bluuebunny/crossref_metadata_2025 huggingface dataset:
Interfacial Peptides as Affinity Modulating Agents of Protein-Protein Interactions
Authors: Ershov Pavel V. , Mezentsev Yuri V. , Ivanov Alexis S.
Published: January 2022

The identification of disease-related protein-protein interactions (PPIs) creates objective conditions for their pharmacological modulation. The contact area (interfaces) of the vast majority of PPIs has some features, such as geometrical and biochemical complementarities, “hot spots”, as well as an extremely low mutation rate that give us key knowledge to influence these PPIs. Exogenous regulation of PPIs is aimed at both inhibiting the assembly and/or destabilization of protein complexes. Often, the design of such modulators is associated with some specific problems in targeted delivery, cell penetration and proteolytic stability, as well as selective binding to cellular targets. Recent progress in interfacial peptide design has been achieved in solving all these difficulties and has provided a good efficiency in preclinical models (in vitro and in vivo). The most promising peptide-containing therapeutic formulations are under investigation in clinical trials. In this review, we update the current state-of-the-art in the field of interfacial peptides as potent modulators of a number of disease-related PPIs. Over the past years, the scientific interest has been focused on following clinically significant heterodimeric PPIs MDM2/p53, PD-1/PD-L1, HIF/HIF, NRF2/KEAP1, RbAp48/MTA1, HSP90/CDC37, BIRC5/CRM1, BIRC5/XIAP, YAP/TAZ–TEAD, TWEAK/FN14, Bcl-2/Bax, YY1/AKT, CD40/CD40L and MINT2/APP.
The Mucolipin TRPML2 Channel Enhances the Sensitivity of Multiple Myeloma Cell Lines to Ibrutinib and/or Bortezomib Treatment
Authors: Santoni Giorgio , Amantini Consuelo , Maggi Federica , Marinelli Oliviero , Santoni Matteo , Morelli Maria Beatrice
Published: January 2022

Multiple myeloma (MM) is a haematological B cell malignancy characterised by clonal proliferation of plasma cells and their accumulation in the bone marrow. The aim of the present study is the evaluation of biological effects of Ibrutinib in human MM cell lines alone or in combination with different doses of Bortezomib. In addition, the relationship between the expression of TRPML2 channels and chemosensitivity of different MM cell lines to Ibrutinib administered alone or in combination with Bortezomib has been evaluated. By RT-PCR and Western blot analysis, we found that the Ibrutinib-resistant U266 cells showed lower TRPML2 expression, whereas higher TRPML2 mRNA and protein levels were evidenced in RPMI cells. Moreover, TRPML2 gene silencing in RPMI cells markedly reverted the effects induced by Ibrutinib alone or in combination with Bortezomib suggesting that the sensitivity to Ibrutinib is TRPML2 mediated. In conclusion, this study suggests that the expression of TRPML2 in MM cells increases the sensitivity to Ibrutinib treatment, suggesting for a potential stratification of Ibrutinib sensitivity of MM patients on the basis of the TRPML2 expression. Furthermore, studies in vitro and in vivo should still be necessary to completely address the molecular mechanisms and the potential role of TRPML2 channels in therapy and prognosis of MM patients.
The Builders of the Junction: Roles of Junctophilin1 and Junctophilin2 in the Assembly of the Sarcoplasmic Reticulum–Plasma Membrane Junctions in Striated Muscle
Authors: Perni Stefano
Published: January 2022

Contraction of striated muscle is triggered by a massive release of calcium from the sarcoplasmic reticulum (SR) into the cytoplasm. This intracellular calcium release is initiated by membrane depolarization, which is sensed by voltage-gated calcium channels CaV1.1 (in skeletal muscle) and CaV1.2 (in cardiac muscle) in the plasma membrane (PM), which in turn activate the calcium-releasing channel ryanodine receptor (RyR) embedded in the SR membrane. This cross-communication between channels in the PM and in the SR happens at specialized regions, the SR-PM junctions, where these two compartments come in close proximity. Junctophilin1 and Junctophilin2 are responsible for the formation and stabilization of SR-PM junctions in striated muscle and actively participate in the recruitment of the two essential players in intracellular calcium release, CaV and RyR. This short review focuses on the roles of junctophilins1 and 2 in the formation and organization of SR-PM junctions in skeletal and cardiac muscle and on the functional consequences of the absence or malfunction of these proteins in striated muscle in light of recently published data and recent advancements in protein structure prediction.
Perspectives on Light-Based Disinfection to Reduce the Risk of COVID-19 Transmission during Dental Care
Authors: Balhaddad Abdulrahman A. , Mokeem Lamia , Khajotia Sharukh S. , Florez Fernando L. Esteban , Melo Mary A. S.
Published: January 2022

Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is a positive-sense single-stranded RNA coronavirus capable of causing potentially lethal pneumonia-like infectious diseases in mammals and birds. The main mechanisms by which SARS-CoV-2 spreads include airborne transmission (aerosols and droplets) and the direct exposure of tissues (conjunctival, nasal, and oral mucosa) to contaminated fluids. The aerosol formation is universal in dentistry due to the use of rotary instruments (handpieces), ultrasonic scalers, and air–water syringes. Several layers of infection control should protect key stakeholders such as dentists, dental staff, and patients. These include the utilization of personal protective equipment, high-volume evacuation systems, pre-procedural mouthwashes, rubber dam, and more recently, antimicrobial photodynamic therapy and intra-oral visible light irradiation. These non-specific light-based approaches are relatively simple, inexpensive, and effective against viruses, bacteria, and fungi. Therefore, the present perspective review discusses the current efforts and limitations on utilizing biophotonic approaches as adjunct infection control methods to prevent the transmission of SARS-CoV-2 in dental settings. In addition, the present perspective review may positively impact subsequent developments in the field, as it offers relevant information regarding the intricacies and complexities of infection control in dental settings.
Local Structure Awareness-Based Retinal Microaneurysm Detection with Multi-Feature Combination
Authors: Deng Jiakun , Tang Puying , Zhao Xuegong , Pu Tian , Qu Chao , Peng Zhenming
Published: January 2022

Retinal microaneurysm (MA) is the initial symptom of diabetic retinopathy (DR). The automatic detection of MA is helpful to assist doctors in diagnosis and treatment. Previous algorithms focused on the features of the target itself; however, the local structural features of the target and background are also worth exploring. To achieve MA detection, an efficient local structure awareness-based retinal MA detection with the multi-feature combination (LSAMFC) is proposed in this paper. We propose a novel local structure feature called a ring gradient descriptor (RGD) to describe the structural differences between an object and its surrounding area. Then, a combination of RGD with the salience and texture features is used by a Gradient Boosting Decision Tree (GBDT) for candidate classification. We evaluate our algorithm on two public datasets, i.e., the e-ophtha MA dataset and retinopathy online challenge (ROC) dataset. The experimental results show that the performance of the trained model significantly improved after combining traditional features with RGD, and the area under the receiver operating characteristic curve (AUC) values in the test results of the datasets e-ophtha MA and ROC increased from 0.9615 to 0.9751 and from 0.9066 to 0.9409, respectively.
Definition of an Inflammatory Biomarker Signature in Plasma-Derived Extracellular Vesicles of Glioblastoma Patients
Authors: Cilibrasi Chiara , Simon Thomas , Vintu Marian , Tolias Christos , Samuels Mark , Mazarakis Nektarios K. , Eravci Murat , Stewart Nicolas , Critchley Giles , Giamas Georgios
Published: January 2022

Glioblastoma (GB) is an aggressive type of tumour for which therapeutic options and biomarkers are limited. GB diagnosis mostly relies on symptomatic presentation of the tumour and, in turn, brain imaging and invasive biopsy that can delay its diagnosis. Description of easily accessible and effective biomarkers present in biofluids would thus prove invaluable in GB diagnosis. Extracellular vesicles (EVs) derived from both GB and stromal cells are essential to intercellular crosstalk in the tumour bulk, and circulating EVs have been described as a potential reservoir of GB biomarkers. Therefore, EV-based liquid biopsies have been suggested as a promising tool for GB diagnosis and follow up. To identify GB specific proteins, sEVs were isolated from plasma samples of GB patients as well as healthy volunteers using differential ultracentrifugation, and their content was characterised through mass spectrometry. Our data indicate the presence of an inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation including VWF, FCGBP, C3, PROS1, and SERPINA1. Overall, this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GB diagnosis and, consequently, patients’ prognosis and quality of life.
Prevalence, Risk Factors, and Pathophysiology of Nonalcoholic Fatty Liver Disease (NAFLD) in Women with Polycystic Ovary Syndrome (PCOS)
Authors: Spremović Rađenović Svetlana , Pupovac Miljan , Andjić Mladen , Bila Jovan , Srećković Svetlana , Gudović Aleksandra , Dragaš Biljana , Radunović Nebojša
Published: January 2022

Background: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders in women’s reproductive period of life. The presence of nonalcoholic fatty liver disease NAFLD, one of the leading causes of chronic liver disease in the Western world, is increased in women with PCOS. This review aims to present current knowledge in epidemiology, pathophysiology, diagnostics, and treatment of NAFLD in PCOS with an emphasis on the molecular basis of development of NAFLD in PCOS women. Methods: Authors investigated the available data on PCOS and NAFLD by a MEDLINE and Pub Med search during the years 1990–2021 using a combination of keywords such as “PCOS”, “NAFLD”, “steatohepatitis”, “insulin resistance”, “hyperandrogenaemia”, “inflammation”, “adipose tissue”, and “obesity”. Peer-reviewed articles regarding NAFLD and PCOS were included in this manuscript. Additional articles were identified from the references of relevant papers. Results: PCOS and NAFLD are multifactorial diseases, The development of NAFLD in PCOS women is linked to insulin resistance, hyperandrogenemia, obesity, adipose tissue dysfunction, and inflammation. There is the possible role of the gut microbiome, mitochondrial dysfunction, and endocannabinoid system in the maintenance of NAFLD in PCOS women. Conclusions: There is a need for further investigation about the mechanism of the development of NAFLD in PCOS women. New data about the molecular basis of development of NAFLD in PCOS integrated with epidemiological and clinical information could influence the evolution of new diagnostic and therapeutic approaches of NAFLD in PCOS.
Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis
Authors: Pohl Rebekka , Feder Susanne , Haberl Elisabeth M. , Rein-Fischboeck Lisa , Weiss Thomas S. , Spirk Marlen , Bruckmann Astrid , McMullen Nichole , Sinal Christopher J. , Buechler Christa
Published: January 2022

Non-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH. Therefore, mice were infected with adeno-associated virus 8 to direct hepatic overexpression of prochemerin in a methionine–choline deficient dietary model of NASH. At the end of the study, hepatic and serum chemerin were higher in the chemerin-expressing mice. These animals had less hepatic oxidative stress, F4/80 and CC-chemokine ligand 2 (CCL2) protein, and mRNA levels of inflammatory genes than the respective control animals. In order to identify the underlying mechanisms, prochemerin was expressed in hepatocytes and the hepatic stellate cells, LX-2. Here, chemerin had no effect on cell viability, production of inflammatory, or pro-fibrotic factors. Notably, cultivation of human peripheral blood mononuclear cells (PBMCs) in the supernatant of Huh7 cells overexpressing chemerin reduced CCL2, interleukin-6, and osteopontin levels in cell media. CCL2 was also low in RAW264.7 cells exposed to Hepa1–6 cell produced chemerin. In summary, the current study showed that prochemerin overexpression had little effect on hepatocytes and hepatic stellate cells. Of note, hepatocyte-produced chemerin deactivated PBMCs and protected against inflammation in experimental NASH.
Chlorin Endogenous to the North Pacific Brittle Star Ophiura sarsii for Photodynamic Therapy Applications in Breast Cancer and Glioblastoma Models
Authors: Klimenko Antonina , Rodina Elvira E. , Silachev Denis , Begun Maria , Babenko Valentina A. , Benditkis Anton S. , Kozlov Anton S. , Krasnovsky Alexander A. , Khotimchenko Yuri S. , Katanaev Vladimir L.
Published: January 2022

Photodynamic therapy (PDT) represents a powerful avenue for anticancer treatment. PDT relies on the use of photosensitizers—compounds accumulating in the tumor and converted from benign to cytotoxic upon targeted photoactivation. We here describe (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) as a major metabolite of the North Pacific brittle stars Ophiura sarsii. As a chlorin, ETPA efficiently produces singlet oxygen upon red-light photoactivation and exerts powerful sub-micromolar phototoxicity against a panel of cancer cell lines in vitro. In a mouse model of glioblastoma, intravenous ETPA injection combined with targeted red laser irradiation induced strong necrotic ablation of the brain tumor. Along with the straightforward ETPA purification protocol and abundance of O. sarsii, these studies pave the way for the development of ETPA as a novel natural product-based photodynamic therapeutic.
Implication of Sphingolipid Metabolism Gene Dysregulation and Cardiac Sphingosine-1-Phosphate Accumulation in Heart Failure
Authors: Pérez-Carrillo Lorena , Giménez-Escamilla Isaac , Martínez-Dolz Luis , Sánchez-Lázaro Ignacio José , Portolés Manuel , Roselló-Lletí Esther , Tarazón Estefanía
Published: January 2022

Disturbances in sphingolipid metabolism lead to biological function dysregulation in many diseases, but it has not been described in heart failure (HF). Sphingosine-1-phosphate (S1P) levels have not ever been measured in the myocardium. Therefore, we analyze the gene dysregulation of human cardiac tissue by mRNA-seq (n = 36) and ncRNA-seq (n = 50). We observed most major changes in the expression of genes belonging to de novo and salvage pathways, and the tight gene regulation by their miRNAs is largely dysregulated in HF. We verified using ELISA (n = 41) that ceramide and S1P accumulate in HF cardiac tissue, with an increase in the ceramide/S1P ratio of 57% in HF. Additionally, changes in left ventricular mass and diameters are directly related to CERS1 expression and inversely related to S1P levels. Altogether, we define changes in the main components of the sphingolipid metabolism pathways in HF, mainly de novo and salvage, which lead to an increase in ceramide and S1P in cardiac tissue, as well as an increase in the ceramide/S1P ratio in HF patients. Therapeutic gene modulation focused on restoring ceramide levels or reversing the ceramide/S1P ratio could be a potential therapy to be explored for HF patients.
Transfer RNA-Derived Fragments and isomiRs Are Novel Components of Chronic TBI-Induced Neuropathology
Authors: Puhakka Noora , Das Gupta Shalini , Vuokila Niina , Pitkänen Asla
Published: January 2022

Neuroinflammation is a secondary injury mechanism that evolves in the brain for months after traumatic brain injury (TBI). We hypothesized that an altered small non-coding RNA (sncRNA) signature plays a key role in modulating post-TBI secondary injury and neuroinflammation. At 3threemonths post-TBI, messenger RNA sequencing (seq) and small RNAseq were performed on samples from the ipsilateral thalamus and perilesional cortex of selected rats with a chronic inflammatory endophenotype, and sham-operated controls. The small RNAseq identified dysregulation of 2 and 19 miRNAs in the thalamus and cortex, respectively. The two candidates from the thalamus and the top ten from the cortex were selected for validation. In the thalamus, miR-146a-5p and miR-155-5p levels were upregulated, and in the cortex, miR-375-3p and miR-211-5p levels were upregulated. Analysis of isomiRs of differentially expressed miRNAs identified 3′ nucleotide additions that were increased after TBI. Surprisingly, we found fragments originating from 16 and 13 tRNAs in the thalamus and cortex, respectively. We further analyzed two upregulated fragments, 3′tRF-IleAAT and 3′tRF-LysTTT. Increased expression of the full miR-146a profile, and 3′tRF-IleAAT and 3′tRF-LysTTT was associated with a worse behavioral outcome in animals with chronic neuroinflammation. Our results highlight the importance of understanding the regulatory roles of as-yet unknown sncRNAs for developing better strategies to treat TBI and neuroinflammation.
Differential Expression of Decorin in Metastasising Colorectal Carcinoma Is Regulated by miR-200c and Long Non-Coding RNAs
Authors: Žlajpah Margareta , Urh Kristian , Grosek Jan , Zidar Nina , Boštjančič Emanuela
Published: January 2022

Decorin (DCN) is one of the matricellular proteins that participate in normal cells’ function as well as in cancerogenesis. While its expression in primary tumours is well known, there is limited data about its expression in metastases. Furthermore, the post-transcriptional regulation of DCN is still questionable, although it is well accepted that it is an important mechanism of developing metastatic cancer. The aim of our study was to analyse the expression of DCN and its potential regulatory ncRNAs in metastatic colorectal carcinoma (CRC). Nineteen patients with metastatic CRC were included. Using qPCR, we analysed the expression of DCN, miR-200c and five lncRNAs (LUCAT1, MALAT1, lncTCF7, XIST, and ZFAS1) in lymph node and liver metastases in comparison to the invasive front and central part of a primary tumour. Our results showed insignificant upregulation of DCN and significant upregulation for miR-200c, MALAT1, lncTCF7 and ZFAS1 in metastases compared to the primary tumour. miR-200c showed a positive correlation with DCN, and the aforementioned lncRNAs exhibited a significant positive correlation with miR-200c expression in metastatic CRC. Our results suggest that DCN as well as miR-200c, MALAT1, lncTCF7 and ZFAS1 contribute to the development of metastases in CRC and that regulation of DCN expression in CRC by ncRNAs is accomplished in an indirect manner.
Affordable Biocidal Ultraviolet Cured Cuprous Oxide Filled Vat Photopolymerization Resin Nanocomposites with Enhanced Mechanical Properties
Authors: Petousis Markos , Vidakis Nectarios , Velidakis Emmanuel , Kechagias John D. , David Constantine N. , Papadakis Stefanos , Mountakis Nikolaos
Published: January 2022

In this study, Cuprous Oxide (Cu2O), known for its mechanism against bacteria, was used as filler to induce biocidal properties on a common commercial resin stereolithography (SLA) 3D printing resin. The aim was to develop nanocomposites suitable for the SLA process with a low-cost process that mimic host defense peptides (HDPs). Such materials have a huge economic and societal influence on the global technological war on illness and exploiting 3D printing characteristics is an additional asset for these materials. Their mechanical performance was also investigated with tensile, flexural, Charpy’s impact, and Vickers microhardness tests. Morphological analysis was performed through scanning electron microscopy (SEM), atomic force microscopy (AFM), and energy-dispersive X-ray spectroscopy (EDS) analysis, while the thermal behavior was studied through Thermogravimetric Analysis (TGA). The antibacterial activity of the fabricated nanocomposites was investigated using a screening agar well diffusion method, for a gram-negative and a gram-positive bacterium. Three-dimensional printed nanocomposites exhibited antibacterial performance in all loadings studied, while their mechanical enhancement was approximately 20% even at low filler loadings, revealing a multi-functional performance and a potential of Cuprous Oxide implementation in SLA resin matrices for engineering and medical applications.
Nascent Adhesion Clustering: Integrin-Integrin and Integrin-Substrate Interactions
Authors: Lin Kuanpo , Asaro Robert J.
Published: January 2022

Nascent adhesions (NAs) are a general precursor to the formation of focal adhesions (FAs) that provide a fundamental mechanism for cell adhesion that is, in turn, involved in cell proliferation, migration, and mechanotransduction. Nascent adhesions form when cells come into contact with substrates at all rigidities and generally involve the clustering of ligated integrins that may recruit un-ligated integrins. Nascent adhesions tend to take on characteristic sizes in the range of O(100nm–150nm) in diameter and tend to contain integrin numbers of O(∼20–60). The flexible, adaptable model we present provides and clear explanation of how these conserved cluster features come about. Our model is based on the interaction among ligated and un-ligated integrins that arise due to deformations that are induced in the cell membrane-cell glycocalyx and substrate system due to integrin activation and ligation. This model produces a clearly based interaction potential, and from it an explicit interaction force among integrins, that our stochastic diffusion-interaction simulations then show will produce nascent clusters with experimentally observed characteristics. Our simulations reveal effects of various key parameters related to integrin activation and ligation as well as some unexpected and previously unappreciated effects of parameters including integrin mobility and substrate rigidity. Moreover, the model’s structure is such that refinements are readily incorporated and specific suggestions are made as to what is required for further progress in understanding nascent clustering and the development of mature focal adhesions in a truly predictive manner.
Hyaluronic Acid Allows Enzyme Immobilization for Applications in Biomedicine
Authors: Arnold Jackie , Chapman Jordan , Arnold Myra , Dinu Cerasela Zoica
Published: January 2022

Enzymes are proteins that control the efficiency and effectiveness of biological reactions and systems, as well as of engineered biomimetic processes. This review highlights current applications of a diverse range of enzymes for biofuel production, plastics, and chemical waste management, as well as for detergent, textile, and food production and preservation industries respectively. Challenges regarding the transposition of enzymes from their natural purpose and environment into synthetic practice are discussed. For example, temperature and pH-induced enzyme fragilities, short shelf life, low-cost efficiency, poor user-controllability, and subsequently insufficient catalytic activity were shown to decrease pertinence and profitability in large-scale production considerations. Enzyme immobilization was shown to improve and expand upon enzyme usage within a profit and impact-oriented commercial world and through enzyme-material and interfaces integration. With particular focus on the growing biomedical market, examples of enzyme immobilization within or onto hyaluronic acid (HA)-based complexes are discussed as a definable way to improve upon and/or make possible the next generation of medical undertakings. As a polysaccharide formed in every living organism, HA has proven beneficial in biomedicine for its high biocompatibility and controllable biodegradability, viscoelasticity, and hydrophilicity. Complexes developed with this molecule have been utilized to selectively deliver drugs to a desired location and at a desired rate, improve the efficiency of tissue regeneration, and serve as a viable platform for biologically accepted sensors. In similar realms of enzyme immobilization, HA’s ease in crosslinking allows the molecule to user-controllably enhance the design of a given platform in terms of both chemical and physical characteristics to thus best support successful and sustained enzyme usage. Such examples do not only demonstrate the potential of enzyme-based applications but further, emphasize future market trends and accountability.
Advances in the Development of Phage-Based Probes for Detection of Bio-Species
Authors: Paramasivam Kameshpandian , Shen Yuanzhao , Yuan Jiasheng , Waheed Ibtesam , Mao Chuanbin , Zhou Xin
Published: January 2022

Bacteriophages, abbreviated as “phages”, have been developed as emerging nanoprobes for the detection of a wide variety of biological species, such as biomarker molecules and pathogens. Nanosized phages can display a certain length of exogenous peptides of arbitrary sequence or single-chain variable fragments (scFv) of antibodies that specifically bind to the targets of interest, such as animal cells, bacteria, viruses, and protein molecules. Metal nanoparticles generally have unique plasmon resonance effects. Metal nanoparticles such as gold, silver, and magnetism are widely used in the field of visual detection. A phage can be assembled with metal nanoparticles to form an organic–inorganic hybrid probe due to its nanometer-scale size and excellent modifiability. Due to the unique plasmon resonance effect of this composite probe, this technology can be used to visually detect objects of interest under a dark-field microscope. In summary, this review summarizes the recent advances in the development of phage-based probes for ultra-sensitive detection of various bio-species, outlining the advantages and limitations of detection technology of phage-based assays, and highlighting the commonly used editing technologies of phage genomes such as homologous recombination and clustered regularly interspaced palindromic repeats/CRISPR-associated proteins system (CRISPR-Cas). Finally, we discuss the possible scenarios for clinical application of phage-probe-based detection methods.
Green Interactive Installations as Conceptual Experiments towards a New Meaning of Smart Design
Authors: Anghel Anamaria Andreea , Giurea Diana , Mohora Irina , Hapenciuc Alma-Dia , Milincu Octavian Camil , Frigura-Iliasa Flaviu Mihai
Published: January 2022

Nature-based design process with its embedded concept of form that follows function can be materialized as products capable of incorporating aesthetics and functionality similar to the characteristics of its natural role models. The paper addresses the topic of green installations created through a design process that simulates nature’s smart developmental mechanisms. The aim is to create an interactive installation capable of receiving and interpreting external factors that would determine the ensemble’s behavior and influence its future development and evolution. The main challenge lies in the fact that the smart feature is often achieved by intensive use of technology, which often overshadows inventive ways in which the behavioral and aesthetic properties of the material can be reinterpreted. The interactive green installation “Modgrew” investigates the possibilities of obtaining smart features through the experimental testing of two main types of configurations. The results underline the fact that, by applying the principles of biomimetic design, technologies from different fields can be combined towards obtaining a smart product. The conclusions highlight the need for future studies cover subjects such as the efficiency of automation, the possible reconfiguration of modules, behavioral optimization over time, the identification of minimal tech alternatives and the reduction of maintenance necessities.
Kinetic Resolution in Transannular Morita-Baylis-Hillman Reaction: An Approximation to the Synthesis of Sesquiterpenes from Guaiane Family
Authors: Mato Raquel , Manzano Rubén , Reyes Efraím , Prieto Liher , Uria Uxue , Carrillo Luisa , Vicario Jose L.
Published: January 2022

An approximation to the synthesis of several sesquiterpenes from the Guaiane family is described in which the core structure was obtained through a transannular Morita-Baylis-Hillman reaction performed under kinetic resolution. Several manipulations of the obtained MBH adduct have been carried out directed towards the total synthesis of γ-Gurjunene, to the formal synthesis of Clavukerin A, to the synthesis of a non-natural isomer of isoguaiane and to the synthesis of an advanced intermediate in the total synthesis of Palustrol.
Supported Metal Catalysts for the Synthesis of N-Heterocycles
Authors: Aronica Laura Antonella , Albano Gianluigi
Published: January 2022

Nitrogen-containing heterocycles are important scaffolds for a large number of compounds with biological, pharmaceutical, industrial and optoelectronic applications. A wide range of different methodologies for the preparation of N-heterocycles are based on metal-catalyzed cyclization of suitable substrates. Due to the growing interest in Green Chemistry criteria over the past two decades, the use of supported metal catalysts in the preparation of N-heterocycles has become a central topic in Organic Chemistry. Here we will give a critical overview of all the solid supported metal catalysts applied in the synthesis of N-heterocycles, following a systematic approach as a function of the type of support: (i) metal catalysts supported on inorganic matrices; (ii) metal catalysts supported on organic matrices; (iii) metal catalysts supported on hybrid inorganic-organic matrices. In particular, we will try to emphasize the effective heterogeneity and recyclability of the described metal catalysts, specifying which studies were carried out in order to evaluate these aspects.
Correcting Differential Gene Expression Analysis for Cyto—Architectural Alterations in Substantia Nigra of Parkinson’s Disease Patients Reveals Known and Potential Novel Disease—Associated Genes and Pathways
Authors: Ferraro Federico , Fevga Christina , Bonifati Vincenzo , Mandemakers Wim , Mahfouz Ahmed , Reinders Marcel
Published: January 2022

Several studies have analyzed gene expression profiles in the substantia nigra to better understand the pathological mechanisms causing Parkinson’s disease (PD). However, the concordance between the identified gene signatures in these individual studies was generally low. This might have been caused by a change in cell type composition as loss of dopaminergic neurons in the substantia nigra pars compacta is a hallmark of PD. Through an extensive meta-analysis of nine previously published microarray studies, we demonstrated that a big proportion of the detected differentially expressed genes was indeed caused by cyto-architectural alterations due to the heterogeneity in the neurodegenerative stage and/or technical artefacts. After correcting for cell composition, we identified a common signature that deregulated the previously unreported ammonium transport, as well as known biological processes such as bioenergetic pathways, response to proteotoxic stress, and immune response. By integrating with protein interaction data, we shortlisted a set of key genes, such as LRRK2, PINK1, PRKN, and FBXO7, known to be related to PD, others with compelling evidence for their role in neurodegeneration, such as GSK3β, WWOX, and VPC, and novel potential players in the PD pathogenesis. Together, these data show the importance of accounting for cyto-architecture in these analyses and highlight the contribution of multiple cell types and novel processes to PD pathology, providing potential new targets for drug development.
CerS1 but Not CerS5 Gene Silencing, Improves Insulin Sensitivity and Glucose Uptake in Skeletal Muscle
Authors: Błachnio-Zabielska Agnieszka U. , Roszczyc-Owsiejczuk Kamila , Imierska Monika , Pogodzińska Karolina , Rogalski Paweł , Daniluk Jarosław , Zabielski Piotr
Published: January 2022

Skeletal muscle is perceived as a major tissue in glucose and lipid metabolism. High fat diet (HFD) lead to the accumulation of intramuscular lipids, including: long chain acyl-CoA, diacylglycerols, and ceramides. Ceramides are considered to be one of the most important lipid groups in the generation of skeletal muscle insulin resistance. So far, it has not been clearly established whether all ceramides adversely affect the functioning of the insulin pathway, or whether there are certain ceramide species that play a pivotal role in the induction of insulin resistance. Therefore, we designed a study in which the expression of CerS1 and CerS5 genes responsible for the synthesis of C18:0-Cer and C16:0-Cer, respectively, was locally silenced in the gastrocnemius muscle of HFD-fed mice through in vivo electroporation-mediated shRNA plasmids. Our study indicates that HFD feeding induced both, the systemic and skeletal muscle insulin resistance, which was accompanied by an increase in the intramuscular lipid levels, decreased activation of the insulin pathway and, consequently, a decrease in the skeletal muscle glucose uptake. CerS1 silencing leads to a reduction in C18:0-Cer content, with a subsequent increase in the activity of the insulin pathway, and an improvement in skeletal muscle glucose uptake. Such effects were not visible in case of CerS5 silencing, which indicates that the accumulation of C18:0-Cer plays a decisive role in the induction of skeletal muscle insulin resistance.
Performance of the EQ-5D-Y Interviewer Administered Version in Young Children
Authors: Amien Razia , Scott Desiree , Verstraete Janine
Published: January 2022

(1) Background: An estimated 78% of South African children aged 9–10 years have not mastered basic reading, therefore potentially excluding them from self-reporting on health-related outcome measures. Thus, the aim of this study was to compare the performance of the EQ-5D-Y-3L self-complete to the newly developed interviewer-administered version in children 8–10 years. (2) Methods: Children (n = 207) with chronic respiratory illnesses, functional disabilities, orthopaedic conditions and from the general population completed the EQ-5D-Y-3L self-complete and interviewer-administered versions, Moods and Feelings Questionnaire (MFQ) and Faces Pain Scale-Revised (FPS-R). A functional independence measure (WeeFIM) was completed by the researcher. (3) Results: The 8-year-olds had significantly higher missing responses (x2 = 14.23, p < 0.001) on the self-complete version. Known-group and concurrent validity were comparable across dimensions, utility and VAS scores for the two versions. The dimensions showed low to moderate convergent validity with similar items on the MFQ, FPS-R and WeeFIM with significantly higher correlations between the interviewer-administered dimensions of Mobility and WeeFIM mobility total (z = 1.91, p = 0.028) and Looking After Myself and WeeFIM self-care total (z = 3.24, p = 0.001). Children preferred the interviewer-administered version (60%) (x2 = 21.87, p < 0.001) with 22% of the reasons attributed to literacy level. (4) Conclusions: The EQ-5D-Y-3L interviewer-administered version is valid and reliable in children aged 8–10 years. The results were comparable to the self-complete version indicating that versions can be used interchangeably.
Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome
Authors: Podolak Amira , Liss Joanna , Kiewisz Jolanta , Pukszta Sebastian , Cybulska Celina , Rychlowski Michal , Lukaszuk Aron , Jakiel Grzegorz , Lukaszuk Krzysztof
Published: January 2022

A retrospective case control study was undertaken at the molecular biology department of a private center for reproductive medicine in order to determine whether any correlation exists between mitochondrial DNA (mtDNA) content of cleavage-stage preimplantation embryos and their developmental potential. A total of 69 couples underwent IVF treatment (averaged women age: 36.5, SD 4.9) and produced a total of 314 embryos. A single blastomere was biopsied from each embryo at the cleavage stage (day-3 post-fertilization) subjected to low-pass next generation sequencing (NGS), for the purpose of detecting aneuploidy. For each sample, the number of mtDNA reads obtained after analysis using NGS was divided by the number of reads attributable to the nuclear genome. The mtDNA copy number amount was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 6.3 ± 7.5 versus 7.1 ± 5.8, p < 0.004; U Mann–Whitney test), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (6.6 ± 4.8 vs. 8.5 ± 13.6, p 0.09), sex (6.6 ± 4.1 vs. 6.2 ± 6.8, p 0.16), maternal age (6.9 ± 7.8 vs. 6.7 ± 4.5, p 0.14) or its ability to implant (7.4 ± 6.6 vs. 5.1 ± 4.6, p 0.18). The mtDNA content cannot serve as a useful biomarker at this point in development. However, further studies investigating both quantitative and qualitative aspects of mtDNA are still required to fully evaluate the relationship between mitochondrial DNA and human reproduction.
Circulating Exosomal miR-1290 for Diagnosis of Epithelial Ovarian Cancer
Authors: Jeon Hyeji , Seo Su Min , Kim Tae Wan , Ryu Jaesung , Kong Hyejeong , Jang Si Hyeong , Jang Yong Soo , Kim Kwang Seock , Kim Jae Hoon , Ryu Seongho , Jeon Seob
Published: January 2022

The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 cases of ovarian masses and sera were enrolled, comprising EOC (n = 71), benign ovarian neoplasms (n = 13). We detected expression of candidate miRNAs in the serum and tissue of both benign ovarian neoplasm group and EOC group using real-time polymerase chain reaction. Immunohistochemistry were constructed using formalin fixed paraffin embedded (FFPE) tissue to detect expression level of suppressor of cytokine signaling 4 (SOCS4). In the EOC group, miRNA-1290 was significantly overexpressed in serum exosomes and tissues as compared to benign ovarian neoplasm group (fold change ≥ 2, p < 0.05). We observed area under the receiver operating characteristic curve (AUC) for miR-1290, using a cut-off of 0.73, the exosomal miR-1290 from serum had AUC, sensitivity, and specificity values of 0.794, 69.2 and 87.3, respectively. In immunohistochemical study, expression of SOCS4 in EOC was lower than that in benign ovarian neoplasm. Serum exosomal miR-1290 could be considered as a biomarker for differential diagnosis of EOC from benign ovarian neoplasm and SOCS4 might be potential target gene of miR-1290 in EOC.
Therapeutic Success in Swiss COPD Patients Receiving Dual Bronchodilation Therapy as COPD Maintenance Treatment
Authors: Spielmanns Marc , Schildge Sebastian , Diedrich Jens Peter , Valipour Arschang
Published: January 2022

Health-related quality of life (HRQoL) in patients with moderate to severe chronic obstructive pulmonary disease (COPD) is often reduced by high symptom burden and frequent exacerbations. So far, data on therapeutic success in Swiss COPD patients receiving dual bronchodilation therapy as COPD maintenance treatment are limited. Data from a recently published, non-interventional study on clinical benefit after the start of combined tiotropium–olodaterol treatment were analyzed focusing on Swiss patients compared to the overall cohort including patients from various European countries. Demographic data on the changes in Clinical COPD Questionnaire (CCQ) for the assessment of HRQoL in correlation to symptoms and the number of exacerbations, as well as physician’s global assessment (PGE), were evaluated 6 weeks after treatment start. In Switzerland (n = 61), significantly more patients had comorbidities and exacerbations but showed less symptoms compared to the overall cohort (n = 4639). HRQoL improved in both cohorts, with a negative correlation to symptom burden and number of exacerbations in the overall cohort. PGE scores improved after 6 weeks with a better general condition at baseline in Swiss patients (PGE score 4/5: 68.9% [Swiss cohort] vs. 49.0% [overall cohort]. Despite significant differences regarding the presence of symptoms and exacerbations, therapeutic success was similar in both patient groups. Highly symptomatic patients benefited mostly from tiotropium–olodaterol treatment.
TBCOV: Two Billion Multilingual COVID-19 Tweets with Sentiment, Entity, Geo, and Gender Labels
Authors: Imran Muhammad , Qazi Umair , Ofli Ferda
Published: January 2022

As the world struggles with several compounded challenges caused by the COVID-19 pandemic in the health, economic, and social domains, timely access to disaggregated national and sub-national data are important to understand the emergent situation but it is difficult to obtain. The widespread usage of social networking sites, especially during mass convergence events, such as health emergencies, provides instant access to citizen-generated data offering rich information about public opinions, sentiments, and situational updates useful for authorities to gain insights. We offer a large-scale social sensing dataset comprising two billion multilingual tweets posted from 218 countries by 87 million users in 67 languages. We used state-of-the-art machine learning models to enrich the data with sentiment labels and named-entities. Additionally, a gender identification approach is proposed to segregate user gender. Furthermore, a geolocalization approach is devised to geotag tweets at country, state, county, and city granularities, enabling a myriad of data analysis tasks to understand real-world issues at national and sub-national levels. We believe this multilingual data with broader geographical and longer temporal coverage will be a cornerstone for researchers to study impacts of the ongoing global health catastrophe and to manage adverse consequences related to people’s health, livelihood, and social well-being.
Study on the Reliability and Accuracy of Scolioscope, a New Digital Scoliometer
Authors: Krekoukias Georgios , Koumantakis George A. , Nikolaou Vasileios S. , Soultanis Konstantinos
Published: January 2022

Early detection of scoliosis with school screening and quick, easy, and reliable assessment of its progress are of paramount importance in the management of patients. There have been several tools described, with the most common being the analog scoliometer. Most recently, smartphone applications have entered this area with and without the use of sleeves for the device. There is no research that has evaluated the accuracy of measurements both left and right in either digital or analog devices. In this study, we evaluated the reliability and validity of a new digital scoliometer called the Scolioscope. Thirty subjects were included for the intra-rater reliability study. ICC values >0.9 were calculated both for same-day and between-day measurements. The device was highly accurate with an average difference from the ones set on the sine bar of 0.03° for right-side measurements and 0.18° for the left. These measurements suggest a highly accurate and reliable tool.
Identification of Hotspot Mutations in the N Gene of SARS-CoV-2 in Russian Clinical Samples That May Affect the Detection by Reverse Transcription-PCR
Authors: Kiryanov Sergei A. , Levina Tatiana A. , Konopleva Maria V. , Suslov Anatoly P.
Published: January 2022

Sensitive and reliable diagnostic test systems based on real-time PCR are of great importance in the fight against the ongoing SARS-CoV-2 pandemic. The genetic variability of the SARS-CoV-2 virus leads to the accumulation of mutations, some of which may affect the sensitivity of modern PCR assays. The aim of this study was to search in Russian clinical samples for new mutations in SARS-CoV-2 gene N that can affect the detection by RT-PCR. In this study, the polymorphisms in the regions of the target gene N causing failed or poor detection of the target N in the RT-PCR assay on 12 selected samples were detected. Sequencing the entire N and E genes in these samples along with other 195 samples that were positive for both target regions was performed. Here, we identified a number of nonsynonymous mutations and one novel deletion in the N gene that affected the ability to detect a target in the N gene as well a few mutations in the E gene of SARS-CoV-2 that did not affect detection. Sequencing revealed that majority of the mutations in the N gene were located in the variable region between positions 193 and 235 aa, inside and nearby the phosphorylated serine-rich region of the protein N. This study highlights the importance of the further characterization of the genetic variability and evolution of gene N, the most common target for detecting SARS-CoV-2. The use of at least two targets for detecting SARS-CoV-2, including one for the E gene, will be necessary for reliable diagnostics.
Primary Pericardial Synovial Sarcoma: A Case Report and Literature Review
Authors: Manole Simona , Pintican Roxana , Palade Emanuel , Duma Maria Magdalena , Dadarlat-Pop Alexandra , Schiau Calin , Bene Ioana , Rancea Raluca , Miclea Diana , Manole Viorel , Molnar Adrian , Solomon Carolina
Published: January 2022

We report a case of a 52-year-old woman who was referred to our institution with a superior vena cava syndrome and was investigated through echocardiography, CT and MRI revealing a well-defined, encapsulated pericardial mass. The pathology, correlated with the immunohistochemical analysis, concluded it was an extremely rare primary pericardial synovial sarcoma. The patient underwent surgery and chemotherapy with a 16-month disease-free survival and passed away after a contralateral aggressive relapse. Moreover, we discuss the role of each imaging modality together with their pericardial synovial sarcoma reported features.