bluuebunny/crossref_metadata_2025 huggingface dataset:
Connection to... Addressing Digital Inequities in Supporting the Well-Being of Young Indigenous Australians in the Wake of COVID-19
Authors: Walker Roz , Usher Kim , Jackson Debra , Reid Corinne , Hopkins Katrina , Shepherd Carrington , Smallwood Reakeeta , Marriott Rhonda
Published: February 2021

(1) Background: This article examines whether connection to digital technologies helps connect young Indigenous people in Australia to culture, community and country to support good mental health and well-being and protect against indirect and potentially long-term effects of COVID-19. (2) Method: We reviewed literature published between February and November 2020 and policy responses related to digital strategies. We searched PubMed, Google Scholar, government policy websites and key Indigenous literature sources, identifying 3460 articles. Of these, 30 articles and 26 policy documents were included and analysed to identify existing and expected mental health outcomes among Indigenous young people associated with COVID-19 and more broadly. (3) Results: There are inequities in affordable access to digital technologies. Only 63% of Indigenous people have access to internet at home. Digital technologies and social media contribute to strong cultural identity, enhance connections to community and country and improve mental health and social and emotional well-being outcomes. (4) Discussion: Access to digital technologies can facilitate healing and cultural continuity, self-determination and empowerment for young people to thrive, not just survive, in the future. (5) Conclusion: More targeted policies and funding is urgently needed to promote digital technologies to enhance Indigenous young people’s access to mental health and well-being services, maintain cultural connections and evaluate the effectiveness of these initiatives using Indigenous well-being indicators.
Mini-Map for Gamers Who Walk and Teleport in a Virtual Stronghold
Authors: Zagata Krzysztof , Gulij Jacek , Halik Łukasz , Medyńska-Gulij Beata
Published: February 2021

Studies of the effectiveness of multimedia cartography products may include mini-map design for navigation. In this study, we have touched upon designing gameplay to indicate the impact of the mini-map on the time effectiveness of a player that can walk or teleport himself/herself along marked out points in virtual topographic space. The eye-tracking examination of gamers’ effectiveness in a non-complex game of collecting coins in a reconstructed stronghold on the holm provided us with a new perspective on the role of mini-maps. The more time gamers took to examine the mini-map, the more time they needed to finish the game, thus decreasing their effectiveness. The teleporting gamers had significantly higher time effectiveness than walking gamers, however, the data obtained showed only a minor difference between the proportions of the mini-map examination time to the total game time for walking and teleportation.
Framework for Indoor Elements Classification via Inductive Learning on Floor Plan Graphs
Authors: Song Jaeyoung , Yu Kiyun
Published: February 2021

This paper presents a new framework to classify floor plan elements and represent them in a vector format. Unlike existing approaches using image-based learning frameworks as the first step to segment the image pixels, we first convert the input floor plan image into vector data and utilize a graph neural network. Our framework consists of three steps. (1) image pre-processing and vectorization of the floor plan image; (2) region adjacency graph conversion; and (3) the graph neural network on converted floor plan graphs. Our approach is able to capture different types of indoor elements including basic elements, such as walls, doors, and symbols, as well as spatial elements, such as rooms and corridors. In addition, the proposed method can also detect element shapes. Experimental results show that our framework can classify indoor elements with an F1 score of 95%, with scale and rotation invariance. Furthermore, we propose a new graph neural network model that takes the distance between nodes into account, which is a valuable feature of spatial network data.
Artificial Neural Network Model Development to Predict Theft Types in Consideration of Environmental Factors
Authors: Kwon Eunseo , Jung Sungwon , Lee Jaewook
Published: February 2021

Crime prediction research using AI has been actively conducted to predict potential crimes—generally, crime locations or time series flows. It is possible to predict these potential crimes in detail if crime characteristics, such as detailed techniques, targets, and environmental factors affecting the crime’s occurrence, are considered simultaneously. Therefore, this study aims to categorize theft by performing k-modes clustering using crime-related characteristics as variables and to propose an ANN model that predicts the derived categorizations. As the prediction of theft types allows people to estimate the features of the possibly most frequent thefts in random areas in advance, it enables the efficient deployment of police and the most appropriate tactical measures. Dongjak District was selected as the target area for analysis; thefts in the district showed four types of clusters. Environmental factors, representative elements affecting theft occurrence, were used as input data for a prediction model, while the factors affecting each cluster were derived through multiple linear regression analysis. Based on the results, input variables were selected for the ANN model training per cluster, and the model was implemented to predict theft type based on environmental factors. This study is significant for providing diversity to prediction methods using ANN.
The Benefits and Hazards of Intravitreal Mesenchymal Stem Cell (MSC) Based-Therapies in the Experimental Ischemic Optic Neuropathy
Authors: Wen Yao-Tseng , Ho Yu-Chieh , Lee Yueh-Chang , Ding Dah-Ching , Liu Pei-Kang , Tsai Rong-Kung
Published: February 2021

