bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events
Authors: Belinky Frida , Ganguly Ishan , Poliakov Eugenia , Yurchenko Vyacheslav , Rogozin Igor B.
Published: February 2021

Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels.
Prokaryotic Solute/Sodium Symporters: Versatile Functions and Mechanisms of a Transporter Family
Authors: Henriquez Tania , Wirtz Larissa , Su Dan , Jung Heinrich
Published: February 2021

The solute/sodium symporter family (SSS family; TC 2.A.21; SLC5) consists of integral membrane proteins that use an existing sodium gradient to drive the uphill transport of various solutes, such as sugars, amino acids, vitamins, or ions across the membrane. This large family has representatives in all three kingdoms of life. The human sodium/iodide symporter (NIS) and the sodium/glucose transporter (SGLT1) are involved in diseases such as iodide transport defect or glucose-galactose malabsorption. Moreover, the bacterial sodium/proline symporter PutP and the sodium/sialic acid symporter SiaT play important roles in bacteria–host interactions. This review focuses on the physiological significance and structural and functional features of prokaryotic members of the SSS family. Special emphasis will be given to the roles and properties of proteins containing an SSS family domain fused to domains typically found in bacterial sensor kinases.
Intestinal Epithelial Barrier Maturation by Enteric Glial Cells Is GDNF-Dependent
Authors: Meir Michael , Kannapin Felix , Diefenbacher Markus , Ghoreishi Yalda , Kollmann Catherine , Flemming Sven , Germer Christoph-Thomas , Waschke Jens , Leven Patrick , Schneider Reiner , Wehner Sven , Burkard Natalie , Schlegel Nicolas
Published: February 2021

Enteric glial cells (EGCs) of the enteric nervous system are critically involved in the maintenance of intestinal epithelial barrier function (IEB). The underlying mechanisms remain undefined. Glial cell line-derived neurotrophic factor (GDNF) contributes to IEB maturation and may therefore be the predominant mediator of this process by EGCs. Using GFAPcre x Ai14floxed mice to isolate EGCs by Fluorescence-activated cell sorting (FACS), we confirmed that they synthesize GDNF in vivo as well as in primary cultures demonstrating that EGCs are a rich source of GDNF in vivo and in vitro. Co-culture of EGCs with Caco2 cells resulted in IEB maturation which was abrogated when GDNF was either depleted from EGC supernatants, or knocked down in EGCs or when the GDNF receptor RET was blocked. Further, TNFα-induced loss of IEB function in Caco2 cells and in organoids was attenuated by EGC supernatants or by recombinant GDNF. These barrier-protective effects were blunted when using supernatants from GDNF-deficient EGCs or by RET receptor blockade. Together, our data show that EGCs produce GDNF to maintain IEB function in vitro through the RET receptor.
Plant HKT Channels: An Updated View on Structure, Function and Gene Regulation
Authors: Riedelsberger Janin , Miller Julia K. , Valdebenito-Maturana Braulio , Piñeros Miguel A. , González Wendy , Dreyer Ingo
Published: February 2021

HKT channels are a plant protein family involved in sodium (Na+) and potassium (K+) uptake and Na+-K+ homeostasis. Some HKTs underlie salt tolerance responses in plants, while others provide a mechanism to cope with short-term K+ shortage by allowing increased Na+ uptake under K+ starvation conditions. HKT channels present a functionally versatile family divided into two classes, mainly based on a sequence polymorphism found in the sequences underlying the selectivity filter of the first pore loop. Physiologically, most class I members function as sodium uniporters, and class II members as Na+/K+ symporters. Nevertheless, even within these two classes, there is a high functional diversity that, to date, cannot be explained at the molecular level. The high complexity is also reflected at the regulatory level. HKT expression is modulated at the level of transcription, translation, and functionality of the protein. Here, we summarize and discuss the structure and conservation of the HKT channel family from algae to angiosperms. We also outline the latest findings on gene expression and the regulation of HKT channels.
Low-Temperature Argon Plasma Regulates Skin Moisturizing and Melanogenesis-Regulating Markers through Yes-Associated Protein
Authors: Kim Hae-Young , Agrahari Gaurav , Lee Min Jung , Tak Lee-Jung , Ham Won-Kook , Kim Tae-Yoon
Published: February 2021

