bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Marrow Hypocellularity in Patients with End-Stage Kidney Disease
Authors: Hsieh Chia-Chen , Chan Ming-Jen , Su Yi-Jiun , Fu Jen-Fen , Wang I-Kuan , Chen Chao-Yu , Weng Cheng-Hao , Huang Wen-Hung , Hsu Ching-Wei , Yen Tzung-Hai
Published: October 2021

Background. Anemia and pancytopenia are not uncommon in patients with chronic kidney disease (CKD). Nevertheless, there is insufficient literature analyzing bone marrow pathology in patients with CKD or end-stage kidney disease (ESKD) receiving dialysis. Methods. This observational cohort study included 22 patients with ESKD and 23 patients with CKD that received bone marrow biopsy and aspiration at Chang Gung Memorial Hospital. Demographic, hematological, and biochemical data were collected at the time of bone marrow study for analysis. Results. Bone marrow aspiration demonstrated that patients with ESKD had a lower percentage of blasts than patients with CKD (0.52 ± 0.84 versus 1.06 ± 0.78 %, p = 0.033). Bone marrow biopsy revealed that the overall incidence of hypocellular bone marrow was 55.6%. Furthermore, patients with ESKD had higher proportion of hypocellular bone marrow than patients with CKD (72.7% versus 39.1%, p = 0.023). In a multivariate logistic regression model, it was revealed that ESKD status (odds ratio 9.43, 95% confidence interval 1.66–53.63, p = 0.011) and megakaryocyte count within bone marrow (odds ratio 0.48, 95% confidence interval 0.29–0.79, p = 0.004) were significant predictors for bone marrow hypocellularity. Conclusion. Bone marrow hypocellularity is common in patients with kidney dysfunction. Hypocellular marrow occurs more frequently in patients with ESKD than patients with CKD.
The Social Robot and the Digital Physiotherapist: Are We Ready for the Team Play?
Authors: Simeoni Rossella , Colonnelli Federico , Eutizi Veronica , Marchetti Matteo , Paolini Elena , Papalini Valentina , Punturo Alessio , Salvò Alice , Scipinotti Nicoletta , Serpente Christian , Barbini Emanuele , Troscia Riccardo , Maccioni Giovanni , Giansanti Daniele
Published: October 2021

Motivation: We are witnessing two phenomena. The first is that the physiotherapist is increasingly becoming a figure that must interact with Digital Health. On the other hand, social robots through research are improving more and more in the aspects of social interaction thanks also to artificial intelligence and becoming useful in rehabilitation processes. It begins to become strategic to investigate the intersections between these two phenomena. Objective: Therefore, we set ourselves the goal of investigating the consensus and opinion of physiotherapists around the introduction of social robots in clinical practice both in rehabilitation and assistance. Procedure: An electronic survey has been developed focused on social robot-based rehabilitation and assistance and has been submitted to subjects focused on physiotherapy sciences to investigate their opinion and their level of consent regarding the use of the social robot in rehabilitation and assistance. Two samples of subjects were recruited: the first group (156 participating subjects, 79 males, 77 females, mean age 24.3 years) was in the training phase, and the second (167 participating subjects, 86 males, 81 females, mean age 42.4 years) group was involved in the work processes. An electronic feedback form was also submitted to investigate the acceptance of the proposed methodology. Results: The survey showed a consistency of the results between the two samples from which interesting considerations emerge. Contrary to stereotypes that report how AI-based devices put jobs at risk, physiotherapists are not afraid of these devices. The subjects involved in the study believe the following: (a) social robots can be reliable co-workers but will remain a complementary device; (b) their role will be of the utmost importance as an operational manager in their use and in performance monitoring; (c) these devices will allow an increase in working capacity and facilitate integration. All those involved in the study believe that the proposed electronic survey has proved to be a useful and effective tool that can be useful as a periodic monitoring tool and useful for scientific societies. Conclusions: The evolution of social robots represents an unstoppable process as does the increase in the aging of the population. Stakeholders must not look with suspicion toward these devices, which can represent an important resource, but rather invest in monitoring and consensus training initiatives.
Effect of Collaborative Governance on Medical and Nursing Service Combination: An Evaluation Based on Delphi and Entropy Method
Authors: Chang Beiquan , Yang Yansui , Buitrago Leon Guillermo Andres , Lu Yuzhong
Published: October 2021

