bluuebunny/crossref_metadata_2025 huggingface dataset:
MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System
Authors: Teuber-Hanselmann Sarah , Worm Karl , Macha Nicole , Junker Andreas
Published: April 2021

Quantifying O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation plays an essential role in assessing the potential efficacy of alkylating agents in the chemotherapy of malignant gliomas. MGMT promoter methylation is considered to be a characteristic of subgroups of certain malignancies but has also been described in various peripheral inflammatory diseases. However, MGMT promoter methylation levels have not yet been investigated in non-neoplastic brain diseases. This study demonstrates for the first time that one can indeed detect slightly enhanced MGMT promoter methylation in individual cases of inflammatory demyelinating CNS diseases such as multiple sclerosis and progressive multifocal leucencephalopathy (PML), as well as in other demyelinating diseases such as central pontine and exptrapontine myelinolysis, and diseases with myelin damage such as Wallerian degeneration. In this context, we identified a reduction in the expression of the demethylase TET1 as a possible cause for the enhanced MGMT promoter methylation. Hence, we show for the first time that MGMT hypermethylation occurs in chronic diseases that are not strictly associated to distinct pathogens, oncogenic viruses or neoplasms but that lead to damage of the myelin sheath in various ways. While this gives new insights into epigenetic and pathophysiological processes involved in de- and remyelination, which might offer new therapeutic opportunities for demyelinating diseases in the future, it also reduces the specificity of MGMT hypermethylation as a tumor biomarker.
Effects of Human and Porcine Adipose Extracellular Matrices Decellularized by Enzymatic or Chemical Methods on Macrophage Polarization and Immunocompetence
Authors: Cicuéndez Mónica , Casarrubios Laura , Feito María José , Madarieta Iratxe , Garcia-Urkia Nerea , Murua Olatz , Olalde Beatriz , Briz Nerea , Diez-Orejas Rosalía , Portolés María Teresa
Published: April 2021

The decellularized extracellular matrix (ECM) obtained from human and porcine adipose tissue (AT) is currently used to prepare regenerative medicine bio-scaffolds. However, the influence of these natural biomaterials on host immune response is not yet deeply understood. Since macrophages play a key role in the inflammation/healing processes due to their high functional plasticity between M1 and M2 phenotypes, the evaluation of their response to decellularized ECM is mandatory. It is also necessary to analyze the immunocompetence of macrophages after contact with decellularized ECM materials to assess their functional role in a possible infection scenario. In this work, we studied the effect of four decellularized adipose matrices (DAMs) obtained from human and porcine AT by enzymatic or chemical methods on macrophage phenotypes and fungal phagocytosis. First, a thorough biochemical characterization of these biomaterials by quantification of remnant DNA, lipids, and proteins was performed, thus indicating the efficiency and reliability of both methods. The proteomic analysis evidenced that some proteins are differentially preserved depending on both the AT origin and the decellularization method employed. After exposure to the four DAMs, specific markers of M1 proinflammatory and M2 anti-inflammatory macrophages were analyzed. Porcine DAMs favor the M2 phenotype, independently of the decellularization method employed. Finally, a sensitive fungal phagocytosis assay allowed us to relate the macrophage phagocytosis capability with specific proteins differentially preserved in certain DAMs. The results obtained in this study highlight the close relationship between the ECM biochemical composition and the macrophage’s functional role.
Structure Driven Prediction of Chromatographic Retention Times: Applications to Pharmaceutical Analysis
Authors: Szucs Roman , Brown Roland , Brunelli Claudio , Heaton James C. , Hradski Jasna
Published: April 2021

Pharmaceutical drug development relies heavily on the use of Reversed-Phase Liquid Chromatography methods. These methods are used to characterize active pharmaceutical ingredients and drug products by separating the main component from related substances such as process related impurities or main component degradation products. The results presented here indicate that retention models based on Quantitative Structure Retention Relationships can be used for de-risking methods used in pharmaceutical analysis and for the identification of optimal conditions for separation of known sample constituents from postulated/hypothetical components. The prediction of retention times for hypothetical components in established methods is highly valuable as these compounds are not usually readily available for analysis. Here we discuss the development and optimization of retention models, selection of the most relevant structural molecular descriptors, regression model building and validation. We also present a practical example applied to chromatographic method development and discuss the accuracy of these models on selection of optimal separation parameters.
Mechanisms Contributing to the Dysregulation of miRNA-124 in Pulmonary Hypertension
Authors: Zhang Hui , Laux Aya , Stenmark Kurt R. , Hu Cheng-Jun
Published: April 2021

