bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Effects of Meldonium in Experimental Models of Cardiovascular Complications with a Potential Application in COVID-19
Authors: Vilskersts Reinis , Kigitovica Dana , Korzh Stanislava , Videja Melita , Vilks Karlis , Cirule Helena , Skride Andris , Makrecka-Kuka Marina , Liepinsh Edgars , Dambrova Maija
Published: December 2021

Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.
MicroRNA 630 Represses NANOG Expression through Transcriptional and Post-Transcriptional Regulation in Human Embryonal Carcinoma Cells
Authors: Chu Wing-Keung , Hung Li-Man , Hou Chun-Wei , Chen Jan-Kan
Published: December 2021

The pluripotent transcription factor NANOG is essential for maintaining embryonic stem cells and driving tumorigenesis. We previously showed that PKC activity is involved in the regulation of NANOG expression. To explore the possible involvement of microRNAs in regulating the expression of key pluripotency factors, we performed a genome-wide analysis of microRNA expression in the embryonal carcinoma cell line NT2/D1 in the presence of the PKC activator, PMA. We found that MIR630 was significantly upregulated in PMA-treated cells. Experimentally, we showed that transfection of MIR630 mimic into embryonal carcinoma cell lines directly targeted the 3′UTR of OCT4, SOX2, and NANOG and markedly suppressed their expression. RNAhybrid and RNA22 algorithms were used to predict miRNA target sites in the NANOG 3′UTR, four possible target sites of MIR630 were identified. To examine the functional interaction between MIR630 and NANOG mRNA, the predicted MIR630 target sites in the NANOG 3′UTR were deleted and the activity of the reporters were compared. After targeted mutation of the predicted MIR630 target sites, the MIR630 mimic inhibited NANOG significantly less than the wild-type reporters. It is worth noting that mutation of a single putative binding site in the 3′UTR of NANOG did not completely abolish MIR630-mediated suppression, suggesting that MIR630 in the NANOG 3′UTR may have multiple binding sites and act together to maximally repress NANOG expression. Interestingly, MIR630 mimics significantly downregulated NANOG gene transcription. Exogenous expression of OCT4, SOX2, and NANOG lacking the 3′UTR almost completely rescued the reduced transcriptional activity of MIR630. MIR630 mediated the expression of differentiation markers in NT2/D1 cells, suggesting that MIR630 leads to the differentiation of NT2/D1 cell. Our findings show that MIR630 represses NANOG through transcriptional and post-transcriptional regulation, suggesting a direct link between core pluripotency factors and MIR630.
Reconceptualization of Hormetic Responses in the Frame of Redox Toxicology
Authors: Skaperda Zoi , Tekos Fotios , Vardakas Periklis , Nepka Charitini , Kouretas Demetrios
Published: December 2021

Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date.
Mutation Analysis of Radioresistant Early-Stage Cervical Cancer
Authors: Oike Tae , Sekiguchi Yoshihito , Yoshimoto Yuya , Oike Takahiro , Ando Ken , Gu Wenchao , Sasaki Yasushi , Tokino Takashi , Iwase Akira , Ohno Tatsuya
Published: December 2021

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRASmt/SMAD4mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRASmt/SMAD4mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRASmt/SMAD4mt cancer cells. These data indicate that the KRASmt/SMAD4mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRASmt/SMAD4mt signature.
Cumulus Extracellular Matrix Is an Important Part of Oocyte Microenvironment in Ovarian Follicles: Its Remodeling and Proteolytic Degradation
Authors: Nagyová Eva , Němcová Lucie , Camaioni Antonella
Published: December 2021

The extracellular matrix (ECM) is an essential structure with biological activities. It has been shown that the ECM influences gene expression via cytoskeletal components and the gene expression is dependent upon cell interactions with molecules and hormones. The development of ovarian follicles is a hormone dependent process. The surge in the luteinizing hormone triggers ovulatory changes in oocyte microenvironment. In this review, we discuss how proteolytic cleavage affects formation of cumulus ECM following hormonal stimulation; in particular, how the specific proteasome inhibitor MG132 affects gonadotropin-induced cytoskeletal structure, the organization of cumulus ECM, steroidogenesis, and nuclear maturation. We found that after the inhibition of proteolytic cleavage, gonadotropin-stimulated oocyte–cumulus complexes (OCCs) were without any signs of cumulus expansion; they remained compact with preserved cytoskeletal F-actin-rich transzonal projections through the oocyte investments. Concomitantly, a significant decrease was detected in progesterone secretion and in the expression of gonadotropin-stimulated cumulus expansion–related transcripts, such as HAS2 and TNFAIP6. In agreement, the covalent binding between hyaluronan and the heavy chains of serum-derived the inter-alpha-trypsin inhibitor, essential for the organization of cumulus ECM, was missing.
Buccal Mucosa Cells as a Potential Diagnostic Tool to Study Onset and Progression of Arrhythmogenic Cardiomyopathy
Authors: Driessen Helen E. , van der Voorn Stephanie M. , Bourfiss Mimount , van Lint Freyja H. M. , Mirzad Ferogh , Onsri Laila El , Vos Marc A. , van Veen Toon A. B.
Published: December 2021