[Background]: Improvement of synergies in medical and nursing services can help governments to optimize the allocation of medical resources; however, an appropriate evaluation method is critical for a suitable decision process in this regard. [Method]: To assess the medical and nursing service combination (MNSC) at a regional level, this study applied a five-dimension evaluation index composed of 28 basic response areas related to the MNSC development status in China, determining its respective weight through the Delphi and entropy methods. [Result]: This empirical exercise analyzed the MNSC supply system by interviewing nine heads of medical and nursing institutions and eleven healthcare-related government personnel during August of 2020 in Xinxiang City, Henan province, P.R China. Results showed: (1) public satisfaction with the fees charged by Medical and Nursing service Institutions (MNSI); (2) Medicare and supply services’ policy publicity; (3) the external financing situation of MNSI; (4) the medical staff’s professional quality; (5) the medical facilities and supply of MNSI; and (6) that the recognition level of the development plan of MNSI scored the highest effect on the synergy of MNSC supply among the assessed factors. [Conclusion]: These results showed that an evaluation based on the Delphi and entropy methods can effectively integrate the opinions of experts and related institutions to evaluate synergies on the medical and nursing service supply.
Assessing the Prediction Accuracy of Geomorphon-Based Automated Landform Classification: An Example from the Ionian Coastal Belt of Southern Italy
Authors: Gioia Dario , Danese Maria , Corrado Giuseppe , Di Leo Paola , Minervino Amodio Antonio , Schiattarella Marcello
Published: October 2021

Automatic procedures for landform extraction is a growing research field but extensive quantitative studies of the prediction accuracy of Automatic Landform Classification (ACL) based on a direct comparison with geomorphological maps are rather limited. In this work, we test the accuracy of an algorithm of automatic landform classification on a large sector of the Ionian coast of the southern Italian belt through a quantitative comparison with a detailed geomorphological map. Automatic landform classification was performed by using an algorithm based on the individuation of basic landform classes named geomorphons. Spatial overlay between the main mapped landforms deriving from traditional geomorphological analysis and the automatic landform classification results highlighted a satisfactory percentage of accuracy (higher than 70%) of the geomorphon-based method for the coastal plain area and drainage network. The percentage of accuracy decreased by about 20–30% for marine and fluvial terraces, while the overall accuracy of the ACL map is 69%. Our results suggest that geomorphon-based classification could represent a basic and robust tool to recognize the main geomorphological elements of landscape at a large scale, which can be useful for the advanced steps of geomorphological mapping such as genetic interpretation of landforms and detailed delineation of complex and composite geomorphic elements.
Potentiating the Benefits of Melatonin through Chemical Functionalization: Possible Impact on Multifactorial Neurodegenerative Disorders
Authors: Galano Annia , Guzmán-López Eduardo G. , Reiter Russel J.
Published: October 2021

Although melatonin is an astonishing molecule, it is possible that chemistry will help in the discovery of new compounds derived from it that may exceed our expectations regarding antioxidant protection and perhaps even neuroprotection. This review briefly summarizes the significant amount of data gathered to date regarding the multiple health benefits of melatonin and related compounds. This review also highlights some of the most recent directions in the discovery of multifunctional pharmaceuticals intended to act as one-molecule multiple-target drugs with potential use in multifactorial diseases, including neurodegenerative disorders. Herein, we discuss the beneficial activities of melatonin derivatives reported to date, in addition to computational strategies to rationally design new derivatives by functionalization of the melatonin molecular framework. It is hoped that this review will promote more investigations on the subject from both experimental and theoretical perspectives.
Design of High-Relaxivity Polyelectrolyte Nanocapsules Based on Citrate Complexes of Gadolinium(III) of Unusual Composition
Authors: Burilova Evgenia , Solodov Alexander , Shayimova Julia , Zhuravleva Julia , Shurtakova Darya , Evtjugin Vladimir , Zhiltsova Elena , Zakharova Lucia , Kashapov Ruslan , Amirov Rustem
Published: October 2021

Through nuclear magnetic relaxation and pH-metry, the details of the complexation of gadolinium(III) ions with citric acid (H4L) in water and aqueous solutions of cationic polyelectrolytes are established. It is shown that the presence of poly(ethylene imine) (PEI) in solution affects magnetic relaxation behavior of gadolinium(III) complexes with citric acid (Cit) to a greater extent than polydiallyldimethylammonium chloride (PDDC). A large increase in relaxivity (up to 50 mM−1s−1) in the broad pH range (4–8) is revealed for the gadolinium(III)–citric acid–PEI system, which is particularly strong in the case of PEI with the molecular weight of 25 and 60 kDa. In weakly acidic medium (pH 3–7), the presence of PEI results in the formation of two tris-ligand associates [Gd(H2L)3]3− and [Gd(H2L)2(HL)]4−, which do not exist in aqueous medium. In weakly alkaline medium (pH 7–10), formation of ternary complexes Gd(III)–Cit–PEI with the Gd(III)–to–Cit ratio of 1:2 is evidenced. Using transmission electron microscopy (TEM) and dynamic light scattering techniques (DLS), the formation of the particles with the size of 50–100 nm possessing narrow molecular-mass distribution (PDI 0.08) is determined in the solution containing associate of PEI with tris-ligand complex [Gd(H2L)2(HL)]4−.
Genomic Marks Associated with Chromatin Compartments in the CTCF, RNAPII Loop and Genomic Windows
Authors: Szczepińska Teresa , Mollah Ayatullah Faruk , Plewczynski Dariusz
Published: October 2021