Chronic pulmonary hypertension (PH) is a fatal disease characterized by the persistent activation of pulmonary vascular cells that exhibit aberrant expression of genes including miRNAs. We and others reported that decreased levels of mature microRNA-124 (miR-124) plays an important role in modulating the activated phenotype of pulmonary vascular cells and HDAC inhibitors (HDACi) can restore the levels of mature miR-124 and reverse the persistently activated phenotype of PH vascular cells. In this study, we sought to determine the mechanisms contributing to reduced levels of miRNAs, as well as how HDACi restores the levels of reduced miRNA in PH vascular cells. We found that pulmonary artery fibroblasts isolated from IPAH patients (PH-Fibs) exhibit reduced levels of mature miR-124 and several other miRNAs including let-7i, miR-224, and miR-210, and that these reduced levels can be restored by HDACi. Using miR-124 expression in human PH-Fibs as a model, we determined that reduced miR-124 gene transcription, not decreased expression of miRNA processing genes, is responsible for reduced levels of mature miR-124 in human PH-Fibs. Using both DNase I Sensitivity and chromatin immunoprecipitation assays, we found that the miR-124-1 gene exhibits a more condensed chromatin structure in human PH-Fibs, compared to corresponding controls. HDACi relaxed miR-124-1 chromatin structure, evidenced by increased levels of the open chromatin mark H3K27Ac, but decreased levels of closed chromatin mark H3K27Me3. Most importantly, the delivery of histone acetyltransferase (HAT) via CRISPR-dCas9-HAT and guiding RNAs to the promoter of the miR-124-1 gene increased miR-124-1 gene transcription. Thus, our data indicate epigenetic events play important role in controlling miR-124 and likely other miRNA levels and epigenetic regulators such as HDACs appear to be promising therapeutic targets for chronic PH.
Prebiotic Pathway from Ribose to RNA Formation
Authors: Banfalvi Gaspar
Published: April 2021

At the focus of abiotic chemical reactions is the synthesis of ribose. No satisfactory explanation was provided as to the missing link between the prebiotic synthesis of ribose and prebiotic RNA (preRNA). Hydrogen cyanide (HCN) is assumed to have been the principal precursor in the prebiotic formation of aldopentoses in the formose reaction and in the synthesis of ribose. Ribose as the best fitting aldopentose became the exclusive sugar component of RNA. The elevated yield of ribose synthesis at higher temperatures and its protection from decomposition could have driven the polymerization of the ribose-phosphate backbone and the coupling of nucleobases to the backbone. RNA could have come into being without the involvement of nucleotide precursors. The first nucleoside monophosphate is likely to have appeared upon the hydrolysis of preRNA contributed by the presence of reactive 2′-OH moieties in the preRNA chain. As a result of phosphorylation, nucleoside monophosphates became nucleoside triphosphates, substrates for the selective synthesis of genRNA.
Bacterial Membrane Vesicles in Pneumonia: From Mediators of Virulence to Innovative Vaccine Candidates
Authors: Behrens Felix , Funk-Hilsdorf Teresa C. , Kuebler Wolfgang M. , Simmons Szandor
Published: April 2021

Pneumonia due to respiratory infection with most prominently bacteria, but also viruses, fungi, or parasites is the leading cause of death worldwide among all infectious disease in both adults and infants. The introduction of modern antibiotic treatment regimens and vaccine strategies has helped to lower the burden of bacterial pneumonia, yet due to the unavailability or refusal of vaccines and antimicrobials in parts of the global population, the rise of multidrug resistant pathogens, and high fatality rates even in patients treated with appropriate antibiotics pneumonia remains a global threat. As such, a better understanding of pathogen virulence on the one, and the development of innovative vaccine strategies on the other hand are once again in dire need in the perennial fight of men against microbes. Recent data show that the secretome of bacteria consists not only of soluble mediators of virulence but also to a significant proportion of extracellular vesicles—lipid bilayer-delimited particles that form integral mediators of intercellular communication. Extracellular vesicles are released from cells of all kinds of organisms, including both Gram-negative and Gram-positive bacteria in which case they are commonly termed outer membrane vesicles (OMVs) and membrane vesicles (MVs), respectively. (O)MVs can trigger inflammatory responses to specific pathogens including S. pneumonia, P. aeruginosa, and L. pneumophila and as such, mediate bacterial virulence in pneumonia by challenging the host respiratory epithelium and cellular and humoral immunity. In parallel, however, (O)MVs have recently emerged as auspicious vaccine candidates due to their natural antigenicity and favorable biochemical properties. First studies highlight the efficacy of such vaccines in animal models exposed to (O)MVs from B. pertussis, S. pneumoniae, A. baumannii, and K. pneumoniae. An advanced and balanced recognition of both the detrimental effects of (O)MVs and their immunogenic potential could pave the way to novel treatment strategies in pneumonia and effective preventive approaches.
Current Immunological and Clinical Perspective on Vaccinations in Multiple Sclerosis Patients: Are They Safe after All?
Authors: Witman Tsur Shani , Adrian Zaher Eli , Tsur Meydan , Kania Karolina , Kalinowska-Łyszczarz Alicja
Published: April 2021

Vaccines work by stimulating the immune system, and their immunogenicity is key in achieving protection against specific pathogens. Questions have been raised whether in Multiple Sclerosis (MS) patients they could induce disease exacerbation and whether vaccines could possibly act as a trigger in the onset of MS in susceptible populations. So far, no correlation has been found between the vaccinations against influenza, hepatitis B, tetanus, human papillomavirus, measles, mumps, rubella, varicella zoster, tuberculosis, yellow fever, or typhoid fever and the risk of MS. Further research is needed for the potential protective implications of the tetanus and Bacillus Calmette–Guerin vaccines in MS patients. Nowadays with the emerging coronavirus disease 2019 (COVID-19) and recent vaccinations approval and arrival, the risk-benefit in MS patients with regards to safety and efficacy of COVID-19 vaccination in those treated with immunosuppressive therapies is of paramount importance. In this manuscript, we demonstrate how different vaccine types could be related to the immunopathogenesis of MS and discuss the risks and benefits of different vaccinations in MS patients.
The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy
Authors: Mattei Vincenzo , Santilli Francesca , Martellucci Stefano , Delle Monache Simona , Fabrizi Jessica , Colapietro Alessandro , Angelucci Adriano , Festuccia Claudio
Published: April 2021

