bluuebunny/crossref_metadata_2025 huggingface dataset:
Intimate Partner Violence: A Risk Factor for Gestational Diabetes
Authors: Pheiffer Carmen , Dias Stephanie , Adam Sumaiya
Published: October 2020

The early detection and management of gestational diabetes mellitus (GDM) is an important public health goal. GDM, which is defined as a glucose intolerance that develops during pregnancy, affects about 14% of pregnancies globally, and without effective treatment, it is associated with adverse short- and long-term maternal and neonatal outcomes. Risk-factor screening is an acceptable and affordable strategy to enable risk stratification and intervention. However, common biological risk factors such as overweight or obesity, excessive gestational weight gain, and family history of diabetes often have poor predictive ability, failing to identify a large proportion of women at risk of developing GDM. Accumulating evidence implicate psychosocial factors in contributing to GDM risk. As such, intimate partner violence (IPV), through its contributing effects on maternal stress and depression, presents a plausible risk factor for GDM. Experiencing IPV during pregnancy may dysregulate the hypothalamus–pituitary–adrenal (HPA) axis, leading to increased cortisol secretion and insulin resistance. These effects may exacerbate the insulin-resistant environment characteristic of pregnancy, thus increasing GDM risk. This review explores the relationship between IPV and GDM. We highlight studies that have linked IPV with GDM and propose a biological mechanism that connects IPV and GDM. Recommendations for IPV screening strategies to prevent GDM are discussed.
Spatio-Temporal Research Data Infrastructure in the Context of Autonomous Driving
Authors: Fischer Colin , Sester Monika , Schön Steffen
Published: October 2020

In this paper, we present an implementation of a research data management system that features structured data storage for spatio-temporal experimental data (environmental perception and navigation in the framework of autonomous driving), including metadata management and interfaces for visualization and parallel processing. The demands of the research environment, the design of the system, the organization of the data storage, and computational hardware as well as structures and processes related to data collection, preparation, annotation, and storage are described in detail. We provide examples for the handling of datasets, explaining the required data preparation steps for data storage as well as benefits when using the data in the context of scientific tasks.
What Influences Customer Flows in Shopping Malls: Perspective from Indoor Positioning Data
Authors: Pei Tao , Liu Yaxi , Shu Hua , Ou Yang , Wang Meng , Xu Lianming
Published: October 2020

Offline stores are seriously challenged by online shops. To attract more customers to compete with online shops, the patterns of customer flows and their influence factors are important knowledge. To address this issue, we collected indoor positioning data of 534,641 and 59,160 customers in two shopping malls (i.e., Dayuecheng (DYC) in Beijing and Longhu (LH) in Chongqing, China) for one week, respectively. The temporal patterns of the customer flows show that (1) total customer flows are high on weekends and low midweek and (2) peak hourly flow is related to mealtimes for LH and only on weekdays for DYC. The difference in temporal patterns between the two malls may be attributed to the difference in their locations. The customer flows to stores reveal that the customer flows to clothing, food and general stores are the highest; specifically, in DYC, the order is clothing, food and general, while in LH, it is food, clothing and general. To identify the factors influencing customer flow, we applied linear regression to the inflow density of stores (customers per square meter) of two major classes (clothing and food stores), with 10 locational and social factors as independent variables. The results indicate that flow density is significantly influenced by store location, visibility (except for food stores in DYC) and reputation. Besides, the difference between the two store classes is that clothing stores are influenced by more convenience factors, including distance to an elevator and distance to the floor center (only for LH). Overall, the two shopping malls demonstrate similar customer flow patterns and influencing factors with some obvious differences also attributed to their layout, functions and locations.
A Novel Rapid Method for Viewshed Computation on DEM through Max-Pooling and Min-Expected Height
Authors: Pan Zhibin , Tang Jin , Tjahjadi Tardi , Wu Zhihu , Xiao Xiaoming
Published: October 2020

Viewshed computation of a digital elevation model (DEM) plays an important role in a geographic information system, but the required high computational time is a serious problem for a practical application. Hitherto, the mainstream methods of viewshed computing include line-of-sight method, reference planes method, etc. Based on these classical algorithms, a new algorithm for viewshed computation is proposed in this paper: the Matryoshka doll algorithm. Through a pooling operation, the minimum expected height of the DEM is introduced as max-pooling with minimum expected height in the viewshed computing optimization. This is to increase the efficiency and adaptability of the computation of the visibility range. The experimental results demonstrate that the algorithm has obvious advantages in computing speed, but with the accuracy only slightly reduced.
Adsorption of Anthocyanins by Cation and Anion Exchange Resins with Aromatic and Aliphatic Polymer Matrices
Authors: Pismenskaya Natalia , Sarapulova Veronika , Klevtsova Anastasia , Mikhaylin Sergey , Bazinet Laurent
Published: October 2020

