bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure of Immunotherapy—The Molecular and Immunological Origin of Immunotherapy Resistance in Lung Cancer
Authors: Błach Justyna , Wojas-Krawczyk Kamila , Nicoś Marcin , Krawczyk Paweł
Published: August 2021

Immune checkpoint inhibitors (ICIs) have a huge impact on clinical treatment results in non-small cell lung cancer (NSCLC). Blocking antibodies targeting programmed cell death protein 1 (PD-1), programmed cell death protein ligand 1 (PD-L1) or CTLA-4 (cytotoxic T cell antigen 4) have been developed and approved for the treatment of NSCLC patients. However, a large number of patients develop resistance to this type of treatment. Primary and secondary immunotherapy resistance are distinguished. No solid biomarkers are available that are appropriate to predict the unique sensitivity to immunotherapy. Knowledge of predictive markers involved in treatment resistance is fundamental for planning of new treatment combinations. Scientists focused research on the use of immunotherapy as an essential treatment in combination with other therapy strategies, which could increase cancer immunogenicity by generating tumor cells death and new antigen release as well as by targeting other immune checkpoints and tumor microenvironment. In the present review, we summarize the current knowledge of molecular bases underlying immunotherapy resistance and discuss the capabilities and the reason of different therapeutic combinations.
Multistep Signaling in Nature: A Close-Up of Geobacter Chemotaxis Sensing
Authors: Silva Marta A. , Salgueiro Carlos A.
Published: August 2021

Environmental changes trigger the continuous adaptation of bacteria to ensure their survival. This is possible through a variety of signal transduction pathways involving chemoreceptors known as methyl-accepting chemotaxis proteins (MCP) that allow the microorganisms to redirect their mobility towards favorable environments. MCP are two-component regulatory (or signal transduction) systems (TCS) formed by a sensor and a response regulator domain. These domains synchronize transient protein phosphorylation and dephosphorylation events to convert the stimuli into an appropriate cellular response. In this review, the variability of TCS domains and the most common signaling mechanisms are highlighted. This is followed by the description of the overall cellular topology, classification and mechanisms of MCP. Finally, the structural and functional properties of a new family of MCP found in Geobacter sulfurreducens are revisited. This bacterium has a diverse repertoire of chemosensory systems, which represents a striking example of a survival mechanism in challenging environments. Two G. sulfurreducens MCP—GSU0582 and GSU0935—are members of a new family of chemotaxis sensor proteins containing a periplasmic PAS-like sensor domain with a c-type heme. Interestingly, the cellular location of this domain opens new routes to the understanding of the redox potential sensing signaling transduction pathways.
Effects of Abiotic Stress on Soil Microbiome
Authors: Abdul Rahman Nur Sabrina Natasha , Abdul Hamid Nur Wahida , Nadarajah Kalaivani
Published: August 2021

Rhizospheric organisms have a unique manner of existence since many factors can influence the shape of the microbiome. As we all know, harnessing the interaction between soil microbes and plants is critical for sustainable agriculture and ecosystems. We can achieve sustainable agricultural practice by incorporating plant-microbiome interaction as a positive technology. The contribution of this interaction has piqued the interest of experts, who plan to do more research using beneficial microorganism in order to accomplish this vision. Plants engage in a wide range of interrelationship with soil microorganism, spanning the entire spectrum of ecological potential which can be mutualistic, commensal, neutral, exploitative, or competitive. Mutualistic microorganism found in plant-associated microbial communities assist their host in a number of ways. Many studies have demonstrated that the soil microbiome may provide significant advantages to the host plant. However, various soil conditions (pH, temperature, oxygen, physics-chemistry and moisture), soil environments (drought, submergence, metal toxicity and salinity), plant types/genotype, and agricultural practices may result in distinct microbial composition and characteristics, as well as its mechanism to promote plant development and defence against all these stressors. In this paper, we provide an in-depth overview of how the above factors are able to affect the soil microbial structure and communities and change above and below ground interactions. Future prospects will also be discussed.
Combination of Drugs and Cell Transplantation: More Beneficial Stem Cell-Based Regenerative Therapies Targeting Neurological Disorders
Authors: Nishimura Kaneyasu , Takata Kazuyuki
Published: August 2021

Cell transplantation therapy using pluripotent/multipotent stem cells has gained attention as a novel therapeutic strategy for treating neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, ischemic stroke, and spinal cord injury. To fully realize the potential of cell transplantation therapy, new therapeutic options that increase cell engraftments must be developed, either through modifications to the grafted cells themselves or through changes in the microenvironment surrounding the grafted region. Together these developments could potentially restore lost neuronal function by better supporting grafted cells. In addition, drug administration can improve the outcome of cell transplantation therapy through better accessibility and delivery to the target region following cell transplantation. Here we introduce examples of drug repurposing approaches for more successful transplantation therapies based on preclinical experiments with clinically approved drugs. Drug repurposing is an advantageous drug development strategy because drugs that have already been clinically approved can be repurposed to treat other diseases faster and at lower cost. Therefore, drug repurposing is a reasonable approach to enhance the outcomes of cell transplantation therapies for neurological diseases. Ideal repurposing candidates would result in more efficient cell transplantation therapies and provide a new and beneficial therapeutic combination.
Nitro-Oleic Acid (NO2-OA) Improves Systolic Function in Dilated Cardiomyopathy by Attenuating Myocardial Fibrosis
Authors: Braumann Simon , Schumacher Wibke , Im Nam Gyu , Nettersheim Felix Sebastian , Mehrkens Dennis , Bokredenghel Senai , Hof Alexander , Nies Richard Julius , Adler Christoph , Winkels Holger , Knöll Ralph , Freeman Bruce A. , Rudolph Volker , Klinke Anna , Adam Matti , Baldus Stephan , Mollenhauer Martin , Geißen Simon
Published: August 2021