Glioblastoma (GBM) is known to be the most common and lethal primary malignant brain tumor. Therapies against this neoplasia have a high percentage of failure, associated with the survival of self-renewing glioblastoma stem cells (GSCs), which repopulate treated tumors. In addition, despite new radical surgery protocols and the introduction of new anticancer drugs, protocols for treatment, and technical advances in radiotherapy, no significant improvement in the survival rate for GBMs has been realized. Thus, novel antitarget therapies could be used in conjunction with standard radiochemotherapy approaches. Targeted therapy, indeed, may address specific targets that play an essential role in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Significant cellular heterogeneity and the hierarchy with GSCs showing a therapy-resistant phenotype could explain tumor recurrence and local invasiveness and, therefore, may be a target for new therapies. Therefore, the forced differentiation of GSCs may be a promising new approach in GBM treatment. This article provides an updated review of the current standard and experimental therapies for GBM, as well as an overview of the molecular characteristics of GSCs, the mechanisms that activate resistance to current treatments, and a new antitumor strategy for treating GSCs for use as therapy.
Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model
Authors: Oh Youri , Jung Hoyong , Kim Hyejin , Baek Jihyun , Jun Joonhong , Cho Hyunwook , Im Daseul , Hah Jung-Mi
Published: April 2021

Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two series of known PLK1 inhibitors and proposed a new structure based on a hybridized 3D-QSAR model. Given the hybridized 3D-QSAR models, we designed and synthesized 4-benzyloxy-1-(2-arylaminopyridin-4-yl)-1H-pyrazole-3-carboxamides, and we inspected its inhibitory activities to identify novel PLK1 inhibitors with decent potency and selectivity.
Physiological Imaging Methods for Evaluating Response to Immunotherapies in Glioblastomas
Authors: Chawla Sanjeev , Shehu Vanessa , Gupta Pradeep K. , Nath Kavindra , Poptani Harish
Published: April 2021

Glioblastoma (GBM) is the most malignant brain tumor in adults, with a dismal prognosis despite aggressive multi-modal therapy. Immunotherapy is currently being evaluated as an alternate treatment modality for recurrent GBMs in clinical trials. These immunotherapeutic approaches harness the patient’s immune response to fight and eliminate tumor cells. Standard MR imaging is not adequate for response assessment to immunotherapy in GBM patients even after using refined response assessment criteria secondary to amplified immune response. Thus, there is an urgent need for the development of effective and alternative neuroimaging techniques for accurate response assessment. To this end, some groups have reported the potential of diffusion and perfusion MR imaging and amino acid-based positron emission tomography techniques in evaluating treatment response to different immunotherapeutic regimens in GBMs. The main goal of these techniques is to provide definitive metrics of treatment response at earlier time points for making informed decisions on future therapeutic interventions. This review provides an overview of available immunotherapeutic approaches used to treat GBMs. It discusses the limitations of conventional imaging and potential utilities of physiologic imaging techniques in the response assessment to immunotherapies. It also describes challenges associated with these imaging methods and potential solutions to avoid them.
Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy
Authors: Inoue Yasuteru , Ando Yukio , Misumi Yohei , Ueda Mitsuharu
Published: April 2021

Cerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid β (Aβ) in walls of leptomeningeal vessels and cortical capillaries in the brain. The loss of integrity of these vessels caused by cerebrovascular Aβ deposits results in fragile vessels and lobar intracerebral hemorrhages. CAA also manifests with progressive cognitive impairment or transient focal neurological symptoms. Although development of therapeutics for CAA is urgently needed, the pathogenesis of CAA remains to be fully elucidated. In this review, we summarize the epidemiology, pathology, clinical and radiological features, and perspectives for future research directions in CAA therapeutics. Recent advances in mass spectrometric methodology combined with vascular isolation techniques have aided understanding of the cerebrovascular proteome. In this paper, we describe several potential key CAA-associated molecules that have been identified by proteomic analyses (apolipoprotein E, clusterin, SRPX1 (sushi repeat-containing protein X-linked 1), TIMP3 (tissue inhibitor of metalloproteinases 3), and HTRA1 (HtrA serine peptidase 1)), and their pivotal roles in Aβ cytotoxicity, Aβ fibril formation, and vessel wall remodeling. Understanding the interactions between cerebrovascular Aβ deposits and molecules that accumulate with Aβ may lead to discovery of effective CAA therapeutics and to the identification of biomarkers for early diagnosis.
Cytokinin-Controlled Gradient Distribution of Auxin in Arabidopsis Root Tip
Authors: Wu Lei , Wang Jun-Li , Li Xiao-Feng , Guo Guang-Qin
Published: April 2021