This study examines the mechanisms of adsorption of anthocyanins from model aqueous solutions at pH values of 3, 6, and 9 by ion-exchange resins making the main component of heterogeneous ion-exchange membranes. This is the first report demonstrating that the pH of the internal solution of a KU-2-8 aromatic cation-exchange resin is 2-3 units lower than the pH of the external bathing anthocyanin-containing solution, and the pH of the internal solution of some anion-exchange resins with an aromatic (AV-17-8, AV-17-2P) or aliphatic (EDE-10P) matrix is 2–4 units higher than the pH of the external solution. This pH shift is caused by the Donnan exclusion of hydroxyl ions (in the KU-2-8 resin) or protons (in the AV-17-8, AV-17-2P, and EDE-10P resins). The most significant pH shift is observed for the EDE-10P resin, which has the highest ion-exchange capacity causing the highest Donnan exclusion. Due to the pH shift, the electric charge of anthocyanin inside an ion-exchange resin differs from its charge in the external solution. At pH 6, the external solution contains uncharged anthocyanin molecules. However, in the AV-17-8 and AV-17-2P resins, the anthocyanins are present as singly charged anions, while in the EDE-10P resin, they are in the form of doubly charged anions. Due to the electrostatic interactions of these anions with the positively charged fixed groups of anion-exchange resins, the adsorption capacities of AV-17-8, AV-17-2P, and EDE-10P were higher than expected. It was established that the electrostatic interactions of anthocyanins with the charged fixed groups increase the adsorption capacity of the aromatic resin by a factor of 1.8–2.5 compared to the adsorption caused by the π–π (stacking) interactions. These results provide new insights into the fouling mechanism of ion-exchange materials by polyphenols; they can help develop strategies for membrane cleaning and for extracting anthocyanins from juices and wine using ion-exchange resins and membranes.
Monitoring Cannabinoid CB2 -Receptor Mediated cAMP Dynamics by FRET-Based Live Cell Imaging
Authors: Mensching Leonore , Rading Sebastian , Nikolaev Viacheslav , Karsak Meliha
Published: October 2020

G-protein coupled cannabinoid CB2 receptor signaling and function is primarily mediated by its inhibitory effect on adenylate cyclase. The visualization and monitoring of agonist dependent dynamic 3′,5′-cyclic adenosine monophosphate (cAMP) signaling at the single cell level is still missing for CB2 receptors. This paper presents an application of a live cell imaging while using a Förster resonance energy transfer (FRET)-based biosensor, Epac1-camps, for quantification of cAMP. We established HEK293 cells stably co-expressing human CB2 and Epac1-camps and quantified cAMP responses upon Forskolin pre-stimulation, followed by treatment with the CB2 ligands JWH-133, HU308, β-caryophyllene, or 2-arachidonoylglycerol. We could identify cells showing either an agonist dependent CB2-response as expected, cells displaying no response, and cells with constitutive receptor activity. In Epac1-CB2-HEK293 responder cells, the terpenoid β-caryophyllene significantly modified the cAMP response through CB2. For all of the tested ligands, a relatively high proportion of cells with constitutively active CB2 receptors was identified. Our method enabled the visualization of intracellular dynamic cAMP responses to the stimuli at single cell level, providing insights into the nature of heterologous CB2 expression systems that contributes to the understanding of Gαi-mediated G-Protein coupled receptor (GPCR) signaling in living cells and opens up possibilities for future investigations of endogenous CB2 responses.
MicroRNA Biomarkers in IBD—Differential Diagnosis and Prediction of Colitis-Associated Cancer
Authors: James Jaslin P. , Riis Lene Buhl , Malham Mikkel , Høgdall Estrid , Langholz Ebbe , Nielsen Boye S
Published: October 2020

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). These are chronic autoimmune diseases of unknown etiology affecting the gastrointestinal tract. The IBD population includes a heterogeneous group of patients with varying disease courses requiring personalized treatment protocols. The complexity of the disease often delays the diagnosis and the initiation of appropriate treatments. In a subset of patients, IBD leads to colitis-associated cancer (CAC). MicroRNAs are single-stranded regulatory noncoding RNAs of 18 to 22 nucleotides with putative roles in the pathogenesis of IBD and colorectal cancer. They have been explored as biomarkers and therapeutic targets. Both tissue-derived and circulating microRNAs have emerged as promising biomarkers in the differential diagnosis and in the prognosis of disease severity of IBD as well as predictive biomarkers in drug resistance. In addition, knowledge of the cellular localization of differentially expressed microRNAs is a prerequisite for deciphering the biological role of these important epigenetic regulators and the cellular localization may even contribute to an alternative repertoire of biomarkers. In this review, we discuss findings based on RT-qPCR, microarray profiling, next generation sequencing and in situ hybridization of microRNA biomarkers identified in the circulation and in tissue biopsies.
Copper(II) Binding by the Earliest Vertebrate Gonadotropin-Releasing Hormone, the Type II Isoform, Suggests an Ancient Role for the Metal
Authors: Peacey Lorraine , Peacey Charlotte , Gutzinger Adele , Jones Christopher E.
Published: October 2020

