bluuebunny/crossref_metadata_2025 huggingface dataset:
ENDS Flavor Preference by Menthol Cigarette Smoking Status among US Adults, 2018–2019
Authors: Rostron Brian L. , Chang Joanne T. , Chang Cindy M. , Jackson Rebecca A. , Ambrose Bridget K.
Published: December 2020

E-cigarette flavor preference may differ among smokers using e-cigarettes, but little information is available on preferences by menthol cigarette status. Using nationally representative data for US adults from the 2018–2019 Tobacco Use Supplement to the Current Population Survey, we analyzed e-cigarette flavor preference by menthol cigarette status and e-cigarette device type for dual-cigarette and e-cigarette users and e-cigarette users who had recently quit smoking by trying to switch to e-cigarettes (“switchers”). Approximately half (52.2%) of dual users of menthol cigarettes and e-cigarettes reported using menthol/mint-flavored e-cigarettes as did 41.4% of “switchers” who had smoked menthol cigarettes; exclusive menthol/mint flavor use was 13.1% for dual users and 21.3% for “switchers.” A similar proportion (45.1%) of dual users who smoked nonmenthol cigarettes used tobacco-flavored e-cigarettes, but only 26.7% of “switchers” who had smoked nonmenthol cigarettes used tobacco-flavored e-cigarettes. Approximately 60% of dual users and “switchers” used fruit/other flavors, regardless of menthol cigarette use. By device type, 63.9% of dual users of cartridge-based e-cigarettes and menthol cigarettes used menthol/mint-flavored e-cigarettes. Approximately 75% of dual users and 85% of “switchers” who used tank or mod systems used fruit/other flavors. Menthol cigarette smokers may be particularly likely to use menthol/mint e-cigarettes, and a majority of dual users and “switchers” used fruit/other flavors. These results can inform policy measures concerning flavored electronic nicotine delivery system products.
Reported Neighborhood Traffic and the Odds of Asthma/Asthma-Like Symptoms: A Cross-Sectional Analysis of a Multi-Racial Cohort of Children
Authors: Commodore Sarah , Ferguson Pamela L. , Neelon Brian , Newman Roger , Grobman William , Tita Alan , Pearce John , Bloom Michael S. , Svendsen Erik , Roberts James , Skupski Daniel , Sciscione Anthony , Palomares Kristy , Miller Rachel , Wapner Ronald , Vena John E. , Hunt Kelly J.
Published: December 2020

Asthma in children poses a significant clinical and public health burden. We examined the association between reported neighborhood traffic (a proxy for traffic-related air pollution) and asthma among 855 multi-racial children aged 4–8 years old who participated in the Environmental Influences on Child Health Outcomes (ECHO) cohort. We hypothesized that high neighborhood traffic density would be associated with the prevalence of asthma. Asthma/asthma-like symptoms (defined as current and/or past physician diagnosed asthma, past wheezing, or nighttime cough or wheezing in the past 12 months) was assessed by parental report. The relationship between neighborhood traffic and asthma/asthma-like symptoms was assessed using logistic regression. The prevalence of asthma/asthma-like symptoms among study participants was 23%, and 15% had high neighborhood traffic. Children with significant neighborhood traffic had a higher odds of having asthma/asthma-like symptoms than children without neighborhood traffic [adjusted OR = 2.01 (95% CI: 1.12, 3.62)] after controlling for child’s race-ethnicity, age, sex, maternal education, family history of asthma, play equipment in the home environment, public parks, obesity and prescribed asthma medication. Further characterization of neighborhood traffic is needed since many children live near high traffic zones and significant racial/ethnic disparities exist.
Within-Session Sequence of the Tennis Serve Training in Youth Elite Players
Authors: Fernandez-Fernandez Jaime , Moya-Ramon Manuel , Santos-Rosa Francisco Javier , Gantois Petrus , Nakamura Fábio Yuzo , Sanz-Rivas David , Granacher Urs
Published: December 2020

The influence of muscular fatigue on tennis serve performance within regular training sessions is unclear. Therefore, the aim of the present study was to examine the within-session sequence of the tennis serve in youth tennis. Twenty-five young male (14.9 ± 0.9 years) and female (14.5 ± 0.9 years) players participated in this within-subject crossover study, and they were randomly but sex-matched assigned to different training sequences (serve exercise before tennis training (BTS) or after tennis training (ATS)). Pre- and post-tests included serve velocity performance and accuracy, shoulder strength, and range-of-motion (ROM) performance (internal/external rotation). Results showed that after one week of serve training conducted following the ATS sequence, significant decreases were found in serve performance (e.g., speed and accuracy), with standardized differences ranging from d = 0.29 to 1.13, as well as the shoulder function (strength [d = 0.20 to 1.0] and ROM [d = 0.17 to 0.31]) in both female and male players, compared to the BTS sequence. Based on the present findings, it appears more effective to implement serve training before the regular tennis training in youth players. If applied after training, excessive levels of fatigue may cause shoulder imbalances that could be related to an increased injury risk.
Mapping Assessments Instruments for Headache Disorders against the ICF Biopsychosocial Model of Health and Disability
Authors: D'Amico Domenico , Tepper Stewart , Guastafierro Erika , Toppo Claudia , Leonardi Matilde , Grazzi Licia , Martelletti Paolo , Raggi Alberto
Published: December 2020

Headache disorders have a strong impact on sufferers’ lives. However, the “content” of assessment instruments addressing concepts, such as disability and quality of life (QoL), has not comprehensively been addressed. We searched SCOPUS for research papers in which outcome measures were used in adult populations of patients with migraine, tension-type headache (TTH), and cluster headache (CH). The content of single instruments was then mapped against the International Classification of Functioning, Disability, and Health. A total of 150 papers and 26 instruments were included: 15 addressed disability or impact, two addressed work-related difficulties, and nine addressed QoL. Few instruments were commonly used across the conditions and covered domains of functioning were impact on daily life activities, homework, school, and work-related tasks, leisure time, informal and family relations, pain, emotional difficulties, energy level, and impulse control. Most of the research is based on instruments that were developed for migraine, which is critical for CH, and the impact of headache disorders on work-related activities is poorly acknowledged. Further research is needed to expand the scope of headaches impact on daily life activities, and on environmental factors relevant to headache disorders to raise knowledge on the less represented areas, e.g., TTH impact.
Association of Health Utility Score with Physical Activity Outcomes in Stroke Survivors
Authors: Kanai Masashi , Izawa Kazuhiro P. , Kubo Hiroki , Nozoe Masafumi , Mase Kyoshi , Shimada Shinichi
Published: December 2020

Health-related quality of life (HRQoL) after stroke tends to vary across studies or across stages of stroke. It is useful to use the health utility score to compare HRQoL across studies. Physical activity after stroke also tends to vary similarly. The purpose of the present study was to determine associations between the health utility score and physical activity outcomes in stroke survivors. This cross-sectional study recruited stroke survivors who could ambulate outside, free of assistance. We assessed the health utility score with the EuroQoL 5-Dimension 3-Level questionnaire. The physical activity outcomes were the number of steps taken and duration of moderate-to-vigorous physical activity (MVPA) as measured with an accelerometer. Multiple linear regression analyses were used to determine whether the physical activity outcomes were independently associated with the health utility score. Fifty patients (age: 68.0 years; 40 men, 10 women) were included. Multiple linear regression analysis showed the health utility score to be significantly associated with the number of steps taken (β = 0.304, p = 0.035) but not with MVPA. This is the first study to examine the association between the health utility score and objectively measured physical activity in stroke survivors. Promoting physical activity especially by increasing the number of steps taken might be a priority goal in improving a patient’s health utility score after stroke.
Uncovering the Role of Different Instructional Designs When Learning Tactical Scenes of Play through Dynamic Visualizations: A Systematic Review
Authors: Rekik Ghazi , Belkhir Yosra , Jarraya Mohamed , Bouzid Mohamed Amine , Chen Yung-Sheng , Kuo Cheng-Deng
Published: December 2020

Dynamic visualizations such as videos or animations have been developed to exchange information that transforms over time across a broad range of professional/academic contexts. However, such visual tools may impose substantial demands on the learner’s cognitive resources that are very limited in current knowledge. Cognitive load theory has been used to improve learning from dynamic visualizations by providing different instructional designs to manage learner cognitive load. This paper reviews a series of experimental studies assessing the effects of certain instructional designs on learning of tactical scenes of play through dynamic visualizations. An electronic database search was performed on the Web of Science and PubMed/Medline databases from inception to July 2020 using a combination of relevant keywords. Manual searches were also made. The search was limited to English language. A total of 515 records were screened by two researchers using the Population/Intervention/Comparison/Outcome(s) (PICO) criteria. The quality and validity of the included studies were assessed using “QualSyst”. Learning indicators in students and/or players (male and female) at any age category and competitive level were considered. Eleven studies met the inclusion criteria for this review, which focused on the effects of four instructional designs (i.e., using static visualizations, employing sequential presentation, applying segmentation, and decreasing presentation speed) on learning various game systems through dynamic visualizations. These studies indicate that (i) the effectiveness of all instructional designs depend upon the level of learners’ expertise when learning soccer/Australian football scenes through animations/videos, (ii) the effectiveness of using static visualizations instead of animations/videos showing soccer/basketball scenes depend upon the type of the depicted knowledge (i.e., motor knowledge or descriptive knowledge) for novice learners, (iii) the effectiveness of employing static visualizations and decreasing presentation speed when learning soccer/basketball scenes from animations/videos depend upon the level of content complexity, for novice learners. The current review demonstrated important practical implications for both coaches and physical education teachers using either animations and/or videos to communicate game systems. Indeed, findings suggested that adapting instructional designs to the level of learners’ expertise, type of depicted knowledge, and level of content complexity is a crucial part of effective tactical learning from dynamic visualizations.
Revisiting the Village Where Arsenic Contamination of Underground Water Was First Discovered in Bangladesh: Twenty-Five Years Later
Authors: Sakamoto Maiko
Published: December 2020

A survey was conducted in an As-affected village of Bangladesh—the first discovery of As contamination in the country—to assess the current situation and how implementation activities have worked to mitigate the problem. The As testing showed that the levels were less than the Bangladesh standard (50 µg/L) in all shallow tube-wells throughout the village. The questionnaire survey was conducted in the village as well as a neighboring As-affected village for comparison. The results revealed that there was a significant number of people using shallow tube-wells in both villages despite knowing that these wells could be contaminated with As and that safe water was available through a pipeline water supply. About 70% of responding households possessed their own water sources, mostly shallow tube-wells, and owners were less likely to choose tap water for drinking purpose than nonowners. In the village where As contamination was first reported, those individuals with a higher level of education and strong ties with neighbors were more likely to use shallow tube-well water for drinking purposes rather than tap water. This study suggests several measures to mobilize people to get safe water, namely providing subsides to install private taps, supplying public taps, and marketing and distributing handy water quality tests for households.
Sugary Liquids in the Baby Bottle: Risk for Child Undernutrition and Severe Tooth Decay in Rural El Salvador
Authors: Achalu Priyanka , Bhatia Abhishek , Turton Bathsheba , Luna Lucy , Sokal-Gutierrez Karen
Published: December 2020

As communities worldwide shift from consuming traditional diets to more processed snacks and sugar-sweetened beverages (SSBs), increases in child obesity and tooth decay and persistence of undernutrition are particularly apparent in Latin American countries. Further evidence of shared risk factors between child undernutrition and poor oral health outcomes is needed to structure more effective health interventions for children’s nutrition. This study aims to identify dietary, oral health, and sociodemographic risk factors for child undernutrition and severe early childhood caries (sECC) among a convenience sample of 797 caregiver–child pairs from rural Salvadoran communities. Caregiver interviews on child dietary and oral health practices were conducted, and their children’s height, weight, and dental exam data were collected. Multivariable regression analyses were performed using RStudio (version 1.0.143). Caregiver use of SSBs in the baby bottle was identified as a common significant risk factor for child undernutrition (p = 0.011) and sECC (p = 0.047). Early childhood caries (p = 0.023) was also a risk factor for developing undernutrition. Future maternal–child health and nutrition programs should coordinate with oral health interventions to discourage feeding children SSBs in the baby bottle and to advocate for policies limiting SSB marketing to young children and their families.
The Effectiveness of Educational Interventions on Breast Cancer Screening Uptake, Knowledge, and Beliefs among Women: A Systematic Review
Authors: Noman Sarah , Shahar Hayati Kadir , Abdul Rahman Hejar , Ismail Suriani , Abdulwahid Al-Jaberi Musheer , Azzani Meram
Published: December 2020

There have been various systematic reviews on the significance of educational interventions as necessary components to encourage breast cancer screening (BCS) and reduce the burden of breast cancer (BC). However, only a few studies have attempted to examine these educational interventions comprehensively. This review paper aimed to systematically evaluate the effectiveness of various educational interventions in improving BCS uptake, knowledge, and beliefs among women in different parts of the world. Following the PRISMA guidelines, a comprehensive literature search on four electronic databases, specifically PubMed, Scopus, Web of Science, and ScienceDirect, was performed in May 2019. A total of 22 interventional studies were reviewed. Theory- and language-based multiple intervention strategies, which were mainly performed in community and healthcare settings, were the commonly shared characteristics of the educational interventions. Most of these studies on the effectiveness of interventions showed favorable outcomes in terms of the BCS uptake, knowledge, and beliefs among women. Educational interventions potentially increase BCS among women. The interpretation of the reported findings should be treated with caution due to the heterogeneity of the studies in terms of the characteristics of the participants, research designs, intervention strategies, and outcome measures.
The Associations between Functional Fitness Test Performance and Abdominal Obesity in Healthy Elderly People: Results from the National Physical Fitness Examination Survey in Taiwan
Authors: Chen Hsin-Han , Chen Hui-Ling , Lin Yi-Tien , Lin Chaou-Wen , Ho Chien-Chang , Lin Hsueh-Yi , Lee Po-Fu
Published: December 2020

The relationships between different functional fitness performance and abdominal obesity among the elderly have not been widely discussed in the literature. The present study aimed to investigate the associations between functional fitness test performance and abdominal obesity in Taiwanese elderly people. A total of 22,399 items of data from the National Physical Fitness Survey Databases in Taiwan (NPFSD 2014-15) were reviewed and analyzed. The quartiles of functional fitness test results were identified as the dependent variable in the multiple linear regression analysis to examine the association between functional fitness and abdominal obesity status. The results showed that body balance (odds ratios (ORs) listed from 1.18 to 2.29, p < 0.05) and flexibility (ORs listed from 1.23 to 2.16, p < 0.05) were critically associated with abdominal obesity. However, measurements related to muscle strength revealed the limited effect sizes for abdominal obesity. From a disability prevention perspective, the development of muscle strength in the elderly should be emphasized and encouraged to maintain their daily capabilities instead of satisfaction with a lean body.
Searching for General Model of Conspiracy Theories and Its Implication for Public Health Policy: Analysis of the Impacts of Political, Psychological, Structural Factors on Conspiracy Beliefs about the COVID-19 Pandemic
Authors: Kim Seoyong , Kim Sunhee
Published: December 2020

Along with the spread of the COVID-19 pandemic, beliefs in conspiracy theories are spreading within and across countries. This study aims to analyze predictors of beliefs in conspiracy theories. Because previous studies have emphasized only specific political, psychological, or structural factors or variables, this study constructs an integrated analytical model that includes all three factors. We analyze data from a large-scale survey of Koreans (N = 1525) and find several results. First, political, psychological, and structural factors influence beliefs in conspiracy theories. Second, when we examine the specific influences of the variables, we find that authoritarianism, support for minority parties, religiosity, trust in SNS (social networking services), perceived risk, anxiety, negative emotions, blame attribution, the quantity of information, health status, and health after COVID-19, all positively influence beliefs in conspiracy theories. Conversely, support for President Moon Jae-In’s government, Christianity, trust in the government, perceived control, analytic thinking, knowledge, the quality of information, and gender, all negatively impact these beliefs. Among the predictors, the quality of information, health status, support for President Moon Jae-In’s government, perceived risk, and anxiety have the most decisive impacts on beliefs in conspiracy theories.
Monounsaturated Fatty Acids in Obesity-Related Inflammation
Authors: Ravaut Gaetan , Légiot Alexandre , Bergeron Karl-F. , Mounier Catherine
Published: December 2020

Obesity is an important aspect of the metabolic syndrome and is often associated with chronic inflammation. In this context, inflammation of organs participating in energy homeostasis (such as liver, adipose tissue, muscle and pancreas) leads to the recruitment and activation of macrophages, which secrete pro-inflammatory cytokines. Interleukin-1β secretion, sustained C-reactive protein plasma levels and activation of the NLRP3 inflammasome characterize this inflammation. The Stearoyl-CoA desaturase-1 (SCD1) enzyme is a central regulator of lipid metabolism and fat storage. This enzyme catalyzes the generation of monounsaturated fatty acids (MUFAs)—major components of triglycerides stored in lipid droplets—from saturated fatty acid (SFA) substrates. In this review, we describe the molecular effects of specific classes of fatty acids (saturated and unsaturated) to better understand the impact of different diets (Western versus Mediterranean) on inflammation in a metabolic context. Given the beneficial effects of a MUFA-rich Mediterranean diet, we also present the most recent data on the role of SCD1 activity in the modulation of SFA-induced chronic inflammation.
Deletion of KLF10 Leads to Stress-Induced Liver Fibrosis upon High Sucrose Feeding
Authors: Lee Junghoon , Oh Ah-Reum , Lee Hui-Young , Moon Young-Ah , Lee Ho-Jae , Cha Ji-Young
Published: December 2020

Liver fibrosis is a consequence of chronic liver injury associated with chronic viral infection, alcohol abuse, and nonalcoholic fatty liver. The evidence from clinical and animal studies indicates that transforming growth factor-β (TGF-β) signaling is associated with the development of liver fibrosis. Krüppel-like factor 10 (KLF10) is a transcription factor that plays a significant role in TGF-β-mediated cell growth, apoptosis, and differentiation. In recent studies, it has been reported to be associated with glucose homeostasis and insulin resistance. In the present study, we investigated the role of KLF10 in the progression of liver disease upon a high-sucrose diet (HSD) in mice. Wild type (WT) and Klf10 knockout (KO) mice were fed either a control chow diet or HSD (50% sucrose) for eight weeks. Klf10 KO mice exhibited significant hepatic steatosis, inflammation, and liver injury upon HSD feeding, whereas the WT mice exhibited mild hepatic steatosis with no apparent liver injury. The livers of HSD-fed Klf10 KO mice demonstrated significantly increased endoplasmic reticulum stress, oxidative stress, and proinflammatory cytokines. Klf10 deletion led to the development of sucrose-induced hepatocyte cell death both in vivo and in vitro. Moreover, it significantly increased fibrogenic gene expression and collagen accumulation in the liver. Increased liver fibrosis was accompanied by increased phosphorylation and nuclear localization of Smad3. Here, we demonstrate that HSD-fed mice develop a severe liver injury in the absence of KLF10 due to the hyperactivation of the endoplasmic reticulum stress response and CCAAT/enhance-binding protein homologous protein (CHOP)-mediated apoptosis of hepatocytes. The current study suggests that KLF10 plays a protective role against the progression of hepatic steatosis into liver fibrosis in a lipogenic state.
Genetics of Ocular Melanoma: Insights into Genetics, Inheritance and Testing
Authors: van Poppelen Natasha M. , de Bruyn Daniël P. , Bicer Tolga , Verdijk Rob , Naus Nicole , Mensink Hanneke , Paridaens Dion , de Klein Annelies , Brosens Erwin , Kiliҫ Emine
Published: December 2020

Ocular melanoma consists of posterior uveal melanoma, iris melanoma and conjunctival melanoma. These malignancies derive from melanocytes in the uveal tract or conjunctiva. The genetic profiles of these different entities differ from each other. In uveal melanoma, GNAQ and GNA11 gene mutations are frequently found and prognosis is based on mutation status of BAP1, SF3B1 and EIF1AX genes. Iris melanoma, also originating from the uvea, has similarities to the genetic makeups of both posterior uveal melanoma (UM) and conjunctival melanoma since mutations in GNAQ and GNA11 are less common and genes involved in conjunctival melanoma such as BRAF have been described. The genetic spectrum of conjunctival melanoma, however, includes frequent mutations in the BRAF, NRAS and TERT promoter genes, which are found in cutaneous melanoma as well. The BRAF status of the tumor is not correlated to prognosis, whereas the TERT promoter gene mutations are. Clinical presentation, histopathological characteristics and copy number alterations are associated with survival in ocular melanoma. Tissue material is needed to classify ocular melanoma in the different subgroups, which creates a need for the use of noninvasive techniques to prognosticate patients who underwent eye preserving treatment.
Astroglial Connexin43 as a Potential Target for a Mood Stabiliser
Authors: Okada Motohiro , Oka Tomoka , Nakamoto Misaki , Fukuyama Kouji , Shiroyama Takashi
Published: December 2020

Mood disorders remain a major public health concern worldwide. Monoaminergic hypotheses of pathophysiology of bipolar and major depressive disorders have led to the development of monoamine transporter-inhibiting antidepressants for the treatment of major depression and have contributed to the expanded indications of atypical antipsychotics for the treatment of bipolar disorders. In spite of psychopharmacological progress, current pharmacotherapy according to the monoaminergic hypothesis alone is insufficient to improve or prevent mood disorders. Recent approval of esketamine for treatment of treatment-resistant depression has attracted attention in psychopharmacology as a glutamatergic hypothesis of the pathophysiology of mood disorders. On the other hand, in the last decade, accumulated findings regarding the pathomechanisms of mood disorders emphasised that functional abnormalities of tripartite synaptic transmission play important roles in the pathophysiology of mood disorders. At first glance, the enhancement of astroglial connexin seems to contribute to antidepressant and mood-stabilising effects, but in reality, antidepressive and mood-stabilising actions are mediated by more complicated interactions associated with the astroglial gap junction and hemichannel. Indeed, several depressive mood-inducing stress stimulations suppress connexin43 expression and astroglial gap junction function, but enhance astroglial hemichannel activity. On the other hand, monoamine transporter-inhibiting antidepressants suppress astroglial hemichannel activity and enhance astroglial gap junction function, whereas several non-antidepressant mood stabilisers activate astroglial hemichannel activity. Based on preclinical findings, in this review, we summarise the effects of antidepressants, mood-stabilising antipsychotics, and anticonvulsants on astroglial connexin, and then, to establish a novel strategy for treatment of mood disorders, we reveal the current progress in psychopharmacology, changing the question from “what has been revealed?” to “what should be clarified?”.
Synergy between Readthrough and Nonsense Mediated Decay Inhibition in a Murine Model of Cystic Fibrosis Nonsense Mutations
Authors: McHugh Daniel R. , Cotton Calvin U. , Hodges Craig A.
Published: December 2020

Many heritable genetic disorders arise from nonsense mutations, which generate premature termination codons (PTCs) in transcribed mRNA. PTCs ablate protein synthesis by prematurely terminating the translation of mutant mRNA, as well as reducing mutant mRNA quantity through targeted degradation by nonsense-mediated decay (NMD) mechanisms. Therapeutic strategies for nonsense mutations include facilitating ribosomal readthrough of the PTC and/or inhibiting NMD to restore protein function. However, the efficacy of combining readthrough agents and NMD inhibitors has not been thoroughly explored. In this study, we examined combinations of known NMD inhibitors and readthrough agents using functional analysis of the CFTR protein in primary cells from a mouse model carrying a G542X nonsense mutation in Cftr. We observed synergy between an inhibitor of the NMD component SMG-1 (SMG1i) and the readthrough agents G418, gentamicin, and paromomycin, but did not observe synergy with readthrough caused by amikacin, tobramycin, PTC124, escin, or amlexanox. These results indicate that treatment with NMD inhibitors can increase the quantity of functional protein following readthrough, and that combining NMD inhibitors and readthrough agents represents a potential therapeutic option for treating nonsense mutations.
Enhanced Suppression of Immune Cells In Vitro by MSC Overexpressing FasL
Authors: Vacaru Ana-Maria , Dumitrescu Madalina , Vacaru Andrei Mircea , Fenyo Ioana Madalina , Ionita Radu , Gafencu Anca Violeta , Simionescu Maya
Published: December 2020

Mesenchymal stromal cells (MSC) display several mechanisms of action that may be harnessed for therapeutic purposes. One of their most attractive features is their immunomodulatory activity that has been extensively characterized both in vitro and in vivo. While this activity has proven to be very efficient, it is transient. We aimed to enhance it by transforming MSC to overexpress a first apoptosis signal (Fas) ligand (FasL). In this study, our goal was to induce FasL overexpression through adenoviral transduction in MSC to improve their immunomodulatory activity. We characterized the impact of FasL overexpression on the morphology, proliferation, viability, phenotype, multilineage differentiation potential and immunomodulation of MSC. Moreover, we determined their suppressive properties in mixed reactions with A20 cells, as well as with stimulated splenocytes. Our findings demonstrate that FasL-overexpressing MSC exhibit improved immunosuppressive properties, while maintaining their MSC-characteristic features. In conclusion, we establish, in a proof-of-concept set-up, that FasL-overexpressing MSC represent good candidates for therapeutic intervention targeted at autoimmune disorders.
Pick’s Tau Fibril Shows Multiple Distinct PET Probe Binding Sites: Insights from Computational Modelling
Authors: Mishra Sushil K. , Yamaguchi Yoshiki , Higuchi Makoto , Sahara Naruhiko
Published: December 2020

In recent years, it has been realized that the tau protein is a key player in multiple neurodegenerative diseases. Positron emission tomography (PET) radiotracers that bind to tau filaments in Alzheimer’s disease (AD) are in common use, but PET tracers binding to tau filaments of rarer, age-related dementias, such as Pick’s disease, have not been widely explored. To design disease-specific and tau-selective PET tracers, it is important to determine where and how PET tracers bind to tau filaments. In this paper, we present the first molecular modelling study on PET probe binding to the structured core of tau filaments from a patient with Pick’s disease (TauPiD). We have used docking, molecular dynamics simulations, binding-affinity and tunnel calculations to explore TauPiD binding sites, binding modes, and binding energies of PET probes (AV-1451, MK-6240, PBB3, PM-PBB3, THK-5351 and PiB) with TauPiD. The probes bind to TauPiD at multiple surface binding sites as well as in a cavity binding site. The probes show unique surface binding patterns, and, out of them all, PM-PBB3 proves to bind the strongest. The findings suggest that our computational workflow of structural and dynamic details of the tau filaments has potential for the rational design of TauPiD specific PET tracers.
Delayed Exercise Training Improves Obesity-Induced Chronic Kidney Disease by Activating AMPK Pathway in High-Fat Diet-Fed Mice
Authors: Juszczak Florian , Vlassembrouck Maud , Botton Olivia , Zwakhals Thomas , Decarnoncle Morgane , Tassin Alexandra , Caron Nathalie , Declèves Anne-Emilie
Published: December 2020

Exercise training is now recognized as an interesting therapeutic strategy in managing obesity and its related disorders. However, there is still a lack of knowledge about its impact on obesity-induced chronic kidney disease (CKD). Here, we investigated the effects of a delayed protocol of endurance exercise training (EET) as well as the underlying mechanism in obese mice presenting CKD. Mice fed a high-fat diet (HFD) or a low-fat diet (LFD) for 12 weeks were subsequently submitted to an 8-weeks EET protocol. Delayed treatment with EET in obese mice prevented body weight gain associated with a reduced calorie intake. EET intervention counteracted obesity-related disorders including glucose intolerance, insulin resistance, dyslipidaemia and hepatic steatosis. Moreover, our data demonstrated for the first time the beneficial effects of EET on obesity-induced CKD as evidenced by an improvement of obesity-related glomerulopathy, tubulo-interstitial fibrosis, inflammation and oxidative stress. EET also prevented renal lipid depositions in the proximal tubule. These results were associated with an improvement of the AMPK pathway by EET in renal tissue. AMPK-mediated phosphorylation of ACC and ULK-1 were particularly enhanced leading to increased fatty acid oxidation and autophagy improvement with EET in obese mice.
Molecular Mechanisms of Treatment Resistance in Glioblastoma
Authors: Ou Alexander , Yung W. K. Alfred , Majd Nazanin
Published: December 2020

Glioblastoma is the most common malignant primary brain tumor in adults and is almost invariably fatal. Despite our growing understanding of the various mechanisms underlying treatment failure, the standard-of-care therapy has not changed over the last two decades, signifying a great unmet need. The challenges of treating glioblastoma are many and include inadequate drug or agent delivery across the blood–brain barrier, abundant intra- and intertumoral heterogeneity, redundant signaling pathways, and an immunosuppressive microenvironment. Here, we review the innate and adaptive molecular mechanisms underlying glioblastoma’s treatment resistance, emphasizing the intrinsic challenges therapeutic interventions must overcome—namely, the blood–brain barrier, tumoral heterogeneity, and microenvironment—and the mechanisms of resistance to conventional treatments, targeted therapy, and immunotherapy.
Polymer-Decorated Cellulose Nanocrystals as Environmentally Friendly Additives for Olefin-Based Drilling Fluids
Authors: Pinheiro José Aurélio , Marques Nívia do Nascimento , Villetti Marcos Antônio , Balaban Rosangela de Carvalho
Published: December 2020

In this study, we intended to evaluate the performance of olefin-based drilling fluids after addition of cellulose nanocrystal (CNC) derivatives. For this purpose, firstly, cellulose nanocrystals, produced from sulfuric acid hydrolysis of cotton fibers, were functionalized with poly(N-isopropylacrylamide) (PNIPAM) chains via free radicals. The samples were then characterized via Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), confocal microscopy, dynamic light scattering (DLS), and zeta potential measurements in water. The FTIR and NMR spectra exhibited the characteristic signals of CNC and PNIPAM groups, indicating successful grafting. As expected, X-ray diffractograms showed that the crystallinity of CNCs reduces after chemical modification. TGA revealed that the surface-functionalized CNCs present higher thermal stability than pure CNCs. The confocal microscopy, zeta potential, and DLS results were consistent with the behavior of cellulose nanocrystals decorated by a shell of PNIPAM chains. The fluids with a small amount of modified CNCs presented a much lower volume of filtrate after high-temperature and high-pressure (HTHP) filtration tests than the corresponding standard fluid, indicating the applicability of the environmentally friendly particles for olefin-based drilling fluids.
Effect of Cavity Disinfectants on Dentin Bond Strength and Clinical Success of Composite Restorations—A Systematic Review of In Vitro, In Situ and Clinical Studies
Authors: Coelho Ana , Amaro Inês , Rascão Beatriz , Marcelino Inês , Paula Anabela , Saraiva José , Spagnuolo Gianrico , Marques Ferreira Manuel , Miguel Marto Carlos , Carrilho Eunice
Published: December 2020

Cavity disinfection becomes an important step before a dental restorative procedure. The disinfection can be obtained cleaning the dental cavity with antimicrobial agents before the use of adhesive systems. The aim of this study was to conduct a systematic review on the effect of different cavity disinfectants on restorations’ adhesion and clinical success. A search was carried out through the Cochrane Library, PubMed, and Web of Science. In vitro and in situ studies reporting results on dentin bond strength tests, and clinical studies published until August 2020, in English, Spanish and Portuguese were included. The methodological quality assessment of the clinical studies was carried out using the Revised Cochrane risk-of-bias tool. Chlorhexidine could preserve adhesion to dentin. EDTA and ethanol had positive results that should be further confirmed. Given the significant lack of scientific evidence, the use of lasers, fluoridated agents, sodium hypochlorite, or other products as cavity disinfectants should be avoided. Chlorhexidine is a safe option for cavity disinfection with adequate preservation of adhesion to dentin. Moreover, future researches should be focused on the efficacy of these disinfectants against cariogenic bacteria and their best application methods.
Signal Integration by Cyclin-Dependent Kinase 8 (CDK8) Module and Other Mediator Subunits in Biotic and Abiotic Stress Responses
Authors: Chong Leelyn , Shi Xiaoning , Zhu Yingfang
Published: December 2020

Environmental stresses have driven plants to develop various mechanisms to acclimate in adverse conditions. Extensive studies have demonstrated that a significant reprogramming occurs in the plant transcriptome in response to biotic and abiotic stresses. The highly conserved and large multi-subunit transcriptional co-activator of eukaryotes, known as the Mediator, has been reported to play a substantial role in the regulation of important genes that help plants respond to environmental perturbances. CDK8 module is a relatively new component of the Mediator complex that has been shown to contribute to plants’ defense, development, and stress responses. Previous studies reported that CDK8 module predominantly acts as a transcriptional repressor in eukaryotic cells by reversibly associating with core Mediator. However, growing evidence has demonstrated that depending on the type of biotic and abiotic stress, the CDK8 module may perform a contrasting regulatory role. This review will summarize the current knowledge of CDK8 module as well as other previously documented Mediator subunits in plant cell signaling under stress conditions.
Pancreatic Islets Accumulate Cadmium in a Rodent Model of Cadmium-Induced Hyperglycemia
Authors: Fitzgerald Ryan , Olsen Andrew , Nguyen Jessica , Wong Winifred , El Muayed Malek , Edwards Joshua
Published: December 2020

Cadmium (Cd) is an anthropogenic as well as a naturally occurring toxicant associated with prediabetes and T2DM in humans and experimental models of Cd exposure. However, relatively few studies have examined the mechanism(s) of Cd-induced hyperglycemia. The purpose of this study was to examine the role of pancreatic islets in Cd-induced hyperglycemia. Male Sprague–Dawley rats were given daily subcutaneous doses of Cd at 0.6 mg/kg over 12 weeks. There was a resulting time-dependent increase in fasting blood glucose and altered insulin release in vitro. Islets isolated from control (saline-treated) and Cd-treated animals were incubated in low (0.5 mg/mL) or high (3 mg/mL) glucose conditions. Islets from 12 week Cd-treated animals had significantly less glucose-stimulated insulin release compared to islets from saline-treated control animals. The actual Cd content of isolated islets was 5 fold higher than the whole pancreas (endocrine + exocrine) and roughly 70% of that present in the renal cortex. Interestingly, islets isolated from Cd-treated animals and incubated in high glucose conditions contained significantly less Cd and zinc than those incubated in low glucose. These results show that within whole pancreatic tissue, Cd selectively accumulates in pancreatic islets and causes altered islet function that likely contributes to dysglycemia.
The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells
Authors: Muñoz-Hidalgo Lisandra , San-Miguel Teresa , Megías Javier , Serna Eva , Calabuig-Fariñas Silvia , Monleón Daniel , Gil-Benso Rosario , Cerdá-Nicolás Miguel , López-Ginés Concha
Published: December 2020

Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups. We investigated the effect of miR-200c on ZEB1 expression and cell migration in an in vitro transfection model with a miR-200c mimic, a miR-200c inhibitor and siRNA targeting EGFR in three short-term cultures with different levels of EGFR amplification obtained from resected glioblastomas. The cell culture with the highest EGFR amplification level presented the lowest miR-200c expression and the status of EGFR modulated the effect of miR-200c on ZEB1 expression. Silencing EGFR led to miR-200c upregulation and ZEB1 downregulation in transfected cultures, except in the presence of high levels of EGFR. Likewise, miR-200c upregulation decreased ZEB1 expression and inhibited cell migration, especially when EGFR was not amplified. Our results suggest that modulating miR-200c may serve as a novel therapeutic approach for glioblastoma depending on EGFR status.
Spontaneous Mutations in HIV-1 Gag, Protease, RT p66 in the First Replication Cycle and How They Appear: Insights from an In Vitro Assay on Mutation Rates and Types
Authors: Yeo Joshua Yi , Koh Darius Wen-Shuo , Yap Ping , Goh Ghin-Ray , Gan Samuel Ken-En
Published: December 2020

While drug resistant mutations in HIV-1 are largely credited to its error prone HIV-1 RT, the time point in the infection cycle that these mutations can arise and if they appear spontaneously without selection pressures both remained enigmatic. Many HIV-1 RT mutational in vitro studies utilized reporter genes (LacZ) as a template to investigate these questions, thereby not accounting for the possible contribution of viral codon usage. To address this gap, we investigated HIV-1 RT mutation rates and biases on its own Gag, protease, and RT p66 genes in an in vitro selection pressure free system. We found rare clinical mutations with a general avoidance of crucial functional sites in the background mutations rates for Gag, protease, and RT p66 at 4.71 × 10−5, 6.03 × 10−5, and 7.09 × 10−5 mutations/bp, respectively. Gag and p66 genes showed a large number of ‘A to G’ mutations. Comparisons with silently mutated p66 sequences showed an increase in mutation rates (1.88 × 10−4 mutations/bp) and that ‘A to G’ mutations occurred in regions reminiscent of ADAR neighbor sequence preferences. Mutational free energies of the ‘A to G’ mutations revealed an avoidance of destabilizing effects, with the natural p66 gene codon usage providing barriers to disruptive amino acid changes. Our study demonstrates the importance of studying mutation emergence in HIV genes in a RT-PCR in vitro selection pressure free system to understand how fast drug resistance can emerge, providing transferable applications to how new viral diseases and drug resistances can emerge.
MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts
Authors: Eiro Noemi , Cid Sandra , Aguado Nuria , Fraile María , de Pablo Nagore , Fernández Berta , Domínguez Francisco , González Luis O. , Vizoso Francisco J.
Published: December 2020

Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior.
In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II
Authors: Rivera-Quiroga Raúl E. , Cardona Néstor , Padilla Leonardo , Rivera Wbeimar , Rocha-Roa Cristian , Diaz De Rienzo Mayri A. , Morales Sandra M. , Martinez María C.
Published: December 2020

Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates.