bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioids and Sepsis: Elucidating the Role of the Microbiome and microRNA-146
Authors: Abu Yaa , Vitari Nicolas , Yan Yan , Roy Sabita
Published: January 2022

Sepsis has recently been defined as life-threatening organ dysfunction caused by the dysregulated host response to an ongoing or suspected infection. To date, sepsis continues to be a leading cause of morbidity and mortality amongst hospitalized patients. Many risk factors contribute to development of sepsis, including pain-relieving drugs like opioids, which are frequently prescribed post-operatively. In light of the opioid crisis, understanding the interactions between opioid use and the development of sepsis has become extremely relevant, as opioid use is associated with increased risk of infection. Given that the intestinal tract is a major site of origin of sepsis-causing microbes, there has been an increasing focus on how alterations in the gut microbiome may predispose towards sepsis and mediate immune dysregulation. MicroRNAs, in particular, have emerged as key modulators of the inflammatory response during sepsis by tempering the immune response, thereby mediating the interaction between host and microbiome. In this review, we elucidate contributing roles of microRNA 146 in modulating sepsis pathogenesis and end with a discussion of therapeutic targeting of the gut microbiome in controlling immune dysregulation in sepsis.
The Ketogenic Diet Improves Gut–Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems
Authors: Orlando Antonella , Chimienti Guglielmina , Notarnicola Maria , Russo Francesco
Published: January 2022

Altered gut–brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.
Cryo-Treatment Enhances the Embryogenicity of Mature Somatic Embryos via the lncRNA–miRNA–mRNA Network in White Spruce
Authors: Gao Ying , Cui Ying , Zhao Ruirui , Chen Xiaoyi , Zhang Jinfeng , Zhao Jian , Kong Lisheng
Published: January 2022

In conifers, somatic embryogenesis is uniquely initiated from immature embryos in a narrow time window, which is considerably hindered by the difficulty to induce embryogenic tissue (ET) from other tissues, including mature somatic embryos. In this study, the embryogenic ability of newly induced ET and DNA methylation levels was detected, and whole-transcriptome sequencing analyses were carried out. The results showed that ultra-low temperature treatment significantly enhanced ET induction from mature somatic embryos, with the induction rate from 0.4% to 15.5%, but the underlying mechanisms remain unclear. The newly induced ET showed higher capability in generating mature embryos than the original ET. DNA methylation levels fluctuated during the ET induction process. Here, WGCNA analysis revealed that OPT4, TIP1-1, Chi I, GASA5, GST, LAX3, WRKY7, MYBS3, LRR-RLK, PBL7, and WIN1 genes are involved in stress response and auxin signal transduction. Through co-expression analysis, lncRNAs MSTRG.505746.1, MSTRG.1070680.1, and MSTRG.33602.1 might bind to pre-novel_miR_339 to promote the expression of WRKY7 genes for stress response; LAX3 could be protected by lncRNAs MSTRG.1070680.1 and MSTRG.33602.1 via serving as sponges for novel_miR_495 to initiate auxin signal transduction; lncRNAs MSTRG.505746.1, MSTRG.1070680.1, and MSTRG.33602.1 might serve as sponges for novel_miR_527 to enhance the expression of Chi I for early somatic embryo development. This study provides new insight into the area of stress-enhanced early somatic embryogenesis in conifers, which is also attributable to practical applications.
Salviolone from Salvia miltiorrhiza Roots Impairs Cell Cycle Progression, Colony Formation, and Metalloproteinase-2 Activity in A375 Melanoma Cells: Involvement of P21(Cip1/Waf1) Expression and STAT3 Phosphorylation
Authors: Zanrè Valentina , Campagnari Rachele , Cerulli Antonietta , Masullo Milena , Cardile Alessia , Piacente Sonia , Menegazzi Marta
Published: January 2022

Melanoma is a highly malignant solid tumor characterized by an elevated growth and propagation rate. Since, often, melanoma treatment cannot prevent recurrences and the appearance of metastasis, new anti-melanoma agents need to be discovered. Salvia miltiorrhiza roots are a source of diterpenoid derivatives, natural compounds with several biological activities, including antiproliferative and anticancer effects. Seven diterpenoid derivatives were purified from S. miltiorrhiza roots and identified by NMR and MS analysis. Tanshinone IIA and cryptotanshinone were detected as the main components of S. miltiorrhiza root ethanol extract. Although their antitumor activity is already known, they have been confirmed to induce a reduction in A375 and MeWo melanoma cell growth. Likewise, salviolone has been shown to impair the viability of melanoma cells without affecting the growth of normal melanocytes. The underlying anticancer activity of salviolone has been investigated and compared to that of cryptotanshinone in A375 cells, showing an increased P21 protein expression in a P53-dependent manner. In that way, salviolone, even more than cryptotanshinone, displays a multitarget effect on cell-cycle-related proteins. Besides, it modulates the phosphorylation level of the signal transducer and activator of transcription (STAT)3. Unexpectedly, salviolone and cryptotanshinone induce sustained activation of the extracellular signal-regulated kinases (ERK)1/2 and the protein kinase B (Akt). However, the blockage of ERK1/2 or Akt activities suggests that kinase activation does not hinder their ability to inhibit A375 cell growth. Finally, salviolone and cryptotanshinone inhibit to a comparable extent some crucial malignancy features of A375 melanoma cells, such as colony formation in soft agar and metalloproteinase-2 activity. In conclusion, it has been shown for the first time that salviolone, harboring a different molecular structure than tanshinone IIA and cryptotanshinone, exhibits a pleiotropic effect against melanoma by hampering cell cycle progression, STAT3 signaling, and malignant phenotype of A375 melanoma cells.
Inflammation Regulates Haematopoietic Stem Cells and Their Niche
Authors: Ho Nicole Pui-Yu , Takizawa Hitoshi
Published: January 2022

