bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Supplement of Marichromatium gracile YL28 on Water Quality and Microbial Structures in Shrimp Mariculture Ecosystems
Authors: Cui Liang , Zhu Bitong , Zhang Xiaobo , Chan Zhuhua , Zhao Chungui , Zeng Runying , Yang Suping , Chen Shicheng
Published: December 2020

The elevated NH3-N and NO2-N pollution problems in mariculture have raised concerns because they pose threats to animal health and coastal and offshore environments. Supplement of Marichromatium gracile YL28 (YL28) into polluted shrimp rearing water and sediment significantly decreased ammonia and nitrite concentrations, showing that YL28 functioned as a novel safe marine probiotic in the shrimp culture industry. The diversity of aquatic bacteria in the shrimp mariculture ecosystems was studied by sequencing the V4 region of 16S rRNA genes, with respect to additions of YL28 at the low and high concentrations. It was revealed by 16S rRNA sequencing analysis that Proteobacteria, Planctomycete and Bacteroidetes dominated the community (>80% of operational taxonomic units (OTUs)). Up to 41.6% of the predominant bacterial members were placed in the classes Gammaproteobacteria (14%), Deltaproteobacteria (14%), Planctomycetacia (8%) and Alphaproteobacteria (5.6%) while 40% of OTUs belonged to unclassified ones or others, indicating that the considerable bacterial populations were novel in our shrimp mariculture. Bacterial communities were similar between YL28 supplements and control groups (without addition of YL28) revealed by the β-diversity using PCoA, demonstrating that the additions of YL28 did not disturb the microbiota in shrimp mariculture ecosystems. Instead, the addition of YL28 increased the relative abundance of ammonia-oxidizing and denitrifying bacteria. The quantitative PCR analysis further showed that key genes including nifH and amoA involved in nitrification and nitrate or nitrite reduction significantly increased with YL28 supplementation (p < 0.05). The supplement of YL28 decreased the relative abundance of potential pathogen Vibrio. Together, our studies showed that supplement of YL28 improved the water quality by increasing the relative abundance of ammonia-oxidizing and denitrifying bacteria while the microbial community structure persisted in shrimp mariculture ecosystems.
Investigation of Pre-Earthquake Ionospheric and Atmospheric Disturbances for Three Large Earthquakes in Mexico
Authors: Oikonomou Christina , Haralambous Haris , Pulinets Sergey , Khadka Aakriti , Paudel Shukra R. , Barta Veronika , Muslim Buldan , Kourtidis Konstantinos , Karagioras Athanasios , İnyurt Samed
Published: December 2020

The purpose of the present study is to investigate simultaneously pre-earthquake ionospheric and atmospheric disturbances by the application of different methodologies, with the ultimate aim to detect their possible link with the impending seismic event. Three large earthquakes in Mexico are selected (8.2 Mw, 7.1 Mw and 6.6 Mw during 8 and 19 September 2017 and 21 January 2016 respectively), while ionospheric variations during the entire year 2017 prior to 37 earthquakes are also examined. In particular, Total Electron Content (TEC) retrieved from Global Navigation Satellite System (GNSS) networks and Atmospheric Chemical Potential (ACP) variations extracted from an atmospheric model are analyzed by performing statistical and spectral analysis on TEC measurements with the aid of Global Ionospheric Maps (GIMs), Ionospheric Precursor Mask (IPM) methodology and time series and regional maps of ACP. It is found that both large and short scale ionospheric anomalies occurring from few hours to a few days prior to the seismic events may be linked to the forthcoming events and most of them are nearly concurrent with atmospheric anomalies happening during the same day. This analysis also highlights that even in low-latitude areas it is possible to discern pre-earthquake ionospheric disturbances possibly linked with the imminent seismic events.
Suicide Attempts and Perceived Social Support among Chinese Drug Users: The Mediating Role of Self-Esteem and Depression
Authors: Deng Yali , Li Xuemeng , Liu Liu , Chui Wing Hong
Published: December 2020

Suicidal behavior is a severe problem among drug users. This study examines influential factors related to suicide attempts and analyzes possible mediators of the relationship between perceived social support and suicide attempts amongst Chinese drug users under compulsory institutional drug treatment. Taking perceived social support as the independent variable, we found that the relationship between suicide attempts and perceived social support is mediated by self-esteem as a protective factor and depression as a risk factor. Path analysis shows that self-esteem contributes relatively more to the indirect effects than depression does, accounting for 31.1% and 24.2% of the total effect, respectively. Generally speaking, the findings of this study point to an urgent need for addressing suicide attempts among Chinese drug users while treating self-esteem as the protective factor that deserves as substantial attention as depression receives.
A Critical Comparison of 3D Digitization Techniques for Heritage Objects
Authors: Adamopoulos Efstathios , Rinaudo Fulvio , Ardissono Liliana
Published: December 2020