Extensive water loss and melanin hyperproduction can cause various skin disorders. Low-temperature argon plasma (LTAP) has shown the possibility of being used for the treatment of various skin diseases, such as atopic dermatitis and skin cancer. However, the role of LTAP in regulating skin moisturizing and melanogenesis has not been investigated. In this study, we aimed to determine the effect of LTAP on yes-associated protein (YAP), a major transcriptional coactivator in the Hippo signaling pathway that is involved in skin moisturizing and melanogenesis-regulating markers. In normal human epidermal keratinocytes (NHEKs), the human epidermal keratinocyte line HaCaT, and human dermal fibroblasts (HDFs), we found that LTAP exhibited increased expression levels of YAP protein. In addition, the expression levels of filaggrin (FLG), which is involved in natural moisturizing factors (NMFs), and hyaluronic acid synthase (HAS), transglutaminase (TGM), and involucrin (IVL), which regulate skin barrier and moisturizing, were also increased after exposure to LTAP. Furthermore, collagen type I alpha 1 and type III alpha 1 (COL1A1, COL3A1) were increased after LTAP exposure, but the expression level of matrix metalloproteinase-3 (MMP-3) was reduced. Moreover, LTAP was found to suppress alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in murine melanoma B16F10 cells and normal human melanocytes (NHEMs). LTAP regulates melanogenesis of the melanocytes through decreased YAP pathway activation in a melanocortin 1 receptor (MC1R)-dependent manner. Taken together, our data show that LTAP regulates skin moisturizing and melanogenesis through modulation of the YAP pathway, and the effect of LTAP on the expression level of YAP varies from cell to cell. Thus, LTAP might be developed as a treatment method to improve the skin barrier, moisture content, and wrinkle formation, and to reduce melanin generation.
Transglutaminase 2 as a Marker for Inflammation and Therapeutic Target in Sepsis
Authors: Su Ting , Qin Xian-Yang , Furutani Yutaka
Published: February 2021

Sepsis results in lethal organ malfunction due to dysregulated host response to infection, which is a condition with increasing prevalence worldwide. Transglutaminase 2 (TG2) is a crosslinking enzyme that forms a covalent bond between lysine and glutamine. TG2 plays important roles in diverse cellular processes, including extracellular matrix stabilization, cytoskeletal function, cell motility, adhesion, signal transduction, apoptosis, and cell survival. We have shown that the co-culture of Candida albicans and hepatocytes activates and induces the translocation of TG2 into the nucleus. In addition, the expression and activation of TG2 in liver macrophages was dramatically induced in the lipopolysaccharide-injected and cecal ligation puncture-operated mouse models of sepsis. Based on these findings and recently published research, we have reviewed the current understanding of the relationship between TG2 and sepsis. Following the genetic and pharmacological inhibition of TG2, we also assessed the evidence regarding the use of TG2 as a potential marker and therapeutic target in inflammation and sepsis.
Phylogenetic Relationships and Adaptation in Deep-Sea Mussels: Insights from Mitochondrial Genomes
Authors: Zhang Kai , Sun Jin , Xu Ting , Qiu Jian-Wen , Qian Pei-Yuan
Published: February 2021

Mitochondrial genomes (mitogenomes) are an excellent source of information for phylogenetic and evolutionary studies, but their application in marine invertebrates is limited. In the present study, we utilized mitogenomes to elucidate the phylogeny and environmental adaptation in deep-sea mussels (Mytilidae: Bathymodiolinae). We sequenced and assembled seven bathymodioline mitogenomes. A phylogenetic analysis integrating the seven newly assembled and six previously reported bathymodioline mitogenomes revealed that these bathymodiolines are divided into three well-supported clades represented by five Gigantidas species, six Bathymodiolus species, and two “Bathymodiolus” species, respectively. A Common interval Rearrangement Explorer (CREx) analysis revealed a gene order rearrangement in bathymodiolines that is distinct from that in other shallow-water mytilids. The CREx analysis also suggested that reversal, transposition, and tandem duplications with subsequent random gene loss (TDRL) may have been responsible for the evolution of mitochondrial gene orders in bathymodiolines. Moreover, a comparison of the mitogenomes of shallow-water and deep-sea mussels revealed that the latter lineage has experienced relaxed purifying selection, but 16 residues of the atp6, nad4, nad2, cob, nad5, and cox2 genes have underwent positive selection. Overall, this study provides new insights into the phylogenetic relationships and mitogenomic adaptations of deep-sea mussels
Comprehensive Comparison of Amnion Stromal Cells and Chorion Stromal Cells by RNA-Seq
Authors: Jones Brielle , Li Chaoyang , Park Min Sung , Lerch Anne , Jacob Vimal , Johnson Nicholas , Kuang Jin-Qiang , Dhall Sandeep , Sathyamoorthy Malathi
Published: February 2021

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.
Investigation of Nanoparticle Metallic Core Antibacterial Activity: Gold and Silver Nanoparticles against Escherichia coli and Staphylococcus aureus
Authors: Gouyau Jimmy , Duval Raphaël E. , Boudier Ariane , Lamouroux Emmanuel
Published: February 2021