Mesenchymal stem cell (MSC) therapy has been investigated intensively for many years. However, there is a potential risk related to MSC applications in various cell niches. Methods: The safety of intravitreal MSC application and the efficacy of MSC-derived conditioned medium (MDCM) were evaluated in the normal eye and the diseased eye, respectively. For safety evaluation, the fundus morphology, visual function, retinal function, and histological changes of the retina were examined. For efficacy evaluation, the MDCM was intravitreally administrated in a rodent model of anterior ischemic optic neuropathy (rAION). The visual function, retinal ganglion cell (RGC) density, and neuroinflammation were evaluated at day 28 post-optic nerve (ON) infarct. Results: The fundus imaging showed that MSC transplantation induced retinal distortion and venous congestion. The visual function, retinal function, and RGC density were significantly decreased in MSC-treated eyes. MSC transplantation induced astrogliosis, microgliosis, and macrophage infiltration in the retina due to an increase in the HLA-DR-positive MSC proportion in vitreous. Treatment with the MDCM preserved the visual function and RGC density in rAION via inhibition of macrophage infiltration and RGC apoptosis. Conclusions: The vitreous induced the HLA-DR expression in the MSCs to cause retinal inflammation and retina injury. However, the MDCM provided the neuroprotective effects in rAION.
Alterations of Gut Microbiota by Overnutrition Impact Gluconeogenic Gene Expression and Insulin Signaling
Authors: He Ling
Published: February 2021

A high-fat, Western-style diet is an important predisposing factor for the onset of type 2 diabetes and obesity. It causes changes in gut microbial profile, reduction of microbial diversity, and the impairment of the intestinal barrier, leading to increased serum lipopolysaccharide (endotoxin) levels. Elevated lipopolysaccharide (LPS) induces acetyltransferase P300 both in the nucleus and cytoplasm of liver hepatocytes through the activation of the IRE1-XBP1 pathway in the endoplasmic reticulum stress. In the nucleus, induced P300 acetylates CRTC2 to increase CRTC2 abundance and drives Foxo1 gene expression, resulting in increased expression of the rate-limiting gluconeogenic gene G6pc and Pck1 and abnormal liver glucose production. Furthermore, abnormal cytoplasm-appearing P300 acetylates IRS1 and IRS2 to disrupt insulin signaling, leading to the prevention of nuclear exclusion and degradation of FOXO1 proteins to further exacerbate the expression of G6pc and Pck1 genes and liver glucose production. Inhibition of P300 acetyltransferase activity by chemical inhibitors improved insulin signaling and alleviated hyperglycemia in obese mice. Thus, P300 acetyltransferase activity appears to be a therapeutic target for the treatment of type 2 diabetes and obesity.
Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space
Authors: Wise Petra M. , Neviani Paolo , Riwaldt Stefan , Corydon Thomas Juhl , Wehland Markus , Braun Markus , Krüger Marcus , Infanger Manfred , Grimm Daniela
Published: February 2021

Space travel has always been the man’s ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in cell growth, gene, and protein expression have been described in different models on Earth and in space. Extracellular vesicles, and in particular exosomes, are important cell-cell communicators, being secreted from almost all the cells and therefore, are a perfect target to further investigate the underlying reasons of the organism’s adaptations to microgravity. Here, we studied supernatants harvested from the CellBox-1 experiment, which featured human thyroid cancer cells flown to the International Space Station during the SpaceX CRS-3 cargo mission. The initial results show differences in the number of secreted exosomes, as well as in the distribution of subpopulations in regards to their surface protein expression. Notably, alteration of their population regarding the tetraspanin surface expression was observed. This is a promising step into a new area of microgravity research and will potentially lead to the discovery of new biomarkers and pathways of cellular cross-talk.
mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target
Authors: Babicheva Aleksandra , Makino Ayako , Yuan Jason X.-J.
Published: February 2021

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease without a cure. The exact pathogenic mechanisms of PAH are complex and poorly understood, yet a number of abnormally expressed genes and regulatory pathways contribute to sustained vasoconstriction and vascular remodeling of the distal pulmonary arteries. Mammalian target of rapamycin (mTOR) is one of the major signaling pathways implicated in regulating cell proliferation, migration, differentiation, and protein synthesis. Here we will describe the canonical mTOR pathway, structural and functional differences between mTOR complexes 1 and 2, as well as the crosstalk with other important signaling cascades in the development of PAH. The pathogenic role of mTOR in pulmonary vascular remodeling and sustained vasoconstriction due to its contribution to proliferation, migration, phenotypic transition, and gene regulation in pulmonary artery smooth muscle and endothelial cells will be discussed. Despite the progress in our elucidation of the etiology and pathogenesis of PAH over the two last decades, there is a lack of effective therapeutic agents to treat PAH patients representing a significant unmet clinical need. In this review, we will explore the possibility and therapeutic potential to use inhibitors of mTOR signaling cascade to treat PAH.
Approaches to Targeting Bacterial Biofilms in Cystic Fibrosis Airways
Authors: Martin Isaac , Waters Valerie , Grasemann Hartmut
Published: February 2021

