bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineral and Trace Element Analysis of Australian/Queensland Apis mellifera Honey
Authors: Hungerford Natasha L. , Tinggi Ujang , Tan Benjamin L. L. , Farrell Madeleine , Fletcher Mary T.
Published: August 2020

Honey is an extensively utilized sweetener containing sugars and water, together with small quantities of vitamins, minerals, fatty acids, amino acids and proteins. Naturally produced by honeybees (Apis mellifera) from floral nectar, honey is increasingly sold as a health food product due to its nutritious features. Certain honeys are retailed as premium, trendy products. Honeybees are regarded as environmental monitors, but few reports examine the impact of environment on Australian honey trace elements and minerals. In higher density urban and industrial environments, heavy metals can be common, while minerals and trace elements can have ubiquitous presence in both agricultural and urban areas. Honey hives are traditionally placed in rural and forested areas, but increasingly the trend is to keep hives in more urban areas. This study aimed to determine the levels of 26 minerals and trace elements and assess elemental differences between honeys from various regional Queensland and Australian sources. Honey samples (n = 212) were acquired from markets, shops and supermarkets in Queensland while urban honeys were purchased online. The honey samples were classified into four groups according to their regional sources: urban, rural, peri-urban and blend honey. Elemental analyses of honey were performed using ICP-MS and ICP-OES after microwave and hot block digestion. Considerable variations of essential trace elements (Co, Cu, Cr, Fe, Mn, Mo and Zn) and mineral levels (Ca, K, Mg, Na and P) were found in honeys surveyed. There were significant differences (p < 0.05) between urban and rural honey samples for B, Na, P, Mn, K, Ca and Cu. Significant differences (p < 0.05) were also found between blend and urban honey samples for K, Cu, P, Mn, Sr, Ni, B and Na. Peri-urban versus urban honeys showed significant differences in P, K and Mn. For rural and peri-urban honeys, the only significant difference (p < 0.05) was for Na. Toxic heavy metals were detected at relatively low levels in honey products. The study revealed that the Queensland/Australian honey studied is a good source of K and Zn and would constitute a good nutritional source of these elements.
Correlates of Healthy Eating in Urban Food Desert Communities
Authors: Karpyn Allison , Young Candace R. , Collier Zachary , Glanz Karen
Published: August 2020

The food environment is well documented as an important emphasis for public health intervention. While theoretical models of the relationship between the food environment and dietary outcomes have been proposed, empirical testing of conceptual models has been limited. The purpose of this study was to explore which factors in nutrition environments are significantly associated with dietary outcomes in two urban, low-income, and minority food desert communities. This study analyzed cross-sectional data based on 796 participants from the Food in Our Neighborhood Study. Participants were recruited based on a random sample of addresses in neighborhood study areas, Philadelphia, PA (n = 393) and Trenton, NJ (n = 403). Main dietary outcomes were Healthy Eating Index (HEI) scores and fruit and vegetable consumption subscores computed from ASA24® assessments. Exploratory factor analysis was conducted and yielded a model of four factors with 22 items. Among four factors that emerged, three factors (Perceptions of Neighborhood Food Availability; and Household Food Challenges) were significantly correlated with dietary outcomes. My Store’s Quality and Perceptions of Neighborhood Food Availability were positively correlated with vegetable consumption subscore. The Household Food Challenges factor was negatively correlated with both vegetable subscore and overall HEI score (i.e., more household challenges were associated with lower dietary scores). These findings confirmed the importance of perceived nutrition environments and household food challenges in predicting dietary outcomes among residents of two urban, low-income, and minority food desert communities.
The Burden of Cervical Cancer in Korea: A Population-Based Study
Authors: Kim Jinhee , Lee Donghwan , Son Kyung-Bok , Bae SeungJin
Published: August 2020

This study used the Korean National Health Insurance (NHI) claims database from 2011 to 2017 to estimate the incidence and the incidence-based cost of cervical cancer and carcinoma in situ of cervix uteri (CIS) in Korea. The primary outcome was the direct medical cost per patient not diagnosed with cervical cancer (C53) or CIS (D06) 2 years prior to the index date in the first year after diagnosis. A regression analysis was conducted to adjust for relevant covariates. The incidence of cervical cancer tended to decrease from 2013 to 2016, while that of CIS increased. In particular, the incidence rate of CIS in women in their 20 s and 30 s increased by 56.8% and 28.4%, respectively, from 2013 to 2016. The incidence-based cost of cervical cancer and CIS was USD 13,058 and USD 2695 in 2016, respectively, which increased from 2013. Multivariate regression analysis suggested that age was the most influential variable of the cost in both patient groups, and the cost was highest in those aged over 60, i.e., the medical cost was significantly lower in younger women than their older counterparts. These findings suggest that targeting younger women in cervical cancer prevention is a reasonable option from both economic and public health perspectives.
Investigation of a Staphylococcus argenteus Strain Involved in a Chronic Prosthetic-Joint Infection
Authors: Diot Alan , Dyon-Tafani Virginie , Bergot Marine , Tasse Jason , Martins-Simões Patricia , Josse Jérôme , Valour Florent , Laurent Frédéric
Published: August 2020

Staphylococcus argenteus is an emerging species responsible for infections comparable to those induced by Staphylococcus aureus. It has been involved in few chronic or persistent infections so far. In this study, we described a case of a persistent prosthetic-joint infection (PJI) affecting a young woman. We investigated in vitro the virulence traits of the incriminated S. argenteus strain (bone cell invasion, biofilm formation and induction of inflammation) and analyzed its genome, in comparison with two other strains of S. argenteus and two S. aureus isolates. It appeared that this S. argenteus PJI strain combined biofilm formation, osteoblast invasion and intracellular persistence abilities together with genes potentially involved in the escape of the host immune defenses, which might explain the chronicization of the infection.
Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat
Authors: Anan’ina Tatiana , Kisel Alena , Kudabaeva Marina , Chernysheva Galina , Smolyakova Vera , Usov Konstantin , Krutenkova Elena , Plotnikov Mark , Khodanovich Marina
Published: August 2020

(1) Background: Although myelin disruption is an integral part of ischemic brain injury, it is rarely the subject of research, particularly in animal models. This study assessed for the first time, myelin and oligodendrocyte loss in a three-vessel model of global cerebral ischemia (GCI), which causes hippocampal damage. In addition, we investigated the relationships between demyelination and changes in microglia and astrocytes, as well as oligodendrogenesis in the hippocampus; (2) Methods: Adult male Wistar rats (n = 15) underwent complete interruption of cerebral blood flow for 7 min by ligation of the major arteries supplying the brain or sham-operation. At 10 and 30 days after the surgery, brain slices were stained for neurodegeneration with Fluoro-Jade C and immunohistochemically to assess myelin content (MBP+ percentage of total area), oligodendrocyte (CNP+ cells) and neuronal (NeuN+ cells) loss, neuroinflammation (Iba1+ cells), astrogliosis (GFAP+ cells) and oligodendrogenesis (NG2+ cells); (3) Results: 10 days after GCI significant myelin and oligodendrocyte loss was found only in the stratum oriens and stratum pyramidale. By the 30th day, demyelination in these hippocampal layers intensified and affected the substratum radiatum. In addition to myelin damage, activation and an increase in the number of microglia and astrocytes in the corresponding layers, a loss of the CA1 pyramidal neurons, and neurodegeneration in the neocortex and thalamus was observed. At a 10-day time point, we observed rod-shaped microglia in the substratum radiatum. Parallel with ongoing myelin loss on the 30th day after ischemia, we found significant oligodendrogenesis in demyelinated hippocampal layers; (4) Conclusions: Our study showed that GCI-simulating cardiac arrest in humans—causes not only the loss of pyramidal neurons in the CA1 field, but also the myelin loss of adjacent layers of the hippocampus.
Wnt Signaling in Leukemia and Its Bone Marrow Microenvironment
Authors: Ruan Yongsheng , Kim Hye Na , Ogana Heather , Kim Yong-Mi
Published: August 2020

Leukemia is an aggressive hematologic neoplastic disease. Therapy-resistant leukemic stem cells (LSCs) may contribute to the relapse of the disease. LSCs are thought to be protected in the leukemia microenvironment, mainly consisting of mesenchymal stem/stromal cells (MSC), endothelial cells, and osteoblasts. Canonical and noncanonical Wnt pathways play a critical role in the maintenance of normal hematopoietic stem cells (HSC) and LSCs. In this review, we summarize recent findings on the role of Wnt signaling in leukemia and its microenvironment and provide information on the currently available strategies for targeting Wnt signaling.
Proliferation and Cluster Analysis of Neurons and Glial Cell Organization on Nanocolumnar TiN Substrates
Authors: Abend Alice , Steele Chelsie , Schmidt Sabine , Frank Ronny , Jahnke Heinz-Georg , Zink Mareike
Published: August 2020

Biomaterials employed for neural stimulation, as well as brain/machine interfaces, offer great perspectives to combat neurodegenerative diseases, while application of lab-on-a-chip devices such as multielectrode arrays is a promising alternative to assess neural function in vitro. For bioelectronic monitoring, nanostructured microelectrodes are required, which exhibit an increased surface area where the detection sensitivity is not reduced by the self-impedance of the electrode. In our study, we investigated the interaction of neurons (SH-SY5Y) and glial cells (U-87 MG) with nanocolumnar titanium nitride (TiN) electrode materials in comparison to TiN with larger surface grains, gold, and indium tin oxide (ITO) substrates. Glial cells showed an enhanced proliferation on TiN materials; however, these cells spread evenly distributed over all the substrate surfaces. By contrast, neurons proliferated fastest on nanocolumnar TiN and formed large cell agglomerations. We implemented a radial autocorrelation function of cellular positions combined with various clustering algorithms. These combined analyses allowed us to quantify the largest cluster on nanocolumnar TiN; however, on ITO and gold, neurons spread more homogeneously across the substrates. As SH-SY5Y cells tend to grow in clusters under physiologic conditions, our study proves nanocolumnar TiN as a potential bioactive material candidate for the application of microelectrodes in contact with neurons. To this end, the employed K-means clustering algorithm together with radial autocorrelation analysis is a valuable tool to quantify cell-surface interaction and cell organization to evaluate biomaterials’ performance in vitro.
Measuring Extracellular Vesicles by Conventional Flow Cytometry: Dream or Reality?
Authors: Lucchetti Donatella , Battaglia Alessandra , Ricciardi-Tenore Claudio , Colella Filomena , Perelli Luigi , De Maria Ruggero , Scambia Giovanni , Sgambato Alessandro , Fattorossi Andrea
Published: August 2020

Intense research is being conducted using flow cytometers available in clinically oriented laboratories to assess extracellular vesicles (EVs) surface cargo in a variety of diseases. Using EVs of various sizes purified from the HT29 human colorectal adenocarcinoma cell line, we report on the difficulty to assess small and medium sized EVs by conventional flow cytometer that combines light side scatter off a 405 nm laser with the fluorescent signal from the EVs general labels Calcein-green and Calcein-violet, and surface markers. Small sized EVs (~70 nm) immunophenotyping failed, consistent with the scarcity of monoclonal antibody binding sites, and were therefore excluded from further investigation. Medium sized EVs (~250 nm) immunophenotyping was possible but their detection was plagued by an excess of coincident particles (swarm detection) and by a high abort rate; both factors affected the measured EVs concentration. By running samples containing equal amounts of Calcein-green and Calcein-violet stained medium sized EVs, we found that swarm detection produced false double positive events, a phenomenon that was significantly reduced, but not totally eliminated, by sample dilution. Moreover, running highly diluted samples required long periods of cytometer time. Present findings raise questions about the routine applicability of conventional flow cytometers for EV analysis.
Exhaustive Search of the Receptor Ligands by the CyCLOPS (Cytometry Cell-Labeling Operable Phage Screening) Technique
Authors: Ishina Irina A. , Filimonova Ioanna N. , Zakharova Maria Y. , Ovchinnikova Leyla A. , Mamedov Azad E. , Lomakin Yakov A. , Belogurov Alexey A.
Published: August 2020

Effective and versatile screening of the peptide ligands capable of selectively binding to diverse receptors is in high demand for the state-of-the-art technologies in life sciences, including probing of specificity of the cell surface receptors and drug development. Complex microenvironment and structure of the surface receptors significantly reduce the possibility to determine their specificity, especially when in vitro conditions are utilized. Previously, we designed a publicly available platform for the ultra-high-throughput screening (uHTS) of the specificity of surface-exposed receptors of the living eukaryotic cells, which was done by consolidating the phage display and flow cytometry techniques. Here, we significantly improved this methodology and designed the fADL-1e-based phage vectors that do not require a helper hyperphage for the virion assembly. The enhanced screening procedure was tested on soluble human leukocyte antigen (HLA) class II molecules and transgenic antigen-specific B cells that express recombinant lymphoid B-cell receptor (BCR). Our data suggest that the improved vector system may be successfully used for the comprehensive search of the receptor ligands in either cell-based or surface-immobilized assays.
Insight into the Folding and Dimerization Mechanisms of the N-Terminal Domain from Human TDP-43
Authors: Vivoli-Vega Mirella , Guri Prandvera , Chiti Fabrizio , Bemporad Francesco
Published: August 2020

TAR DNA-binding protein 43 (TDP-43) is a 414-residue long nuclear protein whose deposition into intraneuronal insoluble inclusions has been associated with the onset of amyotrophic lateral sclerosis (ALS) and other diseases. This protein is physiologically a homodimer, and dimerization occurs through the N-terminal domain (NTD), with a mechanism on which a full consensus has not yet been reached. Furthermore, it has been proposed that this domain is able to affect the formation of higher molecular weight assemblies. Here, we purified this domain and carried out an unprecedented characterization of its folding/dimerization processes in solution. Exploiting a battery of biophysical approaches, ranging from FRET to folding kinetics, we identified a head-to-tail arrangement of the monomers within the dimer. We found that folding of NTD proceeds through the formation of a number of conformational states and two parallel pathways, while a subset of molecules refold slower, due to proline isomerism. The folded state appears to be inherently prone to form high molecular weight assemblies. Taken together, our results indicate that NTD is inherently plastic and prone to populate different conformations and dimeric/multimeric states, a structural feature that may enable this domain to control the assembly state of TDP-43.
Promiscuous Enzyme Activity as a Driver of Allo and Iso Convergent Evolution, Lessons from the β-Lactamases
Authors: Keshri Vivek , Chabrière Eric , Pinault Lucile , Colson Philippe , Diene Seydina M , Rolain Jean-Marc , Raoult Didier , Pontarotti Pierre
Published: August 2020

The probability of the evolution of a character depends on two factors: the probability of moving from one character state to another character state and the probability of the new character state fixation. The more the evolution of a character is probable, the more the convergent evolution will be witnessed, and consequently, convergent evolution could mean that the convergent character evolution results as a combination of these two factors. We investigated this phenomenon by studying the convergent evolution of biochemical functions. For the investigation we used the case of β-lactamases. β-lactamases hydrolyze β-lactams, which are antimicrobials able to block the DD-peptidases involved in bacterial cell wall synthesis. β-lactamase activity is present in two different superfamilies: the metallo-β-lactamase and the serine β-lactamase. The mechanism used to hydrolyze the β-lactam is different for the two superfamilies. We named this kind of evolution an allo-convergent evolution. We further showed that the β-lactamase activity evolved several times within each superfamily, a convergent evolution type that we named iso-convergent evolution. Both types of convergent evolution can be explained by the two evolutionary mechanisms discussed above. The probability of moving from one state to another is explained by the promiscuous β-lactamase activity present in the ancestral sequences of each superfamily, while the probability of fixation is explained in part by positive selection, as the organisms having β-lactamase activity allows them to resist organisms that secrete β-lactams. Indeed, an organism that has a mutation that increases the β-lactamase activity will be selected, as the organisms having this activity will have an advantage over the others.
Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling
Authors: Brivio Paola , Sbrini Giulia , Corsini Giulia , Paladini Maria Serena , Racagni Giorgio , Molteni Raffaella , Calabrese Francesca
Published: August 2020

Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize during symptoms remission, facilitating the relapse to the pathology. Hence, we investigated the long-lasting effects of chronic restraint stress (CRS) and its influence on the modifications induced by the exposure to a second hit on brain-derived neurotrophic factor (BDNF) signaling in the prefrontal cortex (PFC). We exposed adult male Sprague Dawley rats to 4 weeks of CRS, we left them undisturbed for the subsequent 3 weeks, and then we exposed animals to one hour of acute restraint stress (ARS). We found that CRS influenced the release of corticosterone induced by ARS and inhibited the ability of ARS to activate mature BDNF, its receptor Tropomyosin receptor kinase B (TRKB), and their associated intracellular cascades: the TRKB-PI3K-AKT), the MEK-MAPK/ERK, and the Phospholipase C γ (PLCγ) pathways, positively modulated by ARS in non-stressed animals. These results suggest that CRS induces protracted and detrimental consequences that interfere with the ability of PFC to cope with a challenging situation.
Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma
Authors: Wójcik-Gryciuk Anna , Gajewska-Woźniak Olga , Kordecka Katarzyna , Boguszewski Paweł M. , Waleszczyk Wioletta , Skup Małgorzata
Published: August 2020

Intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury (ONI) or laser-induced ocular hypertension (OHT). In models of glaucoma, BDNF therapy can delay or halt RGCs loss, but this protection is time-limited. The decreased efficacy of BDNF supplementation has been in part attributed to BDNF TrkB receptor downregulation. However, whether BDNF overexpression causes TrkB downregulation, impairing long-term BDNF signaling in the retina, has not been conclusively proven. After ONI or OHT, when increased retinal BDNF was detected, a concomitant increase, no change or a decrease in TrkB was reported. We examined quantitatively the retinal concentrations of the TrkB protein in relation to BDNF, in a course of adeno-associated viral vector gene therapy (AAV2-BDNF), using a microbead trabecular occlusion model of glaucoma. We show that unilateral glaucoma, with intraocular pressure ( IOP) increased for five weeks, leads to a bilateral decrease of BDNF in the retina at six weeks, accompanied by up to four-fold TrkB upregulation, while a moderate BDNF overexpression in a glaucomatous eye triggers changes that restore normal TrkB concentrations, driving signaling towards long-term RGCs neuroprotection. We conclude that for glaucoma therapy, the careful selection of the appropriate BDNF concentration is the main factor securing the long-term responsiveness of RGCs and the maintenance of normal TrkB levels.
Aldo-Keto Reductase 1C1 (AKR1C1) as the First Mutated Gene in a Family with Nonsyndromic Primary Lipedema
Authors: Michelini Sandro , Chiurazzi Pietro , Marino Valerio , Dell’Orco Daniele , Manara Elena , Baglivo Mirko , Fiorentino Alessandro , Maltese Paolo Enrico , Pinelli Michele , Herbst Karen Louise , Dautaj Astrit , Bertelli Matteo
Published: August 2020

Lipedema is an often underdiagnosed chronic disorder that affects subcutaneous adipose tissue almost exclusively in women, which leads to disproportionate fat accumulation in the lower and upper body extremities. Common comorbidities include anxiety, depression, and pain. The correlation between mood disorder and subcutaneous fat deposition suggests the involvement of steroids metabolism and neurohormones signaling, however no clear association has been established so far. In this study, we report on a family with three patients affected by sex-limited autosomal dominant nonsyndromic lipedema. They had been screened by whole exome sequencing (WES) which led to the discovery of a missense variant p.(Leu213Gln) in AKR1C1, the gene encoding for an aldo-keto reductase catalyzing the reduction of progesterone to its inactive form, 20-α-hydroxyprogesterone. Comparative molecular dynamics simulations of the wild-type vs. variant enzyme, corroborated by a thorough structural and functional bioinformatic analysis, suggest a partial loss-of-function of the variant. This would result in a slower and less efficient reduction of progesterone to hydroxyprogesterone and an increased subcutaneous fat deposition in variant carriers. Overall, our results suggest that AKR1C1 is the first candidate gene associated with nonsyndromic lipedema.
Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease
Authors: Ghavami Shaghayegh Baradaran , Yadegar Abbas , Aghdaei Hamid Asadzadeh , Sorrentino Dario , Farmani Maryam , Mir Adil Shamim , Azimirad Masoumeh , Balaii Hedieh , Shahrokh Shabnam , Zali Mohammad Reza
Published: August 2020

In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs). Herein, we assessed the immunomodulatory effects of four probiotic strains including Lactobacillus salivarius, Bifidobacterium bifidum, Bacillus coagulans and Bacillus subtilis natto on the expression of co-stimulatory molecules, cytokine production and gene expression of signal-transducing receptors in DCs from IBD patients. Human monocyte-derived DCs from IBD patients and healthy controls were exposed to four probiotic strains. The expression of co-stimulatory molecules was assessed and supernatants were analyzed for anti-inflammatory cytokines. The gene expression of toll-like receptors (TLRs), IL-12p40 and integrin αvβ8 were also analyzed. CD80 and CD86 were induced by most probiotic strains in ulcerative colitis (UC) patients whereas only B. bifidum induced CD80 and CD86 expression in Crohn’s disease (CD) patients. IL-10 and TGF-β production was increased in a dose-independent manner while TLR expression was decreased by all probiotic bacteria except B. bifidum in DCs from UC patients. TLR-4 and TLR-9 expression was significantly downregulated while integrin ß8 was significantly increased in the DCs from CD patients. IL-12p40 expression was only significantly downregulated in DCs from CD patients. Our findings point to the general beneficial effects of probiotics in DC immunomodulation and indicate that probiotic bacteria favorably modulate the expression of co-stimulatory molecules, proinflammatory cytokines and TLRs in DCs from IBD patients.
Ionic Liquids Toxicity—Benefits and Threats
Authors: Flieger Jolanta , Flieger Michał
Published: August 2020

Ionic liquids (ILs) are solvents with salt structures. Typically, they contain organic cations (ammonium, imidazolium, pyridinium, piperidinium or pyrrolidinium), and halogen, fluorinated or organic anions. While ILs are considered to be environmentally-friendly compounds, only a few reasons support this claim. This is because of high thermal stability, and negligible pressure at room temperature which makes them non-volatile, therefore preventing the release of ILs into the atmosphere. The expansion of the range of applications of ILs in many chemical industry fields has led to a growing threat of contamination of the aquatic and terrestrial environments by these compounds. As the possibility of the release of ILs into the environment s grow systematically, there is an increasing and urgent obligation to determine their toxic and antimicrobial influence on the environment. Many bioassays were carried out to evaluate the (eco)toxicity and biodegradability of ILs. Most of them have questioned their “green” features as ILs turned out to be toxic towards organisms from varied trophic levels. Therefore, there is a need for a new biodegradable, less toxic “greener” ILs. This review presents the potential risks to the environment linked to the application of ILs. These are the following: cytotoxicity evaluated by the use of human cells, toxicity manifesting in aqueous and terrestrial environments. The studies proving the relation between structures versus toxicity for ILs with special emphasis on directions suitable for designing safer ILs synthesized from renewable sources are also presented. The representants of a new generation of easily biodegradable ILs derivatives of amino acids, sugars, choline, and bicyclic monoterpene moiety are collected. Some benefits of using ILs in medicine, agriculture, and the bio-processing industry are also presented.
Polar Infection of Echovirus-30 Causes Differential Barrier Affection and Gene Regulation at the Blood–Cerebrospinal Fluid Barrier
Authors: Wiatr Marie , Figueiredo Ricardo , Stump-Guthier Carolin , Winter Peter , Ishikawa Hiroshi , Adams Ortwin , Schwerk Christian , Schroten Horst , Rudolph Henriette , Tenenbaum Tobias
Published: August 2020

Echovirus-30 (E-30) is responsible for the extensive global outbreaks of meningitis in children. To gain access to the central nervous system, E-30 first has to cross the epithelial blood–cerebrospinal fluid barrier. Several meningitis causing bacteria preferentially infect human choroid plexus papilloma (HIBCPP) cells in a polar fashion from the basolateral cell side. Here, we investigated the polar infection of HIBCPP cells with E-30. Both apical and basolateral infections caused a significant decrease in the transepithelial electrical resistance of HIBCPP cells. However, to reach the same impact on the barrier properties, the multiplicity of infection of the apical side had to be higher than that of the basolateral infection. Furthermore, the number of infected cells at respective time-points after basolateral infection was significantly higher compared to apical infection. Cytotoxic effects of E-30 on HIBCPP cells during basolateral infection were observed following prolonged infection and appeared more drastically compared to the apical infection. Gene expression profiles determined by massive analysis of cDNA ends revealed distinct regulation of specific genes depending on the side of HIBCPP cells’ infection. Altogether, our data highlights the polar effects of E-30 infection in a human in vitro model of the blood–cerebrospinal fluid barrier leading to central nervous system inflammation.
Anti-Fibrotic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1
Authors: Choi Alee , Park Sang Eon , Jeong Jang Bin , Choi Suk-joo , Oh Soo-young , Ryu Gyu Ha , Lee Jeehun , Jeon Hong Bae , Chang Jong Wook
Published: August 2020

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2–5-month-old mdx mice intravenously injected with 1 × 105 Wharton’s jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.
Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models
Authors: Krenacs Tibor , Meggyeshazi Nora , Forika Gertrud , Kiss Eva , Hamar Peter , Szekely Tamas , Vancsik Tamas
Published: August 2020

The benefits of high-fever range hyperthermia have been utilized in medicine from the Ancient Greek culture to the present day. Amplitude-modulated electro-hyperthermia, induced by a 13.56 MHz radiofrequency current (mEHT, or Oncothermia), has been an emerging means of delivering loco-regional clinical hyperthermia as a complementary of radiation-, chemo-, and molecular targeted oncotherapy. This unique treatment exploits the metabolic shift in cancer, resulting in elevated oxidative glycolysis (Warburg effect), ion concentration, and electric conductivity. These promote the enrichment of electric fields and induce heat (controlled at 42 °C), as well as ion fluxes and disequilibrium through tumor cell membrane channels. By now, accumulating preclinical studies using in vitro and in vivo models of different cancer types have revealed details of the mechanism and molecular background of the oncoreductive effects of mEHT monotherapy. These include the induction of DNA double-strand breaks, irreversible heath and cell stress, and programmed cells death; the upregulation of molecular chaperones and damage (DAMP) signaling, which may contribute to a secondary immunogenic tumor cell death. In combination therapies, mEHT proved to be a good chemosensitizer through increasing drug uptake and tumor reductive effects, as well as a good radiosensitizer by downregulating hypoxia-related target genes. Recently, immune stimulation or intratumoral antigen-presenting dendritic cell injection have been able to extend the impact of local mEHT into a systemic “abscopal” effect. The complex network of pathways emerging from the published mEHT experiments has not been overviewed and arranged yet into a framework to reveal links between the pieces of the “puzzle”. In this paper, we review the mEHT-related damage mechanisms published in tumor models, which may allow some geno-/phenotype treatment efficiency correlations to be exploited both in further research and for more rational clinical treatment planning when mEHT is involved in combination therapies.
Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going?
Authors: Pardo Juan Carlos , Ruiz de Porras Vicenç , Plaja Andrea , Carrato Cristina , Etxaniz Olatz , Buisan Oscar , Font Albert
Published: August 2020

Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the recommended treatment, with the highest level of evidence, for patients with muscle-invasive bladder cancer (MIBC). However, only a minority of patients receive this treatment, mainly due to patient comorbidities, the relatively small survival benefit, and the lack of predictive biomarkers to select those patients most likely to benefit from this multimodal approach. In addition, adjuvant chemotherapy has been recommended for patients with high-risk MIBC, although randomized trials have not provided conclusive evidence on the impact of this approach. At present, however, this situation is changing, largely due to our improved knowledge of the molecular biology of bladder cancer, which has enabled us to identify new prognostic and predictive biomarkers that can be used to select the most appropriate treatment for each patient. Moreover, new active treatments, especially immunotherapy, have shown promising results in the neoadjuvant setting. In addition, the gene expression profile of bladder tumors can be used to classify them into different subtypes, which correlate with specific clinical-pathological characteristics and with treatment response or resistance. Therefore, the main objective for the near future is to introduce these translational breakthroughs into routine clinical practice in order to personalize treatment for each patient.
Tetrapeptide Ac-HAEE-NH2 Protects α4β2 nAChR from Inhibition by Aβ
Authors: Barykin Evgeny P. , Garifulina Aleksandra I. , Tolstova Anna P. , Anashkina Anastasia A. , Adzhubei Alexei A. , Mezentsev Yuri V. , Shelukhina Irina V. , Kozin Sergey A. , Tsetlin Victor I. , Makarov Alexander A.
Published: August 2020

The cholinergic deficit in Alzheimer’s disease (AD) may arise from selective loss of cholinergic neurons caused by the binding of Aβ peptide to nicotinic acetylcholine receptors (nAChRs). Thus, compounds preventing such an interaction are needed to address the cholinergic dysfunction. Recent findings suggest that the 11EVHH14 site in Aβ peptide mediates its interaction with α4β2 nAChR. This site contains several charged amino acid residues, hence we hypothesized that the formation of Aβ-α4β2 nAChR complex is based on the interaction of 11EVHH14 with its charge-complementary counterpart in α4β2 nAChR. Indeed, we discovered a 35HAEE38 site in α4β2 nAChR, which is charge-complementary to 11EVHH14, and molecular modeling showed that a stable Aβ42-α4β2 nAChR complex could be formed via the 11EVHH14:35HAEE38 interface. Using surface plasmon resonance and bioinformatics approaches, we further showed that a corresponding tetrapeptide Ac-HAEE-NH2 can bind to Aβ via 11EVHH14 site. Finally, using two-electrode voltage clamp in Xenopus laevis oocytes, we showed that Ac-HAEE-NH2 tetrapeptide completely abolishes the Aβ42-induced inhibition of α4β2 nAChR. Thus, we suggest that 35HAEE38 is a potential binding site for Aβ on α4β2 nAChR and Ac-HAEE-NH2 tetrapeptide corresponding to this site is a potential therapeutic for the treatment of α4β2 nAChR-dependent cholinergic dysfunction in AD.
Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study
Authors: Forcione Mario , Chiarelli Antonio Maria , Perpetuini David , Davies David James , O’Halloran Patrick , Hacker David , Merla Arcangelo , Belli Antonio
Published: August 2020

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed.
Proteomics and Metabolomics Approaches towards a Functional Insight onto AUTISM Spectrum Disorders: Phenotype Stratification and Biomarker Discovery
Authors: Ristori Maria Vittoria , Mortera Stefano Levi , Marzano Valeria , Guerrera Silvia , Vernocchi Pamela , Ianiro Gianluca , Gardini Simone , Torre Giuliano , Valeri Giovanni , Vicari Stefano , Gasbarrini Antonio , Putignani Lorenza
Published: August 2020

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by behavioral alterations and currently affect about 1% of children. Significant genetic factors and mechanisms underline the causation of ASD. Indeed, many affected individuals are diagnosed with chromosomal abnormalities, submicroscopic deletions or duplications, single-gene disorders or variants. However, a range of metabolic abnormalities has been highlighted in many patients, by identifying biofluid metabolome and proteome profiles potentially usable as ASD biomarkers. Indeed, next-generation sequencing and other omics platforms, including proteomics and metabolomics, have uncovered early age disease biomarkers which may lead to novel diagnostic tools and treatment targets that may vary from patient to patient depending on the specific genomic and other omics findings. The progressive identification of new proteins and metabolites acting as biomarker candidates, combined with patient genetic and clinical data and environmental factors, including microbiota, would bring us towards advanced clinical decision support systems (CDSSs) assisted by machine learning models for advanced ASD-personalized medicine. Herein, we will discuss novel computational solutions to evaluate new proteome and metabolome ASD biomarker candidates, in terms of their recurrence in the reviewed literature and laboratory medicine feasibility. Moreover, the way to exploit CDSS, performed by artificial intelligence, is presented as an effective tool to integrate omics data to electronic health/medical records (EHR/EMR), hopefully acting as added value in the near future for the clinical management of ASD.
A Deep-Learning-Based Framework for Automated Diagnosis of COVID-19 Using X-ray Images
Authors: Khan Irfan Ullah , Aslam Nida
Published: August 2020

The emergence and outbreak of the novel coronavirus (COVID-19) had a devasting effect on global health, the economy, and individuals’ daily lives. Timely diagnosis of COVID-19 is a crucial task, as it reduces the risk of pandemic spread, and early treatment will save patients’ life. Due to the time-consuming, complex nature, and high false-negative rate of the gold-standard RT-PCR test used for the diagnosis of COVID-19, the need for an additional diagnosis method has increased. Studies have proved the significance of X-ray images for the diagnosis of COVID-19. The dissemination of deep-learning techniques on X-ray images can automate the diagnosis process and serve as an assistive tool for radiologists. In this study, we used four deep-learning models—DenseNet121, ResNet50, VGG16, and VGG19—using the transfer-learning concept for the diagnosis of X-ray images as COVID-19 or normal. In the proposed study, VGG16 and VGG19 outperformed the other two deep-learning models. The study achieved an overall classification accuracy of 99.3%.
A THz Spectrometer Using Band Pass Filters
Authors: Martini Francesco , Giovine Ennio , Chiarello Fabio , Carelli Pasquale
Published: August 2020

We describe a THz spectrometer operating between 1.2 and 10.5 THz, consisting of band pass filters made by metasurfaces. The source is made of a 10 W small black body. The detector is a high sensitivity room temperature pyroelectric sensor. Various techniques that are used to prepare samples are described. The spectra obtained are compared with those measured with a Fourier Transformer Infrared Spectrometer on the same samples. Our instrument, which uses commercial technologies available at the present time, can constitute an economical alternative to very expensive spectrometers. It has already been successfully used, obtaining precise spectroscopic measurements on many inorganic powders.
What Is the Effectiveness of Different Duration Interdisciplinary Treatment Programs in Patients with Chronic Pain? A Large-Scale Longitudinal Register Study
Authors: Tseli Elena , LoMartire Riccardo , Vixner Linda , Grooten Wilhelmus Johannes Andreas , Gerdle Björn , Äng Björn O.
Published: August 2020

Chronic pain is a leading cause of disability globally. Interdisciplinary multimodal pain rehabilitation (IMPR) targets pain with a bio-psycho-social approach, often delivered as composite programs. However, evidence of optimal program duration for the rehabilitation to succeed remains scarce. This study evaluated the effectiveness of different duration IMPR-programs—using within- and between-effects analyses in a pragmatic multicenter register-based controlled design. Using the Swedish Quality Registry for Pain Rehabilitation, data from fifteen clinics specialized in chronic pain rehabilitation across Sweden were retrieved. Participants were patients with chronic musculoskeletal pain who had taken part in short (4–9 weeks; n = 924), moderate (10 weeks; n = 1379), or long (11–18 weeks; n = 395) IMPR programs. Longitudinal patient-reported outcome data were assessed at baseline, post-intervention, and at a 12-month follow-up. Primary outcomes were health-related quality of life, presented as perceived physical and mental health (SF-36). Secondary outcomes included the Hospital Anxiety and Depression Scale (HADS), pain intensity (NRS 0-10), the Multidimensional Pain Inventory (MPI), and perceived health (EQ-5D). Overall, all groups showed improvements. No clinically important effect emerged for different duration IMPR. In conclusion, while our results showed that patients following IMPR report improvement across a bio-psycho-social specter, a longer program duration was no more effective than a shorter one.
Alternatives to the Use of Mechanical Restraints in the Management of Agitation or Aggressions of Psychiatric Patients: A Scoping Review
Authors: Fernández-Costa Damián , Gómez-Salgado Juan , Fagundo-Rivera Javier , Martín-Pereira Jorge , Prieto-Callejero Blanca , García-Iglesias Juan
Published: August 2020

Coercive measures are a highly controversial issue in mental health. Although scientific evidence on their impact is limited, they are frequently used. Furthermore, they lead to a high number of ethical, legal, and clinical repercussions on both patients, and professionals and institutions. This review aims to assess the impact of the main alternative measures to prevent or limit the use of coercive measures with restraints in the management of agitated psychiatric patients. The research was conducted following the guidelines recommended by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) in Medline, Cochrane Library, CINAHL, Web of Science, PsycInfo, LILACS, and Health Database of records between 2015 and 2020. After a critical reading, 21 valid articles were included. Both simple interventions and complex restraint programs were evaluated. Training in de-escalation techniques, risk assessment, and implementation of the “six core strategies” or “Safewards” program were the most assessed and effective interventions to reduce aggressive behaviors and the use of coercive measures. According to the revised literature, it is possible to reduce the use of restraints and coercive measures and not increase the number of incidents and violent behaviors among the patients through a non-invasive and non-pharmacological approach. However, further research and further randomized clinical trials are needed to compare the different alternatives and provide higher quality evidence.
Twelve Weeks of Strengthening Exercise for Patients with Rheumatoid Arthritis: A Prospective Intervention Study
Authors: Sul Bomi , Lee Kyoung Bo , Joo Young Bin , Hong Bo Young , Kim Joon-Sung , Kim Ki-Jo , Park Kyung-Su , Park Yune-Jung , Lim Seong Hoon
Published: August 2020

Rheumatoid arthritis (RA) patients may benefit from exercise for several reasons. However, whole-limb strengthening exercises for such patients remain poorly studied. We hypothesized that systemic strength training that includes the upper and lower extremities would improve strength per se and enhance the quality of life. Here, we investigated the effects of 12 weeks of upper- and lower-limb strengthening exercise on the strength and quality of life of RA patients using the International Classification of Functioning, Disability, and Health model. This was a prospective, interventional controlled trial. Forty female RA patients were recruited and assigned to two groups not based on willingness to exercise, with 20 patients in the exercise group and 20 in the control group. All patients in the exercise group received once-weekly training sessions of 60 min over 12 weeks. All participants were assessed before and after the 12-week intervention period. We measured the hand grip strength and isometric quadriceps contraction, the cross-sectional area of the rectus femoris (CSA-RF) (via ultrasonography), and performed the 30 s sit-to-stand test and the 6 min walk test (6MWT). We derived the Borg scale score after the 6MWT and assessed the extent of social participation and quality of life using a Korean version of the 36-Item Short Form Health Survey (SF-36). A total of 35 subjects completed the experiment (18 in the exercise group, 17 in the control group). After the 12-week intervention period, the lower-limb strength and the CSA-RF were significantly increased in the exercise group. The activity level did not change significantly in either group. The exercise group exhibited significant improvements in the SF-36 mental health domain scores. Thus, strengthening exercise is useful for patients with RA.