In vertebrate reproductive biology copper can influence peptide and protein function both in the pituitary and in the gonads. In the pituitary, copper binds to the key reproductive peptides gonadotropin-releasing hormone I (GnRH-I) and neurokinin B, to modify their structure and function, and in the male gonads, copper plays a role in testosterone production, sperm morphology and, thus, fertility. In addition to GnRH-I, most vertebrates express a second isoform, GnRH-II. GnRH-II can promote testosterone release in some species and has other non-reproductive roles. The primary sequence of GnRH-II has remained largely invariant over millennia, and it is considered the ancestral GnRH peptide in vertebrates. In this work, we use a range of spectroscopic techniques to show that, like GnRH-I, GnRH-II can bind copper. Phylogenetic analysis shows that the proposed copper-binding ligands are retained in GnRH-II peptides from all vertebrates, suggesting that copper-binding is an ancient feature of GnRH peptides.
The Microenvironment of Decellularized Extracellular Matrix from Heart Failure Myocardium Alters the Balance between Angiogenic and Fibrotic Signals from Stromal Primitive Cells
Authors: Belviso Immacolata , Angelini Francesco , Di Meglio Franca , Picchio Vittorio , Sacco Anna Maria , Nocella Cristina , Romano Veronica , Nurzynska Daria , Frati Giacomo , Maiello Ciro , Messina Elisa , Montagnani Stefania , Pagano Francesca , Castaldo Clotilde , Chimenti Isotta
Published: October 2020

Cardiac adverse remodeling is characterized by biological changes that affect the composition and architecture of the extracellular matrix (ECM). The consequently disrupted signaling can interfere with the balance between cardiogenic and pro-fibrotic phenotype of resident cardiac stromal primitive cells (CPCs). The latter are important players in cardiac homeostasis and can be exploited as therapeutic cells in regenerative medicine. Our aim was to compare the effects of human decellularized native ECM from normal (dECM-NH) or failing hearts (dECM-PH) on human CPCs. CPCs were cultured on dECM sections and characterized for gene expression, immunofluorescence, and paracrine profiles. When cultured on dECM-NH, CPCs significantly upregulated cardiac commitment markers (CX43, NKX2.5), cardioprotective cytokines (bFGF, HGF), and the angiogenesis mediator, NO. When seeded on dECM-PH, instead, CPCs upregulated pro-remodeling cytokines (IGF-2, PDGF-AA, TGF-β) and the oxidative stress molecule H2O2. Interestingly, culture on dECM-PH was associated with impaired paracrine support to angiogenesis, and increased expression of the vascular endothelial growth factor (VEGF)-sequestering decoy isoform of the KDR/VEGFR2 receptor. Our results suggest that resident CPCs exposed to the pathological microenvironment of remodeling ECM partially lose their paracrine angiogenic properties and release more pro-fibrotic cytokines. These observations shed novel insights on the crosstalk between ECM and stromal CPCs, suggesting also a cautious use of non-healthy decellularized myocardium for cardiac tissue engineering approaches.
Comparison of Dietary Oils with Different Polyunsaturated Fatty Acid n-3 and n-6 Content in the Rat Model of Cutaneous Wound Healing
Authors: Komprda Tomas , Sladek Zbysek , Sevcikova Zuzana , Svehlova Veronika , Wijacki Jan , Guran Roman , Do Tomas , Lackova Zuzana , Polanska Hana , Vrlikova Lucie , Popelkova Vendula , Michalek Petr , Zitka Ondrej , Buchtova Marcela
Published: October 2020

Dietary supplementation with polyunsaturated fatty acids (PUFA) n-3 can affect cutaneous wound healing; however, recent findings demonstrate the variable extent of their influence on the quality of healing. Here, we compare the effect of several dietary oils, containing different levels of PUFA n-3 and PUFA n-6, on wound healing in the rat model. Rats were fed the feed mixture with 8% palm oil (P), safflower oil (S), fish oil (F) or Schizochytrium microalga extract (Sch) and compared to the animals fed by control feed mixture (C). Dorsal full-thickness cutaneous excisions were performed after 52 days of feeding and skin was left to heal for an additional 12 days. Histopathological analysis of skin wounds was performed, including immune cells immunolabeling and the determination of hydroxyproline amount as well as gene expression analyses of molecules contributing to different steps of the healing. Matrix-assisted-laser-desorption-ionization mass-spectrometry-imaging (MALDI-MSI) was used to determine the amount of collagen α-1(III) chain fragment in healing samples. Treatment by Schizochytrium extract resulted in decrease in the total wound area, in contrast to the safflower oil group where the size of the wound was larger when comparing to control animals. Diet with Schizochytrium extract and safflower oils displayed a tendency to increase the number of new vessels. The number of MPO-positive cells was diminished following any of oil treatment in comparison to the control, but their highest amount was found in animals with a fish oil diet. On the other hand, the number of CD68-positive macrophages was increased, with the most significant enhancement in the fish oil and safflower oil group. Hydroxyproline concentration was the highest in the safflower oil group but it was also enhanced in all other analyzed treatments in comparison to the control. MALDI-MSI signal intensity of a collagen III fragment decreased in the sequence C > S > Sch > P > F treatment. In conclusion, we observed differences in tissue response during healing between dietary oils, with the activation of inflammation observed following the treatment with oil containing high eicosapentaenoic acid (EPA) level (fish oil) and enhanced healing features were induced by the diet with high content of docosahexaenoic acid (DHA, Schizochytrium extract).
Modeling Rheumatoid Arthritis In Vitro: From Experimental Feasibility to Physiological Proximity
Authors: Damerau Alexandra , Gaber Timo
Published: October 2020

