bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of Exosomes in Chronic Rhinosinusitis: A Systematic Review
Authors: Dżaman Karolina , Czerwaty Katarzyna
Published: September 2022

The pathophysiology of chronic rhinosinusitis (CRS) is multifactorial and not entirely clear. The objective of the review was to examine the current state of knowledge concerning the role of exosomes in CRS. For this systematic review, we searched PubMed/MEDLINE, Scopus, CENTRAL, and Web of Science databases for studies published until 7 August 2022. Only original research articles describing studies published in English were included. Reviews, book chapters, case studies, conference papers, and opinions were excluded. The quality of the evidence was assessed with the modified Office and Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies. Of 250 records identified, 17 were eligible, all of which had a low to moderate risk of overall bias. Presented findings indicate that exosomal biomarkers, including proteins and microRNA, act as promising biomarkers in the diagnostics and prognosis of CRS patients and, in addition, may contribute to finding novel therapeutic targets. Exosomes reflecting tissue proteomes are excellent, highly available material for studying proteomic alterations noninvasively. The first steps have already been taken, but more advanced research on nasal exosomes is needed, which might open a wider door for individualized medicine in CRS.
Balanced Force Field ff03CMAP Improving the Dynamics Conformation Sampling of Phosphorylation Site
Authors: Zhong Bozitao , Song Ge , Chen Hai-Feng
Published: September 2022

Phosphorylation plays a key role in plant biology, such as the accumulation of plant cells to form the observed proteome. Statistical analysis found that many phosphorylation sites are located in disordered regions. However, current force fields are mainly trained for structural proteins, which might not have the capacity to perfectly capture the dynamic conformation of the phosphorylated proteins. Therefore, we evaluated the performance of ff03CMAP, a balanced force field between structural and disordered proteins, for the sampling of the phosphorylated proteins. The test results of 11 different phosphorylated systems, including dipeptides, disordered proteins, folded proteins, and their complex, indicate that the ff03CMAP force field can better sample the conformations of phosphorylation sites for disordered proteins and disordered regions than ff03. For the solvent model, the results strongly suggest that the ff03CMAP force field with the TIP4PD water model is the best combination for the conformer sampling. Additional tests of CHARMM36m and FB18 force fields on two phosphorylated systems suggest that the overall performance of ff03CMAP is similar to that of FB18 and better than that of CHARMM36m. These results can help other researchers to choose suitable force field and solvent models to investigate the dynamic properties of phosphorylation proteins.
Metal–Organic Frameworks Meet Metallic Oxide on Carbon Fiber: Synergistic Effect for Enhanced Photodegradation of Antibiotic Pollutant
Authors: Zhu Na , Zhou Sijie , Zhang Chunhua , Fu Zhuan , Gong Junyao , Zhou Zhaozixuan , Wang Xiaofeng , Lyu Pei , Li Li , Xia Liangjun
Published: September 2022

Photodegradation shows a potential strategy for alleviating the excessive antibiotics crisis. The synergistic effect of various metal compounds immobilized on conductive substrates has been considered for wastewater treatment. However, developing a facile and universal approach for rational design and enhancing photocatalytic properties has endured extreme challenges. Herein, we develop a strategy to facilitate the photocatalytic reactions by designing a composite architecture of ZIF–8 ligand binding to the in–situ synthesis ZnO seed layer on carbon fiber. In this architecture, the dissolution and release of the seed layer in the excessive 2–Methylimidazole methanol solution were used as the binder to enhance the interplay between organic ligand and substrate. As an evaluated system for antibiotic contaminants, the photodegradation of tetracycline hydrochloride was performed with a removal efficiency of 88.47% (TC = 50 mg/L, pH = 4, 0.08 g of photocatalyst, illumination within 100 min). Moreover, the photocatalyst exhibited a steady photocatalytic activity (75.0%) after five cycles. The present work demonstrated a strategy for enhancing the photocatalytic performances of carbon fiber and accordingly provided useful perception into the design of the synergistic structure.
The Glutathione S-Transferase PtGSTF1 Improves Biomass Production and Salt Tolerance through Regulating Xylem Cell Proliferation, Ion Homeostasis and Reactive Oxygen Species Scavenging in Poplar
Authors: Gao Hongsheng , Yu Chunyan , Liu Ruichao , Li Xiaoyan , Huang Huiqing , Wang Xueting , Zhang Chao , Jiang Ning , Li Xiaofang , Cheng Shuang , Zhang Hongxia , Li Bei
Published: September 2022

Glutathione S-transferases (GSTs) play an essential role in plant cell detoxification and secondary metabolism. However, their accurate functions in the growth and response to abiotic stress in woody plants are still largely unknown. In this work, a Phi class Glutathione S-transferase encoding gene PtGSTF1 was isolated from poplar (P. trichocarpa), and its biological functions in the regulation of biomass production and salt tolerance were investigated in transgenic poplar. PtGSTF1 was ubiquitously expressed in various tissues and organs, with a predominant expression in leaves and inducible expression by salt stress. Transgenic poplar overexpressing PtGSTF1 showed improved shoot growth, wood formation and improved salt tolerance, consistent with the increased xylem cell number and size under normal condition, and the optimized Na+ and K+ homeostasis and strengthened reactive oxygen species scavenging during salt stress. Further transcriptome analyses demonstrated that the expressions of genes related to hydrolase, cell wall modification, ion homeostasis and ROS scavenging were up- or down-regulated in transgenic plants. Our findings imply that PtGSTF1 improves both biomass production and salt tolerance through regulating hydrolase activity, cell wall modification, ion homeostasis and ROS scavenging in transgenic poplar, and that it can be considered as a useful gene candidate for the genetic breeding of new tree varieties with improved growth under salt stress conditions.
Modulation of ATP Production Influences Inorganic Polyphosphate Levels in Non-Athletes’ Platelets at the Resting State
Authors: Ushiki Takashi , Mochizuki Tomoharu , Suzuki Katsuya , Kamimura Masami , Ishiguro Hajime , Suwabe Tatsuya , Kawase Tomoyuki
Published: September 2022