The nature of genome organization into two basic structural compartments is as yet undiscovered. However, it has been indicated to be a mechanism of gene expression regulation. Using the classification approach, we ranked genomic marks that hint at compartmentalization. We considered a broad range of marks, including GC content, histone modifications, DNA binding proteins, open chromatin, transcription and genome regulatory segmentation in GM12878 cells. Genomic marks were defined over CTCF or RNAPII loops, which are basic elements of genome 3D structure, and over 100 kb genomic windows. Experiments were carried out to empirically assess the whole set of features, as well as the individual features in classification of loops/windows, into compartment A or B. Using Monte Carlo Feature Selection and Analysis of Variance, we constructed a ranking of feature importance for classification. The best simple indicator of compartmentalization is DNase-seq open chromatin measurement for CTCF loops, H3K4me1 for RNAPII loops and H3K79me2 for genomic windows. Among DNA binding proteins, this is RUNX3 transcription factor for loops and RNAPII for genomic windows. Chromatin state prediction methods that indicate active elements like promoters, enhancers or heterochromatin enhance the prediction of loop segregation into compartments. However, H3K9me3, H4K20me1, H3K27me3 histone modifications and GC content poorly indicate compartments.
The Bacterial Amyloids Phenol Soluble Modulins from Staphylococcus aureus Catalyze Alpha-Synuclein Aggregation
Authors: Haikal Caroline , Ortigosa-Pascual Lei , Najarzadeh Zahra , Bernfur Katja , Svanbergsson Alexander , Otzen Daniel E. , Linse Sara , Li Jia-Yi
Published: October 2021

Aggregated α-synuclein (α-syn) is the main constituent of Lewy bodies, which are a pathological hallmark of Parkinson’s disease (PD). Environmental factors are thought to be potential triggers capable of initiating the aggregation of the otherwise monomeric α-syn. Braak’s seminal work redirected attention to the intestine and recent reports of dysbiosis have highlighted the potential causative role of the microbiome in the initiation of pathology of PD. Staphylococcus aureus is a bacterium carried by 30–70% of the general population. It has been shown to produce functional amyloids, called phenol soluble modulins (PSMαs). Here, we studied the kinetics of α-syn aggregation under quiescent conditions in the presence or absence of four different PSMα peptides and observed a remarkable shortening of the lag phase in their presence. Whereas pure α-syn monomer did not aggregate up to 450 h after initiation of the experiment in neither neutral nor mildly acidic buffer, the addition of different PSMα peptides resulted in an almost immediate increase in the Thioflavin T (ThT) fluorescence. Despite similar peptide sequences, the different PSMα peptides displayed distinct effects on the kinetics of α-syn aggregation. Kinetic analyses of the data suggest that all four peptides catalyze α-syn aggregation through heterogeneous primary nucleation. The immunogold electron microscopic analyses showed that the aggregates were fibrillar and composed of α-syn. In addition of the co-aggregated materials to a cell model expressing the A53T α-syn variant fused to GFP was found to catalyze α-syn aggregation and phosphorylation in the cells. Our results provide evidence of a potential trigger of synucleinopathies and could have implications for the prevention of the diseases.
Lyophyllin, a Mushroom Protein from the Peptidase M35 Superfamily Is an RNA N-Glycosidase
Authors: Lu Jia-Qi , Shi Wei-Wei , Xiao Meng-Jie , Tang Yun-Sang , Zheng Yong-Tang , Shaw Pang-Chui
Published: October 2021

Ribosome-inactivating proteins (RIPs) hydrolyze the N-glycosidic bond and depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. In this study, we have purified and characterized lyophyllin, an unconventional RIP from Lyophyllum shimeji, an edible mushroom. The protein resembles peptidase M35 domain of peptidyl-Lys metalloendopeptidases. Nevertheless, protein either from the mushroom or in recombinant form possessed N-glycosidase and protein synthesis inhibitory activities. A homology model of lyophyllin was constructed. It was found that the zinc binding pocket of this protein resembles the catalytic cleft of a classical RIP, with key amino acids that interact with the adenine substrate in the appropriate positions. Mutational studies showed that E122 may play a role in stabilizing the positively charged oxocarbenium ion and H121 for protonating N-3 of adenine. The tyrosine residues Y137 and Y104 may be used for stacking the target adenine ring. This work first shows a protein in the peptidase M35 superfamily based on conserved domain search possessing N-glycosidase activity.
Diazoxide Needs Mitochondrial Connexin43 to Exert Its Cytoprotective Effect in a Cellular Model of CoCl2-Induced Hypoxia
Authors: Pecoraro Michela , Marzocco Stefania , Popolo Ada
Published: October 2021