Haematopoietic stem cells (HSCs) reside in the bone marrow and are supported by the specialised microenvironment, a niche to maintain HSC quiescence. To deal with haematopoietic equilibrium disrupted during inflammation, HSCs are activated from quiescence directly and indirectly to generate more mature immune cells, especially the myeloid lineage cells. In the process of proliferation and differentiation, HSCs gradually lose their self-renewal potential. The extensive inflammation might cause HSC exhaustion/senescence and malignant transformation. Here, we summarise the current understanding of how HSC functions are maintained, damaged, or exhausted during acute, prolonged, and pathological inflammatory conditions. We also highlight the inflammation-altered HSC niche and its impact on escalating the insults on HSCs.
Cysteine 467 of the ASCT2 Amino Acid Transporter Is a Molecular Determinant of the Antiport Mechanism
Authors: Scalise Mariafrancesca , Pappacoda Gilda , Mazza Tiziano , Console Lara , Pochini Lorena , Indiveri Cesare
Published: January 2022

The plasma membrane transporter ASCT2 is a well-known Na+-dependent obligatory antiporter of neutral amino acids. The crucial role of the residue C467 in the recognition and binding of the ASCT2 substrate glutamine, has been highlighted by structure/function relationship studies. The reconstitution in proteoliposomes of the human ASCT2 produced in P. pastoris is here employed to unveil another role of the C467 residue in the transport reaction. Indeed, the site-directed mutant C467A displayed a novel property of the transporter, i.e., the ability of mediating a low but measurable unidirectional transport of [3H]-glutamine. This reaction conforms to the main features of the ASCT2-mediated transport, namely the Na+-dependence, the pH dependence, the stimulation by cholesterol included in the proteoliposome membrane, and the specific inhibition by other common substrates of the reconstituted human ASCT2. Interestingly, the WT protein cannot catalyze the unidirectional transport of [3H]-glutamine, demonstrating an unspecific phenomenon. This difference is in favor of a structural conformational change between a WT and C467A mutant that triggers the appearance of the unidirectional flux; this feature has been investigated by comparing the available 3D structures in two different conformations, and two homology models built on the basis of hEAAT1 and GLTPh.
Probing the Dynamics of Streptococcus pyogenes Cas9 Endonuclease Bound to the sgRNA Complex Using Hydrogen-Deuterium Exchange Mass Spectrometry
Authors: Zhdanova Polina V. , Chernonosov Alexander A. , Prokhorova Daria V. , Stepanov Grigory A. , Kanazhevskaya Lyubov Yu. , Koval Vladimir V.
Published: January 2022

The Cas9 endonuclease is an essential component of the CRISPR–Cas-based genome editing tools. The attainment of high specificity and efficiency of Cas9 during targetted DNA cleavage is the main problem that limits the clinical application of the CRISPR–Cas9 system. A deep understanding of the Cas9 mechanism and its structural-functional relationships is required to develop strategies for precise gene editing. Here, we present the first attempt to describe the solution structure of Cas9 from S. pyogenes using hydrogen-deuterium exchange mass spectrometry (HDX-MS) coupled to molecular dynamics simulations. HDX data revealed multiple protein regions with deuterium uptake levels varying from low to high. By analysing the difference in relative deuterium uptake by apoCas9 and its complex with sgRNA, we identified peptides involved in the complex formation and possible changes in the protein conformation. The REC3 domain was shown to undergo the most prominent conformational change upon enzyme-RNA interactions. Detection of the HDX in two forms of the enzyme provided detailed information about changes in the Cas9 structure induced by sgRNA binding and quantified the extent of the changes. The study demonstrates the practical utility of HDX-MS for the elucidation of mechanistic aspects of Cas9 functioning.
The Mulberry SPL Gene Family and the Response of MnSPL7 to Silkworm Herbivory through Activating the Transcription of MnTT2L2 in the Catechin Biosynthesis Pathway
Authors: Li Hongshun , Ma Bi , Luo Yiwei , Wei Wuqi , Yuan Jianglian , Zhai Changxin , He Ningjia
Published: January 2022

SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes, as unique plant transcription factors, play important roles in plant developmental regulation and stress response adaptation. Although mulberry is a commercially valuable tree species, there have been few systematic studies on SPL genes. In this work, we identified 15 full-length SPL genes in the mulberry genome, which were distributed on 4 Morus notabilis chromosomes. Phylogenetic analysis clustered the SPL genes from five plants (Malus × domestica Borkh, Populus trichocarpa, M. notabilis, Arabidopsis thaliana, and Oryza sativa) into five groups. Two zinc fingers (Zn1 and Zn2) were found in the conserved SBP domain in all of the MnSPLs. Comparative analyses of gene structures and conserved motifs revealed the conservation of MnSPLs within a group, whereas there were significant structure differences among groups. Gene quantitative analysis showed that the expression of MnSPLs had tissue specificity, and MnSPLs had much higher expression levels in older mulberry leaves. Furthermore, transcriptome data showed that the expression levels of MnSPL7 and MnSPL14 were significantly increased under silkworm herbivory. Molecular experiments revealed that MnSPL7 responded to herbivory treatment through promoting the transcription of MnTT2L2 and further upregulating the expression levels of catechin synthesis genes (F3′H, DFR, and LAR).
Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
Authors: Montero Paula , Milara Javier , Pérez-Leal Martín , Estornut Cristina , Roger Inés , Pérez-Fidalgo Alejandro , Sanz Celia , Cortijo Julio
Published: January 2022

