bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair
Authors: Ribitsch Iris , Bileck Andrea , Aldoshin Alexander D. , Kańduła Maciej M. , Mayer Rupert L. , Egerbacher Monika , Gabner Simone , Auer Ulrike , Gültekin Sinan , Huber Johann , Kreil David P. , Gerner Christopher , Jenner Florien
Published: May 2021

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.
Widespread Exaptation of L1 Transposons for Transcription Factor Binding in Breast Cancer
Authors: Jiang Jiayue-Clara , Rothnagel Joseph A. , Upton Kyle R.
Published: May 2021

L1 transposons occupy 17% of the human genome and are widely exapted for the regulation of human genes, particularly in breast cancer, where we have previously shown abundant cancer-specific transcription factor (TF) binding sites within the L1PA2 subfamily. In the current study, we performed a comprehensive analysis of TF binding activities in primate-specific L1 subfamilies and identified pervasive exaptation events amongst these evolutionarily related L1 transposons. By motif scanning, we predicted diverse and abundant TF binding potentials within the L1 transposons. We confirmed substantial TF binding activities in the L1 subfamilies using TF binding sites consolidated from an extensive collection of publicly available ChIP-seq datasets. Young L1 subfamilies (L1HS, L1PA2 and L1PA3) contributed abundant TF binding sites in MCF7 cells, primarily via their 5′ UTR. This is expected as the L1 5′ UTR hosts cis-regulatory elements that are crucial for L1 replication and mobilisation. Interestingly, the ancient L1 subfamilies, where 5′ truncation was common, displayed comparable TF binding capacity through their 3′ ends, suggesting an alternative exaptation mechanism in L1 transposons that was previously unnoticed. Overall, primate-specific L1 transposons were extensively exapted for TF binding in MCF7 breast cancer cells and are likely prominent genetic players modulating breast cancer transcriptional regulation.
Genome-Wide Study of NOT2_3_5 Protein Subfamily in Cotton and Their Necessity in Resistance to Verticillium wilt
Authors: Zhao Pei , Qin Tengfei , Chen Wei , Sang Xiaohui , Zhao Yunlei , Wang Hongmei
Published: May 2021

The Negative on TATA-less (NOT) 2_3_5 domain proteins play key roles in mRNA metabolism and transcription regulation, but few comprehensive studies have focused on this protein family in plants. In our study, a total of 30 NOT2_3_5 genes were identified in four cotton genomes: Gossypium. arboretum, G. raimondii, G. hirsutum and G. barbadense. Phylogenetic analysis showed that all the NOT2_3_5 domain proteins were divided into two classes. The NOT2_3_5 genes were expanded frequently, and segmental duplication had significant effects in their expansion process. The cis-regulatory elements analysis of NOT2_3_5 promoter regions indicated that NOT2_3_5 domain proteins might participate in plant growth and development processes and responds to exogenous stimuli. Expression patterns demonstrated that all of the GhNOT2_3_5 genes were expressed in the majority of tissues and fiber development stages, and that these genes were induced by multiple stresses. Quantitative real-time PCR showed that GbNOT2_3_5 genes were up-regulated in response to verticillium wilt and the silencing of GbNOT2_3_5-3/8 and GbNOT2_3_5-4/9 led to more susceptibility to verticillium wilt than controls. Identification and analysis of the NOT2_3_5 protein family will be beneficial for further research on their biological functions.
Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside
Authors: Urschel Katharina , Tauchi Miyuki , Achenbach Stephan , Dietel Barbara
Published: May 2021

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.
Biochemical and Initial Structural Characterization of the Monocot Chimeric Jacalin OsJAC1
Authors: Huwa Nikolai , Weiergräber Oliver H. , Kirsch Christian , Schaffrath Ulrich , Classen Thomas
Published: May 2021

The monocot chimeric jacalin OsJAC1 from Oryza sativa consists of a dirigent and a jacalin-related lectin domain. The corresponding gene is expressed in response to different abiotic and biotic stimuli. However, there is a lack of knowledge about the basic function of the individual domains and their contribution to the physiological role of the entire protein. In this study, we have established a heterologous expression in Escherichia coli with high yields for the full-length protein OsJAC1 as well as its individual domains. Our findings showed that the secondary structure of both domains is dominated by β-strand elements. Under reducing conditions, the native protein displayed clearly visible transition points of thermal unfolding at 59 and 85 °C, which could be attributed to the lectin and the dirigent domain, respectively. Our study identified a single carbohydrate-binding site for each domain with different specificities towards mannose and glucose (jacalin domain), and galactose moieties (dirigent domain), respectively. The recognition of different carbohydrates might explain the ability of OsJAC1 to respond to different abiotic and biotic factors. This is the first report of specific carbohydrate-binding activity of a DIR domain, shedding new light on its function in the context of this monocot chimeric jacalin.
Induction of the Proinflammatory Chemokine Interleukin-8 Is Regulated by Integrated Stress Response and AP-1 Family Proteins Activated during Coronavirus Infection
Authors: Zhu Qing Chun , Li Shumin , Yuan Li Xia , Chen Rui Ai , Liu Ding Xiang , Fung To Sing
Published: May 2021

Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and IL-6. Although they facilitate local antiviral immunity, their excessive release leads to life-threatening cytokine release syndrome, exemplified by the severe cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated the roles of the integrated stress response (ISR) and activator protein-1 (AP-1) family proteins in regulating coronavirus-induced IL-8 and IL-6 upregulation. The mRNA expression of IL-8 and IL-6 was significantly induced in cells infected with infectious bronchitis virus (IBV), a gammacoronavirus, and porcine epidemic diarrhea virus, an alphacoronavirus. Overexpression of a constitutively active phosphomimetic mutant of eukaryotic translation initiation factor 2α (eIF2α), chemical inhibition of its dephosphorylation, or overexpression of its upstream double-stranded RNA-dependent protein kinase (PKR) significantly enhanced IL-8 mRNA expression in IBV-infected cells. Overexpression of the AP-1 protein cJUN or its upstream kinase also increased the IBV-induced IL-8 mRNA expression, which was synergistically enhanced by overexpression of cFOS. Taken together, this study demonstrated the important regulatory roles of ISR and AP-1 proteins in IL-8 production during coronavirus infection, highlighting the complex interactions between cellular stress pathways and the innate immune response.
Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer
Authors: Chao Yi-Chun , Lee Kang-Yun , Wu Sheng-Ming , Kuo Deng-Yu , Shueng Pei-Wei , Lin Cheng-Wei
Published: May 2021

Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.
Laser Direct Writing via Two-Photon Polymerization of 3D Hierarchical Structures with Cells-Antiadhesive Properties
Authors: Paun Irina A. , Calin Bogdan S. , Mustaciosu Cosmin C. , Tanasa Eugenia , Moldovan Antoniu , Niemczyk Agata , Dinescu Maria
Published: May 2021

We report the design and fabrication by laser direct writing via two photons polymerization of innovative hierarchical structures with cell-repellency capability. The structures were designed in the shape of “mushrooms”, consisting of an underside (mushroom’s leg) acting as a support structure and a top side (mushroom’s hat) decorated with micro- and nanostructures. A ripple-like pattern was created on top of the mushrooms, over length scales ranging from several µm (microstructured mushroom-like pillars, MMP) to tens of nm (nanostructured mushroom-like pillars, NMP). The MMP and NMP structures were hydrophobic, with contact angles of (127 ± 2)° and (128 ± 4)°, respectively, whereas flat polymer surfaces were hydrophilic, with a contact angle of (43 ± 1)°. The cell attachment on NMP structures was reduced by 55% as compared to the controls, whereas for the MMP, a reduction of only 21% was observed. Moreover, the MMP structures preserved the native spindle-like with phyllopodia cellular shape, whereas the cells from NMP structures showed a round shape and absence of phyllopodia. Overall, the NMP structures were more effective in impeding the cellular attachment and affected the cell shape to a greater extent than the MMP structures. The influence of the wettability on cell adhesion and shape was less important, the cellular behavior being mainly governed by structures’ topography.
Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding between Plasmodium falciparum Infected Erythrocytes and Endothelial Receptor ICAM-1
Authors: Chesnokov Olga , Visitdesotrakul Pimnitah , Kalani Komal , Nefzi Adel , Oleinikov Andrew V.
Published: May 2021

Specific adhesion of P. falciparum parasite-infected erythrocytes (IE) in deep vascular beds can result in severe complications, such as cerebral malaria, placental malaria, respiratory distress, and severe anemia. Cerebral malaria and severe malaria syndromes were associated previously with sequestration of IE to a microvasculature receptor ICAM-1. The screening of Torrey Pines Scaffold Ranking library, which consists of more than 30 million compounds designed around 75 molecular scaffolds, identified small molecules that inhibit cytoadhesion of ICAM-1-binding IE to surface-immobilized receptor at IC50 range down to ~350 nM. With their low cytotoxicity toward erythrocytes and human endothelial cells, these molecules might be suitable for development into potentially effective adjunct anti-adhesion drugs to treat cerebral and/or severe malaria syndromes. Our two-step high-throughput screening approach is specifically designed to work with compound mixtures to make screening and deconvolution to single active compounds fast and efficient.
A Confocal Microscopic Study of Gene Transfer into the Mesencephalic Tegmentum of Juvenile Chum Salmon, Oncorhynchus keta, Using Mouse Adeno-Associated Viral Vectors
Authors: Pushchina Evgeniya V. , Kapustyanov Ilya A. , Shamshurina Ekaterina V. , Varaksin Anatoly A.
Published: May 2021