Hypoxia is the leading cause of death in cardiomyocytes. Cells respond to oxygen deprivation by activating cytoprotective programs, such as mitochondrial connexin43 (mCx43) overexpression and the opening of mitochondrial KATP channels, aimed to reduce mitochondrial dysfunction. In this study we used an in vitro model of CoCl2-induced hypoxia to demonstrate that mCx43 and KATP channels cooperate to induce cytoprotection. CoCl2 administration induces apoptosis in H9c2 cells by increasing mitochondrial ROS production, intracellular and mitochondrial calcium overload and by inducing mitochondrial membrane depolarization. Diazoxide, an opener of KATP channels, reduces all these deleterious effects of CoCl2 only in the presence of mCx43. In fact, our results demonstrate that in the presence of radicicol, an inhibitor of Cx43 translocation to mitochondria, the cytoprotective effects of diazoxide disappear. In conclusion, these data confirm that there exists a close functional link between mCx43 and KATP channels.
Suture Fiber Reinforcement of a 3D Printed Gelatin Scaffold for Its Potential Application in Soft Tissue Engineering
Authors: Choi Dong Jin , Choi Kyoung , Park Sang Jun , Kim Young-Jin , Chung Seok , Kim Chun-Ho
Published: October 2021

Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and limit its application in the tissue engineering field. Herein, biodegradable suture fibers were added into a gelatin biomaterial ink to improve the printability, mechanical strength, and dimensional stability of the 3D printed scaffolds. The suture fiber reinforced gelatin 3D scaffolds were fabricated using the thermo-responsive properties of gelatin under optimized 3D printing conditions (−10 °C cryogenic plate, 40–80 kPa pneumatic pressure, and 9 mm/s printing speed), and were crosslinked using EDC/NHS to maintain their 3D structures. Scanning electron microscopy images revealed that the morphologies of the 3D printed scaffolds maintained their 3D structure after crosslinking. The addition of 0.5% (w/v) of suture fibers increased the printing accuracy of the 3D printed scaffolds to 97%. The suture fibers also increased the mechanical strength of the 3D printed scaffolds by up to 6-fold, and the degradation rate could be controlled by the suture fiber content. In in vitro cell studies, DNA assay results showed that human dermal fibroblasts’ proliferation rate of a 3D printed scaffold containing 0.5% suture fiber was 10% higher than that of a 3D printed scaffold without suture fibers after 14 days of culture. Interestingly, the supplement of suture fibers into gelatin biomaterial ink was able to minimize the cell-mediated contraction of the cell cultured 3D scaffolds over the cell culture period. These results show that advanced biomaterial inks can be developed by supplementing biodegradable fibers to improve the poor physical properties of natural polymer-based biomaterial inks.
Fluoroquinolones Suppress TGF-β and PMA-Induced MMP-9 Production in Cancer Cells: Implications in Repurposing Quinolone Antibiotics for Cancer Treatment
Authors: Huang Cheng-Yi , Yang Jenq-Lin , Chen Jih-Jung , Tai Shun-Ban , Yeh Yu-Hsuan , Liu Pei-Feng , Lin Ming-Wei , Chung Chih-Ling , Chen Chun-Lin
Published: October 2021

Background: Fluoroquinolones (FQs) are potent antimicrobials with multiple effects on host cells and tissues. Although FQs can attenuate cancer invasion and metastasis, the underlying molecular mechanisms remain unclear. Matrix metalloproteinase-9 (MMP-9) has functional roles in tumor angiogenesis, invasion, and metastasis, and is associated with cancer progression and poor prognosis, suggesting that inhibitors of MMP-9 activity and transcription are prime candidates for cancer therapy. Despite numerous preclinical data supporting the use of MMP-9 inhibitors as anticancer drugs, the few available examples are not therapeutically useful due to low specificity and off-target effects. We examined the effects of FQs on MMP-9 production in cancer cells following transforming growth factor beta (TGF-β) and phorbol 12-myristate 13-acetate (PMA) stimulation. Experimental approaches: Using confluent cultures of HepG2 and A549 cells, the effects of FQs (ciprofloxacin, levofloxacin, clinafloxacin, gatifloxacin, and enrofloxacin) on TGF-β and PMA-induced MMP-9 mRNA expression and production were studied in RNA extracts and culture supernatants, respectively. FQs specifically abrogated TGF-β and PMA-induced MMP-9 levels and activity in a concentration and time-dependent manner, without affecting other MMPs or proteins involved in epithelial-mesenchymal transition. Additionally, FQs inhibited TGF-β and PMA-induced cell migration via p38 and cyclic AMP signaling pathways. Conclusions and implications: Overall, we demonstrated that FQs inhibit cancer cell migration and invasion by downregulating MMP-9 expression and revealed the cellular mechanisms underlying their potential value in cancer treatment.
Swim Training Ameliorates Hyperlocomotion of ALS Mice and Increases Glutathione Peroxidase Activity in the Spinal Cord
Authors: Dzik Katarzyna Patrycja , Flis Damian Józef , Bytowska Zofia Kinga , Karnia Mateusz Jakub , Ziolkowski Wieslaw , Kaczor Jan Jacek
Published: October 2021