The treatment of lung infection in the context of cystic fibrosis (CF) is limited by a biofilm mode of growth of pathogenic organisms. When compared to planktonically grown bacteria, bacterial biofilms can survive extremely high levels of antimicrobials. Within the lung, bacterial biofilms are aggregates of microorganisms suspended in a matrix of self-secreted proteins within the sputum. These structures offer both physical protection from antibiotics as well as a heterogeneous population of metabolically and phenotypically distinct bacteria. The bacteria themselves and the components of the extracellular matrix, in addition to the signaling pathways that direct their behaviour, are all potential targets for therapeutic intervention discussed in this review. This review touches on the successes and failures of current anti-biofilm strategies, before looking at emerging therapies and the mechanisms by which it is hoped they will overcome current limitations.
The Endothelial Glycocalyx as a Target of Ischemia and Reperfusion Injury in Kidney Transplantation—Where Have We Gone So Far?
Authors: Duni Anila , Liakopoulos Vassilios , Koutlas Vasileios , Pappas Charalampos , Mitsis Michalis , Dounousi Evangelia
Published: February 2021

The damage of the endothelial glycocalyx as a consequence of ischemia and/or reperfusion injury (IRI) following kidney transplantation has come at the spotlight of research due to potential associations with delayed graft function, acute rejection as well as long-term allograft dysfunction. The disintegration of the endothelial glycocalyx induced by IRI is the crucial event which exposes the denuded endothelial cells to further inflammatory and oxidative damage. The aim of our review is to present the currently available data regarding complex links between shedding of the glycocalyx components, like syndecan-1, hyaluronan, heparan sulphate, and CD44 with the activation of intricate immune system responses, including toll-like receptors, cytokines and pro-inflammatory transcription factors. Evidence on modes of protection of the endothelial glycocalyx and subsequently maintenance of endothelial permeability as well as novel nephroprotective molecules such as sphingosine-1 phosphate (S1P), are also depicted. Although advances in technology are making the visualization and the analysis of the endothelial glycocalyx possible, currently available evidence is mostly experimental. Ongoing progress in understanding the complex impact of IRI on the endothelial glycocalyx, opens up a new era of research in the field of organ transplantation and clinical studies are of utmost importance for the future.
Permissive Modulation of Sphingosine-1-Phosphate-Enhanced Intracellular Calcium on BKCa Channel of Chromaffin Cells
Authors: Wu Adonis Z. , Ohn Tzu-Lun , Shei Ren-Jay , Wu Huei-Fang , Chen Yong-Cyuan , Lee Hsiang-Chun , Dai Dao-Fu , Wu Sheng-Nan
Published: February 2021

Sphingosine-1-phosphate (S1P), is a signaling sphingolipid which acts as a bioactive lipid mediator. We assessed whether S1P had multiplex effects in regulating the large-conductance Ca2+-activated K+ channel (BKCa) in catecholamine-secreting chromaffin cells. Using multiple patch-clamp modes, Ca2+ imaging, and computational modeling, we evaluated the effects of S1P on the Ca2+-activated K+ currents (IK(Ca)) in bovine adrenal chromaffin cells and in a pheochromocytoma cell line (PC12). In outside-out patches, the open probability of BKCa channel was reduced with a mean-closed time increment, but without a conductance change in response to a low-concentration S1P (1 µM). The intracellular Ca2+ concentration (Cai) was elevated in response to a high-dose (10 µM) but not low-dose of S1P. The single-channel activity of BKCa was also enhanced by S1P (10 µM) in the cell-attached recording of chromaffin cells. In the whole-cell voltage-clamp, a low-dose S1P (1 µM) suppressed IK(Ca), whereas a high-dose S1P (10 µM) produced a biphasic response in the amplitude of IK(Ca), i.e., an initial decrease followed by a sustained increase. The S1P-induced IK(Ca) enhancement was abolished by BAPTA. Current-clamp studies showed that S1P (1 µM) increased the action potential (AP) firing. Simulation data revealed that the decreased BKCa conductance leads to increased AP firings in a modeling chromaffin cell. Over a similar dosage range, S1P (1 µM) inhibited IK(Ca) and the permissive role of S1P on the BKCa activity was also effectively observed in the PC12 cell system. The S1P-mediated IK(Ca) stimulation may result from the elevated Cai, whereas the inhibition of BKCa activity by S1P appears to be direct. By the differentiated tailoring BKCa channel function, S1P can modulate stimulus-secretion coupling in chromaffin cells.
VEGF-Independent Activation of Müller Cells by the Vitreous from Proliferative Diabetic Retinopathy Patients
Authors: Rezzola Sara , Guerra Jessica , Krishna Chandran Adwaid Manu , Loda Alessandra , Cancarini Anna , Sacristani Piergiuseppe , Semeraro Francesco , Presta Marco
Published: February 2021

Proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus, results from an inflammation-sustained interplay among endothelial cells, neurons, and glia. Even though anti-vascular endothelial growth factor (VEGF) interventions represent the therapeutic option for PDR, they are only partially efficacious. In PDR, Müller cells undergo reactive gliosis, produce inflammatory cytokines/chemokines, and contribute to scar formation and retinal neovascularization. However, the impact of anti-VEGF interventions on Müller cell activation has not been fully elucidated. Here, we show that treatment of MIO-M1 Müller cells with vitreous obtained from PDR patients stimulates cell proliferation and motility, and activates various intracellular signaling pathways. This leads to cytokine/chemokine upregulation, a response that was not mimicked by treatment with recombinant VEGF nor inhibited by the anti-VEGF drug ranibizumab. In contrast, fibroblast growth factor-2 (FGF2) induced a significant overexpression of various cytokines/chemokines in MIO-M1 cells. In addition, the FGF receptor tyrosine kinase inhibitor BGJ398, the pan-FGF trap NSC12, the heparin-binding protein antagonist N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe Boc2, and the anti-inflammatory hydrocortisone all inhibited Müller cell activation mediated by PDR vitreous. These findings point to a role for various modulators beside VEGF in Müller cell activation and pave the way to the search for novel therapeutic strategies in PDR.
CD28 Gene Polymorphisms in the Promoter Region Are Associated with Transfusion Reactions: A Functional Study
Authors: Wen Ying-Hao , Lin Wei-Tzu , Wang Wei-Ting , Chen Ding-Ping
Published: February 2021

Transfusion reactions are mainly induced by the interaction of an antigen and antibody. However, transfusion reactions still occur with the implementing of crossmatching and usage of pre-storage leukoreduced blood products. The roles of CD28 and CTLA4 gene polymorphisms in transfusion reaction have been shown, and subjects with certain single nucleotide polymorphisms (SNPs) of the CD28 or CTLA4 gene had a significantly higher risk of transfusion reactions. In total, 40 patients with transfusion reactions after receiving pre-storage leukoreduced blood products were enrolled in this study. We focused on the SNPs located in the CD28 promoter region (rs1879877, rs3181096, rs3181097, and rs3181098) to find out the significant SNP. A luciferase reporter assay was used to investigate the expression level of protein affected by promoter SNP variation. We found that the polymorphism of rs3181097 was associated with transfusion reactions (p = 0.003 in additive model and p = 0.015 in dominant model). Consequently, we investigated the biological function in the CD28 promoter polymorphisms (rs1879877 G > T, rs3181096 C > T, rs3181097 G > A, and rs3181098 G > A) by using dual-spectral luciferase reporter assay. The results showed that the ex-pression level of CD28 was decreased under the effect of rs3181097 with A-allele. This suggested that rs3181097 may regulate immune response through decreasing CD28 protein expression and then lead to development of transfusion reactions.
Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease
Authors: Kaur Kawaljit , Vaziri Shahram , Romero-Reyes Marcela , Paranjpe Avina , Jewett Anahid
Published: February 2021

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.
Relationship between Tooth Loss and the Medications Used for the Treatment of Rheumatoid Arthritis in Japanese Patients with Rheumatoid Arthritis: A Cross-Sectional Study
Authors: Hashimoto Hiroko , Hashimoto Shimpei , Shimazaki Yoshihiro
Published: February 2021

Background: There is limited information regarding the association between tooth loss and the medications used for the treatment of rheumatoid arthritis (RA). Here, we examined the association between tooth loss, disease severity, and drug treatment regimens in RA patients. Method: This study recruited 94 Japanese patients with RA. The severity of RA was assessed using the Steinbrocker classification of class and stage. Data on RA medications were obtained from medical records. We examined the associations between tooth loss, RA severity, and drug treatment regi mens using multinomial logistic regression analyses. Results: Patients with 1–19 teeth had significantly higher odds ratios (ORs) of taking methotrexate (MTX) (OR, 8.74; 95% confidence interval (CI), 1.11–68.8) and biologic disease-modifying antirheumatic drugs (bDMARDs) (OR, 21.0; 95% CI, 1.3–339.1) compared to those with 27–28 teeth when adjusted for RA severity (class). Furthermore, patients with 1–19 teeth had significantly higher ORs of taking MTX (OR, 9.71; 95% CI, 1.22–77.1) and bDMARDs (OR, 50.2; 95% CI, 2.55–990.6) compared to those with 27–28 teeth when adjusted for RA severity (stage). Conclusion: RA patients with fewer teeth were more likely to take stronger RA therapies, independent of RA severity and other factors.
Thrombocytopenia in Virus Infections
Authors: Raadsen Matthijs , Du Toit Justin , Langerak Thomas , van Bussel Bas , van Gorp Eric , Goeijenbier Marco
Published: February 2021

Thrombocytopenia, which signifies a low platelet count usually below 150 × 109/L, is a common finding following or during many viral infections. In clinical medicine, mild thrombocytopenia, combined with lymphopenia in a patient with signs and symptoms of an infectious disease, raises the suspicion of a viral infection. This phenomenon is classically attributed to platelet consumption due to inflammation-induced coagulation, sequestration from the circulation by phagocytosis and hypersplenism, and impaired platelet production due to defective megakaryopoiesis or cytokine-induced myelosuppression. All these mechanisms, while plausible and supported by substantial evidence, regard platelets as passive bystanders during viral infection. However, platelets are increasingly recognized as active players in the (antiviral) immune response and have been shown to interact with cells of the innate and adaptive immune system as well as directly with viruses. These findings can be of interest both for understanding the pathogenesis of viral infectious diseases and predicting outcome. In this review, we will summarize and discuss the literature currently available on various mechanisms within the relationship between thrombocytopenia and virus infections.
Prognostic Significance of Survivin Expression in Patients with Ovarian Carcinoma: A Meta-Analysis
Authors: Gąsowska-Bajger Beata , Gąsowska-Bodnar Agnieszka , Knapp Paweł , Bodnar Lubomir
Published: February 2021