Platelets produce inorganic polyphosphate (polyP) upon activation to stimulate blood coagulation. Some researchers have linked polyP metabolism to ATP production, although the metabolic linkage is yet to be elucidated. We found evidence for this possibility in our previous study on professional athletes (versus non-athletes), and proposed that the regulatory mechanism might be different for these two groups. To explore this aspect further, we investigated the effects of modulated ATP production on polyP levels. Blood samples were obtained from Japanese healthy, non-athletes in the presence of acid-citrate-dextrose. The platelets in the plasma were treated with oligomycin, rotenone, and GlutaMAX to modulate ATP production. PolyP level was quantified fluorometrically and visualized using 4′,6-diamidino-2-phenylindole. Correlations between polyP and ATP or NADH were then calculated. Contrary to the hypothesis, inhibitors of ATP production increased polyP levels, whereas amino acid supplementation produced the opposite effect. In general, however, polyP levels were positively correlated with ATP levels and negatively correlated with NADH levels. Since platelets are metabolically active, they exhibit high levels of ATP turnover rate. Therefore, these findings suggest that ATP may be involved in polyP production in the resting platelets of non-athletes.
Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens
Authors: Timsina Raju , Wellisch Samantha , Haemmerle Dieter , Mainali Laxman
Published: September 2022

Several studies reported that α-crystallin concentrations in the eye lens cytoplasm decrease with a corresponding increase in membrane-bound α-crystallin with age and cataracts. The influence of the lipid and cholesterol composition difference between cortical membrane (CM) and nuclear membrane (NM) on α-crystallin binding to membranes is still unclear. This study uses the electron paramagnetic resonance (EPR) spin-labeling method to investigate the α-crystallin binding to bovine CM and NM derived from the total lipids extracted from a single lens. Compared to CMs, NMs have a higher percentage of membrane surface occupied by α-crystallin and binding affinity, correlating with less mobility and more order below and on the surface of NMs. α-Crystallin binding to CM and NM decreases mobility with no significant change in order and hydrophobicity below and on the surface of membranes. Our results suggest that α-crystallin mainly binds on the surface of bovine CM and NM and such surface binding of α-crystallin to membranes in clear and young lenses may play a beneficial role in membrane stability. However, with decreased cholesterol content within the CM, which mimics the decreased cholesterol content in the cataractous lens membrane, α-crystallin binding increases the hydrophobicity below the membrane surface, indicating that α-crystallin binding forms a hydrophobic barrier for the passage of polar molecules, supporting the barrier hypothesis in developing cataracts.
Structural Insights into the Binding Propensity of Human SHIP2 SH2 to Oncogenic CagA Isoforms from Helicobacter pylori
Authors: Wang Zi , Shan Yubao , Wang Ru , Zhou Heng , Hu Rui , Li Ying , Zhu Jiang , Yang Yunhuang , Liu Maili
Published: September 2022

SHIP2 is a multi-domain inositol 5-phosphatase binding to a variety of phosphotyrosine (pY)-containing proteins through its SH2 domain, so as to regulate various cell signaling pathways by modulating the phosphatidylinositol level in the plasma membrane. Unfavorably, Helicobacter pylori can hijack SHIP2 through the CagA protein to induce gastric cell carcinogenesis. To date, the interaction between SHIP2 and CagA was not analyzed from a structural point of view. Here, the binding of SHIP2-SH2 with Tyr-phosphorylated peptides from four EPIYA motifs (A/B/C/D) in CagA was studied using NMR spectroscopy. The results showed that EPIYA-C and -D bind to a similar interface of SHIP2-SH2, including a pY-binding pocket and a hydrophobic pocket, to achieve high affinity, while EPIYA-A and -B bind to a smaller interface of SHIP2-SH2 with weak affinity. By summarizing the interface and affinity of SHIP2-SH2 for CagA EPIYA-A/B/C/D, c-MET and FcgR2B ITIM, it was proposed that, potentially, SHIP2-SH2 has a selective preference for L > I > V for the aliphatic residues at the pY+3 position in its ligand. This study reveals the rule of the ligand sequence bound by SHIP2-SH2 and the mechanism by which CagA protein hijacks SHIP2, which will help design a peptide inhibitor against SHIP2-SH2.
Development, Evaluation, and Implementation of a House-Made Targeted Next-Generation Sequencing Spoligotyping in a French Laboratory
Authors: Genestet Charlotte , Baffert Yannick , Vallée Maxime , Bernard Albin , Benito Yvonne , Lina Gérard , Hodille Elisabeth , Dumitrescu Oana
Published: September 2022