To date, data on the presence of adenoviral receptors in fish are very limited. In the present work, we used mouse recombinant adeno-associated viral vectors (rAAV) with a calcium indicator of the latest generation GCaMP6m that are usually applied for the dorsal hippocampus of mice but were not previously used for gene delivery into fish brain. The aim of our work was to study the feasibility of transduction of rAAV in the mouse hippocampus into brain cells of juvenile chum salmon and subsequent determination of the phenotype of rAAV-labeled cells by confocal laser scanning microscopy (CLSM). Delivery of the gene in vivo was carried out by intracranial injection of a GCaMP6m-GFP-containing vector directly into the mesencephalic tegmentum region of juvenile (one-year-old) chum salmon, Oncorhynchus keta. AAV incorporation into brain cells of the juvenile chum salmon was assessed at 1 week after a single injection of the vector. AAV expression in various areas of the thalamus, pretectum, posterior-tuberal region, postcommissural region, medial and lateral regions of the tegmentum, and mesencephalic reticular formation of juvenile O. keta was evaluated using CLSM followed by immunohistochemical analysis of the localization of the neuron-specific calcium binding protein HuCD in combination with nuclear staining with DAPI. The results of the analysis showed partial colocalization of cells expressing GCaMP6m-GFP with red fluorescent HuCD protein. Thus, cells of the thalamus, posterior tuberal region, mesencephalic tegmentum, cells of the accessory visual system, mesencephalic reticular formation, hypothalamus, and postcommissural region of the mesencephalon of juvenile chum salmon expressing GCaMP6m-GFP were attributed to the neuron-specific line of chum salmon brain cells, which indicates the ability of hippocampal mammal rAAV to integrate into neurons of the central nervous system of fish with subsequent expression of viral proteins, which obviously indicates the neuronal expression of a mammalian adenoviral receptor homolog by juvenile chum salmon neurons.
Could Histamine H1 Receptor Antagonists Be Used for Treating COVID-19?
Authors: Qu Changbo , Fuhler Gwenny , Pan Yihang
Published: May 2021

COVID-19 has rapidly become a pandemic worldwide, causing extensive and long-term health issues. There is an urgent need to identify therapies that limit SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Unbalanced lung inflammation is a common feature in severe COVID-19 patients; therefore, reducing lung inflammation can undoubtedly benefit the clinical manifestations. Histamine H1 receptor (H1 receptor) antagonists are widely prescribed medications to treat allergic diseases, while recently it has emerged that they show significant promise as anti-SARS-CoV-2 agents. Here, we briefly summarize the novel use of H1 receptor antagonists in combating SARS-CoV-2 infection. We also describe the potential antiviral mechanisms of H1 receptor antagonists on SARS-CoV-2. Finally, the opportunities and challenges of the use of H1 receptor antagonists in managing COVID-19 are discussed.
Beneficial Effects of Remote Medical Care for Patients with Hereditary Hemorrhagic Telangiectasia during the COVID-19 Pandemic
Authors: Gaetani Eleonora , Agostini Fabiana , Di Martino Luigi , Occhipinti Denis , Passali Giulio , Santantonio Mariaconsiglia , Marano Giuseppe , Mazza Marianna , Pola Roberto ,   on behalf of the Multidisciplinary Gemelli Group for HHT
Published: May 2021

Background: Hereditary hemorrhagic telangiectasia (HHT) needs high-quality care and multidisciplinary management. During the COVID-19 pandemic, most non-urgent clinical activities for HHT outpatients were suspended. We conducted an analytical observational cohort study to evaluate whether medical and psychological support, provided through remote consultation during the COVID-19 pandemic, could reduce the complications of HHT. Methods: A structured regimen of remote consultations, conducted by either video-calls, telephone calls, or e-mails, was provided by a multidisciplinary group of physicians to a set of patients of our HHT center. The outcomes considered were: number of emergency room visits/hospitalizations, need of blood transfusions, need of iron supplementation, worsening of epistaxis, and psychological status. Results: The study included 45 patients who received remote assistance for a total of eight months. During this period, 9 patients required emergency room visits, 6 needed blood transfusions, and 24 needed iron supplementation. This was not different from what was registered among the same 45 patients in the same period of the previous year. Remote care also resulted in better management of epistaxis and improved quality of life, with the mean epistaxis severity score and the Euro-Quality of Life-Visual Analogue Scale that were significantly better at the end than at the beginning of the study. Discussion: Remote medical care might be a valid support for HHT subjects during periods of suspended outpatient surveillance, like the COVID-19 pandemic.
Pleiotropic Effects of Acetylsalicylic Acid after Coronary Artery Bypass Grafting—Beyond Platelet Inhibition
Authors: Siwik Dominika , Gajewska Magdalena , Karoń Katarzyna , Pluta Kinga , Wondołkowski Mateusz , Wilimski Radosław , Szarpak Łukasz , Filipiak Krzysztof J. , Gąsecka Aleksandra
Published: May 2021