(1) Background: Amyotrophic lateral sclerosis (ALS) is an incurable, neurodegenerative disease. In some cases, ALS causes behavioral disturbances and cognitive dysfunction. Swimming has revealed a neuroprotective influence on the motor neurons in ALS. (2) Methods: In the present study, a SOD1-G93A mice model of ALS were used, with wild-type B6SJL mice as controls. ALS mice were analyzed before ALS onset (10th week of life), at ALS 1 onset (first symptoms of the disease, ALS 1 onset, and ALS 1 onset SWIM), and at terminal ALS (last stage of the disease, ALS TER, and ALS TER SWIM), and compared with wild-type mice. Swim training was applied 5 times per week for 30 min. All mice underwent behavioral tests. The spinal cord was analyzed for the enzyme activities and oxidative stress markers. (3) Results: Pre-symptomatic ALS mice showed increased locomotor activity versus control mice; the swim training reduced these symptoms. The metabolic changes in the spinal cord were present at the pre-symptomatic stage of the disease with a shift towards glycolytic processes at the terminal stage of ALS. Swim training caused an adaptation, resulting in higher glutathione peroxidase (GPx) and protection against oxidative stress. (4) Conclusion: Therapeutic aquatic activity might slow down the progression of ALS.
Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice
Authors: Van den Bergh Geoffrey , De Moudt Sofie , Van den Branden Astrid , Neven Ellen , Leysen Hanne , Maudsley Stuart , De Meyer Guido R. Y. , D’Haese Patrick , Verhulst Anja
Published: October 2021

Arterial media calcification (AMC) is predominantly regulated by vascular smooth muscle cells (VSMCs), which transdifferentiate into pro-calcifying cells. In contrast, there is little evidence for endothelial cells playing a role in the disease. The current study investigates cellular functioning and molecular pathways underlying AMC, respectively by, an ex vivo isometric organ bath set-up to explore the interaction between VSMCs and ECs and quantitative proteomics followed by functional pathway interpretation. AMC development, which was induced in mice by dietary warfarin administration, was proved by positive Von Kossa staining and a significantly increased calcium content in the aorta compared to that of control mice. The ex vivo organ bath set-up showed calcified aortic segments to be significantly more sensitive to phenylephrine induced contraction, compared to control segments. This, together with the fact that calcified segments as compared to control segments, showed a significantly smaller contraction in the absence of extracellular calcium, argues for a reduced basal NO production in the calcified segments. Moreover, proteomic data revealed a reduced eNOS activation to be part of the vascular calcification process. In summary, this study identifies a poor endothelial function, next to classic pro-calcifying stimuli, as a possible initiator of arterial calcification.
Biomolecular Evaluation of Piceatannol’s Effects in Counteracting the Senescence of Mesenchymal Stromal Cells: A New Candidate for Senotherapeutics?
Authors: Alessio Nicola , Squillaro Tiziana , Lettiero Ida , Galano Giovanni , De Rosa Roberto , Peluso Gianfranco , Galderisi Umberto , Di Bernardo Giovanni
Published: October 2021

Several investigations on senescence and its causative role in aging have underscored the importance of developing senotherapeutics, a field focused on killing senescent cells and/or preventing their accumulation within tissues. Using polyphenols in counteracting senescence may facilitate the development of senotherapeutics given their presence in the human diet, their confirmed tolerability and absence of severe side effects, and their role in preventing senescence and inducing the death of senescent cells. Against that background, we evaluated the effect of piceatannol, a natural polyphenol, on the senescence of mesenchymal stromal cells (MSCs), which play a key role in the body’s homeostasis. Among our results, piceatannol reduced the number of senescent cells both after genotoxic stress that induced acute senescence and in senescent replicative cultures. Such senotherapeutics activity, moreover, promoted the recovery of cell proliferation and the stemness properties of MSCs. Altogether, our findings demonstrate piceatannol’s effectiveness in counteracting senescence by targeting its associated pathways and detecting and affecting P53-dependent and P53-independent senescence. Our study thus suggests that, given piceatannol’s various mechanisms to accomplish its pleiotropic activities, it may be able to counteract any senescent phenotypes.
The Intervention and Mechanism of Action for Aloin against Subchronic Aflatoxin B1 Induced Hepatic Injury in Rats
Authors: Hua Hanyi , Sheng Jie , Cui Yan , Zhang Wenyi , Hu Bin , Cheng Yuliang , Guo Yahui , Qian He
Published: October 2021

As a class of difurancoumarin compounds with similar structures, aflatoxins (AF) are commonly found in the environment, soil, and food crops. AF pose a serious threat to the health of humans, poultry, and livestock. This study aimed to investigate the neuroprotective effect and detailed mechanism of aloin on hepatic injury induced by subchronic AFB1 in rats. The result showed that aloin could significantly inhibit the decrease in food intake, body weight growth, immune organ index, and serum albumin content caused by long-term AFB1 exposure. Meanwhile, aloin reduced the level of serum liver function and improved renal swelling and pathological changes of liver tissue. Aloin could also inhibit liver lipid peroxidation and improve liver antioxidant capacity. Further investigation revealed that aloin inhibited the activity and expression of hepatic CYP1A2 and CYP3A4 and down-regulated IL-1β expression in subchronic AFB1-induced liver injury rats. The above study demonstrated that aloin played an important role in blocking or delaying the development process of subchronic AFB1-induced hepatotoxicity. Therefore, aloin is considered to have a potential role as a protective agent against AFB1.
ATRvD1 Attenuates Renal Tubulointerstitial Injury Induced by Albumin Overload in Sepsis-Surviving Mice
Authors: Silva José Bruno N. F. , Calcia Thayanne B. B. , Silva Cyntia P. , Guilherme Rafael F. , Almeida-Souza Fernando , Lemos Felipe S. , Calabrese Kátia S. , Caruso-Neves Celso , Neves Josiane S. , Benjamim Claudia F.
Published: October 2021

