bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining the Cell Wall, Cell Cycle and Chromatin Landmarks in the Responses of Brachypodium distachyon to Salinity
Authors: Wolny Elzbieta , Skalska Aleksandra , Braszewska Agnieszka , Mur Luis A. J. , Hasterok Robert
Published: January 2021

Excess salinity is a major stress that limits crop yields. Here, we used the model grass Brachypodium distachyon (Brachypodium) reference line Bd21 in order to define the key molecular events in the responses to salt during germination. Salt was applied either throughout the germination period (“salt stress”) or only after root emergence (“salt shock”). Germination was affected at ≥100 mM and root elongation at ≥75 mM NaCl. The expression of arabinogalactan proteins (AGPs), FLA1, FLA10, FLA11, AGP20 and AGP26, which regulate cell wall expansion (especially FLA11), were mostly induced by the “salt stress” but to a lesser extent by “salt shock”. Cytological assessment using two AGP epitopes, JIM8 and JIM13 indicated that “salt stress” increases the fluorescence signals in rhizodermal and exodermal cell wall. Cell division was suppressed at >75 mM NaCl. The cell cycle genes (CDKB1, CDKB2, CYCA3, CYCB1, WEE1) were induced by “salt stress” in a concentration-dependent manner but not CDKA, CYCA and CYCLIN-D4-1-RELATED. Under “salt shock”, the cell cycle genes were optimally expressed at 100 mM NaCl. These changes were consistent with the cell cycle arrest, possibly at the G1 phase. The salt-induced genomic damage was linked with the oxidative events via an increased glutathione accumulation. Histone acetylation and methylation and DNA methylation were visualized by immunofluorescence. Histone H4 acetylation at lysine 5 increased strongly whereas DNA methylation decreased with the application of salt. Taken together, we suggest that salt-induced oxidative stress causes genomic damage but that it also has epigenetic effects, which might modulate the cell cycle and AGP expression gene. Based on these landmarks, we aim to encourage functional genomics studies on the responses of Brachypodium to salt.
A Peek Inside the Machines of Bacterial Nucleotide Excision Repair
Authors: Kraithong Thanyalak , Hartley Silas , Jeruzalmi David , Pakotiprapha Danaya
Published: January 2021

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). Below, we discuss the architecture of key proteins in bacterial NER and recent biochemical, structural and single-molecule studies that shed light on the lesion recognition steps of both the GGR and the TCR sub-pathways. Although a great deal has been learned about both of these sub-pathways, several important questions, including damage discrimination, roles of ATP and the orchestration of protein binding and conformation switching, remain to be addressed.
Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke
Authors: Hasumi Keiji , Suzuki Eriko
Published: January 2021

Stachybotrys microspora triprenyl phenol (SMTP) is a large family of small molecules derived from the fungus S. microspora. SMTP acts as a zymogen modulator (specifically, plasminogen modulator) that alters plasminogen conformation to enhance its binding to fibrin and subsequent fibrinolysis. Certain SMTP congeners exert anti-inflammatory effects by targeting soluble epoxide hydrolase. SMTP congeners with both plasminogen modulation activity and anti-inflammatory activity ameliorate various aspects of ischemic stroke in rodents and primates. A remarkable feature of SMTP efficacy is the suppression of hemorrhagic transformation, which is exacerbated by conventional thrombolytic treatments. No drug with such properties has been developed yet, and SMTP would be the first to promote thrombolysis but suppress disease-associated bleeding. On the basis of these findings, one SMTP congener is under clinical study and development. This review summarizes the discovery, mechanism of action, pharmacological activities, and development of SMTP.
Mechanical Stress Induces Ca2+-Dependent Signal Transduction in Erythroblasts and Modulates Erythropoiesis
Authors: Aglialoro Francesca , Abay Asena , Yagci Nurcan , Rab Minke A. E. , Kaestner Lars , van Wijk Richard , von Lindern Marieke , van den Akker Emile
Published: January 2021

Bioreactors are increasingly implemented for large scale cultures of various mammalian cells, which requires optimization of culture conditions. Such upscaling is also required to produce red blood cells (RBC) for transfusion and therapy purposes. However, the physiological suitability of RBC cultures to be transferred to stirred bioreactors is not well understood. PIEZO1 is the most abundantly expressed known mechanosensor on erythroid cells. It is a cation channel that translates mechanical forces directly into a physiological response. We investigated signaling cascades downstream of PIEZO1 activated upon transitioning stationary cultures to orbital shaking associated with mechanical stress, and compared the results to direct activation of PIEZO1 by the chemical agonist Yoda1. Erythroblasts subjected to orbital shaking displayed decreased proliferation, comparable to incubation in the presence of a low dose of Yoda1. Epo (Erythropoietin)-dependent STAT5 phosphorylation, and Calcineurin-dependent NFAT dephosphorylation was enhanced. Phosphorylation of ERK was also induced by both orbital shaking and Yoda1 treatment. Activation of these pathways was inhibited by intracellular Ca2+ chelation (BAPTA-AM) in the orbital shaker. Our results suggest that PIEZO1 is functional and could be activated by the mechanical forces in a bioreactor setup, and results in the induction of Ca2+-dependent signaling cascades regulating various aspects of erythropoiesis. With this study, we showed that Yoda1 treatment and mechanical stress induced via orbital shaking results in comparable activation of some Ca2+-dependent pathways, exhibiting that there are direct physiological outcomes of mechanical stress on erythroblasts.
Antiinflammatory Actions of Klotho: Implications for Therapy of Diabetic Nephropathy
Authors: Typiak Marlena , Piwkowska Agnieszka
Published: January 2021