In arrhythmogenic cardiomyopathy (ACM) pathogenic variants are found in genes encoding desmosomal proteins and in non-desmosomal genes, such as phospholamban (PLN, p.Arg14del variant). Previous research showed that plakoglobin protein levels and localization in the cardiac tissue of ACM patients, and PLN p.Arg14del patients diagnosed with an ACM phenotype, are disturbed. Moreover, the effects of pathogenic variants in desmosomal genes are reflected in non-cardiac tissues like buccal mucosa cells (BMC) which could serve as a promising new and non-invasive tool to support diagnosis. We collected the BMC of 33 ACM patients, 17 PLN p.Arg14del patients and 34 controls, labelled the BMC with anti-plakoglobin antibodies at different concentrations, and scored their membrane labelling. We found that plakoglobin protein levels were significantly reduced in BMC obtained from diagnosed ACM patients and preclinical variant carriers when compared to controls. This effect was independent from age and sex. Moderate to strong correlations were found with the revised 2010 Task Force Criteria score which is commonly used for ACM diagnosis (rs = −0.67, n = 64, p < 0.0001 and rs = −0.71, n = 64, p < 0.0001). In contrast, plakoglobin scores in PLN p.Arg14del patients were comparable to controls (p > 0.209), which suggests differences in underlying etiology. However, for the individual diagnosis of the ‘classical’ ACM patient, this method might not be discriminative enough to distinguish true patients from variant carriers and controls, because of the high interindividual variability.
Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice
Authors: Recio-López Patricia , Valladolid-Acebes Ismael , Berggren Per-Olof , Juntti-Berggren Lisa
Published: December 2021

Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes’ size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII.
Galectins in Early Pregnancy and Pregnancy-Associated Pathologies
Authors: Jovanović Krivokuća Milica , Vilotić Aleksandra , Nacka-Aleksić Mirjana , Pirković Andrea , Ćujić Danica , Legner Janko , Dekanski Dragana , Bojić-Trbojević Žanka
Published: December 2021

Galectins are a family of conserved soluble proteins defined by an affinity for β-galactoside structures present on various glycoconjugates. Over the past few decades, galectins have been recognized as important factors for successful implantation and maintenance of pregnancy. An increasing number of studies have demonstrated their involvement in trophoblast cell function and placental development. In addition, several lines of evidence suggest their important roles in feto-maternal immune tolerance regulation and angiogenesis. Changed or dysregulated galectin expression is also described in pregnancy-related disorders. Although the data regarding galectins’ clinical relevance are still at an early stage, evidence suggests that some galectin family members are promising candidates for better understanding pregnancy-related pathologies, as well as predicting biomarkers. In this review, we aim to summarize current knowledge of galectins in early pregnancy as well as in pregnancy-related pathologies.
Inflammation, Oxidative Stress, Senescence in Atherosclerosis: Thioredoxine-1 as an Emerging Therapeutic Target
Authors: El Hadri Khadija , Smith Rémy , Duplus Eric , El Amri Chahrazade
Published: December 2021

Atherosclerosis is a leading cause of cardiovascular diseases (CVD) worldwide and intimately linked to aging. This pathology is characterized by chronic inflammation, oxidative stress, gradual accumulation of low-density lipoproteins (LDL) particles and fibrous elements in focal areas of large and medium arteries. These fibrofatty lesions in the artery wall become progressively unstable and thrombogenic leading to heart attack, stroke or other severe heart ischemic syndromes. Elevated blood levels of LDL are major triggering events for atherosclerosis. A cascade of molecular and cellular events results in the atherosclerotic plaque formation, evolution, and rupture. Moreover, the senescence of multiple cell types present in the vasculature were reported to contribute to atherosclerotic plaque progression and destabilization. Classical therapeutic interventions consist of lipid-lowering drugs, anti-inflammatory and life style dispositions. Moreover, targeting oxidative stress by developing innovative antioxidant agents or boosting antioxidant systems is also a well-established strategy. Accumulation of senescent cells (SC) is also another important feature of atherosclerosis and was detected in various models. Hence, targeting SCs appears as an emerging therapeutic option, since senolytic agents favorably disturb atherosclerotic plaques. In this review, we propose a survey of the impact of inflammation, oxidative stress, and senescence in atherosclerosis; and the emerging therapeutic options, including thioredoxin-based approaches such as anti-oxidant, anti-inflammatory, and anti-atherogenic strategy with promising potential of senomodulation.
Sterically Hindered Quaternary Phosphonium Salts (QPSs): Antimicrobial Activity and Hemolytic and Cytotoxic Properties
Authors: Ermolaev Vadim V. , Arkhipova Daria M. , Miluykov Vasili A. , Lyubina Anna P. , Amerhanova Syumbelya K. , Kulik Natalia V. , Voloshina Alexandra D. , Ananikov Valentine P.
Published: December 2021