Multidrug-resistant (MDR) bacteria constitute a global health issue. Over the past ten years, interest in nanoparticles, particularly metallic ones, has grown as potential antibacterial candidates. However, as there is no consensus about the procedure to characterize the metallic nanoparticles (MNPs; i.e., metallic aggregates) and evaluate their antibacterial activity, it is impossible to conclude about their real effectiveness as a new antibacterial agent. To give part of the answer to this question, 12 nm gold and silver nanoparticles have been prepared by a chemical approach. After their characterization by transmission electronic microscopy (TEM), Dynamic Light Scattering (DLS), and UltraViolet-visible (UV-vis) spectroscopy, their surface accessibility was tested through the catalytic reduction of the 4-nitrophenol, and their stability in bacterial culture medium was studied. Finally, the antibacterial activities of 12 nm gold and silver nanoparticles facing Staphylococcus aureus and Escherichia coli have been evaluated using the broth microdilution method. The results show that gold nanoparticles have a weak antibacterial activity (i.e., slight inhibition of bacterial growth) against the two bacteria tested. In contrast, silver nanoparticles have no activity on S. aureus but demonstrate a high antibacterial activity against Escherichia coli, with a minimum inhibitory concentration of 128 µmol/L. This high antibacterial activity is also maintained against two MDR-E. coli strains.
Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies
Authors: Nasillo Vincenzo , Riva Giovanni , Paolini Ambra , Forghieri Fabio , Roncati Luca , Lusenti Beatrice , Maccaferri Monica , Messerotti Andrea , Pioli Valeria , Gilioli Andrea , Bettelli Francesca , Giusti Davide , Barozzi Patrizia , Lagreca Ivana , Maffei Rossana , Marasca Roberto , Potenza Leonardo , Comoli Patrizia , Manfredini Rossella , Maiorana Antonino , Tagliafico Enrico , Luppi Mario , Trenti Tommaso
Published: February 2021

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches.
Human iPSC-Derived 2D and 3D Platforms for Rapidly Assessing Developmental, Functional, and Terminal Toxicities in Neural Cells
Authors: Slavin Ileana , Dea Steven , Arunkumar Priyanka , Sodhi Neha , Montefusco Sandro , Siqueira-Neto Jair , Seelke Janet , Lofstrom Mary Anne , Anson Blake , Zanella Fabian , Carromeu Cassiano
Published: February 2021

With increasing global health threats has come an urgent need to rapidly develop and deploy safe and effective therapies. A common practice to fast track clinical adoption of compounds for new indications is to repurpose already approved therapeutics; however, many compounds considered safe to a specific application or population may elicit undesirable side effects when the dosage, usage directives, and/or clinical context are changed. For example, progenitor and developing cells may have different susceptibilities than mature dormant cells, which may yet be different than mature active cells. Thus, in vitro test systems should reflect the cellular context of the native cell: developing, nascent, or functionally active. To that end, we have developed high-throughput, two- and three-dimensional human induced pluripotent stem cell (hiPSC)-derived neural screening platforms that reflect different neurodevelopmental stages. As a proof of concept, we implemented this in vitro human system to swiftly identify the potential neurotoxicity profiles of 29 therapeutic compounds that could be repurposed as anti-virals. Interestingly, many compounds displayed high toxicity on early-stage neural tissues but not on later stages. Compounds with the safest overall viability profiles were further evaluated for functional assessment in a high-throughput calcium flux assay. Of the 29 drugs tested, only four did not modulate or have other potentially toxic effects on the developing or mature neurospheroids across all the tested dosages. These results highlight the importance of employing human neural cultures at different stages of development to fully understand the neurotoxicity profile of potential therapeutics across normal ontogeny.
The Cutinase Bdo_10846 Play an Important Role in the Virulence of Botryosphaeria dothidea and in Inducing the Wart Symptom on Apple Plant
Authors: Dong Bao-Zhu , Zhu Xiao-Qiong , Fan Jun , Guo Li-Yun
Published: February 2021