Klotho was initially introduced as an antiaging molecule. Klotho deficiency significantly reduces lifespan, and its overexpression extends it and protects against various pathological phenotypes, especially renal disease. It was shown to regulate phosphate and calcium metabolism, protect against oxidative stress, downregulate apoptosis, and have antiinflammatory and antifibrotic properties. The course of diabetes mellitus and diabetic nephropathy resembles premature cellular senescence and causes the activation of various proinflammatory and profibrotic processes. Klotho was shown to exert many beneficial effects in these disorders. The expression of Klotho protein is downregulated in early stages of inflammation and diabetic nephropathy by proinflammatory factors. Therefore, its therapeutic effects are diminished in this disorder. Significantly lower urine levels of Klotho may serve as an early biomarker of renal involvement in diabetes mellitus. Recombinant Klotho administration and Klotho overexpression may have immunotherapeutic potential for the treatment of both diabetes and diabetic nephropathy. Therefore, the current manuscript aims to characterize immunopathologies occurring in diabetes and diabetic nephropathy, and tries to match them with antiinflammatory actions of Klotho. It also gives reasons for Klotho to be used in diagnostics and immunotherapy of these disorders.
The Prognostic Impact of Retinoid X Receptor and Thyroid Hormone Receptor alpha in Unifocal vs. Multifocal/Multicentric Breast Cancer
Authors: Zehni Alaleh Zati , Batz Falk , Vattai Aurelia , Kaltofen Till , Schrader Svenja , Jacob Sven-Niclas , Mumm Jan-Niclas , Heidegger Helene Hildegard , Ditsch Nina , Mahner Sven , Jeschke Udo , Vilsmaier Theresa
Published: January 2021

The aim of this study was to assess the prognostic value of the steroid hormone receptor expression, counting the retinoid X receptor (RXR) and thyroid hormone receptors (THRs), on the two different breast cancer (BC) entities: multifocal/multicentric versus unifocal. The overall and disease-free survival were considered as the prognosis determining aspects and analyzed by uni- and multi-variate analysis. Furthermore, histopathological grading and TNM staging (T = tumor size, N = lymph node involvement, M = distant metastasis) were examined in relation to RXR and THRs expression. A retrospective statistical analysis was carried out on survival-related events in a series of 319 sporadic BC patients treated at the Department of Gynecology and Obstetrics at the Ludwig-Maximillian’s University in Munich between 2000 and 2002. The expression of RXR and THRs, including its two major isoforms THRα1 and THRα2, was analyzed by immunohistochemistry and showed to have a significant correlation for both BC entities in regard to survival analysis. Patients with multifocal/multicentric BC were exposed to a significantly worse disease-free survival (DFS) when expressing RXR. Patients with unifocal BC showed a significantly worse DFS when expressing THRα1. In contrast, a statistically significant positive association between THRα2 expression and enhanced DFS in multifocal/multicentric BC was shown. Especially the RXR expression in multifocal/multicentric BC was found to play a remarkably contradictory role for BC prognosis. The findings imply the need for a critical review of possible molecular therapies targeting steroid hormone receptors in BC treatment. Our results strengthen the need to further investigate the behavior of the nuclear receptor family, especially in relation to BC focality.
Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro
Authors: Tamò Luca , Fytianos Kleanthis , Caldana Fabienne , Simillion Cedric , Feki Anis , Nita Izabela , Heller Manfred , Geiser Thomas , Gazdhar Amiq
Published: January 2021

Induced pluripotent stem cell secretome (iPSC-CM) mitigate organ injury and help in repair. Macrophages play a critical role in tissue repair and regeneration and can be directed to promote tissue repair by iPSC-CM, although the exact mechanisms are not known. In the current investigative study, we evaluated the possible mechanism by which iPSC-CM regulates the phenotype and secretory pattern of macrophages in vitro. Macrophages were obtained from human peripheral blood mononuclear cells and differentiated to various subpopulations and treated with either iPSC-CM or control media in vitro. Macrophage phenotype was assessed by flow cytometry, gene expression changes by qRT PCR and secretory pattern by multiplex protein analysis. The protein and gene interaction network revealed the involvement of Amyloid precursor protein (APP) and ELAV-like protein 1 (ELAVL-1) both present in the iPSC-CM to play an important role in regulating the macrophage phenotype and their secretory pattern. This exploratory study reveals, in part, the possible mechanism and identifies two potential targets by which iPSC-CM regulate macrophages and help in repair and regeneration.
Substrate Stiffness Mediates Formation of Novel Cytoskeletal Structures in Fibroblasts during Cell–Microspheres Interaction
Authors: Adamczyk Olga , Baster Zbigniew , Szczypior Maksymilian , Rajfur Zenon
Published: January 2021