Structure–activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have been studied to a lesser extent. In the present study, a broad range of sterically hindered quaternary phosphonium salts (QPSs) based on tri-tert-butylphosphine was tested for their activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans, Trichophyton mentagrophytes var. gypseum). The cation structure was confirmed to determine their biological activity. A number of QPSs not only exhibit high activity against both Gram-positive and -negative bacteria but also possess antifungal properties. Additionally, the hemolytic and cytotoxic properties of QPSs were determined using blood and a normal liver cell line, respectively. The results show that tri-tert-butyl(n-dodecyl)phosphonium and tri-tert-butyl(n-tridecyl)phosphonium bromides exhibit both low cytotoxicity against normal human cells and high antimicrobial activity against bacteria, including methicillin-resistant strains S. aureus (MRSA). The mechanism of QPS action on microbes is discussed. Due to their high selectivity for pathogens, sterically hindered QPSs could serve as effective tunable biocides.
Impact of Spatially Heterogeneous Trop-2 Expression on Prognosis in Oral Squamous Cell Carcinoma
Authors: Erber Ramona , Spoerl Steffen , Mamilos Andreas , Krupar Rosemarie , Hartmann Arndt , Ruebner Matthias , Taxis Juergen , Wittenberg Mareike , Reichert Torsten E. , Spanier Gerrit , Spoerl Silvia
Published: December 2021

Oral cancer often presents with aggressive behavior and a high risk of recurrence and metastasis. For oral squamous cell carcinoma (OSCC), which is the most frequent histological subtype, therapy strategies include surgery, radiation therapy, chemotherapy, immune checkpoint inhibitors, and EGFR inhibitors. Recently, a Trop-2 antibody-drug conjugate (ADC) has been approved in the United States of America for the treatment of advanced triple-negative breast cancer. However, this ADC has also been tested in other solid tumors including head & neck squamous cell carcinoma. The prognostic impact of Trop-2 has already been reported for several cancers. We studied the prognostic influence of Trop-2 protein expression on OSCC patients’ survival. The cohort comprised n = 229 OSCC patients with available archived tumor tissue and corresponding non-neoplastic oral mucosa tissue. Using immunohistochemistry, we investigated Trop-2 expression in both the central and peripheral regions of each tumor and in corresponding non-neoplastic oral mucosa. In patients suffering from OSCC with combined high central and low peripheral Trop-2 expression, five-year overall survival (OS) was 41.2%, whereas 55.6% of OSCC patients who presented lower central and/or higher peripheral tumoral Trop-2 expression were alive after five years (p = 0.075). In multivariate Cox regression, the expression pattern of high central tumoral and lower peripheral Trop-2 expression was significantly correlated with impaired OS (HR = 1.802, 95%-CI: 1.134–2.864; p = 0.013) and recurrence-free survival (RFS) (HR = 1.633, 95%-CI: 1.042–2.560; p = 0.033), respectively, when adjusting for co-variables. Hence, Trop-2 may serve as an independent prognostic biomarker in OSCC. In subsequent studies, the pathophysiological meaning of downregulated Trop-2 expression in the OSCC periphery has to be analyzed.
Chloride Induced Corrosion and Carbonation in 3D Printed Concrete
Authors: Malan Jean De’M , van Rooyen Algurnon Steve , van Zijl Gideon P. A. G.
Published: December 2021