Botryosphaeria dothidea is a pathogen with worldwide distribution, infecting hundreds of species of economically important woody plants. It infects and causes various symptoms on apple plants, including wart and canker on branches, twigs, and stems. However, the mechanism of warts formation is unclear. In this study, we investigated the mechanism of wart formation by observing the transection ultrastructure of the inoculated cortical tissues at various time points of the infection process and detecting the expression of genes related to the pathogen pathogenicity and plant defense response. Results revealed that wart induced by B. dothidea consisted of proliferous of phelloderm cells, the newly formed secondary phellem, and the suberized phelloderm cells surrounding the invading mycelia. The qRT-PCR analysis revealed the significant upregulation of apple pathogenesis-related and suberification-related genes and a pathogen cutinase gene Bdo_10846. The Bdo_10846 knockout transformants showed reduced cutinase activity and decreased virulence. Transient expression of Bdo_10846 in Nicotiana benthamiana induced ROS burst, callose formation, the resistance of N. benthamiana to Botrytis cinerea, and significant upregulation of the plant pathogenesis-related and suberification-related genes. Additionally, the enzyme activity is essential for the induction. Virus-induced gene silencing demonstrated that the NbBAK1 and NbSOBIR1 expression were required for the Bdo_10846 induced defense response in N. benthamiana. These results revealed the mechanism of wart formation induced by B. dothidea invasion and the important roles of the cutinase Bdo_10846 in pathogen virulence and in inducing plant immunity.
Deep Learning-Based Indoor Distance Estimation Scheme Using FMCW Radar
Authors: Park Kyung-Eun , Lee Jeong-Pyo , Kim Youngok
Published: February 2021

In the distance estimation scheme using Frequency-Modulated-Continuous-Wave (FMCW) radar, the frequency difference, which was caused by the time delay of the received signal reflected from the target, is calculated to estimate the distance information of the target. In this paper, we propose a distance estimation scheme exploiting the deep learning technology of artificial neural network to improve the accuracy of distance estimation over the conventional Fast Fourier Transform (FFT) Max value index-based distance estimation scheme. The performance of the proposed scheme is compared with that of the conventional scheme through the experiments evaluating the accuracy of distance estimation. The average estimated distance error of the proposed scheme was 0.069 m, while that of the conventional scheme was 1.9 m.
Natural Occurrence of Entomopathogenic Fungi as Endophytes of Sugarcane (Saccharum officinarum) and in Soil of Sugarcane Fields
Authors: Kasambala Donga Trust , Meadow Richard , Meyling Nicolai V. , Klingen Ingeborg
Published: February 2021

The natural occurrence of entomopathogenic fungal endophytes in sugarcane (Saccharum officinarum) and in soil samples from sugarcane fields was evaluated in Chikwawa District, southern Malawi. Fungi from soil were isolated by baiting using Galleria mellonella larva. Fungal endophytes were isolated from surface-sterilized plant tissue sections. Forty-seven isolates resembled the genus Beauveria, 9 isolates were Metarhizium, and 20 isolates were Isaria. There was no significant difference in the number and type of fungal isolates collected from soil and from plant tissue. There was, however, a significant difference in the part of the plant where fungal species were isolated, which fungal species were isolated, and the number of fungal species isolated at each location. Phylogenetic analysis of 47 Beauveria isolates based on DNA sequencing of the Bloc intergenic region indicated that these isolates all belonged to B. bassiana and aligned with sequences of B. bassiana isolates of African and Neotropical origin. The Malawian B. bassiana isolates formed a distinct clade. No larvae died from infestation by multiple fungi. To the best of our knowledge, this is the first report of B. bassiana and Isaria spp. occurring naturally as endophytes in sugarcane. Further, it is the first report of B. bassiana, Isaria spp., and Metarhizium spp. in the soil of sugarcane fields in Africa.
Evaluating the Impact of Post-Emergence Weed Control in Honeybee Colonies Located in Different Agricultural Surroundings
Authors: Macri Ivana N. , Vázquez Diego E. , Pagano Eduardo A. , Zavala Jorge A. , Farina Walter M.
Published: February 2021

The honeybee Apis mellifera is exposed to agricultural intensification, which leads to an improved reliance upon pesticide use and the reduction of floral diversity. In the present study, we assess the changes in the colony activity and the expression profile of genes involved in xenobiotic detoxification in larvae and adult honeybees from three apiaries located in agricultural environments that differ in their proportion of the crop/wild flora. We evaluated these variables before and after the administration of a mixture of three herbicides during the summer season. The expression of several cytochrome P450 monooxygenases decreased significantly in larvae after post-emergence weed control and showed significant differences between apiaries in the case of honeybee workers. Principal component analysis (PCA) revealed that colonies located in the plot near to a wetland area exhibited a different relative gene expression profile after herbicide application compared with the other plots. Moreover, we found significant positive correlations between pollen collection and the pesticide detoxification genes that discriminated between plots in the PCA. Our results suggest that nutrition may modify herbicide impact on honeybees and that larvae are more harmed than adults in agroecosystems, a factor that will alter the colonies’ population growth at the end of the blooming period.
The Relationship between Research and Casework in Forensic Entomology
Authors: Hall Martin J. R.
Published: February 2021