It is well known that living cells interact mechanically with their microenvironment. Many basic cell functions, like migration, proliferation, gene expression, and differentiation, are influenced by external forces exerted on the cell. That is why it is extremely important to study how mechanical properties of the culture substrate influence the cellular molecular regulatory pathways. Optical microscopy is one of the most common experimental method used to visualize and study cellular processes. Confocal microscopy allows to observe changes in the 3D organization of the cytoskeleton in response to a precise mechanical stimulus applied with, for example, a bead trapped with optical tweezers. Optical tweezers-based method (OT) is a microrheological technique which employs a focused laser beam and polystyrene or latex beads to study mechanical properties of biological systems. Latex beads, functionalized with a specific protein, can interact with proteins located on the surface of the cellular membrane. Such interaction can significantly affect the cell’s behavior. In this work, we demonstrate that beads alone, placed on the cell surface, significantly change the architecture of actin, microtubule, and intermediate filaments. We also show that the observed molecular response to such stimulus depends on the duration of the cell–bead interaction. Application of cytoskeletal drugs: cytochalasin D, jasplakinolide, and docetaxel, abrogates remodeling effects of the cytoskeleton. More important, when cells are plated on elastic substrates, which mimic the mechanical properties of physiological cellular environment, we observe formation of novel, “cup-like” structures formed by the microtubule cytoskeleton upon interaction with latex beads. These results provide new insights into the function of the microtubule cytoskeleton. Based on these results, we conclude that rigidity of the substrate significantly affects the cellular processes related to every component of the cytoskeleton, especially their architecture.
Terpenoids from Abies holophylla Attenuate LPS-Induced Neuroinflammation in Microglial Cells by Suppressing the JNK-Related Signaling Pathway
Authors: Subedi Lalita , Yumnam Silvia
Published: January 2021

We have previously reported that phytochemicals from Abies holophylla exhibit anti-inflammatory and neuroprotective effects by decreasing nitrite production and increasing nerve growth factor production. However, the exact mechanism underscoring these effects has not been revealed. In the present study, we aimed to explore the underlying anti-inflammatory mechanisms of A. holophylla and its phytochemicals. We studied various solvent fractions of A. holophylla and found the chloroform and hexane sub-fractions showed the most significant anti-neuroinflammatory effects in lipopolysaccharide (LPS)-activated murine microglia. Concomitantly, the terpenoids isolated from chloroform and hexane fractions showed similar anti-neuroinflammatory effects with significant inhibition of NO and reactive oxygen species production, and decreased protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase. Interestingly, these terpenoids inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), which further inhibited the production of pro-inflammatory mediators, including prostaglandin E2, tumor necrosis factor, and interleukins (IL-6 and IL-1β), with a potency greater than that of the well-known iNOS inhibitor NG-mono-methyl-L-arginine (L-NMMA). These results suggest that the chloroform- and hexane-soluble fraction mediated the mitogen-activated protein kinase (MAPK) inhibition, in particular the JNK pathway, thereby lowering the inflammatory cascades in LPS-activated murine microglia. Thus, our study suggests that the chloroform and hexane fractions of A. holophylla and their terpenoids may be potential drug candidates for drug discovery against LPS-induced neuroinflammation and neuroinflammatory-related neurodegeneration.
Metabolomic Profiles in Adipocytes Differentiated from Adipose-Derived Stem Cells Following Exercise Training or High-Fat Diet
Authors: Osawa Seita , Kato Hisashi , Maeda Yuki , Takakura Hisashi , Ogasawara Junetsu , Izawa Tetsuya
Published: January 2021

Controlling the differentiation potential of adipose-derived stem cells (ADSCs) is attracting attention as a new strategy for the prevention and treatment of obesity. Here, we aimed to observe the effect of exercise training (TR) and high-fat diet (HFD) on the metabolic profiles of ADSCs-derived adipocytes. The rats were divided into four groups: normal diet (ND)-fed control (ND-SED), ND-fed TR (ND-TR), HFD-fed control (HFD-SED), and HFD-fed TR (HFD-TR). After 9 weeks of intervention, ADSCs of epididymal and inguinal adipose tissues were differentiated into adipocytes. In the metabolome analysis of adipocytes after isoproterenol stimulation, 116 metabolites were detected. The principal component analysis demonstrated that ADSCs-derived adipocytes segregated into four clusters in each fat pad. Amino acid accumulation was greater in epididymal ADSCs-derived adipocytes of ND-TR and HFD-TR, but lower in inguinal ADSCs-derived adipocytes of ND-TR, than in the respective controls. HFD accumulated several metabolites including amino acids in inguinal ADSCs-derived adipocytes and more other metabolites in epididymal ones. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that TR mainly affected the pathways related to amino acid metabolism, except in inguinal ADSCs-derived adipocytes of HFD-TR rats. These findings provide a new way to understand the mechanisms underlying possible changes in the differentiation of ADSCs due to TR or HFD.
The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction
Authors: Spiroski Ana-Mishel , Sanders Rachel , Meloni Marco , McCracken Ian R. , Thomson Adrian , Brittan Mairi , Gray Gillian A. , Baker Andrew H.
Published: January 2021

Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR (small regulatory polypeptide of amino acid response) locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression, we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response, and tissue-specific response to myocardial infarction. To investigate the influence of the LINC00961/SPAAR locus on longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961–/– mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest the LINC00961/SPAAR locus contributes to cardiac endothelial cell and fibroblast function and hypoxic response, growth and development, and basal cardiovascular function in adulthood.
The Complex Interplay between Endocannabinoid System and the Estrogen System in Central Nervous System and Periphery
Authors: Santoro Antonietta , Mele Elena , Marino Marianna , Viggiano Andrea , Nori Stefania Lucia , Meccariello Rosaria
Published: January 2021

The endocannabinoid system (ECS) is a lipid cell signaling system involved in the physiology and homeostasis of the brain and peripheral tissues. Synaptic plasticity, neuroendocrine functions, reproduction, and immune response among others all require the activity of functional ECS, with the onset of disease in case of ECS impairment. Estrogens, classically considered as female steroid hormones, regulate growth, differentiation, and many other functions in a broad range of target tissues and both sexes through the activation of nuclear and membrane estrogen receptors (ERs), which leads to genomic and non-genomic cell responses. Since ECS function overlaps or integrates with many other cell signaling systems, this review aims at updating the knowledge about the possible crosstalk between ECS and estrogen system (ES) at both central and peripheral level, with focuses on the central nervous system, reproduction, and cancer.
Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis
Authors: Ungefroren Hendrik
Published: January 2021

Autocrine signaling is defined as the production and secretion of an extracellular mediator by a cell followed by the binding of that mediator to receptors on the same cell to initiate signaling. Autocrine stimulation often operates in autocrine loops, a type of interaction, in which a cell produces a mediator, for which it has receptors, that upon activation promotes expression of the same mediator, allowing the cell to repeatedly autostimulate itself (positive feedback) or balance its expression via regulation of a second factor that provides negative feedback. Autocrine signaling loops with positive or negative feedback are an important feature in cancer, where they enable context-dependent cell signaling in the regulation of growth, survival, and cell motility. A growth factor that is intimately involved in tumor development and progression and often produced by the cancer cells in an autocrine manner is transforming growth factor-β (TGF-β). This review surveys the many observations of autocrine TGF-β signaling in tumor biology, including data from cell culture and animal models as well as from patients. We also provide the reader with a critical discussion on the various experimental approaches employed to identify and prove the involvement of autocrine TGF-β in a given cellular response.
Impact of Selected Signaling Proteins on SNAIL 1 and SNAIL 2 Expression in Ovarian Cancer Cell Lines in Relation to Cells’ Cisplatin Resistance and EMT Markers Level
Authors: Kielbik Michal , Szulc-Kielbik Izabela , Klink Magdalena
Published: January 2021

It has been increasingly recognized that SNAIL1 and SNAIL2, as major EMT-inducers, might also be involved in drug resistance of cancer cells. We sought to determine a relation between SNAIL1/2, E-cadherin and N-cadherin expression, as well as ovarian cancer cells’ resistance to cisplatin and EMT markers’ level. Thus, four ovarian cancer cell lines, were used: A2780, A2780cis, SK-OV-3 and OVCAR-3. We assessed the impact of ERK1/2, AKT and STAT3 proteins (chosen by the profiling activity of over 40 signaling proteins) on SNAIL1/2 expression, along with E-cadherin and N-cadherin levels. We showed that expression of SNAIL1 and N-cadherin are the highest in cisplatin-resistant A2780cis and SK-OV-3 cells, while high SNAIL2 and E-cadherin levels were observed in cisplatin-sensitive A2780 cells. The highest E-cadherin level was noticed in OVCAR-3 cells. SNAIL1/2 expression was dependent on ERK1/2 activity in cisplatin-resistant and potentially invasive SK-OV-3 and OVCAR-3 cells. STAT-3 regulates expression of SNAIL1/2 and leads to the so-called “cadherin switch” in cancer cells, independently of their chemoresistance. In conclusion, SNAIL1, but not SNAIL2, seems to be involved in ovarian cancer cells’ cisplatin resistance. STAT3 is a universal factor determining the expression of SNAIL1/2 in ovarian cancer cells regardless of their chemoresitance or invasive capabilities.
A Framework for Generating Extractive Summary from Multiple Malayalam Documents
Authors: Manju K. , David Peter S. , Idicula Sumam
Published: January 2021

Automatic extractive text summarization retrieves a subset of data that represents most notable sentences in the entire document. In the era of digital explosion, which is mostly unstructured textual data, there is a demand for users to understand the huge amount of text in a short time; this demands the need for an automatic text summarizer. From summaries, the users get the idea of the entire content of the document and can decide whether to read the entire document or not. This work mainly focuses on generating a summary from multiple news documents. In this case, the summary helps to reduce the redundant news from the different newspapers. A multi-document summary is more challenging than a single-document summary since it has to solve the problem of overlapping information among sentences from different documents. Extractive text summarization yields the sensitive part of the document by neglecting the irrelevant and redundant sentences. In this paper, we propose a framework for extracting a summary from multiple documents in the Malayalam Language. Also, since the multi-document summarization data set is sparse, methods based on deep learning are difficult to apply. The proposed work discusses the performance of existing standard algorithms in multi-document summarization of the Malayalam Language. We propose a sentence extraction algorithm that selects the top ranked sentences with maximum diversity. The system is found to perform well in terms of precision, recall, and F-measure on multiple input documents.
AI-Based Semantic Multimedia Indexing and Retrieval for Social Media on Smartphones
Authors: Wagenpfeil Stefan , Engel Felix , Kevitt Paul Mc , Hemmje Matthias
Published: January 2021

To cope with the growing number of multimedia assets on smartphones and social media, an integrated approach for semantic indexing and retrieval is required. Here, we introduce a generic framework to fuse existing image and video analysis tools and algorithms into a unified semantic annotation, indexing and retrieval model resulting in a multimedia feature vector graph representing various levels of media content, media structures and media features. Utilizing artificial intelligence (AI) and machine learning (ML), these feature representations can provide accurate semantic indexing and retrieval. Here, we provide an overview of the generic multimedia analysis framework (GMAF) and the definition of a multimedia feature vector graph framework (MMFVGF). We also introduce AI4MMRA to detect differences, enhance semantics and refine weights in the feature vector graph. To address particular requirements on smartphones, we introduce an algorithm for fast indexing and retrieval of graph structures. Experiments to prove efficiency, effectiveness and quality of the algorithm are included. All in all, we describe a solution for highly flexible semantic indexing and retrieval that offers unique potential for applications such as social media or local applications on smartphones.
Mountain Tourism in the Perception of Romanian Tourists: A Case Study of the Rodna Mountains National Park
Authors: Cozma Adeline-Cristina , Coroș Monica-Maria , Pop Cornelia
Published: January 2021

As a country, Romania tries to communicate abroad its authenticity, intact nature and unique cultural heritage. This message matches perfectly the main attributes associated to Rodna Mountains National Park, as it is the second national park in Romanian. The aim of the research is to identify and analyze the prospects for sustainable development of rural tourism in the area of Rodna Mountains National Park, taking into account its impact on the social and economic life of the inhabitants of the Rodna commune, but also factors that may positively or negatively influence the whole process. From a methodological perspective, quantitative methods were used; a survey-based research was carried out among Romanian mountain tourists, aiming at identifying and analyzing their opinions and suggestions regarding tourism in protected areas in Romania, as well as the impact of the tourist flows generated by the Park upon the surrounding communities. Rodna Mountains National Park seems to be among the favorite destinations of tourists, as the respondents have a good and very good general impression about the interaction with the mountain and protected areas, prefer internal to external destinations regardless of the season, budgets allocated per night, per stay and annually are quite high, so the purchasing power is also high; they constitute a solid foundation for the decisions of the tourist development of the area. The need for holidays and the savings that tourists make throughout the year to go on vacation, regardless of income level, give viability to this opportunity. Other results of this research are related to the problems tourists helped to identify and the solutions they proposed.
The Role of Back Optic Zone Diameter in Myopia Control with Orthokeratology Lenses
Authors: Pauné Jaume , Fonts Silvia , Rodríguez Lina , Queirós Antonio
Published: January 2021

We compared the efficacy of controlling the annual increase in axial length (AL) in myopic Caucasian children based on two parameters: the back optic zone diameter (BOZD) of the orthokeratology (OK) lens and plus power ring diameter (PPRD) or mid-peripheral annular ring of corneal steepening. Data from 71 myopic patients (mean age, 13.34 ± 1.38 years; range, 10–15 years; 64% male) corrected with different BOZD OK lenses (DRL, Precilens) were collected retrospectively from a Spanish optometric clinic. The sample was divided into groups with BOZDs above or below 5.00 mm and the induced PPRD above or below 4.5 mm, and the relation to AL and refractive progression at 12 months was analyzed. Three subgroups were analyzed, i.e., plus power ring (PPR) inside, outside, or matching the pupil. The mean baseline myopia was −3.11 ± 1.46 D and the AL 24.65 ± 0.88 mm. Significant (p < 0.001) differences were found after 12 months of treatment in the refractive error and AL for the BOZD and PPRD. AL changes in subjects with smaller BOZDs decreased significantly regarding larger diameters (0.09 ± 0.12 and 0.15 ± 0.11 mm, respectively); in subjects with a horizontal sector of PPRD falling inside the pupil, the AL increased less (p = 0.035) than matching or outside the pupil groups by 0.04 ± 0.10 mm, 0.10 ± 0.11 mm, and 0.17 ± 0.12 mm, respectively. This means a 76% lesser AL growth or 0.13 mm/year in absolute reduction. OK corneal parameters can be modified by changing the OK lens designs, which affects myopia progression and AL elongation. Smaller BOZD induces a reduced PPRDs that slows AL elongation better than standard OK lenses. Further investigations should elucidate the effect of pupillary diameter, PPRD, and power change on myopia control.
Prevalence of Sarcopenia Employing Population-Specific Cut-Points: Cross-Sectional Data from the Geelong Osteoporosis Study, Australia
Authors: Sui Sophia X. , Holloway-Kew Kara L. , Hyde Natalie K. , Williams Lana J. , Tembo Monica C. , Leach Sarah , Pasco Julie A.
Published: January 2021