The durability of reinforced concrete structures is dependent on the ability of the concrete cover to combat the ingress of chlorides and carbon dioxide in marine and urban environments. In recent years, interest in additive manufacturing, specifically referring to extrusion based three-dimensional concrete printing (3DCP), has been growing in the construction industry. Despite this being a promising technology that can save construction time, costs and resources, certain issues regarding the lack of fusion between subsequent printed layers have been brought to light. Research has shown that the lack of fusion at the interlayer regions can act as ingress pathways for corrosion contaminants, such as carbon dioxide and chloride aqueous solution, that can cause deterioration. This study investigates the interlayer bond strength (flexural strength) and durability performance of 3D printed concrete subjected to pass times between 0 and 30 min and compares the results to reference cast concrete of the same concrete mixture. The durability study includes Durability Index testing (oxygen permeability, water sorptivity and chloride conductivity index), accelerated concrete carbonation and chloride-induced corrosion. The results show that the cast samples outperform printed samples, yielding greater flexural strength and durability properties, and emphasize the importance of improving the 3DCP interfacial bond. Cast samples are shown to have randomly distributed, compact voids compared to the interconnected and elongated pores located at the interlayer regions of printed samples. In addition, printed samples yield lower interlayer bond strength and durability properties with an increase in pass time, which is attributed to surface moisture evaporation as well as the thixotropic behaviour of the concrete mixture. Good relationships between the mechanical strength and durability performance are also presented.
Multiple Data Demonstrate That Bacteria Regulating Reproduction Could Be Not the Cause for the Thelytoky of Diglyphus wani (Hymenoptera: Eulophidae)
Authors: Du Sujie , Ye Fuyu , Wang Qijing , Liang Yongxuan , Wan Weijie , Guo Jianyang , Liu Wanxue
Published: December 2021

In Hymenoptera parasitoids, the reproductive mode is arrhenotoky, while a few species reproduce by thelytoky. The thelytoky of Hymenoptera parasitoids is generally genetically determined by the parasitoids themselves or induced by bacteria, including Wolbachia, Cardinium, and Rickettsia. Diglyphus wani (Hymenoptera: Eulophidae), a recently reported thelytokous species is a main parasitoid attacking agromyzid leafminers. To assess whether endosymbionts induce thelytoky in D. wani, we performed universal PCR detection and sequenced the V3-V4 region of 16S ribosomal RNA gene. In addition, bacteria were removed through high-temperature and antibiotic treatments, and the localized bacteria were detected using FISH. Based on general PCR detection, Wolbachia, Cardinium, Rickettsia, Arsenophonus, Spiroplasma, and Microsporidia were absent in laboratory and field individuals of thelytokous D. wani. Furthermore, 16S rRNA gene sequencing revealed that the dominant endosymbionts in thelytokous D. wani were not reproductive manipulators. High-temperature and antibiotic treatment for five consecutive generations cannot reverse the thelytokous pattern of D. wani, and no male offspring were produced. Moreover, no bacterial spots were found in the ovaries of D. wani. Thus, it is considered that the thelytoky of D. wani does not result in the presence of endosymbionts. This species is thus the second reported eulophid parasitoid whose thelytoky appears not to be associated with endosymbionts.
Is Forensic Entomology Lost in Space?
Authors: Boudreau Denis R. , Moreau Gaétan
Published: December 2021

Spatial and scale effects have barely been considered in forensic entomology, despite their pervasive influence on most of the parameters affecting the development of insect larval stages and the progression of insect succession on cadavers. Here, we used smoothing/interpolation techniques and semivariograms to document the spatial dynamics of sarcosaprophageous Calliphoridae, an important forensic taxon, in the Greater Moncton area in New Brunswick, Canada. Results indicated that the spatial dynamics of Calliphoridae differed between species, some species showing strong patterns of regional aggregation while others did not. Multivariate spatial correlations indicated that interspecific relationships in space varied widely, ranging from local and large-scale aggregation to spatial anticorrelation between species. Overall, this study suggested that even within a restricted timescale, the spatial dynamics of Calliphoridae can operate at many scales, manifest in different patterns, and be attributed to multiple different causes. We stress that forensic entomology has much to benefit from the use of spatial analysis because many important forensic questions, both at the fundamental and practical levels, require a spatial solution.
Drosophila Lysophospholipase Gene swiss cheese Is Required for Survival and Reproduction
Authors: Melentev Pavel A. , Sharapenkov Eduard G. , Surina Nina V. , Ivanova Ekaterina A. , Ryabova Elena V. , Sarantseva Svetlana V.
Published: December 2021

Drosophila melanogaster is one of the most famous insects in biological research. It is widely used to analyse functions of different genes. The phosphatidylcholine lysophospholipase gene swiss cheese was initially shown to be important in the fruit fly nervous system. However, the role of this gene in non-nervous cell types has not been elucidated yet, and the evolutional explanation for the conservation of its function remains elusive. In this study, we analyse expression pattern and some aspects of the role of the swiss cheese gene in the fitness of Drosophila melanogaster. We describe the spatiotemporal expression of swiss cheese throughout the fly development and analyse the survival and productivity of swiss cheese mutants. We found swiss cheese to be expressed in salivary glands, midgut, Malpighian tubes, adipocytes, and male reproductive system. Dysfunction of swiss cheese results in severe pupae and imago lethality and decline of fertility, which is impressive in males. The latter is accompanied with abnormalities of male locomotor activity and courtship behaviour, accumulation of lipid droplets in testis cyst cells and decrease in spermatozoa motility. These results suggest that normal swiss cheese is important for Drosophila melanogaster fitness due to its necessity for both specimen survival and their reproductive success.
The Complete Mitochondrial Genomes of Four Species in the Subfamily Limenitidinae (Lepidoptera, Nymphalidae) and a Phylogenetic Analysis
Authors: Liu Ning , Fang Lijun , Zhang Yalin
Published: December 2021