Techniques for the three-dimensional digitization of tangible heritage are continuously updated, as regards active and passive sensors, data acquisition approaches, implemented algorithms and employed computational systems. These developments enable higher automation and processing velocities, increased accuracy, and precision for digitizing heritage assets. For large-scale applications, as for investigations on ancient remains, heritage objects, or architectural details, scanning and image-based modeling approaches have prevailed, due to reduced costs and processing durations, fast acquisition, and the reproducibility of workflows. This paper presents an updated metric comparison of common heritage digitization approaches, providing a thorough examination of sensors, capturing workflows, processing parameters involved, metric and radiometric results produced. A variety of photogrammetric software were evaluated (both commercial and open sourced), as well as photo-capturing equipment of various characteristics and prices, and scanners employing different technologies. The experimentations were performed on case studies of different geometrical and surface characteristics to thoroughly assess the implemented three-dimensional modeling pipelines.
Cyclophilin Inhibition Protects Against Experimental Acute Kidney Injury and Renal Interstitial Fibrosis
Authors: Leong Khai Gene , Ozols Elyce , Kanellis John , Badal Shawn S. , Liles John T. , Nikolic-Paterson David J. , Ma Frank Y.
Published: December 2020

Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochondrial-dependent cell death. This study investigated the therapeutic potential of a selective cyclophilin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment significantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.
Use of Fourier-Transform Infrared Spectroscopy (FT-IR) for Monitoring Experimental Helicobacter pylori Infection and Related Inflammatory Response in Guinea Pig Model
Authors: Gonciarz Weronika , Lechowicz Łukasz , Urbaniak Mariusz , Kaca Wiesław , Chmiela Magdalena
Published: December 2020

Infections due to Gram-negative bacteria Helicobacter pylori may result in humans having gastritis, gastric or duodenal ulcer, and even gastric cancer. Investigation of quantitative changes of soluble biomarkers, correlating with H. pylori infection, is a promising tool for monitoring the course of infection and inflammatory response. The aim of this study was to determine, using an experimental model of H. pylori infection in guinea pigs, the specific characteristics of infrared spectra (IR) of sera from H. pylori infected (40) vs. uninfected (20) guinea pigs. The H. pylori status was confirmed by histological, molecular, and serological examination. The IR spectra were measured using a Fourier-transform (FT)-IR spectrometer Spectrum 400 (PerkinElmer) within the range of wavenumbers 3000–750 cm−1 and converted to first derivative spectra. Ten wavenumbers correlated with H. pylori infection, based on the chi-square test, were selected for a K-nearest neighbors (k-NN) algorithm. The wavenumbers correlating with infection were identified in the W2 and W3 windows associated mainly with proteins and in the W4 window related to nucleic acids and hydrocarbons. The k-NN for detection of H. pylori infection has been developed based on chemometric data. Using this model, animals were classified as infected with H. pylori with 100% specificity and 97% sensitivity. To summarize, the IR spectroscopy and k-NN algorithm are useful for monitoring experimental H. pylori infection and related inflammatory response in guinea pig model and may be considered for application in humans.
Linear Copolymers Based on Choline Ionic Liquid Carrying Anti-Tuberculosis Drugs: Influence of Anion Type on Physicochemical Properties and Drug Release
Authors: Niesyto Katarzyna , Neugebauer Dorota
Published: December 2020

In this study, drug nanocarriers were designed using linear copolymers with different contents of cholinium-based ionic liquid units, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA/Cl: 25, 50, and 75 mol%). The amphiphilicity of the copolymers was evaluated on the basis of their critical micelle concentration (CMC = 0.055–0.079 mg/mL), and their hydrophilicities were determined by water contact angles (WCA = 17°–46°). The chloride anions in the polymer chain were involved in ionic exchange reactions to introduce pharmaceutical anions, i.e., p-aminosalicylate (PAS−), clavulanate (CLV−), piperacillin (PIP−), and fusidate (FUS−), which are established antibacterial agents for treating lung and respiratory diseases. The exchange reaction efficiency decreased in the following order: CLV− > PAS− > PIP− >> FUS−. The hydrophilicity of the ionic drug conjugates was slightly reduced, as indicated by the increased WCA values. The major fraction of particles with sizes ~20 nm was detected in systems with at least 50% TMAMA carrying PAS or PIP. The influence of the drug character and carrier structure was also observed in the kinetic profiles of the release processes driven by the exchange with phosphate anions (0.5–6.4 μg/mL). The obtained polymer-drug ionic conjugates (especially that with PAS) are promising carriers with potential medical applications.
Proteomics of Muscle Microdialysates Identifies Potential Circulating Biomarkers in Facioscapulohumeral Muscular Dystrophy
Authors: Corasolla Carregari Victor , Monforte Mauro , Di Maio Giuseppe , Pieroni Luisa , Urbani Andrea , Ricci Enzo , Tasca Giorgio
Published: December 2020

Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD.
Trifostigmanoside I, an Active Compound from Sweet Potato, Restores the Activity of MUC2 and Protects the Tight Junctions through PKCα/β to Maintain Intestinal Barrier Function
Authors: Parveen Amna , Choi Seungho , Kang Ju-Hee , Oh Seung Hyun , Kim Sun Yeou
Published: December 2020

Sweet potato (Ipomoea batata) is considered a superfood among vegetables and has been consumed for centuries. Traditionally, sweet potato is used to treat several illnesses, including diarrhea and stomach disorders. This study aimed to explore the protective effect of sweet potato on intestinal barrier function, and to identify the active compounds of sweet potato and their underlying mechanism of action. To this purpose, bioactivity-guided isolation, Western blotting, and immunostaining assays were applied. Interestingly, our bioactivity-guided approach enabled the first isolation and identification of trifostigmanoside I (TS I) from sweet potato. TS I induced mucin production and promoted the phosphorylation of PKCα/β in LS174T human colon cancer cells. In addition, it protected the function of tight junctions in the Caco-2 cell line. These findings suggest that TS I rescued the impaired abilities of MUC2, and protected the tight junctions through PKCα/β, to maintain intestinal barrier function.
Promoting Effect of Basic Fibroblast Growth Factor in Synovial Mesenchymal Stem Cell-Based Cartilage Regeneration
Authors: Okamura Gensuke , Ebina Kosuke , Hirao Makoto , Chijimatsu Ryota , Yonetani Yasukazu , Etani Yuki , Miyama Akira , Takami Kenji , Goshima Atsushi , Yoshikawa Hideki , Ishimoto Takuya , Nakano Takayoshi , Hamada Masayuki , Kanamoto Takashi , Nakata Ken
Published: December 2020

Synovial mesenchymal stem cell (SMSC) is the promising cell source of cartilage regeneration but has several issues to overcome such as limited cell proliferation and heterogeneity of cartilage regeneration ability. Previous reports demonstrated that basic fibroblast growth factor (bFGF) can promote proliferation and cartilage differentiation potential of MSCs in vitro, although no reports show its beneficial effect in vivo. The purpose of this study is to investigate the promoting effect of bFGF on cartilage regeneration using human SMSC in vivo. SMSCs were cultured with or without bFGF in a growth medium, and 2 × 105 cells were aggregated to form a synovial pellet. Synovial pellets were implanted into osteochondral defects induced in the femoral trochlea of severe combined immunodeficient mice, and histological evaluation was performed after eight weeks. The presence of implanted SMSCs was confirmed by the observation of human vimentin immunostaining-positive cells. Interestingly, broad lacunae structures and cartilage substrate stained by Safranin-O were observed only in the bFGF (+) group. The bFGF (+) group had significantly higher O’Driscoll scores in the cartilage repair than the bFGF (−) group. The addition of bFGF to SMSC growth culture may be a useful treatment option to promote cartilage regeneration in vivo.
Mast Cell Chymase and Kidney Disease
Authors: Vibhushan Shamila , Bratti Manuela , Montero-Hernández Juan Eduardo , El Ghoneimi Alaa , Benhamou Marc , Charles Nicolas , Daugas Eric , Blank Ulrich
Published: December 2020

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.
A Very Bright Far-Red Bioluminescence Emitting Combination Based on Engineered Railroad Worm Luciferase and 6′-Amino-Analogs for Bioimaging Purposes
Authors: Viviani Vadim R. , Bevilaqua Vanessa R. , de Souza Daniel R. , Pelentir Gabriel F. , Kakiuchi Michio , Hirano Takashi
Published: December 2020

Beetle luciferases produce bioluminescence (BL) colors ranging from green to red, having been extensively used for many bioanalytical purposes, including bioimaging of pathogen infections and metastasis proliferation in living animal models and cell culture. For bioimaging purposes in mammalian tissues, red bioluminescence is preferred, due to the lower self-absorption of light at longer wavelengths by hemoglobin, myoglobin and melanin. Red bioluminescence is naturally produced only by Phrixothrix hirtus railroad worm luciferase (PxRE), and by some engineered beetle luciferases. However, Far-Red (FR) and Near-Infrared (NIR) bioluminescence is best suited for bioimaging in mammalian tissues due to its higher penetrability. Although some FR and NIR emitting luciferin analogs have been already developed, they usually emit much lower bioluminescence activity when compared to the original luciferin-luciferases. Using site-directed mutagenesis of PxRE luciferase in combination with 6′-modified amino-luciferin analogs, we finally selected novel FR combinations displaying BL ranging from 636–655 nm. Among them, the combination of PxRE-R215K mutant with 6′-(1-pyrrolidinyl)luciferin proved to be the best combination, displaying the highest BL activity with a catalytic efficiency ~2.5 times higher than the combination with native firefly luciferin, producing the second most FR-shifted bioluminescence (650 nm), being several orders of magnitude brighter than commercial AkaLumine with firefly luciferase. Such combination also showed higher thermostability, slower BL decay time and better penetrability across bacterial cell membranes, resulting in ~3 times higher in vivo BL activity in bacterial cells than with firefly luciferin. Overall, this is the brightest FR emitting combination ever reported, and is very promising for bioimaging purposes in mammalian tissues.
Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer
Authors: Singh Tanya , Neal Adam S. , Moatamed Neda A. , Memarzadeh Sanaz
Published: December 2020