Acetylsalicylic acid (ASA) is one of the most frequently used medications worldwide. Yet, the main indications for ASA are the atherosclerosis-based cardiovascular diseases, including coronary artery disease (CAD). Despite the increasing number of percutaneous procedures to treat CAD, coronary artery bypass grafting (CABG) remains the treatment of choice in patients with multivessel CAD and intermediate or high anatomical lesion complexity. Taking into account that CABG is a potent activator of inflammation, ASA is an important part in the postoperative therapy, not only due to ASA antiplatelet action, but also as an anti-inflammatory agent. Additional benefits of ASA after CABG include anticancerogenic, hypotensive, antiproliferative, anti-osteoporotic, and neuroprotective effects, which are especially important in patients after CABG, prone to hypertension, graft occlusion, atherosclerosis progression, and cognitive impairment. Here, we discuss the pleiotropic effects of ASA after CABG and provide insights into the mechanisms underlying the benefits of treatment with ASA, beyond platelet inhibition. Since some of ASA pleiotropic effects seem to increase the risk of bleeding, it could be considered a starting point to investigate whether the increase of the intensity of the treatment with ASA after CABG is beneficial for the CABG group of patients.
Estradiol–Testosterone Imbalance Is Associated with Erectile Dysfunction in Patients with Klinefelter Syndrome
Authors: De Rocco Ponce Maurizio , Selice Riccardo , Di Mambro Antonella , De Toni Luca , Foresta Carlo , Garolla Andrea
Published: May 2021

Erectile dysfunction (ED) is a frequent sexual disorder in adult men. Klinefelter syndrome (KS) is the most common sex chromosomal disorder and a frequent cause of male hypogonadism. Psychological and cognitive aspects are quite typical in KS and have been linked to ED, while the role of testosterone (T) levels in sexual function of KS subjects has not been fully elucidated. The purpose of the present study is to investigate the role of hormonal disturbances in erectile function of subjects with KS. We conducted a retrospective study involving 52 Klinefelter patients newly diagnosed who never received androgen replacing therapy. All the subjects underwent medical history, accurate physical examination, and blood tests. The International Index of Erectile Function questionnaire (IIEF-EF) score correlated negatively with estradiol/testosterone ratio (E2/T); this correlation remained statistically significant after correction for age (ρ −0.320 p = 0.018). A multiple linear regression analysis identified age and E2/T as the main predictors of IIEF-EF score (R2 0.169 F = 3.848 p = 0.008). Our findings corroborate previous KS data obtained in the general population showing an association between higher E2/T ratio and impaired erectile function. Larger studies are required to better elucidate the pathophysiology of ED in patients with KS.
Benefits and Risks of Antiviral Treatment during Pregnancy in Patients with Chronic Hepatitis B
Authors: Lee Yoon Seok , Bang Soo Min , Lee Young-Sun
Published: May 2021

Hepatitis B virus (HBV) is a main cause of chronic liver disease worldwide and can lead to severe liver diseases. The World Health Organization has planned to eliminate viral hepatitis, including hepatitis caused by HBV and hepatitis C virus, by 2030. As mother-to-child transmission (MTCT) of HBV is a main cause of chronic HBV infection, MTCT prevention is the main target to reduce the risk of chronic HBV infection and eliminate the disease. Recent clinical trials and meta-analyses found that antiviral therapy could prevent MTCT effectively in mothers with ≥200,000 IU/mL of HBV DNA, in combination with serial vaccination and hepatitis B immune globulin administration in infants. Despite the preventive role of antivirals for MTCT of HBV, there are several concerns regarding antiviral therapy with respect to the safety of the mother and fetus during pregnancy. This review summarizes the benefits and risks of antiviral treatment during pregnancy in women with chronic HBV infection.
Day-Time Declamping Is Associated with Better Outcomes in Kidney Transplantation: The Circarein Study
Authors: Montaigne David , Alhawajri Nasser , Jacquelinet Mathilde , Coppin Amandine , Frimat Marie , Bouyé Sébastien , Lebuffe Gilles , Staels Bart , Jacquelinet Christian , Hazzan Marc
Published: May 2021

Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischemia–reperfusion (IR) injury remains associated with poor graft function and long-term survival in kidney transplantation. We recently demonstrated a clinically significant day-time variation in myocardial tolerance to IR, transcriptionally orchestrated by the circadian clock. Patient and graft post-transplant survival were studied in a cohort of 10,291 patients first transplanted between 2006 and 2017 to test whether kidney graft tolerance to IR depends on the time-of-the-day of clamping/declamping, and thus impacts graft and patient survival. Post-transplant 1- and 3-year survival decreased with increasing ischemia duration. Time-of-the-day of clamping did not influence outcomes. However, night-time (vs. day-time) declamping was associated with a significantly worse post-transplant survival. After adjustment for other predictors, night-time (vs. day-time) declamping remained associated with a worse 1-year (HR = 1.26 (1.08–1.47), p = 0.0028 by Cox multivariable analysis) and 3-year (HR = 1.14 (1.02–1.27), p = 0.021) outcome. Interestingly, the deleterious impact of prolonged ischemia time (>15 h) was partially compensated by day-time (vs. night-time) declamping. Compared to night-time declamping, day-time declamping was associated with a better prognosis of kidney transplantation despite a longer duration of cold ischemia.
Prognostic Factors to Predict ICU Mortality in Patients with Severe ARDS Who Received Early and Prolonged Prone Positioning Therapy
Authors: Lee Po-Hsin , Kuo Chen-Tsung , Hsu Chiann-Yi , Lin Shih-Pin , Fu Pin-Kuei
Published: May 2021

Early and prolonged prone positioning (PP) therapy improve survival in advanced ARDS; however, the predictors of mortality remain unclear. The study aims to identify predictive factors correlated with mortality and build-up the prognostic score in patients with severe ARDS who received early and prolonged PP therapy. A total of 116 patients were enrolled in this retrospective cohort study. Univariate and multivariate regression models were used to estimate the odds ratio (OR) of mortality. Factors associated with mortality were assessed by Cox regression analysis and presented as the hazard ratio (HR) and 95% CI. In the multivariate regression model, renal replacement therapy (RRT; OR: 4.05, 1.54–10.67), malignant comorbidity (OR: 8.86, 2.22–35.41), and non-influenza-related ARDS (OR: 5.17, 1.16–23.16) were significantly associated with ICU mortality. Age, RRT, non-influenza-related ARDS, malignant comorbidity, and APACHE II score were included in a composite prone score, which demonstrated an area under the curve of 0.816 for predicting mortality risk. In multivariable Cox proportional hazard model, prone score more than 3 points was significantly associated with ICU mortality (HR: 2.13, 1.12–4.07, p = 0.021). We suggest prone score ≥3 points could be a good predictor for mortality in severe ARDS received PP therapy.
The Role of Snail-1 in Thyroid Cancer—What We Know So Far
Authors: Wieczorek-Szukala Katarzyna , Lewinski Andrzej
Published: May 2021

Thyroid carcinomas, despite the usually indolent behaviour and relatively good overall prognosis, show a high tendency to gain invasive phenotype and metastasise in some cases. However, due to a relatively slow progression, the exact mechanisms governing the metastatic process of thyroid carcinomas, including the epithelial-to-mesenchymal transition (EMT), are poorly described. One of the best-known regulators of cancer invasiveness is Snail-1—a zinc-finger transcription factor that plays a key role as an EMT inducer. More and more attention is being paid to the role of Snail with regard to thyroid cancer development. Apart from the obvious implications in the EMT process, Snail-1 plays an important role in the regulation of chemoresistance of the thyroid cells and cancer stem cell (CSC) formation, and it also interacts with miRNA specific to the thyroid gland. The aim of this review was to summarise the knowledge on Snail-1, especially in the context of thyroid oncogenesis.
Glioma-Specific Diffusion Signature in Diffusion Kurtosis Imaging
Authors: Hempel Johann-Martin , Brendle Cornelia , Adib Sasan Darius , Behling Felix , Tabatabai Ghazaleh , Castaneda Vega Salvador , Schittenhelm Jens , Ernemann Ulrike , Klose Uwe
Published: May 2021

