bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Linkages between BMI, Body Image, and SATAQ among Young Asian Females
Authors: Hsu Jane Lu , Hung Rainbow Tsai-Ling , Antoine Melchior
Published: July 2021

Sociocultural attitudes toward appearance and its linkage to body mass index (BMI) and body image is a relationship worth studying, especially in Asia, where the idealization of thinness can be prominent. The Sociocultural Attitudes Toward Appearance Questionnaire (SATAQ) developed by Heinberg et al. in 1995 was used in this study to examine whether these beliefs have been internalized. Furthermore, the Body Esteem Scale (BES) was used to quantify body image. The formal in-person survey was administered in Taipei, Taiwan. There were 301 valid samples out of 330 surveyed respondents. To enhance the representativeness of the samples, a stratified sampling technique was applied to generate survey data with valid samples following gender and age distributions of the population between the ages of 14 and 28. The internalization dimension represented how strongly the respondents considered the importance of the socially accepted concept of appearance based on personal perceived social norms. The other dimension, awareness, represented the sociocultural pressures from the outside world, such as from the image of slimness illustrated in the media or group, in comparison to personal beliefs. Our results demonstrated that respondents with above-normal BMIs internalized the socially preferred standards of thinness more than respondents with normal or under-normal BMIs. Furthermore, results also revealed, overall, a negative relationship between SATAQ and body image and between body image and BMI. The study highlights the need to emphasize “fitness over thinness” to help improve negative body image among young Asian females.
High Performance of Biohydrogen Production in Packed-Filter Bioreactor via Optimizing Packed-Filter Position
Authors: Chu Chen-Yeon , Zheng Jin-Long , Chen Tsung-Hsien , Bhuyar Prakash
Published: July 2021

In this present investigation, a packed-filter bioreactor was employed to produce hydrogen utilizing an expired soft drink as a substrate. The effects of feeding substrate concentrations ranging from 19.51, 10.19, 5.34, 3.48, to 2.51 g total sugar/L were examined, and the position of the packed filter installed in the bioreactor at dimensionless heights (h/H) of 1/4, 2/4, 3/4, and 4/4 was studied. The results revealed that with a substrate concentration of 20 g total sugar/L and a hydraulic retention time (HRT) of 1 h, a packed filter placed at the half-height position of the bioreactor (h/H 2/4) has the optimal hydrogen production rate, hydrogen yield, and average biomass concentration in the bioreactor, resulting in 55.70 ± 2.42 L/L/d, 0.90 ± 0.06 mol H2/mol hexose, and 17.86 ± 1.09 g VSS/L. When feeding substrate concentrations varied from 20, 10, to 5 g total sugar/L with the packed-filter position at h/H 2/4, Clostridium sp., Clostridium tyrobutyricum, and Bifidobacterium crudilactis were the predominant bacteria community. Finally, it was discovered that the packed-filter bioreactor can produce stable hydrogen in high-strength organic effluent.
Classical and Neural Network Machine Learning to Determine the Risk of Marijuana Use
Authors: Zoboroski Laura , Wagner Torrey , Langhals Brent
Published: July 2021

Marijuana is the most commonly abused drug for military personnel tested at the Air Force Drug Testing Laboratory. A publicly available dataset of drug use, personality trait scores and demographic data was modeled with logistic regression, decision tree and neural network models to determine the extent to which marijuana use can be predicted using personality traits. While the logistic regression model had lower performance than the neural network model, it matched the sensitivity of prior work (0.80), achieved a high level of significance (p < 0.05) and yielded valuable inferences. It implied that younger, less educated individuals who exhibit sensation-seeking behavior and are open to experience tend to be at higher risk for THC use. A method for performing an iterative multidimensional neural network hyperparameter search is presented, and two iterations of a 6-dimensional search were performed. Metrics were used to select a family of 8 promising models from a cohort of 4600 models, and the best NN model’s 0.87 sensitivity improved upon the literature. The model met an f1 overfitting threshold on the test and holdout datasets, and an accuracy sensitivity analysis on a holdout-equivalent dataset yielded a 95% CI of 0.86 ± 0.04. These results have the potential to increase the efficacy of drug prevention and intervention programs.
Economic Evaluation of Mental Health Effects of Flooding Using Bayesian Networks
Authors: Sedighi Tabassom , Varga Liz , Hosseinian-Far Amin , Daneshkhah Alireza
Published: July 2021

The appraisal of appropriate levels of investment for devising flooding mitigation and to support recovery interventions is a complex and challenging task. Evaluation must account for social, political, environmental and other conditions, such as flood state expectations and local priorities. The evaluation method should be able to quickly identify evolving investment needs as the incidence and magnitude of flood events continue to grow. Quantification is essential and must consider multiple direct and indirect effects on flood related outcomes. The method proposed is this study is a Bayesian network, which may be used ex-post for evaluation, but also ex-ante for future assessment, and near real-time for the reallocation of investment into interventions. The particular case we study is the effect of flood interventions upon mental health, which is a gap in current investment analyses. Natural events such as floods expose people to negative mental health disorders including anxiety, distress and post-traumatic stress disorder. Such outcomes can be mitigated or exacerbated not only by state funded interventions, but by individual and community skills and experience. Success is also dampened when vulnerable and previously exposed victims are affected. Current measures evaluate solely the effectiveness of interventions to reduce physical damage to people and assets. This paper contributes a design for a Bayesian network that exposes causal pathways and conditional probabilities between interventions and mental health outcomes as well as providing a tool that can readily indicate the level of investment needed in alternative interventions based on desired mental health outcomes.
Arthroscopic Tenotomy of the Long Head of the Biceps Tendon and Section of the Anterior Joint Capsule Produce Moderate Osteoarthritic Changes in an Experimental Sheep Model
Authors: Longo Umile Giuseppe , Forriol Francisco , Candela Vincenzo , Tecce Salvatore Maria , De Salvatore Sergio , Altonaga Jose R. , Wallace Andrew L. , Denaro Vincenzo
Published: July 2021

Osteoarthritis (OA) of the glenohumeral (GH) joint is a common cause of shoulder pain, resulting in considerable invalidity. Unfortunately, the study of its pathogenesis is challenging. Models of OA are necessary to identify specific targets for therapy and to be able to interfere with the development and evolution of OA. This study aims to assess the effect of an arthroscopic tenotomy of the long head of the biceps tendon (LHBT) and section of the anterior glenohumeral joint capsule on the ovine glenohumeral joint. In addition, the authors aim to validate and evaluate the reliability of a modified semi-quantitative MRI score to assess joint degeneration in a sheep’s shoulder. Eight skeletally mature sheep received an arthroscopic tenotomy of the LHBT and section of the anterior joint capsule and were euthanized four months after surgery. All animals tolerated the surgery well, and no complication was recorded for six weeks. Moderate degenerative changes to the ovine shoulder joint were found on MRI and histological evaluation. The arthroscopic tenotomy of the LHBT and the anterior glenohumeral joint capsule section caused moderate degenerative changes to the ovine shoulder joint.
HIV/AIDS Awareness Among Young Adults in Hong Kong: The Roles of Knowledge, Acceptance and Stigma
Authors: Zhang Fan , Chung Louisa
Published: July 2021

In the past decade, HIV (Human Immunodeficiency Virus) infection risk and the prevalence of infected cases in the younger generation have increased in Hong Kong. To promote HIV prevention and control, it is critical to understand the situation of HIV-related knowledge, stigma, and awareness among the younger adults, especially college students. 810 college students (mean age = 20.63 ± 2.05) have participated in the current survey. In mediation pathway analysis, the results show that participants’ greater knowledge about HIV is associated with higher awareness, and this relationship is partially mediated by the knowledge-related increase in accepting attitudes toward the people with HIV, but not via reducing stigma. Our findings provide an updated profile of HIV-related knowledge, attitude and awareness among college students in Hong Kong. In addition, we have clarified the mediating role of acceptance in the relationship between knowledge and awareness and pinpointed the importance of knowledge education and workshops to promote acceptance of people with HIV. Insights were provided for tailoring health-promotion programs to reduce risky sex and prevent HIV infection on college campuses.
Effect of Infodemic Regarding the Illegal Sale of Medications on the Internet: Evaluation of Demand and Online Availability of Ivermectin during the COVID-19 Pandemic
Authors: Fittler András , Adeniye Latifat , Katz Zoltán , Bella Richárd
Published: July 2021

The COVID-19 pandemic and the related infodemic generated confusion and increased demand of various pharmaceuticals, ushering in the opportunity for illicit online vendors to fill a gap in the marketplace using potentially dangerous products. The aim of our study is to provide evidence regarding increased demand, online availability and consumer accessibility of ivermectin, an anthelmintic agent, without substantiated indications in reference to SARS-CoV-2. In our study, we combined infodemiology methodology aligned with search engine result assessment and website analytics to evaluate patient safety risks. Users’ Google queries regarding ivermectin were trending and peaked during the last week of November 2020 and March 2021. Consumers more likely found links leading directly or indirectly (via redirection) to illegal online retailers representing nearly half (53.3%) of search engine result links regarding the first three result pages in December 2020 and topped off at 73.3% by March 2021. Illicit medicine retailers outnumbered and outranked their legitimate counterparts and dominated the first search engine results page. A vast majority (77.7%) of the identified online pharmacies were characteristically rogue; more than half (55.5%) offered prescription-only products without a valid medical prescription. Our results illustrate connection between infodemic and its consequences on the illicit online pharmacy market
Mental Health Consequences of the Three Mile Island, Chernobyl, and Fukushima Nuclear Disasters: A Scoping Review
Authors: Oe Misari , Takebayashi Yui , Sato Hideki , Maeda Masaharu
Published: July 2021

Many individuals who were affected by the Great East Japan earthquake and tsunami and the subsequent Fukushima Daiichi Nuclear Power Plant accident continue to face a challenging recovery. We reviewed the long-term mental health consequences of three major nuclear power plant accidents: the Three Mile Island (TMI, 1979), Chernobyl (1986), and Fukushima (2011) nuclear disasters. We examined the relevant prospective cohort studies and before-and-after studies that covered more than two timepoints, searching four databases (PubMed, Ichushi, PsyArticles, and PTSDPub). We identified a total of 35 studies: TMI, n = 11; Chernobyl, n = 6; and Fukushima, n = 18. The smaller numbers of early-phase studies (within 6 months) of the Chernobyl and Fukushima disasters may also indicate the chaotic situation at those timepoints, as large-scale interviews were conducted in the early phase after the TMI disaster. Although the patterns of effects on mental health outcomes were diverse, more than half of the participants in the studies we evaluated were categorized into low or under-threshold symptom groups in all three disasters. Across the three disasters, the radiation exposure level estimated by the proximity and stigma were the common risk factors for mental health outcomes. Our findings will contribute to a comprehensive understanding of the impact of the worst nuclear accidents in history on the affected individuals’ mental health, and our results illustrate the longitudinal consequences of such disasters.
The Use of Fitness Testing to Predict Occupational Performance in Tactical Personnel: A Critical Review
Authors: Orr Robin , Sakurai Takato , Scott Jordan , Movshovich Jason , Dawes J. Jay , Lockie Robert , Schram Ben
Published: July 2021

Tactical personnel work in an occupation that involves tasks requiring a high level of cardiovascular fitness as well as muscular strength and endurance. The aim of this literature review was to identify and critique studies investigating the relationship between physical fitness, quantified by fitness assessment measures, and occupational task performance. Databases were searched for relevant articles which assessed a fitness measure and a measure of occupational performance. A total of 15 articles were included and were deemed to be of acceptable methodological quality (8.4/12 on the Critical Appraisal Skills Programme checklist). Included articles assessed a variety of fitness attributes and occupational tasks. Across tactical groups, there appear to be no standardized fitness tests that can determine occupational performance, with aerobic fitness, anaerobic fitness, strength, endurance, power, and agility all being associated with occupational task performance. A wide range of fitness assessments appears to be required to predict occupational performance within tactical personnel. Efforts should be made to base fitness assessments on occupational demands unique to both the environment and requirements of each individual tactical unit.
Identifying Behavior Change Techniques Used in Tobacco Cessation Interventions by Oral Health Professionals and Their Relation to Intervention Effects—A Review of the Scientific Literature
Authors: Moafa Ibtisam , Hoving Ciska , van den Borne Bart , Jafer Mohammed
Published: July 2021

This review aimed to identify the behavioral change techniques (BCTs) used in behavioral interventions for tobacco cessation at dental practices in relation to their effect on tobacco use. Six scientific databases were searched for behavior change interventions for tobacco cessation and were coded using the BCT taxonomy of behavioral support for smoking cessation (BCTTsm). Fifteen interventions were identified, and data related to intervention characteristics were abstracted. Sixteen BCTs were identified, mainly related to increased motivation and teaching regulatory skills. Goal setting was the most commonly used BCT. Ten out of fifteen interventions effectively impacted tobacco cessation outcomes (OR = 2 to 5.25). Effective interventions more frequently included goal setting, written materials, readiness to quit and ability assessment, tobacco-use assessment, self-efficacy boost, listing reasons for quitting, action planning and environment restructuring. Other BCTs were not clearly associated with an increased effect. Among the behavioral interventions, certain techniques were associated with successful tobacco quitting. Tobacco cessation interventions in a dental setting appear to benefit from using BCTs that increase motivation and teach regulatory skills. The identified BCTs in this review could provide a source to better inform researchers and dentists about the active ingredients in behavior change interventions for tobacco cessation in a dental setting.
Phase Angle and Bio-Impedance Values during the First Year after Delivery in Women with Previous Excessive Gestational Weight Gain: Innovative Data from the Belgian INTER-ACT Study
Authors: Bijlholt Margriet , Maslin Kate , Ameye Lieveke , Shawe Jill , Bogaerts Annick , Devlieger Roland
Published: July 2021

Phase angle (PhA) is a body composition parameter that measures changes in the amount and quality of soft tissue. Few studies have explored PhA in pregnancy or postpartum. The aim of this study was to explore the PhA during the first year postpartum in a Belgian cohort using data from the control group of the INTER-ACT study, an intervention trial targeting those with excess gestational weight gain. A secondary aim was to examine associations between PhA and potential explanatory variables. Women aged ≥18 with excessive weight gain in a singleton pregnancy and without a chronic disease were eligible. Data collection included anthropometry as well as demographic and lifestyle questionnaires at 6 weeks, 6 months and 12 months postpartum. Body composition, including PhA, was measured with the Tanita MC780SMA device. Data was analysed using correlation and mixed model analyses. A total of 509 participants (median age 31.2) were included. The median PhA at 6 weeks postpartum was 5.8°. Higher PhA values were seen in multiparous women (p = 0.02) but there was no association with any other lifestyle or demographic factors. PhA values were positively associated with muscle mass and BMI (r = 0.13, p = 0.004 and r = 0.18, p < 0.001) at 6 weeks postpartum. PhA increased slightly in the 12 months postpartum, which was related to a decrease in fat percentage (p = 0.004). Further research in the pregnant/postpartum population is needed to elucidate any links with perinatal or future health outcomes.
A Qualitative Study toward Technologies for Active and Healthy Aging: A Thematic Analysis of Perspectives among Primary, Secondary, and Tertiary End Users
Authors: Rampioni Margherita , Moșoi Adrian Alexandru , Rossi Lorena , Moraru Sorin-Aurel , Rosenberg Dan , Stara Vera
Published: July 2021

It is expected that, by 2050, people aged over 60 in 65 nations will constitute 30% of the total population. Healthy aging is at the top of the world political agenda as a possible means for hindering the collapse of care systems. How can ICT/sensing technology meet older people’s needs for active and healthy aging? This qualitative study carried out in Italy and Romania in 2020 involved 30 participants: older adults, caregivers, and stakeholders. Based on a user-centered design approach, this study aimed to understand which requirements of ICT/sensing technologies could match people’s needs of active and healthy aging. Findings highlighted that ICT/sensing technology needs to focus on six major themes: (1) learnability, (2) security, (3) independence, empowerment, and coaching values, (4) social isolation, (5) impact of habit, culture, and education variables, and (6) personalized solutions. These themes are consistent with the Active Aging framework and the factors that influence perceived usefulness and potential benefits among older adults. Consequently, this study shows how well-known, but still unresolved, issues affect the field of information and communication technologies (ICTs) to promote active and healthy aging. This suggests that the reinforcement of the public health system, especially considering the pandemic effect, requires a concrete and formidable effort from an interdisciplinary research network.
Bioinformatics Approach to Mitigate Mislabeling in EU Seafood Market and Protect Consumer Health
Authors: Vindigni Gabriella , Pulvirenti Alfredo , Alaimo Salvatore , Monaco Clara , Spina Daniela , Peri Iuri
Published: July 2021

Fisheries products are some of the most traded commodities world-wide and the potential for fraud is a serious concern. Fish fraud represents a threat to human health and poses serious concerns due to the consumption of toxins, highly allergenic species, contaminates or zoonotic parasites, which may be present in substituted fish. The substitution of more expensive fish by cheaper species, with similar morphological characteristics but different origins, reflects the need for greater transparency and traceability upon which which the security of the entire seafood value-chain depends. Even though EU regulations have made significant progress in consumer information by stringent labelling requirements, fraud is still widespread. Many molecular techniques such as DNA barcoding provide valuable support to enhance the Common Fisheries Policy (CFP) in the protection of consumer interests by unequivocally detecting any kind of fraud. This paper aims to highlight both the engagement of EU fishery policy and the opportunity offered by new biotechnology instruments to mitigate the growing fraud in the globalized fish market and to enforce the food security system to protect consumers’ health. In this paper, after a presentation of EU rules on fish labeling and a general overview on the current state of the global fish market, we discuss the public health implications and the opportunities offered by several techniques based on genetics, reporting a case study to show the efficacy of the DNA barcoding methodology in assessing fish traceability and identification, comparing different species of the Epinephelus genus, Mottled Grouper (Mycteroperca rubra) and Wreckfish (Polyprion americanus), often improperly sold with the commercial name of “grouper”.
Community-Level Participation in Volunteer Groups and Individual Depressive Symptoms in Japanese Older People: A Three-Year Longitudinal Multilevel Analysis Using JAGES Data
Authors: Tamura Motoki , Hattori Shinji , Tsuji Taishi , Kondo Katsunori , Hanazato Masamichi , Tsuno Kanami , Sakamaki Hiroyuki
Published: July 2021

Background: The current study aimed to investigate the contextual effect of volunteer group participation on subsequent depressive symptoms in older people. Methods: We analyzed the longitudinal data of 37,552 people aged 65 years and older in 24 municipalities surveyed in the Japan Gerontological Evaluation Study. Volunteer group participation of older people was assessed in 2013 by one question and depressive symptoms were assessed by the Geriatric Depression Scale 15 in 2016. To investigate a contextual effect, we aggregated individual-level volunteer group participation by each residence area as a community-level independent variable. We conducted a two-level multilevel Poisson regression analysis using the Random Intercepts and Fixed Slopes Model. Results: The average proportion of community-level volunteer group participation was 10.6%. The results of the Poisson regression analysis showed that community-level volunteer group participation reduced the risk for the onset of depressive symptoms by 13% with a 10 percentage point increase in participation, after adjusting for sex, age, population density, total annual sunshine hours and annual rainfall (incident rate ratio, 0.87; 95% confidence interval, 0.78–0.98). Conclusions: Older people living in areas with higher volunteer group participation had a lower risk of developing depressive symptoms regardless of whether or not they participated in a volunteer group.
Validation of an Attributional and Distributive Justice Mediational Model on the Effects of Surface Acting on Emotional Exhaustion: An Experimental Study
Authors: García-Romero Alejandro , Martinez-Iñigo David
Published: July 2021

Previous research has shown that surface acting—displaying an emotion that is dissonant with inner feelings—negatively impacts employees’ well-being. However, most studies have neglected the meaning that employees develop around emotional demands requiring surface acting. This study examined how employees’ responsibility attributions of client behavior demanding surface acting influence employees’ emotional exhaustion, and the mediational role of distributive justice in this relationship. Relying on Fairness Theory, it was expected that employees’ responsibility attributions of client behavior demanding emotion regulation would be related to their perceptions of distributive injustice during the service encounter, which in turn would mediate the effects of responsibility attribution on emotional exhaustion. In addition, drawing on the conservation of resources model, we contended that leader support would moderate the impact of distributive injustice on emotional exhaustion. Two scenario-based experiments were conducted. Study 1 (N = 187) manipulated the attribution of responsibility for emotional demands. The findings showed that distributive injustice and emotional exhaustion were higher when responsibility for the surface acting demands was attributed to the client. A bootstrapping mediational analysis confirmed employees’ attributions have an indirect effect on emotional exhaustion through distributive justice. Study 2 (N = 227) manipulated responsibility attribution and leader support. The leader support moderation effect was confirmed.
Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS)
Authors: Wacinski Piotr , Gadzinowski Mariusz , Dabrowski Wojciech , Szumilo Justyna , Wacinski Jakub , Oru Nathalie , Vicaut Eric , Czuczwar Stanislaw , Kocki Janusz , Basinska Teresa , Slomkowski Stanislaw
Published: July 2021

Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.
High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future
Authors: Julve Josep , Escolà-Gil Joan Carles
Published: July 2021

Epidemiological, clinical, and experimental studies have shown that low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with increased atherosclerotic cardiovascular disease (CVD) [...]
AMIDE v2: High-Throughput Screening Based on AutoDock-GPU and Improved Workflow Leading to Better Performance and Reliability
Authors: Darme Pierre , Dauchez Manuel , Renard Arnaud , Voutquenne-Nazabadioko Laurence , Aubert Dominique , Escotte-Binet Sandie , Renault Jean-Hugues , Villena Isabelle , Steffenel Luiz-Angelo , Baud Stéphanie
Published: July 2021

Molecular docking is widely used in computed drug discovery and biological target identification, but getting fast results can be tedious and often requires supercomputing solutions. AMIDE stands for AutoMated Inverse Docking Engine. It was initially developed in 2014 to perform inverse docking on High Performance Computing. AMIDE version 2 brings substantial speed-up improvement by using AutoDock-GPU and by pulling a total revision of programming workflow, leading to better performances, easier use, bug corrections, parallelization improvements and PC/HPC compatibility. In addition to inverse docking, AMIDE is now an optimized tool capable of high throughput inverse screening. For instance, AMIDE version 2 allows acceleration of the docking up to 12.4 times for 100 runs of AutoDock compared to version 1, without significant changes in docking poses. The reverse docking of a ligand on 87 proteins takes only 23 min on 1 GPU (Graphics Processing Unit), while version 1 required 300 cores to reach the same execution time. Moreover, we have shown an exponential acceleration of the computation time as a function of the number of GPUs used, allowing a significant reduction of the duration of the inverse docking process on large datasets.
The Glymphatic System (En)during Inflammation
Authors: Mogensen Frida Lind-Holm , Delle Christine , Nedergaard Maiken
Published: July 2021

The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation.
Optimization of Lyophilized Hyperacute Serum (HAS) as a Regenerative Therapeutic in Osteoarthritis
Authors: Olmos Calvo Isabel , Kuten-Pella Olga , Kramer Karina , Madár Ágnes , Takács Szilvia , Kardos Dorottya , Simon Diána , Erdö-Bonyár Szabina , Berki Timea , De Luna Andrea , Nehrer Stefan , Lacza Zsombor
Published: July 2021

Hyperacute serum (HAS) is a blood derivative product that promotes the proliferation of various cell types and controls inflammation in vitro. The aim of this study is to investigate the regenerative potential of different formulations of HAS, including lyophilized and hyaluronic acid combined versions, to obtain a stable and standardized therapeutic in osteoarthritis (OA), which may be able to overcome the variability limitations of platelet-rich plasma (PRP). Primary human osteoarthritic chondrocytes were used for testing cellular viability and gene expression of OA-related genes. Moreover, a co-culture of human explants of cartilage, bone and synovium under inflammatory conditions was used for investigating the inflammatory control capacities of the different therapeutics. In this study, one formulation of lyophilized HAS achieved the high cell viability rates of liquid HAS and PRP. Gene expression analysis showed that HAS induced higher Col1a1 expression than PRP. Cytokine quantification from supernatant fluids revealed that HAS treatment of inflamed co-cultures significantly reduced levels of IL-5, IL-15, IL-2, TNFα, IL-7 and IL-12. To conclude, lyophilized HAS is a stable and standardized therapeutic with high potential in joint regeneration.
Extension of Collagen Deposition in COVID-19 Post Mortem Lung Samples and Computed Tomography Analysis Findings
Authors: Ball Lorenzo , Barisione Emanuela , Mastracci Luca , Campora Michela , Costa Delfina , Robba Chiara , Battaglini Denise , Micali Marco , Costantino Federico , Cittadini Giuseppe , Patroniti Nicolò , Pelosi Paolo , Fiocca Roberto , Grillo Federica
Published: July 2021

Lung fibrosis has specific computed tomography (CT) findings and represents a common finding in advanced COVID-19 pneumonia whose reversibility has been poorly investigated. The aim of this study was to quantify the extension of collagen deposition and aeration in postmortem cryobiopsies of critically ill COVID-19 patients and to describe the correlations with qualitative and quantitative analyses of lung CT. Postmortem transbronchial cryobiopsy samples were obtained, formalin fixed, paraffin embedded and stained with Sirius red to quantify collagen deposition, defining fibrotic samples as those with collagen deposition above 10%. Lung CT images were analyzed qualitatively with a radiographic score and quantitatively with computer-based analysis at the lobe level. Thirty samples from 10 patients with COVID-19 pneumonia deceased during invasive mechanical ventilation were included in this study. The median [interquartile range] percent collagen extension was 6.8% (4.6–16.2%). In fibrotic compared to nonfibrotic samples, the qualitative score was higher (260 (250–290) vs. 190 (120–270), p = 0.036) while the gas fraction was lower (0.46 (0.32–0.47) vs. 0.59 (0.37–0.68), p = 0.047). A radiographic score above 230 had 100% sensitivity (95% confidence interval, CI: 66.4% to 100%) and 66.7% specificity (95% CI: 41.0% to 92.3%) to detect fibrotic samples, while a gas fraction below 0.57 had 100% sensitivity (95% CI: 66.4% to 100%) and 57.1% specificity (95% CI: 26.3% to 88.0%). In COVID-19 pneumonia, qualitative and quantitative analyses of lung CT images have high sensitivity but moderate to low specificity to detect histopathological fibrosis. Pseudofibrotic CT findings do not always correspond to increased collagen deposition.
Evasion of the Host Immune Response by Betaherpesviruses
Authors: Sausen Daniel , Reed Kirstin , Bhutta Maimoona , Gallo Elisa , Borenstein Ronen
Published: July 2021

The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. In this review, we will highlight the complex interplay between betaherpesviruses and the human immune response, focusing on protein function. We will explore methods by which the immune system first responds to betaherpesvirus infection as well as mechanisms by which viruses subvert normal cellular functions to evade the immune system and facilitate viral latency, persistence, and reactivation. Lastly, we will briefly discuss recent advances in vaccine technology targeting betaherpesviruses. This review aims to further elucidate the dynamic interactions between betaherpesviruses and the human immune system.
Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells
Authors: Huang Hai , Yi Jun-Koo , Lim Su-Geun , Park Sijun , Zhang Haibo , Kim Eungyung , Jang Soyoung , Lee Mee-Hyun , Liu Kangdong , Kim Ki-Rim , Kim Eun-Kyong , Lee Youngkyun , Kim Sung-Hyun , Ryoo Zae-Young , Kim Myoung Ok
Published: July 2021

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.
A Novel NFIX-STAT6 Gene Fusion in Solitary Fibrous Tumor: A Case Report
Authors: Moura David S. , Díaz-Martín Juan , Bagué Silvia , Orellana-Fernandez Ruth , Sebio Ana , Mondaza-Hernandez Jose L. , Salguero-Aranda Carmen , Rojo Federico , Hindi Nadia , Fletcher Christopher D. M. , Martin-Broto Javier
Published: July 2021

Solitary fibrous tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive tumors. The defining genetic driver alteration is the gene fusion NAB2–STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (signal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2–STAT6 gene fusion is required for the diagnostic confirmation of solitary fibrous tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated solitary fibrous tumor in the pelvis. Histopathologically, the neoplasm did not display nuclear pleomorphism or tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8–STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in solitary fibrous tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity.
Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9
Authors: Nigro Ersilia , Mallardo Marta , Polito Rita , Scialò Filippo , Bianco Andrea , Daniele Aurora
Published: July 2021

Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel’s formation, to candidate them as therapeutic targets.
Emerging Opportunities in Human Pluripotent Stem-Cells Based Assays to Explore the Diversity of Botulinum Neurotoxins as Future Therapeutics
Authors: Duchesne de Lamotte Juliette , Perrier Anselme , Martinat Cécile , Nicoleau Camille
Published: July 2021

Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and are responsible for botulism, a fatal disorder of the nervous system mostly induced by food poisoning. Despite being one of the most potent families of poisonous substances, BoNTs are used for both aesthetic and therapeutic indications from cosmetic reduction of wrinkles to treatment of movement disorders. The increasing understanding of the biology of BoNTs and the availability of distinct toxin serotypes and subtypes offer the prospect of expanding the range of indications for these toxins. Engineering of BoNTs is considered to provide a new avenue for improving safety and clinical benefit from these neurotoxins. Robust, high-throughput, and cost-effective assays for BoNTs activity, yet highly relevant to the human physiology, have become indispensable for a successful translation of engineered BoNTs to the clinic. This review presents an emerging family of cell-based assays that take advantage of newly developed human pluripotent stem cells and neuronal function analyses technologies.
Potential Application of Peppermint (Mentha piperita L.), German Chamomile (Matricaria chamomilla L.) and Yarrow (Achillea millefolium L.) as Active Fillers in Natural Rubber Biocomposites
Authors: Masłowski Marcin , Aleksieiev Andrii , Miedzianowska Justyna , Strzelec Krzysztof
Published: July 2021

In this study, peppermint (Mentha piperita L.), German chamomile (Matricaria chamomilla L.) and yarrow (Achillea millefolium L.) were applied as natural fibrous fillers to create biocomposites containing substances of plant origin. The purpose of the work was to investigate the activity and effectiveness of selected plants as a material for the modification of natural rubber composites. This research was the first approach to examine the usefulness of peppermint, German chamomile and yarrow in the field of polymer technology. Dried and ground plant particles were subjected to Fourier transmission infrared spectroscopy (FTIR) and UV–Vis spectroscopy, thermogravimetric analysis (TGA), goniometric measurements (contact angle) and scanning electron microscopy (SEM). The characterization of natural rubber composites filled with bio-additives was performed including rheometric measurements, FTIR, TGA, cross-linking density, mechanical properties and colour change after simulated aging processes. Composites filled with natural fillers showed improved barrier properties and mechanical strength. Moreover, an increase in the cross-linking density of the materials before and after the simulated aging processes, compared to the reference sample, was observed.
The Effect of Liposomal Curcumin as an Anti-Inflammatory Strategy on Lipopolysaccharide e from Porphyromonas gingivalis Treated Endothelial Committed Neural Crest Derived Stem Cells: Morphological and Molecular Mechanisms
Authors: Diomede Francesca , Fonticoli Luigia , Guarnieri Simone , Della Rocca Ylenia , Rajan Thangavelu Soundara , Fontana Antonella , Trubiani Oriana , Marconi Guya Diletta , Pizzicannella Jacopo
Published: July 2021

Curcumin, a yellow polyphenol extracted from the turmeric root is used as a diet supplement. It exhibits anti-inflammatory, antioxidant, and antitumor properties by modulating different intracellular mechanisms. Due to their low solubility in water, the curcumin molecules must be encapsulated into liposomes to improve the bioavailability and biomedical potential. For the periodontal tissue and systemic health, it is essential to regulate the local inflammatory response. In this study, the possible beneficial effect of liposomes loaded with curcumin (CurLIP) in neural crest-derived human periodontal ligament stem cells (hPDLSCs) and in endothelial-differentiated hPDLSCs (e-hPDLSCs) induced with an inflammatory stimulus (lipopolysaccharide obtained from Porphyromonas gingivalis, LPS-G) was evaluated. The CurLIP formulation exhibited a significant anti-inflammatory effect by the downregulation of Toll-like receptor-4 (TLR4)/Myeloid differentiation primary response 88 (MyD88)/nuclear factor kappa light chain enhancer of activated B cells (NFkB)/NLR Family Pyrin Domain Containing 3 (NLRP3)/Caspase-1/Interleukin (IL)-1β inflammation cascade and reactive oxygen species (ROS) formation. Moreover, the exposure to LPS-G caused significant alterations in the expression of epigenetic modifiers, such as DNA Methyltransferase 1 (DNMT1) and P300, while the CurLIP treatment showed physiological expression. Overall, our in vitro study provides novel mechanistic insights into the intracellular pathway exert by CurLIP in the regulation of inflammation and epigenetic modifications.
Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies
Authors: Wens Inez , Janssens Ibo , Derdelinckx Judith , Meena Megha , Willekens Barbara , Cools Nathalie
Published: July 2021

Currently, there is still no cure for multiple sclerosis (MS), which is an autoimmune and neurodegenerative disease of the central nervous system. Treatment options predominantly consist of drugs that affect adaptive immunity and lead to a reduction of the inflammatory disease activity. A broad range of possible cell-based therapeutic options are being explored in the treatment of autoimmune diseases, including MS. This review aims to provide an overview of recent and future advances in the development of cell-based treatment options for the induction of tolerance in MS. Here, we will focus on haematopoietic stem cells, mesenchymal stromal cells, regulatory T cells and dendritic cells. We will also focus on less familiar cell types that are used in cell therapy, including B cells, natural killer cells and peripheral blood mononuclear cells. We will address key issues regarding the depicted therapies and highlight the major challenges that lie ahead to successfully reverse autoimmune diseases, such as MS, while minimising the side effects. Although cell-based therapies are well known and used in the treatment of several cancers, cell-based treatment options hold promise for the future treatment of autoimmune diseases in general, and MS in particular.