One of the major challenges in the treatment of cancer are differential responses of patients to existing standard of care anti-cancer drugs. These differential responses may, in part, be due to a diverse range of genomic, epigenomic, proteomic, and metabolic alterations among individuals suffering from the same type of cancer. Precision medicine is an emerging approach in cancer therapeutics that takes into account specific molecular alterations, environmental factors as well as lifestyle of individual patients. This approach allows clinicians and researchers to select or predict treatments that would most likely benefit the patient based on their individual tumor characteristics. One class of precision medicine tools are predictive, in vitro drug-response assays designed to test the sensitivity of patient tumor cells to existing or novel therapies. These assays have the potential to rapidly identify the most effective treatments for cancer patients and thus hold great promise in the field of precision medicine. In this review, we have highlighted several drug-response assays developed in ovarian cancer and discussed the current challenges and future prospects of these assays in the clinical management of this disease.
Nonylphenol Induces Apoptosis through ROS/JNK Signaling in a Spermatogonia Cell Line
Authors: Park Hyun-Jung , Lee Ran , Yoo Hyunjin , Hong Kwonho , Song Hyuk
Published: December 2020

Nonylphenol (NP) is an endocrine-disruptor chemical that negatively affects reproductive health. Testes exposure to NP results in testicular structure disruption and a reduction in testicular size and testosterone levels. However, the effects of NP on spermatogonia in testes have not been fully elucidated. In this study, the molecular mechanisms of NP in GC-1 spermatogonia (spg) cells were investigated. We found that cell viability significantly decreased and apoptosis increased in a dose-dependent manner when GC-1 spg cells were exposed to NP. Furthermore, the expression levels of the pro-apoptotic proteins increased, whereas anti-apoptosis markers decreased in NP-exposed GC-1 spg cells. We also found that NP increased reactive oxygen species (ROS) generation, suggesting that ROS-induced activation of the MAPK signaling pathway is the molecular mechanism of NP-induced apoptosis in GC-1 spg cells. Thus, NP could induce c-Jun phosphorylation; dose-dependent expression of JNK, MKK4, p53, and p38; and the subsequent inhibition of ERK1/2 and MEK1/2 phosphorylation. The genes involved in apoptosis and JNK signaling were also upregulated in GC-1 spg cells treated with NP compared to those in the controls. Our findings suggest that NP induces apoptosis through ROS/JNK signaling in GC-1 spg cells.
Structural Aspects and Prediction of Calmodulin-Binding Proteins
Authors: Andrews Corey , Xu Yiting , Kirberger Michael , Yang Jenny J.
Published: December 2020

Calmodulin (CaM) is an important intracellular protein that binds Ca2+ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca2+ concentration through interactions with CaM.
Glyoxalase System in the Progression of Skin Aging and Skin Malignancies
Authors: Yumnam Silvia , Subedi Lalita , Kim Sun Yeou
Published: December 2020

Dicarbonyl compounds, including methylglyoxal (MGO) and glyoxal (GO), are mainly formed as byproducts of glucose metabolism. The main glyoxalase system consists of glyoxalase I and II (Glo1 and Glo2) and is the main enzyme involved in the detoxification of dicarbonyl stress, which occurs as an accumulation of MGO or GO due to decreased activity or expression of Glo1. Dicarbonyl stress is a major cause of cellular and tissue dysfunction that causes various health issues, including diabetes, aging, and cancer. The skin is the largest organ in the body. In this review, we discuss the role of the glyoxalase system in the progression of skin aging, and more importantly, skin malignancies. We also discuss the future prospects of the glyoxalase system in other skin abnormalities such as psoriasis and vitiligo, including hyperpigmentation. Finally, in the present review, we suggest the role of glyoxalase in the progression of skin aging and glyoxalase system as a potential target for anticancer drug development for skin cancer.
Optomechanical Processing of Silver Colloids: New Generation of Nanoparticle–Polymer Composites with Bactericidal Effect
Authors: Siegel Jakub , Kaimlová Markéta , Vyhnálková Barbora , Trelin Andrii , Lyutakov Oleksiy , Slepička Petr , Švorčík Václav , Veselý Martin , Vokatá Barbora , Malinský Petr , Šlouf Miroslav , Hasal Pavel , Hubáček Tomáš
Published: December 2020