Rheumatoid arthritis (RA) is a chronic, inflammatory, and systemic autoimmune disease that affects the connective tissue and primarily the joints. If not treated, RA ultimately leads to progressive cartilage and bone degeneration. The etiology of the pathogenesis of RA is unknown, demonstrating heterogeneity in its clinical presentation, and is associated with autoantibodies directed against modified self-epitopes. Although many models already exist for RA for preclinical research, many current model systems of arthritis have limited predictive value because they are either based on animals of phylogenetically distant origin or suffer from overly simplified in vitro culture conditions. These limitations pose considerable challenges for preclinical research and therefore clinical translation. Thus, a sophisticated experimental human-based in vitro approach mimicking RA is essential to (i) investigate key mechanisms in the pathogenesis of human RA, (ii) identify targets for new therapeutic approaches, (iii) test these approaches, (iv) facilitate the clinical transferability of results, and (v) reduce the use of laboratory animals. Here, we summarize the most commonly used in vitro models of RA and discuss their experimental feasibility and physiological proximity to the pathophysiology of human RA to highlight new human-based avenues in RA research to increase our knowledge on human pathophysiology and develop effective targeted therapies.
Transcriptomic Analysis of Age-Associated Periventricular Lesions Reveals Dysregulation of the Immune Response
Authors: Fadul Motaz M. , Heath Paul R. , Cooper-Knock Johnathan , Kurz Julian M. , Al-Azzawi Hayder A. , Ali Zarki , Smith Taylor , Matthews Fiona E. , Brayne Carol , Wharton Stephen B. , Simpson Julie E.
Published: October 2020

White matter lesions (WML) are a common feature of the ageing brain associated with cognitive impairment. The gene expression profiles of periventricular lesions (PVL, n = 7) and radiologically-normal-appearing (control) periventricular white matter cases (n = 11) obtained from the Cognitive Function and Ageing Study (CFAS) neuropathology cohort were interrogated using microarray analysis and NanoString to identify novel mechanisms potentially underlying their formation. Histological characterisation of control white matter cases identified a subgroup (n = 4) which contained high levels of MHC-II immunoreactive microglia, and were classified as “pre-lesional.” Microarray analysis identified 2256 significantly differentially-expressed genes (p ≤ 0.05, FC ≥ 1.2) in PVL compared to non-lesional control white matter (1378 upregulated and 878 downregulated); 2649 significantly differentially-expressed genes in “pre-lesional” cases compared to PVL (1390 upregulated and 1259 downregulated); and 2398 significantly differentially-expressed genes in “pre-lesional” versus non-lesional control cases (1527 upregulated and 871 downregulated). Whilst histological evaluation of a single marker (MHC-II) implicates immune-activated microglia in lesion pathology, transcriptomic analysis indicates significant downregulation of a number of activated microglial markers and suggests established PVL are part of a continuous spectrum of white matter injury. The gene expression profile of “pre-lesional” periventricular white matter suggests upregulation of several signalling pathways may be a neuroprotective response to prevent the pathogenesis of PVL.
Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock
Authors: Hänninen Mikko , Jäntti Toni , Tolppanen Heli , Segersvärd Heli , Tarvasmäki Tuukka , Lassus Johan , Vausort Mélanie , Devaux Yvan , Sionis Alessandro , Tikkanen Ilkka , Harjola Veli-Pekka , Lakkisto Päivi ,   for the CardShock Study Group
Published: October 2020

Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5–10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1–3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.
The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease
Authors: Blondelle Jordan , Biju Andrea , Lange Stephan
Published: October 2020

The well-orchestrated turnover of proteins in cross-striated muscles is one of the fundamental processes required for muscle cell function and survival. Dysfunction of the intricate protein degradation machinery is often associated with development of cardiac and skeletal muscle myopathies. Most muscle proteins are degraded by the ubiquitin–proteasome system (UPS). The UPS involves a number of enzymes, including E3-ligases, which tightly control which protein substrates are marked for degradation by the proteasome. Recent data reveal that E3-ligases of the cullin family play more diverse and crucial roles in cross striated muscles than previously anticipated. This review highlights some of the findings on the multifaceted functions of cullin-RING E3-ligases, their substrate adapters, muscle protein substrates, and regulatory proteins, such as the Cop9 signalosome, for the development of cross striated muscles, and their roles in the etiology of myopathies.
An Extended Version of an Algebraic Intermittency Model for Prediction of Separation-Induced Transition at Elevated Free-Stream Turbulence Level
Authors: Kubacki Slawomir , Simoni Daniele , Lengani Davide , Dick Erik
Published: October 2020