Background: Prevalence estimates for sarcopenia vary depending on the ascertainment criteria and thresholds applied. We aimed to estimate the prevalence of sarcopenia using two international definitions but employing Australian population-specific cut-points. Methods: Participants (n = 665; 323 women) aged 60–96 years old were from the Geelong Osteoporosis Study. Handgrip strength (HGS) was measured by dynamometers and appendicular lean mass (ALM) by whole-body dual-energy X-ray absorptiometry. Physical performance was assessed using gait speed (GS, men only) and/or the timed up-and-go (TUG) test. Using cut-points equivalent to two standard deviations (SDs) below the mean young reference range from the same population and recommendations from the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was identified by low ALM/height2 (<5.30 kg for women; <6.94 kg for men) + low HGS (<16 kg women; <31 kg men); low ALM/height2 + slow TUG (>9.3 s); low ALM/height2 + slow GS (<0.8 m/s). For the Foundation for the National Institutes of Health (FNIH) equivalent, sarcopenia was identified as low ALM/BMI (<0.512 m2 women, <0.827 m2 men) + low HGS (<16 kg women, <31 kg men). Receiver Operating Characteristic curves were also applied to determine optimal cut-points for ALM/BMI (<0.579 m2 women, <0.913 m2 men) that discriminated poor physical performance. Prevalence estimates were standardized to the Australian population and compared to estimates using international thresholds. Results: Using population-specific cut-points and low ALM/height2 + HGS, point-estimates for sarcopenia prevalence were 0.9% for women and 2.9% for men. Using ALM/height2 + TUG, prevalence was 2.5% for women and 4.1% for men, and using ALM/height2 + GS, sarcopenia was identified for 1.6% of men. Using ALM/BMI + HGS, prevalence estimates were 5.5–10.4% for women and 11.6–18.4% for men. Conclusions: This study highlights the range of prevalence estimates that result from employing different criteria for sarcopenia. While population-specific criteria could be pertinent for some populations, a consensus is needed to identify which deficits in skeletal muscle health are important for establishing an operational definition for sarcopenia.
Contributing Factors to Perinatal Outcome in Pregnancies with Gestational Diabetes—What Matters Most? A Retrospective Analysis
Authors: Weschenfelder Friederike , Hein Friederike , Lehmann Thomas , Schleußner Ekkehard , Groten Tanja
Published: January 2021

The aim of diabetes care of pregnant women with gestational diabetes mellitus (GDM) is to attain pregnancy outcomes including rates of large-for-gestational-age (LGA) newborns, pre-eclampsia, C-sections (CS) and other neonatal outcomes similar to those of the non-GDM pregnant population. Obesity and excessive weight gain during pregnancy have been shown to also impact perinatal outcome. Since GDM is frequently associated with elevated body mass index (BMI), we evaluated the impact of maternal prepregnancy BMI, development of GDM and gestational weight gain (GWG) during pregnancy on perinatal outcome. We compared 614 GDM patients with 5175 non-diabetic term deliveries who gave birth between 2012 and 2016. Multivariate regression analysis was used to evaluate the independent contribution of each factor on selected perinatal outcome variables. Additionally, subgroup analysis for obese (BMI ≥ 30 kg/m2) and non-obese women (BMI < 30 kg/m2) was performed. LGA was significantly influenced by BMI, GWG and GDM, while Neonatal Intensive Care Unit (NICU) admission was solely impacted by GDM. Maternal outcomes were not dependent on GDM but on GWG and prepregnancy BMI. These results remained significant in the non-obese subgroup only. Thus, GDM still affects perinatal outcomes and requires further improvement in diabetic care and patient counseling.
Stratification of Hepatocellular Carcinoma Risk Following HCV Eradication or HBV Control
Authors: Nahon Pierre , Vo Quang Erwan , Ganne-Carrié Nathalie
Published: January 2021

Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV control whatever the stage of fibrosis remains at risk of liver cancer development. Cancer predictors in these virus-free patients include routine parameters estimating coexisting comorbidities, persisting liver inflammation or function impairment, and results of non-invasive tests which can be easily combined into HCC risk scoring systems. The latter enables stratification according to various liver cancer incidences and allocation of patients into low, intermediate or high HCC risk probability groups. All international guidelines endorse lifelong surveillance of these patients using semi-annual ultrasound, with known sensibility issues. Refining HCC prediction in this growing population ultimately will trigger personalized management using more effective surveillance tools such as contrast-enhanced imaging techniques or circulating biomarkers while taking into account cost-effectiveness parameters.
Erratum: Iyer, A., et al. Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells. J. Clin. Med. 2020, 9, 1206
Authors: Iyer Arvind , Gupta Krishan , Sharma Shreya , Hari Kishore , Lee Yi , Ramalingam Neevan , Yap Yoon , West Jay , Bhagat Ali , Subramani Balaram , Sabuwala Burhanuddin , Zea Tan Tuan , Thiery Jean , Jolly Mohit , Ramalingam Naveen , Sengupta Debarka
Published: January 2021

In the published manuscript [...]
Surgical Treatment of Diabetic Foot Ulcers Complicated by Osteomyelitis with Gentamicin-Loaded Calcium Sulphate-Hydroxyapatite Biocomposite
Authors: Hutting Kor H. , aan de Stegge Wouter B. , van Netten Jaap J. , ten Cate Wouter A. , Smeets Luuk , Welten Gijs M. J. M. , Scharn Dick M. , de Vries Jean-Paul P. M. , van Baal Jeff G.
Published: January 2021

Diabetic foot ulcers, complicated by osteomyelitis, can be treated by surgical resection, dead space filling with gentamicin-loaded calcium sulphate-hydroxyapatite (CaS-HA) biocomposite, and closure of soft tissues and skin. To assess the feasibility of this treatment regimen, we conducted a multicenter retrospective cohort study of patients after failed conventional treatments. From 13 hospitals we included 64 patients with forefoot (n = 41 (64%)), midfoot (n = 14 (22%)), or hindfoot (n = 9 (14%)) ulcers complicated by osteomyelitis. Median follow-up was 43 (interquartile range, 20–61) weeks. We observed wound healing in 54 patients (84%) and treatment success (wound healing without ulcer recurrence) in 42 patients (66%). Treatment failures (no wound healing or ulcer recurrence) led to minor amputations in four patients (6%) and major amputations in seven patients (11%). Factors associated with treatment failures in univariable Cox regression analysis were gentamicin-resistant osteomyelitis (hazard ratio (HR), 3.847; 95%-confidence interval (CI), 1.065–13.899), hindfoot ulcers (HR, 3.624; 95%-CI, 1.187–11.060) and surgical procedures with gentamicin-loaded CaS-HA biocomposite that involved minor amputations (HR, 3.965; 95%-CI, 1.608–9.777). In this study of patients with diabetic foot ulcers, complicated by osteomyelitis, surgical treatment with gentamicin-loaded CaS-HA biocomposite was feasible and successful in 66% of patients. A prospective trial of this treatment regimen, based on a uniform treatment protocol, is required.
The Neutron Imaging Instrument CONRAD—Post-Operational Review
Authors: Kardjilov Nikolay , Manke Ingo , Hilger André , Arlt Tobias , Bradbury Robert , Markötter Henning , Woracek Robin , Strobl Markus , Treimer Wolfgang , Banhart John
Published: January 2021

The neutron imaging instrument CONRAD was operated as a part of the user program of the research reactor BER-II at Helmholtz-Zentrum Berlin (HZB) from 2005 to 2020. The instrument was designed to use the neutron flux from the cold source of the reactor, transported by a curved neutron guide. The pure cold neutron spectrum provided a great advantage in the use of different neutron optical components such as focusing lenses and guides, solid-state polarizers, monochromators and phase gratings. The flexible setup of the instrument allowed for implementation of new methods including wavelength-selective, dark-field, phase-contrast and imaging with polarized neutrons. In summary, these developments helped to attract a large number of scientists and industrial customers, who were introduced to neutron imaging and subsequently contributed to the expansion of the neutron imaging community.
Visual Appearance of Oil on the Sea
Authors: Fingas Merv
Published: January 2021

The visual appearance of oil spills at sea is often used as an indicator of spilled oil properties, state and slick thickness. These appearances and the oil properties that are associated with them are reviewed in this paper. The appearance of oil spills is an estimator of thickness of thin oil slicks, thinner than a rainbow sheen (<3 µm). Rainbow sheens have a strong physical explanation. Thicker oil slicks (e.g., >3 µm) are not correlated with a given oil appearance. At one time, the appearance of surface discharges from ships was thought to be correlated with discharge rate and vessel speed; however, this approach is now known to be incorrect. Oil on the sea can sometimes form water-in-oil emulsions, dependent on the properties of the oil, and these are often reddish in color. These can be detected visually, providing useful information on the state of the oil. Oil-in-water emulsions can be seen as a coffee-colored cloud below the water surface. Other information gleaned from the oil appearance includes coverage and distribution on the surface.
Relationship Between Tree Size, Sediment Mud Content, Oxygen Levels, and Pneumatophore Abundance in the Mangrove Tree Species Avicennia Marina (Forssk.) Vierh
Authors: Al-Khayat Jassim A. , Alatalo Juha M.
Published: January 2021

Mangroves are important in protecting and stabilizing coastal zones. Pneumatophores of the mangrove species Avicennia marina can form a large aboveground complex of aerial roots, which are important in supporting mangrove growth in low-oxygen environments. We examined the relationship between mangrove tree height, tree girth, sediment mud content, and oxygen levels with pneumatophore abundance. As sediments with higher mud content have more anaerobic conditions due to their lower porosity, we hypothesized that pneumatophore abundance would be positively correlated with sediment mud content and negatively correlated with sediment oxygen levels. Pneumatophore abundance of A. marina ranged from 14 to 516 per m2 (mean 171.8 ± 0.61 per m2), pneumatophore height from 6.6 to 27.5 cm (14.1 ± 0.86 cm), and maximum pneumatophore diameter from 8.5–12.7 mm (8.5 ± 0.24 mm). Pneumatophore abundance was positively correlated with tree height and tree girth. As hypothesized, pneumatophore abundance was positively correlated with percentage of mud content in sediment and negatively correlated with oxygen percentage. This suggests that mangrove trees can adapt to anaerobic and water-logged conditions by increasing their number of pneumatophores, hence providing greater surface area for gas exchange. In addition, there was a significant effect of mangrove (natural and planted), tidal position, and their interaction. With natural mangrove having higher abundance of pneumatophores compared to the planted mangrove, with the highest number closest to the sea. While pneumatophore abundance did not differ among tidal zones in planted mangrove.
The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients
Authors: Ivanoshchuk Dinara E. , Shakhtshneider Elena V. , Rymar Oksana D. , Ovsyannikova Alla K. , Mikhailova Svetlana V. , Fishman Veniamin S. , Valeev Emil S. , Orlov Pavel S. , Voevoda Mikhail I.
Published: January 2021

Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. The most common subtypes of MODY are associated with mutations in the genes GCK, HNF1A, HNF4A, and HNF1B. Among them, up to 70% of cases are caused by mutations in GCK and HNF1A. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in HNF4A, GCK, HNF1A, and ABCC8. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 −1G>T, Cys371*, and Glu443Lys in GCK and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in HNF1A.
Effect of Aging on Homeostasis in the Soft Tissue of the Periodontium: A Narrative Review
Authors: Kim Yu Gyung , Lee Sang Min , Bae Sungeun , Park Taejun , Kim Hyeonjin , Jang Yujeong , Moon Keonwoo , Kim Hyungmin , Lee Kwangmin , Park Joonyoung , Byun Jin-Seok , Kim Do-Yeon
Published: January 2021

Aging is characterized by a progressive decline or loss of physiological functions, leading to increased susceptibility to disease or death. Several aging hallmarks, including genomic instability, cellular senescence, and mitochondrial dysfunction, have been suggested, which often lead to the numerous aging disorders. The periodontium, a complex structure surrounding and supporting the teeth, is composed of the gingiva, periodontal ligament, cementum, and alveolar bone. Supportive and protective roles of the periodontium are very critical to sustain life, but the periodontium undergoes morphological and physiological changes with age. In this review, we summarize the current knowledge of molecular and cellular physiological changes in the periodontium, by focusing on soft tissues including gingiva and periodontal ligament.
Tracking the Role of Policies and Economic Factors in Driving the Forest Change Trajectories within the Guangdong-Hongkong-Macao Region of China: A Remote Sensing Perspective
Authors: Xian Yuyang , Lu Yongquan , Musyimi Zipporah , Liu Guilin
Published: January 2021

Though forest ecosystems play a critical role in enhancing ecological, environmental, economic, and societal sustainability, on a global scale, their future outlooks are uncertain given the wide-ranging threats they are exposed to. The uniqueness of this study is to provide a line of evidence in which forest change trajectories are not only tracked but also evaluated through the lenses of forestry and economic oriented events’ timelines. The dynamics of forest change trajectories were mined using a temporal model. To understand the forces driving the changes, the change trajectories were linked to the timelines when forestry policies and economic factors where adopted. During 1980–1990, the forest change trajectory assumed a peak (forest gain). This was interpreted as a response to the adoption of policies that promoted ecological conservation. During 1995–2010, the forest change trajectories reflected the response to the antagonistic effects of forest-oriented policies and the economy-oriented drivers. During 2010–2015, the forest change trajectories assumed a deep (forest loss). This was attributed as a response to the economy-oriented factors. However, inferences from the results indicated that deforestation driven by economic factors was restricted by forest management policies. Though the role of economic factors has promoted developments within the study area, forest policies still constrain illegal logging and play a key role in protecting forests. We hope that insights from this study will inform, support and guide decisions for precise and smart sustainable forest management plans.
Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV
Authors: Vinhaes Caian L. , Araujo-Pereira Mariana , Tibúrcio Rafael , Cubillos-Angulo Juan M. , Demitto Fernanda O. , Akrami Kevan M. , Andrade Bruno B.
Published: January 2021

Antiretroviral therapy (ART) has represented a major advancement in the care of people living with HIV (PLWHH), resulting in significant reductions in morbidity and mortality through immune reconstitution and attenuation of homeostatic disruption. Importantly, restoration of immune function in PLWH with opportunistic infections occasionally leads to an intense and uncontrolled cytokine storm following ART initiation known as immune reconstitution inflammatory syndrome (IRIS). IRIS occurrence is associated with the severe and rapid clinical deterioration that results in significant morbidity and mortality. Here, we detail the determinants underlying IRIS development in PLWH, compiling the available knowledge in the field to highlight details of the inflammatory responses in IRIS associated with the most commonly reported opportunistic pathogens. This review also highlights gaps in the understanding of IRIS pathogenesis and summarizes therapeutic strategies that have been used for IRIS.