The properties of materials at the nanoscale open up new methodologies for engineering prospective materials usable in high-end applications. The preparation of composite materials with a high content of an active component on their surface is one of the current challenges of materials engineering. This concept significantly increases the efficiency of heterogeneous processes moderated by the active component, typically in biological applications, catalysis, or drug delivery. Here we introduce a general approach, based on laser-induced optomechanical processing of silver colloids, for the preparation of polymer surfaces highly enriched with silver nanoparticles (AgNPs). As a result, the AgNPs are firmly immobilized in a thin surface layer without the use of any other chemical mediators. We have shown that our approach is applicable to a broad spectrum of polymer foils, regardless of whether they absorb laser light or not. However, if the laser radiation is absorbed, it is possible to transform smooth surface morphology of the polymer into a roughened one with a higher specific surface area. Analyses of the release of silver from the polymer surface together with antibacterial tests suggested that these materials could be suitable candidates in the fight against nosocomial infections and could inhibit the formation of biofilms with a long-term effect.
Radon Exposure—Therapeutic Effect and Cancer Risk
Authors: Maier Andreas , Wiedemann Julia , Rapp Felicitas , Papenfuß Franziska , Rödel Franz , Hehlgans Stephanie , Gaipl Udo S. , Kraft Gerhard , Fournier Claudia , Frey Benjamin
Published: December 2020

Largely unnoticed, all life on earth is constantly exposed to low levels of ionizing radiation. Radon, an imperceptible natural occurring radioactive noble gas, contributes as the largest single fraction to radiation exposure from natural sources. For that reason, radon represents a major issue for radiation protection. Nevertheless, radon is also applied for the therapy of inflammatory and degenerative diseases in galleries and spas to many thousand patients a year. In either case, chronic environmental exposure or therapy, the effect of radon on the organism exposed is still under investigation at all levels of interaction. This includes the physical stage of diffusion and energy deposition by radioactive decay of radon and its progeny and the biological stage of initiating and propagating a physiologic response or inducing cancer after chronic exposure. The purpose of this manuscript is to comprehensively review the current knowledge of radon and its progeny on physical background, associated cancer risk and potential therapeutic effects.
Recent Advances in Carbon and Nitrogen Metabolism in C3 Plants
Authors: Baslam Marouane , Mitsui Toshiaki , Sueyoshi Kuni , Ohyama Takuji
Published: December 2020

C and N are the most important essential elements constituting organic compounds in plants. The shoots and roots depend on each other by exchanging C and N through the xylem and phloem transport systems. Complex mechanisms regulate C and N metabolism to optimize plant growth, agricultural crop production, and maintenance of the agroecosystem. In this paper, we cover the recent advances in understanding C and N metabolism, regulation, and transport in plants, as well as their underlying molecular mechanisms. Special emphasis is given to the mechanisms of starch metabolism in plastids and the changes in responses to environmental stress that were previously overlooked, since these changes provide an essential store of C that fuels plant metabolism and growth. We present general insights into the system biology approaches that have expanded our understanding of core biological questions related to C and N metabolism. Finally, this review synthesizes recent advances in our understanding of the trade-off concept that links C and N status to the plant’s response to microorganisms.
Epiretinal Membrane Surgery: Structural Retinal Changes Correlate with the Improvement of Visual Function
Authors: Cacciamani Andrea , Cosimi Pamela , Ripandelli Guido , Di Nicola Marta , Scarinci Fabio
Published: December 2020

Several parameters have been studied for identifying the visual outcomes after pars plana vitrectomy (PPV) for epiretinal membrane (ERM) peeling. This retrospective study aimed to analyze structural retinal changes with spectral domain-optical coherence tomography (SD-OCT) and their correlations with visual acuity improvement in patients with ERM undergoing PPV. Twenty-one pseudophakic eyes were enrolled in the study. Ophthalmic evaluations included best corrected visual acuity (BCVA) and retinal layer thickness measurements with SD-OCT. The segmentation of the retina was divided into four parts: the inner retinal layer (IRL), composed of an internal limiting membrane, retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer; inner nuclear layer (INL); outer plexiform layer (OPL); and outer nuclear layer (ONL). Correlations between changes in retinal layer thicknesses and BCVA were explored over a 6 month follow-up period. The postoperative thickness decrease of the INL was significantly correlated with thickness changes in all other measured retinal layers (p < 0.001). Non-parametric linear regression showed that postoperative improvement in BCVA was associated with a postoperatively decreased thickness in the IRL (p = 0.021), INL (p = 0.039), and OPL (p = 0.021). In eyes undergoing PPV, postoperative thickness decreases of the IRL, INL, and OPL were correlated with visual acuity improvements. Re-compaction of these retinal layers after relieving ERM-induced traction may be an important factor in postoperative visual function improvement.
Triglyceride Glucose-Waist Circumference Better Predicts Coronary Calcium Progression Compared with Other Indices of Insulin Resistance: A Longitudinal Observational Study
Authors: Cho Yun Kyung , Lee Jiwoo , Kim Hwi Seung , Kim Eun Hee , Lee Min Jung , Yang Dong Hyun , Kang Joon-Won , Jung Chang Hee , Park Joong-Yeol , Kim Hong-Kyu , Lee Woo Je
Published: December 2020

