bluuebunny/crossref_metadata_2025 huggingface dataset:
Dental and Periodontal Care at the Bedside Using a Portable Dental Unit in Hospitalized Special Needs Patients: The Experience of an Italian Pediatric Hospital
Authors: Galeotti Angela , Ciribè Massimiliano , Matarazzo Giorgio , Antonielli Giancarlo , Festa Paola , Inserra Alessandro , Garret-Bernardin Annelyse , Callea Michele , Raponi Massimiliano
Published: July 2021

Patients with special needs (SNPs) include individuals who are disabled due to physical limitations, medical complications, developmental problems, and cognitive impairments. SNPs may be at an increased risk of oral diseases throughout their lifetime. These patients have difficulties in accessing traditional dental studios or clinics. Moreover, orodental problems may cause local and generalized infections, leading to worrisome complications when not properly treated. In this paper, we describe the preliminary experience of treating dental problems in a series of nine hospitalized patients with special needs. This innovative protocol at the Bambino Gesù Children’s Hospital (Rome, Italy) provides an introduction to a portable dental unit in order to perform oral care for hospitalized patients at the bedside. A multidisciplinary team composed of pediatric dentists, dental hygienists, nursing staff, and the patient’s case manager was involved in the operative protocol. The SNPs described were affected by congenital heart or oncohematological diseases and neurodisabilities, and they were all hospitalized for different reasons: Open heart surgery, chemotherapy, organ transplantation, and rehabilitation. The oral evaluation was mandatory for ruling out or treating problems that could cause complications. Dental extractions, caries and fracture fillings, sealing, and oral hygiene procedures were performed at the bedside of the patients in the reference unit of their pediatric hospital. The results of this protocol confirm the feasibility of dental procedures at patients’ bedside with portable dental units, encourage implementation of their use, and may represent an actionable model for oral care management in hospitalized SNPs.
Reducible Nonunited Type II Odontoid Fracture with Atlantoaxial Instability: Outcomes of Two Different Fixation Techniques
Authors: Bunmaprasert Torphong , Trirattanapikul Vorapop , Sugandhavesa Nantawit , Phanphaisarn Areerak , Liawrungrueang Wongthawat , Phinyo Phichayut
Published: July 2021

Displaced nonunited type II odontoid fracture can result in atlantoaxial instability, causing delayed cervical myelopathy. Both Magerl’s C1-C2 transarticular screw fixation technique and Harms-Goel C1-C2 screw-rod segmental fixation technique are effective techniques to provide stability. This study aimed to demonstrate the results of two surgical fixation techniques for the treatment of reducible nonunited type II odontoid fracture with atlantoaxial instability. Medical records of patients with reducible nonunited type II odontoid fracture hospitalized for spinal fusion between April 2007 and April 2018 were reviewed. For each patient, specific surgical fixation, either Magerl’s C1-C2 transarticular screw fixation technique augmented with supplemental wiring or Harms-Goel C1-C2 screw-rod fixation technique, was performed according to our management protocol. We reported the fusion rate, fusion period, and complications for each technique. Of 21 patients, 10 patients were treated with Magerl’s C1-C2 transarticular screw fixation technique augmented with supplemental wiring, and 11 were treated with Harms-Goel C1-C2 screw-rod fixation technique. The bony fusion rate was 100% in both groups. The mean time to fusion was 69.7 (95%CI 53.1, 86.3) days in Magerl’s C1-C2 transarticular screw fixation technique and 75.2 (95%CI 51.8, 98.6) days in Harms-Goel C1-C2 screw-rod fixation technique. No severe complications were observed in either group. Displaced reducible, nonunited type II odontoid fracture with cervical myelopathy should be treated by surgery. Both fixation techniques promote bony fusion and provide substantial construct stability.
The Influence of Traffic-Related Air Pollution (TRAP) in Primary Schools and Residential Proximity to Traffic Sources on Histone H3 Level in Selected Malaysian Children
Authors: Suhaimi Nur Faseeha , Jalaludin Juliana , Abu Bakar Suhaili
Published: July 2021

This study aimed to investigate the association between traffic-related air pollution (TRAP) exposure and histone H3 modification among school children in high-traffic (HT) and low-traffic (LT) areas in Malaysia. Respondents’ background information and personal exposure to traffic sources were obtained from questionnaires distributed to randomly selected school children. Real-time monitoring instruments were used for 6-h measurements of PM10, PM2.5, PM1, NO2, SO2, O3, CO, and total volatile organic compounds (TVOC). Meanwhile, 24-h measurements of PM2.5-bound black carbon (BC) were performed using air sampling pumps. The salivary histone H3 level was captured using an enzyme-linked immunosorbent assay (ELISA). HT schools had significantly higher PM10, PM2.5, PM1, BC, NO2, SO2, O3, CO, and TVOC than LT schools, all at p < 0.001. Children in the HT area were more likely to get higher histone H3 levels (z = −5.13). There were positive weak correlations between histone H3 level and concentrations of NO2 (r = 0.37), CO (r = 0.36), PM1 (r = 0.35), PM2.5 (r = 0.34), SO2 (r = 0.34), PM10 (r = 0.33), O3 (r = 0.33), TVOC (r = 0.25), and BC (r = 0.19). Overall, this study proposes the possible role of histone H3 modification in interpreting the effects of TRAP exposure via non-genotoxic mechanisms.
Microblog Topic-Words Detection Model for Earthquake Emergency Responses Based on Information Classification Hierarchy
Authors: Su Xiaohui , Ma Shurui , Qiu Xiaokang , Shi Jiabin , Zhang Xiaodong , Chen Feixiang
Published: July 2021

Social media data are constantly updated, numerous, and characteristically prominent. To quickly extract the needed information from the data to address earthquake emergencies, a topic-words detection model of earthquake emergency microblog messages is studied. First, a case analysis method is used to analyze microblog information after earthquake events. An earthquake emergency information classification hierarchy is constructed based on public demand. Then, subject sets of different granularities of earthquake emergency information classification are generated through the classification hierarchy. A detection model of new topic-words is studied to improve and perfect the sets of topic-words. Furthermore, the validity, timeliness, and completeness of the topic-words detection model are verified using 2201 messages obtained after the 2014 Ludian earthquake. The results show that the information acquisition time of the model is short. The validity of the whole set is 96.96%, and the average and maximum validity of single words are 78% and 100%, respectively. In the Ludian and Jiuzhaigou earthquake cases, new topic-words added to different earthquakes only reach single digits in validity. Therefore, the experiments show that the proposed model can quickly obtain effective and pertinent information after an earthquake, and the complete performance of the earthquake emergency information classification hierarchy can meet the needs of other earthquake emergencies.
Effect of Virtual Reality Exercises on the Cognitive Status and Dual Motor Task Performance of the Aging Population
Authors: Nobari Hadi , Rezaei Saeed , Sheikh Mahmoud , Fuentes-García Juan Pedro , Pérez-Gómez Jorge
Published: July 2021

Aging is a global phenomenon affecting numerous developed and developing countries. During this process, the functional state of the body, especially the cognitive state, declines. This research investigated the impact of virtual reality exercises on the cognitive status and dual-task performance in the elderly of Tabriz city, Iran. Forty men with a mean age of 71.5 were selected and assigned to either the experimental (n = 20) or control groups (n = 20). Both groups completed the Mini-Mental State Examination for cognitive status. The pre-test was performed through the Timed Up and Go test (TUG) along with a countdown of numbers. Then, the experimental group practiced virtual driving for six weeks, while the control group received no treatment. After the treatment, both groups completed the post-test. At each stage, the test was performed as a dual motor task as well. Data were analyzed using the paired t-test and the independent sample t-test to show the intra-group and inter-group differences, respectively. The results showed a significant improvement in the cognitive status and dual-task performance of the elderly men after the six-week training period, which was also significant compared to the control group. Virtual reality driving can be used to improve the cognitive status and dual task performance of elderly men.
Hierarchical Regression of Wellbeing and Self-Rated Health among Older Adults in Abu Dhabi
Authors: Badri Masood A. , Yang Guang , Al Khaili Mugheer , Al Bahar Muna , Al Rashdi Asma , Al Hyas Layla
Published: July 2021

This study investigates the wellbeing factors related to self-rated health for older adults in Abu Dhabi (≥55 years). The purpose is to provide a comprehensive analysis of the determinants of self-rated health, considering various wellbeing factors, controlling for factors such as gender, nationality and long-standing illness if present. This research drew from a sample of 2375 older adults who participated in the Abu Dhabi Quality-of-Life Survey (QoL) conducted in 2018. Hierarchical multiple regression analysis was employed where the first two models corresponded to gender, nationality and having a long-standing illness or not. The third model focused on the wellbeing factors of Abu Dhabi citizens (i.e., social networks and connection, income and housing, sports and activities, mental feelings). The analysis revealed the insignificance of gender and nationality as controlled variables while having a long-standing illness showed significant adverse effects. The most significant variables were social support networks, family and social arrangements and connections. Other variables of significance included housing satisfaction, household income satisfaction, frequency of practicing sports, current mental status and life satisfaction. Policymakers could use the outcomes as insider intelligence for policymakers and social work professionals to create policies, programs and services to enhance the lives of older people in Abu Dhabi.
Wearable Inertial Measurement Unit to Accelerometer-Based Training Monotony and Strain during a Soccer Season: A within-Group Study for Starters and Non-Starters
Authors: Nobari Hadi , Sögüt Mustafa , Oliveira Rafael , Pérez-Gómez Jorge , Suzuki Katsuhiko , Zouhal Hassane
Published: July 2021

The purpose of this study was to analyze the intragroup differences in weekly training monotony (TM) and training strain (TS) between starter and non-starter male professional soccer players at accelerometry based variables throughout the periods of a season. TM and TS of different accelerations and decelerations zones for twenty-one players were followed for forty-eight weeks. Regardless of group, players obtained the highest mean TM (starters = 3.3 ± 0.6, non-starters = 2.2 ± 1.1, in arbitrary unit, AU) and TS (starters = 1288.9 ± 265.2, non-starters = 765.4 ± 547.5, AU) scores in the pre-season for accelerations at Zone 1 (<2 m/s2). The results also indicated that both groups exhibited similar TM and TS scores in accelerations at Zones 2 (2 to 4 m/s2) and 3 (>4 m/s2) across the entire season. While the starters showed the highest TM and TS scores at deceleration Zone 1 (<−2 m/s2) in the end-season, the non-starters exhibited the highest scores at the deceleration Zone 1 in pre-season. It seems that in pre-season, coaches applied higher levels of training with greater emphasis on deceleration for non-starters. This tendency was reduced over time for non-starters, while starters presented higher values of deceleration Zone 1. These results highlight the variations in TM and TS across the different periods of a full season according to match starting status among professional soccer players, and the results suggest that non-starter players should receive higher levels of load to compensate for non-participation in matches throughout a soccer season.
Financial Inclusion in Emerging Economies: The Application of Machine Learning and Artificial Intelligence in Credit Risk Assessment
Authors: Mhlanga David
Published: July 2021

In banking and finance, credit risk is among the important topics because the process of issuing a loan requires a lot of attention to assessing the possibilities of getting the loaned money back. At the same time in emerging markets, the underbanked individuals cannot access traditional forms of collateral or identification that is required by financial institutions for them to be granted loans. Using the literature review approach through documentary and conceptual analysis to investigate the impact of machine learning and artificial intelligence in credit risk assessment, this study discovered that artificial intelligence and machine learning have a strong impact on credit risk assessments using alternative data sources such as public data to deal with the problems of information asymmetry, adverse selection, and moral hazard. This allows lenders to do serious credit risk analysis, to assess the behaviour of the customer, and subsequently to verify the ability of the clients to repay the loans, permitting less privileged people to access credit. Therefore, this study recommends that financial institutions such as banks and credit lending institutions invest more in artificial intelligence and machine learning to ensure that financially excluded households can obtain credit.
Spatiotemporal Dynamic of COVID-19 Diffusion in China: A Dynamic Spatial Autoregressive Model Analysis
Authors: Yu Hanchen , Li Jingwei , Bardin Sarah , Gu Hengyu , Fan Chenjing
Published: July 2021

COVID-19 has seriously threatened people’s health and well-being across the globe since it was first reported in Wuhan, China in late 2019. This study investigates the mechanism of COVID-19 transmission in different periods within and between cities in China to better understand the nature of the outbreak. We use Moran’s I, a measure of spatial autocorrelation, to examine the spatial dependency of COVID-19 and a dynamic spatial autoregressive model to explore the transmission mechanism. We find that the spatial dependency of COVID-19 decreased over time and that the transmission of the disease could be divided into three distinct stages: an eruption stage, a stabilization stage, and a declination stage. The infection rate between cities was close to one-third of the infection rate within cities at the eruption stage, while it reduced to zero at the declination stage. We also find that the infection rates within cities at the eruption stage and declination stage were similar. China’s policies for controlling the spread of the epidemic, specifically with respect to limiting inter-city mobility and implementing intra-city travel restrictions (social isolation), were most effective in reducing the viral transmission of COVID-19. The findings from this study indicate that the elimination of inter-city mobility had the largest impact on controlling disease transmission.
Antiradical Properties of N-Oxide Surfactants—Two in One
Authors: Lewińska Agnieszka , Kulbacka Julita , Domżał-Kędzia Marta , Witwicki Maciej
Published: July 2021

Surfactants are molecules that lower surface or interfacial tension, and thus they are broadly used as detergents, wetting agents, emulsifiers, foaming agents, or dispersants. However, for modern applications, substances that can perform more than one function are desired. In this study we evaluated antioxidant properties of two homological series of N-oxide surfactants: monocephalic 3-(alkanoylamino)propyldimethylamine-N-oxides and dicephalic N,N-bis[3,3′-(dimethylamino)propyl]alkylamide di-N-oxides. Their antiradical properties were tested against stable radicals using electron paramagnetic resonance (EPR) and UV-vis spectroscopy. The experimental investigation was supported by theoretical density functional theory (DFT) and ab initio modeling of the X–H bonds dissociation enthalpies, ionization potentials, and Gibbs free energies for radical scavenging reactions. The evaluation was supplemented with a study of biological activity. We found that the mono- and di-N-oxides are capable of scavenging reactive radicals; however, the dicephalic surfactants are more efficient than their linear analogues.
Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer
Authors: Huang Ching-Wen , Chen Yen-Cheng , Yin Tzu-Chieh , Chen Po-Jung , Chang Tsung-Kun , Su Wei-Chih , Ma Cheng-Jen , Li Ching-Chun , Tsai Hsiang-Lin , Wang Jaw-Yuan
Published: July 2021

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-–5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal–epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.
Blue Light Improves Photosynthetic Performance during Healing and Acclimatization of Grafted Watermelon Seedlings
Authors: Moosavi-Nezhad Moein , Salehi Reza , Aliniaeifard Sasan , Tsaniklidis Georgios , Woltering Ernst J. , Fanourakis Dimitrios , Żuk-Gołaszewska Krystyna , Kalaji Hazem M.
Published: July 2021

To investigate the importance of light on healing and acclimatization, in the present study, grafted watermelon seedlings were exposed to darkness (D) or light, provided by blue (B), red (R), a mixture of R (68%) and B (RB), or white (W; 35% B, 49% intermediate spectra, 16% R) LEDs for 12 days. Survival ratio, root and shoot growth, soluble carbohydrate content, photosynthetic pigments content, and photosynthetic performance were evaluated. Seedling survival was not only strongly limited in D but the survived seedlings had an inferior shoot and root development, reduced chlorophyll content, and attenuated photosynthetic efficiency. RB-exposed seedlings had a less-developed root system. R-exposed seedlings showed leaf epinasty, and had the smallest leaf area, reduced chlorophyll content, and suppressed photosynthetic apparatus performance. The R-exposed seedlings contained the highest amount of soluble carbohydrate and together with D-exposed seedlings the lowest amount of chlorophyll in their scions. B-exposed seedlings showed the highest chlorophyll content and improved overall PSII photosynthetic functioning. W-exposed seedling had the largest leaf area, and closely resembled the photosynthetic properties of RB-exposed seedlings. We assume that, during healing of grafted seedlings monochromatic R light should be avoided. Instead, W and monochromatic B light may be willingly adopted due to their promoting effect on shoot, pigments content, and photosynthetic efficiency.
Reduced Placental CD24 in Preterm Preeclampsia Is an Indicator for a Failure of Immune Tolerance
Authors: Sammar Marei , Siwetz Monika , Meiri Hamutal , Sharabi-Nov Adi , Altevogt Peter , Huppertz Berthold
Published: July 2021

Introduction: CD24 is a mucin-like glycoprotein expressed at the surface of hematopoietic and tumor cells and was recently shown to be expressed in the first trimester placenta. As it was postulated as an immune suppressor, CD24 may contribute to maternal immune tolerance to the growing fetus. Preeclampsia (PE), a major pregnancy complication, is linked to reduced immune tolerance. Here, we explored the expression of CD24 in PE placenta in preterm and term cases. Methods: Placentas were derived from first and early second trimester social terminations (N = 43), and third trimester normal term delivery (N = 67), preterm PE (N = 18), and preterm delivery (PTD) (N = 6). CD24 expression was determined by quantitative polymerase chain reaction (qPCR) and Western blotting. A smaller cohort included 3–5 subjects each of term and early PE, and term and preterm delivery controls analyzed by immunohistochemistry. Results: A higher expression (2.27-fold) of CD24 mRNA was determined in the normal term delivery compared to first and early second trimester cases. The mRNA of preterm PE cases was only higher by 1.31-fold compared to first and early second trimester, while in the age-matched PTD group had a fold increase of 5.72, four times higher compared to preterm PE. The delta cycle threshold (ΔCt) of CD24 mRNA expression in the preterm PE group was inversely correlated with gestational age (r = 0.737) and fetal size (r = 0.623), while correlation of any other group with these parameters was negligible. Western blot analysis revealed that the presence of CD24 protein in placental lysate of preterm PE was significantly reduced compared to term delivery controls (p = 0.026). In immunohistochemistry, there was a reduction of CD24 staining in villous trophoblast in preterm PE cases compared to gestational age-matched PTD cases (p = 0.042). Staining of PE cases at term was approximately twice higher compared to preterm PE cases (p = 0.025) but not different from normal term delivery controls. Conclusion: While higher CD24 mRNA expression levels were determined for normal term delivery compared to earlier pregnancy stages, this expression level was found to be lower in preterm PE cases, and could be said to be linked to reduced immune tolerance in preeclampsia.
Cardiac-Specific Overexpression of ERRγ in Mice Induces Severe Heart Dysfunction and Early Lethality
Authors: Lasheras Jaime , Pardo Rosario , Velilla Marc , Poncelas Marcos , Salvatella Núria , Simó Rafael , Ruiz-Meana Marisol , Zamora Mònica , Villena Josep A.
Published: July 2021

Proper cardiac function depends on the coordinated expression of multiple gene networks related to fuel utilization and mitochondrial ATP production, heart contraction, and ion transport. Key transcriptional regulators that regulate these gene networks have been identified. Among them, estrogen-related receptors (ERRs) have emerged as crucial modulators of cardiac function by regulating cellular metabolism and contraction machinery. Consistent with this role, lack of ERRα or ERRγ results in cardiac derangements that lead to functional maladaptation in response to increased workload. Interestingly, metabolic inflexibility associated with diabetic cardiomyopathy has been recently associated with increased mitochondrial fatty acid oxidation and expression of ERRγ, suggesting that sustained expression of this nuclear receptor could result in a cardiac pathogenic outcome. Here, we describe the generation of mice with cardiac-specific overexpression of ERRγ, which die at young ages due to heart failure. ERRγ transgenic mice show signs of dilated cardiomyopathy associated with cardiomyocyte hypertrophy, increased cell death, and fibrosis. Our results suggest that ERRγ could play a role in mediating cardiac pathogenic responses.
High-Fat Diet Impairs Mouse Median Eminence: A Study by Transmission and Scanning Electron Microscopy Coupled with Raman Spectroscopy
Authors: Severi Ilenia , Fosca Marco , Colleluori Georgia , Marini Federico , Imperatori Luca , Senzacqua Martina , Di Vincenzo Angelica , Barbatelli Giorgio , Fiori Fabrizio , Rau Julietta V. , Giordano Antonio
Published: July 2021

Hypothalamic dysfunction is an initial event following diet-induced obesity, primarily involving areas regulating energy balance such as arcuate nucleus (Arc) and median eminence (ME). To gain insights into the early hypothalamic diet-induced alterations, adult CD1 mice fed a high-fat diet (HFD) for 6 weeks were studied and compared with normo-fed controls. Transmission and scanning electron microscopy and histological staining were employed for morphological studies of the ME, while Raman spectroscopy was applied for the biochemical analysis of the Arc-ME complex. In HFD mice, ME β2-tanycytes, glial cells dedicated to blood-liquor crosstalk, exhibited remarkable ultrastructural anomalies, including altered alignment, reduced junctions, degenerating organelles, and higher content of lipid droplets, lysosomes, and autophagosomes. Degenerating tanycytes also displayed an electron transparent cytoplasm filled with numerous vesicles, and they were surrounded by dilated extracellular spaces extending up to the subependymal layer. Consistently, Raman spectroscopy analysis of the Arc-ME complex revealed higher glycogen, collagen, and lipid bands in HFD mice compared with controls, and there was also a higher band corresponding to the cyanide group in the former compared to the last. Collectively, these data show that ME β2-tanycytes exhibit early structural and chemical alterations due to HFD and reveal for the first-time hypothalamic cyanide presence following high dietary lipids consumption, which is a novel aspect with potential implications in the field of obesity.
Coordination Complexes as a New Generation Photosensitizer for Photodynamic Anticancer Therapy
Authors: Pobłocki Kacper , Drzeżdżon Joanna , Kostrzewa Tomasz , Jacewicz Dagmara
Published: July 2021

Photodynamic therapy (PDT) has become an alternative to standard cancer treatment methods such as surgery, chemotherapy and radiotherapy. The uniqueness of this method relies on the possibility of using various photosensitizers (PS) that absorb and convert light emission in radical oxygen-derived species (ROS). They can be present alone or in the presence of other compounds such as metal organic frameworks (MOFs), non-tubules or polymers. The interaction between DNA and metal-based complexes plays a key role in the development of new anti-cancer drugs. The use of coordination compounds in PDT has a significant impact on the amount ROS generated, quantum emission efficiency (Φem) and phototoxic index (PI). In this review, we will attempt to systematically review the recent literature and analyze the coordination complexes used as PS in PDT. Finally, we compared the anticancer activities of individual coordination complexes and discuss future perspectives. So far, only a few articles link so many transition metal ion coordination complexes of varying degrees of oxidation, which is why this review is needed by the scientific community to further expand this field worldwide. Additionally, it serves as a convenient collection of important, up-to-date information.
Brillouin Spectroscopy: From Biomedical Research to New Generation Pathology Diagnosis
Authors: Rioboó Rafael J. Jiménez , Gontán Nuria , Sanderson Daniel , Desco Manuel , Gómez-Gaviro Maria Victoria
Published: July 2021

Brillouin spectroscopy has recently gained considerable interest within the biomedical field as an innovative tool to study mechanical properties in biology. The Brillouin effect is based on the inelastic scattering of photons caused by their interaction with thermodynamically driven acoustic modes or phonons and it is highly dependent on the material’s elasticity. Therefore, Brillouin is a contactless, label-free optic approach to elastic and viscoelastic analysis that has enabled unprecedented analysis of ex vivo and in vivo mechanical behavior of several tissues with a micrometric resolution, paving the way to a promising future in clinical diagnosis. Here, we comprehensively review the different studies of this fast-moving field that have been performed up to date to provide a quick guide of the current literature. In addition, we offer a general view of Brillouin’s biomedical potential to encourage its further development to reach its implementation as a feasible, cost-effective pathology diagnostic tool.
Dieckol Attenuated Glucocorticoid-Induced Muscle Atrophy by Decreasing NLRP3 Inflammasome and Pyroptosis
Authors: Oh Seyeon , Yang Jinyoung , Park Chulhyun , Son Kukhui , Byun Kyunghee
Published: July 2021

Dexamethasone (Dexa), frequently used as an anti-inflammatory agent, paradoxically leads to muscle inflammation and muscle atrophy. Receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) lead to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome formation through nuclear factor-κB (NF-κB) upregulation. NLRP3 inflammasome results in pyroptosis and is associated with the Murf-1 and atrogin-1 upregulation involved in protein degradation and muscle atrophy. The effects of Ecklonia cava extract (ECE) and dieckol (DK) on attenuating Dexa-induced muscle atrophy were evaluated by decreasing NLRP3 inflammasome formation in the muscles of Dexa-treated animals. The binding of AGE or high mobility group protein 1 to RAGE or TLR4 was increased by Dexa but significantly decreased by ECE or DK. The downstream signaling pathways of RAGE (c-Jun N-terminal kinase or p38) were increased by Dexa but decreased by ECE or DK. NF-κB, downstream of RAGE or TLR4, was increased by Dexa but decreased by ECE or DK. The NLRP3 inflammasome component (NLRP3 and apoptosis-associated speck-like), cleaved caspase -1, and cleaved gasdermin D, markers of pyroptosis, were increased by Dexa but decreased by ECE and DK. Interleukin-1β/Murf-1/atrogin-1 expression was increased by Dexa but restored by ECE or DK. The mean muscle fiber cross-sectional area and grip strength were decreased by Dexa but restored by ECE or DK. In conclusion, ECE or DK attenuated Dexa-induced muscle atrophy by decreasing NLRP3 inflammasome formation and pyroptosis.
N-Glycomics of Human Erythrocytes
Authors: Bua Rosaria Ornella , Messina Angela , Sturiale Luisa , Barone Rita , Garozzo Domenico , Palmigiano Angelo
Published: July 2021

Glycosylation is a complex post-translational modification that conveys functional diversity to glycoconjugates. Cell surface glycosylation mediates several biological activities such as induction of the intracellular signaling pathway and pathogen recognition. Red blood cell (RBC) membrane N-glycans determine blood type and influence cell lifespan. Although several proteomic studies have been carried out, the glycosylation of RBC membrane proteins has not been systematically investigated. This work aims at exploring the human RBC N-glycome by high-sensitivity MALDI-MS techniques to outline a fingerprint of RBC N-glycans. To this purpose, the MALDI-TOF spectra of healthy subjects harboring different blood groups were acquired. Results showed the predominant occurrence of neutral and sialylated complex N-glycans with bisected N-acetylglucosamine and core- and/or antennary fucosylation. In the higher mass region, these species presented with multiple N-acetyllactosamine repeating units. Amongst the detected glycoforms, the presence of glycans bearing ABO(H) antigens allowed us to define a distinctive spectrum for each blood group. For the first time, advanced glycomic techniques have been applied to a comprehensive exploration of human RBC N-glycosylation, providing a new tool for the early detection of distinct glycome changes associated with disease conditions as well as for understanding the molecular recognition of pathogens.
Manufacturing of 3D-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations
Authors: Ballacchino Giulia , Weaver Edward , Mathew Essyrose , Dorati Rossella , Genta Ida , Conti Bice , Lamprou Dimitrios A.
Published: July 2021

Microfluidic technique has emerged as a promising tool for the production of stable and monodispersed nanoparticles (NPs). In particular, this work focuses on liposome production by microfluidics and on factors involved in determining liposome characteristics. Traditional fabrication techniques for microfluidic devices suffer from several disadvantages, such as multistep processing and expensive facilities. Three-dimensional printing (3DP) has been revolutionary for microfluidic device production, boasting facile and low-cost fabrication. In this study, microfluidic devices with innovative micromixing patterns were developed using fused deposition modelling (FDM) and liquid crystal display (LCD) printers. To date, this work is the first to study liposome production using LCD-printed microfluidic devices. The current study deals with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes with cholesterol (2:1) prepared using commercial and 3D-printed microfluidic devices. We evaluated the effect of microfluidic parameters, chip manufacturing, material, and channel design on liposomal formulation by analysing the size, PDI, and ζ-potential. Curcumin exhibits potent anticancer activity and it has been reported that curcumin-loaded liposomes formulated by microfluidics show enhanced encapsulation efficiency when compared with other reported systems. In this work, curcumal liposomes were produced using the developed microfluidic devices and particle sizing, ζ-potential, encapsulation efficiency, and in vitro release studies were performed at 37 °C.
Plasma Exosome Profile in ST-Elevation Myocardial Infarction Patients with and without Out-of-Hospital Cardiac Arrest
Authors: Zarà Marta , Campodonico Jeness , Cosentino Nicola , Biondi Maria Luisa , Amadio Patrizia , Milanesi Gloria , Assanelli Emilio , Cerri Silvia , Biggiogera Marco , Sandrini Leonardo , Tedesco Calogero Claudio , Veglia Fabrizio , Trabattoni Daniela , Blandini Fabio , Tremoli Elena , Marenzi Giancarlo , Barbieri Silvia S.
Published: July 2021

The identification of new biomarkers allowing an early and more accurate characterization of patients with ST-segment elevation myocardial infarction (STEMI) is still needed, and exosomes represent an attractive diagnostic tool in this context. However, the characterization of their protein cargo in relation to cardiovascular clinical manifestation is still lacking. To this end, 35 STEMI patients (17 experiencing resuscitated out-of-hospital cardiac arrest (OHCA-STEMI) and 18 uncomplicated) and 32 patients with chronic coronary syndrome (CCS) were enrolled. Plasma exosomes were characterized by the nanoparticle tracking analysis and Western blotting. Exosomes from STEMI patients displayed a higher concentration and size and a greater expression of platelet (GPIIb) and vascular endothelial (VE-cadherin) markers, but a similar amount of cardiac troponin compared to CCS. In addition, a difference in exosome expression of acute-phase proteins (ceruloplasmin, transthyretin and fibronectin) between STEMI and CCS patients was found. GPIIb and brain-associated marker PLP1 accurately discriminated between OHCA and uncomplicated STEMI. In conclusion, the exosome profile of STEMI patients has peculiar features that differentiate it from that of CCS patients, reflecting the pathophysiological mechanisms involved in STEMI. Additionally, the exosome expression of brain- and platelet-specific markers might allow the identification of patients experiencing ischemic brain injury in STEMI.
Photoreceptor Compartment-Specific TULP1 Interactomes
Authors: Ebke Lindsey A. , Sinha Satyabrata , Pauer Gayle J. T. , Hagstrom Stephanie A.
Published: July 2021

Photoreceptors are highly compartmentalized cells with large amounts of proteins synthesized in the inner segment (IS) and transported to the outer segment (OS) and synaptic terminal. Tulp1 is a photoreceptor-specific protein localized to the IS and synapse. In the absence of Tulp1, several OS-specific proteins are mislocalized and synaptic vesicle recycling is impaired. To better understand the involvement of Tulp1 in protein trafficking, our approach in the current study was to physically isolate Tulp1-containing photoreceptor compartments by serial tangential sectioning of retinas and to identify compartment-specific Tulp1 binding partners by immunoprecipitation followed by liquid chromatography tandem mass spectrometry. Our results indicate that Tulp1 has two distinct interactomes. We report the identification of: (1) an IS-specific interaction between Tulp1 and the motor protein Kinesin family member 3a (Kif3a), (2) a synaptic-specific interaction between Tulp1 and the scaffold protein Ribeye, and (3) an interaction between Tulp1 and the cytoskeletal protein microtubule-associated protein 1B (MAP1B) in both compartments. Immunolocalization studies in the wild-type retina indicate that Tulp1 and its binding partners co-localize to their respective compartments. Our observations are compatible with Tulp1 functioning in protein trafficking in multiple photoreceptor compartments, likely as an adapter molecule linking vesicles to molecular motors and the cytoskeletal scaffold.
CD39 Regulation and Functions in T Cells
Authors: Timperi Eleonora , Barnaba Vincenzo
Published: July 2021

CD39 is an enzyme which is responsible, together with CD73, for a cascade converting adenosine triphosphate into adenosine diphosphate and cyclic adenosine monophosphate, ultimately leading to the release of an immunosuppressive form of adenosine in the tumor microenvironment. Here, we first review the environmental and genetic factors shaping CD39 expression. Second, we report CD39 functions in the T cell compartment, highlighting its role in regulatory T cells, conventional CD4+ T cells and CD8+ T cells. Finally, we compile a list of studies, from preclinical models to clinical trials, which have made essential contributions to the discovery of novel combinatorial approaches in the treatment of cancer.
Bifidobacterium bifidum Enhances the Intestinal Epithelial Tight Junction Barrier and Protects against Intestinal Inflammation by Targeting the Toll-like Receptor-2 Pathway in an NF-κB-Independent Manner
Authors: Al-Sadi Rana , Dharmaprakash Viszwapriya , Nighot Prashant , Guo Shuhong , Nighot Meghali , Do Toan , Ma Thomas Y.
Published: July 2021

Defective intestinal tight junction (TJ) barrier is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). To date, there are no effective therapies that specifically target the intestinal TJ barrier. Among the various probiotic bacteria, Bifidobacterium, is one of the most widely studied to have beneficial effects on the intestinal TJ barrier. The main purpose of this study was to identify Bifidobacterium species that cause a sustained enhancement in the intestinal epithelial TJ barrier and can be used therapeutically to target the intestinal TJ barrier and to protect against or treat intestinal inflammation. Our results showed that Bifidobacterium bifidum caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The Bifidobacterium bifidum effect on TJ barrier was strain-specific, and only the strain designated as BB1 caused a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier required live bacterial cell/enterocyte interaction and was mediated by the BB1 attachment to Toll-like receptor-2 (TLR-2) at the apical membrane surface. The BB1 enhancement of the intestinal epithelial TJ barrier function was mediated by the activation of the p38 kinase pathway, but not the NF-κB signaling pathway. Moreover, the BB1 caused a marked enhancement in mouse intestinal TJ barrier in a TLR-2-dependent manner and protected against dextran sodium sulfate (DSS)-induced increase in mouse colonic permeability, and treated the DSS-induced colitis in a TJ barrier-dependent manner. These studies show that probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway.
LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells
Authors: Laurentino Talita de S. , Soares Roseli da S. , Lerario Antonio M. , Marie Suely K. N. , Oba-Shinjo Sueli M.
Published: July 2021

Lysyl oxidase-like 3 (LOXL3), belonging to the lysyl oxidase family, is responsible for the crosslinking in collagen or elastin. The cellular localization of LOXL3 is in the extracellular space by reason of its canonical function. In tumors, the presence of LOXL3 has been associated with genomic stability, cell proliferation, and metastasis. In silico analysis has shown that glioblastoma was among tumors with the highest LOXL3 expression levels. LOXL3 silencing of U87MG cells by siRNA led to the spreading of the tumor cell surface, and the transcriptome analysis of these cells revealed an upregulation of genes coding for extracellular matrix, cell adhesion, and cytoskeleton components, convergent to an increase in cell adhesion and a decrease in cell invasion observed in functional assays. Significant correlations of LOXL3 expression with genes coding for tubulins were observed in the mesenchymal subtype in the TCGA RNA-seq dataset of glioblastoma (GBM). Conversely, genes involved in endocytosis and lysosome formation, along with MAPK-binding proteins related to focal adhesion turnover, were downregulated, which may corroborate the observed decrease in cell viability and increase in the rate of cell death. Invasiveness is a major determinant of the recurrence and poor outcome of GBM patients, and downregulation of LOXL3 may contribute to halting the tumor cell invasion.
Coming from the Wild: Multidrug Resistant Opportunistic Pathogens Presenting a Primary, Not Human-Linked, Environmental Habitat
Authors: Sanz-García Fernando , Gil-Gil Teresa , Laborda Pablo , Ochoa-Sánchez Luz E. , Martínez José L. , Hernando-Amado Sara
Published: July 2021

The use and misuse of antibiotics have made antibiotic-resistant bacteria widespread nowadays, constituting one of the most relevant challenges for human health at present. Among these bacteria, opportunistic pathogens with an environmental, non-clinical, primary habitat stand as an increasing matter of concern at hospitals. These organisms usually present low susceptibility to antibiotics currently used for therapy. They are also proficient in acquiring increased resistance levels, a situation that limits the therapeutic options for treating the infections they cause. In this article, we analyse the most predominant opportunistic pathogens with an environmental origin, focusing on the mechanisms of antibiotic resistance they present. Further, we discuss the functions, beyond antibiotic resistance, that these determinants may have in the natural ecosystems that these bacteria usually colonize. Given the capacity of these organisms for colonizing different habitats, from clinical settings to natural environments, and for infecting different hosts, from plants to humans, deciphering their population structure, their mechanisms of resistance and the role that these mechanisms may play in natural ecosystems is of relevance for understanding the dissemination of antibiotic resistance under a One-Health point of view.
A Novel Genetic Variant in the WFS1 Gene in a Patient with Partial Uniparental Mero-Isodisomy of Chromosome 4
Authors: Delvecchio Maurizio , Ortolani Federica , Palumbo Orazio , Aloi Concetta , Salina Alessandro , Susca Francesco Claudio , Palumbo Pietro , Carella Massimo , Resta Nicoletta , Piccinno Elvira
Published: July 2021

Wolfram syndrome is a rare autosomal recessive disorder characterized by optic atrophy and diabetes mellitus. Wolfram syndrome type 1 (WFS1) is caused by bi-allelic pathogenic variations in the wolframin gene. We described the first case of WFS1 due to a maternal inherited mutation with uniparental mero-isodisomy of chromosome 4. Diabetes mellitus was diagnosed at 11 years of age, with negative anti-beta cells antibodies. Blood glucose control was optimal with low insulin requirement. No pathogenic variations in the most frequent gene causative of maturity-onset diabetes of the young subtypes were detected. At 17.8 years old, a rapid reduction in visual acuity occurred. Genetic testing revealed the novel homozygous variant c.1369A>G; p.Arg457Gly in the exon 8 of wolframin gene. It was detected in a heterozygous state only in the mother while the father showed a wild type sequence. In silico disease causing predictions performed by Polyphen2 classified it as “likely damaging”, while Mutation Tester and Sift suggested it was “polymorphism” and “tolerated”, respectively. High resolution SNP-array analysis was suggestive of segmental uniparental disomy on chromosome 4. In conclusion, to the best of our knowledge, we describe the first patient with partial uniparental mero-isodisomy of chromosome 4 carrying a novel mutation in the wolframin gene. The clinical phenotype observed in the patient and the analysis performed suggest that the genetic variant detected is pathogenetic.
Effects of Dihydrotanshinone I on Proliferation and Invasiveness of Paclitaxel-Resistant Anaplastic Thyroid Cancer Cells
Authors: Allegri Lorenzo , Capriglione Francesca , Maggisano Valentina , Damante Giuseppe , Baldan Federica
Published: July 2021

ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono- or combined chemotherapy, which is often not fully effective for the appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches for this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel and investigated the characteristics of these cells by analyzing the profile of gene expression and comparing it with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-κB compared to sensitive cells. DHT treatment resulted in a reduction of viability and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-κB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro.