincent , Thys Tom , De Clercq Patrick , Bylemans Dany , Beliën Tim
Published: March 2022

The invasion of Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) worldwide has disrupted existing or developing integrated pest management (IPM) programs in soft-skinned fruits. Currently, with a reliance on only broad-spectrum insecticides, there is a critical call for alternative control measures. Behavioural control is one of the pillars of IPM, and, in the present study, it is investigated whether mass trapping could be viable for D. suzukii management. By quantifying trap interference in 4 × 4 replicate trapping grids, an estimate of the attraction radius for a certain attractant and context can be obtained. Traps designed for dry trapping (no drowning solution, but a killing agent inside) and synthetic controlled released experimental lures were tested in a two-year field study. Apple cider vinegar (ACV) was included as a reference bait and trials were performed with 5, 10 and 15 m inter-trap spacings at different seasonal timings. Clear trap interference and, hence, overlapping attraction radii were observed both in spring and summer for both the synthetic lures and ACV. In early spring, ACV shows the most potential for mass trapping, however from June onwards, the experimental dry lures show equal or better results than ACV. Based on our findings, workable trap densities are deemed possible, encouraging further development of mass trapping strategies for the control of D. suzukii.
Comparative Transcriptome Investigation of Nosema ceranae Infecting Eastern Honey Bee Workers
Authors: Fan Yuanchan , Wang Jie , Yu Kejun , Zhang Wende , Cai Zongbing , Sun Minghui , Hu Ying , Zhao Xiao , Xiong Cuiling , Niu Qingsheng , Chen Dafu , Guo Rui
Published: March 2022

Apis cerana is the original host for Nosema ceranae, a widespread fungal parasite resulting in honey bee nosemosis, which leads to severe losses to the apiculture industry throughout the world. However, knowledge of N. ceranae infecting eastern honey bees is extremely limited. Currently, the mechanism underlying N. ceranae infection is still largely unknown. Based on our previously gained high-quality transcriptome datasets derived from N. ceranae spores (NcCK group), N. ceranae infecting Apis cerana cerana workers at seven days post inoculation (dpi) and 10 dpi (NcT1 and NcT2 groups), comparative transcriptomic investigation was conducted in this work, with a focus on virulence factor-associated differentially expressed genes (DEGs). Microscopic observation showed that the midguts of A. c. cerana workers were effectively infected after inoculation with clean spores of N. ceranae. In total, 1411, 604, and 38 DEGs were identified from NcCK vs. NcT1, NcCK vs. NcT2, and NcT1 vs. NcT2 comparison groups. Venn analysis showed that 10 upregulated genes and nine downregulated ones were shared by the aforementioned comparison groups. The GO category indicated that these DEGs were involved in a series of functional terms relevant to biological process, cellular component, and molecular function such as metabolic process, cell part, and catalytic activity. Additionally, KEGG pathway analysis suggested that the DEGs were engaged in an array of pathways of great importance such as metabolic pathway, glycolysis, and the biosynthesis of secondary metabolites. Furthermore, expression clustering analysis demonstrated that the majority of genes encoding virulence factors such as ricin B lectins and polar tube proteins displayed apparent upregulation, whereas a few virulence factor-associated genes such as hexokinase gene and 6-phosphofructokinase gene presented downregulation during the fungal infection. Finally, the expression trend of 14 DEGs was confirmed by RT-qPCR, validating the reliability of our transcriptome datasets. These results together demonstrated that an overall alteration of the transcriptome of N. ceranae occurred during the infection of A. c. cerana workers, and most of the virulence factor-related genes were induced to activation to promote the fungal invasion. Our findings not only lay a foundation for clarifying the molecular mechanism underlying N. ceranae infection of eastern honey bee workers and microsporidian–host interaction.
Mutualism between Gut-Borne Yeasts and Their Host, Thaumatotibia leucotreta, and Potential Usefulness in Pest Management
Authors: van der Merwe Marcel , Jukes Michael D. , Knox Caroline , Moore Sean D. , Hill Martin P.
Published: March 2022

Thaumatotibia leucotreta is endemic to southern Africa and is highly significant for various fruit industries, including the South African citrus industry, due to its classification as a phytosanitary pest. Mutualistic associations between C. pomonella, closely related to T. leucotreta, and yeasts have previously been described and reported to reduce larval mortality and enhance larval development. Here, we determined which yeast species occur naturally in the gut of T. leucotreta larvae and investigated whether any of the isolated yeast species affect their behaviour and development. Navel oranges infested with T. leucotreta larvae were collected from geographically distinct provinces in South Africa, and the larvae were processed for analysis of naturally occurring associated yeasts. Six yeast species were isolated and identified from the guts of these T. leucotreta larvae via PCR amplification and sequencing of the ITS region of rDNA and D1/D2 domain of large ribosomal subunit. Larval development and attraction assays were conducted, and T. leucotreta larvae that fed on Navel oranges inoculated with yeast had accelerated developmental periods and reduced mortality rates. Neonate T. leucotreta were also attracted to YPD broth cultures inoculated with yeast for feeding. Oviposition preference assays were conducted with adult T. leucotreta females. Navel oranges inoculated with yeast were shown to influence the oviposition preference of adult females. Yeasts harbour the potential for use in biocontrol, especially when combined with other well-established control methods. This study provides a platform for future research into incorporating yeast with current biological control agents as a novel option for controlling T. leucotreta in the field.
Chemical Compounds Emitted from Mentha spicata Repel Aromia bungii Females
Authors: Cao Dandan , Liu Jianfeng , Zhao Zhengping , Yan Xuewu , Wang Weichao , Wei Jianrong
Published: March 2022

Aromia bungii (Coleoptera: Cerambycidae) is an economically important wood-boring insect pest of stone fruit trees, particularly Prunus persica, in China. It has entered Japan and several European countries as an invasive species in recent years. It is difficult to control because of the cryptic feeding behaviour of larvae beneath the bark. Identification of repellent constituents from non-host plants has potential for use in management strategies against this beetle. Mentha spicata is cultivated extensively in Hebei Province (China) as a medicinal plant. Firstly, antennal responses of female A. bungii to M. spicata volatiles were evaluated by coupled gas chromatography-electroantennograms (GC-EAD), and then the EAD-active components were tested in semi-field trials. The results showed that A. bungii females were significantly repelled by myrcene, (S)-(+)-carvone, (E)-β-caryophyllene, and borneol compared with the control. The presence of myrcene (100 µL; 90% purity), (S)-(+)-carvone (200 µL; 96% purity), (E)-β-caryophyllene (500 µL; 98.5% purity), and borneol (800 µL; 80% purity) significantly reduced the perching rates of A. bungii females on both peach logs and leaves. Considering cost and commercial availability, we suggest that myrcene, (S)-(+)-carvone, and (E)-β-caryophyllene could be promising repellents against A. bungii females in the field.
Effect of the Amount of Ephestia kuehniella Eggs for Rearing on Development, Survival, and Reproduction of Orius laevigatus
Authors: Gallego Francisco Javier , Rodríguez-Gómez Amador , Reche María del Carmen , Balanza Virginia , Bielza Pablo
Published: March 2022

Orius laevigatus is a key tool for the success of augmentative biological control programs in protected crops. This biological control agent is mass-reared feeding on eggs of Ephestia kuehniella. However, this factitious prey is expensive, accounting for a significant percentage of the rearing costs. Therefore, there is a need to optimize the amount of Ephestia eggs needed per individual leading to a cost reduction, which in turn will favor biological control adoption. This study investigated the effect of the amount of Ephestia eggs provided on the developmental and reproductive fitness of O. laevigatus. At least a daily supply of 1 and 3 Ephestia eggs was needed for optimal development of the first two nymphal instars, respectively, although for maximum survival, 1 egg was enough for both instars. For subsequent development until adulthood, a minimum of 8 eggs per day were needed to fully support growth, but only 3 eggs for optimal survival. Similarly, male body size was also maximized by feeding 8 eggs, but for maximum female body size 10 eggs per day were required. Oviposition rate of females increased with the daily number of Ephestia eggs provided, until a plateau was reached at 8 eggs/day. Benefits and savings for industrial production of O. laevigatus are discussed.
Strategies for Studying Acidification and Eutrophication Potentials, a Case Study of 150 Countries
Authors: Kameni Nematchoua Modeste
Published: March 2022

Acidification and eutrophication are two environmental impacts that have a significant effect on air pollution and human health. The quantitative analysis of these two impacts remains hitherto unknown at the scale of new neighborhoods. The main objective of this study is to evaluate, analyze and compare the acidification and eutrophication potentials of one neighborhood initially located in Belgium. For making this comparison, this neighborhood was built in 149 other countries by applying four parameters such as building materials, energy mix, occupants’ mobility and local climate. The environmental costs of acidification and eutrophication coming from this neighborhood were assessed over 100 years. This research, extended to the scale of several nations, will enable new researchers, and especially policy-makers, to measure the effectiveness of sustainable neighborhoods. Eutrophication and acidification potentials were assessed under different phases (construction, use, renovation and demolition), with Pleiades software (version 4.19.1.0). The effects of the energy mix were the most significant among the other parameters. The results show that 72%, and 65% of acidification and eutrophication potentials are produced during the operational phase of the neighborhood. In the case of sustainable neighborhoods, the acidification potential is 22.1% higher in the 10 top low-income countries than in the 10 top high-income countries. At the neighborhood scale, the main eutrophication potential component is water (34.2%), while the main source of acidification potential is electricity production (45.1%).
Technical Recommendations for Real-Time Echocardiography and Fluoroscopy Imaging Fusion in Catheter-Based Mitral Valve Paravalvular Leak and Other Procedures
Authors: Zorinas Aleksejus , Zakarkaitė Diana , Janušauskas Vilius , Austys Donatas , Puodžiukaitė Lina , Zuozienė Gitana , Samalavičius Robertas , Jovaišienė Ieva , Davidavičius Giedrius , Ručinskas Kęstutis , Onorato Eustaquio
Published: March 2022

Widespread catheter-based interventions for structural heart disease have overtaken the treatment of paravalvular leaks (PVL). Multimodality imaging techniques play a crucial role in accurate diagnosis, procedure planning and performance. However, PVL closure is often technically challenging due to the complex anatomy of the defects and their relation to surrounding anatomical structures. The application of echocardiography and fluoroscopy imaging fusion (EFF) may simplify challenging imaginative three-dimensional reconstruction of the intracardiac anatomy and facilitate the procedure. To master new technology, personnel must make cognitive changes, overcome a learning curve, and obtain adequate theoretical knowledge. Main aim of this manuscript is to present basic recommendations for EFF application in practice, alongside, each scenario is supported by technically challenging clinical examples. We may conclude that our manuscript may provide useful information for physicians on EEF application in clinical practice.
Efficacy of Flotetuzumab in Combination with Cytarabine in Patient-Derived Xenograft Models of Pediatric Acute Myeloid Leukemia
Authors: Barwe Sonali P. , Kisielewski Anne , Bonvini Ezio , Muth John , Davidson-Moncada Jan , Kolb Edward Anders , Gopalakrishnapillai Anilkumar
Published: March 2022

Children with acute myeloid leukemia (AML) have a poor prognosis despite the intensification of chemotherapy. Future efforts to improve outcomes should focus on more precise targeting of leukemia cells. CD123, or IL3RA, is expressed on the surface of nearly all pediatric AML samples and is a high-priority target for immunotherapy. The efficacy of an investigational dual-affinity retargeting antibody (DART) molecule (CD123 × CD3; MGD006 or flotetuzumab) was assessed in two distinct patient-derived xenograft (PDX) models of pediatric AML. MGD006 simultaneously binds to CD123 on target cells and CD3 on effector T cells, thereby activating T cells and redirecting them to induce cytotoxicity in target cells. The concurrent treatment of cytarabine and MGD006 was performed to determine the effect of cytarabine on T-cell counts and MGD006 activity. Treatment with MGD006 along with an allogeneic human T-cell infusion to act as effector cells induced durable responses in both PDX models, with CD123 positivity. This effect was sustained in mice treated with a combination of MGD006 and cytarabine in the presence of T cells. MGD006 enhanced T-cell proliferation and decreased the burden of AML blasts in the peripheral blood with or without cytarabine treatment. These data demonstrate the efficacy of MGD006 in prolonging survival in pediatric AML PDX models in the presence of effector T cells and show that the inclusion of cytarabine in the treatment regimen does not interfere with MGD006 activity.
Circulating HDL and Non-HDL Associated Apolipoproteins and Breast Cancer Severity
Authors: Bobin-Dubigeon Christine , Nazih Hassan , Blanchard Valentin , Croyal Mikaël , Bard Jean-Marie
Published: March 2022

Plasma lipids are carried within lipoproteins with various apolipoprotein content. This study evaluates the interest of measuring the apolipoproteins of circulating lipoproteins in breast cancer. Patients with early-stage breast cancer (n = 140) were included. Tumors differed by the expression of estrogen and progesterone receptor (HR− and HR+ for negative and positive expression) and the proliferation marker Ki-67 (≤20% or ≥30%). Apolipoprotein concentrations were determined in plasma, HDL and non-HDL fractions, and results are given in mg/dL, median (25th–75th). Patients did not differ in their plasma and lipoprotein lipid concentrations. HDL apoC-I and non-HDL apoC-II were reduced (1.34 (1.02–1.80) vs. 1.61 (1.32–2.04), p = 0.04; 0.31 (0.18–0.65) vs. 0.63 (0.39–1.02), p = 0.01; respectively), in RH-/high Ki-67 patients in comparison to RH-/low Ki-67 patients, while plasma apoD and HDL apoD were higher (3.24 (2.99–4.16) vs. 3.07 (2.39–3.51), p = 0.04; 2.74 (2.36–3.35) vs. 2.45 (2.01–2.99), p = 0.04; respectively). When RH+/high Ki-67 patients were compared with RH+/low Ki-67 patients, HDL apoC-I and HDL apoC-III were higher (1.56 (1.20–1.95) vs. 1.35 (1.10–1.62), p = 0.02; 2.80 (2.42–3.64) vs. 2.38 (1.69–2.96), p = 0.02; respectively). The distribution of exchangeable apolipoproteins, such as apoC-I, apoC-II, apoC-III, apoD, between lipoproteins is linked to the severity of breast cancer.
Factors Influencing Pain Management of Patients with Osteoarthritis: A Cross-Sectional Study
Authors: Mezey Gyöngyi Anna , Máté Zsuzsanna , Paulik Edit
Published: March 2022

Background: Osteoarthritis (OA) is a complex disease associated with chronic pain. Many patients treat their joint pain at a symptomatic level with over-the-counter (OTC) pain medications, often without the knowledge of their physicians. The aim of this study was to provide physicians with data about osteoarthritic patients’ habits of pain management and to examine the explanatory factors of various ways of self-treatment. Methods: A cross-sectional study involving 189 patients with hip or knee OA and scheduled for joint replacement surgery was carried out. Participants filled out a self-administered questionnaire consisting of the Western Ontario and McMaster Universities Osteoarthritis Index and questions about their methods of alleviating pain. Results: 2.6% of patients did not use anything to alleviate their pain, while 63% practiced a non-pharmacological method. Diclofenac was the most frequently used drug, followed by ibuprofen. Profession had the greatest impact on medication habits; patients doing manual work were significantly more likely to take OTC non-steroidal anti-inflammatory drugs and use topical analgesics. Conclusions: Patients utilized a wide variety of pain management techniques. They seemed to use well-known painkillers, even if their side effects were less desirable. Such patients require comprehensive pain management, including educational and behavioural interventions, complemented by topical and oral medication.
Osseointegration at Implants Installed in Composite Bone: A Randomized Clinical Trial on Sinus Floor Elevation
Authors: Kotsu Mitsuo , Apaza Alccayhuaman Karol Alí , Ferri Mauro , Iezzi Giovanna , Piattelli Adriano , Fortich Mesa Natalia , Botticelli Daniele
Published: March 2022

Osseointegration of implants installed in conjunction with sinus floor elevation might be affected by the presence of residual graft. The implant surface characteristics and the protection of the access window using a collagen membrane might influence the osseointegration. To evaluate these factors, sinus floor elevation was performed in patients using a natural bovine bone grafting material. The access windows were either covered with a collagen membrane made of porcine corium (Mb group) or left uncovered (No-Mb group) and, after six months, two mini-implants with either a moderate rough or turned surfaces were installed. After 3 months, biopsies containing the mini-implants were retrieved, processed histologically, and analyzed. Twenty patients, ten in each group, were included in the study. The two mini-implants were retrieved from fourteen patients, six belonging to the Mb group, and eight to the No-Mb group. No statistically significant differences were found in osseointegration between groups. However, statistically significant differences were found between the two surfaces. It was concluded that implants with a moderately rough surface installed in a composite bone presented much higher osseointegration compared to those with a turned surface. The present study failed to show an effect of the use of a collagen membrane on the access window.
The Comparison of Advanced Electrospun Materials Based on Poly(-3-hydroxybutyrate) with Natural and Synthetic Additives
Authors: Tyubaeva Polina , Varyan Ivetta , Krivandin Alexey , Shatalova Olga , Karpova Svetlana , Lobanov Anton , Olkhov Anatoly , Popov Anatoly
Published: March 2022

The comparison of the effect of porphyrins of natural and synthetic origin containing the same metal atom on the structure and properties of the semi-crystalline polymer matrix is of current concern. A large number of modifying additives and biodegradable polymers for biomedical purposes, composed of poly(-3-hydroxybutyrate)-porphyrin, are of particular interest because of the combination of their unique properties. The objective of this work are electrospun fibrous material based on poly(-3-hydroxybutyrate) (PHB), hemin (Hmi), and tetraphenylporphyrin with iron (Fe(TPP)Cl). The structure of these new materials was investigated by methods such as optical and scanning electron microscopy, X-ray diffraction analysis, Electron paramagnetic resonance method, and Differential scanning calorimetry. The properties of the electrospun materials were analyzed by mechanical and biological tests, and the wetting contact angle was measured. In this work, it was found that even small concentrations of porphyrin can increase the antimicrobial properties by 12 times, improve the physical and mechanical properties by at least 3.5 times, and vary hydrophobicity by at least 5%. At the same time, additives similar in the structure had an oppositely directed effect on the supramolecular structure, the composition of the crystalline, and the amorphous phases. The article considers assumptions about the nature of such differences due to the influence of Hmi and Fe(TPP)Cl) on the macromolecular and fibrous structure of PHB.
In Silico, Combined Plasmonic Photothermal and Photodynamic Therapy in Mice
Authors: Kareliotis Georgios , Chronopoulou Eleni , Makropoulou Mersini
Published: March 2022

Plasmonic photothermal and photodynamic therapy (PPTT and PDT, respectively) are two cancer treatments that have the potential to be combined in a synergistic scheme. The aim of this study is to optimize the PPTT treatment part, in order to account for the PDT lack of coverage in the hypoxic tumor volume and in cancer areas laying in deep sites. For the needs of this study, a mouse was modeled, subjected to PDT and its necrotic area was estimated by using the MATLAB software. The same procedure was repeated for PPTT, using COMSOL Multiphysics. PPTT treatment parameters, namely laser power and irradiation time, were optimized in order to achieve the optimum therapeutic effect of the combined scheme. The PDT alone resulted in 54.8% tumor necrosis, covering the upper cancer layers. When the PPTT was also applied, the total necrosis percentage raised up to 99.3%, while all of the surrounding studied organs (skin, heart, lungs and trachea, ribs, liver and spleen) were spared. The optimized values of the PPTT parameters were 550 mW of laser power and 70 s of irradiation time. Hence, the PPTT–PDT combination shows great potential in achieving high levels of tumor necrosis while sparing the healthy tissues.
Taxonomic Reappraisal of Periconiaceae with the Description of Three New Periconia Species from China
Authors: Yang Er-Fu , Phookamsak Rungtiwa , Jiang Hong-Bo , Tibpromma Saowaluck , Bhat Darbhe J. , Karunarathna Samantha C. , Dai Dong-Qin , Xu Jian-Chu , Promputtha Itthayakorn
Published: March 2022