Research is a vital component of all forensic sciences and is often stimulated by casework, which identifies gaps in our knowledge. In such a niche area of forensic science as entomology there should be a close and mutually beneficial relationship between research and casework: to some extent there is a continuum between the two and many forensic entomologists are involved in both to a greater or lesser degree. However, research and casework involve quite differing challenges, from the replicated, highly controlled, sometimes esoteric aspects of research to the very individual, sometimes chaotic and disruptive, but highly applied aspects of casework. Ideally casework will include the full involvement of a forensic entomologist, who will collect the insect and climate evidence at the scene and produce a robust expert witness statement based on a full analysis of this data. Unfortunately, it can also include situations where samples, if collected at all, are poorly preserved, not representative of the full cadaver fauna available and presented to the entomologist months or years after the event, without local temperature data. While research is recognised through publications and their citation indices, casework and its associated expert witness statements often receive no credit in an academic workplace, although they do have a positive societal impact and many other benefits of teaching and public engagement value. This manuscript examines the relationship between research and casework from a UK perspective, to raise awareness of the need to create an environment that values the contribution of both, for future generations to flourish in both areas.
Biventricular Unloading with Impella and Venoarterial Extracorporeal Membrane Oxygenation in Severe Refractory Cardiogenic Shock: Implications from the Combined Use of the Devices and Prognostic Risk Factors of Survival
Authors: Chatzis Georgios , Syntila Styliani , Markus Birgit , Ahrens Holger , Patsalis Nikolaos , Luesebrink Ulrich , Divchev Dimitar , Parahuleva Mariana , Al Eryani Hanna , Schieffer Bernhard , Karatolios Konstantinos
Published: February 2021

Since mechanical circulatory support (MCS) devices have become integral component in the therapy of refractory cardiogenic shock (RCS), we identified 67 patients in biventricular support with Impella and venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) for RCS between February 2013 and December 2019 and evaluated the risk factors of mortality in this setting. Mean age was 61.07 ± 10.7 and 54 (80.6%) patients were male. Main cause of RCS was acute myocardial infarction (AMI) (74.6%), while 44 (65.7%) were resuscitated prior to admission. The mean Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment Score (SOFA) score on admission was 73.54 ± 16.03 and 12.25 ± 2.71, respectively, corresponding to an expected mortality of higher than 80%. Vasopressor doses and lactate levels were significantly decreased within 72 h on biventricular support (p < 0.05 for both). Overall, 17 (25.4%) patients were discharged to cardiac rehabilitation and 5 patients (7.5%) were bridged successfully to ventricular assist device implantation, leading to a total of 32.8% survival on hospital discharge. The 6-month survival was 31.3%. Lactate > 6 mmol/L, vasoactive score > 100 and pH < 7.26 on initiation of biventricular support, as well as Charlson comorbity index > 3 and prior resuscitation were independent predictors of survival. In conclusion, biventricular support with Impella and VA-ECMO in patients with RCS is feasible and efficient leading to a better survival than predicted through traditional risk scores, mainly via significant hemodynamic improvement and reduction in lactate levels.
Clinical Factors Associated with Reinfection versus Relapse in Infective Endocarditis: Prospective Cohort Study
Authors: Calderón-Parra Jorge , Kestler Martha , Ramos-Martínez Antonio , Bouza Emilio , Valerio Maricela , de Alarcón Arístides , Luque Rafael , Goenaga Miguel , Echeverría Tomás , Fariñas Mª , Pericàs Juan , Ojeda-Burgos Guillermo , Fernández-Cruz Ana , Plata Antonio , Vinuesa David , Muñoz Patricia ,   on behalf of the GAMES Investigators
Published: February 2021

We aimed to identify clinical factors associated with recurrent infective endocarditis (IE) episodes. The clinical characteristics of 2816 consecutive patients with definite IE (January 2008–2018) were compared according to the development of a second episode of IE. A total of 2152 out of 2282 (94.3%) patients, who were discharged alive and followed-up for at least the first year, presented a single episode of IE, whereas 130 patients (5.7%) presented a recurrence; 70 cases (53.8%) were due to other microorganisms (reinfection), and 60 cases (46.2%) were due to the same microorganism causing the first episode. Thirty-eight patients (29.2%), whose recurrence was due to the same microorganism, were diagnosed during the first 6 months of follow-up and were considered relapses. Relapses were associated with nosocomial endocarditis (OR: 2.67 (95% CI: 1.37–5.29)), enterococci (OR: 3.01 (95% CI: 1.51–6.01)), persistent bacteremia (OR: 2.37 (95% CI: 1.05–5.36)), and surgical treatment (OR: 0.23 (0.1–0.53)). On the other hand, episodes of reinfection were more common in patients with chronic liver disease (OR: 3.1 (95% CI: 1.65–5.83)) and prosthetic endocarditis (OR: 1.71 (95% CI: 1.04–2.82)). The clinical factors associated with reinfection and relapse in patients with IE appear to be different. A better understanding of these factors would allow the development of more effective therapeutic strategies.
Improving Familial Hypercholesterolemia Index Case Detection: Sequential Active Screening from Centralized Analytical Data
Authors: Sabatel-Pérez Fernando , Sánchez-Prieto Joaquín , Becerra-Muñoz Víctor Manuel , Alonso-Briales Juan Horacio , Mata Pedro , Rodríguez-Padial Luis
Published: February 2021

The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3–5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% (n = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold (p < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies.
Is There an Oncological Benefit of Performing Bilateral Pelvic Lymph Node Dissection in Patients with Penile Cancer and Inguinal Lymph Node Metastasis?
Authors: Suarez-Ibarrola Rodrigo , Basulto-Martinez Mario , Sigle August , Abufaraj Mohammad , Gratzke Christian , Miernik Arkadiusz
Published: February 2021

We aim to review the literature for studies investigating the oncological outcomes of patients with penile cancer (PC) undergoing bilateral pelvic lymph node dissection (PLND) in the presence of inguinal lymph node metastasis (LNM) who are at risk of harboring pelvic metastasis. A search of English language literature was performed using the PubMed-MEDLINE database up to 3 December 2020 to identify articles addressing bilateral PLND in PC patients. Eight articles investigating bilateral PLND met our inclusion criteria. Patients with pelvic LNM have a dismal prognosis and, therefore, PLND has an important role in both the staging and treatment of PC patients. Ipsilateral PLND is recommended in the presence of ≥2 positive inguinal nodes and/or extranodal extension (ENE). Significant survival improvements were observed with a higher pelvic lymph node yield, in patients with pN2 disease, and in men treated with bilateral PLND as opposed to ipsilateral PLND. Nevertheless, the role of bilateral PLND for unilateral inguinal LNM remains unclear. Although the EAU guidelines state that pelvic nodal disease does not occur without ipsilateral inguinal LNM, metastatic spread from one inguinal side to the contralateral pelvic side has been reported in a number of studies. Further studies are needed to clarify the disseminative pattern of LNM, in order to establish PLND templates according to patients’ risk profiles and to investigate the benefit of performing bilateral PLND for unilateral inguinal disease.
Osteopontin Serum Concentration and Metabolic Syndrome in Male Psoriatic Patients
Authors: Bartosińska Joanna , Przepiórka-Kosińska Joanna , Sarecka-Hujar Beata , Raczkiewicz Dorota , Kowal Małgorzata , Chyl-Surdacka Katarzyna , Bartosiński Jarosław , Kosiński Jakub , Krasowska Dorota , Chodorowska Grażyna
Published: February 2021

Psoriasis (Ps) is an immune-mediated inflammatory skin disease that is widely associated with the clinical features of metabolic syndrome (MetS), including hypertension, abdominal obesity, insulin resistance, type 2 diabetes and dyslipidemia. Osteopontin (OPN), a multifunctional protein involved in the modulation of inflammatory processes, may contribute to the development of atherosclerosis and MetS. Therefore, the aim of the study was the assessment of the correlation between OPN concentration in the peripheral blood and the presence of MetS as well as its particular components in the Ps patients. The study comprised 107 male Ps patients (50 patients with MetS and 57 without MetS) and 38 healthy volunteers (HVs). The concentration of OPN in serum was determined using enzyme-linked immunosorbent assay (ELISA) method. Fasting blood glucose and lipid profile components: total cholesterol (total CHOL), high-density lipoprotein cholesterol (HDL-CHOL), low-density lipoprotein cholesterol (LDL-CHOL), triglycerides (TG) were examined. Ps patients with MetS had significantly higher obesity, systolic blood pressure, TG, CHOL/HDL, LDL/HDL and TG/HDL ratios than Ps patients without MetS. OPN serum concentration was significantly higher in the Ps patients than in the HVs (p = 0.022) but not significantly different between the Ps patients with and without MetS (p = 0.275). OPN serum concentration in Ps patients correlated negatively with total CHOL (p = 0.004) and TG (p = 0.009). OPN is increased in Ps patients and may serve as a biomarker of some lipid abnormalities in them.
Parameters of Off-Vertical Axis Rotation in Unilateral and Bilateral Vestibulopathy and Their Correlation with Vestibular Evoked Myogenic Potentials
Authors: Kim Shin Hye , Lee Sang-Yeon , Kim Ji-Soo , Koo Ja-Won
Published: February 2021

Off-vertical axis rotation (OVAR) is a laboratory test to assess the otolith function. This study aimed to analyze the parameters of OVAR in patients with unilateral vestibular hypofunction (UVH) and bilateral vestibulopathy (BVP), and to correlate the parameters of OVAR with those of VEMPs. Ten healthy volunteers, 41 UVH, and 13 BVP patients performed OVAR. Bias component (BIC) and modulation component (MOC) of UVH and BVP patients were compared with those of healthy controls. BIC and MOC were correlated with amplitude and interaural difference (IAD) of cervical VEMP (cVEMP) and ocular VEMP (oVEMP). In UVH patients, the direction of BICs to affected side rotation were reversed and the absolute value of BICs were decreased when they were compared to healthy controls. In BVP patients, BICs were markedly attenuated. MOCs were not changed in UVH and BVP patients. There was no statistically significant correlation between VEMPs and OVAR.
Effects of Methylprednisolone on Ventilator-Free Days in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome and COVID-19: A Retrospective Study
Authors: Badr Mohamed , De Oliveira Bruno , Abdallah Khaled , Nadeem Ashraf , Varghese Yeldho , Munde Dnyaseshwar , Salam Shameen , Abduljawad Baraa , Saleh Khaled , Elkambergy Hussam , Taha Ahmed , Bayrlee Ahmed , Wahla Ali , Dibu Jamil , Haque Rehan , Hamed Fadi , Rahman Nadeem , Mallat Jihad
Published: February 2021

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone is associated with increases in the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study. Setting: Intensive care unit. Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included. Interventions: None. Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) for the first 28 days. Defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional sub hazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg·kg−1 (IQR: 1–1.3 mg·kg−1) and median duration for 5 days (IQR: 5–7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6–20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6–16.7) in patients who did not receive methylprednisolone (difference, 4.61, 95% CI, 1.10–8.12, p = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95% CI: 0.02–0.45, p = 0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p = 0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR: 15–41 days] vs. 37 days [IQR: 23–52 days], p = 0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p = 0.052). However, 81% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.
International Practice Variability in Treatment of Aneurysmal Subarachnoid Hemorrhage
Authors: de Winkel Jordi , van der Jagt Mathieu , Lingsma Hester F. , Roozenbeek Bob , Calvillo Eusebia , Chou Sherry H-Y. , Dziedzic Peter H. , Etminan Nima , Huang Judy , Ko Nerissa U. , Loch MacDonald Robert , Martin Renee L. , Potu Niteesh R. , Venkatasubba Rao Chethan P. , Vergouwen Mervyn D. I. , Suarez Jose I.
Published: February 2021

Prior research suggests substantial between-center differences in functional outcome following aneurysmal subarachnoid hemorrhage (aSAH). One hypothesis is that these differences are due to practice variability. To characterize practice variability, we sent a survey to 230 centers, of which 145 (63%) responded. Survey respondents indicated that an estimated 65% of ruptured aneurysms were treated endovascularly. Sixty-five percent of aneurysms were treated within 24 h of symptom onset, 18% within 24–48 h, and eight percent within 48–72 h. Centers in the United States (US) and Europe (EU) treat aneurysms more often endovascularly (72% and 70% vs. 51%, respectively, US vs. other p < 0.001, and EU vs. other p < 0.01) and more often within 24 h (77% and 64% vs. 46%, respectively, US vs. other p < 0.001, EU vs. other p < 0.01) compared to other centers. Most centers aim for euvolemia (96%) by administrating intravenous fluids to 0 (53%) or +500 mL/day (41%) net fluid balance. Induced hypertension is more often used in US centers (100%) than in EU (87%, p < 0.05) and other centers (81%, p < 0.05), and endovascular therapies for cerebral vasospasm are used more often in US centers than in other centers (91% and 60%, respectively, p < 0.05). We observed significant practice variability in aSAH treatment worldwide. Future comparative effectiveness research studies are needed to investigate how practice variation leads to differences in functional outcome.
The Effect of COVID-19 Lockdown Measures on Physical Activity Levels and Sedentary Behaviour in a Relatively Young Population Living in Kosovo
Authors: Gjaka Masar , Feka Kaltrina , Bianco Antonino , Tishukaj Faton , Giustino Valerio , Parroco Anna Maria , Palma Antonio , Battaglia Giuseppe
Published: February 2021

To abate the spread of the COVID-19 virus, different restriction measures were imperative, limiting the possibility to be engaged in physical activity. Therefore, this study aimed to evaluate the effect of COVID-19 lockdown on physical activity (PA) levels expressed as energy expenditure (MET-min/week) and sedentary behaviour in Kosovo. The possible association between PA levels and other factors was analyzed. 1633 participants (age range: 13 to 63 years; mean: 24.70 ± 9.33 years; body height: 172 ± 10.57 cm; body mass: 69.10 ± 13.80 kg; BMI: 23.09 ± 3.63 kg/m2) participated in the study, categorized by age, gender, BMI, and living area. An online survey, including an adapted version of the IPAQ-SF, was administered once during lockdown to assess PA levels and sedentary behaviour both before and during COVID-19 lockdown. The Wilcoxon signed-rank, Mann–Whitney U and Kruskal–Wallis rank of sum tests were used for statistical analysis. COVID-19 restrictions had a negative impact on the types of and overall PA levels MET-min/week (p < 0.001). Sedentary behaviour significantly increased during COVID-19 restrictions (p < 0.001). Higher decreases in MET-min/week during lockdown were observed among males, young and young adults, overweight, and urban-living participants. Finally, COVID-19 restrictions decreased the PA levels and MET-min/week, and increased sedentary behaviour also in a relatively young cohort. Such differences were dependent on several factors.
AI and Big Data in Healthcare: Towards a More Comprehensive Research Framework for Multimorbidity
Authors: Majnarić Ljiljana Trtica , Babič František , O’Sullivan Shane , Holzinger Andreas
Published: February 2021

Multimorbidity refers to the coexistence of two or more chronic diseases in one person. Therefore, patients with multimorbidity have multiple and special care needs. However, in practice it is difficult to meet these needs because the organizational processes of current healthcare systems tend to be tailored to a single disease. To improve clinical decision making and patient care in multimorbidity, a radical change in the problem-solving approach to medical research and treatment is needed. In addition to the traditional reductionist approach, we propose interactive research supported by artificial intelligence (AI) and advanced big data analytics. Such research approach, when applied to data routinely collected in healthcare settings, provides an integrated platform for research tasks related to multimorbidity. This may include, for example, prediction, correlation, and classification problems based on multiple interaction factors. However, to realize the idea of this paradigm shift in multimorbidity research, the optimization, standardization, and most importantly, the integration of electronic health data into a common national and international research infrastructure is needed. Ultimately, there is a need for the integration and implementation of efficient AI approaches, particularly deep learning, into clinical routine directly within the workflows of the medical professionals.
The Cybersecurity Focus Area Maturity (CYSFAM) Model
Authors: Yigit Ozkan Bilge , van Lingen Sonny , Spruit Marco
Published: February 2021

The cost of recovery after a cybersecurity attack is likely to be high and may result in the loss of business at the extremes. Evaluating the acquired cybersecurity capabilities and evolving them to a desired state in consideration of risks are inevitable. This research proposes the CYberSecurity Focus Area Maturity (CYSFAM) Model for assessing cybersecurity capabilities. In this design science research, CYSFAM was evaluated at a large financial institution. From the many cybersecurity standards, 11 encompassing focus areas were identified. An assessment instrument—containing 144 questions—was developed. The in-depth single case study demonstrates how and to what extent cybersecurity related deficiencies can be identified. The novel scoring metric has been proven to be adequate, but can be further improved upon. The evaluation results show that the assessment questions suit the case study target audience; the assessment can be performed within four hours; the organization recognizes itself in the result.
Studies on the Geometrical Design of Spider Webs for Reinforced Composite Structures
Authors: Regassa Yohannes , Lemu Hirpa G. , Sirabizuh Belete , Rahimeto Samuel
Published: February 2021

Spider silk is an astonishingly tough biomaterial that consists almost entirely of large proteins. Studying the secrets behind the high strength nature of spider webs is very challenging due to their miniature size. In spite of their complex nature, researchers have always been inspired to mimic Nature for developing new products or enhancing the performance of existing technologies. Accordingly, the spider web can be taken as a model for optimal fiber orientation for composite materials to be used in critical structural applications. In this study an attempt is made to analyze the geometrical characteristics of the web construction building units such as spirals and radials. As a measurement tool, we have used a developed MATLAB algorithm code for measuring the node to node of rings and radials angle of orientation. Spider web image samples were collected randomly from an ecological niche with black background sample collection tools. The study shows that the radial angle of orientation is 12.7 degrees with 5 mm distance for the spirals’ mesh size. The extracted geometrical numeric values from the spider web show moderately skewed statistical data. The study sheds light on spider web utilization to develop an optimized fiber orientation reinforced composite structure for constructing, for instance, shell structures, pressure vessels and fuselage cones for the aviation industry.