The complete mitogenomes of four species, Neptis thisbe, Neptis obscurior, Athyma zeroca, and Aldania raddei, were sequenced with sizes ranging from 15,172 bp (N. obscurior) to 16,348 bp (Al. raddei). All four mitogenomes display similar nucleotide content and codon usage of protein-coding genes (PCGs). Typical cloverleaf secondary structures are identified in 21 tRNA genes, while trnS1 (AGN) lacks the dihydrouridine (DHC) arm. The gene orientation and arrangement of the four mitogenomes are similar to that of other typical mitogenomes of Lepidoptera. The Ka/Ks ratio of 13 PCGs among 58 Limenitidinae species reveals that cox1 had the slowest evolutionary rate, while atp8 and nad6 exhibited a higher evolutionary rate. The phylogenetic analysis reveals that tribe-levels are well-supported monophyletic groups. Additionally, Maximum Likelihood analysis recovered the relationship (Parthenini + ((Chalingini + (Cymothoini + Neptini)) + (Adoliadini + Limenitidini))). However, a Bayesian analysis based on the same dataset recovered the relationship (Parthenini + (Adoliadini + ((Cymothoini + Neptini) + (Chalingini + Limenitidini)))). These results will offer valuable data for the future study of the phylogenetic relationships for Limenitidinae.
Clinical, Histological, and Genetic Features of 25 Patients with Autosomal Dominant Progressive External Ophthalmoplegia (ad-PEO)/PEO-Plus Due to TWNK Mutations
Authors: Bermejo-Guerrero Laura , de Fuenmayor-Fernández de la Hoz Carlos Pablo , Serrano-Lorenzo Pablo , Blázquez-Encinar Alberto , Gutiérrez-Gutiérrez Gerardo , Martínez-Vicente Laura , Galán-Dávila Lucía , García-García Jorge , Arenas Joaquín , Muelas Nuria , Hernández-Laín Aurelio , Domínguez-González Cristina , Martín Miguel A.
Published: December 2021

Autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. In this retrospective observational study, we describe clinical and complementary data from 25 PEO patients with mutations in TWNK recruited from the Hospital 12 de Octubre Mitochondrial Disorders Laboratory Database. The mean ages of onset and diagnosis were 43 and 63 years, respectively. Family history was positive in 22 patients. Ptosis and PEO (92% and 80%) were the most common findings. Weakness was present in 48%, affecting proximal limbs, neck, and bulbar muscles. Exercise intolerance was present in 28%. Less frequent manifestations were cardiac (24%) and respiratory (4%) involvement, neuropathy (8%), ataxia (4%), and parkinsonism (4%). Only 28% had mild hyperCKemia. All 19 available muscle biopsies showed signs of mitochondrial dysfunction. Ten different TWNK mutations were identified, with c.1361T>G (p.Val454Gly) and c.1070G>C (p.Arg357Pro) being the most common. Before definitive genetic confirmation, 56% of patients were misdiagnosed (36% with myasthenia, 20% with oculopharyngeal muscle dystrophy). Accurate differential diagnosis and early confirmation with appropriately chosen complementary studies allow genetic counseling and the avoidance of unnecessary treatments. Thus, mitochondrial myopathies must be considered in PEO/PEO-plus presentations, and particularly, TWNK is an important cause when positive family history is present.
Lichen Planus Activity and Damage Index (LiPADI)–Creation of the Questionnaire
Authors: Stępień Katarzyna , Żabska Ewa , Rahnama-Hezavah Mansur , Reich Adam
Published: December 2021