Background: Survivin belongs to the protein family of inhibitors of apoptosis (IAP) and is a regulator of the cell cycle and apoptosis. The aim of this study was to assess the clinical and prognostic significance of expression survivin in patients with ovarian cancer. Methods: We systematically searched for articles in PubMed, the American Chemical Society (Publications), Medline, the Royal Society of Chemistry, Scopus and the Web of Science. Patient clinical data, overall survival (OS), disease-free survival (DFS), and survivin expression were extracted from individual studies. We performed statistical analysis using the STATA 16 package. Eighteen publications containing data from 2233 patients with ovarian cancer were included in this meta-analysis. Results: We found an adverse effect of survivin expression on OS (risk ratio (HR): 1.60; 95% confidence interval (CI): 1.33–1.93, p = 0.00) but this was not observed on DFS (HR: 1.06; 95% CI: 0.55–2.05, p = 0.87). The analysis of clinicopathological parameters showed that survivin expression was associated with the histological grades (G1–2 vs. G3) (odds ratio (OR) = 0.53, 95% CI: 0.34–0.83, p = 0.01) and: International Federation Gynecology and Obstetrics (FIGO) stage (I–II vs. III–IV) (OR = 0.22, 95% CI: 0.09–0.55, p = 0.00), but it was not significantly correlated with the histological subtype (OR = 1.14, 95% CI: 0.83–1.58, p = 0.42). Conclusions: Our meta-analysis suggests that survivin expression may be a marker of poor prognosis in ovarian cancer. Survivin expression was associated with parameters of greater aggressiveness of ovarian cancer. Prospective studies are needed to confirm our results indicating that survivin expression can be used as an ovarian cancer biomarker.
Pearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist
Authors: Katz Jason B. , Owusu Kent , Nussbaum Ilisa , Beekman Rachel , DeFilippo Nicholas A. , Gilmore Emily J. , Hirsch Lawrence J. , Cervenka Mackenzie C. , Maciel Carolina B.
Published: February 2021

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe our experience, including the challenges of achieving and maintaining ketosis, in an adult with new onset refractory status epilepticus (NORSE). Case Vignette: A previously healthy 29-year-old woman was admitted with cryptogenic NORSE following a febrile illness; course was complicated by prolonged super-refractory SE. A comprehensive work-up was notable only for mild cerebral spinal fluid (CSF) pleocytosis, elevated nonspecific serum inflammatory markers, and edematous hippocampi with associated diffusion restriction on magnetic resonance imaging (MRI). Repeat CSF testing was normal and serial MRIs demonstrated resolution of edema and diffusion restriction with progressive hippocampal and diffuse atrophy. She required prolonged therapeutic coma with high anesthetic infusion rates, 16 antiseizure drug (ASD) trials, empiric immunosuppression and partial bilateral oophorectomy. Enteral ketogenic formula was started on hospital day 28. However, sustained beta-hydroxybutyrate levels >2 mmol/L were only achieved 37 days later following a comprehensive adjustment of the care plan. KD was challenging to maintain in the intensive care unit (ICU) and was discontinued due to poor nutritional state and pressure ulcers. KD was restarted again in a non-ICU unit facilitating ASD tapering without re-emergence of SE. Discussion: There are inconspicuous carbohydrates in commonly administered medications for SE including antibiotics, electrolyte repletion formulations, different preparations of the same drug (i.e., parenteral, tablet, or suspension) and even solutions used for oral care―all challenging the use of KD in the hospitalized patient. Tailoring comprehensive care and awareness of possible complications of KD are important for the successful implementation and maintenance of ketosis.
Pharmacological Management of Neurogenic Bowel Dysfunction after Spinal Cord Injury and Multiple Sclerosis: A Systematic Review and Clinical Implications
Authors: Johns Jeffery S , Krogh Klaus , Ethans Karen , Chi Joanne , Querée Matthew , Eng Janice J ,   Spinal Cord Injury Research Evidence Team
Published: February 2021

Neurogenic bowel dysfunction (NBD) is a common problem for people with spinal cord injury (SCI) and multiple sclerosis (MS), which seriously impacts quality of life. Pharmacological management is an important component of conservative bowel management. The objective of this study was to first assemble a list of pharmacological agents (medications and medicated suppositories) used in current practice. Second, we systematically examined the current literature on pharmacological agents to manage neurogenic bowel dysfunction of individuals specifically with SCI or MS. We searched Medline, EMBASE and CINAHL databases up to June 2020. We used the GRADE System to provide a systematic approach for evaluating the evidence. Twenty-eight studies were included in the review. We found a stark discrepancy between the large number of agents currently prescribed and a very limited amount of literature. While there was a small amount of literature in SCI, there was little to no literature available for MS. There was low-quality evidence supporting rectal medications, which are a key component of conservative bowel care in SCI. Based on the findings of the literature and the clinical experience of the authors, we have provided clinical insights on proposed treatments and medications in the form of three case study examples on patients with SCI or MS.
RETRACTED: De Vecchis et al. Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea. J. Clin. Med. 2016, 5, 85
Authors: De Vecchis Renato , Baldi Cesare , Ariano Carmelina ,   JCM Editorial Office
Published: February 2021