As a result of an ongoing research survey of microfungi in Yunnan, China, several saprobic ascomycetes were collected from various host substrates. Preliminary morphological analyses identified a few of these taxa as Periconia species. We obtained DNA sequence data of the Periconia species from pure cultures and investigated their phylogenetic affinities. Phylogenetic analyses of a combined LSU, ITS, SSU and tef1-α sequence dataset demonstrated that five isolates of Periconia formed well-resolved subclades within Periconiaceae. Accordingly, three new Periconia species are introduced viz. P. artemisiae, P. chimonanthi and P. thysanolaenae, and new host and geographical records of P. byssoides and P. pseudobyssoides, are also reported from dead branches of Prunus armeniaca and Scrophularia ningpoensis. Periconia celtidis formed a monophyletic clade with P. byssoides in the present phylogenetic analyses. Results of the pairwise homoplasy index (PHI) test indicated significant recombination between P. byssoides and P. celtidis. Therefore, P. celtidis has been synonymized under P. byssoides. In addition, we re-illustrated and studied the type specimen of the sexual genus Bambusistroma. As a type species of Bambusistroma, B. didymosporum features similar morphology to the sexual morph of Periconia homothallica and P. pseudodigitata. We therefore synonymize Bambusistroma under Periconia based on morphological and phylogenetic evidence. Furthermore, our new isolates produced brown conidia of asexual morph in agar media typical of the genus Noosia. Based on morphological comparison with Periconia in vitro and phylogenetic status of Noosia, we also treat Noosia as a synonym of Periconia. Detailed descriptions and illustrations of three novel taxa and two new records of Periconia byssoides and P. pseudobyssoides as well as the illustration of P. didymosporum comb. nov. are provided. An updated phylogenetic tree of Periconiaceae using maximum likelihood and Bayesian inference analyses is constructed. Generic circumscription of Periconia is amended.
Correlation of Genetic Variants and the Incidence, Prevalence and Mortality Rates of Acute Lymphoblastic Leukemia
Authors: Fernandes Marianne Rodrigues , Souza Vinagre Lui Wallacy Morikawa , Rodrigues Juliana Carla Gomes , Wanderley Alayde Vieira , Fernandes Sweny Marinho , Gellen Laura Patrícia Albarello , Alcântara Angélica Leite de , Sousa Beatriz Brilhante de , Burbano Rommel Mario Rodríguez , Assumpção Paulo Pimentel de , Santos Sidney Emanuel Batista dos , Santos Ney Pereira Carneiro dos
Published: March 2022

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, representing about 30–35% of cases. Its etiology is complex and not fully understood. ALL is influenced by genetic variants, and their frequencies (Fq) vary in different ethnic groups, which consequently could influence the epidemiology of this cancer worldwide. The aim of this study was to investigate the correlation between the genetic variants and their impacts on incidence (IC), mortality (MT), and prevalence (PV) rates of ALL in different world populations. Methods: Sixty variants were selected from the literature with Genome Wide Association studies (GWAS). Information regarding allele Fq was selected from the 1000 Genomes platform. Epidemiological data were taken from the Global Burden of disease visualisations (GBD) Compare website. Statistical analyses were calculated in RStudio v.3.5.1 software. Results: Four variants demonstrated significant results in correlations with epidemiological data for ALL. The PAX5 gene variant (rs2297105) had an indirect relationship with PV and IC of ALL, showing that an increased Fq of this variant is related to low rates of both. An increased Fq of rs915172 in EPB4IL2 gene was also correlated with a lower IC of ALL. The rs1048943 of the CYP1A1 gene and the rs3088440 polymorphism of the CDKN2A gene were shown to have a direct proportional relationship with MT rate, showing that an increased Fq of these variants correlates with a worse prognosis worldwide. Conclusion: Our study points out four important variants for understanding the IC, PV, and MT rates for ALL. The ascertainment of these data may help to choose molecular markers to investigate the susceptibility and prognosis of ALL.
Oral Health among Elderly, Impact on Life Quality, Access of Elderly Patients to Oral Health Services and Methods to Improve Oral Health: A Narrative Review
Authors: Janto Michael , Iurcov Raluca , Daina Cristian Marius , Neculoiu Daniela Carmen , Venter Alina Cristiana , Badau Dana , Cotovanu Adrian , Negrau Marcel , Suteu Corina Lacramioara , Sabau Monica , Daina Lucia Georgeta
Published: March 2022

Dental health is often neglected among the elderly because of the numerous comorbidities in this population, such as cardiovascular diseases. However, dental health influences general health and quality of life by impacting both the general health and the psychological state of the individual. The present review highlights the main dental comorbidities in the elderly population, their impact on the quality of life, the barriers towards access to dental care in the elderly and methods to improve their dental health. Information related to dental care and its importance must be provided both to older individuals and their caregivers in order to detect dental pathology and treat it adequately. Ensuring dental health involves the whole society of elders, caregivers, dental care providers, the public sector, health policymakers, and the private sector.
Relapsed/Refractory Mantle Cell Lymphoma: Beyond BTK Inhibitors
Authors: Burkart Madelyn , Karmali Reem
Published: March 2022

Mantle cell lymphoma (MCL) is a rare mature B-cell non-Hodgkin lymphoma (B-NHL) with historically poor outcomes. Virtually all patients will eventually experience refractory or relapsed (R/R) disease, with a virulent course of resistance and serial relapses, making treatment challenging. The available therapies for R/R MCL are not curative with conventional therapy, their goal being to palliate and prolong survival. A variety of agents approved for R/R MCL, including Bruton’s tyrosine kinase inhibitors (BTKi), changed the treatment landscape of R/R MCL. In the pre-BTKi era, the median progression-free survival (PFS) in R/R disease was 4–9 months. With the introduction of ibrutinib, the median PFS improved to 13–14.6 months. Despite these impressive results, the duration of response is limited, and resistance to BTKi inevitably develops in a subset of patients. Outcomes after progression on BTKi are extremely poor, with a median overall survival (OS) of 6 to 10 months. Certain therapies, such as chimeric antigen receptor (CAR) T cells, have shown promising results after BTKi failure. The preferred combination and sequencing of therapies beyond BTKi remain unestablished and are currently being investigated. In this review, we describe the current evidence for the available treatment of R/R MCL after progression on BTKi.
Adjective Placement in English/Spanish Mixed Determiner Phrases: Insights from Acceptability Judgments
Authors: De Nicolás Irati , López Luis
Published: March 2022

The present study examines the relative order of noun-adjective sequences within code-switched Determiner Phrases. Several hypotheses have been considered: (i) Order is a property defined by the noun; (ii) it is a property defined by the adjective; (iii) it is a property governed by the carrier phrase. The studies that have investigated the issue all assume that the class of adjectives is homogeneous, but in fact, there exist several sub-classes of adjectives which in many languages, including Spanish, exhibit distinct ordering properties. We propose to add the variable ‘adjective type’ to our study and use code-switching of English/Spanish, two languages that differ in the position of adjectives, as our database. A total of thirty English/Spanish heritage speakers took part in an experiment. Our results show that both the language of the adjective and the carrier phrase are significant factors of word order in the noun phrase; on the other hand, the noun itself does not seem to play a role.
The Extreme Right as a Defender of Human Rights? Parliamentary Debates on COVID-19 Emergency Legislation in Slovakia
Authors: Steuer Max
Published: March 2022

During the COVID-19 pandemic, the protection of public health became a political priority worldwide. Slovakia’s COVID-19 response was initially praised as a global success. However, major rights restrictions were introduced in spring 2020, with some of these endorsed by the parliament. This article uses Rossiter’s and Schmitt’s concepts of the exception and Agamben’s distinction between life and survival to highlight the risks pertaining to the framing of the protection of public health as contradictory to human rights guarantees. It investigates how human rights were discussed by Slovak parliamentarians in relation to key legislation, that introduced a COVID-19 contact tracing app and allowed repeated prolongation of health emergencies by the executive with parliamentary approval. The findings indicate that democratic parliamentarians prioritized public health considerations framed in terms of security and effectiveness rather than rights, dissociating biological survival from political life. In contrast, extreme political actors became outspoken critics of emergencies, referring to human rights. As such, the deliberations represent a missed opportunity by democratic legislators to justify public health protection via a human rights lens and risk undermining democracy in Slovakia.
Piceatannol Affects Gastric Ulcers Induced by Indomethacin: Association of Antioxidant, Anti-Inflammatory, and Angiogenesis Mechanisms in Rats
Authors: Shaik Rasheed A. , Eid Basma G.
Published: March 2022

One of the major aggressive factors that affect gastric injury is non-steroidal anti-inflammatory drugs (NSAIDs). Indomethacin (Indo) showed higher potentiality in gastric injury over conventional NSAIDs. Piceatannol (PIC) is a natural polyphenolic stilbene that possesses potent antioxidant and anti-inflammatory properties. The gastroprotective properties of PIC have been overlooked previously. Hence, we aim to study gastric injury induced by Indo and the protective action manifested by PIC, as well as to elucidate the likely underlying mechanisms of action in a rat model. The rats have been treated with vehicle, Indo alone, combined treatment with Indo, and PIC at (5 mg/kg or 10 mg/kg), respectively. The rats were also treated with Indo and omeprazole. In our study, we found that PIC at both 5 and 10 mg/kg doses was effective by averting the rise in ulcer and lesion indices, acid production, and histological variations persuaded by Indo. Mechanistically, PIC significantly reduced lipid peroxidation product (MDA), increased the GSH content, and enhanced SOD and CAT activity. In addition, PIC exhibits a distinct reduction in the levels of inflammatory parameters (Cox-2, IL-6, TNF-α, and NFκB). Contrastingly, PIC augmented both mucin and PGE2 content. Moreover, PIC fostered angiogenesis by increasing the expression of proangiogenic factors (VEGF, bFGF, and PDGF). Overall, the above results suggest PIC exhibits a potential protective effect against Indo-induced gastric ulcers by the antioxidant, anti-inflammatory, and angiogenic mechanisms.
Microstructure and Properties of Additively Manufactured AlCoCr0.75Cu0.5FeNi Multicomponent Alloy: Controlling Magnetic Properties by Laser Powder Bed Fusion via Spinodal Decomposition
Authors: Yang Xuan , Heczko Oleg , Lehtonen Joonas , Björkstrand Roy , Salmi Mika , Uhlenwinkel Volker , Ge Yanling , Hannula Simo-Pekka
Published: March 2022

A non-equiatomic AlCoCr0.75Cu0.5FeNi alloy has been identified as a potential high strength alloy, whose microstructure and consequently properties can be widely varied. In this research, the phase structure, hardness, and magnetic properties of AlCoCr0.75Cu0.5FeNi alloy fabricated by laser powder bed fusion (LPBF) are investigated. The results demonstrate that laser power, scanning speed, and volumetric energy density (VED) contribute to different aspects in the formation of microstructure thus introducing alterations in the properties. Despite the different input parameters studied, all the as-built specimens exhibit the body-centered cubic (BCC) phase structure, with the homogeneous elemental distribution at the micron scale. A microhardness of up to 604.6 ± 6.8 HV0.05 is achieved owing to the rapidly solidified microstructure. Soft magnetic behavior is determined in all as-printed samples. The saturation magnetization (Ms) is dependent on the degree of spinodal decomposition, i.e., the higher degree of decomposition into A2 and B2 structure results in a larger Ms. The results introduce the possibility to control the degree of spinodal decomposition and thus the degree of magnetization by altering the input parameters of the LPBF process. The disclosed application potentiality of LPBF could benefit the development of new functional materials.