Introduction: Lichen planus (LP) is a chronic autoimmune disease that affects skin, oral and genital mucosa, and other sites. Basic difficulties in assessment of LP are multitude of disease forms and diverse locations of lesions. Moreover, there is lack of objective and consolidated tool for assessment of disease severity and LP progression. Objective: The aim of the study was to develop a valid evaluation tool of LP severity, which will enable disease assessment in a repetitive way. Materials and methods: A combined tool called Lichen Planus Activity and Damage Index (LiPADI) was developed to assess the severity of LP skin, mucosal, and nail lesions as well as hair loss/scaring alopecia to provide an integrative scoring for LP activity and damage caused by the disease. Skin lesions were assessed in nine locations: scalp, face, chest, abdomen, back and buttocks, arms, hands, legs, and feet. The assessment of lesion activity included erythema, hypertrophy, and scaling, while the damage was reflected by the assessment of hyperpigmentation and scaring/atrophy. In addition, mucosal lesions, nail abnormalities, hair loss, and scarring alopecia were evaluated as well. LiPADI scoring was compared with quality of life assessed with the Dermatology Life Quality Index, EQ-5D calculator, pain and pruritus intensity assessed with the Numerical Rating Scale as well as with the patient and physician global assessment. Results: Our results show that LiPADI well reflects the LP patient’s clinical condition. The obtained results were in line with other indicators assessed. In addition, it was possible to evaluate patients with various forms and locations of LP, what indicates its versatility. Conclusions: LiPADI seems to be a useful tool for measurement the severity of the LP and its progress over time, which could help to monitor the effectiveness of the patients’ treatment.
Prevalence and Prognosis of Fever Symptoms, Hypo-, and Hyperthermia in Unselected Emergency Patients
Authors: Malinovska Alexandra , Malinovska Liliana , Nickel Christian H. , Bingisser Roland
Published: December 2021

Assessments of history and body temperature are cornerstones of the diagnostic workup in all patients presenting to emergency departments (ED). Yet, the objective measurement of temperature and the subjective perception of fever can differ. This is a secondary exploratory analysis of a consecutive all-comer study, performed at an adult ED in Switzerland. Trained medical students interviewed all patients if fever was present. Altered temperature (>38.0 °C/<36.0 °C) measured at triage using an ear thermometer was used as the reference standard for diagnostic performance. In case of a disagreement between fever symptoms and altered temperature, discordance was noted. Outcome measures for case severity (acute morbidity, hospitalization, intensive care, and in-hospital mortality) were extracted from the electronic health records. Odds ratios (OR) for discordance between signs and symptoms and outcomes were calculated. Among 2183 patients, 325 patients reported fever symptoms. The sensitivity of fever symptoms as a test for altered temperature was 36.3%. Specificity was 91.5%. The negative predictive value was 84.1%, positive likelihood ratio was 4.2 and negative likelihood ratio was 0.7. The adjusted OR for discordance between fever symptoms and altered temperature was 1.71 (95% CI: 1.2–2.44) for acute morbidity, 1.56 (95% CI: 1.13–2.15) for hospitalization, and 1.12 (95% CI: 0.64–1.59) for intensive care. Unadjusted OR for mortality was 1.5 (95% CI: 0.69–3.25). Fever symptoms and altered temperature broadly overlap, but presentations can be stratified according to concordance between signs and symptoms. In case of discordance, the odds for acute morbidity and hospitalization are increased. Discordance may therefore be further investigated as a red flag for a serious outcome.
Long-Term Survival and Causes of Death in Patients below the Age of 60 with Traumatic Spinal Cord Injury in Germany
Authors: Thietje Roland , Kowald Birgitt , Böthig Ralf , Schulz Arndt P. , Northmann Markus , Rau Yannick , Hirschfeld Sven
Published: December 2021

To study the mortality, cause and risk indicators of death in German patients with traumatic spinal cord injury, patients with traumatic spinal cord injury admitted to Berufsgenossenschaftliches Trauma Hospital Hamburg between 1 January 1997 and 31 December 2018, aged between 16 and 60 with a minimal survival of one year after injury, were included. Further criteria were the absence of life-limiting comorbidities at the time of injury. 223 deceased patients with traumatic spinal cord injury were identified, investigated on and partly compared to the surviving subjects. We aimed to discover specific complications that were related to Spinal Cord Injury and responsible for a possibly limited life expectancy. Data collection was performed during in- and outpatient treatment. A statistical analysis was performed to compare groups. The post-injury life expectancy was 25.0 years with a significant correlation regarding the level of lesion and severity of injury. The leading causes of death were cardiovascular diseases and pneumonia. Bladder cancer was the most common fatal malignant tumor. The life expectancy of patients suffering from traumatic spinal cord injury is limited. The longer a patient survives after injury and the lower the level of lesion, the more likely an age-related cause of death becomes. Bladder cancer is significantly more frequent when compared to the overall distribution of tumor diseases in Germany.
Association of COVID-19 with Intracranial Hemorrhage during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A 10-Year Retrospective Observational Study
Authors: Pantel Tobias , Roedl Kevin , Jarczak Dominik , Yu Yuanyuan , Frings Daniel Peter , Sensen Barbara , Pinnschmidt Hans , Bernhardt Alexander , Cheng Bastian , Lettow Iris , Westphal Manfred , Czorlich Patrick , Kluge Stefan , Fischer Marlene
Published: December 2021

Extracorporeal membrane oxygenation (ECMO) is potentially lifesaving for patients with acute respiratory distress syndrome (ARDS) but may be accompanied by serious adverse events, including intracranial hemorrhage (ICRH). We hypothesized that ICRH occurs more frequently in patients with COVID-19 than in patients with ARDS of other etiologies. We performed a single-center retrospective analysis of adult patients treated with venovenous (vv-) ECMO for ARDS between January 2011 and April 2021. Patients were included if they had received a cranial computed tomography (cCT) scan during vv-ECMO support or within 72 h after ECMO removal. Cox regression analysis was used to identify factors associated with ICRH. During the study period, we identified 204 patients with vv-ECMO for ARDS, for whom a cCT scan was available. We observed ICRH in 35.4% (n = 17/48) of patients with COVID-19 and in 16.7% (n = 26/156) of patients with ARDS attributable to factors other than COVID-19. COVID-19 (HR: 2.945; 95%; CI: 1.079–8.038; p = 0.035) and carboxyhemoglobin (HR: 0.330; 95%; CI: 0.135–0.806; p = 0.015) were associated with ICRH during vv-ECMO. In patients receiving vv-ECMO, the incidence of ICRH is doubled in patients with COVID-19 compared to patients suffering from ARDS attributable to other causes. More studies on the association between COVID-19 and ICRH during vv-ECMO are urgently needed to identify risk patterns and targets for potential therapeutic interventions.
Inflammation of Unknown Origin: Evaluation and Prognosis of 57 Cases
Authors: Béra Suzanne , Jamilloux Yvan , Gerfaud-Valentin Mathieu , Durupt Stéphane , Nove-Josserand Raphaèle , Lega Jean-Christophe , Durieu Isabelle , Hot Arnaud , Sève Pascal
Published: December 2021

(1) Background: there are few studies on the inflammation of unknown origin (IUO). We sought to determine the etiologies and prognosis of IUO, as well as the contribution of complementary examinations. (2) Methods: this retrospective study analyzed patients meeting the Vanderschueren’s criteria in the Hospices Civils de Lyon from 2005 to 2020. (3) Results: a total of 57 patients (mean age: 67 years; interquartile range: 55–79) were included. Final diagnoses were made for 26 (46%) patients. Non-infectious inflammatory diseases were the most common diagnoses (13/26, 50%), followed by neoplasms (10/26, 38%; 8/10 hematological malignancies), infections (2/26, 8%), and miscellaneous causes (1/26, 4%). Moreover, 18-FDG-PET/CT was contributory in 12/42 cases. Anti-neutrophil cytoplasmic antibodies, serology, temporal biopsies, and bone marrow aspirates were contributory in 3/41, 1/57, 5/23, and 3/19 cases, respectively. At last follow-up (mean follow-up duration: 48 months), 8/31 undiagnosed patients were cured (five received an empirical treatment), and 5/31 died (one death was related to the empirical treatment). (4) Conclusion: more than half of the IUO remained undiagnosed. Non-infectious inflammatory diseases and hematological malignancies were the most common etiologies. Moreover, 18-FDG-PET/CT had the highest diagnostic value. Most IUO without final diagnosis persisted. The role of empirical treatments remains to be explored.
In Situ Consolidation of Thermoplastic Prepreg by Generating Harmonic Oscillations on the Consolidation Roller
Authors: Bahar Mohammad , Brysch Marco , Sinapius Michael
Published: December 2021

Automation technologies such as Automated Fiber Placement (AFP) or Automated Tape Laying (ATL) are widely used in the aerospace industry today. However, these processes can still be further improved for higher productivity. Fiber-reinforced plastics allow the production of components with extremely high specific strength and stiffness. Regarding the automated manufacturing processes, the thermoplastic tape placement offers efficiency improvements compared to the nowadays more commonly used thermoset tape placement, especially through the substitution of the expensive and time-consuming autoclave process. The consolidation of thermoplastic Prepregs is achieved with an elastic or rigid roller according to the current state of the art. The Prepregs must be consolidated precisely on the substrate or on top of each other. The most important process parameters for high-quality laminate structure with low porosity are the control of heat source, consolidation force, consolidation roll speed, and tape tension. The efficiency of the AFP process can generally be improved by increasing the speed of the consolidation roller. By increasing the speed of the consolidation roller, porosity is increased and mechanical properties of the laminate are reduced significantly due to the short contact time between consolidation roller and Prepregs. This study investigates a process that can reduce these challenges by increasing the contact time and force duration of the consolidation roller on the Prepregs. The consolidation roller in this study is additionally to be driven by the harmonic oscillations. The new method allows the consolidation roller to oscillate forward and backward during the fiber placement process. This creates another force vector in addition to the compressive force of the consolidation roller and increases the bonding strength between the layers.
Personalized 5-Year Prostate Cancer Risk Prediction Model in Korea Based on Nationwide Representative Data
Authors: Yeo Yohwan , Shin Dong Wook , Lee Jungkwon , Han Kyungdo , Park Sang Hyun , Jeon Keun Hye , Shin Jungeun , Shin Aesun , Park Jinsung
Published: December 2021

Prostate cancer is the fourth most common cause of cancer in men in Korea, and there has been a rapid increase in cases. In the present study, we constructed a risk prediction model for prostate cancer using representative data from Korea. Participants who completed health examinations in 2009, based on the Korean National Health Insurance database, were eligible for the present study. The crude and adjusted risks were explored with backward selection using the Cox proportional hazards model to identify possible risk variables. Risk scores were assigned based on the adjusted hazard ratios, and the standardized points for each risk factor were proportional to the β-coefficient. Model discrimination was assessed using the concordance statistic (c-statistic), and calibration ability was assessed by plotting the mean predicted probability against the mean observed probability of prostate cancer. Among the candidate predictors, age, smoking intensity, body mass index, regular exercise, presence of type 2 diabetes mellitus, and hypertension were included. Our risk prediction model showed good discrimination (c-statistic: 0.826, 95% confidence interval: 0.821–0.832). The relationship between model predictions and actual prostate cancer development showed good correlation in the calibration plot. Our prediction model for individualized prostate cancer risk in Korean men showed good performance. Using easily accessible and modifiable risk factors, this model can help individuals make decisions regarding prostate cancer screening.
Analysis of the Spatiotemporal Heterogeneity of Various Landscape Processes and Their Driving Factors Based on the OPGD Model for the Jiaozhou Bay Coast Zone, China
Authors: Wang Wei , Hu Yecui , Song Rong , Guo Zelian
Published: December 2021

To date, various studies have analyzed changes in the landscape but there are few studies which have explored landscape processes and the corresponding driving factors. This study makes up for this deficiency in the systematic theoretical exposition and the spatiotemporal analysis of landscape processes. The results show that the amount of arable land outflow and built-up land inflow have resulted in an increase of 92,311.11 ha of built-up land that is mostly distributed around the administrative center and along the coast of Jiaozhou Bay. The outflow of ecological land is a major resource for replenishing arable land, by 37,016.19 ha, especially in terms of the grassland that is distributed in the hilly areas west of Jiaozhou Bay. The outflow of the salt-field, fish-farm and ecological land outflow have good connectivity, a large patch size, and an irregular shape. The ecological type, elevation, slope, and vegetation coverage are the four factors that have a great influence on all landscape processes. A gentler slope and lower elevation, and proximity to cities and towns land will produce more arable land outflow and built-up land inflow. However, arable land inflow and ecological land outflow are the opposite. This research will guide natural resource management for a rapidly developing coastal zone.
Degree of Abandoned Cropland and Socioeconomic Impact Factors in China: Multi-Level Analysis Model Based on the Farmer and District/County Levels
Authors: Jiang Chong , Song Wei
Published: December 2021

At present, abandoned cropland has become a common phenomenon spreading to countries around the world. China has seen widespread abandoned cropland in recent years. However, there are extremely few empirical studies of cropland abandonment and influencing factors nationwide. In this study, survey data from 8071 farmer households in 14 Chinese provinces were used to analyze the degree of cropland abandonment in China and its spatial distribution. A multi-level model was constructed to quantitatively explore the socioeconomic factors affecting the degree of cropland abandonment, at both the farmer and district/county levels. The results show that: (1) the proportion of farmers and the spatial distribution of abandoned cropland are consistent. (2) Chongqing City, Guangdong Province, and Shanxi Province are high-value areas of abandoned cropland, while Shandong, Liaoning, Henan and Jiangsu provinces are low-value areas. (3) Among the differences in cropland abandonment, 68.5% and 31.5% can be explained at the farmer and district/county level, respectively. (4) At the farmer level, all labor and cropland transfer indicators, including land labor quantity per unit area, male agricultural labor ratio, farmers mainly of middle-aged labor, cropland transfer area and cropland subcontract amount, have significant negative effects on the degree of abandoned cropland. There is a significant negative correlation between the value of agricultural operating fixed assets in the agricultural input indicators and the degree of abandoned cropland, but participation in professional, cooperative, economic, agricultural organizations has no significant impact on the degree of abandoned cropland. The per capita disposable income, which represents the quality of life indicator, has a significant positive impact on the degree of abandoned cropland. (5) At the district/county level, the proportion of the total co-working labor force and the transfer rate of cropland are negatively related to the degree of cropland abandonment, and the proportion of the co-working labor force outside the district/county is positively related to the degree of cropland abandonment. In addition, we briefly analyzed the mechanism and process of cropland abandonment from the perspective of farmers’ decision-making. Finally, the policy suggestions to alleviate the abandonment of cropland were put forward from the district/county and farmer level, respectively.