An algebraic intermittency model for boundary layer flow transition from laminar to turbulent state, is extended using an experimental data base on boundary layer flows with various transition types and results by large eddy simulation of transition in a separated boundary layer. The originating algebraic transition model functions well for bypass transition in an attached boundary layer under a moderately high or elevated free-stream turbulence level, and for transition by Kelvin–Helmholtz instability in a separated boundary layer under a low free-stream turbulence level. It also functions well for transition in a separated layer, caused by a very strong adverse pressure gradient under a moderately high or elevated free-stream turbulence level. It is not accurate for transition in a separated layer under a moderately strong adverse pressure gradient, in the presence of a moderately high or elevated free-stream turbulence level. The extension repairs this deficiency. Therefore, a sensor function for detection of the front part of a separated boundary layer activates two terms that express the effect of free-stream turbulence on the breakdown of a separated layer, without changing the functioning of the model in other flow regions. The sensor and the breakdown terms use only local variables.
Deciphering the Genetics of Primary Angioedema with Normal Levels of C1 Inhibitor
Authors: Loules Gedeon , Parsopoulou Faidra , Zamanakou Maria , Csuka Dorottya , Bova Maria , González-Quevedo Teresa , Psarros Fotis , Porebski Gregor , Speletas Matthaios , Firinu Davide , del Giacco Stefano , Suffritti Chiara , Makris Michael , Vatsiou Sofia , Zanichelli Andrea , Farkas Henriette , Germenis Anastasios E.
Published: October 2020

The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with F12 alterations as well as those with histaminergic acquired angioedema were excluded. A variant pathogenicity curation strategy was followed, including a comparison of the results with those of genotyping 169 patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), and only filtered-in variants were studied further. Among the examined nl-C1-INH-HAE patients, carriers of neither the ANGPT1 p.Ala119Ser nor the KNG1 p.Met379Lys variant were found, whereas the PLG p.Lys330Glu was detected in four (3%) unrelated probands (one homozygote). In total, 182 different variants were curated, 21 of which represented novel mutations. Although the frequency of variants per gene was comparable between nl-C1-INH-HAE and C1-INH-HAE, variants of the KNG1 and XPNPEP1 genes were detected only in nl-C1-INH-HAE patients (six and three, respectively). Twenty-seven filtered variants in 23 different genes were detected in nl-C1-INH-HAE more than once, whereas 69/133 nl-C1-INH-HAE patients had compound heterozygotes of filtered variants located in the same or different genes. Pedigree analysis was performed where feasible. Our results indicate the role that alterations in some genes, like KNG1, may play in disease pathogenesis, the complex trait that is possibly underlying in some cases, and the existence of hitherto unrecognized disease endotypes.
Efficacy of Manual Therapy in Temporomandibular Joint Disorders and Its Medium-and Long-Term Effects on Pain and Maximum Mouth Opening: A Systematic Review and Meta-Analysis
Authors: Herrera-Valencia Andres , Ruiz-Muñoz Maria , Martin-Martin Jaime , Cuesta-Vargas Antonio , González-Sánchez Manuel
Published: October 2020

The aim of this study was to conduct a systematic review of the medium- and long-term efficacy of manual therapy for temporomandibular joint disorders, alone or in combination with therapeutic exercise. Information was compiled from the PubMed, SCOPUS, Cochrane, SciELO and PEDro databases. The inclusion criteria were established: randomized controlled trials only; participants must present any kind of temporomandibular disorder; the treatments must include manual therapy in at least one of the experimental groups; a minimum of 3 months of follow-up; pain must be one of the primary or secondary outcomes; and the article must be available in English, Spanish, Italian, Portuguese or French. Six documents that fulfilled all the criteria were obtained for analysis, two of them considered low quality and four considered high quality. A significant improvement in pain and mouth opening compared to baseline was observed after manual therapy treatment. Manual therapy seems to be an effective treatment for temporomandibular disorders in the medium term, although the effect appears to decrease over time. However, when complemented with therapeutic exercise, these effects can be maintained in the long term. This review underlines the importance of manual therapy and therapeutic exercise for the medium- and long-term treatment of temporomandibular joint disorders in daily practice.
Inhaled Corticosteroids and COVID-19 Risk and Mortality: A Nationwide Cohort Study
Authors: Choi Jae Chol , Jung Sun-Young , Yoon Una A. , You Seung-Hun , Kim Myo-Song , Baek Moon Seong , Jung Jae-Woo , Kim Won-Young
Published: October 2020

