bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B Virus-Like Particle: Targeted Delivery of Plasmid Expressing Short Hairpin RNA for Silencing the Bcl-2 Gene in Cervical Cancer Cells
Authors: Akwiditya Made Angga , Yong Chean Yeah , Yusof Mohd Termizi , Mariatulqabtiah Abdul Razak , Ho Kok Lian , Tan Wen Siang
Published: February 2021

Gene therapy research has advanced to clinical trials, but it is hampered by unstable nucleic acids packaged inside carriers and there is a lack of specificity towards targeted sites in the body. This study aims to address gene therapy limitations by encapsidating a plasmid synthesizing a short hairpin RNA (shRNA) that targets the anti-apoptotic Bcl-2 gene using truncated hepatitis B core antigen (tHBcAg) virus-like particle (VLP). A shRNA sequence targeting anti-apoptotic Bcl-2 was synthesized and cloned into the pSilencer 2.0-U6 vector. The recombinant plasmid, namely PshRNA, was encapsidated inside tHBcAg VLP and conjugated with folic acid (FA) to produce FA-tHBcAg-PshRNA VLP. Electron microscopy revealed that the FA-tHBcAg-PshRNA VLP has an icosahedral structure that is similar to the unmodified tHBcAg VLP. Delivery of FA-tHBcAg-PshRNA VLP into HeLa cells overexpressing the folate receptor significantly downregulated the expression of anti-apoptotic Bcl-2 at 48 and 72 h post-transfection. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay demonstrated that the cells’ viability was significantly reduced from 89.46% at 24 h to 64.52% and 60.63%, respectively, at 48 and 72 h post-transfection. As a conclusion, tHBcAg VLP can be used as a carrier for a receptor-mediated targeted delivery of a therapeutic plasmid encoding shRNA for gene silencing in cancer cells.
Neural-Induced Human Adipose Tissue-Derived Stem Cells Conditioned Medium Ameliorates Rotenone-Induced Toxicity in SH-SY5Y Cells
Authors: Ramalingam Mahesh , Jang Sujeong , Jeong Han-Seong
Published: February 2021

Parkinson’s disease (PD) is an age-related neurodegenerative disease (NDD) characterized by the degenerative loss of dopaminergic neurons in the substantia nigra along with aggregation of α-synuclein (α-syn). Neurogenic differentiation of human adipose-derived stem cells (NI-hADSCs) by supplementary factors for 14 days activates different biological signaling pathways. In this study, we evaluated the therapeutic role of NI-hADSC-conditioned medium (NI-hADSC-CM) in rotenone (ROT)-induced toxicity in SH-SY5Y cells. Increasing concentrations of ROT led to decreased cell survival at 24 and 48 h in a dose- and time-dependent manner. Treatment of NI-hADSC-CM (50% dilution in DMEM) against ROT (0.5 μM) significantly increased the cell survival. ROT toxicity decreased the expression of tyrosine hydroxylase (TH). Western blot analysis of the Triton X-100-soluble fraction revealed that ROT significantly decreased the oligomeric, dimeric, and monomeric phosphorylated Serine129 (p-S129) α-syn, as well as the total monomeric α-syn expression levels. ROT toxicity increased the oligomeric, but decreased the dimeric and monomeric p-S129 α-syn expression levels. Total α-syn expression (in all forms) was increased in the Triton X-100-insoluble fraction, compared to the control. NI-hADSC-CM treatment enhanced the TH expression, stabilized α-syn monomers, reduced the levels of toxic insoluble p-S129 α-syn, improved the expression of neuronal functional proteins, regulated the Bax/Bcl-2 ratio, and upregulated the expression of pro-caspases, along with PARP-1 inactivation. Moreover, hADSC-CM treatment decreased the cell numbers and have no effect against ROT toxicity on SH-SY5Y cells. The therapeutic effects of NI-hADSC-CM was higher than the beneficial effects of hADSC-CM on cellular signaling. From these results, we conclude that NI-hADSC-CM exerts neuroregenerative effects on ROT-induced PD-like impairments in SH-SY5Y cells.
Establishment of Novel Protein Interaction Assays between Sin3 and REST Using Surface Plasmon Resonance and Time-Resolved Fluorescence Energy Transfer
Authors: Harada Masamitsu , Nagai Jun , Kurata Riho , Cui Xiaofeng , Isagawa Takayuki , Semba Hiroaki , Yoshida Yasuhiro , Takeda Norihiko , Maemura Koji , Yonezawa Tomo
Published: February 2021

Repressor element-1 (RE-1) or neural restrictive silencer element (NRSE) bound with a zinc finger transcription repressor, RE-1 silencing transcription factor (REST, also known as neural restrictive silencer factor, NRSF) has been identified as a fundamental repressor element in many genes, including neuronal genes. Genes regulated by REST/NRSF regulate multifaceted neuronal phenotypes, and their defects in the machinery cause neuropathies, disorders of neuron activity), autism and so on. In REST repressions, the N-terminal repressor domain recruits Sin3B via its paired amphipathic helix 1 (PAH1) domain, which plays an important role as a scaffold for histone deacetylase 1 and 2. This machinery has a critical role in maintaining neuronal robustness. In this study, in order to establish protein–protein interaction assays mimicking a binding surface between Sin3B and REST, we selected important amino acids from structural information of the PAH1/REST complex and then tried to reconstitute it using recombinant short peptides derived from PAH1/REST. Initially, we validated whether biotinylated REST interacts with glutathione S-transferase (GST)-tagged PAH1 and whether another PAH1 peptide (PAH1-FLAG) competitively binds with biotinylated REST using surface plasmon resonance (SPR). We observed a direct interaction and competitive binding of two PAH1 peptides. Secondly, in order to establish a high-throughput and high-dynamic-range assay, we utilized an easily performed novel time-resolved fluorescence energy transfer (TR-FRET) assay, and closely monitored this interaction. Finally, we succeeded in establishing a novel high-quality TR-FRET assay and a novel interaction assay based on SPR.
The Presence of Colony-Stimulating Factor-1 and Its Receptor in Different Cells of the Testis; It Involved in the Development of Spermatogenesis In Vitro
Authors: Sawaied Alaa , Arazi Eden , AbuElhija Ahmad , Lunenfeld Eitan , Huleihel Mahmoud
Published: February 2021

Spermatogenesis is a complex process, in which spermatogonial cells proliferate and differentiate in the seminiferous tubules of the testis to generate sperm. This process is under the regulation of endocrine and testicular paracrine/autocrine factors. In the present study, we demonstrated that colony stimulating factor-1 (CSF-1) is produced by mouse testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells (such as CDH1-positively stained cells; a marker of spermatogonial cells). In addition, we demonstrated the presence of CSF-1 and its receptor (CSF-1R) in testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells of human testis. We also show that the protein levels of CSF-1 were the highest in testis of 1-week-old mice and significantly decreased with age (2–12-week-old). However, the transcriptome levels of CSF-1 significantly increased in 2–3-week-old compared to 1-week-old, and thereafter significantly decreased with age. On the other hand, the transcriptome levels of CSF-1R was significantly higher in mouse testicular tissue of all examined ages (2–12-week-old) compared to 1-week-old. Our results demonstrate the involvement of CSF-1 in the induction the proliferation and differentiation of spermatogonial cells to meiotic and postmeiotic stages (BOULE- and ACROSIN-positive cells) under in vitro culture conditions, using methylcellulose culture system (MCS). Thus, it is possible to suggest that CSF-1 system, as a testicular paracrine/autocrine system, is involved in the development of different stages of spermatogenesis and may be used in the development of future therapeutic strategies for treatment of male infertility.
Myopathy-Sensitive G-Actin Segment 227-235 Is Involved in Salt-Induced Stabilization of Contacts within the Actin Filament
Authors: Gruszczynska-Biegala Joanna , Stefan Andrzej , Kasprzak Andrzej A. , Dobryszycki Piotr , Khaitlina Sofia , Strzelecka-Gołaszewska Hanna
Published: February 2021

Formation of stable actin filaments, critically important for actin functions, is determined by the ionic strength of the solution. However, not much is known about the elements of the actin fold involved in ionic-strength-dependent filament stabilization. In this work, F-actin was destabilized by Cu2+ binding to Cys374, and the effects of solvent conditions on the dynamic properties of F-actin were correlated with the involvement of Segment 227-235 in filament stabilization. The results of our work show that the presence of Mg2+ at the high-affinity cation binding site of Cu-modified actin polymerized with MgCl2 strongly enhances the rate of filament subunit exchange and promotes the filament instability. In the presence of 0.1 M KCl, the filament subunit exchange was 2–3-fold lower than that in the MgCl2-polymerized F-actin. This effect correlates with the reduced accessibility of the D-loop and Segment 227-235 on opposite filament strands, consistent with an ionic-strength-dependent conformational change that modulates involvement of Segment 227-235 in stabilization of the intermonomer interface. KCl may restrict the mobility of the α-helix encompassing part of Segment 227-235 and/or be bound to Asp236 at the boundary of Segment 227-235. These results provide experimental evidence for the involvement of Segment 227-235 in salt-induced stabilization of contacts within the actin filament and suggest that they can be weakened by mutations characteristic of actin-associated myopathies.
Synthesis of New Steroidal Carbamates with Plant-Growth-Promoting Activity: Theoretical and Experimental Evidence
Authors: Pacheco Daylin Fernández , González Ceballos Leonardo , Castro Armando Zaldo , Conde González Marcos R. , González de la Torre Laura , Rostgaard Lia Pérez , Espinoza Luis , Díaz Katy , Olea Andrés F. , Coll García Yamilet
Published: February 2021

A priority of modern agriculture is to use novel and environmentally friendly plant-growth promoter compounds to increase crop yields and avoid the indiscriminate use of synthetic fertilizers. Brassinosteroids are directly involved in the growth and development of plants and are considered attractive candidates to solve this problem. Obtaining these metabolites from their natural sources is expensive and cumbersome since they occur in extremely low concentrations in plants. For this reason, much effort has been dedicated in the last decades to synthesize brassinosteroids analogs. In this manuscript, we present the synthesis and characterization of seven steroidal carbamates starting from stigmasterol, β-sitosterol, diosgenin and several oxygenated derivatives of it. The synthesis route for functionalization of diosgenin included epoxidation and epoxy opening reactions, reduction of carbonyl groups, selective oxidation of hydroxyl groups, among others. All the obtained compounds were characterized by 1H and 13C NMR, HRMS, and their melting points are also reported. Rice lamina inclination test performed at different concentrations established that all reported steroidal carbamates show plant-growth-promoting activity. A molecular docking study evaluated the affinity of the synthesized compounds towards the BRI1-BAK1 receptor from Arabidopsis thaliana and three of the docked compounds displayed a binding energy lower than brassinolide.
Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans
Authors: Lilja Stephanie , Stoll Carina , Krammer Ulrike , Hippe Berit , Duszka Kalina , Debebe Tewodros , Höfinger Ingrid , König Jürgen , Pointner Angelika , Haslberger Alexander
Published: February 2021

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.
Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine
Authors: Visser Nienke , Lourens Harm Jan , Huls Gerwin , Bremer Edwin , Wiersma Valerie R.
Published: February 2021

Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.
From FISH to Hi-C: The Chromatin Architecture of the Chromosomal Region 7q36.3, Frequently Rearranged in Leukemic Cells, Is Evolutionary Conserved
Authors: Gulino Gesualda M. , Bruno Francesca , Sturiale Valentina , Brancato Desiree , Ragusa Denise , Tosi Sabrina , Saccone Salvatore , Federico Concetta
Published: February 2021

Fluorescence in situ hybridization (FISH) and Hi-C methods are largely used to investigate the three-dimensional organization of the genome in the cell nucleus and are applied here to study the organization of genes (LMBR1, NOM1, MNX1, UBE3C, PTPRN2) localized in the human 7q36.3 band. This region contains the MNX1 gene, which is normally not expressed in human lymphocytes beyond embryonic development. However, this homeobox gene is frequently activated in leukemic cells and its expression is associated with an altered gene positioning in the leukemia cell nuclei. In this study, we used FISH on 3D-preserved nuclei to investigate the nuclear positioning of MNX1 in the leukemia-derived cell line K562. Of the five copies of the MNX1 gene present in K562, four alleles were positioned in the nuclear periphery and only one in the nuclear interior. Using the Juicebox’s Hi-C dataset, we identified five chromatin loops in the 7q36.3 band, with different extensions related to the size and orientation of the genes located here, and independent from their expression levels. We identified similar loops in 11 human and three mouse cell lines, showing that these loops are highly conserved in different human cell lines and during evolution. Moreover, the chromatin loop organization is well conserved also during neuronal cell differentiation, showing consistency in genomic organization of this region in development. In this report, we show that FISH and Hi-C are two different approaches that complement one another and together give complete information on the nuclear organization of specific chromosomal regions in different conditions, including cellular differentiation and genetic diseases.
Senescence Marker Protein 30 (SMP30): A Novel Pan-Species Diagnostic Marker for the Histopathological Diagnosis of Breast Cancer in Humans and Animals
Authors: Baek Su-Min , Lee Seoung-Woo , Kim Tae-Un , Choi Seong-Kyoon , Yun Sungho , Lee Won-Jae , Han Se-Hyeon , Hong Il-Hwa , Park Sang-Joon , Kim Tae-Hwan , Jeong Kyu-Shik , Park Jin-Kyu
Published: February 2021

Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.
Metabolic Analysis of Vitreous/Lens and Retina in Wild Type and Retinal Degeneration Mice
Authors: Murenu Elisa , Kostidis Sarantos , Lahiri Shibojyoti , Geserich Anna S. , Imhof Axel , Giera Martin , Michalakis Stylianos
Published: February 2021

Photoreceptors are the light-sensing cells of the retina and the major cell type affected in most inherited retinal degenerations. Different metabolic pathways sustain their high energetic demand in physiological conditions, particularly aerobic glycolysis. The principal metabolome of the mature retina has been studied, but only limited information is available on metabolic adaptations in response to key developmental events, such as eye opening. Moreover, dynamic metabolic changes due to retinal degeneration are not well understood. Here, we aimed to explore and map the ocular metabolic dynamics induced by eye opening in healthy (wild type) or Pde6b-mutant (retinal degeneration 1, Rd1) mice, in which photoreceptors degenerate shortly after eye opening. To unravel metabolic differences emerging before and after eye opening under physiological and pathophysiological conditions, we performed nuclear magnetic resonance (NMR) spectrosco-py-based metabolome analysis of wild type and Rd1 retina and vitreous/lens. We show that eye opening is accompanied by changes in the concentration of selected metabolites in the retina and by alterations in the vitreous/lens composition only in the retinal degeneration context. As such, we identify N-Acetylaspartate as a potential novel vitreous/lens marker reflecting progressive retinal degeneration. Thus, our data can help elucidating mechanisms underlying key events in retinal physiology and reveal changes occurring in pathology, while highlighting the importance of the vitreous/lens in the characterization of retinal diseases.
A Bioinformatics Model of Human Diseases on the Basis of Differentially Expressed Genes (of Domestic Versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes
Authors: Vasiliev Gennady , Chadaeva Irina , Rasskazov Dmitry , Ponomarenko Petr , Sharypova Ekaterina , Drachkova Irina , Bogomolov Anton , Savinkova Ludmila , Ponomarenko Mikhail , Kolchanov Nikolay , Osadchuk Alexander , Oshchepkov Dmitry , Osadchuk Ludmila
Published: February 2021

Earlier, after our bioinformatic analysis of single-nucleotide polymorphisms of TATA-binding protein-binding sites within gene promoters on the human Y chromosome, we suggested that human reproductive potential diminishes during self-domestication. Here, we implemented bioinformatics models of human diseases using animal in vivo genome-wide RNA-Seq data to compare the effect of co-directed changes in the expression of orthologous genes on human reproductive potential and during the divergence of domestic and wild animals from their nearest common ancestor (NCA). For example, serotonin receptor 3A (HTR3A) deficiency contributes to sudden death in pregnancy, consistently with Htr3a underexpression in guinea pigs (Cavia porcellus) during their divergence from their NCA with cavy (C. aperea). Overall, 25 and three differentially expressed genes (hereinafter, DEGs) in domestic animals versus 11 and 17 DEGs in wild animals show the direction consistent with human orthologous gene-markers of reduced and increased reproductive potential. This indicates a reliable association between DEGs in domestic animals and human orthologous genes reducing reproductive potential (Pearson’s χ2 test p < 0.001, Fisher’s exact test p < 0.05, binomial distribution p < 0.0001), whereas DEGs in wild animals uniformly match human orthologous genes decreasing and increasing human reproductive potential (p > 0.1; binomial distribution), thus enforcing the norm (wild type).
Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes
Authors: Capoor Manu N. , Konieczna Anna , McDowell Andrew , Ruzicka Filip , Smrcka Martin , Jancalek Radim , Maca Karel , Lujc Michael , Ahmed Fahad S. , Birkenmaier Christof , Dudli Stefan , Slaby Ondrej
Published: February 2021

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.
On the Role of Curved Membrane Nanodomains and Passive and Active Skeleton Forces in the Determination of Cell Shape and Membrane Budding
Authors: Mesarec Luka , Drab Mitja , Penič Samo , Kralj-Iglič Veronika , Iglič Aleš
Published: February 2021

Biological membranes are composed of isotropic and anisotropic curved nanodomains. Anisotropic membrane components, such as Bin/Amphiphysin/Rvs (BAR) superfamily protein domains, could trigger/facilitate the growth of membrane tubular protrusions, while isotropic curved nanodomains may induce undulated (necklace-like) membrane protrusions. We review the role of isotropic and anisotropic membrane nanodomains in stability of tubular and undulated membrane structures generated or stabilized by cyto- or membrane-skeleton. We also describe the theory of spontaneous self-assembly of isotropic curved membrane nanodomains and derive the critical concentration above which the spontaneous necklace-like membrane protrusion growth is favorable. We show that the actin cytoskeleton growth inside the vesicle or cell can change its equilibrium shape, induce higher degree of segregation of membrane nanodomains or even alter the average orientation angle of anisotropic nanodomains such as BAR domains. These effects may indicate whether the actin cytoskeleton role is only to stabilize membrane protrusions or to generate them by stretching the vesicle membrane. Furthermore, we demonstrate that by taking into account the in-plane orientational ordering of anisotropic membrane nanodomains, direct interactions between them and the extrinsic (deviatoric) curvature elasticity, it is possible to explain the experimentally observed stability of oblate (discocyte) shapes of red blood cells in a broad interval of cell reduced volume. Finally, we present results of numerical calculations and Monte-Carlo simulations which indicate that the active forces of membrane skeleton and cytoskeleton applied to plasma membrane may considerably influence cell shape and membrane budding.
Perspectives on Building Sustainable Newborn Screening Programs for Sickle Cell Disease: Experience from Tanzania
Authors: Bukini Daima , Nkya Siana , McCurdy Sheryl , Mbekenga Columba , Manji Karim , Parker Michael , Makani Julie
Published: February 2021

The prevalence of sickle cell disease is high in Africa, with significant public health effects on the affected countries. Many of the countries with the highest prevalence of the disease also have poor health care systems and a high burden of infectious diseases with many other competing health care priorities. Although considerable efforts have been made to implement newborn screening for sickle cell disease programs in Africa, coverage is still low. Tanzania has one of the highest birth prevalence of children with sickle cell disease in Africa. In 2015, the country implemented a pilot project for Newborn Screening for Sickle Cell Disease to assess feasibility. Several efforts have been made afterwards to continue providing the screening services as well as related comprehensive care services. Using qualitative methods, we conducted in-depth interviews and focus group discussions with policy makers (n = 4), health care providers (n = 21) and families (n = 15) to provide an analysis of their experiences and perspectives on efforts to expand and sustain newborn screening for sickle cell disease and related comprehensive care services in the country. Thematic content analysis was used to analyze the data through the framework analysis method. The findings have demonstrated both the opportunities and areas that need addressing in the implementation and sustainability of the services in low resource settings. A key area of strengthening is full integration of the services in countries’ health care systems to facilitate the coverage, accessibility and affordability of the services. Although the coverage of newborn screening services for sickle cell disease is still low, efforts at the local level to sustain the implementation of the programs and related comprehensive care services are encouraging and can be used as a model for other programs implemented in low resources settings.
Informing Parents about Newborn Screening: A European Comparison Study
Authors: IJzebrink Amber , van Dijk Tessa , Franková Věra , Loeber Gerard , Kožich Viktor , Henneman Lidewij , Jansen Marleen
Published: February 2021

Knowledge about newborn screening (NBS) is an important factor for parents to make an informed decision about participation. In Europe, countries inform parents differently about their NBS program, potentially including different knowledge aspects in their information. The aim of this study was to assess twenty-six European parental information products and to analyze their knowledge aspects through a content analysis. The analyzed aspects were compared to a list of eight knowledge aspects from scientific literature. The list includes aspects important for parents’ decision-making, such as the purpose of screening. The study showed that most of the eight knowledge aspects are included in NBS information products of the majority of countries. However, there were differences between countries, for example in the amount of detail and phrasing of the information. Additional relevant knowledge aspects have also been identified and are recommended to optimize information products, such as the handling of residual bloodspot samples. This study only assessed knowledge aspects in information products meant for printing, but many countries also use other communication methods, and the impact on knowledge of the delivery of the information needs further study. Preferences of parents on alternative communication methods need to be considered and evaluated on their effectiveness.
Axial Compressor Mean-Line Analysis: Choking Modelling and Fully-Coupled Integration in Engine Performance Simulations
Authors: Kolias Ioannis , Alexiou Alexios , Aretakis Nikolaos , Mathioudakis Konstantinos
Published: February 2021

A mean-line compressor performance calculation method is presented that covers the entire operating range, including the choked region of the map. It can be directly integrated into overall engine performance models, as it is developed in the same simulation environment. The code materializing the model can inherit the same interfaces, fluid models, and solvers, as the engine cycle model, allowing consistent, transparent, and robust simulations. In order to deal with convergence problems when the compressor operates close to or within the choked operation region, an approach to model choking conditions at blade row and overall compressor level is proposed. The choked portion of the compressor characteristics map is thus numerically established, allowing full knowledge and handling of inter-stage flow conditions. Such choking modelling capabilities are illustrated, for the first time in the open literature, for the case of multi-stage compressors. Integration capabilities of the 1D code within an overall engine model are demonstrated through steady state and transient simulations of a contemporary turbofan layout. Advantages offered by this approach are discussed, while comparison of using alternative approaches for representing compressor performance in overall engine models is discussed.
Research on the Role of Influencing Factors on Hotel Customer Satisfaction Based on BP Neural Network and Text Mining
Authors: Wang Jiaying , Zhao Zhijie , Liu Yang , Guo Yiqi
Published: February 2021

With the flourishing development of the hotel industry, the study of customer satisfaction based on online reviews and data has become a new model. In this paper, customer reviews and ratings on Ctrip.com are used, and TF-IDF and K-means algorithms are used to extract and cluster the keywords of reviews texts. Finally, 10 first-level influencing factors of hotel customer satisfaction are determined: epidemic prevention, consumption emotion, convenience, environment, facilities, catering, target group, perceived value, price, and service. Based on backpropagation neural network and weight matrix operation, an influencing factor analysis model of hotel customer satisfaction is constructed to explore the role of these factors. The results show that consumption emotion, perceived value, epidemic prevention, target group, and convenience would significantly affect customer satisfaction, among which epidemic prevention becomes a new factor affecting customer satisfaction. Environment, facilities, catering, and service have relatively little effect on customer satisfaction, while price has the least effect. This study provides a path and method for online reviews of hotel management to improve customer satisfaction and provides a theoretical basis for the study of online reviews of hotels.
Western Corn Rootworm (Diabrotica virgifera virgifera LeConte) in Europe: Current Status and Sustainable Pest Management
Authors: Bažok Renata , Lemić Darija , Chiarini Francesca , Furlan Lorenzo
Published: February 2021

Western corn rootworm (WCR), or Diabrotica virgifera virgifera LeConte, became a very serious quarantine maize pest in Europe in the mid-1990s. Between 1995 and 2010, European countries were involved in international projects to share information and plan common research for integrated pest management (IPM) implementation. Since 2011, however, common efforts have declined, and an overview of WCR population spread, density, and research is in serious need of update. Therefore, we retained that it was necessary to (1) summarize the research activities carried out in the last 12 years in various countries and the research topics addressed, and analyze how these activities have contributed to IPM for WCR and (2) present the current distribution of WCR in the EU and analyze the current population levels in different European countries, focusing on different management strategies. A review of scientific papers published from 2008 to 2020, in addition to direct interviews with experts in charge of WCR management in a range of European countries, was conducted. Over the past 12 years, scientists in Europe have continued their research activities to investigate various aspects of WCR management by implementing several approaches to WCR control. A considerable amount of new knowledge has been produced, contributing to the development of pest management strategies applicable in EU farming systems. Among the 10 EU countries analyzed, there is no country reporting economic damage on a large scale. Thanks to intensive research leading to specific agricultural practices and the EU Common Agricultural Policy, there are crop-rotation-based solutions that can adequately control this pest avoiding insecticide use.
Space Charge Effects in Noble-Liquid Calorimeters and Time Projection Chambers
Authors: Palestini Sandro
Published: February 2021

The subject of space charge in ionization detectors is reviewed, showing how the observations and the formalism used to describe the effects have evolved, starting with applications to calorimeters and reaching recent, large time-projection chambers. General scaling laws, and different ways to present and model the effects are presented. The relations between space-charge effects and the boundary conditions imposed on the side faces of the detector are discussed, together with a design solution that mitigates some of the effects. The implications of the relative size of drift length and transverse detector size are illustrated. Calibration methods are briefly discussed.
COVID-19 and the Kidney: A Worrisome Scenario of Acute and Chronic Consequences
Authors: Sanchez-Russo Luis , Billah Marzuq , Chancay Jorge , Hindi Judy , Cravedi Paolo
Published: February 2021

Acute kidney injury (AKI) is a common finding in patients with coronavirus disease 2019 (COVID-19) and has been associated with higher rates of death when compared to COVID-19 patients without kidney injury. Whereas the definitive pathogenesis of COVID-19-related AKI (CoV-AKI) is not clear, histopathologic evidence seems to point at multiple etiologies for the disease, including indirect and direct viral kidney injury. The high incidence of CoV-AKI, along with the aggressive clinical presentation of this entity, have increased the demands for kidney replacement therapies, rapidly overwhelming the supplies of healthcare systems even in major tertiary care centers. As a result, nephrologists have come up with alternatives to maximize the efficiency of treatments and have developed non-conventional therapeutic alternatives such as the implementation of acute peritoneal dialysis for critically ill patients. The long-term implications of CoV-AKI are yet unknown, though early studies suggest that around one third of the patients who survive will remain dependent on kidney replacement therapy. Nephrologists and healthcare workers need to be familiar with the clinical presentation and therapeutic challenges of CoV-AKI in order to develop strategies to mitigate the burden of the disease for patients, and for services providing kidney replacement therapies.
Pathogenic Mutations and Putative Phenotype-Affecting Variants in Polish Myofibrillar Myopathy Patients
Authors: Potulska-Chromik Anna , Jędrzejowska Maria , Gos Monika , Rosiak Edyta , Kierdaszuk Biruta , Maruszak Aleksandra , Opuchlik Andrzej , Zekanowski Cezary , Fichna Jakub P.
Published: February 2021

Myofibrillar myopathies (MFM) are heterogeneous hereditary muscle diseases with characteristic myopathological features of Z-disk dissolution and aggregates of its degradation products. The onset and progression of the disease are variable, with an elusive genetic background, and around half of the cases lacking molecular diagnosis. Here, we attempted to establish possible genetic foundations of MFM by performing whole exome sequencing (WES) in eleven unrelated families of 13 patients clinically diagnosed as MFM spectrum. A filtering strategy aimed at identification of variants related to the disease was used and included integrative analysis of WES data and human phenotype ontology (HPO) terms, analysis of muscle-expressed genes, and analysis of the disease-associated interactome. Genetic diagnosis was possible in eight out of eleven cases. Putative causative mutations were found in the DES (two cases), CRYAB, TPM3, and SELENON (four cases) genes, the latter typically presenting with a rigid spine syndrome. Moreover, a variety of additional, possibly phenotype-affecting variants were found. These findings indicate a markedly heterogeneous genetic background of MFM and show the usefulness of next generation sequencing in the identification of disease-associated mutations. Finally, we discuss the emerging concept of variant load as the basis of phenotypic heterogeneity.
Head-Shaking Nystagmus in Posterior Canal Benign Paroxysmal Positional Vertigo with Canalolithiasis
Authors: Lee Hyung , Kim Hyun Ah
Published: February 2021

Background: There have been several studies about head-shaking nystagmus (HSN) in posterior canal benign paroxysmal positional vertigo (PC-BPPV). The purpose of the study was to determine the characteristics of HSN and its relationship with head-bending nystagmus (HBN) and lying-down nystagmus (LDN) in PC-BPPV and to suggest a possible pathomechanism of HSN based on these findings. Methods: During the study period, 992 patients with BPPV were initially enrolled. After excluding horizontal or anterior canal BPPV, multiple canals involvement, secondary causes of BPPV, identifiable central nervous system (CNS) disorders, unidentifiable lesion side, or poor cooperation, 240 patients with unilateral PC-BPPV were enrolled. We assessed the frequency, pattern of HSN, and correlation with other induced nystagmus after positional maneuvers such as head bending, lying down, head-turning, and Dix-Hallpike test. Results: Approximately 32% of patients with PC-BPPV showed HSN. Among patients with HSN, approximately 61% of patients showed predominantly downbeat nystagmus, and two-third of them had a torsional component. The torsional component was mostly directed to the contralesional side. Horizontal nystagmus (36%) and upbeat nystagmus (3%) were also observed after head-shaking in PC-BPPV. The presence of HSN was significantly correlated with that of HBN in PC-BPPV (p = 0.00). The presence of a torsional component of HSN was also significantly correlated with that of HBN in PC- BPPV (p = 0.00). Discussion: Perverted HSN, a typical sign of central vestibulopathy, is common in posterior canal BPPV and related to HBN. For generating HSN in PC-BPPV, the otolithic movements related to the endolymph dynamics seem to be more important than the velocity storage mechanism.
Management of Parathyroid Disease during the COVID-19 Pandemic
Authors: Aojula Nivaran , Ready Andrew , Gittoes Neil , Hassan-Smith Zaki
Published: February 2021

The coronavirus disease, COVID-19, has caused widespread and sustained disruption to healthcare, not only in the delivery of emergency care, but knock-on consequences have resulted in major delays to the delivery of elective care, including surgery. COVID-19 has accelerated novel pathways for delivering clinical services, many of which have an increased reliance on technology. COVID-19 has impacted care for patients with both hypoparathyroidism and hyperparathyroidism. The role of vitamin D in the prevention of severe COVID-19 infection has also been widely debated. Severe hypocalcemia can be precipitated by infection in patients with hypoparathyroidism. With this in mind, compliance with medical management, including calcium and vitamin D supplementation, is crucial. Technology in the form of text message reminders and smartphone apps may have a key role in ensuring this. Furthermore, clinicians should ensure that patients are educated on the symptoms of hypocalcemia and the steps needing to be taken should these symptoms be experienced. Patients with primary hyperparathyroidism (PHPT) should be educated on the symptoms of hypercalcemia, as well as the importance of remaining adequately hydrated. In addition, patients should be reassured that the postponement of parathyroidectomy is likely to have negligible impact on their condition; for those with symptomatic hypercalcemia, cinacalcet can be considered as an interim measure.
Morphodynamic Evolution of a Nourished Beach with Artificial Sandbars: Field Observations and Numerical Modeling
Authors: Kuang Cuiping , Han Xuejian , Zhang Jiabo , Zou Qingping , Dong Boling
Published: February 2021

Beach nourishment, a common practice to replenish an eroded beach face with filling sand, has become increasingly popular as an environmentally friendly soft engineering measure to tackle coastal erosion. In this study, three 200 m long offshore submerged sandbars were placed about 200 m from the shore in August 2017 for both coastal protection and beach nourishment at Shanhai Pass, Bohai Sea, northeastern China. A series of 21 beach profiles were collected from August 2017 to July 2018 to monitor the morphological changes of the nourished beach. Field observations of wave and tide levels were conducted for one year and tidal current for 25 h, respectively. To investigate the spatial-temporal responses of hydrodynamics, sediment transport, and morphology to the presence of three artificial submerged sandbars, a two-dimensional depth-averaged (2DH) multi-fraction sediment transport and morphological model were coupled with wave and current model and implemented over a spatially varying nested grid. The model results compare well with the field observations of hydrodynamics and morphological changes. The tidal range was around 1.0 m and the waves predominately came from the south-south-east (SSE) direction in the study area. The observed and predicted beach profiles indicate that the sandbars moved onshore and the morphology experienced drastic changes immediately after the introduction of sandbars and reached an equilibrium state in about one year. The morphological change was mainly driven by waves. Under the influences of the prevailing waves and the longshore drift toward the northeast, the coastline on the leeside of the sandbars advanced seaward by 35 m maximally while the rest adjacent coastline retreated severely by 44 m maximally within August 2017–July 2018. The model results demonstrate that the three sandbars have little effect on the tidal current but attenuate the incoming wave significantly. As a result, the medium-coarse sand of sandbars is transported onshore and the background silt is mainly transported offshore and partly in the longshore direction toward the northeast. The 2- and 5-year model simulation results further indicate that shoreline salient may form behind the sandbars and protrude offshore enough to reach the sandbars, similar to the tombolo behind the breakwater.
Which Green Transport Corridors (GTC) Are Efficient? A Dual-Step Approach Using Network Equilibrium Model (NEM) and Data Envelopment Analysis (DEA)
Authors: Alves Junior Paulo Nocera , Melo Isotilia Costa , Branco José Eduardo Holler , Bartholomeu Daniela Bacchi , Caixeta-Filho José Vicente
Published: February 2021

The development of Green Transport Corridors (GTCs) is an important strategy to help a region achieve more sustainable solutions. When such GTCs are implemented, multimodal supply chains and environmentally-friendly alternatives for freight transportation through economically relevant hubs and long-distance routes can be facilitated. Based on previous efforts for evaluating single routes, this paper aimed to propose a single multi-criteria Logistics Composite Index (LCI), constructed based on a set of Key Performance Indicators (KPIs), to evaluate the efficiency of GTCs considering the integration of multiple transport modes (highways, railways, and waterways). This approach consists of a dual-step procedure, applying a Network Equilibrium Model (NEM) and Data Envelopment Analysis (DEA). It was applied to Brazilian agricultural bulk transport export corridors, considering the existing and planned infrastructure in the harvest year of 2018/2019. In general, the best indexes were those from corridors considering planned railways. Specifically, the best index was from a corridor from the Northeast region. The second was from the South. The third was from the North (Amazon), and was one of the few corridors with adequate waterways. This approach is useful for decision-makers to determine the most efficient corridors as well as for policy-makers to guide infrastructure investments and address public policies.