Novel strategies for the prevention and treatment of sepsis-associated acute kidney injury and its long-term outcomes have been required and remain a challenge in critical care medicine. Therapeutic strategies using lipid mediators, such as aspirin-triggered resolvin D1 (ATRvD1), can contribute to the resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called the subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, the urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing proteinuria excretion, the UPC ratio, the glomerular cell number, and extracellular matrix deposition. Pro-fibrotic markers, such as transforming growth factor β (TGFβ), type 3 collagen, and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from the recruitment of IBA1+ cells. The interleukin-1β (IL-1β) levels were increased in the subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-α (TNF-α), IL-10, and IL-4 mRNA expression were increased in the kidney of BSA-challenged post-septic mice, and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult such as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis.
Isolated Growth Hormone Deficiency and Idiopathic Short Stature: Comparative Efficiency after Growth Hormone Treatment up to Adult Height
Authors: Ariza-Jimenez Ana-Belen , Leiva Gea Isabel , Martinez-Aedo Ollero Maria Jose , Lopez-Siguero Juan Pedro
Published: October 2021

Introduction: Treatment with growth hormone (GH) is not approved for idiopathic short stature (ISS) in Europe. Objectives: To compare the growth of children treated with isolated GH deficiency (IGHD) vs. ISS-treated and untreated children. Methods: A retrospective descriptive study of patients treated in the last 14 years for IGHD (Group A), in comparison with ISS-treated (Group B) and untreated (Group C) subjects. Results: Group A had 67 males, who showed a height gain of 1.24 SD. Group B had 30 boys, who showed a height gain of 1.47 SD. Group C had 42 boys, who showed an improvement of 0.37 SD. The final heights were −1.52 SD, −1.31 SD, and −2.03 SD, respectively. Group A and C did not reach their target heights (with differences of 0.27 SD and 0.59 SD, respectively). Group B surpassed their target height by 0.29 SD. Conclusions: The final heights of the IGHD and treated ISS are similar. Treated groups were taller than untreated groups.
Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy
Authors: Abumayyaleh Mohammad , Pilsinger Christina , El-Battrawy Ibrahim , Kummer Marvin , Kuschyk Jürgen , Borggrefe Martin , Mügge Andreas , Aweimer Assem , Akin Ibrahim
Published: October 2021

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.
Epstein–Barr Virus in Salivary Samples from Systemic Lupus Erythematosus Patients with Oral Lesions
Authors: Buonavoglia Alessio , Leone Patrizia , Prete Marcella , Solimando Antonio Giovanni , Guastadisegno Chiara , Lanave Gianvito , Camero Michele , Martella Vito , Lo Muzio Lorenzo , Racanelli Vito
Published: October 2021

In order to investigate the possible role of Epstein–Barr virus (EBV) in systemic lupus erythematosus (SLE) and its associated oral lesions, a pilot case–control study was performed. A total of 31 patients (18 females and 13 males) were enrolled in the study and divided into two groups: group A included 16 patients with diagnosis of SLE and group B included 15 healthy individuals. Salivary swab samples were collected and subjected to molecular screening by real-time quantitative PCR (qPCR) for the detection of EBV DNA. EBV DNA was significantly detected in 8/16 (50%) SLE patients and in 5/7 (71.4%) subjects with SLE-associated oral lesions. Since EBV is one of the most common viruses in the human population, it is difficult to understand if it is the causative agent of SLE or, vice versa, if SLE is able to trigger the reactivation of EBV. This study highlights a significant association between the presence of EBV and both SLE and SLE-related oral lesions and provides rationale for further investigation into the role of EBV in SLE pathogenesis.
Long-Term Prognosis of Febrile Individuals with Right Precordial Coved-Type ST-Segment Elevation Brugada Pattern: A 10-Year Prospective Follow-Up Study
Authors: Tsai Chin-Feng , Chuang Yao-Tsung , Huang Jing-Yang , Ueng Kwo-Chang
Published: October 2021

A febrile state may provoke a Brugada electrocardiogram (ECG) pattern and trigger ventricular tachyarrhythmias in susceptible individuals. However, the prognostic value of fever-induced Brugada ECG pattern remains unclear. We analyzed the clinical and extended long-term follow-up data of consecutive febrile patients with a type 1 Brugada ECG presented to the emergency department. A total of 21 individuals (18 males; mean age, 43.7 ± 18.6 years at diagnosis) were divided into symptomatic (resuscitated cardiac arrest in one, syncope in two) and asymptomatic (18, 86%) groups. Sustained polymorphic ventricular tachycardias were inducible in two patients with previous syncope. All 18 asymptomatic patients had no spontaneous type 1 Brugada ECG recorded at second intercostal space and no family history of sudden death. Among asymptomatic individuals, 4 had a total 12 of repeated non-arrhythmogenic febrile episodes all with recurrent type 1 Brugada ECGs, and none had a ventricular arrhythmic event during 116 ± 19 months of follow-up. In the symptomatic group, two had defibrillator shocks for a new arrhythmic event at 31- and 49 months follow-up, respectively, and one without defibrillator therapy died suddenly at 8 months follow-up. A previous history of aborted sudden death or syncope was significantly associated with adverse outcomes in symptomatic compared with asymptomatic individuals (log-rank p < 0.0001). In conclusion, clinical presentation or history of syncope is the most important parameter in the risk stratification of febrile patients with type 1 Brugada ECG. Asymptomatic individuals with a negative family history of sudden death and without spontaneous type 1 Brugada ECG, have an exceptionally low future risk of arrhythmic events. Careful follow-up with timely and aggressive control of fever is an appropriate management option.
Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury
Authors: Kim Sang-Mi , Lee Hyun-Seung , Kim Min-Ji , Park Hyung-Doo , Lee Soo-Youn
Published: October 2021

Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = −0.71; cystatin C, r = −0.70; TNF-R1, r = −0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI.
Path Planning for Underwater Information Gathering Based on Genetic Algorithms and Data Stochastic Models
Authors: Bresciani Matteo , Ruscio Francesco , Tani Simone , Peralta Giovanni , Timperi Andrea , Guerrero-Font Eric , Bonin-Font Francisco , Caiti Andrea , Costanzi Riccardo
Published: October 2021

Recent technological developments have paved the way to the employment of Autonomous Underwater Vehicles (AUVs) for monitoring and exploration activities of marine environments. Traditionally, in information gathering scenarios for monitoring purposes, AUVs follow predefined paths that are not efficient in terms of information content and energy consumption. Informative Path Planning (IPP) represents a valid alternative, defining the path that maximises the gathered information. This work proposes a Genetic Path Planner (GPP), which consists in an IPP strategy based on a Genetic Algorithm, with the aim of generating a path that simultaneously maximises the information gathered and the coverage of the inspected area. The proposed approach has been tested offline for monitoring and inspection applications of Posidonia Oceanica (PO) in three different geographical areas. The a priori knowledge about the presence of PO, in probabilistic terms, has been modelled utilising a Gaussian Process (GP), trained on real marine data. The GP estimate has then been exploited to retrieve an information content of each position in the areas of interest. A comparison with other two IPP approaches has been carried out to assess the performance of the proposed algorithm.
A Model-Derived Empirical Formulation for Wave Run-Up on Naturally Sloping Beaches
Authors: van Ormondt Maarten , Roelvink Dano , van Dongeren Ap
Published: October 2021

A new set of empirical formulations has been derived to predict wave run-up at naturally sloping sandy beaches. They are obtained by fitting the results of hundreds of XBeach-NH+ model simulations. The simulations are carried out over a wide range of offshore wave conditions (wave heights ranging from 1 to 12 m and periods from 6 to 16 s), and surf zone (Dean parameters aD ranging from 0.05 to 0.30) and beach geometries (slopes ranging from 1:100 to 1:5). The empirical formulations provide estimates of wave set-up, incident and infragravity wave run-up, and total run-up R2%. Reduction coefficients are included to account for the effects of incident wave angle and directional spreading. The formulations have been validated against the Stockdon dataset and show better skill at predicting R2% run-up than the widely used Stockdon relationships. Unlike most existing run-up predictors, the relations presented here include the effect of the surf zone slope, which is shown to be an important parameter for predicting wave run-up. Additionally, this study shows a clear relationship between infragravity run-up and beach slope, unlike most existing predictors.
Atmospheric Emissions in Ports Due to Maritime Traffic in Mexico
Authors: Fuentes García Gilberto , Sosa Echeverría Rodolfo , Baldasano Recio José María , W. Kahl Jonathan D. , Granados Hernández Elías , Alarcón Jímenez Ana Luisa , Antonio Durán Rafael Esteban
Published: October 2021

Atmospheric emissions from vessels at 38 Pacific and Gulf-Caribbean Mexican ports were determined for nitrogen oxides, sulfur dioxide, particulates, carbon monoxide, non-methane volatile organic compounds, and carbon dioxide. The emissions have been estimated using a bottom-up methodology in the maneuver and hoteling phases, by vessel type, from 2005 to 2020. Maritime traffic in Mexico’s Pacific zone contributes approximately with 60% of the country’s total ship emissions, with the remaining 40% in Gulf-Caribbean ports. The highest atmospheric emissions were found at the Manzanillo and Lázaro Cárdenas ports on the Pacific coast, as well as the Altamira and Veracruz ports on the Gulf-Caribbean coast. The contribution of the atmospheric emissions by vessel type at Pacific ports was Container 67%, Bulk Carrier 32%, Tanker 0.8%, and RoRo 0.4%. For Gulf-Caribbean ports it was Container 76%, Bulk Carrier 19%, Tanker 3%, and RoRo 2%. This study incorporates the International Maritime Organization implementations on reductions of sulfur content in marine fuel, from 4.5% mass by mass from 2005 to 2011, to 3.5% from 2012 to 2019, to 0.5% beginning in 2020. Overall, sulfur dioxide emissions were reduced by 89%.
Structure, Activity, and Function of PRMT1
Authors: Thiebaut Charlène , Eve Louisane , Poulard Coralie , Le Romancer Muriel
Published: October 2021

PRMT1, the major protein arginine methyltransferase in mammals, catalyzes monomethylation and asymmetric dimethylation of arginine side chains in proteins. Initially described as a regulator of chromatin dynamics through the methylation of histone H4 at arginine 3 (H4R3), numerous non-histone substrates have since been identified. The variety of these substrates underlines the essential role played by PRMT1 in a large number of biological processes such as transcriptional regulation, signal transduction or DNA repair. This review will provide an overview of the structural, biochemical and cellular features of PRMT1. After a description of the genomic organization and protein structure of PRMT1, special consideration was given to the regulation of PRMT1 enzymatic activity. Finally, we discuss the involvement of PRMT1 in embryonic development, DNA damage repair, as well as its participation in the initiation and progression of several types of cancers.
Effects of HPMC on Workability and Mechanical Properties of Concrete Using Iron Tailings as Aggregates
Authors: Gu Xiaowei , Li Xiaohui , Zhang Weifeng , Gao Yuxin , Kong Yaning , Liu Jianping , Zhang Xinlong
Published: October 2021

Iron ore tailings (IOTs) are gradually used as building materials to solve the severe ecological and environmental problems caused by their massive accumulation. However, the bulk density of IOT as aggregate is too large, which seriously affects the concrete properties. Therefore, in this paper, the effect of hydroxypropyl methylcellulose (HPMC) on the workability, mechanical properties, and durability of concrete prepared from IOT recycled aggregate was studied. The action mechanism of HPMC on the workability and the mechanical properties of the IOT concrete was analyzed by mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM). The results show that HPMC can effectively improve the segregation problem caused by the sinking and air entrainment of IOT aggregate and improve the crack resistance of concrete with little effect on its compressive strength and electric flux. These results are due to the air-entraining thickening effect of HPMC, which improves the slurry viscosity, hinders the sinking of aggregate, and improves the workability. At the same time, HPMC film, after concrete hardening, will bridge the slurry and aggregate through physical and chemical effects, hinder the propagation of microcracks, and improve the crack resistance.
Adjustment of Force–Gradient Operator in Symplectic Methods
Authors: Zhang Lina , Wu Xin , Liang Enwei
Published: October 2021

Many force–gradient explicit symplectic integration algorithms have been designed for the Hamiltonian H=T(p)+V(q) with kinetic energy T(p)=p2/2 in the existing references. When a force–gradient operator is appropriately adjusted as a new operator, it is still suitable for a class of Hamiltonian problems H=K(p,q)+V(q) with integrable part K(p,q)=∑i=1n∑j=1naijpipj+∑i=1nbipi, where aij=aij(q) and bi=bi(q) are functions of coordinates q. The newly adjusted operator is not a force–gradient operator but is similar to the momentum-version operator associated to the potential V. The newly extended (or adjusted) algorithms are no longer solvers of the original Hamiltonian, but are solvers of slightly modified Hamiltonians. They are explicit symplectic integrators with symmetry or time reversibility. Numerical tests show that the standard symplectic integrators without the new operator are generally poorer than the corresponding extended methods with the new operator in computational accuracies and efficiencies. The optimized methods have better accuracies than the corresponding non-optimized counterparts. Among the tested symplectic methods, the two extended optimized seven-stage fourth-order methods of Omelyan, Mryglod and Folk exhibit the best numerical performance. As a result, one of the two optimized algorithms is used to study the orbital dynamical features of a modified Hénon–Heiles system and a spring pendulum. These extended integrators allow for integrations in Hamiltonian problems, such as the spiral structure in self-consistent models of rotating galaxies and the spiral arms in galaxies.
Heavy-Traffic Comparison of a Discrete-Time Generalized Processor Sharing Queue and a Pure Randomly Alternating Service Queue
Authors: Devos Arnaud , Walraevens Joris , Fiems Dieter , Bruneel Herwig
Published: October 2021

This paper compares two discrete-time single-server queueing models with two queues. In both models, the server is available to a queue with probability 1/2 at each service opportunity. Since obtaining easy-to-evaluate expressions for the joint moments is not feasible, we rely on a heavy-traffic limit approach. The correlation coefficient of the queue-contents is computed via the solution of a two-dimensional functional equation obtained by reducing it to a boundary value problem on a hyperbola. In most server-sharing models, it is assumed that the system is work-conserving in the sense that if one of the queues is empty, a customer of the other queue is served with probability 1. In our second model, we omit this work-conserving rule such that the server can be idle in case of a non-empty queue. Contrary to what we would expect, the resulting heavy-traffic approximations reveal that both models remain different for critically loaded queues.