Inhaled corticosteroids (ICS) could increase both the risk of coronavirus disease 2019 (COVID-19) and experiencing poor outcomes. To compare the clinical outcomes between ICS users and nonusers, COVID-19-related claims in the Korean Health Insurance Review and Assessment database were evaluated. To evaluate susceptibility to COVID-19 among patients with COPD or asthma, a nested case-control study was performed using the same database. In total, 7341 patients were confirmed to have COVID-19, including 114 ICS users and 7227 nonusers. Among 5910 patients who were hospitalized, death was observed for 9% of ICS users and 4% of nonusers. However, this association was not significant when adjusted for age, sex, region, comorbidities, and hospital type (aOR, 0.94; 95% CI, 0.43–2.07). The case-control analysis of COPD compared 640 cases with COVID-19 to 2560 matched controls without COVID-19, and the analysis of asthma compared 90 cases with COVID-19 to 360 matched controls without COVID-19. Use of ICS was not significantly associated with COVID-19 among patients with COPD (aOR, 1.02; 95% CI, 0.46–2.25) or asthma (aOR, 0.38; 95% CI, 0.13–1.17). Prior ICS use was not significantly associated with COVID-19 in patients with COPD or asthma, nor with clinical outcomes among patients with COVID-19.
Impact of Diabetes Mellitus on Outcomes after High-Risk Interventional Coronary Procedures
Authors: Johannsen Laura , Soldat Julian , Krueger Andrea , Mahabadi Amir A. , Dykun Iryna , Totzeck Matthias , Jánosi Rolf Alexander , Rassaf Tienush , Al-Rashid Fadi
Published: October 2020

An increasing number of patients with coronary artery disease are at high operative risk due to advanced age, severe comorbidities, complex coronary anatomy, and reduced ejection fraction. Consequently, these high-risk patients are often offered percutaneous coronary intervention (PCI) as an alternative to coronary artery bypass grafting (CABG). We aimed to investigate the outcome of patients with diabetes mellitus (DM) undergoing high-risk PCI. We analyzed consecutive patients undergoing high-risk PCI (period 01/2016–08/2018). In-hospital major adverse cardiac and cerebrovascular events (MACCEs), defined as in-hospital stroke, myocardial infarction and death, and the one-year incidence of death from any cause were assessed in patients with and without DM. There were 276 patients (age 70 years, 74% male) who underwent high-risk PCI. Eighty-six patients (31%) presented with DM (insulin-dependent DM: n = 24; non-insulin-dependent DM: n = 62). In-hospital MACCEs occurred in 9 patients (3%) with a non-significant higher rate in patients with DM (n = 5/86, 6% vs. n = 4/190 2%; p = 0.24). In patients without DM, the survival rate was insignificantly higher than in patients with DM (93.6% vs. 87.1%; p = 0.07). One-year survival was not significantly different in DM patients with more complex coronary artery disease (SYNTAX I-score ≤ 22: 89.3% vs. > 22: 84.5%; p = 0.51). In selected high-risk patients undergoing high-risk PCI, DM was not associated with an increased incidence of in-hospital MACCEs or a decreased one-year survival rate.
Anterior Scleral Regional Variation between Asian and Caucasian Populations
Authors: Consejo Alejandra , Wu Richard , Abass Ahmed
Published: October 2020

Purpose: To evaluate the anterior scleral shape regional differences between Asian and Caucasian populations. Methods: The study included 250 Asian eyes and 235 Caucasian eyes from participants aged 22 to 67 years (38.5 ± 7.6). Three-dimensional (3D) corneo-scleral maps were acquired using a corneo-scleral topographer (Eye Surface Profiler, Eaglet Eye BV) and used to calculate sagittal height. For each 3D map, the sclera (maximum diameter of 18 mm) and cornea were separated at the limbus using an automated technique. Advanced data processing steps were applied to ensure levelled artefact-free datasets to build an average scleral shape map for each population. Results: Statistically, Asian and Caucasian sclerae are significantly different from each other in sagittal height (overall sclera, p = 0.001). The largest difference in sagittal height between groups was found in the inferior-temporal region (271 ± 203 µm, p = 0.03), whereas the smallest difference was found in the superior-temporal region (84 ± 105 µm, p = 0.17). The difference in sagittal height between Caucasian and Asian sclera increases with the distance from the limbus. Conclusions: Asian anterior sclera was found to be less elevated than Caucasian anterior sclera. However, the nasal area of the sclera is less elevated than the temporal area, independently of race. Gaining knowledge in race-related scleral topography differences could assist contact lens manufacturers in the process of lens design and practitioners during the process of contact lens fitting.
The Role of Alcohol Metabolism in the Pathology of Alcohol Hangover
Authors: Mackus Marlou , Loo Aurora JAE van de , Garssen Johan , Kraneveld Aletta D. , Scholey Andrew , Verster Joris C.
Published: October 2020