The journal retracts the article “Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea” by De Vecchis, R [...]
Importance of Preoperative Screening Strategies for Coronavirus Disease 2019 in Patients Undergoing Cesarean Sections: A Retrospective, Large Single-Center, Observational Cohort Study
Authors: Kim Ha-Jung , Cho Hyun-Seok , Lee Mi-Young , Kim Hyungtae , Choi Woo-Jong , Won Hye-Sung , Ro Young-Jin , Choi In-Cheol
Published: February 2021

During the coronavirus disease 2019 (COVID-19) pandemic, many guidelines have recommended postponing non-emergency operations. However, cesarean sections cannot be indefinitely delayed. Our institution has established a COVID-19 screening strategy for patients undergoing cesarean section. We evaluated the usefulness of this screening strategy. Parturients undergoing cesarean section at our center during the first peak of the COVID-19 outbreak were retrospectively analyzed. Each parturient underwent a questionnaire survey evaluating epidemiological correlation and symptoms at admission. Reverse transcriptase–polymerase chain reaction (RT–PCR) testing and/or chest radiography were performed. In total, 296 parturients underwent cesarean section. All elective and 37 emergency cesarean sections were performed in general operating rooms because they were considered to have a low risk of COVID-19 infection through the screening process. However, 42 emergency cases were performed in negative-pressure operating rooms with full personal protective equipment (PPE) because the RT–PCR results could not be confirmed in a timely manner. None of them were positive for RT–PCR, and there were no cases of nosocomial infection. A comprehensive preoperative screening strategy, including symptomatic and epidemiological correlation, PCR, and/or imaging test, should be performed in patients undergoing cesarian section. Further, cesarean sections in parturients with unconfirmed COVID-19 status should be performed in a negative-pressure operating room with appropriate PPE.
Lipid-Lowering Therapy in Patients with Coronary Heart Disease and Prior Stroke: Mission Impossible?
Authors: Temporelli Pier Luigi , Arca Marcello , D’Erasmo Laura , De Caterina Raffaele
Published: February 2021

Hyperlipidemia is a powerful risk factor for coronary heart disease (CHD). It has been known for a long time that lipid-lowering drugs significantly reduce morbidity from CHD, thus proving a causal role for cholesterol in coronary events. Conversely, the relationship between low-density lipoprotein cholesterol (LDL-C) levels and stroke has been less clear and debated for many years. Recent data conclusively demonstrate not only the inverse epidemiological relationship of blood LDL-C with stroke, but also the efficacy of different strategies to attain cholesterol-lowering on stroke. They also dissipate lingering doubts about the possibility that lipid-lowering is linked to an increase in hemorrhagic stroke. However, despite current international lipid guidelines now strongly recommend aggressive lipid-lowering therapy in patients with atherosclerotic cardiovascular disease, including CHD and cerebrovascular disease (CeVD), secondary prevention patients are often undertreated with lipid-lowering therapies in routine clinical practice. This review highlights that patients with CHD and concomitant CeVD do not receive aggressive lipid-lowering therapy despite being at very high risk and with clear evidence of benefit from lowering LDL-C levels below current targets.
Epidermal Barrier Function and Skin Homeostasis in Skin with Permanent and Adhesive Tattoos: A Cross-Sectional Study
Authors: Serrano-Serra Jose-Pablo , Montero-Vilchez Trinidad , Buendia-Eisman Agustin , Arias-Santiago Salvador
Published: February 2021

Tattoos are a current trend, but their impact on skin homeostasis and epidermal barrier function is not well known. So, the aims of this study are (1) to investigate epidermal barrier function and skin homeostasis in skin with permanent tattoos, adhesive temporary tattoos and non-tattooed skin, and (2) to analyze the effect of petrolatum on skin with permanent and adhesive tattoos. In total, 67 tattoos were enrolled (34 permanent tattoos and 33 adhesive tattoos). Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), erythema and total antioxidant capacity (TAC) were measured in skin with permanent tattoos, adhesive tattoos and non-tattooed skin before and after petrolatum application. The temperature was lower (30.47 °C vs. 31.01 °C; p = 0.001) on skin with permanent tattoos than non-tattooed skin, while SCH (48.24 Arbitrary Units (AU) vs. 44.15 AU; p = 0.008) was higher. Skin with adhesive tattoos showed lower temperature, SCH (21.19 AU vs. 41.31 AU; p < 0.001) and TAC (1.27 microcoulombs (uC) vs. 3.48 uC; p < 0.001), and higher TEWL (8.65 g/h/m2 vs. 6.99 g/h/m2; p = 0.003), than non-tattooed skin. After petrolatum application, the temperature decreased on skin with permanent tattoos, and TEWL and SCH decreased on skin with adhesive tattoos. Adhesive tattoos may affect skin barrier function, while permanent tattoos may have a lower impact. Tattooed and non-tattooed skin responds in different ways to moisturizers.
Circulating Free DNA and Its Emerging Role in Autoimmune Diseases
Authors: Mondelo-Macía Patricia , Castro-Santos Patricia , Castillo-García Adrián , Muinelo-Romay Laura , Diaz-Peña Roberto
Published: February 2021

Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid biopsy, we found clinical application in nontumour pathologies, including autoimmune diseases. Since the discovery of the presence of high levels of cfDNA in patients with systemic lupus erythaematosus (SLE) in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and its association with disease activity. However, with technological advancements and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity, interest in cfDNA and autoimmune diseases has not expanded until recently. In this review, we provide an overview of the basic biology of cfDNA in the context of autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response. We discuss and integrate available information about these important aspects.
Immediate Prosthetic Breast Reconstruction after Nipple-Sparing Mastectomy: Traditional Subpectoral Technique versus Direct-to-Implant Prepectoral Reconstruction without Acellular Dermal Matrix
Authors: Franceschini Gianluca , Scardina Lorenzo , Di Leone Alba , Terribile Daniela Andreina , Sanchez Alejandro Martin , Magno Stefano , D’Archi Sabatino , Franco Antonio , Mason Elena Jane , Carnassale Beatrice , Murando Federica , Orlandi Armando , Barone Adesi Liliana , Visconti Giuseppe , Salgarello Marzia , Masetti Riccardo
Published: February 2021

Background: The aim of this study was to compare outcomes of immediate prosthetic breast reconstruction (IPBR) using traditional submuscular (SM) positioning of implants versus prepectoral (PP) positioning of micropolyurethane-foam-coated implants (microthane) without further coverage. Methods: We retrospectively reviewed the medical records of breast cancer patients treated by nipple-sparing mastectomy (NSM) and IPBR in our institution during the two-year period from January 2018 to December 2019. Patients were divided into two groups based on the plane of implant placement: SM versus PP. Results: 177 patients who received IPBR after NSM were included in the study; implants were positioned in a SM plane in 95 patients and in a PP plane in 82 patients. The two cohorts were similar for mean age (44 years and 47 years in the SM and PP groups, respectively) and follow-up (20 months and 16 months, respectively). The mean operative time was 70 min shorter in the PP group. No significant differences were observed in length of hospital stay or overall major complication rates. Statistically significant advantages were observed in the PP group in terms of aesthetic results, chronic pain, shoulder dysfunction, and skin sensibility (p < 0.05), as well as a trend of better outcomes for sports activity and sexual/relationship life. Cost analysis revealed that PP-IPBR was also economically advantageous over SM-IPBR. Conclusions: Our preliminary experience seems to confirm that PP positioning of a polyurethane-coated implant is a safe, reliable and effective method to perform IPBR after NSM.
Disturbance of Mitochondrial Dynamics and Mitochondrial Therapies in Atherosclerosis
Authors: Markin Alexander M. , Khotina Viktoria A. , Zabudskaya Xenia G. , Bogatyreva Anastasia I. , Starodubova Antonina V. , Ivanova Ekaterina , Nikiforov Nikita G. , Orekhov Alexander N.
Published: February 2021

Mitochondrial dysfunction is associated with a wide range of chronic human disorders, including atherosclerosis and diabetes mellitus. Mitochondria are dynamic organelles that undergo constant turnover in living cells. Through the processes of mitochondrial fission and fusion, a functional population of mitochondria is maintained, that responds to the energy needs of the cell. Damaged or excessive mitochondria are degraded by mitophagy, a specialized type of autophagy. These processes are orchestrated by a number of proteins and genes, and are tightly regulated. When one or several of these processes are affected, it can lead to the accumulation of dysfunctional mitochondria, deficient energy production, increased oxidative stress and cell death—features that are described in many human disorders. While severe mitochondrial dysfunction is known to cause specific and mitochondrial disorders in humans, progressing damage of the mitochondria is also observed in a wide range of other chronic diseases, including cancer and atherosclerosis, and appears to play an important role in disease development. Therefore, correction of mitochondrial dynamics can help in developing new therapies for the treatment of these conditions. In this review, we summarize the recent knowledge on the processes of mitochondrial turnover and the proteins and genes involved in it. We provide a list of known mutations that affect mitochondrial function, and discuss the emerging therapeutic approaches.
Status of Nutrition in Hemodialysis Patients Survey (SNIPS): Nutrition Intake in Obese and Overweight vs. Healthy Weight Patients
Authors: Boaz Mona , Kaufman-Shriqui Vered , Azoulay Odile , Weinstein Talia
Published: February 2021