The plant root is a dynamic system, which is able to respond promptly to external environmental stimuli by constantly adjusting its growth and development. A key component regulating this growth and development is the finely tuned cross-talk between the auxin and cytokinin phytohormones. The gradient distribution of auxin is not only important for the growth and development of roots, but also for root growth in various response. Recent studies have shed light on the molecular mechanisms of cytokinin-mediated regulation of local auxin biosynthesis/metabolism and redistribution in establishing active auxin gradients, resulting in cell division and differentiation in primary root tips. In this review, we focus our attention on the molecular mechanisms underlying the cytokinin-controlled auxin gradient in root tips.
Anticancer Half-Sandwich Rhodium(III) Complexes
Authors: Máliková Klaudia , Masaryk Lukáš , Štarha Pavel
Published: April 2021

Platinum-based anticancer drugs are most likely the most successful group of bioinorganic compounds. Their apparent disadvantages have led to the development of anticancer compounds of other noble metals, resulting in several ruthenium-based drugs which have entered clinical trials on oncological patients. Besides ruthenium, numerous rhodium complexes have been recently reported as highly potent antiproliferative agents against various human cancer cells, making them potential alternatives to Pt- and Ru-based metallodrugs. In this review, half-sandwich Rh(III) complexes are overviewed. Many representatives show higher in vitro potency than and different mechanisms of action (MoA) from the conventional anticancer metallodrugs (cisplatin in most cases) or clinically studied Ru drug candidates. Furthermore, some of the reviewed Rh(III) arenyl complexes are also anticancer in vivo. Pioneer anticancer organorhodium compounds as well as the recent advances in the field are discussed properly, and adequate attention is paid to their anticancer activity, solution behaviour and various processes connected with their MoA. In summary, this work summarizes the types of compounds and the most important biological results obtained in the field of anticancer half-sandwich Rh complexes.
Sequential and Binomial Sampling Plans to Estimate Thrips tabaci Population Density on Onion
Authors: Soto-Rojas Lauro , Rodríguez-Leyva Esteban , Bautista-Martínez Néstor , Ruíz-Galván Isabel , García-Palacios Daniel
Published: April 2021

Thrips tabaci Lindeman is a worldwide onion pest that causes economic losses of 10–60%, depending on many factors. Population sampling is essential for applying control tactics and preventing damage by the insect. Conventional sampling methods are criticized as time consuming, while fixed-precision binomial and sequential sampling plans may allow reliable estimations with a more efficient use of time. The aim of this work was to develop binomial and sequential sampling for fast reliable estimation of T. tabaci density on an onion. Forty-one commercial 1.0-ha onion plots were sampled (sample size n = 200) to characterize the spatial distribution of T. tabaci using Taylor’s power law (a = 2.586 and b = 1.511). Binomial and sequential enumerative sampling plans were then developed with precision levels of 0.10, 0.15 and 0.25. Sampling plans were validated with bootstrap simulations (1000 samples) using 10 independent data sets. Bootstrap simulation indicated that precision was satisfactory for all repetitions of the sequential sampling plan, while binomial sampling met the fixed precision in 80% of cases. Both methods reduced sampling time by around 80% relative to conventional sampling. These precise and less time-consuming sampling methods can contribute to implementation of control tactics within the integrated pest management approach.
Conversion of Spent Coffee and Donuts by Black Soldier Fly (Hermetia illucens) Larvae into Potential Resources for Animal and Plant Farming
Authors: Fischer Hayden , Romano Nicholas , Sinha Amit Kumar
Published: April 2021

Nutritionally unbalanced organic waste can be converted into potential resources for animal and plant farming by culturing black soldier fly (Hermetia illucens) larvae (BSFL) and prepupae (BSFP). BSFL and BSFP are rich sources of protein and lipids, while the leftover excrement called “frass” can be used as an organic fertilizer. Using readily available resources, BSFL were cultured on spent coffee, donut dough or an equal blend for 35 days. Survival, productivity, daily pupation and biochemical composition of BSFL and BSFP were measured along with the nitrogen-phosphorus-potassium values of the frass. Survival was highest in the blend compared (81%) to spent coffee (45%) or dough (24%); however, BSFL and BSFP were significantly longer and heavier from dough. Stage and food significantly influenced the protein, lipid and glycogen content of the BSFL and BSFP, which tended to be higher in the latter. While fatty acids were often significantly higher in BSFL fed spent coffee, the amino acid composition of BSFL was generally higher in dough. Frass from the blend had significantly highest nitrogen content, while potassium and phosphorus were significantly higher and lower from spent coffee, respectively. Although coffee and donut dough were suboptimal substrates for BSFL, a blend of these produced BSFL and frass that were nutritionally comparable to soybean meal and many organic fertilizers, respectively.
The Influence of Drying Methods on the Chemical Composition and Body Color of Yellow Mealworm (Tenebrio molitor L.)
Authors: Selaledi Letlhogonolo , Mabelebele Monnye
Published: April 2021

To preserve the quality of the yellow mealworm, different drying methods are being explored by farmers and processors. However, the energy costs associated with these methods are usually high for smallholder insect-rearing farmers. Thus, the core aim of this study was to investigate different drying procedures and their impact on the chemical composition of yellow mealworm larvae. Yellow mealworms (exposed to sun, oven and freeze drying) were later analyzed for their chemical composition and body color. Crude protein (CP) content of freeze and oven-dried mealworms were similar (p > 0.05), but higher (p < 0.05) than those of the sun-dried samples. The b (yellowness) color of the sun-dried samples scored the lowest value (p < 0.05) in comparison with both oven and freeze-dried samples. The majority of the essential amino acids were higher (p < 0.05) in the sun-dried mealworms than both oven and freeze-dried samples. Similarly, the fat content of sun-dried mealworms was higher (p < 0.05) than if they had been oven or freeze dried. However, SFA (saturated fatty acids), PUFA (polyunsaturated fatty acids) and n-6 fatty acids were similar (p > 0.05) for all drying methods. We, therefore, conclude that sun drying resulted in the same nutritional composition as freeze and oven drying despite the noted color changes. Freeze and oven-drying strategies can be used to formulate mealworm-based feed and food products without noticeable nutritional changes. For the benefit of small-scale insect-rearing farmers, an appropriate drying technology that is affordable and easy to use should be developed considering the needs and experiences of these farmers.
Digital Assessment of Gingival Dimensions of Healthy Periodontium
Authors: Lim Hyun-Chang , Lee Jaemin , Kang Dae-Young , Cho In-Woo , Shin Hyun-Seung , Park Jung-Chul
Published: April 2021

The aim of the present study was to re-visit the gingival dimension using digital scanning in a healthy Korean population. Forty-eight periodontally healthy volunteers (38 males and 10 females, mean age: 24.3 ± 2.2 years) were included. The mucogingival junction was highlighted using 2.5% diluted iodine solution. Then, the facial gingiva and mucosa of both jaws were digitally scanned using an intraoral digital scanner. Using computer software and periodontal probing, the heights and areas of keratinized gingiva (KG) and attached gingiva (AG) were measured. Similar distribution patterns in the gingival heights were noted in the maxilla and mandible. The maxilla showed substantially greater gingival values than the mandible. The heights of the KG and AG were notably smaller on the mandibular first premolar (2.37 mm and 1.07 mm, median value) and second molar (3.28 mm and 1.78 mm) than on the other teeth. The area of the KG was the largest in the canine (63.74 mm2 and 46.85 mm2) and first molar (64.14 mm2 and 58.82 mm2) in each jaw. Mandibular first and second molars, mandibular canine, and maxillary canine showed the highest value of the area under the receiver operation characteristics curve (>0.7) for differentiating between males and females. The gingival dimensions recorded using intraoral scanner demonstrated similar distribution patterns as in previous studies.
Impact of Platelet Reactivity in ACS Patients on Clinical Outcomes with Triple Antithrombotic Therapy
Authors: Gruttemeier Julia , Cottin Yves , Yao Hermann , De Maistre Emmanuel , Maza Maud , Bonello Laurent , Laine Marc , Resseguier Noemie , Zeller Marianne , Camoin-Jau Laurence , Paganelli Franck
Published: April 2021

Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients on oral anticoagulants (OAC) remains a clinical conundrum. In fact, combining an OAC with dual antiplatelet therapy (triple antithrombotic therapy, TAT) increases the risk of bleeding. Clopidogrel is the only thienopyridine recommended in TAT patients. Whether its response plays a relevant role in this setting remains uncertain. We aimed to evaluate the level of platelet reactivity inhibition (PRI) achieved by oral TAT in Acute Coronary Syndrome (ACS) patients undergoing PCI and its relationship with outcomes. We performed a multicenter prospective observational study and assessed PRI by vasodilator-stimulated phosphoprotein (VASP) index following a loading dose of clopidogrel. The primary endpoint was the incidence of major adverse cerebral or cardiovascular events (MACCE) at six months based on High on Treatment Platelet Reactivity (HTPR, VASP > 50%). The secondary endpoint was the incidence of bleeding at six months based on Low on Treatment Platelet Reactivity (LTPR, VASP < 16%). 491 patients were followed up for six months: 7.7% experienced MACCE and 17.3% experienced bleeding. There was no significant relationship between HTPR and MACCE, neither between LTPR and bleeding. Vitamin-K antagonist (VKA) treatment was associated with more MACCE and bleeding events, and the majority of events occurred within the first months. VASP index failed to predict outcomes in post-ACS patients with TAT. We confirm that direct acting OAC should be prioritized over VKA in TAT regimen.
Interplay between Heart Disease and Metabolic Steatosis: A Contemporary Perspective
Authors: Ramadan Mohammad Said , Russo Vincenzo , Nigro Gerardo , Durante-Mangoni Emanuele , Zampino Rosa
Published: April 2021

The liver-heart axis is a growing field of interest owing to rising evidence of complex bidirectional interplay between the two organs. Recent data suggest non-alcoholic fatty liver disease (NAFLD) has a significant, independent association with a wide spectrum of structural and functional cardiac diseases, and seems to worsen cardiovascular disease (CVD) prognosis. Conversely, the effect of cardiac disease on NAFLD is not well studied and data are mostly limited to cardiogenic liver disease. We believe it is important to further investigate the heart-liver relationship because of the tremendous global health and economic burden the two diseases pose, and the impact of such investigations on clinical decision making and management guidelines for both diseases. In this review, we summarize the current knowledge on NAFLD diagnosis, its systemic manifestations, and associations with CVD. More specifically, we review the pathophysiological mechanisms that govern the interplay between NAFLD and CVD and evaluate the relationship between different CVD treatments and NAFLD progression.
Identification of Fungi Isolated from Oral Cavity of Patients with HIV Using MALDI–TOF MS
Authors: Pawlak Zuzanna , Andrusiów Szymon , Pajączkowska Magdalena , Janczura Adriana
Published: April 2021

Background: A growing incidence of invasive fungal infections, especially among immunocompromised patients, has given increased significance to microbiological diagnostics of yeast-like fungi. More accurate and faster fungi identification methods that can compete with classical methods are being searched for. In this paper, classical microbiological methods are compared to MALDI–TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry). Methods: The diagnostic material was collected from buccal mucosa from 98 adults, including 69 with HIV. Only positive cultures were included in the study. Results: Matching results were obtained in 45 samples, and there were nonmatching results in 35 samples, with the majority of these in the study group, constituting 50% of identifications within this group. A particularly common mistake resulting from the use of classical methods is the false identification of C. dubliniensis as C. albicans. Additionally, C. tropicalis proves to be difficult to identify. Conclusions: Our results and literature data suggest that MALDI–TOF MS should be considered an effective alternative to classical methods in terms of fungi identification, especially among HIV-positive patients, due to the different morphology of fungal colonies.
Use of ECMO for Cardiogenic Shock in Pediatric Population
Authors: Bhaskar Priya , Davila Samuel , Hoskote Aparna , Thiagarajan Ravi
Published: April 2021

In children with severe advanced heart failure where medical management has failed, mechanical circulatory support in the form of veno-arterial extracorporeal membrane oxygenation (VA ECMO) or ventricular assist device represents life-sustaining therapy. This review provides an overview of VA ECMO used for cardiovascular support including medical and surgical heart disease. Indications, contraindications, and outcomes of VA ECMO in the pediatric population are discussed.VA ECMO provides biventricular and respiratory support and can be deployed in rapid fashion to rescue patient with failing physiology. There have been advances in conduct and technologic aspects of VA ECMO, but survival outcomes have not improved. Stringent selection and optimal timing of deployment are critical to improve mortality and morbidity of the patients supported with VA ECMO.
Musculoskeletal Manifestations in Sjogren’s Syndrome: An Orthopedic Point of View
Authors: Rozis Meletios , Vlamis John , Vasiliadis Elias , Mavragani Clio , Pneumaticos Spiros , Evangelopoulos Dimitrios Stergios
Published: April 2021

Sjogren’s syndrome (SS) is a frequent entity with a broad symptomatology spectrum, mainly affecting the salivary and lachrymal glands. The disease also affects the musculoskeletal system targeting bones, specific joints, muscles, and the peripheral nerve system. Disease related clinical manifestations canhave an accumulative impact, as the syndrome is commonly associated with other rheumatic diseases. A literature review was performed with the aim to assess the in-depth association of Sjogren’s syndrome and its treatment agents with the musculoskeletal system and further investigate its potential relevance with common orthopedic postoperative complications.
A Low Body Mass Index Is Associated with Unsuccessful Treatment in Patients with Mycobacterium avium Complex Pulmonary Disease
Authors: Sadamatsu Hironori , Takahashi Koichiro , Tashiro Hiroki , Kusaba Koji , Haraguchi Tetsuro , Kurihara Yuki , Komiya Natsuko , Nakashima Chiho , Nakamura Tomomi , Kimura Shinya , Sueoka-Aragane Naoko
Published: April 2021

Background: A low body mass index (BMI) has been reported to be a poor prognostic factor for Mycobacterium avium complex pulmonary disease (MAC-PD). The purpose of this study was to clarify the clinical features of MAC-PD in cases with a low BMI. Methods: This retrospective study analyzed the data of patients diagnosed with MAC-PD at Saga University Hospital between 2008 and 2019. The analyzed patient characteristics included age, gender, BMI, symptoms, laboratory data, chest computed tomography findings, and the treatment courses. We also investigated the factors associated with successful treatment. Results: In total, 144 patients were included in this study. The low-BMI group (BMI < 18.5 kg/m2) had a higher incidence of sputum, Mycobacterium intracellurare infection, and cavitary lesions, in addition to lower blood lymphocyte counts, higher neutrophil–lymphocyte ratios, and a lower prognostic nutritional index (PNI) when compared to the preserved-BMI group (BMI ≥ 18.5 kg/m2). Sixty-six of the 144 patients (45.8%) received treatment. Hemosputum, acid-fast bacillus sputum smear positivity, low lymphocyte counts, a low PNI, and unsuccessful treatment (48.5% vs. 24.2%, p < 0.05) were found to be associated with a low BMI. Conclusions: A low BMI is associated with cavitary lesions, malnutrition, and unsuccessful treatment in MAC-PD.
Public Concerns during the COVID-19 Lockdown: A Multicultural Cross-Sectional Study among Internet Survey Respondents in Three Countries
Authors: Emodi-Perlman Alona , Eli Ilana , Uziel Nir , Smardz Joanna , Khehra Anahat , Gilon Efrat , Wieckiewicz Gniewko , Levin Liran , Wieckiewicz Mieszko
Published: April 2021

(1) Background: this study aimed to evaluate the worries, anxiety, and depression in the public during the initial coronavirus disease 2019 (COVID-19) pandemic lockdown in three culturally different groups of internet survey respondents: Middle Eastern (Israel), European (Poland), and North American (Canada). (2) Methods: a cross-sectional online survey was conducted in the mentioned countries during the lockdown periods. The survey included a demographic questionnaire, a questionnaire on personal concerns, and the Patient Health Questionnaire-4 (PHQ-4). A total of 2207 people successfully completed the survey. (3) Results: Polish respondents were the most concerned about being infected. Canadian respondents worried the most about their finances, relations with relatives and friends, and both physical and mental health. Polish respondents worried the least about their physical health, and Israeli respondents worried the least about their mental health and relations with relatives and friends. Canadian respondents obtained the highest score in the PHQ-4, while the scores of Israeli respondents were the lowest. (4) Conclusions: various factors should be considered while formulating appropriate solutions in emergency circumstances such as a pandemic. Understanding these factors will aid in the development of strategies to mitigate the adverse effects of stress, social isolation, and uncertainty on the well-being and mental health of culturally different societies.
Delayed Improvement of Depression and Anxiety after Transcatheter Aortic Valve Implantation (TAVI) in Stages of Extended Extra-Valvular Cardiac Damage
Authors: Bäz Laura , Puscholt Marisa , Lasch Claudia , Diab Mahmoud , Möbius-Winkler Sven , Schulze P. Christian , Dannberg Gudrun , Franz Marcus
Published: April 2021

Background: Depression and anxiety are frequently occurring and likely to be linked to the severity of cardiac diseases like aortic stenosis (AS). This seems to be of interest since a staging classification of extra-valvular cardiac damage in AS has been introduced and shown to be of prognostic relevance. Objective: The current study aimed to investigate the frequency of depression and anxiety in association to staging and their dynamics after transcatheter aortic valve implantation (TAVI). Methods: A total number of 224 AS patients undergoing TAVI were classified according to the 2017 staging classification into stage 0 to 4 and further dichotomized into group A (stage 0 to 2) and B (stage 3 and 4). Using the Hospital Anxiety and Depression Scale (HADS-D), patients were assigned to depressive versus non-depressive or anxious versus non-anxious per staging group respectively, and analyzed at baseline, 6 weeks, 6 months and 12 months after TAVI. Results: After dichotomization, 158 patients (70.5%) were assigned to group A and 66 patients (29.5%) to group B. The part showing pathologic values for depression was 25.4% (57/224 patients) in the entire collective, 26.6% (42/158 patients) in group A and 22.7% (15/66 patients) in group B (p = n.s.). The proportion showing pathologic values for anxiety was 26.8% (60/224 patients) in the entire collective and did not differ between group A (24.7%, 39/158 patients) and B (31.8%, 21/66 patients) (p = n.s.). In patients revealing pathologic values for depression or anxiety prior to TAVI, there were significant and stable improvements over time observable already in short-term (6 weeks) follow-up in group A, and likewise, but later, in long-term (6/12 months) follow-up in group B. Conclusions: Although of proven prognostic relevance, higher stages of extra-valvular cardiac damage are not associated with higher rates of pre-existing depression or anxiety. The TAVI procedure resulted in a persisting reduction of depression and anxiety in patients showing pathologic values at baseline. Notably, these improvements are timely delayed in higher stages.
Evaluation of a Broad Panel of SARS-CoV-2 Serological Tests for Diagnostic Use
Authors: Werner Maren , Pervan Philip , Glück Vivian , Zeman Florian , Koller Michael , Burkhardt Ralph , Glück Thomas , Wenzel Jürgen J. , Schmidt Barbara , Gessner André , Peterhoff David
Published: April 2021

Serological testing is crucial in detection of previous infection and in monitoring convalescent and vaccine-induced immunity. During the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic, numerous assay platforms have been developed and marketed for clinical use. Several studies recently compared clinical performance of a limited number of serological tests, but broad comparative evaluation is currently missing. Within this study, a panel of 161 sera from SARS-CoV-2 infected, seasonal CoV-infected and SARS-CoV-2 naïve subjects was enrolled to evaluate 16 ELISA/ECLIA-based and 16 LFA-based tests. Specificities of all ELISA/ECLIA-based assays were acceptable and generally in agreement with the providers’ specifications, but sensitivities were lower as specified. Results of the LFAs were less accurate as compared to the ELISAs, albeit with some exceptions. We found a sporadic unequal immune response for different antigens and thus recommend the use of a nucleocapsid protein (N)- and spike protein (S)-based test combination when maximal sensitivity is necessary. Finally, the quality of the immune response in terms of neutralization should be tested using S-based IgG tests.
Association of Myocardial Energetic Efficiency with Circumferential and Longitudinal Left Ventricular Myocardial Function in Subjects with Increased Body Mass Index (the FATCOR Study)
Authors: Mancusi Costantino , Midtbø Helga , De Luca Nicola , Halland Hilde , de Simone Giovanni , Gerdts Eva
Published: April 2021

Lower myocardial mechanic-energetic efficiency (MEEi), expressed as stroke volume/heart rate ratio (SV/HR) in mL/s/g of the left ventricular (LV) mass, is associated with the incidence of heart failure in subjects with cardiometabolic disorders. We explored the association of MEEi with LV systolic circumferential and longitudinal myocardial function in 480 subjects with increased body mass index (BMI) without known cardiovascular disease (mean age 47 ± 9 years, 61% women, 63% obese, 74% with hypertension) participating in the fat-associated cardiovascular dysfunction (FATCOR) study. Insulin resistance was assessed by the homeostasis model assessment insulin-resistance index (HOMA-IR). SV was calculated by Doppler echocardiography. The LV systolic circumferential myocardial function was evaluated by midwall fractional shortening (MFS) and longitudinal function by global longitudinal strain (GLS). Patients were grouped into MEEi quartiles. The lowest MEEi quartile (<0.41 mL/s per g) was considered low MEEi. The association of MEEi with MFS and GLS were tested in multivariable linear regression analyses. Patients with low MEEi were more frequently men, with obesity and hypertension, dyslipidemia and higher HOMA-IR index (all p for trend <0.05). In multivariable analyses, lower MEEi was associated with lower LV myocardial function by MFS and GLS independent of higher LV mass and clinical variables, including older age, male sex, presence of hypertension and a higher triglycerides level (all p < 0.05). In conclusion, in subjects with increased BMI without known cardiovascular disease participating in the FATCOR study, reduced MEEi was associated with lower LV myocardial function both in the circumferential and longitudinal direction, independent of cardiometabolic factors.
Marine Vision-Based Situational Awareness Using Discriminative Deep Learning: A Survey
Authors: Qiao Dalei , Liu Guangzhong , Lv Taizhi , Li Wei , Zhang Juan
Published: April 2021

The primary task of marine surveillance is to construct a perfect marine situational awareness (MSA) system that serves to safeguard national maritime rights and interests and to maintain blue homeland security. Progress in maritime wireless communication, developments in artificial intelligence, and automation of marine turbines together imply that intelligent shipping is inevitable in future global shipping. Computer vision-based situational awareness provides visual semantic information to human beings that approximates eyesight, which makes it likely to be widely used in the field of intelligent marine transportation. We describe how we combined the visual perception tasks required for marine surveillance with those required for intelligent ship navigation to form a marine computer vision-based situational awareness complex and investigated the key technologies they have in common. Deep learning was a prerequisite activity. We summarize the progress made in four aspects of current research: full scene parsing of an image, target vessel re-identification, target vessel tracking, and multimodal data fusion with data from visual sensors. The paper gives a summary of research to date to provide background for this work and presents brief analyses of existing problems, outlines some state-of-the-art approaches, reviews available mainstream datasets, and indicates the likely direction of future research and development. As far as we know, this paper is the first review of research into the use of deep learning in situational awareness of the ocean surface. It provides a firm foundation for further investigation by researchers in related fields.
Generation of the TSL for Zirconium Hydrides from Ab Initio Methods
Authors: Wormald Jonathan , Zerkle Michael , Holmes Jesse
Published: April 2021

Zirconium hydride (ZrHx) is a moderator material used in TRIGA and other reactors that may exist in multiple phases with varying stoichiometry, which include the δ phase and the ϵ phase. Current ENDF/B-VIII.0 ZrHx thermal scattering law (TSL) evaluations do not distinguish between phases. These sub-libraries were generated with the LEAPR module of NJOY using historic phonon spectra derived from a central force model and assume incoherent elastic scattering for both bound hydrogen and zirconium, which neglects the effects of crystal structures important for scattering from zirconium bound in ZrHx. In this work, the TSLs for hydrogen and zirconium bound in δ-ZrHx and ϵ-ZrH2 were generated from phonon spectra derived from modern ab initio lattice dynamics methods and ab initio molecular dynamics. Subsequently, TSLs for hydrogen and zirconium in ZrHx and ZrH2 were generated using the Full Law Analysis Scattering System Hub (FLASSH) code. The built-in generalized coherent elastic routine was used to generate the previously neglected elastic contribution from zirconium for this material. The present TSLs provide both a re-evaluation of the current ZrH sub-libraries and expansion of the set of TSLs available for the examination of neutrons in systems with zirconium hydride, permitting explicit treatment of δ and ϵ phases.
Infections due to Rare Cryptococcus Species. A Literature Review
Authors: Morales-López Soraya E. , Garcia-Effron Guillermo
Published: April 2021

Infections due to rare Cryptococcus species (other than C. neoformans species complex, C. gattii species complex, C. albidus or C. laurentii) are barely reported. The aim of this work is to present a comprehensive literature review of all the papers describing infections due to these species referenced in the main databases (PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar). Clinical and epidemiological data together with laboratory findings (identification and antifungal susceptibility) of each isolate were analyzed. Fifty-eight cryptococosis due to rare species were described in 46 papers between 1934–2018. These reports included 16 rare Cryptococcus spp. that were generally associated with nervous system infections and fungemias. Some species are non-capsulated and are not able to grow at 37 °C. Few species were identified by commercially available methods, making internal transcriber spacer (ITS) and D1/D2 regions sequencing mandatory. The most potent antifungal was amphotericin B (although some species showed high MIC values). The studied strains showed high MICs values to 5-fluorocytosine (all >64 µg/mL), echinocandins (all >8 µg/mL), and fluconazole (>80% of the MICs >4 µg/mL). Due to the scarcity of the data and the absence of guidelines for the treatment of these infections, this review could be informative and could help in the diagnosis and treatment of these infections.