Epidemiological studies investigating transmission chains of tuberculosis are undertaken worldwide to tackle its spread. CRISPR locus diversity, called spoligotyping, is a widely used genotyping assay for Mycobacterium tuberculosis complex (MTBC) characterization. Herein, we developed a house-made targeted next-generation sequencing (tNGS) spoligotyping, and compared its outputs with those of membrane-based spoligotyping. A total of 144 clinical MTBC strains were retrospectively selected to be representative of the local epidemiology. Data analysis of a training set allowed for the setting of “presence”/“absence” thresholds for each spacer to maximize the sensibility and specificity related to the membrane-based spoligotyping. The thresholds above, in which the spacer was considered present, were 50 read per millions for spacers 10 and 14, 20,000 for spacers 20, 21, and 31, and 1000 for the other spacers. The confirmation of these thresholds was performed using a validation set. The overall agreement on the training and validation sets was 97.5% and 93.8%, respectively. The discrepancies concerned six strains: Two for spacer 14, two for spacer 31, and two for spacer 32. The tNGS spoligotyping, whose thresholds were finely-tuned during a careful bioinformatics pipeline development process, appears be a technique that is reliable, inexpensive, free of handling errors, and automatable through automatic transfer into the laboratory computer system.
Structural Basis for the Binding of Allosteric Activators Leucine and ADP to Mammalian Glutamate Dehydrogenase
Authors: Aleshin Vasily A. , Bunik Victoria I. , Bruch Eduardo M. , Bellinzoni Marco
Published: September 2022

Glutamate dehydrogenase (GDH) plays a key role in the metabolism of glutamate, an important compound at a cross-road of carbon and nitrogen metabolism and a relevant neurotransmitter. Despite being one of the first discovered allosteric enzymes, GDH still poses challenges for structural characterization of its allosteric sites. Only the structures with ADP, and at low (3.5 Å) resolution, are available for mammalian GDH complexes with allosteric activators. Here, we aim at deciphering a structural basis for the GDH allosteric activation using bovine GDH as a model. For the first time, we report a mammalian GDH structure in a ternary complex with the activators leucine and ADP, co-crystallized with potassium ion, resolved to 2.45 Å. An improved 2.4-angstrom resolution of the GDH complex with ADP is also presented. The ternary complex with leucine and ADP differs from the binary complex with ADP by the conformation of GDH C-terminus, involved in the leucine binding and subunit interactions. The potassium site, identified in this work, may mediate interactions between the leucine and ADP binding sites. Our data provide novel insights into the mechanisms of GDH activation by leucine and ADP, linked to the enzyme regulation by (de)acetylation.
Coronavirus Disease 2019-Associated Thrombotic Microangiopathy: Literature Review
Authors: Malgaj Vrečko Marija , Aleš Rigler Andreja , Večerić-Haler Željka
Published: September 2022

Coronavirus disease 2019 (COVID-19) can lead to clinically significant multisystem disorders that also affect the kidney. According to recent data, renal injury in the form of thrombotic microangiopathy (TMA) in native kidneys ranks third in frequency. Our review of global literature revealed 46 cases of TMA in association with COVID-19. Among identified cases, 18 patients presented as thrombotic thrombocytopenic purpura (TTP) and 28 cases presented as atypical hemolytic uremic syndrome (aHUS). Altogether, seven patients with aHUS had previously proven pathogenic or likely pathogenic genetic complement abnormalities. TMA occurred at the time of viremia or even after viral clearance. Infection with COVID-19 resulted in almost no or only mild respiratory symptoms in the majority of patients, while digestive symptoms occurred in almost one-third of patients. Regarding the clinical presentation of COVID-19-associated TMA, the cases showed no major deviations from the known presentation. Patients with TTP were treated with plasma exchange (88.9%) or fresh frozen plasma (11.1%), corticosteroids (88.9%), rituximab (38.9%), and caplacizumab (11.1%). Furthermore, 53.6% of patients with aHUS underwent plasma exchange with or without steroid as initial therapy, and 57.1% of patients received a C5 complement inhibitor. Mortality in the studied cohort was 16.7% for patients with TTP and 10.7% for patients with aHUS. The exact role of COVID-19 in the setting of COVID-19-associated TMA remains unclear. COVID-19 likely represents a second hit of aHUS or TTP that manifests in genetically predisposed individuals. Early identification of the TMA subtype and appropriate prompt and specific treatment could lead to good outcomes comparable to survival and recovery statistics for TMA of all causes.
Protein Acetylation Going Viral: Implications in Antiviral Immunity and Viral Infection
Authors: Xue Minfei , Feng Tingting , Chen Zhiqiang , Yan Yongdong , Chen Zhengrong , Dai Jianfeng
Published: September 2022

During viral infection, both host and viral proteins undergo post-translational modifications (PTMs), including phosphorylation, ubiquitination, methylation, and acetylation, which play critical roles in viral replication, pathogenesis, and host antiviral responses. Protein acetylation is one of the most important PTMs and is catalyzed by a series of acetyltransferases that divert acetyl groups from acetylated molecules to specific amino acid residues of substrates, affecting chromatin structure, transcription, and signal transduction, thereby participating in the cell cycle as well as in metabolic and other cellular processes. Acetylation of host and viral proteins has emerging roles in the processes of virus adsorption, invasion, synthesis, assembly, and release as well as in host antiviral responses. Methods to study protein acetylation have been gradually optimized in recent decades, providing new opportunities to investigate acetylation during viral infection. This review summarizes the classification of protein acetylation and the standard methods used to map this modification, with an emphasis on viral and host protein acetylation during viral infection.
Target of Rapamycin Regulates Photosynthesis and Cell Growth in Auxenochlorella pyrenoidosa
Authors: Zhu Tingting , Li Linxuan , Chang Huimin , Zhan Jiasui , Ren Maozhi
Published: September 2022