Elevated body mass index (BMI) has been associated with improved survival and fewer hospitalizations in hemodialysis patients; however, it is not clear that dietary intake is associated with increased BMI in hemodialysis patients. The present analysis was designed to compare energy and macronutrient intake and distribution, as well as compliance with the International Society of Renal Nutrition and Metabolism (ISRNM) dietary guidelines, by body weight status (overweight/obese vs. normal weight) in hemodialysis patients. The status of nutrition in hemodialysis patients survey (SNIPS) cohort is a cross-sectional study including a representative sample of individuals on hemodialysis treated in hospital dialysis centers throughout Israel. Of the 375 patients eligible for the current analysis, 60.1% had BMI ≥ 25 kg/m2 (overweight/obese). For each participant, the following measures were recorded: dietary intake, blood biochemistry, anthropometric and hemodynamic measures. These were compared by body weight status. Compared to their normal-weight counterparts, overweight/obese hemodialysis patients did not differ by energy and macronutrient intake, distribution of these nutrients in the diet. Regardless of body weight status, hemodialysis patients have poor compliance with ISRNM dietary guidelines.
Post-Infectious Guillain–Barré Syndrome Related to SARS-CoV-2 Infection: A Systematic Review
Authors: Sansone Pasquale , Giaccari Luca Gregorio , Aurilio Caterina , Coppolino Francesco , Esposito Valentina , Fiore Marco , Paladini Antonella , Passavanti Maria Beatrice , Pota Vincenzo , Pace Maria Caterina
Published: February 2021

Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to give a comprehensive overview of the demographic characteristics, clinical features, diagnostic investigations, and outcome of SARS-CoV-2-related GBS patients. Methods. Embase, MEDLINE, Google Scholar, and Cochrane Central Trials Register were systematically searched on 24 September 2020 for studies reporting on GBS secondary to COVID-19. Results. We identified 63 articles; we included 32 studies in our review. A total of 41 GBS cases with a confirmed or probable COVID-19 infection were reported: 26 of them were single case reports and 6 case series. Published studies on SARS-CoV-2-related GBS typically report a classic sensorimotor type of GBS often with a demyelinating electrophysiological subtype. Miller Fisher syndrome was reported in a quarter of the cases. In 78.1% of the cases, the response to immunomodulating therapy is favourable. The disease course is frequently severe and about one-third of the patients with SARS-CoV-2-associated GBS requires mechanical ventilation and Intensive Care Unit (ICU) admission. Rarely the outcome is poor or even fatal (10.8% of the cases). Conclusion. Clinical presentation, course, response to treatment, and outcome are similar in SARS-CoV-2-associated GBS and GBS due to other triggers.
RNase A Domain-Swapped Dimers Produced Through Different Methods: Structure–Catalytic Properties and Antitumor Activity
Authors: Montioli Riccardo , Campagnari Rachele , Fasoli Sabrina , Fagagnini Andrea , Caloiu Andra , Smania Marcello , Menegazzi Marta , Gotte Giovanni
Published: February 2021

Upon oligomerization, RNase A can acquire important properties, such as cytotoxicity against leukemic cells. When lyophilized from 40% acetic acid solutions, the enzyme self-associates through the so-called three-dimensional domain swapping (3D-DS) mechanism involving both N- and/or C-terminals. The same species are formed if the enzyme is subjected to thermal incubation in various solvents, especially in 40% ethanol. We evaluated here if significant structural modifications might occur in RNase A N- or C-swapped dimers and/or in the residual monomer(s), as a function of the oligomerization protocol applied. We detected that the monomer activity vs. ss-RNA was partly affected by both protocols, although the protein does not suffer spectroscopic alterations. Instead, the two N-swapped dimers showed differences in the fluorescence emission spectra but almost identical enzymatic activities, while the C-swapped dimers displayed slightly different activities vs. both ss- or ds-RNA substrates together with not negligible fluorescence emission alterations within each other. Besides these results, we also discuss the reasons justifying the different relative enzymatic activities displayed by the N-dimers and C-dimers. Last, similarly with data previously registered in a mouse model, we found that both dimeric species significantly decrease human melanoma A375 cell viability, while only N-dimers reduce human melanoma MeWo cell growth.
Protolytic Equilibria in Organized Solutions: Ionization and Tautomerism of Fluorescein Dyes and Related Indicators in Cetyltrimethylammonium Chloride Micellar Solutions at High Ionic Strength of the Bulk Phase
Authors: Mchedlov-Petrossyan Nikolay O. , Vodolazkaya Natalya A.
Published: February 2021

Ionic equilibrium of 22 hydroxyxanthenes, including halogen and nitro derivatives of fluorescein, and their thio- and aza analogues, were studied spectrophotometrically in micellar solutions of cetyltrimethylammonium chloride at ionic strength of the bulk phase 4.0 M KCl. This micellar pseudophase is characterized by the electrostatic surface potential of +(15–16) mV and the ETN value of 0.623. In the case of dyes bearing the COOH group, colorless lactone is the predominant tautomer of the molecular form H2R. A new classification of fluoresceins is developed. The dyes were divided into four groups based on the nature of tautomerism of the anions. In the case of the fluorescein type, the monoanions HR− exist predominantly as “carboxylate” tautomers, with ionized carboxylic and non–ionized hydroxylic group. For the dyes of the eosin type, the situation is opposite, while for the intervening type of compounds, the concentrations of the two tautomers are comparable. Dyes capable of forming lactone anions HR− were classified as the fourth type. For some of them, even the dianion R2− exists as a lactone. The relationship between the stepwise ionization constants, Ka1/Ka2, varies from 1.3 to 1.07 × 105 and is determined by the state of tautomeric equilibrium of molecules and ions.