Nitro-oleic acid (NO2-OA), a nitric oxide (NO)- and nitrite (NO2−)-derived electrophilic fatty acid metabolite, displays anti-inflammatory and anti-fibrotic signaling actions and therapeutic benefit in murine models of ischemia-reperfusion, atrial fibrillation, and pulmonary hypertension. Muscle LIM protein-deficient mice (Mlp−/−) develop dilated cardiomyopathy (DCM), characterized by impaired left ventricular function and increased ventricular fibrosis at the age of 8 weeks. This study investigated the effects of NO2-OA on cardiac function in Mlp−/− mice both in vivo and in vitro. Mlp−/− mice were treated with NO2-OA or vehicle for 4 weeks via subcutaneous osmotic minipumps. Wildtype (WT) littermates treated with vehicle served as controls. Mlp−/− mice exhibited enhanced TGFβ signalling, fibrosis and severely reduced left ventricular systolic function. NO2-OA treatment attenuated interstitial myocardial fibrosis and substantially improved left ventricular systolic function in Mlp−/− mice. In vitro studies of TGFβ-stimulated primary cardiac fibroblasts further revealed that the anti-fibrotic effects of NO2-OA rely on its capability to attenuate fibroblast to myofibroblast transdifferentiation by inhibiting phosphorylation of TGFβ downstream targets. In conclusion, we demonstrate a substantial therapeutic benefit of NO2-OA in a murine model of DCM, mediated by interfering with endogenously activated TGFβ signaling.
SecProCT: In Silico Prediction of Human Secretory Proteins Based on Capsule Network and Transformer
Authors: Du Wei , Zhao Xuan , Sun Yu , Zheng Lei , Li Ying , Zhang Yu
Published: August 2021

Identifying secretory proteins from blood, saliva or other body fluids has become an effective method of diagnosing diseases. Existing secretory protein prediction methods are mainly based on conventional machine learning algorithms and are highly dependent on the feature set from the protein. In this article, we propose a deep learning model based on the capsule network and transformer architecture, SecProCT, to predict secretory proteins using only amino acid sequences. The proposed model was validated using cross-validation and achieved 0.921 and 0.892 accuracy for predicting blood-secretory proteins and saliva-secretory proteins, respectively. Meanwhile, the proposed model was validated on an independent test set and achieved 0.917 and 0.905 accuracy for predicting blood-secretory proteins and saliva-secretory proteins, respectively, which are better than conventional machine learning methods and other deep learning methods for biological sequence analysis. The main contributions of this article are as follows: (1) a deep learning model based on a capsule network and transformer architecture is proposed for predicting secretory proteins. The results of this model are better than the those of existing conventional machine learning methods and deep learning methods for biological sequence analysis; (2) only amino acid sequences are used in the proposed model, which overcomes the high dependence of existing methods on the annotated protein features; (3) the proposed model can accurately predict most experimentally verified secretory proteins and cancer protein biomarkers in blood and saliva.
Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus
Authors: Palma Esposito Fortunato , Giugliano Rosa , Della Sala Gerardo , Vitale Giovanni Andrea , Buonocore Carmine , Ausuri Janardhan , Galasso Christian , Coppola Daniela , Franci Gianluigi , Galdiero Massimiliano , de Pascale Donatella
Published: August 2021

Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate Rhodococcus sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.
Protective Effects of Black Cumin (Nigella sativa) and Its Bioactive Constituent, Thymoquinone against Kidney Injury: An Aspect on Pharmacological Insights
Authors: Hannan Md. Abdul , Zahan Md. Sarwar , Sarker Partha Protim , Moni Akhi , Ha Hunjoo , Uddin Md Jamal
Published: August 2021

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and a close association between acute kidney injury (AKI) and CKD has recently been identified. Black cumin (Nigella sativa) has been shown to be effective in treating various kidney diseases. Accumulating evidence shows that black cumin and its vital compound, thymoquinone (TQ), can protect against kidney injury caused by various xenobiotics, namely chemotherapeutic agents, heavy metals, pesticides, and other environmental chemicals. Black cumin can also protect the kidneys from ischemic shock. The mechanisms underlying the kidney protective potential of black cumin and TQ include antioxidation, anti-inflammation, anti-apoptosis, and antifibrosis which are manifested in their regulatory role in the antioxidant defense system, NF-κB signaling, caspase pathways, and TGF-β signaling. In clinical trials, black seed oil was shown to normalize blood and urine parameters and improve disease outcomes in advanced CKD patients. While black cumin and its products have shown promising kidney protective effects, information on nanoparticle-guided targeted delivery into kidney is still lacking. Moreover, the clinical evidence on this natural product is not sufficient to recommend it to CKD patients. This review provides insightful information on the pharmacological benefits of black cumin and TQ against kidney damage.
Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart
Authors: Kumar Akhilesh , Tahimic Candice G. T. , Almeida Eduardo A. C. , Globus Ruth K.
Published: August 2021

Spaceflight causes cardiovascular changes due to microgravity-induced redistribution of body fluids and musculoskeletal unloading. Cardiac deconditioning and atrophy on Earth are associated with altered Trp53 and oxidative stress-related pathways, but the effects of spaceflight on cardiac changes at the molecular level are less understood. We tested the hypothesis that spaceflight alters the expression of key genes related to stress response pathways, which may contribute to cardiovascular deconditioning during extended spaceflight. Mice were exposed to spaceflight for 15 days or maintained on Earth (ground control). Ventricle tissue was harvested starting ~3 h post-landing. We measured expression of select genes implicated in oxidative stress pathways and Trp53 signaling by quantitative PCR. Cardiac expression levels of 37 of 168 genes tested were altered after spaceflight. Spaceflight downregulated transcription factor, Nfe2l2 (Nrf2), upregulated Nox1 and downregulated Ptgs2, suggesting a persistent increase in oxidative stress-related target genes. Spaceflight also substantially upregulated Cdkn1a (p21) and cell cycle/apoptosis-related gene Myc, and downregulated the inflammatory response gene Tnf. There were no changes in apoptosis-related genes such as Trp53. Spaceflight altered the expression of genes regulating redox balance, cell cycle and senescence in cardiac tissue of mice. Thus, spaceflight may contribute to cardiac dysfunction due to oxidative stress.
Stress Adaptation and the Brainstem with Focus on Corticotropin-Releasing Hormone
Authors: Chaves Tiago , Fazekas Csilla Lea , Horváth Krisztina , Correia Pedro , Szabó Adrienn , Török Bibiána , Bánrévi Krisztina , Zelena Dóra
Published: August 2021

Stress adaptation is of utmost importance for the maintenance of homeostasis and, therefore, of life itself. The prevalence of stress-related disorders is increasing, emphasizing the importance of exploratory research on stress adaptation. Two major regulatory pathways exist: the hypothalamic–pituitary–adrenocortical axis and the sympathetic adrenomedullary axis. They act in unison, ensured by the enormous bidirectional connection between their centers, the paraventricular nucleus of the hypothalamus (PVN), and the brainstem monoaminergic cell groups, respectively. PVN and especially their corticotropin-releasing hormone (CRH) producing neurons are considered to be the centrum of stress regulation. However, the brainstem seems to be equally important. Therefore, we aimed to summarize the present knowledge on the role of classical neurotransmitters of the brainstem (GABA, glutamate as well as serotonin, noradrenaline, adrenaline, and dopamine) in stress adaptation. Neuropeptides, including CRH, might be co-localized in the brainstem nuclei. Here we focused on CRH as its role in stress regulation is well-known and widely accepted and other CRH neurons scattered along the brain may also complement the function of the PVN. Although CRH-positive cells are present on some parts of the brainstem, sometimes even in comparable amounts as in the PVN, not much is known about their contribution to stress adaptation. Based on the role of the Barrington’s nucleus in micturition and the inferior olivary complex in the regulation of fine motoric—as the main CRH-containing brainstem areas—we might assume that these areas regulate stress-induced urination and locomotion, respectively. Further studies are necessary for the field.
TRIM25 and DEAD-Box RNA Helicase DDX3X Cooperate to Regulate RIG-I-Mediated Antiviral Immunity
Authors: Atkinson Sarah C. , Heaton Steven M. , Audsley Michelle D. , Kleifeld Oded , Borg Natalie A.
Published: August 2021

The cytoplasmic retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiate interferon (IFN) production and antiviral gene expression in response to RNA virus infection. Consequently, RLR signalling is tightly regulated by both host and viral factors. Tripartite motif protein 25 (TRIM25) is an E3 ligase that ubiquitinates multiple substrates within the RLR signalling cascade, playing both ubiquitination-dependent and -independent roles in RIG-I-mediated IFN induction. However, additional regulatory roles are emerging. Here, we show a novel interaction between TRIM25 and another protein in the RLR pathway that is essential for type I IFN induction, DEAD-box helicase 3X (DDX3X). In vitro assays and knockdown studies reveal that TRIM25 ubiquitinates DDX3X at lysine 55 (K55) and that TRIM25 and DDX3X cooperatively enhance IFNB1 induction following RIG-I activation, but the latter is independent of TRIM25’s catalytic activity. Furthermore, we found that the influenza A virus non-structural protein 1 (NS1) disrupts the TRIM25:DDX3X interaction, abrogating both TRIM25-mediated ubiquitination of DDX3X and cooperative activation of the IFNB1 promoter. Thus, our results reveal a new interplay between two RLR-host proteins that cooperatively enhance IFN-β production. We also uncover a new and further mechanism by which influenza A virus NS1 suppresses host antiviral defence.
Photodynamic Inactivation of Legionella pneumophila Biofilm Formation by Cationic Tetra- and Tripyridylporphyrins in Waters of Different Hardness
Authors: Mušković Martina , Ćavar Iva , Lesar Andrija , Lončarić Martin , Malatesti Nela , Gobin Ivana
Published: August 2021

The bacterium Legionella pneumophila is still one of the probable causes of waterborne diseases, causing serious respiratory illnesses. In the aquatic systems, L. pneumophila exists inside free-living amoebae or can form biofilms. Currently developed disinfection methods are not sufficient for complete eradication of L. pneumophila biofilms in water systems of interest. Photodynamic inactivation (PDI) is a method that results in an antimicrobial effect by using a combination of light and a photosensitizer (PS). In this work, the effect of PDI in waters of natural origin and of different hardness, as a treatment against L. pneumophila biofilm, was investigated. Three cationic tripyridylporphyrins, which were previously described as efficient agents against L. pneumophila alone, were used as PSs. We studied how differences in water hardness affect the PSs’ stability, the production of singlet oxygen, and the PDI activity on L. pneumophila adhesion and biofilm formation and in biofilm destruction. Amphiphilic porphyrin showed a stronger tendency for aggregation in hard and soft water, but its production of singlet oxygen was higher in comparison to tri- and tetracationic hydrophilic porphyrins that were stable in all water samples. All three studied porphyrins were shown to be effective as PDI agents against the adhesion of the L. pneumophila to polystyrene, against biofilm formation, and in the destruction of the formed biofilm, in their micromolar concentrations. However, a higher number of dissolved ions, i.e., water hardness, generally reduced somewhat the PDI activity of all the porphyrins at all tested biofilm growth stages.
Collagen Fibrillogenesis in the Mitral Valve: It’s a Matter of Compliance
Authors: Goodwin Richard L. , Kheradvar Arash , Norris Russell A. , Price Robert L. , Potts Jay D.
Published: August 2021

Collagen fibers are essential structural components of mitral valve leaflets, their tension apparatus (chordae tendineae), and the associated papillary muscles. Excess or lack of collagen fibers in the extracellular matrix (ECM) in any of these structures can adversely affect mitral valve function. The organization of collagen fibers provides a sophisticated framework that allows for unidirectional blood flow during the precise opening and closing of this vital heart valve. Although numerous ECM molecules are essential for the differentiation, growth, and homeostasis of the mitral valve (e.g., elastic fibers, glycoproteins, and glycans), collagen fibers are key to mitral valve integrity. Besides the inert structural components of the tissues, collagen fibers are dynamic structures that drive outside-to-inside cell signaling, which informs valvular interstitial cells (VICs) present within the tissue environment. Diversity of collagen family members and the closely related collagen-like triple helix-containing proteins found in the mitral valve, will be discussed in addition to how defects in these proteins may lead to valve disease.
Differential Effects of Comorbid Psychiatric Disorders on Treatment Outcome in Posttraumatic Stress Disorder from Childhood Trauma
Authors: Assmann Nele , Fassbinder Eva , Schaich Anja , Lee Christopher W. , Boterhoven de Haan Katrina , Rijkeboer Marleen , Arntz Arnoud
Published: August 2021

Patients with posttraumatic stress disorder (PTSD) frequently have comorbid diagnoses such as major depressive disorder (MDD) and anxiety disorders (AD). Studies into the impact of these comorbidities on the outcome of PTSD treatment have yielded mixed results. The different treatments investigated in these studies might explain the varied outcome. The purpose of this study was to examine the impact of these comorbidities on the outcome of two specific PTSD treatments. MDD and AD were analyzed as predictors and moderators in a trial comparing 12 sessions of either eye movement desensitization and reprocessing (EMDR) or imagery rescripting (IR) in 155 adult patients with PTSD from childhood trauma. The primary outcome was reduction of PTSD symptoms (clinician-administered PTSD Scale for DSM-5, CAPS-5) assessed at eight-week follow-up and a secondary outcome was self-report PTSD symptoms (Impact of Event Scale, IES-R). MDD was not a predictor of treatment outcome but did have a significant moderator effect. Patients with MDD showed a better outcome if they were treated with IR, whereas patients without MDD improved more in the EMDR condition. No impact of AD emerged. It seems essential to consider comorbid MDD when planning PTSD treatment to improve treatment outcomes. More research is needed to replicate our findings and focus on different kinds of PTSD treatments and other comorbidities.
Differences between Obese and Non-Obese Children and Adolescents Regarding Their Oral Status and Blood Markers of Kidney Diseases
Authors: Maćkowiak-Lewandowicz Katarzyna , Ostalska-Nowicka Danuta , Zachwieja Jacek , Paszyńska Elżbieta
Published: August 2021

(1) Background: A rarely discussed effect of obesity-related glomerulopathy (ORG) may slowly lead to irreversible glomerular damage and the development of chronic kidney disease. These patients need to undertake medical care, but whether they should be included in intensive oral care is still not mandatory. The study aimed to assess a relationship between renal, metabolic, and oral health indicators among pediatric patients affected by simple obesity. (2) Methods: 45 children and adolescents with simple obesity hospitalized (BMI 34.1 ± 4.8 kg/m2, age 15.4 ± 2.3) and compared with 41 aged-matched healthy controls (BMI 16.4 ± 2.4 kg/m2, age 15.4 ± 2.7). Echocardiography, 24-h ambulatory blood pressure monitoring, ultrasound exam with Doppler, and laboratory tests including kidney and metabolic markers were performed. Oral status was examined regarding the occurrence of carious lesions using decay missing filling teeth (DMFT), gingivitis as bleeding on probing (BOP), and bacterial colonization as plaque control record (PCR). (3) Results: The strongest correlation was revealed between BMI and concentration of uric acid, cystatin C, GFR estimated by the Filler formula (r = 0.74; r = 0.48; r = −0.52), and between oral variables such as PCR and BOP (r = 0.54; r = 0.58). Children and adolescents with obesity demonstrated untreated dental caries, less efficient in plaque control and gingivitis. (4) Conclusions: No specific relation to markers of kidney disease were found; however, more frequent gingivitis/bacterial colonization and significant differences in oral status between obese and non-obese patients were revealed. Susceptibility to inflammation may be conducive to developing metabolic syndrome and kidney damage in the form of obesity-related glomerulopathy and contribute to future dental caries. Uric acid seems to indicate metabolic syndrome and cardiovascular complications (LVMI > 95 percentiles). Cystatin C and uric acid might aspire to be early markers of kidney damage leading to obesity-related glomerulopathy.
COVID-19 in Pregnancy—Perinatal Outcomes and Vertical Transmission Preventative Strategies, When Considering More Transmissible SARS-CoV-2 Variants
Authors: Januszewski Marcin , Ziuzia-Januszewska Laura , Santor-Zaczynska Malgorzata , Jakimiuk Alicja A. , Oleksik Tomasz , Pokulniewicz Marek , Pluta Kamil , Wierzba Waldemar , Jakimiuk Artur J.
Published: August 2021

The COVID-19 pandemic affected the physical and mental health of people around the world and left unprepared health care systems struggling to mount an adequate response. Understanding the impact of COVID-19 on pregnancy in terms of perinatal and fetal outcomes is essential to propose strategies for mminimising viral transmission. Overall, 91 pregnant women in labour, or with indication for induction of labour, with COVID-19 were admitted to hospital. On the day of admission, each pregnant woman underwent a nasopharyngeal swab to validate SARS-CoV-2 infection. Whenever delivery was by caesarean section, an amniotic fluid sample was collected after uterus incision. Neonates were tested twice: first by nasopharyngeal swab at birth and secondly either at 24 h after (when babies were isolated) or at discharge (when rooming-in). All samples underwent rRT-PCR testing for SARS-CoV-2. The SARS-CoV-2 RNA tests by nasopharyngeal swab of the pregnant women produced positive results in 47 patients. This cohort gave birth to 48 infants who were double tested by nasopharyngeal swab and included in the prospective observational study. Moreover, in this same cohort, 39 amniotic fluid samples were taken during caesarean section. All samples underwent rRT-PCR testing for SARS-CoV-2 and came back negative. The study results suggest a low risk of vertical transmission of COVID-19 and favourable perinatal outcomes due to adequate preventative strategies. This approach may prove to be more beneficial in the new SARS-CoV-2 variants era.
The Impact of Suture Button Removal in Syndesmosis Fixation
Authors: Kim Jaeyoung , Kwon Minsoo , Day Jonathan , Seilern und Aspang Jesse , Shim Jaehoon , Cho Jaeho
Published: August 2021

The suture button (SB) device was introduced to negate the need for routine hardware removal in the treatment of syndesmosis injuries. However, a considerable SB removal rate has been reported, and the impact of removal is unknown. This study aimed to evaluate the radiographic and clinical outcomes after removal of SB for syndesmosis fixation. A total of 36 patients who underwent removal surgery after syndesmosis fixation using SB were identified. The mean postoperative time to removal was 12.2 months. On a plain radiograph, tibiofibular clear space (TFCS) was measured and compared at three follow-up time points. In patients with computed tomography (CT) imaging (n = 18), the anterior-to-posterior (A/P) ratio was measured to evaluate changes in quality of reduction. Additionally, clinical outcomes were assessed. There were no significant differences in TFCS between the three follow-up periods. None of the patients exhibited recurrent diastasis after SB removal. Although CT analysis demonstrated malreduction in six patients (33.3%), five of six patients had a subsequent spontaneous reduction of the syndesmosis. Clinically, all patients described the resolution of symptoms related to painful hardware at the final follow-up. Our results demonstrate that SB removal at one year following syndesmosis fixation leads to improved clinical symptoms without negatively impacting the quality of syndesmosis reduction.
Decreased Bone Mineral Density Is a Predictor of Poor Survival in Critically Ill Patients
Authors: Schulze-Hagen Maximilian F. , Roderburg Christoph , Wirtz Theresa H. , Jördens Markus S. , Bündgens Lukas , Abu Jhaisha Samira , Hohlstein Philipp , Brozat Jonathan F. , Bruners Philipp , Loberg Christina , Kuhl Christiane , Trautwein Christian , Tacke Frank , Luedde Tom , Loosen Sven H. , Koch Alexander
Published: August 2021

Alterations in bone mineral density (BMD) have been suggested as independent predictors of survival for several diseases. However, little is known about the role of BMD in the context of critical illness and intensive care medicine. We therefore evaluated the prognostic role of BMD in critically ill patients upon admission to an intensive care unit (ICU). Routine computed tomography (CT) scans of 153 patients were used to assess BMD in the first lumbar vertebra. Results were correlated with clinical data and outcomes. While median BMD was comparable between patients with and without sepsis, BMD was lower in patients with pre-existing arterial hypertension or chronic obstructive pulmonary disease. A low BMD upon ICU admission was significantly associated with impaired short-term ICU survival. Moreover, patients with baseline BMD < 122 HU had significantly impaired overall survival. The prognostic relevance of low BMD was confirmed in uni- and multivariate Cox-regression analyses including several clinicopathological parameters. In the present study, we describe a previously unrecognised association of individual BMD with short- and long-term outcomes in critically ill patients. Due to its easy accessibility in routine CT, BMD provides a novel prognostic tool to guide decision making in critically ill patients.
Comparison of COVID-19 and Non-COVID-19 Pneumonia in Down Syndrome
Authors: Real de Asua Diego , Mayer Miguel A. , Ortega María del Carmen , Borrel Jose M. , Bermejo Teresa de Jesús , González-Lamuño Domingo , Manso Coral , Moldenhauer Fernando , Carmona-Iragui María , Hüls Anke , Sherman Stephanie L. , Strydom Andre , de la Torre Rafael , Dierssen Mara
Published: August 2021

Whether the increased risk for coronavirus disease 2019 (COVID-19) hospitalization and death observed in Down syndrome (DS) are disease specific or also occur in individuals with DS and non-COVID-19 pneumonias is unknown. This retrospective cohort study compared COVID-19 cases in persons with DS hospitalized in Spain reported to the Trisomy 21 Research Society COVID-19 survey (n = 86) with admissions for non-COVID-19 pneumonias from a retrospective clinical database of the Spanish Ministry of Health (n = 2832 patients). In-hospital mortality rates were significantly higher for COVID-19 patients (26.7% vs. 9.4%), especially among individuals over 40 and patients with obesity, dementia, and/or epilepsy. The mean length of stay of deceased patients with COVID-19 was significantly shorter than in those with non-COVID-19 pneumonias. The rate of admission to an ICU in patients with DS and COVID-19 (4.3%) was significantly lower than that reported for the general population with COVID-19. Our findings confirm that acute SARS-CoV-2 infection leads to higher mortality than non-COVID-19 pneumonias in individuals with DS, especially among adults over 40 and those with specific comorbidities. However, differences in access to respiratory support might also account for some of the heightened mortality of individuals with DS with COVID-19.
Patient-Reported Outcomes for Quality of Life in SLE: Essential in Clinical Trials and Ready for Routine Care
Authors: Nguyen Matthew H. , Huang Frank F. , O’Neill Sean G.
Published: August 2021

Patient-reported outcome (PRO) instruments are widely used to assess quality of life in Systemic Lupus Erythematosus (SLE) research, and there is growing evidence for their use in clinical care. In this review, we evaluate the current evidence for their use in assessing quality of life in SLE in both research and clinical settings and examine the different characteristics of the commonly used PRO tools. There are now several well-validated generic and SLE-specific tools that have demonstrated utility in clinical trials and several tools that complement activity and damage measures in the clinical setting. PRO tools may help overcome physician–patient discordance in SLE and are valuable in the assessment of fibromyalgia and type 2 symptoms such as widespread pain and fatigue. Future work will identify optimal PRO tools for different settings but, despite current limitations, they are ready to be incorporated into patient care.
A Benchmark Evaluation of Adaptive Image Compression for Multi Picture Object Stereoscopic Images
Authors: Ortis Alessandro , Grisanti Marco , Rundo Francesco , Battiato Sebastiano
Published: August 2021

A stereopair consists of two pictures related to the same subject taken by two different points of view. Since the two images contain a high amount of redundant information, new compression approaches and data formats are continuously proposed, which aim to reduce the space needed to store a stereoscopic image while preserving its quality. A standard for multi-picture image encoding is represented by the MPO format (Multi-Picture Object). The classic stereoscopic image compression approaches compute a disparity map between the two views, which is stored with one of the two views together with a residual image. An alternative approach, named adaptive stereoscopic image compression, encodes just the two views independently with different quality factors. Then, the redundancy between the two views is exploited to enhance the low quality image. In this paper, the problem of stereoscopic image compression is presented, with a focus on the adaptive stereoscopic compression approach, which allows us to obtain a standardized format of the compressed data. The paper presents a benchmark evaluation on large and standardized datasets including 60 stereopairs that differ by resolution and acquisition technique. The method is evaluated by varying the amount of compression, as well as the matching and optimization methods resulting in 16 different settings. The adaptive approach is also compared with other MPO-compliant methods. The paper also presents an Human Visual System (HVS)-based assessment experiment which involved 116 people in order to verify the perceived quality of the decoded images.
Review on Ship Manoeuvrability Criteria and Standards
Authors: Sutulo Serge , Guedes Soares C.
Published: August 2021

Possible reduction of the installed power on newly designed merchant ships triggered by requirements of the Energy Efficiency Design Indices (EEDI) raised concern in possible safety degradation and revived interest in manoeuvrability standards to make them capable to compensate for negative effects of underpowering. A substantial part of the present article presents a detailed analytical review of general principles laid in the foundation of consistent safety standards in the naval architecture and analysis of the existing IMO manoeuvrability criteria and standards. Possible ways of extension of the existing standards to embrace situations associated with adverse sea and wind conditions are discussed and modification of the present standards related to the directional stability is considered as one of the possible solutions. At the same time, it was found that introduction of additional standards for the ship controllability in wind is justified, and the second part of the contribution is dedicated to developing a theoretical basis useful for devising such standards. This includes obtaining a set of analytical solutions related to the steady motion in wind and analysis of wind-tunnel data which resulted in simple equations for conservative generalized envelopes for the aerodynamic forces which are especially convenient for standardizing purposes. Possible design decisions aimed at augmentation of the ship’s capacity to resist adverse environmental factors are outlined.
Design of an Interactive Cellular System for the Remote Operation of Ocean Sensors: A Pilot Study Integrating Radioactivity Sensors
Authors: Alexakis Stylianos , Tsabaris Christos
Published: August 2021

Ocean in-situ sensors are crucial for measuring oceanic parameters directly from the sea in a spatial and temporal basis. Real-time operation is used in many applications related to decision support tools and early warning services in case of accidents, incidents and/or disasters. The design of the proposed system is described as a rapid-response detection system, which aims to measure natural and artificial radioactive contaminants or other crucial ocean parameters, to replace the traditional method of sampling. The development of an interactive cellular system is undertaken using a commercial router that is programmed according to sensor specifications. A radioactivity sensor is integrated in a communication box enabling self-powered operation with a solar panel. The proposed system operates in (near) real-time mode and provides gamma-ray spectra by integrating the sensor and the appropriate electronic modules in it. Additionally, an on-site experiment was conducted to test the operability of the system in a real environment close to the sea, for monitoring fallout due to rainfall and snowfall events. The main intense radionuclides that were observed by different energy lines, were radon progenies (214Bi, 214Pb). The continuous operation of the whole system was controlled by operating the system during the winter period.
A Unified Model for Analyzing Comprehensive Behaviors of Deepwater Anchors
Authors: Liu Haixiao , Yang Yancheng , Peng Jinsong
Published: August 2021

Anchors may exhibit various complicated behaviors in the seabed, especially for deepwater anchors including gravity installed anchors (GIAs) and drag embedment plate anchors (drag anchors), stimulating the development of an efficient analytical tool that applies to a variety of anchors. The present paper introduces a unified model for analyzing different anchor behaviors in both clay and sand, consisting of unified concepts, mechanical models, and analytical procedure. The kinematic behaviors of the anchors are classified uniformly as three types, i.e., diving, pulling out, and keying. By utilizing the least-force principle, various anchor properties, such as the ultimate pullout capacity (UPC), failure mode, movement direction, embedment loss, and kinematic trajectory, can all be determined by the combination and analysis of the three behaviors. Applications of the model are demonstrated summarily, by solving the UPC and the failure mode of anchor piles and suction anchors, the kinematic trajectory of drag anchors in a single soil layer or layered soils, the maximum embedment loss (MEL) of suction embedded plate anchors (SEPLAs) and OMNI-Max anchors, and the kinematic behavior of OMNI-Max anchors. Compared to existing theoretical methods, this unified model shows strong applicability and potentiality in solving a variety of behaviors and properties of different anchors under complicated seabed conditions.
The Underwater Soundscape at Gulf of Riga Marine-Protected Areas
Authors: Prawirasasra Muhammad Saladin , Mustonen Mirko , Klauson Aleksander
Published: August 2021

Passive acoustic monitoring (PAM) is widely used as an initial step towards an assessment of environmental status. In the present study, underwater ambient sound recordings from two monitoring locations in marine-protected areas (MPAs) of the Gulf of Riga were analysed. Both locations belong to the natural habitat of pinnipeds whose vocalisations were detected and analysed. An increase of vocal activity during the mating period in the late winter was revealed, including percussive signallings of grey seals. The ambient sound spectra showed that in the current shallow sea conditions ship traffic noise contributed more in the higher frequency bands. Thus, a 500 Hz one-third octave band was chosen as an indicator frequency band for anthropogenic noise in the monitoring area. It was shown that changes in the soundscape occurring during the freezing period create favourable conditions for ship noise propagation at larger distances. Based on the monitoring data, the environmental risks related to the anthropogenic sound around the monitoring sites were considered as low. However, further analysis showed that for a small percentage of time the ship traffic can cause auditory masking for the ringed seals.
Fungal Pathogen Emergence: Investigations with an Ustilago maydis × Sporisorium reilianum Hybrid
Authors: Storfie Emilee R. M. , Saville Barry J.
Published: August 2021

The emergence of new fungal pathogens threatens sustainable crop production worldwide. One mechanism by which new pathogens may arise is hybridization. To investigate hybridization, the related smut fungi, Ustilago maydis and Sporisorium reilianum, were selected because they both infect Zea mays, can hybridize, and tools are available for their analysis. The hybrid dikaryons of these fungi grew as filaments on plates but their colonization and virulence in Z. mays were reduced compared to the parental dikaryons. The anthocyanin induction caused by the hybrid dikaryon infections was distinct, suggesting its interaction with the host was different from that of the parental dikaryons. Selected virulence genes previously characterized in U. maydis and their predicted S. reilianum orthologs had altered transcript levels during hybrid infection of Z. mays. The downregulated U. maydis effectors, tin2, pit2, and cce1, and transcription factors, rbf1, hdp2, and nlt1, were constitutively expressed in the hybrid. Little impact was observed with increased effector expression; however, increased expression of rbf1 and hdp2, which regulate early pathogenic development by U. maydis, increased the hybrid’s capacity to induce symptoms including the rare induction of small leaf tumors. These results establish a base for investigating molecular aspects of smut fungal hybrid pathogen emergence.
The Prognostic Role of Micro-RNAs in Head and Neck Cancers: An Umbrella Review
Authors: Mariani Marco , Castagna Carolina , Boccia Stefania , Pastorino Roberta
Published: August 2021

We conducted an umbrella review which synthetizes the findings of systematic reviews available in the literature that investigate the prognostic role of miRNAs as potential biomarkers in the field of tertiary prevention of head and neck Cancer (HNC). We selected systematic reviews in English related to HNC, with meta-analysis of observational studies that reported quantitative prognostic measures, hazard ratios (HRs), overall survival (OS) or disease-free survival (DFS). The methodological quality of the included reviews was assessed by using the AMSTAR-2 tool. The most reported miRNAs were the following: miRNA2, Let7 family and miR17, etc. Four out of six reviews particularly emphasized the link between miRNA21 expression and HNC patients. Recently the cumulative effects of sets of miRNAs have been increasingly studied and might be a stronger predictor of survival than single miRNA.
The Spillover of Inflation among the G7 Countries
Authors: Istiak Khandokar , Tiwari Aviral Kumar , Husain Humaira , Sohag Kazi
Published: August 2021

Many global shocks, including the renegotiation of NAFTA, the United States–China trade war, the Brexit, and the COVID-19 pandemic, may have recently influenced the inflation spillover in the G7 countries. The current literature overlooks the influence of these important events on the inflation spillover of the G7 countries. This study fulfills this gap and investigates the nature of inflation spillover in the short, medium, and long term. Using the monthly data from 1956:6 to 2020:12, the study finds that Japan and the United States are the main transmitters of inflation. International trade, purchasing power parity, low-cost technology, and the Abenomics policy were found to be responsible for the inflation spillover. We suggest that the central banks of these countries collaborate to achieve the targeted inflation rate.
Hybrid SDN Performance: Switching between Centralized and Distributed Modes under Unreliable Control Communication Channels
Authors: Osman Mohammed , Mangues-Bafalluy Josep
Published: August 2021

Software-defined networking generally assumes ideal control channels between controller and network nodes. This may not be the case in challenged environments that are becoming more common due to dense and reduced-coverage 5G deployments and use cases requiring cost-effective wireless transport networks. In this paper, we evaluate the impact on network performance of unreliable controller-to-node communication channels, propose a hybrid SDN (hSDN) solution that switches between centralized and distributed operational modes depending on network conditions, and evaluate this solution under a variety of network scenarios (e.g., link impairments or packet loss ratios) designed to assess its operational limits. The results show that the proposed solution substantially improved the aggregated throughput, particularly when control channel packet loss ratios increased, while only showing a slight increase in average latency (e.g., 28% throughput improvement for 20% control packet losses). This enables network operation in hard conditions under which a canonical centralized SDN control would result in a nonoperational network.
Exploring the Impact of Educational Quizzes and Stamp Collecting Trails on Zoo Visitor Learning and Exhibit Observation
Authors: Asari Yushin , Ikuta Chiharu
Published: August 2021

Visitors observe diverse animals during zoo visits and learn more about animals by reading information boards that provide conservation education on animal behavior and habitats. This study revealed differences in effects between reading and understanding during stamp collection and a quiz game focused on “animal observations” and “perception of information boards”. Stamp collection and the quiz game were both effective for reading and observing. These were interesting techniques for learning about various captive species. The quiz game that urged observing target species and reading information boards was found to be a more effective tool to learn about the ecology and conservation of captive species.