Auxenochlorella pyrenoidosa is an efficient photosynthetic microalga with autotrophic growth and reproduction, which has the advantages of rich nutrition and high protein content. Target of rapamycin (TOR) is a conserved protein kinase in eukaryotes both structurally and functionally, but little is known about the TOR signalling in Auxenochlorella pyrenoidosa. Here, we found a conserved ApTOR protein in Auxenochlorella pyrenoidosa, and the key components of TOR complex 1 (TORC1) were present, while the components RICTOR and SIN1 of the TORC2 were absent in Auxenochlorella pyrenoidosa. Drug sensitivity experiments showed that AZD8055 could effectively inhibit the growth of Auxenochlorella pyrenoidosa, whereas rapamycin, Torin1 and KU0063794 had no obvious effect on the growth of Auxenochlorella pyrenoidosaa. Transcriptome data results indicated that Auxenochlorella pyrenoidosa TOR (ApTOR) regulates various intracellular metabolism and signaling pathways in Auxenochlorella pyrenoidosa. Most genes related to chloroplast development and photosynthesis were significantly down-regulated under ApTOR inhibition by AZD8055. In addition, ApTOR was involved in regulating protein synthesis and catabolism by multiple metabolic pathways in Auxenochlorella pyrenoidosa. Importantly, the inhibition of ApTOR by AZD8055 disrupted the normal carbon and nitrogen metabolism, protein and fatty acid metabolism, and TCA cycle of Auxenochlorella pyrenoidosa cells, thus inhibiting the growth of Auxenochlorella pyrenoidosa. These RNA-seq results indicated that ApTOR plays important roles in photosynthesis, intracellular metabolism and cell growth, and provided some insights into the function of ApTOR in Auxenochlorella pyrenoidosa.
Connecting Aortic Stiffness to Vascular Contraction: Does Sex Matter?
Authors: de Oliveira Amanda A. , Priviero Fernanda , Delgado Ana , Dong Pengfei , Mendoza Valentina O. , Gu Linxia , Webb R. Clinton , Nunes Kenia P.
Published: September 2022

This study was designed to connect aortic stiffness to vascular contraction in young male and female Wistar rats. We hypothesized that female animals display reduced intrinsic media-layer stiffness, which associates with improved vascular function. Atomic force microscopy (AFM)-based nanoindentation analysis was used to derive stiffness (Young’s modulus) in biaxially (i.e., longitudinal and circumferential) unloaded aortic rings. Reactivity studies compatible with uniaxial loading (i.e., circumferential) were used to assess vascular responses to a selective α1 adrenergic receptor agonist in the presence or absence of extracellular calcium. Elastin and collagen levels were indirectly evaluated with fluorescence microscopy and a picrosirius red staining kit, respectively. We report that male and female Wistar rats display similar AFM-derived aortic media-layer stiffness, even though female animals withstand higher aortic intima-media thickness-to-diameter ratio than males. Female animals also present reduced phenylephrine-induced aortic force development in concentration-response and time-force curves. Specifically, we observed impaired force displacement in both parts of the contraction curve (Aphasic and Atonic) in experiments conducted with and without extracellular calcium. Additionally, collagen levels were lower in female animals without significant elastin content and fragmentation changes. In summary, sex-related functional differences in isolated aortas appear to be related to dissimilarities in the dynamics of vascular reactivity and extracellular matrix composition rather than a direct response to a shift in intrinsic media-layer stiffness.
Aspirin Resistance in Vascular Disease: A Review Highlighting the Critical Need for Improved Point-of-Care Testing and Personalized Therapy
Authors: Khan Hamzah , Kanny Omar , Syed Muzammil H. , Qadura Mohammad
Published: September 2022

Aspirin resistance describes a phenomenon where patients receiving aspirin therapy do not respond favorably to treatment, and is categorized by continued incidence of adverse cardiovascular events and/or the lack of reduced platelet reactivity. Studies demonstrate that one in four patients with vascular disease are resistant to aspirin therapy, placing them at an almost four-fold increased risk of major adverse limb and adverse cardiovascular events. Despite the increased cardiovascular risk incurred by aspirin resistant patients, strategies to diagnose or overcome this resistance are yet to be clinically validated and integrated. Currently, five unique laboratory assays have shown promise for aspirin resistance testing: Light transmission aggregometry, Platelet Function Analyzer-100, Thromboelastography, Verify Now, and Platelet Works. Newer antiplatelet therapies such as Plavix and Ticagrelor have been tested as an alternative to overcome aspirin resistance (used both in combination with aspirin and alone) but have not proven to be superior to aspirin alone. A recent breakthrough discovery has demonstrated that rivaroxaban, an anticoagulant which functions by inhibiting active Factor X when taken in combination with aspirin, improves outcomes in patients with vascular disease. Current studies are determining how this new regime may benefit those who are considered aspirin resistant.
Genome-Wide Identification and Functional Characterization Reveals the Pivotal Roles of BnaA8.ATG8F in Salt Stress Tolerance and Nitrogen Limitation Adaptation in Allotetraploid Rapeseed
Authors: Zhang Tianyu , Zhou Ting , Zhang Yifan , Chen Junfan , Song Haili , Wu Pengjia , Yue Caipeng , Huang Jinyong , Zhang Zhenhua , Hua Yingpeng
Published: September 2022

Autophagy is a common physiological process in organisms, including higher plants. The ATG8 subfamily, the core member of the autophagy-related gene (ATG) family, plays a key role in plant growth and development and nutrient stress responses. However, the core ATG8 homologs and their roles in stress resistance remain elusive in allotetraploid rapeseed (AACC, Brassica napus L.). In this study, we identified 29 ATG8 subgroup members, consisting of three phylogenetic clades, based on the analysis of genomic annotation and conserved motifs. Differential transcriptional responses of BnaATG8s to salt stress, nitrogen limitation, and other nutrient stresses were investigated, and we identified BnaA8.ATG8F as the core ATG8 member through gene co-expression network analysis. Decreased BnaA8.ATG8F expression repressed the salt tolerance of transgenic rapeseed plants by significantly reducing the root Na+ retention under salt stress. Moreover, downregulation of BnaA8.ATG8F increased nitrogen (N) limitation sensitivity of transgenic rapeseed plants through decreasing N uptake, translocation, and enhancing N remobilization under nitrogen starvation. In summary, we identified the core ATG8 homologs and characterized their physiological and molecular mechanisms underlying salt stress tolerance and nitrogen limitation adaptation. Our results may provide elite genetic resources for the genetic improvement of nutrient stress tolerance in rapeseed.
New Route to Glycosylated Porphyrins via Aromatic Nucleophilic Substitution (SNAr)—Synthesis and Cellular Uptake Studies
Authors: Rosa Mariusz , Jędryka Natalia , Skorupska Sandra , Grabowska-Jadach Ilona , Malinowski Maciej
Published: September 2022

Glycoporphyrins are group of compounds of high value for the purpose of photodynamic therapy and other biomedical applications. Despite great progress in the field, new diversity-oriented syntheses of carbohydrate-porphyrin hybrids are increasingly desired. Herein, we present efficient, mild, and metal-free conditions for synthesis of glycoporphyrins. The versatile nature of the SNAr procedure is presented in 16 examples. Preliminary biological studies have been conducted on the cytotoxicity and cellular uptake of the final molecules.
Enabling Blockchain with IoMT Devices for Healthcare
Authors: Almalki Jameel , Al Shehri Waleed , Mehmood Rashid , Alsaif Khalid , Alshahrani Saeed M. , Jannah Najlaa , Khan Nayyar Ahmed
Published: September 2022

Significant modifications have been seen in healthcare facilities over the past two decades. With the use of IoT-enabled devices, the monitoring and analysis of patient diagnostic parameters is made considerably easy. The new technology shift for medical field is IoMT. However, the problem of privacy for patient data and the security of information still a point to ponder. This research proposed a prototype model to integrate the blockchain and IoMT for providing better analysis of patient health factors. The authors suggested IoMT data to be collected over Edge Computing gateway devices and forward to Cloud Gateway. The three-layered decision making structure ensures the integrity of the data. The further analysis of information collected over sensor-based devices is done in the Cloud IoT Central Hub service. To ensure the secrecy and compliance of the patient data, Smart Contracts are integrated. After the exchange of smart contracts, a block of information is broadcast over the health blockchain. The P2P network makes it viable to retain all health statistics and further processing of information. The paper describes the scenario and experimental setup for a COVID-19 data-set analyzed in the proposed prototype mode. After the collection of information and decision making, the block of data is sent across all peer nodes. Thus, the power of IoMT and blockchain makes it easy for the healthcare worker to diagnose and handle patient data with privacy. The IoMT is integrated with artificial intelligence to enable decision making based on the classification of data. The results are saved as transactions in the blockchain hyperledger. This study demonstrates the prototype model with test data in a testing network with two peer nodes.
Test and Validation of a Multi-Block Solution for Improved Tracking in Outdoor Scenarios: A Case Study in the Pinocchio Park
Authors: Magrini Massimo , Matarese Fabrizio , Moroni Davide
Published: September 2022

Augmented reality techniques have recently found many applications in the field of cultural heritage. When used in outdoor scenarios, however, this technology can face several issues, mainly due to unstable light conditions, jeopardizing the users’ experience. Various solutions to this problem have been proposed in the literature; however, none of them are fully effective. This paper introduces a solution based on a multi-block image target segmentation and a dedicated add-on for the Unity3D game engine. After tests in the lab, the solution was validated in a real scenario at Pinocchio Park (Collodi, Italy), using two different Augmented Reality (AR) libraries and comparing it to a standard methodology. Quantitative results show that the proposed approach provides superior performance and usability. Although the proposed solution is still open to improvement, it combines effectiveness and ease of implementation without any drawbacks.
Relationship between Selected Micronutrient Concentrations, Total Antioxidant Status, Pain Severity, and the Image of 1H MR Spectroscopy in Degenerative Spine Disease: A Case-Control Study
Authors: Jakoniuk Marta , Biegaj Magdalena , Kochanowicz Jan , Łysoń Tomasz , Lankau Agnieszka , Wilkiel Marianna , Socha Katarzyna
Published: September 2022

