bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sirenic Links between Diabetes, Obesity, and Bladder Cancer
Authors: Gill Emily , Sandhu Gurimaan , Ward Douglas G. , Perks Claire M. , Bryan Richard T.
Published: October 2021

There is considerable evidence of a positive association between the incidence of type 2 diabetes mellitus (T2DM) and obesity with bladder cancer (BCa), with the link between T2DM and obesity having already been established. There also appear to be potential associations between Pleckstrin homology domain containing S1 (PLEKHS1) and the Insulin-like Growth Factor (IGF) axis. Seven literature searches were carried out to investigate the backgrounds of these potential links. PLEKHS1 is a candidate biomarker in BCa, with mutations that are easily detectable in urine and increased expression seemingly associated with worse disease states. PLEKHS1 has also been implicated as a potential mediator for the onset of T2DM in people with obesity. The substantial evidence of the involvement of IGF in BCa, the role of the IGF axis in obesity and T2DM, and the global prevalence of T2DM and obesity suggest there is scope for investigating the links between these components. Preliminary findings on the relationship between PLEKHS1 and the IGF axis signal possible associations with BCa progression. This indicates that PLEKHS1 plays a role in the pathogenesis of BCa that may be mediated by members of the IGF axis. Further detailed research is needed to establish the relationship between PLEKHS1 and the IGF axis in BCa and determine how these phenomena overlap with T2DM and obesity.
An Open Question: Is Non-Ionizing Radiation a Tool for Controlling Apoptosis-Induced Proliferation?
Authors: Hack Samantha J. , Kinsey Luke J. , Beane Wendy S.
Published: October 2021

Non-ionizing radiation is commonly used in the clinical setting, despite its known ability to trigger oxidative stress and apoptosis, which can lead to damage and cell death. Although induction of cell death is typically considered harmful, apoptosis can also be beneficial in the right context. For example, cell death can serve as the signal for new tissue growth, such as in apoptosis-induced proliferation. Recent data has shown that exposure to non-ionizing radiation (such as weak static magnetic fields, weak radiofrequency magnetic fields, and weak electromagnetic fields) is able to modulate proliferation, both in cell culture and in living organisms (for example during tissue regeneration). This occurs via in vivo changes in the levels of reactive oxygen species (ROS), which are canonical activators of apoptosis. This review will describe the literature that highlights the tantalizing possibility that non-ionizing radiation could be used to manipulate apoptosis-induced proliferation to either promote growth (for regenerative medicine) or inhibit it (for cancer therapies). However, as uncontrolled growth can lead to tumorigenesis, much more research into this exciting and developing area is needed in order to realize its promise.
Phytoconstituents and Bioactivity of Plants of the Genus Spiraea L. (Rosaceae): A Review
Authors: Kostikova Vera A. , Petrova Natalia V.
Published: October 2021

The genus Spiraea L. belongs to the Rosaceae Juss. family and includes more than 100 species distributed in the temperate zone and subtropical zone of the Northern Hemisphere at the center of species diversity in East Asia. Representatives of the genus are known as ornamental plants with many forms and varieties, are widely used in conventional medicine, and have a high resource potential. This review provides information on the diversity of phenolic compounds (flavonoids, phenolcarboxylic acids, and lignans), terpenoids, alkaloids, steroids, and other classes of secondary metabolites in the species of Spiraea worldwide. The article also presents little-known and hard-to-find data published in Russian concerning Spiraea phytochemistry. The biological activities of extracts and their fractions and of individual compounds having different types of biological activity (e.g., antioxidant, antibacterial, anti-inflammatory, and antifungal) are discussed. Data about biotechnological research on representatives of the genus Spiraea are presented too. The analysis of the literature showed that further chemical and pharmacological studies on Spiraea plants are quite promising.
Cellular Protein Phosphatase 2A Regulates Cell Survival Mechanisms in Influenza A Virus Infection
Authors: Gerlt Vanessa , Mayr Juliane , Del Sarto Juliana , Ludwig Stephan , Boergeling Yvonne
Published: October 2021

Influenza A viruses (IAVs) are respiratory pathogens that are able to hijack multiple cellular mechanisms to drive their replication. Consequently, several viral and cellular proteins undergo posttranslational modifications such as dynamic phosphorylation/dephosphorylation. In eukaryotic cells, dephosphorylation is mainly catalyzed by protein phosphatase 2A (PP2A). While the function of kinases in IAV infection is quite well studied, only little is known about the role of PP2A in IAV replication. Here, we show, by using knockdown and inhibition approaches of the catalytic subunit PP2Ac, that this phosphatase is important for efficient replication of several IAV subtypes. This could neither be attributed to alterations in the antiviral immune response nor to changes in transcription or translation of viral genes. Interestingly, decreased PP2Ac levels resulted in a significantly reduced cell viability after IAV infection. Comprehensive kinase activity profiling identified an enrichment of process networks related to apoptosis and indicated a synergistic action of hyper-activated PI3K/Akt, MAPK/JAK-STAT and NF-kB signaling pathways, collectively resulting in increased cell death. Taken together, while IAV seems to effectively tap leftover PP2A activity to ensure efficient viral replication, reduced PP2Ac levels fail to orchestrate cell survival mechanisms to protect infected cells from early cell death.
A Review of Discovery Profiling of PIWI-Interacting RNAs and Their Diverse Functions in Metazoans
Authors: Huang Songqian , Yoshitake Kazutoshi , Asakawa Shuichi
Published: October 2021