The triglyceride glucose (TyG) index, a product of triglyceride and fasting glucose, is a reliable marker for insulin resistance. We aimed to investigate the association between the TyG-related markers and coronary artery calcification (CAC) progression. We enrolled 1145 asymptomatic participants who underwent repeated CAC score measurements during routine health examinations. Homeostasis model assessment of insulin resistance (HOMA-IR), TyG index, TyG-BMI (body mass index), and TyG-WC (waist circumference) were calculated. Progression of CAC was defined as (1) incident CAC in a CAC-free population, or an (2) increase of ≥2.5 units between the baseline and final square root of the CAC scores in participants with detectable CAC. According to the quartiles of parameters, we stratified the subjects into four groups. The prevalence of progression increased with the TyG-WC quartile (15.0%, 24.1%, 31.0%, and 32.2% for each of the groups; p < 0.001). The multivariate-adjusted odds ratio (95% confidence interval) for CAC score progression was 1.66 (1.01–2.77) when the highest and lowest TyG-WC index quartiles were compared. Furthermore, the predictability of TyG-WC for CAC progression was better than the other indices in terms of the area under the curve. The TyG-WC index predicted CAC progression better than other indices and could be a potential marker of future coronary atherosclerosis.
Candida Infection Associated with Salivary Gland—A Narrative Review
Authors: Ok Soo-Min , Ho Donald , Lynd Tyler , Ahn Yong-Woo , Ju Hye-Min , Jeong Sung-Hee , Cheon Kyounga
Published: December 2020

Candida species are common global opportunistic pathogens that could repeatedly and chronically cause oral mucosa infection and create an inflammatory environment, leading to organ dysfunction. Oral Candida infections may cause temporary or permanent damage to salivary glands, resulting in the destruction of acinar cells and the formation of scar tissue. Restricted function of the salivary glands leads to discomfort and diseases of the oral mucosa, such as dry mouth and associated infection. This narrative review attempts to summarize the anatomy and function of salivary glands, the associations between Candida and saliva, the effects of Candida infection on salivary glands, and the treatment strategies. Overall, clinicians should proactively manage Candida infections by educating patients on oral hygiene management for vulnerable populations, conducting frequent checks for a timely diagnosis, and providing an effective treatment plan.
Update: Microdialysis for Monitoring Cerebral Metabolic Dysfunction after Subarachnoid Hemorrhage
Authors: Spencer Pierce , Jiang Yinghua , Liu Ning , Han Jinrui , Li Yadan , Vodovoz Samuel , Dumont Aaron S. , Wang Xiaoying
Published: December 2020

Cerebral metabolic dysfunction has been shown to extensively mediate the pathophysiology of brain injury after subarachnoid hemorrhage (SAH). The characterization of the alterations of metabolites in the brain can help elucidate pathophysiological changes occurring throughout SAH and the relationship between secondary brain injury and cerebral energy dysfunction after SAH. Cerebral microdialysis (CMD) is a tool that can measure concentrations of multiple bioenergetics metabolites in brain interstitial fluid. This review aims to provide an update on the implication of CMD on the measurement of metabolic dysfunction in the brain after SAH. A literature review was conducted through a general PubMed search with the terms “Subarachnoid Hemorrhage AND Microdialysis” as well as a more targeted search using MeSh with the search terms “Subarachnoid hemorrhage AND Microdialysis AND Metabolism.” Both experimental and clinical papers were reviewed. CMD is a suitable tool that has been used for monitoring cerebral metabolic changes in various types of brain injury. Clinically, CMD data have shown the dramatic changes in cerebral metabolism after SAH, including glucose depletion, enhanced glycolysis, and suppressed oxidative phosphorylation. Experimental studies using CMD have demonstrated a similar pattern of cerebral metabolic dysfunction after SAH. The combination of CMD and other monitoring tools has also shown value in further dissecting and distinguishing alterations in different metabolic pathways after brain injury. Despite the lack of a standard procedure as well as the presence of limitations regarding CMD application and data interpretation for both clinical and experimental studies, emerging investigations have suggested that CMD is an effective way to monitor the changes of cerebral metabolic dysfunction after SAH in real-time, and alternatively, the combination of CMD and other monitoring tools might be able to further understand the relationship between cerebral metabolic dysfunction and brain injury after SAH, determine the severity of brain injury and predict the pathological progression and outcomes after SAH. More translational preclinical investigations and clinical validation may help to optimize CMD as a powerful tool in critical care and personalized medicine for patients with SAH.
Vertical Ridge Augmentation of Fibula Flap in Mandibular Reconstruction: A Comparison between Vertical Distraction, Double-Barrel Flap and Iliac Crest Graft
Authors: Navarro Cuéllar Carlos , Ochandiano Caicoya Santiago , Navarro Cuéllar Ignacio , Valladares Pérez Salvador , Fariña Sirandoni Rodrigo , Antúnez-Conde Raúl , Díez Montiel Alberto , Sánchez Pérez Arturo , López López Ana María , Navarro Vila Carlos , Salmerón Escobar José Ignacio
Published: December 2020

Double-barrel flap, vertical distraction and iliac crest graft are used to reconstruct the vertical height of the fibula. Twenty-four patients with fibula flap were reconstructed comparing these techniques (eight patients in each group) in terms of height of bone, bone resorption, implant success rate and the effects of radiotherapy. The increase in vertical bone with vertical distraction, double-barrel flap and iliac crest was 12.5 ± 0.78 mm, 18.5 ± 0.5 mm, and 17.75 ± 0.6 mm, (p < 0.001). The perimplant bone resorption was 2.31 ± 0.12 mm, 1.23 ± 0.09 mm and 1.43 ± 0.042 mm (p < 0.001), respectively. There were significant differences in vertical bone reconstruction and bone resorption between double-barrel flap and vertical distraction and between iliac crest and vertical distraction (p < 0.001). The study did not show significant differences in implant failure (p = 0.346). Radiotherapy did not affect vertical bone reconstruction (p = 0.125) or bone resorption (p = 0.237) but it showed higher implant failure in radiated patients (p = 0.015). The double-barrel flap and iliac crest graft showed better stability in the height of bone and less bone resorption and higher implant success rates compared with vertical distraction. Radiation therapy did not affect the vertical bone reconstruction but resulted in a higher implant failure.
General Anesthesia Compared to Spinal Anesthesia for Patients Undergoing Lumbar Vertebral Surgery: A Meta-Analysis of Randomized Controlled Trials
Authors: De Cassai Alessandro , Geraldini Federico , Boscolo Annalisa , Pasin Laura , Pettenuzzo Tommaso , Persona Paolo , Munari Marina , Navalesi Paolo
Published: December 2020

Vertebral lumbar surgery can be performed under both general anesthesia (GA) and spinal anesthesia. A clear benefit from spinal anesthesia (SA) remains unproven. The aim of our meta-analysis was to compare the early analgesic efficacy and recovery after SA and GA in adult patients undergoing vertebral lumbar surgery. A systematic investigation with the following criteria was performed: adult patients undergoing vertebral lumbar surgery (P); single-shot SA (I); GA care with or without wound infiltration (C); analgesic efficacy measured as postoperative pain, intraoperative hypotension, bradycardia, length of surgery, blood loss, postoperative side effects (such as postoperative nausea/vomiting and urinary retention), overall patient and surgeon satisfaction, and length of hospital stay (O); and randomized controlled trials (S). The search was performed in Pubmed, the Cochrane Central Register of Controlled Trials, and Google Scholar up to 1 November 2020. Eleven studies were found upon this search. SA in vertebral lumbar surgery decreases postoperative pain and the analgesic requirement in the post anesthesia care unit. It is associated with a reduced incidence of postoperative nausea and vomiting and a higher patient satisfaction. It has no effect on urinary retention, intraoperative bradycardia, or hypotension. SA should be considered as a viable and efficient anesthetic technique in vertebral lumbar surgery.
Increasing the Density of Laboratory Measures for Machine Learning Applications
Authors: Abedi Vida , Li Jiang , Shivakumar Manu K. , Avula Venkatesh , Chaudhary Durgesh P. , Shellenberger Matthew J. , Khara Harshit S. , Zhang Yanfei , Lee Ming Ta Michael , Wolk Donna M. , Yeasin Mohammed , Hontecillas Raquel , Bassaganya-Riera Josep , Zand Ramin
Published: December 2020

Background. The imputation of missingness is a key step in Electronic Health Records (EHR) mining, as it can significantly affect the conclusions derived from the downstream analysis in translational medicine. The missingness of laboratory values in EHR is not at random, yet imputation techniques tend to disregard this key distinction. Consequently, the development of an adaptive imputation strategy designed specifically for EHR is an important step in improving the data imbalance and enhancing the predictive power of modeling tools for healthcare applications. Method. We analyzed the laboratory measures derived from Geisinger’s EHR on patients in three distinct cohorts—patients tested for Clostridioides difficile (Cdiff) infection, patients with a diagnosis of inflammatory bowel disease (IBD), and patients with a diagnosis of hip or knee osteoarthritis (OA). We extracted Logical Observation Identifiers Names and Codes (LOINC) from which we excluded those with 75% or more missingness. The comorbidities, primary or secondary diagnosis, as well as active problem lists, were also extracted. The adaptive imputation strategy was designed based on a hybrid approach. The comorbidity patterns of patients were transformed into latent patterns and then clustered. Imputation was performed on a cluster of patients for each cohort independently to show the generalizability of the method. The results were compared with imputation applied to the complete dataset without incorporating the information from comorbidity patterns. Results. We analyzed a total of 67,445 patients (11,230 IBD patients, 10,000 OA patients, and 46,215 patients tested for C. difficile infection). We extracted 495 LOINC and 11,230 diagnosis codes for the IBD cohort, 8160 diagnosis codes for the Cdiff cohort, and 2042 diagnosis codes for the OA cohort based on the primary/secondary diagnosis and active problem list in the EHR. Overall, the most improvement from this strategy was observed when the laboratory measures had a higher level of missingness. The best root mean square error (RMSE) difference for each dataset was recorded as −35.5 for the Cdiff, −8.3 for the IBD, and −11.3 for the OA dataset. Conclusions. An adaptive imputation strategy designed specifically for EHR that uses complementary information from the clinical profile of the patient can be used to improve the imputation of missing laboratory values, especially when laboratory codes with high levels of missingness are included in the analysis.
Real-World Data on Clinical Features, Outcomes, and Prognostic Factors in Multiple Myeloma from Miyazaki Prefecture, Japan
Authors: Akizuki Keiichi , Matsuoka Hitoshi , Toyama Takanori , Kamiunten Ayako , Sekine Masaaki , Shide Kotaro , Kameda Takuro , Kawano Noriaki , Maeda Kouichi , Takeuchi Masanori , Kawano Hiroshi , Sato Seiichi , Ishizaki Junzo , Tahira Yuki , Shimoda Haruko , Hidaka Tomonori , Yamashita Kiyoshi , Kubuki Yoko , Shimoda Kazuya
Published: December 2020

The prognosis of multiple myeloma (MM) has improved with the introduction of novel agents. These data are largely derived from clinical trials and might not reflect real-world patient outcomes accurately. We surveyed real-world data from 284 patients newly diagnosed with MM between 2010 and 2018 in Miyazaki Prefecture. The median follow-up period was 32.8 months. The median age at diagnosis was 71 years, with 68% of patients aged >65 years. The International Staging System (ISS) stage at diagnosis was I in 18.4% of patients, II in 34.1%, and III in 47.5%. Bortezomib-containing regimens were preferred as initial treatment; they were used in 147 patients (51.8%). In total, 80% of patients were treated with one or more novel agents (thalidomide, lenalidomide, or bortezomib). Among 228 patients who were treated with novel agents as an initial treatment, the overall response rate (partial response (PR) or better) to initial treatment was 78.4%, and the median time to next treatment (TTNT) was 11.6 months. In the multivariate analysis, PR or better responses to initial treatment were independently favorable prognostic factors for TTNT. The median survival time after initial therapy for patients with novel agents was 56.4 months and 3-year overall survival (OS) was 70.4%. In multivariate analysis, ISS stage I/II disease and PR or better response to initial treatment, and autologous stem cell transplantation (ASCT) were identified as independent prognostic factors for overall survival (OS).
Treatment and Prognosis of Myocardial Infarction Outside Cardiology Departments
Authors: Gard Anton , Lindahl Bertil , Hadziosmanovic Nermin , Baron Tomasz
Published: December 2020

Aim: Our aim was to investigate the characteristics, treatment and prognosis of patients with myocardial infarction (MI) treated outside a cardiology department (CD), compared with MI patients treated at a CD. Methods: A cohort of 1310 patients diagnosed with MI at eight Swedish hospitals in 2011 were included in this observational study. Patients were followed regarding all-cause mortality until 2018. Results: A total of 235 patients, exclusively treated outside CDs, were identified. These patients had more non-cardiac comorbidities, were older (mean age 83.7 vs. 73.1 years) and had less often type 1 MIs (33.2% vs. 74.2%), in comparison with the CD patients. Advanced age and an absence of chest pain were the strongest predictors of non-CD care. Only 3.8% of non-CD patients were investigated with coronary angiography and they were also prescribed secondary preventive pharmacological treatments to a lesser degree, with only 32.3% having statin therapy at discharge. The all-cause mortality was higher in non-CD patients, also after adjustment for baseline parameters, both at 30 days (hazard ratio (HR) 2.28; 95% confidence interval (CI) 1.62–3.22), one year (HR 1.82; 95% CI 1.39–2.36) and five years (HR 1.62; 95% CI 1.32–1.98). Conclusions: MI treatment outside CDs is associated with an adverse short- and long-term prognosis. An improved use of percutaneous coronary intervention (PCI) and secondary preventive pharmacological treatment might improve the long-term prognosis in these patients.