Osteoarthritis of the spine is a common disease and constitutes a significant problem in highly developed countries. Due to the aging of the population, the number of patients with advanced degenerative changes continues to grow. Trace elements and antioxidant status may play an active role in the pathogenesis of osteoarthritis of the spine. The aim of this study was to assess the relationship between total antioxidant status (TAS), the concentration of selected elements (Zn, Cu, Se, Mn) in the serum, nutritional and environmental factors, the severity of pain, and images of degenerative changes in the spine demonstrated in proton magnetic resonance spectroscopy (1H MRS). The study included 90 patients with degenerative spine disease and 40 healthy people. Serum Zn, Cu, Se, and Mn concentrations were determined by atomic absorption spectrometry. The Cu/Zn molar ratio was calculated. TAS was determined spectrophotometrically using a ready-made Randox kit. The severity of spine pain was assessed using the visual analogue scale VAS. In the 1H MRS study, the fat/water ratio was determined in L1 and L5 vertebral bodies and in the L4/5 intervertebral disc. In patients with osteoarthritis of the spine, there was a reduced concentration of Zn and Cu in the serum (0.77 ± 0.22 mg/L, 1.1 ± 0.35 mg/L) compared to the control group (0.83 ± 0.13 mg/L, 1.25 ± 0.41 mg/L, respectively). In the study group, we also observed a significantly lower Cu concentration in smokers (1.07 ± 0.35 mg/L) compared to non-smokers (1.17 ± 0.34 mg/L). A relationship between the female sex and a decreased concentration of TAS in the serum, both in people with degenerative spine disease and in healthy people, has been demonstrated. In patients with serum TAS levels below the reference values, the fat/water ratio was higher in the L5 spine shaft, while in those with elevated Mn levels, the value was higher in the L4/L5 intervertebral disc, which indicates a greater degree of degeneration in both cases. Patients with normal serum Cu concentration experienced lower pain intensity assessed in the VAS scale. The study showed some abnormalities in serum trace element levels and TAS in patients with osteoarthritis of the spine.
Effects of Intraoperative Opioid Administration on Postoperative Pain and Pain Threshold: A Randomized Controlled Study
Authors: Kawanaka Ryoko , Sakuma Shoko , Kokubun Hiroshi , Tetsu Shuhei , Tagaito Yugo , Igarashi Toshio , Liang Shan-Guang , Aoe Tomohiko
Published: September 2022

Fentanyl and short-acting remifentanil are often used in combination. We evaluated the effect of intraoperative opioid administration on postoperative pain and pain thresholds when the two drugs were used. Patients who underwent gynecological laparoscopic surgery were randomly assigned into two groups (15 patients each) to receive either sufficient (group A) or minimum (group B) fentanyl (maximum estimated effect site concentration: A: 7.86 ng/mL, B: 1.5 ng/mL). The estimated effect site concentration at the end of surgery was adjusted to the same level (1 ng/mL). Patients in both groups also received continuous intravenous remifentanil during surgery. The primary outcome was the pressure pain threshold, as evaluated by a pressure algometer 3 h postoperatively. The pressure pain threshold at 3 h postoperatively was 51.1% (95% CI: [44.4–57.8]) in group A and 56.6% [49.5–63.6] in group B, assuming a preoperative value of 100% (p = 0.298). There were no significant differences in pressure pain threshold and numeric rating scale scores between the groups after surgery. The pain threshold decreased significantly in both groups at 3 h postoperatively compared to preoperative values, and recovered at 24 h. Co-administration of both opioids caused hyperalgesia regardless of fentanyl dose.
Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation
Authors: Puzzolo Maria Cristina , Breccia Massimo , Mariglia Paola , Colafigli Gioia , Pepe Sara , Scalzulli Emilia , Mariggiò Elena , Latagliata Roberto , Guarini Anna , Foà Robin
Published: September 2022

A deep and stable molecular response (DMR) is a prerequisite for a successful treatment-free remission (TFR) in chronic myeloid leukemia (CML). In order to better identify and analyze potential candidates of successful TFR, we examined the phenotypic and functional host immune compartment in DMR patients who had received TKI treatment only (TKI-only) or had been previously treated with interferon-alpha (IFNα + TKI) or had received IFNα treatment only (IFNα-only). The T/NK-cell subset distribution, NK- and T-cell cytokine production, activation and maturation markers were measured in 44 patients in DMR treated with IFNα only (9), with IFNα + TKI (11) and with TKI-only (24). IFNα + TKI and TKI-only groups were eligible to TKI discontinuation according to the NCCN and ESMO guidelines (stable MR4 for more than two years). In IFNα-treated patients, we documented an increased number of lymphocytes capable of producing IFNγ and TNFα compared to the TKI-only group. In INFα + TKI patients, the percentage of NKG2C expression and its mean fluorescence intensity were significantly higher compared to the TKI-only group and to the INFα-only group in the CD56dim/CD16+ NK cell subsets (INFα + TKI vs. TKI-only p = 0.041, p = 0.037; INFα + TKI vs. INFα-only p = 0.03, p = 0.033, respectively). Furthermore, in INFα-only treated patients, we observed an increase of NKp46 MFI in the CD56bright/CD16- NK cell subset that becomes significant compared to the INFα + TKI group (p = 0.008). Our data indicate that a previous exposure to IFNα substantially and persistently modified the immune system of CML patients in memory T lymphocytes, differentiated NKG2C+ “long-lived” NK cells responses, even years after the last IFNα contact.
Descemet Stripping Automated Endothelial Keratoplasty in Thick Corneas
Authors: Li Chendi , Wu Wenyu , Xiao Gege , Jhanji Vishal , Hong Jing , Feng Yun
Published: September 2022

Purpose: To evaluate the outcomes of Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK) in corneas > 820 microns in thickness. Methods: This retrospective study included 30 eyes of 30 patients who underwent DSAEK. Endothelial cell destiny (ECD) and corneal thickness were recorded before surgery and at 1 and 12 months postoperatively. Patients were divided into two groups (≤ 820 microns and > 820 microns) based on median preoperative corneal thickness. Linear regression analyses were used to investigate the correlations between ECD and preoperative corneal thickness. Results: Recipient corneal thickness (RCT) and postoperative central cornea thickness had a statistically significant difference 1 month after surgery (p = 0.03, p = 0.08, respectively). BCVA and ECD did not have a statistical difference in the two groups at 1 month and 12 months after DSAEK. Conclusions: BCVA, ECD and corneal thickness were similar at 12 months after DSAEK in thick corneas. DSAEK is a viable surgical option in thick corneas.
Initial Vestibular Function May Be Associated with Future Postural Instability in Parkinson’s Disease
Authors: Park Jeong Ho , Kim Min Seung , Kang Suk Yun
Published: September 2022

Backgrounds: We aimed to understand the association between initial vestibular function examination and postural instability (PI) development in Parkinson’s disease (PD). Methods: After screening 51 PD patients, we divided 31 patients into 2 groups based on the presence of PI at the follow-up visit and compared the clinical features and vestibular-evoked myogenic potential (VEMP) variables. Results: The mean values of Hoehn and Yahr stage, Unified Parkinson’s Disease Rating Scale (UPDRS) part III, and item 30 (postural stability) of UPDRS were larger in patients with PI at a follow-up visit (p = 0.000, 0.006, 0.048, respectively). In VEMP analyses, the onset latencies of left and right cervical VEMPs were significantly reduced in patients with PI (p = 0.013, 0.040, respectively). Conclusion: We found that the initial VEMP test may be associated with later postural imbalance in PD, suggesting the baseline evaluation may help predict future PI occurrence. A more significant number of patients and more long-term follow-ups are likely to be required for confirmation.
External Validation of Mortality Scores among High-Risk COVID-19 Patients: A Romanian Retrospective Study in the First Pandemic Year
Authors: Rădulescu Amanda , Lupse Mihaela , Istrate Alexandru , Calin Mihai , Topan Adriana , Kormos Nicholas Florin , Macicasan Raul Vlad , Briciu Violeta
Published: September 2022

Background: We aimed to externally validate three prognostic scores for COVID-19: the 4C Mortality Score (4CM Score), the COVID-GRAM Critical Illness Risk Score (COVID-GRAM), and COVIDAnalytics. Methods: We evaluated the scores in a retrospective study on adult patients hospitalized with severe/critical COVID-19 (1 March 2020–1 March 2021), in the Teaching Hospital of Infectious Diseases, Cluj-Napoca, Romania. We assessed all the deceased patients matched with two survivors by age, gender, and at least two comorbidities. The areas under the receiver-operating characteristic curves (AUROCs) were computed for in-hospital mortality. Results: Among 780 severe/critical COVID-19 patients, 178 (22.8%) died. We included 474 patients according to the case definition (158 deceased/316 survivors). The median age was 75 years; diabetes mellitus, malignancies, chronic pulmonary diseases, and chronic kidney and moderate/severe liver diseases were associated with higher risks of death. According to the predefined 4CM Score, the mortality rates were 0% (low), 13% (intermediate), 27% (high), and 61% (very high). The AUROC for the 4CM Score was 0.72 (95% CI: 0.67–0.77) for in-hospital mortality, close to COVID-GRAM, with slightly greater discriminatory ability for COVIDAnalytics: 0.76 (95% CI: 0.71–0.80). Conclusion: All the prognostic scores showed close values compared to their validation cohorts, were fairly accurate in predicting mortality, and can be used to prioritize care and resources.
The IL-4/-13 Axis and Its Blocking in the Treatment of Atopic Dermatitis
Authors: Pappa Georgia , Sgouros Dimitrios , Theodoropoulos Konstantinos , Kanelleas Antonios , Bozi Evangelia , Gregoriou Stamatios , Krasagakis Konstantinos , Katoulis Alexander
Published: September 2022

Atopic dermatitis (AD) is a common inflammatory skin disease with a complex pathophysiology, intertwining immune dysregulation, epidermal barrier dysfunction, IgE sensitization, environmental factors and genetic predisposition. It has been recently identified that interleukins -4 and -13 play crucial roles in the type-2-driven inflammation that characterizes AD, contributing to its symptomatology. Novel therapeutic approaches that target Th2 cytokines and their respective pathways have been developed, aiming to optimize the treatment of AD.
Effect of Statins on All-Cause Mortality in Adults: A Systematic Review and Meta-Analysis of Propensity Score-Matched Studies
Authors: Nowak Marcin M. , Niemczyk Mariusz , Florczyk Michał , Kurzyna Marcin , Pączek Leszek
Published: September 2022

Statins are lipid-lowering medications used for the prevention of cardiovascular disease (CVD), but the pleiotropic effects of statins might be beneficial in other chronic diseases. This meta-analysis investigated the association between statin use and mortality in different chronic conditions. Eligible studies were real-world studies that compared all-cause mortality over at least 12 months between propensity score-matched statin users and non-users. Overall, 54 studies were included: 21 in CVD, 6 in chronic kidney disease, 6 in chronic inflammatory diseases, 3 in cancer, and 18 in other diseases. The risk of all-cause mortality was significantly reduced in statin users (hazard ratio: 0.72, 95% confidence interval: 0.66–0.76). The reduction in mortality risk was similar in CVD studies (0.73, 0.66–0.76) and non-CVD studies (0.70, 0.67–0.79). There were no significant differences in the risk reduction between cohorts with different diseases (p = 0.179). The greatest mortality reduction was seen in studies from Asia (0.61, 0.61–0.73) and the lowest in studies from North America (0.78, 0.73–0.83) and Australia (0.78, 0.62–0.97). There was a significant heterogeneity (I2 = 95%, tau2 = 0.029, p < 0.01). In conclusion, statin use was associated with a significantly reduced risk of all-cause mortality in real-world cohorts with CVD and non-CVD.
Post-COVID Pain Is Not Associated with Inflammatory Polymorphisms in People Who Had Been Hospitalized by COVID-19
Authors: Fernández-de-las-Peñas César , Giordano Rocco , Díaz-Gil Gema , Gómez-Esquer Francisco , Ambite-Quesada Silvia , Palomar-Gallego Maria , Arendt-Nielsen Lars
Published: September 2022

Our aim was to assess the association between four inflammatory polymorphisms with the development of post-COVID pain and to associate these polymorphisms with the clinical pain phenotype in individuals who had been hospitalized by COVID-19. Three potential genotypes of IL-6 (rs1800796), IL-10 (rs1800896), TNF-α (rs1800629), and IFITM3 (rs12252) single nucleotide polymorphisms (SNPs) were obtained from no-stimulated saliva samples from 293 (49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors by polymerase chain reactions. Pain phenotyping consisted of the evaluation of pain features, sensitization-associated symptoms, anxiety levels, depressive levels, sleep quality, catastrophizing, and kinesiophobia levels in patients with post-COVID pain. Analyses were conducted to associate clinical features with genotypes. One hundred and seventeen (39.9%) patients experienced post-COVID pain 17.8 ± 5.2 months after hospital discharge. No significant differences in the distribution of the genotype variants of any SNPs were identified between COVID-19 survivors with and without post-COVID pain (all, p > 0.47). Similarly, the clinical pain phenotype was not significantly different between patients with and without post-COVID pain since no differences in any variable were observed for any SNPs. In conclusion, four SNPs associated with inflammatory and immune responses did not appear to be associated with post-COVID pain in previously hospitalized COVID-19 survivors. Further, neither of the SNPs were involved in the phenotyping features of post-COVID pain.
The Atypical Manifestation of Pulmonary Tuberculosis in Patients with Bronchial Anthracofibrosis
Authors: Jung Min Kyung , Lee Sang Young , Ko Jeong Min
Published: September 2022

It has been stated that bronchial anthracofibrosis (BAF) has an important relationship with pulmonary tuberculosis (TB), and the coexistence of TB and BAF is high. The purpose of this study was to compare the differences in computed tomography (CT) characteristics of pulmonary TB according to the presence of underlying BAF. Total of 202 consecutive patients who were diagnosed with pulmonary TB and underwent bronchoscopy and CT in our institution were retrospectively reviewed. We classified the patients into two groups according to the presence of BAF and compared the clinicoradiological findings between the two groups (anthracofibrosis group vs. nonanthracofibrosis group). Elderly and female patients were significantly higher in anthracofibrosis group (mean age 79 ± 7 (64–94) vs. 56 ± 17 (16–95), p < 0.001; female 89% vs. 29%, p < 0.001). The frequency of internal low-density area or focal contour bulge within atelectasis (64% vs. 1%, p < 0.001), lower lobe predominance (43% vs. 9%, p < 0.001), endobronchial involvement (46% vs. 15%, p < 0.001), and lymphadenopathy (57% vs. 28%, p = 0.002) were significantly higher in anthracofibrosis group. In contrast, the anthracofibrosis group showed lower frequency of upper lobe predominance (32% vs. 81%, p < 0.001) and cavitation (14% vs. 51%, p = 0.001). In conclusion, being aware of these atypical manifestations of pulmonary TB in the presence of BAF will be of great help in early detection of TB.
Contribution of Different Impairments to Restricted Knee Flexion during Gait in Individuals with Cerebral Palsy
Authors: Manikowska Faustyna , Brazevič Sabina , Jóźwiak Marek , Lebiedowska Maria K.
Published: September 2022

The coexistence of overlapping impairments modulates the knee pattern in the swing phase of walking in children with cerebral palsy (CP). The impact and contribution of each impairment to the reduction of knee range-of-motion is unknown. The aim of the study was to establish the gradation of the impact of individual coexisting impairments on the knee flexion range-of-motion. Passive range-of-motion, selective motor control, strength, and spasticity from 132 patients (Male = 76, Female = 56, age:11 ± 4 years) with spastic CP were tested with clinical tools. Knee flexion range-of-motion at terminal stance, pre-swing, and initial swing phases were assessed by gait analysis. Hypertonia (β = −5.75) and weakness (β = 2.76) of knee extensors were associated with lower range of knee flexion (R2 = 0.0801, F = 11.0963, p < 0.0001). The predictive factors (R2 = 0.0744, F = 7.2135, p < 0.0001) were strength (β = 4.04) and spasticity (β = −2.74) of knee extensors and strength of hip flexors (β = −2.01); in swing those were knee extensors hypertonia (β = −2.55) and passive range of flexion (β = 0.16) (R2 = 0.0398, F = 3.4010, p = 0.01). Hypertonia of knee extensors has the strongest impact on knee flexion range-of-motion; secondary is the strength of knee extensors. The knee extensors strength with knee extensors hypertonia and strength of hip flexors contributes in stance. Knee extensors hypertonia with passive knee flexion range-of-motion contributes in swing.