Paclitaxel is a microtubule-stabilizing chemotherapeutic agent approved for the treatment of ovarian, non-small cell lung, head, neck, and breast cancers. Despite its beneficial effects on cancer and widespread use, paclitaxel also damages healthy tissues, including the skin. However, the mechanisms that drive these skin adverse events are not clearly understood. In the present study, we demonstrated, by using both primary epidermal keratinocytes (NHEK) and a 3D epidermis model, that paclitaxel impairs different cellular processes: paclitaxel increased the release of IL-1α, IL-6, and IL-8 inflammatory cytokines, produced reactive oxygen species (ROS) release and apoptosis, and reduced the endothelial tube formation in the dermal microvascular endothelial cells (HDMEC). Some of the mechanisms driving these adverse skin events in vitro are mediated by the activation of toll-like receptor 4 (TLR-4), which phosphorylate transcription of nuclear factor kappa B (NF-κb). This is the first study analyzing paclitaxel effects on healthy human epidermal cells with an epidermis 3D model, and will help in understanding paclitaxel’s effects on the skin.
High-Performance Thin-Layer Chromatography-Densitometry-Tandem ESI-MS to Evaluate Phospholipid Content in Exosomes of Cancer Cells
Authors: Sancho-Albero María , Jarne Carmen , Savirón María , Martín-Duque Pilar , Membrado Luis , Cebolla Vicente L. , Santamaría Jesús
Published: January 2022

The question of whether exosome lipids can be considered as potential cancer biomarkers faces our current limited knowledge of their composition. This is due to the difficulty in isolating pure exosomes, the variability of the biological sources from which they are extracted, and the uncertainty of the methods for lipid characterization. Here, we present a procedure to isolate exosomes and obtain a deep, repeatable, and rapid phospholipid (PL) composition of their lipid extracts, from embryonic murine fibroblasts (NIH-3T3 cell line) and none (B16-F1) and high (B16-F10) metastatic murine skin melanoma cells. The analytical method is based on High Performance Thin-Layer Chromatography with Ultraviolet and fluorescence densitometry and coupled to Electrospray (ESI)-tandem Mass Spectrometry (MS). Under the conditions described in this work, separation and determination of PL classes, (sphingomyelins, SM; phosphatidylcholines, PC; phosphatidylserines, PS; and phosphatidylethanolamines, PE) were achieved, expressed as µg PL/100 µg exosome protein, obtained by bicinchoninic acid assay (BCA). A detailed structural characterization of molecular species of each PL class was performed by simultaneous positive and negative ESI-MS and MS/MS directly from the chromatographic plate, thanks to an elution-based interface.
Bioadhesion on Textured Interfaces in the Human Oral Cavity—An In Situ Study
Authors: Helbig Ralf , Hannig Matthias , Basche Sabine , Ortgies Janis , Killge Sebastian , Hannig Christian , Sterzenbach Torsten
Published: January 2022

Extensive biofilm formation on materials used in restorative dentistry is a common reason for their failure and the development of oral diseases like peri-implantitis or secondary caries. Therefore, novel materials and strategies that result in reduced biofouling capacities are urgently sought. Previous research suggests that surface structures in the range of bacterial cell sizes seem to be a promising approach to modulate bacterial adhesion and biofilm formation. Here we investigated bioadhesion within the oral cavity on a low surface energy material (perfluorpolyether) with different texture types (line-, hole-, pillar-like), feature sizes in a range from 0.7–4.5 µm and graded distances (0.7–130.5 µm). As a model system, the materials were fixed on splints and exposed to the oral cavity. We analyzed the enzymatic activity of amylase and lysozyme, pellicle formation, and bacterial colonization after 8 h intraoral exposure. In opposite to in vitro experiments, these in situ experiments revealed no clear signs of altered bacterial surface colonization regarding structure dimensions and texture types compared to unstructured substrates or natural enamel. In part, there seemed to be a decreasing trend of adherent cells with increasing periodicities and structure sizes, but this pattern was weak and irregular. Pellicle formation took place on all substrates in an unaltered manner. However, pellicle formation was most pronounced within recessed areas thereby partially masking the three-dimensional character of the surfaces. As the natural pellicle layer is obviously the most dominant prerequisite for bacterial adhesion, colonization in the oral environment cannot be easily controlled by structural means.
Variations in the Human Serum Albumin Gene: Molecular and Functional Aspects
Authors: Caridi Gianluca , Lugani Francesca , Angeletti Andrea , Campagnoli Monica , Galliano Monica , Minchiotti Lorenzo
Published: January 2022

The human albumin gene, the most abundant serum protein, is located in the long arm of chromosome 4, near the centromere, position 4q11–3. It is divided by 14 intervening introns into 15 exons, the last of which is untranslated. To date, 74 nucleotide substitutions (mainly missense) have been reported, determining the circulating variants of albumin or pre-albumin. In a heterozygous state, this condition is known as alloalbuminaemia or bisalbuminaemia (OMIM # 103600). The genetic variants are not associated with disease, neither in the heterozygous nor in the homozygous form. Only the variants resulting in familial dysalbuminaemic hyperthyroxinaemia and hypertriiodothyroninaemia are of clinical relevance because affected individuals are at risk of inappropriate treatment or may have adverse drug effects. In 28 other cases, the pathogenic variants (mainly affecting splicing, nonsense, and deletions), mostly in the homozygous form, cause a premature stop in the synthesis of the protein and lead to the condition known as congenital analbuminaemia. In this review, we will summarize the current knowledge of genetic and molecular aspects, functional consequences and potential therapeutic uses of the variants. We will also discuss the molecular defects resulting in congenital analbuminaemia, as well as the biochemical and clinical features of this rare condition
Metabolome and Transcriptome Analyses Unravel the Molecular Regulatory Mechanisms Involved in Photosynthesis of Cyclocarya paliurus under Salt Stress
Authors: Zhang Lei , Zhang Zijie , Fang Shengzuo , Liu Yang , Shang Xulan
Published: January 2022

Photosynthesis is the primary life process in nature, and how to improve photosynthetic capacity under abiotic stresses is crucial to carbon fixation and plant productivity. As a multi-functional tree species, the leaves of Cyclocarya paliurus possess antihypertensive and hypoglycemic activities. However, the regulatory mechanism involved in the photosynthetic process of C. paliurus exposed to salinity has not yet been elucidated. In this study, the photosynthetic characteristics of C. paliurus seedlings, such as photosynthetic rate (Pn), stomatal conductance (Gs), and electron transfer rate (ETR), were investigated under different salt concentrations, while the metabolome and transcriptome analyses were conducted to unravel its molecular regulatory mechanisms. Salt stress not only significantly affected photosynthetic characteristics of C. paliurus seedlings, but also severely modified the abundance of metabolites (such as fumaric acid, sedoheptulose-7-phosphate, d-fructose-1,6-bisphosphate, and 3-phospho-d-glyceroyl phosphate) involved in central carbon metabolism, and the expression of photosynthetic genes. Through the co-expression network analysis, a total of 27 transcription factors (including ERFs, IDD, DOF, MYB, RAP) were identified to regulate photosynthetic genes under salt stress. Our findings preliminarily clarify the molecular regulatory network involved in the photosynthetic process of C. paliurus under salt stress and would drive progress in improving the photosynthetic capacity and productivity of C. paliurus by molecular technology.
Recent Advances in Metal-Based Antimicrobial Coatings for High-Touch Surfaces
Authors: Birkett Martin , Dover Lynn , Cherian Lukose Cecil , Wasy Zia Abdul , Tambuwala Murtaza M. , Serrano-Aroca Ángel
Published: January 2022

International interest in metal-based antimicrobial coatings to control the spread of bacteria, fungi, and viruses via high contact human touch surfaces are growing at an exponential rate. This interest recently reached an all-time high with the outbreak of the deadly COVID-19 disease, which has already claimed the lives of more than 5 million people worldwide. This global pandemic has highlighted the major role that antimicrobial coatings can play in controlling the spread of deadly viruses such as SARS-CoV-2 and scientists and engineers are now working harder than ever to develop the next generation of antimicrobial materials. This article begins with a review of three discrete microorganism-killing phenomena of contact-killing surfaces, nanoprotrusions, and superhydrophobic surfaces. The antimicrobial properties of metals such as copper (Cu), silver (Ag), and zinc (Zn) are reviewed along with the effects of combining them with titanium dioxide (TiO2) to create a binary or ternary contact-killing surface coatings. The self-cleaning and bacterial resistance of purely structural superhydrophobic surfaces and the potential of physical surface nanoprotrusions to damage microbial cells are then considered. The article then gives a detailed discussion on recent advances in attempting to combine these individual phenomena to create super-antimicrobial metal-based coatings with binary or ternary killing potential against a broad range of microorganisms, including SARS-CoV-2, for high-touch surface applications such as hand rails, door plates, and water fittings on public transport and in healthcare, care home and leisure settings as well as personal protective equipment commonly used in hospitals and in the current COVID-19 pandemic.
Gal3 Plays a Deleterious Role in a Mouse Model of Endotoxemia
Authors: Fernández-Martín Juan Carlos , Espinosa-Oliva Ana María , García-Domínguez Irene , Rosado-Sánchez Isaac , Pacheco Yolanda M. , Moyano Rosario , Monterde José G. , Venero José Luis , de Pablos Rocío M.
Published: January 2022

Lipopolysaccharide (LPS)-induced endotoxemia induces an acute systemic inflammatory response that mimics some important features of sepsis, the disease with the highest mortality rate worldwide. In this work, we have analyzed a murine model of endotoxemia based on a single intraperitoneal injection of 5 mg/kg of LPS. We took advantage of galectin-3 (Gal3) knockout mice and found that the absence of Gal3 decreased the mortality rate oflethal endotoxemia in the first 80 h after the administration of LPS, along with a reduction in the tissular damage in several organs measured by electron microscopy. Using flow cytometry, we demonstrated that, in control conditions, peripheral immune cells, especially monocytes, exhibited high levels of Gal3, which were early depleted in response to LPS injection, thus suggesting Gal3 release under endotoxemia conditions. However, serum levels of Gal3 early decreased in response to LPS challenge (1 h), an indication that Gal3 may be extravasated to peripheral organs. Indeed, analysis of Gal3 in peripheral organs revealed a robust up-regulation of Gal3 36 h after LPS injection. Taken together, these results demonstrate the important role that Gal3 could play in the development of systemic inflammation, a well-established feature of sepsis, thus opening new and promising therapeutic options for these harmful conditions.
ROSSIO Infrastructure: A Digital Humanities Platform to Explore the Portuguese Cultural Heritage
Authors: Silva Gonçalo Melo da , Glória Ana Celeste , Salgueiro Ângela Sofia , Almeida Bruno , Monteiro Daniel , Freitas Marco Roque de , Freire Nuno
Published: January 2022

The ROSSIO Infrastructure is developing a free and open-access platform for aggregating, organising, and connecting the digital resources in the Social Sciences, Arts and Humanities provided by Portuguese higher education and cultural institutions. This paper presents an overview of the ROSSIO Infrastructure, its main objectives, the institutions involved, and the services offered by the infrastructure’s aims through its platform—namely, a discovery portal, digital exhibitions, collections, and a virtual research environment. These services rely on a metadata-aggregation solution for bringing the digital objects’ metadata from the providing institutions into ROSSIO. The aggregated datasets are converted into linked data and undergo an enrichment process based on controlled vocabularies, which are developed and published by ROSSIO. The paper will describe this process, the applications involved, and how they interoperate. We will further reflect on how these services may enhance the dissemination of science, considering the FAIR principles.
Significance of Vascular Cell Adhesion Molecule-1 and Tumor Necrosis Factor-Alpha in HIV-Infected Patients
Authors: Mikuła Tomasz , Suchacz Magdalena , Sapuła Mariusz , Wiercińska-Drapało Alicja
Published: January 2022

Background. The aim of this study was the evaluation of the correlation between VCAM-1 and TNF-alpha serum concentrations and various clinical and laboratory parameters in HIV-infected patients. Methods. All included subjects were patients of the Department of Infectious and Tropical Diseases and Hepatology of the Medical University of Warsaw in Poland in the years 2014–2016. The inclusion criteria were: confirmed HIV infection, Caucasian origin, and age > 18 years old. PCT, CRP, serum HIV-1 RNA, CD4/CD8 T cell count, PCR HCV RNA, HBsAg, VCAM-1, and TNF-alpha were measured. The VCAM-1 and TNF-alpha serum levels were evaluated by ELISA. Results. Seventy-two HIV-infected patients were included (16 women and 56 men: mean age 38.7 years, 66.6% cigarette smokers, 34.7% HCV co-infected HCV, and 27.8% ART-naïve). VCAM-1 concentrations were significantly higher in HIV/HCV co-infected patients than in HIV mono-infected patients (125.6 ± 85.4 vs. 78.4 ± 58.6 ng/mL, p = 0.011) and ART-naïve in comparison to patients on cART (121.9 ± 76.5 vs. 69.4 ± 57.1 ng/mL, p = 0.003). The significant positive correlation between HCV-infection and VCAM-1 and negative correlation between cART use and VCAM-1 was confirmed in multivariate analyses. The only variable associated significantly with TNF-alpha concentration was lymphocytes T CD8+ cell count (p = 0.026, estimate = 0.033). Conclusions. Successful cART and HCV eradication seemed to play an important role in the reduction of endothelial dysfunction and persistent inflammation in HIV-infected patients. CD8 T cell count seemed to be one of the markers of the pro-inflammatory state in HIV-infection patients.
Functional Status Following Pulmonary Rehabilitation: Responders and Non-Responders
Authors: Souto-Miranda Sara , Mendes Maria A. , Cravo João , Andrade Lília , Spruit Martijn A. , Marques Alda
Published: January 2022

The 6 min walking test (6MWT) has been largely studied. Less is, however, known about responders and non-responders to pulmonary rehabilitation (PR) in other meaningful activities. We explored responders and non-responders and the predictors of response to PR in the 1 min sit-to-stand test (1 min STS) and the 6MWT and compared both measures in classifying responders. An observational study was conducted with 121 people with chronic obstructive pulmonary disease (COPD). The functional status was assessed before and after PR. Baseline differences between responders and non-responders were tested with Mann–Whitney U, chi-square, or Fisher exact tests. Predictors were explored with binary logistic regressions. Agreement between both measures was assessed with chi-square, Cohen’s kappa, and McNemar tests. There were 54.5% and 57.0% of responders in the 1 min STS and the 6MWT, respectively. The proportion of responders was significantly different (p = 0.048), with a small agreement between the measures (kappa = 0.180; p = 0.048). The baseline 6MWT was the only significant predictor of response in the 6MWT (OR = 0.995; pseudo-r2 = 0.117; p < 0.001). No significant predictors were found for the 1 min STS. A large number of non-responders in terms of functional status exist. The 1 min STS and the 6MWT should not be used interchangeably. Future studies should explore the added benefit of personalizing PR to this outcome and investigate other potential predictors.
Development of a New Method for Calculating Intraocular Lens Power after Myopic Laser In Situ Keratomileusis by Combining the Anterior–Posterior Ratio of the Corneal Radius of the Curvature with the Double-K Method
Authors: Iida Yoshihiko , Shimizu Kimiya , Shoji Nobuyuki
Published: January 2022

Background: A new method, the Iida–Shimizu–Shoji (ISS) method, is proposed for calculating intraocular lens (IOL) power that combines the anterior–posterior ratio of the corneal radius of the curvature after laser in situ keratomileusis (LASIK) and to compare the predictability of the method with that of other IOL formulas after LASIK. Methods: The estimated corneal power before LASIK (Kpre) in the double-K method was 43.86 D according to the American Society of Cataract and Refractive Surgery calculator, and the K readings of the IOL master were used as the K values after LASIK (Kpost). The factor for correcting the target refractive value (correcting factor [C-factor]) was calculated from the correlation between the anterior–posterior ratio of the corneal radius of the curvature and the refractive error obtained using this method for 30 eyes of 30 patients. Results: Fifty-nine eyes of 59 patients were included. The mean values of the numerical and absolute prediction errors obtained using the ISS method were −0.02 ± 0.45 diopter (D) and 0.35 ± 0.27 D, respectively. The prediction errors using the ISS method were within ±0.25, ±0.50, and ±1.00 D in 49.2%, 76.3%, and 96.6% of the eyes, respectively. The predictability of the ISS method was comparable to or better than some of the other formulas. Conclusions: The ISS method is useful for calculating the IOL power in eyes treated with cataract surgery after LASIK.
Shoulder Replacement in the Elderly with Anatomic versus Reverse Total Prosthesis? A Prospective 2-Year Follow-Up Study
Authors: Simon Maciej , Coghlan Jennifer , Bell Simon
Published: January 2022

Background: In older patients requiring a total shoulder replacement (TSR) and with an intact rotator cuff, there is currently uncertainty on whether an anatomic TSR (aTSR) or a reverse TSR (rTSR) is best for the patient. This comparison study of same-aged patients aims to assess clinical and radiological outcomes of older patients (≥75 years) who received either an aTSR or an rTSR. Methods: Consecutive patients with a minimum age of 75 years who received an aTSR (n = 44) or rTSR (n = 51) were prospectively studied. Pre- and post-operative clinical evaluations included the ASES score, Constant score, SPADI score, DASH score, range of motion (ROM) and pain and patient satisfaction for a follow-up of 2 years. Radiological assessment identified glenoid and humeral component osteolysis, including notching with an rTSR. Results: We found postoperative improvement for ROM and all clinical assessment scores for both groups. There were significantly better patient reported outcome scores (PROMs) in the aTSR group compared with the rTSR patients (p < 0.001). Both groups had only minor osteolysis on radiographs. No revisions were required in either group. The main complications were scapular stress fractures for the rTSR (n = 11) patients and acromioclavicular joint pain for both groups (aTSR = 2; rTSR = 6). Conclusions: This study of older patients (≥75 years) demonstrated that an aTSR for a patient with good rotator cuff muscles can lead to a better clinical outcome and less early complications than an rTSR. Level of evidence: Level II—prospective cohort study.
Research on the Contact Pressure Calculation Method for the Misaligned Elastomeric Journal Bearing
Authors: Zhou Weixin , Zhao Yao , Yuan Hua , Liu Jingxi , Wang Xiaoqiang
Published: January 2022

The pressure distribution of a misaligned elastomeric journal bearing is crucial for analyzing the uneven excessive wearing of the propulsion shaft bearing. However, analysis of the misaligned bearing is usually mainly based on the finite element method (FEM), which lacks a convenient and effective calculation method. This paper uses the influence coefficient factors (ICs) method to analyze the contact pressure of the misaligned bearing. First, the elastic displacement of the cylindrical shell subjected to a single point of concentrated force is derived and used to attain the new influence coefficient factors. Then, the geometric boundary conditions of planar conformal cylindrical contact are extended to the case of non-planar contact. Finally, the proposed method is applied and compared with other methods. The results show that the influence coefficient factors are greatly affected by the shape and constraints of the contact object. The proposed method is suitable for cylindrical shell contact analysis and has the same accuracy as FEM with half of the time consumption. In addition, the bearing capacity and contact stiffness are decreased as the effective contact area decreases due to misalignment.
Deep Learning Application to Clinical Decision Support System in Sleep Stage Classification
Authors: Kim Dongyoung , Lee Jeonggun , Woo Yunhee , Jeong Jaemin , Kim Chulho , Kim Dong-Kyu
Published: January 2022

Recently, deep learning for automated sleep stage classification has been introduced with promising results. However, as many challenges impede their routine application, automatic sleep scoring algorithms are not widely used. Typically, polysomnography (PSG) uses multiple channels for higher accuracy; however, the disadvantages include a requirement for a patient to stay one or more nights in the lab wearing uncomfortable sensors and wires. To avoid the inconvenience caused by the multiple channels, we aimed to develop a deep learning model for use in clinical decision support systems (CDSSs) and combined convolutional neural networks and a transformer for the supervised learning of three classes of sleep stages only with single-channel EEG data (C4-M1). The data for training, validation, and test were derived from 1590, 341, and 343 polysomnography recordings, respectively. The developed model yielded an overall accuracy of 91.4%, comparable with that of human experts. Based on the severity of obstructive sleep apnea, the model’s accuracy was 94.3%, 91.9%, 91.9%, and 90.6% in normal, mild, moderate, and severe cases, respectively. Our deep learning model enables accurate and rapid delineation of three-class sleep staging and could be useful as a CDSS for application in real-world clinical practice.
Acceptance of COVID-19 and Influenza Vaccine Co-Administration: Insights from a Representative Italian Survey
Authors: Domnich Alexander , Grassi Riccardo , Fallani Elettra , Ciccone Roberto , Bruzzone Bianca , Panatto Donatella , Ferrari Allegra , Salvatore Marco , Cambiaggi Maura , Vasco Alessandro , Orsi Andrea , Icardi Giancarlo
Published: January 2022

Co-administration of coronavirus disease 2019 (COVID-19) and seasonal influenza vaccines has several advantages, has been advocated by various public health authorities and should be seen as an opportunity to increase the uptake of both vaccines. The objective of this survey was to quantify the acceptance of concomitant COVID-19/influenza vaccination and to identify its correlates in a representative sample of Italian adults. Of 2463 participants, a total of 22.9% were favorable to vaccine co-administration, while 16.6% declared their firm unwillingness to receive both vaccines simultaneously. The remaining 60.5% of subjects could be dubbed hesitant to some degree. Compliance with the primary COVID-19 vaccination schedule (adjusted proportional odds ratio (aOR) = 7.78), previous influenza vaccination (aOR = 1.89) and trust in public health institutions (aOR = 1.22) were the main determinants of positive attitudes toward vaccine co-administration. Other significant correlates included age, sex, perceived disease severity and vaccination risk–benefit, being offered a more personalized influenza vaccine and recent seeking for influenza-related information. In Italy, hesitancy toward COVID-19/influenza vaccine co-administration is common and appears to be higher than hesitancy toward either vaccine administered alone. This pattern is multifaceted and requires specific and tailored strategies, with public health institutions playing the central role.
The Associations of Single Nucleotide Polymorphisms with Risk and Symptoms of Irritable Bowel Syndrome
Authors: Zhao Tingting , Zhang Yiming , Lee Joochul , Starkweather Angela R. , Young Erin E. , Cong Xiaomei
Published: January 2022

Although several risk single nucleotide polymorphisms (SNPs) have been found to play an important role in etiology of irritable bowel syndrome (IBS), the findings are inconsistent. A descriptive correlational design was used to analyze the baseline data of a randomized controlled trial including participants with IBS and healthy controls (HC). Pain severity and interference, anxiety, sleep, and fatigue were measured using the Brief Pain Inventory (BPI) and patient-reported outcomes measurement information system (PROMIS). Fisher’s exact test and multivariate linear regression were used to investigate the associations between IBS risk alleles and IBS symptoms. Participants were predominantly female, white, and had an average age of 21.13 ± 2.42 years. Polymorphisms within TNFSF15 (rs4263839), SLC6A4 5-HTTLPR, HTR3A (rs1062613), and OXTR (rs2254298) were associated with IBS risk, and TNFSF15 (rs4263839), COMT (rs6269), SLC6A4 5-HTTLPR polymorphisms were associated with pain severity. TNFSF15 (rs4263839) and COMT (rs4680; rs4633) genotypes were associated with sleep disturbance, and the ADRA1D SNP rs1556832 was associated with fatigue in both IBS and HC groups. Genotypic differences were associated with IBS risk and symptoms including abdominal pain, sleep disturbance, and fatigue. Further investigation is warranted to reveal the mechanisms by which these genetic variations influence the dynamic nature of IBS symptoms over time.
Locoregional Recurrence Prediction Using a Deep Neural Network of Radiological and Radiotherapy Images
Authors: Han Kyumin , Joung Joonyoung Francis , Han Minhi , Sung Wonmo , Kang Young-nam
Published: January 2022

Radiation therapy (RT) is an important and potentially curative modality for head and neck squamous cell carcinoma (HNSCC). Locoregional recurrence (LR) of HNSCC after RT is ranging from 15% to 50% depending on the primary site and stage. In addition, the 5-year survival rate of patients with LR is low. To classify high-risk patients who might develop LR, a deep learning model for predicting LR needs to be established. In this work, 157 patients with HNSCC who underwent RT were analyzed. Based on the National Cancer Institute’s multi-institutional TCIA data set containing FDG-PET/CT/dose, a 3D deep learning model was proposed to predict LR without time-consuming segmentation or feature extraction. Our model achieved an averaged area under the curve (AUC) of 0.856. Adding clinical factors into the model improved the AUC to an average of 0.892 with the highest AUC of up to 0.974. The 3D deep learning model could perform individualized risk quantification of LR in patients with HNSCC without time-consuming tumor segmentation.
Numerical Analysis for Wetting Behaviors of an Oil Jet Lubricated Spur Gear
Authors: Dai Yu , Liang Chongyu , Chen Xi , Zhu Xiang
Published: January 2022

As it is widely employed in the aeronautical transmission system, a better understanding of the oil jet lubrication behavior is vital to determine the total system energy consumption. Firstly, this study presents related theoretical models such as the sum of oil jet resistance torque, impingement depth, and wetted area of the oil film for calibrating the physical characteristics of the impact of the oil jet on the gear flank. Then, in terms of the flow phenomenology of the liquid column for the oil jet impact on an isolated spur gear, a detailed transient and spatial flow field analysis becomes available, benefiting from an overset mesh method integrating with a volume-of-fluid (VOF) method. Furthermore, not only the oil jet resistance torque, but also the impingement depth as well as the spatial and temporal evolution of wetted surface by the oil film on the gear tooth given by numerical investigations were compared well with the theoretical calculations.
Corrosion Behavior of Candidate Functional Materials for Molten Salts Reactors in LiF–NaF–KF Containing Actinide Fluoride Imitators
Authors: Karfidov Eduard , Nikitina Evgueniya , Erzhenkov Maxim , Seliverstov Konstantin , Chernenky Pavel , Mullabaev Albert , Tsvetov Vladimir , Mushnikov Peter , Karimov Kirill , Molchanova Natalia , Kuznetsova Alexandra
Published: January 2022

Molten fluorides of alkali metals are considered a technological medium for molten salt reactors (MSRs). However, these media are known to be extremely corrosive. The successful implementation of high-temperature technological devices using molten alkali metal fluorides requires the selection of such structural materials that have high corrosion resistance in melts with compositional characteristic of MSRs. In this research, the corrosion behavior of 12Cr18Ni10Ti steel, the alloy Ni60Cr20Mo15, and the alloy Monel 404 (Ni50Cu50) was investigated in the LiF–NaF–KF eutectic melt, containing additions of CeF3 and NdF3 from 0 to 5 wt.% as imitator fluorides of actinides in an inert argon atmosphere at 550 °C for 100 h. Gravimetry, energy-dispersive X-ray (EDX) microanalysis of surfaces and cross-section of samples, and ICP-MS were used to establish the corrosion behavior of the investigated alloys. Corrosion resistance of the studied materials was found to decrease in a row from Monel 404 > Hastelloy C2000 > 12Cr18Ni10Ti. The addition of cerium fluoride into the melt resulted in the additional etching of the alloy surface. The addition of neodymium fluoride resulted in the formation of the point/inter-crystalline corrosion damages in the sample bulk. The samples of steel 12Cr18Ni10Ti were subjected to local cracking corrosion. The austenitic nickel-based alloys suffered specific local corrosion with formation of subsurface voids. Excellent corrosion resistance of the Monel alloy under the test conditions was found.
Methods to Produce Nicotinic Acid with Potential Industrial Applications
Authors: Lisicki Dawid , Nowak Kinga , Orlińska Beata
Published: January 2022

Nicotinic acid is a naturally occurring pyridine carboxylic acid, contained in vitamin PP, an essential nutrient for humans and animals, and used as an antipelagic agent. Nicotinic acid can be made from tryptophan by plants and animals but is usually not completely bioavailable. Industrially, nicotinic acid is produced mainly by oxidation of 5-ethyl-2-methylpyridine with nitric acid. One of the by-products of the process is nitrous oxide, a gas that is difficult to recycle and manage, with a greenhouse effect 300 times stronger than CO2. A new technology for the industrial production of nicotinic acid is undoubtedly necessary to meet the needs of green chemistry and not burden the environment. We carried out a literature review on ecological methods to produce nicotinic acid from commercially available raw materials such as 3-methylpyridine and 5-ethyl-2-methylpyridine, especially focusing on those methods with potential industrial applications.
A Flavonoid-Rich Extract of Sambucus nigra L. Reduced Lipid Peroxidation in a Rat Experimental Model of Gentamicin Nephrotoxicity
Authors: Ungur Rodica Ana , Borda Ileana Monica , Codea Răzvan Andrei , Ciortea Viorela Mihaela , Năsui Bogdana Adriana , Muste Sevastița , Sarpataky Orsolya , Filip Miuța , Irsay Laszlo , Crăciun Elena Cristina , Căinap Simona , Jivănescu Delia Bunea , Pop Anca Lucia , Singurean Victoria Emilia , Crișan Maria , Groza Oana Bianca , Martiș (Petruț) Georgiana Smaranda
Published: January 2022

The use of gentamicin (GM) is limited due to its nephrotoxicity mediated by oxidative stress. This study aimed to evaluate the capacity of a flavonoid-rich extract of Sambucus nigra L. elderflower (SN) to inhibit lipoperoxidation in GM-induced nephrotoxicity. The HPLC analysis of the SN extract recorded high contents of rutin (463.2 ± 0.0 mg mL−1), epicatechin (9.0 ± 1.1 µg mL−1), and ferulic (1.5 ± 0.3 µg mL−1) and caffeic acid (3.6 ± 0.1 µg mL−1). Thirty-two Wistar male rats were randomized into four groups: a control group (C) (no treatment), GM group (100 mg kg−1 bw day−1 GM), GM+SN group (100 mg kg−1 bw day−1 GM and 1 mL SN extract day−1), and SN group (1 mL SN extract day−1). Lipid peroxidation, evaluated by malondialdehyde (MDA), and antioxidant enzymes activity—superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)—were recorded in renal tissue after ten days of experimental treatment. The MDA level was significantly higher in the GM group compared to the control group (p < 0.0001), and was significantly reduced by SN in the GM+SN group compared to the GM group (p = 0.021). SN extract failed to improve SOD, CAT, and GPX activity in the GM+SN group compared to the GM group (p > 0.05), and its action was most probably due to the ability of flavonoids (rutin, epicatechin) and ferulic and caffeic acids to inhibit synthesis and neutralize reactive species, to reduce the redox-active iron pool, and to inhibit lipid peroxidation. In this study, we propose an innovative method for counteracting GM nephrotoxicity with a high efficiency and low cost, but with the disadvantage of the multifactorial environmental variability of the content of SN extracts.