The limited number of available studies that examined the pathology of alcohol hangover focused on biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol as potentially important determinants of hangover severity. The available literature on alcohol metabolism and oxidative stress is reviewed in this article. The current body of evidence suggests a direct relationship between blood ethanol concentration and hangover severity, whereas this association is not significant for acetaldehyde. The rate of alcohol metabolism seems to be an important determinant of hangover severity. That is, fast elimination of ethanol is associated with experiencing less severe hangovers. An explanation for this observation may be the fact that ethanol—in contrast to acetaldehyde—is capable of crossing the blood–brain barrier. With slower ethanol metabolism, more ethanol is able to reach the brain and elicit hangover symptoms. Hangover severity was also significantly associated with biomarkers of oxidative stress. More oxidative stress in the first hours after alcohol consumption was associated with less severe next-day hangovers (i.e., a significant negative correlation was found between hangover severity and malondialdehyde). On the contrary, more oxidative stress at a later stage after alcohol consumption was associated with having more severe next-day hangovers (i.e., a significant positive correlation was found between hangover severity and 8-isoprostane). In conclusion, assessment of biomarkers of alcohol metabolism suggests that fast elimination of ethanol is associated with experiencing less severe hangovers. More research is needed to further examine the complex interrelationship between alcohol metabolism, the role of acetaldehyde and oxidative stress and antioxidants, and the pathology of the alcohol hangover.
Comparison of the Visibility of Fetal Tooth Buds on 1.5 and 3 Tesla MRI
Authors: Kunzendorf Burkhard , Diogo Mariana C. , Covini Delfina I. , Weber Michael , Gruber Gerlinde M. , Zeilhofer Hans-Florian , Berg Britt-Isabelle , Prayer Daniela
Published: October 2020

Dental anomalies coincide with genetic disorders, and prenatal identification may contribute to a more accurate diagnosis. The aim of this study was to assess whether fetal Magnet Resonance Imaging (MRI) is suitable to visualize and investigate intrauterine dental development in the upper jaw, and to compare the quality of visibility of tooth buds between 1.5 Tesla (T) and 3T images. MR images of fetuses Gestational Week (GW) 26.71 ± 4.97 from 286 pregnant women with diagnoses unrelated to dental anomalies were assessed by three raters. We compared the visibility between groups and field strengths in five gestational age groups, using chi square and Fisher’s exact tests. All ten primary tooth buds were identifiable in 5.4% at GW 18–21, in 75.5% at GW 26–29, and in 90.6% at GW 34+. Before GW 30, more tooth buds were identifiable on 3T images than on 1.5T images. Statistical significance was only reached for identification of incisors (p = 0.047). Therefore, 1.5T and 3T images are viable to visualize tooth buds, particularly after GW 25, and their analysis may serve as diagnostic criterion. MRI tooth bud data might have an impact on various fields of research, such as the maldevelopment of teeth and their causes. Analyzing tooth buds as an additional diagnostic criterion is not time consuming, and could lead to an improvement of syndrome diagnosis.
Diagnosis and Treatment of Early Chronic Obstructive Lung Disease (COPD)
Authors: Choi Joon Young , Rhee Chin Kook
Published: October 2020

Chronic obstructive lung disease (COPD) is responsible for substantial rates of mortality and economic burden, and is one of the most important public-health concerns. As the disease characteristics include irreversible airway obstruction and progressive lung function decline, there has been a great deal of interest in detection at the early stages of COPD during the “at risk” or undiagnosed preclinical stage to prevent the disease from progressing to the overt stage. Previous studies have used various definitions of early COPD, and the term mild COPD has also often been used. There has been a great deal of recent effort to establish a definition of early COPD, but comprehensive evaluation is still required, including identification of risk factors, various physiological and radiological tests, and clinical manifestations for diagnosis of early COPD, considering the heterogeneity of the disease. The treatment of early COPD should be considered from the perspective of prevention of disease progression and management of clinical deterioration. There has been a lack of studies on this topic as the definition of early COPD has been proposed only recently, and therefore further clinical studies are needed.
Development of Machine Learning Model to Predict the 5-Year Risk of Starting Biologic Agents in Patients with Inflammatory Bowel Disease (IBD): K-CDM Network Study
Authors: Choi Youn I , Park Sung Jin , Chung Jun-Won , Kim Kyoung Oh , Cho Jae Hee , Kim Young Jae , Lee Kang Yoon , Kim Kwang Gi , Park Dong Kyun , Kim Yoon Jae
Published: October 2020

Background: The incidence and global burden of inflammatory bowel disease (IBD) have steadily increased in the past few decades. Improved methods to stratify risk and predict disease-related outcomes are required for IBD. Aim: The aim of this study was to develop and validate a machine learning (ML) model to predict the 5-year risk of starting biologic agents in IBD patients. Method: We applied an ML method to the database of the Korean common data model (K-CDM) network, a data sharing consortium of tertiary centers in Korea, to develop a model to predict the 5-year risk of starting biologic agents in IBD patients. The records analyzed were those of patients diagnosed with IBD between January 2006 and June 2017 at Gil Medical Center (GMC; n = 1299) or present in the K-CDM network (n = 3286). The ML algorithm was developed to predict 5- year risk of starting biologic agents in IBD patients using data from GMC and externally validated with the K-CDM network database. Result: The ML model for prediction of IBD-related outcomes at 5 years after diagnosis yielded an area under the curve (AUC) of 0.86 (95% CI: 0.82–0.92), in an internal validation study carried out at GMC. The model performed consistently across a range of other datasets, including that of the K-CDM network (AUC = 0.81; 95% CI: 0.80–0.85), in an external validation study. Conclusion: The ML-based prediction model can be used to identify IBD-related outcomes in patients at risk, enabling physicians to perform close follow-up based on the patient’s risk level, estimated through the ML algorithm.
Exposure to Porphyromonas gingivalis Induces Production of Proinflammatory Cytokine via TLR2 from Human Respiratory Epithelial Cells
Authors: Watanabe Norihisa , Yokoe Sho , Ogata Yorimasa , Sato Shuichi , Imai Kenichi
Published: October 2020

Aspiration pneumonia is a major health problem owing to its high mortality rate in elderly people. The secretion of proinflammatory cytokines such as interleukin (IL)-8 and IL-6 by respiratory epithelial cells, which is induced by infection of respiratory bacteria such as Streptococcus pneumoniae, contributes to the onset of pneumonia. These cytokines thus play a key role in orchestrating inflammatory responses in the lower respiratory tract. In contrast, chronic periodontitis, a chronic inflammatory disease caused by the infection of periodontopathic bacteria, typically Porphyromonas gingivalis, is one of the most prevalent microbial diseases affecting humans globally. Although emerging evidence has revealed an association between aspiration pneumonia and chronic periodontitis, a causal relationship between periodontopathic bacteria and the onset of aspiration pneumonia has not been established. Most periodontopathic bacteria are anaerobic and are therefore unlikely to survive in the lower respiratory organs of humans. Therefore, in this study, we examined whether simple contact by heat-inactivated P. gingivalis induced proinflammatory cytokine production by several human respiratory epithelial cell lines. We found that P. gingivalis induced strong IL-8 and IL-6 secretion by BEAS-2B bronchial epithelial cells. P. gingivalis also induced strong IL-8 secretion by Detroit 562 pharyngeal epithelial cells but not by A549 alveolar epithelial cells. Additionally, Toll-like receptor (TLR) 2 but not TLR4 was involved in the P. gingivalis-induced proinflammatory cytokine production. Furthermore, P. gingivalis induced considerably higher IL-8 and IL-6 production than heat-inactivated S. pneumoniae. Our results suggest that P. gingivalis is a powerful inflammatory stimulant for human bronchial and pharyngeal epithelial cells and can stimulate TLR2-mediated cytokine production, thereby potentially contributing to the onset of aspiration pneumonia.
Ensemble of ERDTs for Spectral–Spatial Classification of Hyperspectral Images Using MRS Object-Guided Morphological Profiles
Authors: Samat Alim , Li Erzhu , Liu Sicong , Miao Zelang , Wang Wei
Published: October 2020

In spectral-spatial classification of hyperspectral image tasks, the performance of conventional morphological profiles (MPs) that use a sequence of structural elements (SEs) with predefined sizes and shapes could be limited by mismatching all the sizes and shapes of real-world objects in an image. To overcome such limitation, this paper proposes the use of object-guided morphological profiles (OMPs) by adopting multiresolution segmentation (MRS)-based objects as SEs for morphological closing and opening by geodesic reconstruction. Additionally, the ExtraTrees, bagging, adaptive boosting (AdaBoost), and MultiBoost ensemble versions of the extremely randomized decision trees (ERDTs) are introduced and comparatively investigated for spectral-spatial classification of hyperspectral images. Two hyperspectral benchmark images are used to validate the proposed approaches in terms of classification accuracy. The experimental results confirm the effectiveness of the proposed spatial feature extractors and ensemble classifiers.
Aspergillus fumigatus and Aspergillus flavus-Specific IgG Cut-Offs for the Diagnosis of Chronic Pulmonary Aspergillosis in Pakistan
Authors: Jabeen Kauser , Farooqi Joveria , Iqbal Nousheen , Wahab Khalid , Irfan Muhammad
Published: October 2020

Despite a high burden of chronic pulmonary aspergillosis (CPA) in Pakistan, Aspergillus-specific IgG testing is currently not available. Establishing cut-offs for Aspergillus-specific IgG for CPA diagnosis is crucial due to geographical variation. In settings such as Pakistan, where non-Aspergillus fumigatus (mainly A. flavus) Aspergillus species account for the majority of CPA cases, there is a need to explore additional benefit of Aspergillus flavus-specific IgG detection along with A. fumigatus-specific IgG detection. This study was conducted at the Aga Khan University, Karachi, Pakistan after ethical approval. Serum for IgG detection were collected after informed consent from healthy controls (n = 21), diseased controls (patients with lung diseases, n = 18), and CPA patients (n = 21). A. fumigatus and A. flavus IgG were detected using Siemens immulite assay. The sensitivity and specificity of A. fumigatus-specific IgG were 80.95% and 82.05%, respectively at a cut-off of 20 mg/L. The sensitivity and specificity of A. flavus-specific IgG were 80.95% and 79.49% at a cut-off of 30 mg/L. We report, for the first time, performance of A. flavus-specific IgG for CPA diagnosis. Although there was no statistically significant difference between the performance of both antigens, it seems contextually relevant to include A. flavus IgG in the CPA diagnostic algorithm in regions with higher non-A. fumigatus CPA infections.