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs (sncRNAs) that perform crucial biological functions in metazoans and defend against transposable elements (TEs) in germ lines. Recently, ubiquitously expressed piRNAs were discovered in soma and germ lines using small RNA sequencing (sRNA-seq) in humans and animals, providing new insights into the diverse functions of piRNAs. However, the role of piRNAs has not yet been fully elucidated, and sRNA-seq studies continue to reveal different piRNA activities in the genome. In this review, we summarize a set of simplified processes for piRNA analysis in order to provide a useful guide for researchers to perform piRNA research suitable for their study objectives. These processes can help expand the functional research on piRNAs from previously reported sRNA-seq results in metazoans. Ubiquitously expressed piRNAs have been discovered in the soma and germ lines in Annelida, Cnidaria, Echinodermata, Crustacea, Arthropoda, and Mollusca, but they are limited to germ lines in Chordata. The roles of piRNAs in TE silencing, gene expression regulation, epigenetic regulation, embryonic development, immune response, and associated diseases will continue to be discovered via sRNA-seq.
Poly(amidoamine) Dendrimers as Nanocarriers for 5-Fluorouracil: Effectiveness of Complex Formation and Cytotoxicity Studies
Authors: Szota Magdalena , Reczyńska-Kolman Katarzyna , Pamuła Elżbieta , Michel Olga , Kulbacka Julita , Jachimska Barbara
Published: October 2021

Two generations of positively charged poly(amidoamine) dendrimers (PAMAMs) were selected for study as potential carriers for the anticancer drug 5-fluorouracil (5FU), a drug primarily used in the treatment of colorectal cancer. Analytical techniques, such as UV-Vis spectrophotometry, NMR Spectroscopy and Laser Doppler Velocimetry (LDV), have shown that the most critical factor determining the formation of a PAMAM–5FU complex is the starting components’ protonation degree. The tests confirmed the system’s ability to attach about 20 5FU molecules per one dendrimer molecule for the G4PAMAM dendrimer and about 25 molecules for the G6PAMAM dendrimer, which gives a system yield of 16% for the fourth generation and 5% for sixth generation dendrimers. Additionally, using the QCM-D method, the adsorption efficiency and the number of drug molecules immobilized in the dendrimer structure were determined. A new aspect in our study was the determination of the change in zeta potential (ζ) induced by the immobilization of 5FU molecules on the dendrimer’s outer shell and the importance of this effect in the direct contact of the carrier with cells. Cytotoxicity tests (resazurin reduction and MTS tests) showed no toxicity of dendrimers against mouse fibroblast cells (L929) and a significant decrease in cell viability in the case of four human malignant cell lines: malignant melanoma (A375), glioblastoma (SNB-19), prostate cancer (Du-145) and colon adenocarcinoma (HT-29) during incubation with PAMAM–5FU complexes. The purpose of our work was to investigate the correlation between the physicochemical properties of the carrier and active substance and the system efficiency and optimizing conditions for the formation of an efficient system based on PAMAM dendrimers as nanocarriers for 5-fluorouracil. An additional aspect was to identify potential application properties of the complexes, as demonstrated by cytotoxicity tests.
Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action
Authors: Drayton Matthew , Deisinger Julia P. , Ludwig Kevin C. , Raheem Nigare , Müller Anna , Schneider Tanja , Straus Suzana K.
Published: October 2021

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed.
Roles for Selenoprotein I and Ethanolamine Phospholipid Synthesis in T Cell Activation
Authors: Ma Chi , Martinez-Rodriguez Verena , Hoffmann Peter R.
Published: October 2021

The selenoprotein family includes 25 members, many of which are antioxidant or redox regulating enzymes. A unique member of this family is Selenoprotein I (SELENOI), which does not catalyze redox reactions, but instead is an ethanolamine phosphotransferase (Ept). In fact, the characteristic selenocysteine residue that defines selenoproteins lies far outside of the catalytic domain of SELENOI. Furthermore, data using recombinant SELENOI lacking the selenocysteine residue have suggested that the selenocysteine amino acid is not directly involved in the Ept reaction. SELENOI is involved in two different pathways for the synthesis of phosphatidylethanolamine (PE) and plasmenyl PE, which are constituents of cellular membranes. Ethanolamine phospholipid synthesis has emerged as an important process for metabolic reprogramming that occurs in pluripotent stem cells and proliferating tumor cells, and this review discusses roles for upregulation of SELENOI during T cell activation, proliferation, and differentiation. SELENOI deficiency lowers but does not completely diminish de novo synthesis of PE and plasmenyl PE during T cell activation. Interestingly, metabolic reprogramming in activated SELENOI deficient T cells is impaired and this reduces proliferative capacity while favoring tolerogenic to pathogenic phenotypes that arise from differentiation. The implications of these findings are discussed related to vaccine responses, autoimmunity, and cell-based therapeutic approaches.
Inhibition of Spinal TRPV1 Reduces NMDA Receptor 2B Phosphorylation and Produces Anti-Nociceptive Effects in Mice with Inflammatory Pain
Authors: Kang Suk-Yun , Seo Su Yeon , Bang Se Kyun , Cho Seong Jin , Choi Kwang-Ho , Ryu Yeonhee
Published: October 2021

Transient receptor potential vanilloid 1 (TRPV1) has been implicated in peripheral inflammation and is a mediator of the inflammatory response to various noxious stimuli. However, the interaction between TRPV1 and N-methyl-D-aspartate (NMDA) receptors in the regulation of inflammatory pain remains poorly understood. This study aimed to investigate the analgesic effects of intrathecal administration of capsazepine, a TRPV1 antagonist, on carrageenan-induced inflammatory pain in mice and to identify its interactions with NMDA receptors. Inflammatory pain was induced by intraplantar injection of 2% carrageenan in male ICR mice. To investigate the analgesic effects of capsazepine, pain-related behaviors were evaluated using von Frey filaments and a thermal stimulator placed on the hind paw. TRPV1 expression and NMDA receptor phosphorylation in the spinal cord and glutamate concentration in the spinal cord and serum were measured. Intrathecal treatment with capsazepine significantly attenuated carrageenan-induced mechanical allodynia and thermal hyperalgesia. Moreover, carrageenan-enhanced glutamate and phosphorylation of NMDA receptor subunit 2B in the spinal cord were suppressed by capsazepine administration. These results indicate that TRPV1 and NMDA receptors in the spinal cord are associated with inflammatory pain transmission, and inhibition of TRPV1 may reduce inflammatory pain via NMDA receptors.
Platelet-Derived PCSK9 Is Associated with LDL Metabolism and Modulates Atherothrombotic Mechanisms in Coronary Artery Disease
Authors: Petersen-Uribe Álvaro , Kremser Marcel , Rohlfing Anne-Katrin , Castor Tatsiana , Kolb Kyra , Dicenta Valerie , Emschermann Frederic , Li Bo , Borst Oliver , Rath Dominik , Müller Karin Anne Lydia , Gawaz Meinrad Paul
Published: October 2021

Platelets play a significant role in atherothrombosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is critically involved in the regulation of LDL metabolism and interacts with platelet function. The effect of PCSK9 in platelet function is poorly understood. The authors of this article sought to characterize platelets as a major source of PCSK9 and PCSK9’s role in atherothrombosis. In a large cohort of patients with coronary artery disease (CAD), platelet count, platelet reactivity, and platelet-derived PCSK9 release were analyzed. The role of platelet PCSK9 on platelet and monocyte function was investigated in vitro. Platelet count and hyper-reactivity correlated with plasma LDL in CAD. The circulating platelets express on their surface and release substantial amounts of PCSK9. Release of PCSK9 augmented platelet-dependent thrombosis, monocyte migration, and differentiation into macrophages/foam cells. Platelets and PCSK9 accumulated in tissue derived from atherosclerotic carotid arteries in areas of macrophages. PCSK9 inhibition reduced platelet activation and platelet-dependent thrombo-inflammation. The authors identified platelets as a source of PCSK9 in CAD, which may have an impact on LDL metabolism. Furthermore, platelet-derived PCSK9 contributes to atherothrombosis, and inhibition of PCSK9 attenuates thrombo-inflammation, which may contribute to the reported beneficial clinical effects.
Tumor-Associated Microglia/Macrophages as a Predictor for Survival in Glioblastoma and Temozolomide-Induced Changes in CXCR2 Signaling with New Resistance Overcoming Strategy by Combination Therapy
Authors: Urbantat Ruth M. , Jelgersma Claudius , Brandenburg Susan , Nieminen-Kelhä Melina , Kremenetskaia Irina , Zollfrank Julia , Mueller Susanne , Rubarth Kerstin , Koch Arend , Vajkoczy Peter , Acker Gueliz
Published: October 2021

Tumor recurrence is the main challenge in glioblastoma (GBM) treatment. Gold standard therapy temozolomide (TMZ) is known to induce upregulation of IL8/CXCL2/CXCR2 signaling that promotes tumor progression and angiogenesis. Our aim was to verify the alterations on this signaling pathway in human GBM recurrence and to investigate the impact of TMZ in particular. Furthermore, a combi-therapy of TMZ and CXCR2 antagonization was established to assess the efficacy and tolerability. First, we analyzed 76 matched primary and recurrent GBM samples with regard to various histological aspects with a focus on the role of TMZ treatment and the assessment of predictors of overall survival (OS). Second, the combi-therapy with TMZ and CXCR2-antagonization was evaluated in a syngeneic mouse tumor model with in-depth immunohistological investigations and subsequent gene expression analyses. We observed a significantly decreased infiltration of tumor-associated microglia/macrophages (TAM) in recurrent tumors, while a high TAM infiltration in primary tumors was associated with a reduced OS. Additionally, more patients expressed IL8 in recurrent tumors and TMZ therapy maintained CXCL2 expression. In mice, enhanced anti-tumoral effects were observed after combi-therapy. In conclusion, high TAM infiltration predicts a survival disadvantage, supporting findings of the tumor-promoting phenotype of TAMs. Furthermore, the combination therapy seemed to be promising to overcome CXCR2-mediated resistance.
Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel
Authors: Maltais René , Roy Jenny , Perreault Martin , Sato Sachiko , Lévesque Julie-Christine , Poirier Donald
Published: October 2021

Aminosteroid derivative RM-581 was previously identified as an endoplasmic-reticulum (ER) stress inducer with potent in vitro and in vivo anticancer activities. We report its evaluation in androgen-independent prostate cancer (PC-3) cells. RM-581 efficiently blocks PC-3 cell proliferation with stronger activity than that of a selection of known antineoplastic agents. This later also showed a synergistic effect with docetaxel, able to block the proliferation of docetaxel-resistant PC-3 cells and, contrary to docetaxel, did not induce cell resistance. RM-581 induced an increase in the expression level of ER stress-related markers of apoptosis, potentially triggered by the presence of RM-581 in the ER of PC-3 cells. These in vitro results were then successfully translated in vivo in a PC-3 xenograft tumor model in nude mice, showing superior blockade than that of docetaxel. RM-581 was also able to stop the progression of PC-3 cells when they had become resistant to docetaxel treatment. Concomitantly, we observed a decrease in gene markers of mevalonate and fatty acid pathways, and intratumoral levels of cholesterol by 19% and fatty acids by 22%. Overall, this work demonstrates the potential of an ER stress inducer as an anticancer agent for the treatment of prostate cancers that are refractory to commonly used chemotherapy treatments.
Adipose-Derived Stem/Stromal Cells in Kidney Transplantation: Status Quo and Future Perspectives
Authors: Storti Gabriele , Favi Evaldo , Albanesi Francesca , Kim Bong-Sung , Cervelli Valerio
Published: October 2021

Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia–reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted.
Linagliptin Protects against Endotoxin-Induced Acute Kidney Injury in Rats by Decreasing Inflammatory Cytokines and Reactive Oxygen Species
Authors: Wu Tsung-Jui , Hsieh Yi-Jen , Lu Chia-Wen , Lee Chung-Jen , Hsu Bang-Gee
Published: October 2021

Septic shock can increase pro-inflammatory cytokines, reactive oxygen species (ROS), and multiple organ dysfunction syndrome (MODs) and even lead to death. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been proven to exert potential antioxidant and anti-inflammatory effects. We investigated the effects of linagliptin on endotoxic shock and acute kidney injury (AKI) in animal and cell models. In the cell model, linagliptin attenuated ROS by activating the AMP-activated protein kinase (AMPK) pathway, restoring nuclear-factor-erythroid-2-related factor (Nrf2) and heme oxygenase 1 (HO-1) protein, and decreasing pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β)). In the animal model, 14-week-old conscious Wistar–Kyoto rats were randomly divided into three groups (n = 8 in each group). Endotoxin shock with MODs was induced by the intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 20 mg/kg). Linagliptin improved animal survival without affecting hemodynamic profiles. In the histopathology and immunohistochemistry examinations of the rat kidneys, linagliptin (10 mg/kg) suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide synthase (iNOS), decreased injury scores, and preserved E-cadherin expression from LPS damage. In conclusion, linagliptin ameliorated endotoxin-shock-induced AKI by reducing ROS via AMPK pathway activation and suppressing the release of TNF-α and IL-1β in conscious rats.
Screening of β1- and β2-Adrenergic Receptor Modulators through Advanced Pharmacoinformatics and Machine Learning Approaches
Authors: Islam Md Ataul , Rallabandi V. P. Subramanyam , Mohammed Sameer , Srinivasan Sridhar , Natarajan Sathishkumar , Dudekula Dawood Babu , Park Junhyung
Published: October 2021

Cardiovascular diseases (CDs) are a major concern in the human race and one of the leading causes of death worldwide. β-Adrenergic receptors (β1-AR and β2-AR) play a crucial role in the overall regulation of cardiac function. In the present study, structure-based virtual screening, machine learning (ML), and a ligand-based similarity search were conducted for the PubChem database against both β1- and β2-AR. Initially, all docked molecules were screened using the threshold binding energy value. Molecules with a better binding affinity were further used for segregation as active and inactive through ML. The pharmacokinetic assessment was carried out on molecules retained in the above step. Further, similarity searching of the ChEMBL and DrugBank databases was performed. From detailed analysis of the above data, four compounds for each of β1- and β2-AR were found to be promising in nature. A number of critical ligand-binding amino acids formed potential hydrogen bonds and hydrophobic interactions. Finally, a molecular dynamics (MD) simulation study of each molecule bound with the respective target was performed. A number of parameters obtained from the MD simulation trajectories were calculated and substantiated the stability between the protein-ligand complex. Hence, it can be postulated that the final molecules might be crucial for CDs subjected to experimental validation.
Engineering Pyrrolysyl-tRNA Synthetase for the Incorporation of Non-Canonical Amino Acids with Smaller Side Chains
Authors: Koch Nikolaj G. , Goettig Peter , Rappsilber Juri , Budisa Nediljko
Published: October 2021

Site-specific incorporation of non-canonical amino acids (ncAAs) into proteins has emerged as a universal tool for systems bioengineering at the interface of chemistry, biology, and technology. The diversification of the repertoire of the genetic code has been achieved for amino acids with long and/or bulky side chains equipped with various bioorthogonal tags and useful spectral probes. Although ncAAs with relatively small side chains and similar properties are of great interest to biophysics, cell biology, and biomaterial science, they can rarely be incorporated into proteins. To address this gap, we report the engineering of PylRS variants capable of incorporating an entire library of aliphatic “small-tag” ncAAs. In particular, we performed mutational studies of a specific PylRS, designed to incorporate the shortest non-bulky ncAA (S-allyl-l-cysteine) possible to date and based on this knowledge incorporated aliphatic ncAA derivatives. In this way, we have not only increased the number of translationally active “small-tag” ncAAs, but also determined key residues responsible for maintaining orthogonality, while engineering the PylRS for these interesting substrates. Based on the known plasticity of PylRS toward different substrates, our approach further expands the reassignment capacities of this enzyme toward aliphatic amino acids with smaller side chains endowed with valuable functionalities.
Method to Address Complexity in Organizations Based on a Comprehensive Overview
Authors: Revina Aleksandra , Aksu Ünal , Meister Vera
Published: October 2021

Digitalization increasingly enforces organizations to accommodate changes and gain resilience. Emerging technologies, changing organizational structures and dynamic work environments bring opportunities and pose new challenges to organizations. Such developments, together with the growing volume and variety of the exchanged data, mainly yield complexity. This complexity often represents a solid barrier to efficiency and impedes understanding, controlling, and improving processes in organizations. Hence, organizations are prevailingly seeking to identify and avoid unnecessary complexity, which is an odd mixture of different factors. Similarly, in research, much effort has been put into measuring, reviewing, and studying complexity. However, these efforts are highly fragmented and lack a joint perspective. Further, this negatively affects the complexity research acceptance by practitioners. In this study, we extend the body of knowledge on complexity research and practice addressing its high fragmentation. In particular, a comprehensive literature analysis of complexity research is conducted to capture different types of complexity in organizations. The results are comparatively analyzed, and a morphological box containing three aspects and ten features is developed. In addition, an established multi-dimensional complexity framework is employed to synthesize the results. Using the findings from these analyses and adopting the Goal Question Metric, we propose a method for complexity management. This method serves to provide key insights and decision support in the form of extensive guidelines for addressing complexity. Thus, our findings can assist organizations in their complexity management initiatives.
Improving Undergraduate Novice Programmer Comprehension through Case-Based Teaching with Roles of Variables to Provide Scaffolding
Authors: Shi Nianfeng
Published: October 2021

A role-based teaching approach was proposed in order to decrease the cognitive load placed by the case-based teaching method in the undergraduate novice programmer comprehension. The results are evaluated by using the SOLO (Structure of Observed Learning Outcomes) taxonomy. Data analysis suggested novice programmers with role-based teaching tended to experience better performances, including the SOLO level of program comprehension, program debugging scores, program explaining scores, except for programming language knowledge scores, compared with the classical case-based teaching method. Considering the SOLO category of program comprehension and performances, evidence that the roles of variables can provide scaffolding to understand case programs through combining its program structure with its related problem domain is discussed, and the SOLO categories for relational reasoning are proposed. Meanwhile, the roles of variables can assist the novice in learning programming language knowledge. These results indicate that combing case-based teaching with the role of variables is an effective way to improve novice program comprehension.
Parasite Prevalence May Drive the Biotic Impoverishment of New England (USA) Bumble Bee Communities
Authors: Averill Anne L. , Couto Andrea V. , Andersen Jeremy C. , Elkinton Joseph S.
Published: October 2021

Numerous studies have reported a diversity of stressors that may explain continental-scale declines in populations of native pollinators, particularly those in the genus Bombus. However, there has been little focus on the identification of the local-scale dynamics that may structure currently impoverished Bombus communities. For example, the historically diverse coastal-zone communities of New England (USA) now comprise only a few species and are primarily dominated by a single species, B. impatiens. To better understand the local-scale factors that might be influencing this change in community structure, we examined differences in the presence of parasites in different species of Bombus collected in coastal-zone communities. Our results indicate that Bombus species that are in decline in this region were more likely to harbor parasites than are B. impatiens populations, which were more likely to be parasite-free and to harbor fewer intense infections or co-infections. The contrasting parasite burden between co-occurring winners and losers in this community may impact the endgame of asymmetric contests among species competing for dwindling resources. We suggest that under changing climate and landscape conditions, increasing domination of communities by healthy, synanthropic Bombus species (such as B. impatiens) may be another factor hastening the further erosion of bumble bee diversity.
Impact of Post-Procedural Change in Left Ventricle Systolic Function on Survival after Percutaneous Edge-to-Edge Mitral Valve Repair
Authors: Hagnäs Magnus J. , Grasso Carmelo , Di Salvo Maria Elena , Caggegi Anna , Barbanti Marco , Scandura Salvatore , Milici Annalisa , Motta Gessica , Bentivegna Agnese , Sardone Andrea , Capodicasa Luigi , Giuffrida Angelo , Biancari Fausto , Mäkikallio Timo , Capodanno Davide , Tamburino Corrado
Published: October 2021

Objectives: To investigate how the changes of left ventricle ejection fraction (LVEF) between admission and discharge affected the long-term outcome in patients who underwent percutaneous edge-to-edge mitral valve repair for secondary mitral regurgitation. Background: An acute impairment of LVEF after surgical repair of mitral regurgitation, known as afterload mismatch, has been associated with increased all-cause mortality. Afterload mismatch after percutaneous edge-to-edge mitral valve repair has been postulated to be a transient phenomenon. Methods: This study is based on a single-center, retrospective, observational registry of patients who underwent percutaneous edge-to-edge mitral valve repair with the MitraClip (Abbot Vascular) system for the treatment of symptomatic, moderate-to-severe mitral regurgitation. We included data on 399 patients who underwent percutaneous edge-to-edge mitral valve repair for secondary mitral regurgitation. Expert echocardiographers assessed LVEF before the procedure and at discharge. The patients were divided into three groups according to the difference of periprocedural LVEF measurements: unchanged (n = 318), improved (n = 40), and decreased (n = 41) LVEF. Results: The median follow-up time was 2.0 years. When adjusted for gender, NYHA class and estimated glomerular filtration rate, decreased postprocedural LVEF was associated with an increased risk of death (adjusted HR 2.05, 95% CI 1.26–3.34) and increased postprocedural LVEF with a reduced risk of death (adjusted HR 0.47, 95% CI 0.24–0.91) compared to unchanged LVEF. Conclusion: Among patients who underwent percutaneous edge-to-edge mitral valve repair, decreased postprocedural LVEF was associated with increased mortality, while improved LVEF was associated with lower mortality compared to unchanged LVEF.
Addition of Bone Marrow Aspirate Concentrate Resulted in High Rate of Healing and Good Functional Outcomes in the Treatment of Clavicle Fracture Nonunion: A Retrospective Case Series
Authors: Benshabat Dvir , Factor Shai , Maman Eran , Khoury Amal , Krespi Raphael , Ashkenazi Itay , Chechik Ofir , Dolkart Oleg
Published: October 2021

Bone marrow aspirate concentrate (BMAC) is an autologous cell composition that is obtained through a needle aspiration from the iliac crest. The purpose of this study was to evaluate the outcomes of patients treated with open reduction and internal fixation with BMAC supplementation for clavicle fracture nonunion. This was a retrospective case series of 21 consecutive patients with clavicle fracture nonunion that were treated with ORIF and BMAC supplementation between 2013 and 2020. Patients were evaluated for fracture union, time to union, complications related to surgical and donor site, and functional outcome using the Quick Disability of the Arm Shoulder and Hand (QDASH), subjective shoulder value (SSV), and pain. The mean age was 41.8 years. The mean follow-up was 36 months. Twenty (95.2%) patients demonstrated fracture union, with a mean time to union of 4.5 months. Good functional scores were achieved: SSV, 74.3; QDASH, 23.3; pain level, 3.1. There were no complications or pain related to the iliac crest donor site. Supplementary BMAC to ORIF in the treatment of clavicle fracture nonunion is a safe method, resulting in high rates of fracture union and good functional outcomes with minimal complications and pain.
When Conventional Oxygen Therapy Fails—The Effectiveness of High-Flow Nasal Oxygen Therapy in Patients with Respiratory Failure in the Course of COVID-19
Authors: Rorat Marta , Szymański Wojciech , Jurek Tomasz , Karczewski Maciej , Zelig Jakub , Simon Krzysztof
Published: October 2021

High-flow nasal oxygen (HFNO) is recommended as a first-line treatment in patients with acute hypoxemic respiratory failure due to COVID-19. We assessed the effectiveness of HFNO and predictors of failure and death. The medical records of 200 consecutive adult patients treated with HFNO were analysed. Ninety-two patients (46%) were successfully cured, 52 (26%) required noninvasive ventilation, and 61 (30.5%) received intubation. Overall mortality was 40.5%. Risk factors of HFNO ineffectiveness were: SpO2 ≤ 90% with conventional oxygen therapy (HR 0.32, 95% CI 0.19–0.53, p < 0.001), SpO2 ≤ 74% without oxygen therapy (HR 0.44, 95% CI 0.27–0.71, p < 0.001), an age ≥ 60, comorbidities, biomarkers (C-reactive protein, procalcitonin, creatinine, lactate dehydrogenase), duration of symptoms before admission to hospital ≤ 9 days, start of treatment with HFNO ≤ 4 days. The multivariate logistic regression models (age ≥ 60, comorbidities, C-reactive protein concentration and SpO2 with oxygen therapy) revealed a high predictive value of death and HFNO failure (AUC 0.851, sensitivity 0.780, specificity 0.802; AUC 0.800, sensitivity 0.776, specificity 0.739, respectively). HFNO is a safe method for treating acute hypoxemic respiratory failure, with effectiveness reaching nearly 50%. Low values of SpO2 without and during oxygen therapy seem to be good diagnostic tools for predicting death and HFNO failure.
The Index of Microcirculatory Resistance after Primary Percutaneous Coronary Intervention Predicts Long-Term Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Yoon Gwang-Seok , Ahn Sung Gyun , Woo Seong-Ill , Yoon Myeong Ho , Lee Man-Jong , Choi Seong Huan , Seo Ji-Yeon , Kwon Sung Woo , Park Sang-Don , Seo Kyoung-Woo
Published: October 2021

The index of microcirculatory resistance (IMR) is a simple method that can measure microvascular function after primary percutaneous coronary intervention (PCI) in patients with ST-segment Elevation Myocardial Infarction (STEMI). This study is to find out whether IMR predicts clinical long-term outcomes in STEMI patients. A total of 316 patients with STEMI who underwent primary PCI from 2005 to 2015 were enrolled. The IMR was measured using pressure sensor/thermistor-tipped guidewire after primary PCI. The primary endpoint was the rate of death or hospitalization for heart failure (HF) over a mean follow-up period of 65 months. The mean corrected IMR was 29.4 ± 20.0. Patients with an IMR > 29 had a higher rate of the primary endpoint compared to patients with an IMR ≤ 29 (10.3% vs. 2.1%, p = 0.001). During the follow-up period, 13 patients (4.1%) died and 6 patients (1.9%) were hospitalized for HF. An IMR > 29 was associated with an increased risk of death or hospitalization for HF (OR 5.378, p = 0.004). On multivariable analysis, IMR > 29 (OR 3.962, p = 0.022) remained an independent predictor of death or hospitalization for HF with age (OR 1.048, p = 0.049) and symptom-to-balloon time (OR 1.002, p = 0.049). High IMR was an independent predictor for poor long-term clinical outcomes in STEMI patients after primary PCI.
Automatic Segmentation of Specific Intervertebral Discs through a Two-Stage MultiResUNet Model
Authors: Cheng Yu-Kai , Lin Chih-Lung , Huang Yi-Chi , Chen Jui-Chi , Lan Tzu-Peng , Lian Zhen-You , Chuang Cheng-Hung
Published: October 2021

The automatic segmentation of intervertebral discs from medical images is an important task for an intelligent clinical system. In this study, a deep learning model based on the MultiResUNet model for the automatic segmentation of specific intervertebral discs is presented. MultiResUNet can easily segment all intervertebral discs in MRI images; however, when only certain specific intervertebral discs need to be segmented, problems with segmentation errors, misalignment, and noise occur. In order to solve these problems, a two-stage MultiResUNet model is proposed. Connected-component labeling, automatic cropping, and distance transform are used in the proposed method. The experimental results show that the segmentation errors and misalignments of specific intervertebral discs are greatly reduced, and the segmentation accuracy is increased to about 94%. The performance of the proposed method proves its usefulness for the automatic segmentation of specific intervertebral discs over other deep learning models, such as the U-Net, CNN-based, Attention U-Net, and MultiResUNet models.
Calcium-Based Biomineralization: A Smart Approach for the Design of Novel Multifunctional Hybrid Materials
Authors: Campodoni Elisabetta , Montanari Margherita , Artusi Chiara , Bassi Giada , Furlani Franco , Montesi Monica , Panseri Silvia , Sandri Monica , Tampieri Anna
Published: October 2021

Biomineralization consists of a complex cascade of phenomena generating hybrid nano-structured materials based on organic (e.g., polymer) and inorganic (e.g., hydroxyapatite) components. Biomineralization is a biomimetic process useful to produce highly biomimetic and biocompatible materials resembling natural hard tissues such as bones and teeth. In detail, biomimetic materials, composed of hydroxyapatite nanoparticles (HA) nucleated on an organic matrix, show extremely versatile chemical compositions and physical properties, which can be controlled to address specific challenges. Indeed, different parameters, including (i) the partial substitution of mimetic doping ions within the HA lattice, (ii) the use of different organic matrices, and (iii) the choice of cross-linking processes, can be finely tuned. In the present review, we mainly focused on calcium biomineralization. Besides regenerative medicine, these multifunctional materials have been largely exploited for other applications including 3D printable materials and in vitro three-dimensional (3D) models for cancer studies and for drug testing. Additionally, biomineralized multifunctional nano-particles can be involved in applications ranging from nanomedicine as fully bioresorbable drug delivery systems to the development of innovative and eco-sustainable UV physical filters for skin protection from solar radiations.
Assimilation Research of Wind Stress Drag Coefficient Based on the Linear Expression
Authors: Xu Junli , Nie Yuling , Ma Kai , Shi Wenqi , Lv Xianqing
Published: October 2021

The wind stress drag coefficient plays an important role in storm surge models. This study reveals the influences of wind stress drag coefficients, which are given in form of formulas and inverted by the data assimilation method, on the storm surge levels in the Bohai Sea, Yellow Sea, and East China Sea during Typhoon 7008. In the process of data assimilation, the drag coefficient is based on the linear expression Cd = (a + b × U10) × 10−3 (generally speaking, a and b are empirical parameters determined by observed data). The results showed that the performance of the data assimilation method was far superior to those of drag coefficient formulas. Additionally, the simulated storm surge levels obviously changed in the neighborhood of typhoon eye. Furthermore, the effect of initial values of a and b in the Cd expression on the storm surge levels was also investigated when employing the data assimilation method. The results indicated that the simulation of storm surge level was the closest to the observation when a and b were simultaneously equal to zero, whereas the simulations had slight differences when the initial values of a and b were separately equal to the drag coefficients from the work of Smith, Wu, and Geernaert et al.. Therefore, we should choose appropriate initial values for a and b by using the data assimilation method. As a whole, the data assimilation method is much better than drag coefficient parameterization formulas in the simulation of storm surges.
Stock Assessment of Exploited Sardine Populations from Northeastern Bay of Bengal Water, Bangladesh Using the Length-Based Bayesian Biomass (LBB) Method
Authors: Barman Partho Protim , Liu Qun , Al-Mamun Md. Abdullah , Schneider Petra , Mozumder Mohammad Mojibul Hoque
Published: October 2021

Stock assessment is necessary to understand the status of fishery stocks. However, for the data-poor fishery, it is very challenging to assess the stock status. The length-based Bayesian biomass (LBB) technique is one of the most powerful methods to assess the data-poor fisheries resources that need simple length frequency (LF) data. Addressing the present gap, this study aimed to assess the stock status of three sardines (Sardinella fimbriata, Dussumieria acuta, and D. elopsoides) in the Bay of Bengal (BoB), Bangladesh using the LBB method. The estimated relative biomass for S. fimbriata was B/B0 < BMSY/B0, indicating the overfished biomass, while the assessed B/B0 > BMSY/B0 for D. acuta and D. elopsoides indicates healthy biomass. Additionally, for S. fimbriata, the length at first landing was smaller than the optimum length at first landing (Lc < Lc_opt), indicating an overfishing status, but a safe fishing status was assessed for D. acuta and D. elopsoides (Lc > Lc_opt). Therefore, increasing the mesh size of fishing gears may help to ensure the long-term viability of sardine populations in the BoB, Bangladesh.
Antimycotic Effects of 11 Essential Oil Components and Their Combinations on 13 Food Spoilage Yeasts and Molds
Authors: Nißl Laura , Westhaeuser Florian , Noll Matthias
Published: October 2021

Food safety is important to reduce food spoilage microorganisms and foodborne pathogens. However, food safety is challenging, as customers’ demand for natural preservatives is increasing. Essential oils (EOs) and their components (EOCs) are alternative antibacterial and antimycotic food additives. In this study, the minimal inhibitory concentrations (MIC) of 11 different EOCs against 13 food spoilage molds and yeasts were investigated via the microdilution method. Cinnamaldehyde (CA) revealed the lowest MIC for all tested strains and all EOCs (32.81–328.1 µg ml−1). However, CA is organoleptic and was therefore combined with other EOCs via the checkerboard method. Overall, 27 out of 91 combinations showed a synergistic effect, and both respective EOC concentrations could be reduced by maintaining MIC. Thereby, the combination with citral or citronellal showed promising results. The concentration-dependent effect of CA was studied in further detail on Saccharomyces cerevisiae, with CA causing delayed growth-kinetics and reduced total cell numbers. In addition, flow cytometric measurements combined with live–dead staining indicate the fungicidal effect of CA, due to decreasing total cell numbers and increasing relative amount of propidium iodide-positive cells. In this study, we demonstrated that CA is a potent candidate for the use as a natural preservative against food-relevant mold and yeasts showing fungistatic and fungicidal effects. Therefore, CA and EOC combinations with respective lower EOC concentrations reduce organoleptic reservations, which ease their application in the food industry.
Sources, Channels and Strategies of Disinformation in the 2020 US Election: Social Networks, Traditional Media and Political Candidates
Authors: Benaissa Pedriza Samia
Published: October 2021

The dissemination of fake news during the conduct of an electoral campaign can significantly distort the process by which voters form their opinion on candidates and decide their vote. Cases of disinformation have been happening since the rise of social networks and the last presidential election held in 2020 in the United States was not an exception. The present research aims at analyzing the ways in which political disinformation is generated by different types of sources (social networks users, the media and political candidates) through various channels for communication (social and traditional media). Quantitative and qalitative methods were used to analyze a sample of news published during the election and verified by the most important fact-checking organizations in the United States and Europe. The results indicate that users of social networks spread false information on equal terms with presidential candidates, although the channel preferred to spread misleading messages was social networks in 67.4% of cases. The candidates relied on the use of classic disinformation strategies through traditional media, although the greatest degree of disinformation occurred when conspiratorial hoaxes were circulated through social networks.