Purpose: This study aimed to assess the relationship between mean kurtosis (MK) and mean diffusivity (MD) values from whole-brain diffusion kurtosis imaging (DKI) parametric maps in preoperative magnetic resonance (MR) images from 2016 World Health Organization Classification of Tumors of the Central Nervous System integrated glioma groups. Methods: Seventy-seven patients with histopathologically confirmed treatment-naïve glioma were retrospectively assessed between 1 August 2013 and 30 October 2017. The area on scatter plots with a specific combination of MK and MD values, not occurring in the healthy brain, was labeled, and the corresponding voxels were visualized on the fluid-attenuated inversion recovery (FLAIR) images. Reversely, the labeled voxels were compared to those of the manually segmented tumor volume, and the Dice similarity coefficient was used to investigate their spatial overlap. Results: A specific combination of MK and MD values in whole-brain DKI maps, visualized on a two-dimensional scatter plot, exclusively occurs in glioma tissue including the perifocal infiltrative zone and is absent in tissue of the normal brain or from other intracranial compartments. Conclusions: A unique diffusion signature with a specific combination of MK and MD values from whole-brain DKI can identify diffuse glioma without any previous segmentation. This feature might influence artificial intelligence algorithms for automatic tumor segmentation and provide new aspects of tumor heterogeneity.
Biomechanical Comparison of Five Fixation Techniques for Unstable Fragility Fractures of the Pelvic Ring
Authors: Lodde Moritz F. , Katthagen J. Christoph , Schopper Clemens O. , Zderic Ivan , Richards Geoff , Gueorguiev Boyko , Raschke Michael J. , Hartensuer René
Published: May 2021

Background: Incidence of pelvic ring fractures has increased over the past four decades, especially after low-impact trauma—classified as fragility fractures of the pelvis (FFP). To date, there is a lack of biomechanical evidence for the superiority of one existing fixation technique over another. An FFP type IIc was simulated in 50 artificial pelvises, assigned to 5 study groups: Sacroiliac (SI) screw, SI screw plus supra-acetabular external fixator, SI screw plus plate, SI screw plus retrograde transpubic screw, or S1/S2 ala–ilium screws. The specimens were tested under progressively increasing cyclic loading. Axial stiffness and cycles to failure were analysed. Displacement at the fracture sites was evaluated, having been continuously captured via motion tracking. Results: Fixation with SI screw plus plate and SI screw plus retrograde transpubic screw led to higher stability than the other tested techniques. The S1/S2 ala–ilium screws were more stable than the SI screw or the SI screw plus external fixator. Conclusions: In cases with displaced fractures, open reduction and plate fixation provides the highest stability, whereas in cases where minimally invasive techniques are applicable, a retrograde transpubic screw or S1/S2 ala–ilium screws can be considered as successful alternative treatment options.
A Well-Structured Follow-Up Program is Required after Recovery from Coronavirus Disease 2019 (COVID-19); Release from Quarantine is Not the End of Treatment
Authors: Lee Keun-Mi , Ko Hae-Jin , Lee Geon Ho , Kim A-Sol , Lee Dong-Wook
Published: May 2021

During the Coronavirus Infection Disease-19 (COVID-19) pandemic, the number of patients released from quarantine is exceeding the number of newly diagnosed cases. This study is a retrospective cohort study in which consultation data were collected from a COVID-19 follow-up health consultation program. The studied population was selected from patients who recovered after quarantine and treatment for COVID-19 in Daegu City and in Gyeongsangbukdo province, Korea, from March to June 2020. The healthcare providers comprised 20 family-medicine specialists who consulted and educated the patients through phone calls in accordance with structured guidelines. Physical and mental status before and after recovery were compared among patients who received a single consultation and those who received two or more consultations. A total of 1604 subjects were selected for the final analysis. Of these, 1145 (71.4%) had one consultation and 459 (28.6%) had two or more. The group that had two or more consultations reported significantly more physical symptoms, more psychological symptoms (including depression), and more psychological stress. Multivariate forward selection logistic regression analysis showed that re-confirmed cases of COVID-19, physical symptoms after quarantine, feelings of depression, and psychological stress had a significant effect on the number of consultations received. In conclusion, COVID-19 has various physical and mental sequelae after discharge from quarantine. Therefore, a well-structured follow-up program is needed after recovery.
Surgical Management and Reconstruction of Diaphragm, Pericardium and Chest Wall in Mesothelioma Surgery: A Review
Authors: Bertoglio Pietro , Garelli Elena , Brandolini Jury , Kawamukai Kenji , Antonacci Filippo , Ricciardi Sara , Cipolli Alessandro , Bonfanti Barbara , Forti Parri Sergio Nicola , Daddi Niccolò , Dolci Giampiero , Solli Piergiorgio
Published: May 2021

Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Extrapleural pneumonectomy (EPP) and extended pleurectomy decortication (EPD) have been recognized as radical surgical procedures. Nevertheless, both operations are technically challenging and associated with a significant rate of peri-operative morbidity and non-negligible mortality. The diaphragmatic and pericardial reconstruction technique is mandatory to avoid respiratory impairment and to reduce post-operative complications like gastric and cardiac herniation. Moreover, in the case of localized chest wall recurrence, surgery might be considered a valuable therapeutical option for highly selected and fit patients. All the technical aspects of the resection and reconstruction of the diaphragm, pericardium, and chest wall are described as well as the possible use of new minimally invasive techniques. In addition, the choice of different prosthetic materials, considering the most recent innovations in the field, are discussed.
Diagnosis, Investigation and Management of Patients with Acute and Chronic Myocardial Injury
Authors: Taggart Caelan , Wereski Ryan , Mills Nicholas L. , Chapman Andrew R.
Published: May 2021

The application of high-sensitivity cardiac troponins in clinical practice has led to an increase in the recognition of elevated concentrations in patients without myocardial ischaemia. The Fourth Universal Definition of Myocardial Infarction encourages clinicians to classify such patients as having an acute or chronic myocardial injury based on the presence or absence of a rise or a fall in cardiac troponin concentrations. Both conditions may be caused by a variety of cardiac and non-cardiac conditions, and evidence suggests that clinical outcomes are worse than patients with myocardial infarction due to atherosclerotic plaque rupture, with as few as one-third of patients alive at 5 years. Major adverse cardiovascular events are comparable between populations, and up to three-fold higher than healthy individuals. Despite this, no evidence-based strategies exist to guide clinicians in the investigation of non-ischaemic myocardial injury. This review explores the aetiology of myocardial injury and proposes a simple framework to guide clinicians in early assessment to identify those who may benefit from further investigation and treatment for those with cardiovascular disease.
Vertical Stiffness Functions of Rigid Skirted Caissons Supporting Offshore Wind Turbines
Authors: Salem AbdelRahman , Jalbi Saleh , Bhattacharya Subhamoy
Published: May 2021

Suction Bucket Jackets (SBJs) need to be fundamentally designed to avoid rocking modes of vibration about the principal axes of the set of foundations and engineered towards sway-bending modes of tower vibration. Whether or not such type of jackets exhibit rocking modes depends on the vertical stiffness of the caissons supporting them. This paper therefore derives closed form solutions for vertical stiffness in three types of ground profiles: linear, homogenous, and parabolic. The expressions are applicable to suction caissons having an aspect ratio (depth: diameter) between 0.2 and 2 (i.e., 0.2 < L/D < 2). The work is based on finite element analysis followed by non-linear regression. The derived expressions are then validated and verified using studies available in literature. Finally, an example problem is taken to demonstrate the application of the methodology whereby fundamental natural frequency of SBJ can be obtained. These formulae can be used for preliminary design and can also be used to verify rigorous finite element analysis during detailed design.
Remote Sensing-Based Automatic Detection of Shoreline Position: A Case Study in Apulia Region
Authors: Spinosa Anna , Ziemba Alex , Saponieri Alessandra , Damiani Leonardo , El Serafy Ghada
Published: May 2021

Remote sensing and satellite imagery have become commonplace in efforts to monitor and model various biological and physical characteristics of the Earth. The land/water interface is a continually evolving landscape of high scientific and societal interest, making the mapping and monitoring thereof particularly important. This paper aims at describing a new automated method of shoreline position detection through the utilization of Synthetic Aperture Radar (SAR) images derived from European Space Agency satellites, specifically the operational SENTINEL Series. The resultant delineated shorelines are validated against those derived from video monitoring systems and in situ monitoring; a mean distance of 1 and a maximum of 3.5 pixels is found.
Improved Velocity Estimation Method for Doppler Sonar Based on Accuracy Evaluation and Selection
Authors: Yang Yongshou , Fang Shiliang
Published: May 2021

The matched filtering method and the waveform-tracking method cannot maintain optimal velocity estimation performance all of the time. In order to solve this problem, this paper proposes an improved velocity estimation method for Doppler sonar, based on accuracy evaluation and selection. The echo of Doppler sonar is divided into several segments with the same width as the transmitted pulse, and each segment is regarded as the echo of the corresponding water layer. According to our study’s results, the velocity estimation accuracy of each segment is positively correlated with the ratio of its autocorrelation modulus to its power. Based on this conclusion, a velocity accuracy criterion with high accuracy and low complexity is designed in order to select the optimal velocity estimation for water layers or bottoms. The proposed accuracy selection method flexibly selects the echo interval to be processed according to the accuracy criterion, so as to maintain the optimal estimation of the current’s or bottom’s velocity. Water tank and field experiments using a prototype Doppler sonar device demonstrates that, compared with the matched filtering method and the waveform-tracking method, the average velocity estimation accuracy and bias of the proposed method are superior.
Language Ideologies and Transnational Migration: A Study of Cape Verdeans in Galicia
Authors: Bermingham Nicola
Published: May 2021

Changes to the global infrastructure have contributed to the growing (linguistic) diversity of large metropolises. However, there have been calls from scholars to explore “emerging superdiversity” (DePalma and Pérez-Caramés 2018) in peripheral regions in order to fully understand the complexities and nuances of the sociolinguistics of globalisation (Wang et al. 2014; Pietikäinen et al. 2016). This article, therefore, explores language ideologies among a purposive sample of five young adults of Cape Verdean origin living in the peripheral region of Galicia, Spain, and draws on interview data to examine the ways in which multilingual migrants engage with the language varieties in their linguistic repertoire. In studying immigration from a former African colony to a bilingual European context, we can see how language ideologies from the migrant community are reflected in local ones. The sociolinguistic dynamics of Cape Verde and Galicia share many similarities: both contexts are officially bilingual (Galician and Spanish in Galicia, Kriolu and Portuguese in Cape Verde), and questions regarding the hierarchisation of languages remain pertinent in both cases. The ideologies about the value and prestige of (minority) languages that Cape Verdean migrants arrive with are thus accommodated by local linguistic ideologies in Galicia, a region which has a history of linguistic minoritisation. This has important implications for the ways in which language, as a symbolic resource, is mobilised by migrants in contexts of transnational migration. The findings of this study show how migrants are key actors in (re)shaping the linguistic dynamics of their host society and how, through their practices and discourses, they challenge long-standing assumptions about language, identity and linguistic legitimacy, and call into question ethno-linguistic boundaries.
Synthesis, Characterization, and DFT Studies of N-(3,5-Bis(trifluoromethyl)benzyl)stearamide
Authors: Salinas-Torres Angélica , Rojas Hugo , Martínez José J. , Becerra Diana , Castillo Juan-Carlos
Published: May 2021

The novel N-(3,5-bis(trifluoromethyl)benzyl)stearamide 3 was prepared in moderate yield by a solventless direct amidation reaction of stearic acid 1 with 3,5-bis(trifluoromethyl)benzylamine 2 at 140 °C for 24 h under metal- and catalyst-free conditions. This practical method was conducted in air without any special treatment or activation. The fatty acid amide 3 was fully characterized by IR, UV–Vis, 1D and 2D NMR spectroscopy, mass spectrometry, and elemental analysis. Moreover, molecular electrostatic potential studies, determination of quantum descriptors, fundamental vibrational frequencies, and intensity of vibrational bands were computed by density functional theory (DFT) using the B3LYP method with 6-311+G(d,p) basis set in gas phase. Simulation of the infrared spectrum using the results of these calculations led to good agreement with the observed spectral patterns.
Marine Natural Products from Tunicates and Their Associated Microbes
Authors: Ramesh Chatragadda , Tulasi Bhushan Rao , Raju Mohanraju , Thakur Narsinh , Dufossé Laurent
Published: May 2021

Marine tunicates are identified as a potential source of marine natural products (MNPs), demonstrating a wide range of biological properties, like antimicrobial and anticancer activities. The symbiotic relationship between tunicates and specific microbial groups has revealed the acquisition of microbial compounds by tunicates for defensive purpose. For instance, yellow pigmented compounds, “tambjamines”, produced by the tunicate, Sigillina signifera (Sluiter, 1909), primarily originated from their bacterial symbionts, which are involved in their chemical defense function, indicating the ecological role of symbiotic microbial association with tunicates. This review has garnered comprehensive literature on MNPs produced by tunicates and their symbiotic microbionts. Various sections covered in this review include tunicates’ ecological functions, biological activities, such as antimicrobial, antitumor, and anticancer activities, metabolic origins, utilization of invasive tunicates, and research gaps. Apart from the literature content, 20 different chemical databases were explored to identify tunicates-derived MNPs. In addition, the management and exploitation of tunicate resources in the global oceans are detailed for their ecological and biotechnological implications.
Reduced Serum Circulation of Cell-Free DNA Following Chemotherapy in Breast Cancer Patients
Authors: Adusei Evelyn , Ahenkorah John , Adu-Aryee Nii Armah , Adutwum-Ofosu Kevin Kofi , Tagoe Emmanuel Ayitey , Koney Nii Koney-Kwaku , Nkansah Emmanuel , Aryee Nii Ayite , Blay Richard Michael , Hottor Bismarck Afedo , Clegg-Lamptey Joe-Nat , Arko-Boham Benjamin
Published: May 2021

Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer.