bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Forest Therapy on Immune Function
Authors: Chae Youngran , Lee Sunhee , Jo Youngmi , Kang Soyean , Park Suyoun , Kang Hyoyoung
Published: August 2021

We conducted a systematic review of the effects of a forest therapy program on adults’ immune function. We used PICO-SD (participants, interventions, comparisons, outcomes, study design) to identify key items. The participants were adults over the age of 18 and the intervention was forest therapy. Our comparisons included studies that comparatively analyzed urban groups or groups that did not participate in forest therapy intervention. Cases without control groups were also included. Immunological outcome measures were included in measuring intervention outcomes. All experimental studies, such as randomized controlled trials (RCTs), non-equivalent control group designs (non-RCTs), and one-group pretest-posttest design were included in the study design. A total of 13 studies were included for comparison. Forest therapy programs were divided into lodging-type and session-type programs. The representative measures for evaluating the effects of immune function were the number of NK cells, the cytotoxic activity of NK cells, and cytotoxic effector molecules. Most studies reported improvement in these measures when comparing values after intervention with values before the forest therapy intervention. Therefore, forest therapy has been found to be effective in improving immune function. More RCT studies on the effects of forest therapy on immune function are necessary.
Optimization of Green Space Planning to Improve Ecosystem Services Efficiency: The Case of Chongqing Urban Areas
Authors: Yan Shuiyu , Tang Jun
Published: August 2021

This paper applied landscape indexes to evaluate the size, form, and structure of green spaces in the mountainous city of Chongqing and found that green spaces benefit from certain advantages in size, but the network suffered from low heterogeneity and limited interconnectivity. To ensure the integrity and continuity of ecological processes and improve the efficiency of ecosystem services (ES), the authors used Geographic Information System (GIS) software to conduct adaptability evaluation and adjacent buffer analysis for the existing green spaces, wetlands, rivers, and other landscapes with relatively high capacity for ES. We designed a comprehensive map of potential areas for UGS expansion by superimposing the maps obtained from adaptability evaluation and buffer analysis. We also proposed some strategies that respect, consider, and evaluate aspects and special features of urban environment to optimize green space planning and improve ES efficiency, such as protection of important areas, development of green corridors, and careful consideration of ecological processes and complex functions in urban areas. Based on these strategies, the paper put forth suggestions for green space planning to improve ES efficiency that can function as foundation for subsequent green space planning.
Suggestion of an Improved Evaluation Method of Construction Companies’ Industrial Accident Prevention Activities in South Korea
Authors: Kang Sung-Yong , Min Seongi , Won Deokhee , Kang Young-Jong , Kim Seungjun
Published: August 2021

Workers in the construction industry are constantly exposed to dangers during work that can lead to death or disability. Despite recent advances in construction technology, the presence of these risks for workers has become an unresolved social problem. In particular, most companies often recognize that it is necessary to mitigate against risks posed to worker only after an accident has occurred. Recently, there has been an increasing demand for the development of new safety technologies and policy proposals to ensure the safety of workers during construction or work. However, the right solution is not coping after an accident but preventing it, and this must be accompanied by voluntary efforts by the company. To work toward such solutions, Korea is implementing an evaluation of construction companies’ industrial accident prevention activities without legal regulations or coercion to encourage voluntary accident prevention activities by companies. The purpose of this study is to propose an effective improvement direction for the system implemented by the Korea Occupational Safety and Health Agency. First, by analyzing the details of the system and the data of the evaluation results, the system’s effectiveness and rationality are reviewed, and steps for improvement are determined. Next, an evaluation model is proposed considering the size of the company to be evaluated and the level of safety and health, and its validity is verified through a survey of construction workers. Finally, a plan to induce the voluntary participation of construction companies in this system and the role of the supervisory authority are presented. This study is expected to serve as an important example of an effective safety policy model by encouraging companies’ voluntary efforts to prevent accidents in the construction industry and raise the level of potential safety and health awareness.
DEM-Based UAV Flight Planning for 3D Mapping of Geosites: The Case of Olympus Tectonic Window, Lesvos, Greece
Authors: Papadopoulou Ermioni-Eirini , Vasilakos Christos , Zouros Nikolaos , Soulakellis Nikolaos
Published: August 2021

Geosites are an important part of geoheritage, thus their detailed mapping is crucial for their management, protection and promotion processes. However, there is no specific approach to three-dimensional (3D) mapping of geosites and a full investigation is required, considering the current advances in the science of Geoinformatics and the need for setting up an integrated system that will suggest a suitable way of mapping areas of geological significance. The main purpose of this study is to explore new approaches to the 3D mapping of geosites, where the unmanned aerial vehicles’ (UAVs) flight planning is based on the digital elevation model (DEM). The case study that is being examined is the tectonic window of Mount Olympus, located in the southeast of Lesvos island, Greece. In this paper, a methodology has been developed to create flight plans for geosite 3D mapping. This methodology consists of three main stages: (a) flight planning based on SRTM-DEM, (b) data acquisition and image-based 3D modelling, and (c) comparison (flight plans and results). A semi-automated algorithm was developed for designing the flights, taking into account the topography of the mapped area (slope, aspect, elevation) and the final cartographic derivatives. The flight plans were compared with each other in levels of data collection, flight characteristics and their results. The results of this study are dense point clouds, DEMs and orthophotomaps. The algorithms that have been used for the comparison of point clouds were (I) surface density, (II) number of neighbours (NN), and (III) roughness and surface profile. The conclusion drawn from this study is that the DEM is a valuable source of information that can be used in designing flight plans specially shaped on the topography of each geosite.
Whose Urban Green? Mapping and Classifying Public and Private Green Spaces in Padua for Spatial Planning Policies
Authors: Pristeri Guglielmo , Peroni Francesca , Pappalardo Salvatore Eugenio , Codato Daniele , Masi Antonio , De Marchi Massimo
Published: August 2021

The rising environmental issues on contemporary cities urgently calls for sustainable planning policies. Implementation of nature-based solutions, ecosystem services, and green infrastructures associated to green spaces management is at present of paramount importance. In contrast to policies mainly focused on public greenery, the inclusion of private green in planning strategies might be a promising pathway. The general aim is mapping and classifying urban green spaces in Padua, a city of 93.3 km2 (Northeast Italy). Specific aims are (i) testing an NDVI-derived extraction from very high-resolution orthophotos; (ii) classifying property status; (iii) highlighting multilevel relationships and strategies for urban green spaces implementation and management; (iv) assessing greenery in relation to per capita population. By performing remote sensing and GIS analyses, a first detailed global map of urban green spaces in Padua was created; then, binary classification and thematic maps for rural/non-rural, public/private, municipal/non-municipal greenery were produced for all urban units. Results show that, among total green spaces (52.23 km2), more than half are rural. Moreover, private green spaces represent 80%, while within public areas (20%) less than 10% are municipal (5 km2). We therefore highlight scenarios for planning policies in Padua by providing tools to policymakers for an integrated management of green spaces, where private greenery might also contribute to ecosystem services implementation for common urban well-being.
Secretory NPC2 Protein-Mediated Free Cholesterol Levels Were Correlated with the Sorafenib Response in Hepatocellular Carcinoma
Authors: Suk Fat-Moon , Wang Yuan-Hsi , Chiu Wan-Chun , Liu Chiao-Fan , Wu Chien-Ying , Chen Tzu-Lang , Liao Yi-Jen
Published: August 2021

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor in the world. Sorafenib is the first-line drug for patients with advanced HCC. However, long-term treatment with sorafenib often results in reduced sensitivity of tumor cells to the drug, leading to acquired resistance. Identifying biomarkers which can predict the response to sorafenib treatment may represent a clinical challenge in the personalized treatment era. Niemann-Pick type C2 (NPC2), a secretory glycoprotein, plays an important role in regulating intracellular free cholesterol homeostasis. In HCC patients, downregulation of hepatic NPC2 is correlated with poor clinical pathological features through regulating mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) activation. This study aimed to investigate the roles of secretory NPC2-mediated free cholesterol levels as biomarkers when undergoing sorafenib treatment and evaluate its impact on acquired sorafenib resistance in HCC cells. Herein, we showed that NPC2 downregulation and free cholesterol accumulation weakened sorafenib’s efficacy through enhancing MAPK/AKT signaling in HCC cells. Meanwhile, NPC2 overexpression slightly enhanced the sorafenib-induced cytotoxic effect. Compared to normal diet feeding, mice fed a high-cholesterol diet had much higher tumor growth rates, whereas treatment with the free cholesterol-lowering agent, hydroxypropyl-β-cyclodextrin, enhanced sorafenib’s tumor-inhibiting ability. In addition, sorafenib treatment induced higher NPC2 secretion, which was mediated by inhibition of the Ras/Raf/MAPK kinase (MEK)/ERK signaling pathway in HCC cells. In both acquired sorafenib-resistant cell and xenograft models, NPC2 and free cholesterol secretion were increased in culture supernatant and serum samples. In conclusion, NPC2-mediated free cholesterol secretion may represent a candidate biomarker for the likelihood of HCC cells developing resistance to sorafenib.
Comparison of Histone H3K4me3 between IVF and ICSI Technologies and between Boy and Girl Offspring
Authors: Yang Huixia , Ma Zhi , Peng Lin , Kuhn Christina , Rahmeh Martina , Mahner Sven , Jeschke Udo , von Schönfeldt Viktoria
Published: August 2021

Epigenetics play a vital role in early embryo development. Offspring conceived via assisted reproductive technologies (ARTs) have a three times higher risk of epigenetic diseases than naturally conceived children. However, investigations into ART-associated placental histone modifications or sex-stratified analyses of ART-associated histone modifications remain limited. In the current study, we carried out immunohistochemistry, chip-sequence analysis, and a series of in vitro experiments. Our results demonstrated that placentas from intra-cytoplasmic sperm injection (ICSI), but not in vitro fertilization (IVF), showed global tri-methylated-histone-H3-lysine-4 (H3K4me3) alteration compared to those from natural conception. However, for acetylated-histone-H3-lysine-9 (H3K9ac) and acetylated-histone-H3-lysine-27 (H3K27ac), no significant differences between groups could be found. Further, sex -stratified analysis found that, compared with the same-gender newborn cord blood mononuclear cell (CBMC) from natural conceptions, CBMC from ICSI-boys presented more genes with differentially enriched H3K4me3 (n = 198) than those from ICSI-girls (n = 79), IVF-girls (n = 5), and IVF-boys (n = 2). We also found that varying oxygen conditions, RNA polymerase II subunit A (Polr2A), and lysine demethylase 5A (KDM5A) regulated H3K4me3. These findings revealed a difference between IVF and ICSI and a difference between boys and girls in H3K4me3 modification, providing greater insight into ART-associated epigenetic alteration.
Anion and Cation Permeability of the Mouse TMEM16F Calcium-Activated Channel
Authors: Stabilini Stefano , Menini Anna , Pifferi Simone
Published: August 2021

TMEM16F is involved in several physiological processes, such as blood coagulation, bone development and virus infections. This protein acts both as a Ca2+-dependent phospholipid scramblase and a Ca2+-activated ion channel but several studies have reported conflicting results about the ion selectivity of the TMEM16F-mediated current. Here, we have performed a detailed side-by-side comparison of the ion selectivity of TMEM16F using the whole-cell and inside-out excised patch configurations to directly compare the results. In inside-out configuration, Ca2+-dependent activation was fast and the TMEM16F-mediated current was activated in a few milliseconds, while in whole-cell recordings full activation required several minutes. We determined the relative permeability between Na+ and Cl¯ (PNa/PCl) using the dilution method in both configurations. The TMEM16F-mediated current was highly nonselective, but there were differences depending on the configuration of the recordings. In whole-cell recordings, PNa/PCl was approximately 0.5, indicating a slight preference for Cl¯ permeation. In contrast, in inside-out experiments the TMEM16F channel showed a higher permeability for Na+ with PNa/PCl reaching 3.7. Our results demonstrate that the time dependence of Ca2+ activation and the ion selectivity of TMEM16F depend on the recording configuration.
Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
Authors: Santiago-Sánchez Ginette S. , Noriega-Rivera Ricardo , Hernández-O’Farrill Eliud , Valiyeva Fatma , Quiñones-Diaz Blanca , Villodre Emilly S. , Debeb Bisrat G. , Rosado-Albacarys Andrea , Vivas-Mejía Pablo E.
Published: August 2021

Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer, highly metastatic, representing 2–4% of all breast cancer cases in the United States. Despite its rare nature, IBC is responsible for 7–10% of all breast cancer deaths, with a 5-year survival rate of 40%. Thus, targeted and effective therapies against IBC are needed. Here, we proposed Lipocalin-2 (LCN2)—a secreted glycoprotein aberrantly abundant in different cancers—as a plausible target for IBC. In immunoblotting, we observed higher LCN2 protein levels in IBC cells than non-IBC cells, where the LCN2 levels were almost undetectable. We assessed the biological effects of targeting LCN2 in IBC cells with small interference RNAs (siRNAs) and small molecule inhibitors. siRNA-mediated LCN2 silencing in IBC cells significantly reduced cell proliferation, viability, migration, and invasion. Furthermore, LCN2 silencing promoted apoptosis and arrested the cell cycle progression in the G0/G1 to S phase transition. We used in silico analysis with a library of 25,000 compounds to identify potential LCN2 inhibitors, and four out of sixteen selected compounds significantly decreased cell proliferation, cell viability, and the AKT phosphorylation levels in SUM149 cells. Moreover, ectopically expressing LCN2 MCF7 cells, treated with two potential LCN2 inhibitors (ZINC00784494 and ZINC00640089) showed a significant decrease in cell proliferation. Our findings suggest LCN2 as a promising target for IBC treatment using siRNA and small molecule inhibitors.
Oncolytic Bovine Herpesvirus 1 Inhibits Human Lung Adenocarcinoma A549 Cell Proliferation and Tumor Growth by Inducing DNA Damage
Authors: Qiu Wencai , Ding Xiuyan , Li Shitao , He Yongming , Zhu Liqian
Published: August 2021

Bovine herpesvirus 1 (BoHV-1) is a promising oncolytic virus with broad antitumor spectrum; however, its oncolytic effects on human lung adenocarcinoma in vivo have not been reported. In this study, we report that BoHV-1 can be used as an oncolytic virus for human lung adenocarcinoma, and elucidate the underlying mechanism of how BoHV-1 suppresses tumor cell proliferation and growth. First, we examined the oncolytic activities of BoHV-1 in human lung adenocarcinoma A549 cells. BoHV-1 infection reduced the protein levels of histone deacetylases (HDACs), including HDAC1-4 that are promising anti-tumor drug targets. Furthermore, the HDAC inhibitor Trichostatin A (TSA) promoted BoHV-1 infection and exacerbated DNA damage and cytopathology, suggesting a synergy between BoHV-1 and TSA. In the A549 tumor xenograft mouse model, we, for the first time, showed that BoHV-1 can infect tumor and suppressed tumor growth with a similar high efficacy as the treatment of TSA, and HDACs have potential effects on the virus replication. Taken together, our study demonstrates that BoHV-1 has oncolytic effects against human lung adenocarcinoma in vivo.
PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering
Authors: Piszko Paweł , Włodarczyk Marcin , Zielińska Sonia , Gazińska Małgorzata , Płociński Przemysław , Rudnicka Karolina , Szwed Aleksandra , Krupa Agnieszka , Grzymajło Michał , Sobczak-Kupiec Agnieszka , Słota Dagmara , Kobielarz Magdalena , Wojtków Magdalena , Szustakiewicz Konrad
Published: August 2021

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1β, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.
Adhesion of Neurons and Glial Cells with Nanocolumnar TiN Films for Brain-Machine Interfaces
Authors: Abend Alice , Steele Chelsie , Jahnke Heinz-Georg , Zink Mareike
Published: August 2021

Coupling of cells to biomaterials is a prerequisite for most biomedical applications; e.g., neuroelectrodes can only stimulate brain tissue in vivo if the electric signal is transferred to neurons attached to the electrodes’ surface. Besides, cell survival in vitro also depends on the interaction of cells with the underlying substrate materials; in vitro assays such as multielectrode arrays determine cellular behavior by electrical coupling to the adherent cells. In our study, we investigated the interaction of neurons and glial cells with different electrode materials such as TiN and nanocolumnar TiN surfaces in contrast to gold and ITO substrates. Employing single-cell force spectroscopy, we quantified short-term interaction forces between neuron-like cells (SH-SY5Y cells) and glial cells (U-87 MG cells) for the different materials and contact times. Additionally, results were compared to the spreading dynamics of cells for different culture times as a function of the underlying substrate. The adhesion behavior of glial cells was almost independent of the biomaterial and the maximum growth areas were already seen after one day; however, adhesion dynamics of neurons relied on culture material and time. Neurons spread much better on TiN and nanocolumnar TiN and also formed more neurites after three days in culture. Our designed nanocolumnar TiN offers the possibility for building miniaturized microelectrode arrays for impedance spectroscopy without losing detection sensitivity due to a lowered self-impedance of the electrode. Hence, our results show that this biomaterial promotes adhesion and spreading of neurons and glial cells, which are important for many biomedical applications in vitro and in vivo.
Differential Retinal Protein Expression in Primary and Secondary Retinal Ganglion Cell Degeneration Identified by Integrated SWATH and Target-Based Proteomics
Authors: Kwong Jacky M. K. , Caprioli Joseph , Sze Ying H. , Yu Feng J. , Li King K. , To Chi H. , Lam Thomas C.
Published: August 2021

To investigate the retinal proteins associated with primary and secondary retinal ganglion cell (RGC) degeneration and explore their molecular pathways, SWATH label-free and target-based mass spectrometry was employed to identify the proteomes in various retinal locations in response to localized optic nerve injury. Unilateral partial optic nerve transection (pONT) was performed on adult Wistar rats and their retinas were harvested 2 weeks later. To confirm the separation of primary and secondary RGC degeneration, immunohistochemistry of RNA binding protein with multiple splicing (RBPMS) and glial fibrillary acidic protein (GFAP) was performed on retinal whole-mounts. Retinal proteomes in the temporal and nasal quadrants were evaluated with high resolution hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS), and SWATH-based acquisition, and their expression was compared to the corresponding retinal quadrant in contralateral control eyes and further validated by multiple reaction monitoring mass spectrometry (MRM-MS). A total of 3641 proteins (FDR < 1%) were identified using QTOF-MS. The raw data are available via ProteomeXchange with the identifier PXD026783. Bioinformatics data analysis showed that there were 37 upregulated and 25 downregulated proteins in the temporal quadrant, whereas 20 and five proteins were upregulated and downregulated, respectively, in the nasal quadrant, respectively (n = 4, p < 0.05; fold change ≥ 1.4-fold or ≤0.7). Six proteins were regulated in both the temporal and the nasal quadrants, including CLU, GFAP, GNG5, IRF2BPL, L1CAM, and CPLX1. Linear regression analysis indicated a strong association between the data obtained by means of SWATH-MS and MRM-MS (temporal, R2 = 0.97; nasal, R2 = 0.96). Gene ontology analysis revealed statistically significant changes in the biological processes and cellular components of primary RGC degeneration. The majority of the significant changes in structural, signaling, and cell death proteins were associated with the loss of RGCs in the area of primary RGC degeneration. The combined use of SWATH-MS and MRM-MS methods detects and quantifies regional changes of retinal protein expressions after localized injury. Future investigation with this integrated approach will significantly increase the understanding of diverse processes of progressive RGC degeneration from a proteomic prospective.
Structural and Functional Insights into the Transmembrane Domain Association of Eph Receptors
Authors: Sahoo Amita R. , Buck Matthias
Published: August 2021

Eph receptors are the largest family of receptor tyrosine kinases and by interactions with ephrin ligands mediate a myriad of processes from embryonic development to adult tissue homeostasis. The interaction of Eph receptors, especially at their transmembrane (TM) domains is key to understanding their mechanism of signal transduction across cellular membranes. We review the structural and functional aspects of EphA1/A2 association and the techniques used to investigate their TM domains: NMR, molecular modelling/dynamics simulations and fluorescence. We also introduce transmembrane peptides, which can be used to alter Eph receptor signaling and we provide a perspective for future studies.
Anti-Inflammatory Effect of Allicin Associated with Fibrosis in Pulmonary Arterial Hypertension
Authors: Sánchez-Gloria José L. , Martínez-Olivares Constanza Estefanía , Rojas-Morales Pedro , Hernández-Pando Rogelio , Carbó Roxana , Rubio-Gayosso Ivan , Arellano-Buendía Abraham S. , Rada Karla M. , Sánchez-Muñoz Fausto , Osorio-Alonso Horacio
Published: August 2021

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1β, IL-6, TNF-α, NFκB p65, Iκβ, TGF-β, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-β were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1β, and Cd68 in the lung. In addition, TGF-β, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-β. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.
Analysis of PPARγ Signaling Activity in Psoriasis
Authors: Sobolev Vladimir , Nesterova Anastasia , Soboleva Anna , Mezentsev Alexandre , Dvoriankova Evgenia , Piruzyan Anastas , Denisova Elena , Melnichenko Olga , Korsunskaya Irina
Published: August 2021

In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3+ Tcells samples (n = 23) and samples of healthy CD3+ T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.
Transcriptome Analysis in a Primary Human Muscle Cell Differentiation Model for Myotonic Dystrophy Type 1
Authors: Todorow Vanessa , Hintze Stefan , Kerr Alastair R. W. , Hehr Andreas , Schoser Benedikt , Meinke Peter
Published: August 2021

Myotonic dystrophy type 1 (DM1) is caused by CTG-repeat expansions leading to a complex pathology with a multisystemic phenotype that primarily affects the muscles and brain. Despite a multitude of information, especially on the alternative splicing of several genes involved in the pathology, information about additional factors contributing to the disease development is still lacking. We performed RNAseq and gene expression analyses on proliferating primary human myoblasts and differentiated myotubes. GO-term analysis indicates that in myoblasts and myotubes, different molecular pathologies are involved in the development of the muscular phenotype. Gene set enrichment for splicing reveals the likelihood of whole, differentiation stage specific, splicing complexes that are misregulated in DM1. These data add complexity to the alternative splicing phenotype and we predict that it will be of high importance for therapeutic interventions to target not only mature muscle, but also satellite cells.
Effect of Reduced Atmosphere Sintering on Blocking Grain Boundaries in Rare-Earth Doped Ceria
Authors: Sulekar Soumitra , Mehr Mehrad , Kim Ji Hyun , Nino Juan Claudio
Published: August 2021

Rare-earth doped ceria materials are amongst the top choices for use in electrolytes and composite electrodes in intermediate temperature solid oxide fuel cells. Trivalent acceptor dopants such as gadolinium, which mediate the ionic conductivity in ceria by creating oxygen vacancies, have a tendency to segregate at grain boundaries and triple points. This leads to formation of ionically resistive blocking grain boundaries and necessitates high operating temperatures to overcome this barrier. In an effort to improve the grain boundary conductivity, we studied the effect of a modified sintering cycle, where 10 mol% gadolinia doped ceria was sintered under a reducing atmosphere and subsequently reoxidized. A detailed analysis of the complex impedance, conductivity, and activation energy values was performed. The analysis shows that for samples processed thus, the ionic conductivity improves when compared with conventionally processed samples sintered in air. Equivalent circuit fitting shows that this improvement in conductivity is mainly due to a drop in the grain boundary resistance. Based on comparison of activation energy values for the conventionally processed vs. reduced-reoxidized samples, this drop can be attributed to a diminished blocking effect of defect-associates at the grain boundaries.
Potential of Fermentation and Vacuum Packaging Followed by Chilling to Preserve Black Soldier Fly Larvae (Hermetia illucens)
Authors: Van Campenhout Leen , Lachi Dario , Vandeweyer Dries
Published: August 2021

Black soldier fly larvae (Hermetia illucens) are currently reared at an industrial scale, mainly as a feed ingredient. The logistic chain not only involves the production of larvae, but also stabilisation, storage, and transport. The aim of this work was to study fermentation and vacuum packaging of larvae as potential preservation technologies. For fermentation, blanched larvae were pulverised into a paste, and a starter culture, NaCl, and glucose were added. The mixture was fermented for 7 days at 35 °C and then stored for 14 days at 4 °C and pH and microbial counts were monitored. Vacuum packaging was applied to living, blanched and frozen larvae. After packaging, they were stored for 6–10 days at several temperatures and gas composition, survival (living larvae) and microbial counts (killed larvae) were recorded. Fermentation allows storage of pulverised larvae, but points to consider are a rapid pH reduction and the presence of bacterial endospores. Vacuum packaging did not bring added value over cooling alone. This was the case for all types of larvae investigated. Vacuum packaging is not considered as a valuable preservation technology to pursue for storage and transport of black soldier fly larvae.
Functional and Cosmetic Outcome after Reconstruction of Isolated, Unilateral Orbital Floor Fractures (Blow-Out Fractures) with and without the Support of 3D-Printed Orbital Anatomical Models
Authors: Sigron Guido R. , Barba Marina , Chammartin Frédérique , Msallem Bilal , Berg Britt-Isabelle , Thieringer Florian M.
Published: August 2021

The present study aimed to analyze if a preformed “hybrid” patient-specific orbital mesh provides a more accurate reconstruction of the orbital floor and a better functional outcome than a standardized, intraoperatively adapted titanium implant. Thirty patients who had undergone surgical reconstruction for isolated, unilateral orbital floor fractures between May 2016 and November 2018 were included in this study. Of these patients, 13 were treated conventionally by intraoperative adjustment of a standardized titanium mesh based on assessing the fracture’s shape and extent. For the other 17 patients, an individual three-dimensional (3D) anatomical model of the orbit was fabricated with an in-house 3D-printer. This model was used as a template to create a so-called “hybrid” patient-specific titanium implant by preforming the titanium mesh before surgery. The functional and cosmetic outcome in terms of diplopia, enophthalmos, ocular motility, and sensory disturbance trended better when “hybrid” patient-specific titanium meshes were used but with statistically non-significant differences. The 3D-printed anatomical models mirroring the unaffected orbit did not delay the surgery’s timepoint. Nonetheless, it significantly reduced the surgery duration compared to the traditional method (58.9 (SD: 20.1) min versus 94.8 (SD: 33.0) min, p-value = 0.003). This study shows that using 3D-printed anatomical models as a supporting tool allows precise and less time-consuming orbital reconstructions with clinical benefits.
Monitored Anesthesia Care with Dexmedetomidine Supplemented by Midazolam/Fentanyl versus Midazolam/Fentanyl Alone in Patients Undergoing Pleuroscopy: Effect on Oxygenation and Respiratory Function
Authors: Kostroglou Andreas , Kapetanakis Emmanouil I. , Matsota Paraskevi , Tomos Periklis , Kostopanagiotou Konstantinos , Tomos Ioannis , Siristatidis Charalampos , Papapanou Michail , Sidiropoulou Tatiana
Published: August 2021

Although pleuroscopy is considered a safe and well tolerated procedure with a low complication rate, it requires the administration of procedural sedation and analgesia. The purpose of this study was to assess the effects of dexmedetomidine administration on oxygenation and respiratory function in patients undergoing diagnostic or therapeutic pleuroscopy. Through a prospective, single center, cohort study, we studied 55 patients receiving either a dexmedetomidine intravenous infusion supplemented by midazolam/fentanyl (Group DEX + MZ/F) or a conventional sedation protocol with midazolam/fentanyl (Group MZ/F). Our primary outcome was the changes in lung gas exchange (PaO2/FiO2 ratio) obtained at baseline and at predetermined end points, while changes in respiratory mechanics (FEV1, FVC and the ratio FEV1/FVC) and PaCO2 levels, drug consumption, time to recover from sedation and adverse events were our secondary endpoints (NCT03597828). We found a lower postoperative decrease in FEV1 volumes in Group DEX + MZ/F compared to Group MZ/F (p = 0.039), while FVC, FEV1/FVC and gas exchange values did not differ between groups. We also found a significant reduction in midazolam (p < 0.001) and fentanyl consumption (p < 0.001), along with a more rapid recovery of alertness postprocedure in Group DEX + MZ/F compared to Group MZ/F (p = 0.003), while pain scores during the postoperative period, favored the Group DEX + MZ/F (p = 0.020). In conclusion, the use of intravenous dexmedetomidine during pleuroscopy is associated with a smaller decrease in FEV1, reduction of the consumption of supplementary sedatives and analgesics and quicker awakening of patients postoperatively, when compared to midazolam/fentanyl. Therefore, dexmedetomidine administration may provide clinically significant benefits in terms of lung mechanics and faster recovery of patients undergoing pleuroscopy.
Evaluation of E148Q and Concomitant AA Amyloidosis in Patients with Familial Mediterranean Fever
Authors: Arici Zehra Serap , Romano Micol , Piskin David , Guzel Ferhat , Sahin Sezgin , Berard Roberta A. , Yilmaz Mahmut I. , Demirkaya Erkan
Published: August 2021

The aim of the study was to compare the clinical phenotype of patients with familial Mediterranean fever (FMF)-related AA amyloidosis, according to the age of FMF diagnosis and E148Q genotype. Patients with biopsy-confirmed FMF-related AA amyloidosis were included in the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. Multiple comparisons were performed according to the age of diagnosis, disease phenotype, mutation, and mortality. Our study included 169 patients with a diagnosis of AA amyloidosis. There were 101 patients diagnosed with FMF < 18 years of age and 68 patients diagnosed who were ≥18 years of age. The three most common clinical manifestations were fever (84.6%), abdominal pain (71.6%), and arthritis (66.9%). The most common allele among FMF patients was M694V (60.6%), followed by E148Q (21.4%), and M680I (10.3%). The most frequent genotypes were M694V/M694V (45.0%), M694V/E148Q (14.8%), and E148Q/E148Q (11.2%) among 169 patients in our cohort. During the follow-up period, 15 patients (10 male, 5 female) died, of whom 14 had M694V homozygous genotype and one was homozygous for E148Q. Clinicians should be aware of patients with homozygous E148Q genotype for close monitoring and further evaluation. The possible relationship between E148Q and AA amyloidosis needs to be confirmed in other ethnicities.
Do Mental Health and Vitality Mediate the Relationship between Perceived Control over Time and Fear of COVID-19? A Survey in an Italian Sample
Authors: Miceli Silvana , Caci Barbara , Roccella Michele , Vetri Luigi , Quatrosi Giuseppe , Cardaci Maurizio
Published: August 2021

Several studies evidenced increased elevated symptomatology levels in anxiety, general stress, depression, and post-traumatic stress related to COVID-19. Real difficulties in the effective control of time that could be responsible for mental health issues and loss of vitality were also reported. Prior literature highlighted how perceived control over time significantly modulates anxiety disorders and promotes psychological well-being. To verify the hypothesis that perceived control over time predicts fear of COVID-19 and mental health and vitality mediate this relationship, we performed an online survey on a sample of 301 subjects (female = 68%; Mage = 22.12, SD = 6.29; age range = 18–57 years), testing a parallel mediation model using PROCESS macro (model 4). All participants responded to self-report measures of perceived control over time, COVID-19 fear, mental health, and vitality subscales of the Short-Form-36 Health Survey. Results corroborate the hypotheses of direct relationships between all the study variables and partially validate the mediation’s indirect effect. Indeed, mental health (a1b1 = −0.06; CI: LL = −0.11; UL = −0.01; p < 0.001) rather than vitality (a2b2 = −0.06; CI: LL = −0.09; UL = 0.03; n.s.) emerges as a significant mediator between perceived control over time and fear of COVID-19. Practical implications of the study about treatment programs based on perceived control over time and emotional coping to prevent fear and anxiety toward the COVID-19 pandemic are discussed.
Temporal and Spatial Variability Scales of Salinity at a Large Microtidal Estuary
Authors: Jackson Michelle , Sienra Gianfranco , Santoro Pablo , Fossati Mónica
Published: August 2021

The Río de la Plata is a large fluvial–estuarine–sea system discharging into the southwestern Atlantic Ocean, which has relevant features such as high fluvial discharge, microtidal astronomical tidal scales, a relevant meteorological tide, and a strong atmospheric forcing effect, due to its large width. The objective of this study is to advance the understanding of the estuarine hydrodynamics and salt transport, as well as discussing the main characteristics of the spatiotemporal variability of the salinity field. To achieve this, the results of a 3D model of the Río de la Plata and its maritime front were used, simulating an extensive period of 10 years. In this study, the model was validated using vertical salinity profiles collected at different locations in the estuary. The temporal variability of the salinity stratification was characterised at different temporal scales: annual, monthly, and storm. At the same time, the influences of fluvial flow and winds were determined. The correlation analysis between fluvial flow and the salinity field showed that high annual fluvial flows generate an extension of the freshwater area, with larger longitudinal salinity gradients and a shift of the salinity front towards the ocean. The tendency at the monthly scale is not as clear as that observed at the annual scale. The results show that the effect of a storm coming from the northwest is quite similar to that of storms coming from the southwest, especially in the central and southern zones of the Río de la Plata, where mixing increases and stratification decreases, according to the intensity of the storm. The effect of south–southeasterly storms increases the mixing process and reduces stratification; the opposite effect was identified with respect to northeasterly storms, under the influence of which the stratified area increases. Synthesising the obtained results, a global zonification of the vertical salinity stratification for the Río de la Plata is proposed.
A Systems Perspective in Examining Industry Clusters: Case Studies of Clusters in Russia and India
Authors: Klarin Anton , Sharmelly Rifat , Suseno Yuliani
Published: August 2021

This article explores an examination of industry clusters from a systems perspective. We analyze Russia’s pharmaceutical clusters and India’s automobile clusters in terms of the systems concepts of holism, emergence, and open systems. We further consider the aspects of human capital investment and the availability of professional labor, infrastructure, private–public sector collaboration, support for funding and commercialization, as well as innovation corporate culture, when examining the institutional pillars supporting the development and growth of industry clusters within the national innovation ecosystems. The findings illustrate how industry clusters can be viewed from a systems perspective. We also highlight how the institutional pillars underpinning national innovation ecosystems can be applied to an industry cluster level, particularly in emerging countries. The article provides implications for theory and practice in the application of a systems perspective as a way to foster industry cluster innovation and promote a more effective national innovation ecosystem.
Conducting Behavioural Research in the Zoo: A Guide to Ten Important Methods, Concepts and Theories
Authors: Rose Paul E. , Riley Lisa M.
Published: August 2021

Behavioural research in zoos is commonplace and is used in the diagnosis and treatment of potential husbandry and management challenges. Robust methods that allow valid data collection and analysis constitute an evidence-based approach to animal care. Understanding behaviour is essential to improving animal management, and behavioural research is therefore popular, with a wide choice of behavioural methodologies and theories available. This review outlines ten methodological approaches, concepts or theories essential to zoo science that are based around behavioural observation. This list is not exhaustive but aims to define and describe key areas of consideration when planning and implementing a zoo-based behavioural project. We discuss the application of well-established methods (the construction of ethograms, use of time–activity patterns and measurement of space/enclosure use) as well as evaluating newer or less-widely applied analytical techniques, such as behavioural diversity indices, social networks analysis and Qualitative Behavioural Assessment. We also consider the importance of fundamental research methods, the application of pure science to understand and interpret zoo animal behaviour (with a review of a Tinbergian approach) and consideration of meta-analyses. The integration of observational techniques into experiments that aim to identify the cause and effect of behavioural performance is then explored, and we examine the assimilation of behavioural methods used in studies of environmental enrichment. By systematically studying animal behaviour, we can attempt to understand the welfare of individual animals in captivity, and here we present an example of our reviewed approaches to this area of zoo science. Combining multiple methodologies can lead to a greater understanding of behaviour and welfare, creating robust research, progressing husbandry and advancing conservation strategies. Collaborations between zoological collections and academic researchers (e.g., in Higher Education Institutions) can further refine and enhance the validity of research and husbandry practice alike.
Evidence of Long-Lasting Humoral and Cellular Immunity against SARS-CoV-2 Even in Elderly COVID-19 Convalescents Showing a Mild to Moderate Disease Progression
Authors: Fischer Bastian , Lindenkamp Christopher , Lichtenberg Christoph , Birschmann Ingvild , Knabbe Cornelius , Hendig Doris
Published: August 2021

We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95% of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein, and measuring interferon-γ (IFN-γ) release thereafter. We modified a commercially available ELISA assay for IFN-γ determination in whole-blood specimens of COVID-19 convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19.