bluuebunny/crossref_metadata_2025 huggingface dataset:
What Matters 2 Adults (WM2Adults): Understanding the Foundations of Aboriginal and Torres Strait Islander Wellbeing
Authors: Garvey Gail , Anderson Kate , Gall Alana , Butler Tamara L. , Cunningham Joan , Whop Lisa J. , Dickson Michelle , Ratcliffe Julie , Cass Alan , Tong Allison , Arley Brian , Howard Kirsten
Published: June 2021

Aboriginal and Torres Strait Islander people experience a greater range of health and social disadvantages compared to other Australians. Wellbeing is a culturally-bound construct, and to date, a national evidence base around the components of wellbeing for Aboriginal and Torres Strait Islander people is lacking. Understanding and measurement of wellbeing for this population is critical in achieving health equity. This paper aims to identify and describe the foundations of wellbeing for Aboriginal and Torres Strait Islander adults. This national qualitative study was underpinned by an Indigenist research approach which privileges the voices of Aboriginal and Torres Strait Islander people. Aboriginal and Torres Strait Islander adults were purposively recruited from around Australia between September 2017 and September 2018 to participate in Yarning Circles, led by Aboriginal and Torres Strait Islander researchers. Yarning Circles were audio recorded, transcribed and analyzed. A Collaborative Yarning Methodology was used, which incorporated reflexive thematic analysis to identify and describe the foundations of wellbeing reported by participants. A total of 359 Aboriginal and Torres Strait Islander adults participated. Our analysis revealed five foundations of wellbeing: belonging and connection; holistic health; purpose and control; dignity and respect; and basic needs. These foundations were deeply interwoven by three interconnected aspects of Aboriginal and Torres Strait Islander life: family, community and culture. The findings of this study will substantially aid our efforts to develop a new wellbeing measure for Aboriginal and Torres Strait Islander adults. The iterative Indigenist methods used in this study provide a robust research methodology for conducting large-scale, nationally-relevant qualitative research with Aboriginal and Torres Strait Islander people. Policies and practices that are informed by our results have the potential to address outcomes that are meaningful for Aboriginal and Torres Strait Islander people.
National Trends in Cycling in Light of the Norwegian Bike Traffic Index
Authors: Nordengen Solveig , Andersen Lars Bo , Riiser Amund , Solbraa Ane K.
Published: June 2021

National and international strategies and recommendations are intended to increase physical activity in the general population. Active transportation is included in interdisciplinary strategies to meet these recommendations. Cycling seems to be more health enhancing than walking for transportation since cycling seems to reduce the risk of cardiovascular disease and associated risk factors. Furthermore, the health benefits of cycling are proven to outrun the risk of injuries and mortality. Politicians seem to approve costly infrastructure strategies to increase the amount of cycling in the population to improve public health and shift to more sustainable travel habits. A linear relationship between cycle-friendly infrastructure and the amount of commuter cycling has been demonstrated. However, in Norway and on a global level, there is a lack of robust evaluations of actions and sensitive monitoring systems to observe possible change. Therefore, we aimed to develop the Norwegian bike traffic index and describe the national, regional, and local trends in counted cycle trips. We used a transparent methodology so that the index can be used, developed, and adapted in other countries. We included 89 stationary counters from the whole country. Counters monitored cycling from 2018 onward. The index is organized at local, regional, and national levels. Furthermore, the index is adjusted for population density at the counter level and presented as ratio of counted cycle trips, comparing 2018 to subsequent years. The index is presented as a percentage change with 95% confidence intervals. In Norway, counted cycle trips increased by 11% from 2018 (100, 100–100) to 2020 (111.0, 106.2–115.1), with large geographical differences. In Southern Norway, there was a significant increase of 23%, and in Northern Norway, there was a nonsignificant decrease by 8% from 2018 to 2020. The indices may indicate possible related effects of local to national cycling strategies and how the COVID-19 pandemic has affected Norwegian travel habits in urban areas.
3D Morphometric Analysis of Human Primary Second Molar Crowns and Its Implications on Interceptive Orthodontics
Authors: Nota Alessandro , Quinzi Vincenzo , Floriani Federico , Cappelli Clizia , Tecco Simona , Marzo Giuseppe
Published: June 2021

The second primary molar represents an anchorage element in interceptive orthodontics. The present study aims to analyze the 3D morphology of primary second molars in order to provide reference data and implications about the development of orthodontic bands for second primary molars. Digital models of dental arches from 150 subjects in primary or mixed dentition were analyzed. Six dimensional variables were digitally measured for each second primary molar, and the mean and standard error of the mean (SEM) were calculated and compared applying Student t-test statistical analysis. The mean value results show statistically significant dimensional differences between the upper and lower teeth, (mostly p < 0.0001), except for the variable h1, while only the variable h1 showed significant differences between the antimetric teeth (left and right). The dimensional variations between the right and left molars were considerably minor compared to those found by comparing the upper and lower arches. A significantly higher dimension of the lower molars and a more rectangular shape were observed.
Comparative UAV Noise-Impact Assessments through Survey and Noise Measurements
Authors: Ivošević Jurica , Ganić Emir , Petošić Antonio , Radišić Tomislav
Published: June 2021

Possibilities to use unmanned aerial vehicles (UAVs) are rapidly growing. With the development of battery technologies, communication, navigation, surveillance, and autonomous systems in general, many UAVs are expected to operate at relatively low altitudes. Thus, the problem of UAV noise impact on human health and well-being will be more pronounced. In this paper, we conducted noise measurements of two UAVs of different performance (quadrotor and hexarotor) in flying up and down, hovering, and overflight procedures. Respondents of good hearing who were confirmed by audiogram measurement and had participated in the survey during UAV noise measurement gave their subjective assessments on the UAV noise perception. UAV noise measurements and subjective respondents’ assessments were analysed and related. UAV noise analysis showed that the parameters measured at the same measurement point for the hexarotor were higher than those for the quadrotor in flying up and down and flying-over procedures. Low frequency noise was present in the noise spectrum of both drones. Participants were able to distinguish between the noise of UAVs and had a generally more negative experience with the hexarotor. Regardless of the noise perception, more than 80% of the respondents believe there are more pros than cons for UAV introduction into everyday life.
Intimate Partner Violence during the COVID-19 Pandemic: A Review of the Phenomenon from Victims’ and Help Professionals’ Perspectives
Authors: Lausi Giulia , Pizzo Alessandra , Cricenti Clarissa , Baldi Michela , Desiderio Rita , Giannini Anna Maria , Mari Emanuela
Published: June 2021

Social isolation is considered one of the main risk factors leading to intimate partner violence episodes; this evidence also emerged during the application of stay-at-home policies to contain the COVID-19 pandemic. For this reason, we aimed to collect data on intimate partner violence over the last year, comparing data reported by victims with data collected by help professionals. In accordance with PRISMA guidelines, through keywords related to abuse, pandemic and containment measures, 3174 articles were identified for screening. After full-text reading and risk of bias analysis, 19 studies were included, and a thematic synthesis was conducted according to two categories: “studies with victims” and “studies with help professionals”. The results of the present review showed that there were significant differences between the data provided by victims and the data collected by health care facilities and police departments; additionally, differences among different forms and severity of victimization emerged. The results have been discussed according to the literature; in particular, we reflected on how containment measures have apparently made it more difficult for victims to report, thus making the existence of the dark figure of crime even more salient.
Factors Related to Breastfeeding Support in Lebanese Daycare Centers: A Qualitative Study among Daycare Directors and Employees
Authors: Abou Jaoude Maya , Moukarzel Sara , Kremers Stef P. J. , Gubbels Jessica S.
Published: June 2021

Breastfeeding has an important impact on maternal and child health, and is affected by several factors influencing its initiation and continuation. This qualitative study aimed to assess the main promoting and hindering factors for breastfeeding support in Lebanese daycare centers (DCCs), through the perspective of their directors and employees. The study was based on semi-structured interviews with 13 directors and 9 employees. It explored the influence of various cognitive factors as well as different environment types (physical, economic, political, and sociocultural) on their breastfeeding support. Findings suggested the directors and employees valued improving breastfeeding support in DCCs and the physical set-up of the DCCs allowed for this. However, various other factors restricted their abilities to support breastfeeding in the DCC, including limited knowledge and training on the topic, absence of written internal policies on breastfeeding, lack of enforcement in the application of national policies, and the current mothers’ work policies that negatively influenced the decision to breastfeed. Improvements could be achieved through integrated interventions, targeting the interaction of internal DCCs factors and national and DCCs breastfeeding policies, as well as several social factors, to create a multilevel approach targeting breastfeeding continuation support in breastfeeding-friendly DCCs in Lebanon and the region.
Modelling the Reallocation of Time Spent Sitting into Physical Activity: Isotemporal Substitution vs. Compositional Isotemporal Substitution
Authors: Biddle Gregory J. H. , Henson Joseph , Biddle Stuart J. H. , Davies Melanie J. , Khunti Kamlesh , Rowlands Alex V. , Sutton Stephen , Yates Thomas , Edwardson Charlotte L.
Published: June 2021

Isotemporal substitution modelling (ISM) and compositional isotemporal modelling (CISM) are statistical approaches used in epidemiology to model the associations of replacing time in one physical behaviour with time in another. This study’s aim was to use both ISM and CISM to examine and compare associations of reallocating 60 min of sitting into standing or stepping with markers of cardiometabolic health. Cross-sectional data collected during three randomised control trials (RCTs) were utilised. All participants (n = 1554) were identified as being at high risk of developing type 2 diabetes. Reallocating 60 min from sitting to standing and to stepping was associated with a lower BMI, waist circumference, and triglycerides and higher high-density lipoprotein cholesterol using both ISM and CISM (p < 0.05). The direction and magnitude of significant associations were consistent across methods. No associations were observed for hemoglobin A1c, total cholesterol, or low-density lipoprotein cholesterol for either method. Results of both ISM and CISM were broadly similar, allowing for the interpretation of previous research, and should enable future research in order to make informed methodological, data-driven decisions.
Genetic Variation and Cardiovascular Risk Factors: A Cohort Study on Migrants from the Former Soviet Union and a Native German Population
Authors: Huebner Marianne , Börnigen Daniela , Deckert Andreas , Holle Rolf , Meisinger Christa , Müller-Nurasyid Martina , Peters Annette , Rathmann Wolfgang , Becher Heiko
Published: June 2021

Resettlers are a large migrant group of more than 2 million people in Germany who migrated mainly from the former Soviet Union to Germany after 1989. We sought to compare the distribution of the major risk factors for cardiovascular disease (CVD) and to investigate the overall genetic differences in a study population which consisted of resettlers and native (autochthone) Germans. This was a joint analysis of two cohort studies which were performed in the region of Augsburg, Bavaria, Germany, with 3363 native Germans and 363 resettlers. Data from questionnaires and physical examinations were used to compare the risk factors for cardiovascular diseases between the resettlers and native Germans. A population-based genome-wide association analysis was performed in order to identify the genetic differences between the two groups. The distribution of the major risk factors for CVD differed between the two groups. The resettlers lead a less active lifestyle. While female resettlers smoked less than their German counterparts, the men showed similar smoking behavior. SNPs from three genes (BTNL2, DGKB, TGFBR3) indicated a difference in the two populations. In other studies, these genes have been shown to be associated with CVD, rheumatoid arthritis and osteoporosis, respectively.
Modelling Voluntary General Population Vaccination Strategies during COVID-19 Outbreak: Influence of Disease Prevalence
Authors: Jovanović Rastko , Davidović Miloš , Lazović Ivan , Jovanović Maja , Jovašević-Stojanović Milena
Published: June 2021

A novel statistical model based on a two-layer, contact and information, graph is suggested in order to study the influence of disease prevalence on voluntary general population vaccination during the COVID-19 outbreak. Details about the structure and number of susceptible, infectious, and recovered/vaccinated individuals from the contact layer are simultaneously transferred to the information layer. The ever-growing wealth of information that is becoming available about the COVID virus was modelled at each individual level by a simplified proxy predictor of the amount of disease spread. Each informed individual, a node in a heterogeneous graph, makes a decision about vaccination “motivated” by their benefit. The obtained results showed that disease information type, global or local, has a significant impact on an individual vaccination decision. A number of different scenarios were investigated. The scenarios showed that in the case of the stronger impact of globally broadcasted disease information, individuals tend to vaccinate in larger numbers at the same time when the infection has already spread within the population. If individuals make vaccination decisions based on locally available information, the vaccination rate is uniformly spread during infection outbreak duration. Prioritising elderly population vaccination leads to an increased number of infected cases and a higher reduction in mortality. The developed model accuracy allows the precise targeting of vaccination order depending on the individuals’ number of social contacts. Precisely targeted vaccination, combined with pre-existing immunity, and public health measures can limit the infection to isolated hotspots inside the population, as well as significantly delay and lower the infection peak.
Regenerative Therapy Modality for Treatment of True Combined Endodontic-Periodontal Lesions: A Randomized Controlled Clinical Trial
Authors: AlJasser Reham , Bukhary Sundus , AlSarhan Mohammed , Alotaibi Dalal , AlOraini Saleh , Habib Syed Rashid
Published: June 2021

The aim of this in-vivo study was to evaluate/compare the clinical periodontal parameters in patients with true combined endo-perio lesions (EPL), treated with gutta-percha (GP) and mineral trioxide (MTA) as an obturation material alone and with addition of bone grafting in such lesions. 120 Saudi patients (mean age = 41yrs) diagnosed with true combined EPL participated in this study. Group I (control group, n = 30) was treated with conventional endodontic treatment using GP for obturation. Group II (n = 30) was treated with conventional endodontic treatment using MTA for obturation. Group III (n = 30) was treated with conventional endodontic treatment using GP for obturation + grafting procedure to fill the bony defect. Group IV (n = 30) was treated with conventional endodontic treatment using MTA for obturation + grafting procedure to fill the bony defect. Clinical parameters (Pocket depth (PD); Clinical attachment loss (CAL); keratinized tissue width (KTW); gingival phenotype (G.Ph.) and Cone Beam Computed Tomography Periapical Index (CBCTPAI)) were recorded and compared at baseline, 3, 6, 12 months’ interval. For the groups III and IV, CBCTPAI showed significant difference (p < 0.0001) with the other groups at 6 months and 1-year interval. The group with MTA + bone graft showed 76% and 90% patients with 0 score at 6 months and 1-year follow-up, respectively. Comparison of mean values of PD among study groups at 3 months, 6 months and 1 year showed significant difference at 3 months, whereas the mean PD values of subjects in GP + bone graft showed significantly higher PD values than other 3 groups (p = 0.025). Use of GP and MTA for root canal obturation along with periodontal therapy and bone augmentation helps in resolving complex endo-perio lesions. Bone grafting in addition to obturation with MTA was found to be the best treatment strategy in management of EPL cases and is recommended for clinicians who are treating EPL patients.
Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities
Authors: Liaci Carla , Camera Mattia , Caslini Giovanni , Rando Simona , Contino Salvatore , Romano Valentino , Merlo Giorgio R.
Published: June 2021

Intellectual disability (ID) is a pathological condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1–3% of the worldwide population, and no pharmacological therapies are currently available. More than 1000 genes have been found mutated in ID patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular level and moving toward higher levels of organization, i.e., cell compartment and functions, circuits, cognition, and behavior. Thus, cytoskeleton alterations that have an impact on cell processes such as neuronal migration, neuritogenesis, and synaptic plasticity rebound on the overall establishment of an effective network and consequently on the cognitive phenotype. Systems biology (SB) approaches are more focused on the overall interconnected network rather than on individual genes, thus encouraging the design of therapies that aim to correct common dysregulated biological processes. This review summarizes current knowledge about cytoskeleton control in neurons and its relevance for the ID pathogenesis, exploiting in silico modeling and translating the implications of those findings into biomedical research.
Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague–Dawley Rats
Authors: Lech Marta Anna , Leśkiewicz Monika , Kamińska Kinga , Rogóż Zofia , Lorenc-Koci Elżbieta
Published: June 2021

Growing body of evidence points to dysregulation of redox status in the brain as an important factor in the pathogenesis of schizophrenia. The aim of our study was to evaluate the effects of l-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, and 1-[2-Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909), a dopamine reuptake inhibitor, given alone or in combination, to Sprague–Dawley pups during early postnatal development (p5–p16), on the time course of the onset of schizophrenia-like behaviors, and on the expression of brain-derived neurotrophic factor (BDNF) mRNA and its protein in the prefrontal cortex (PFC) and hippocampus (HIP) during adulthood. BSO administered alone decreased the levels of BDNF mRNA and its protein both in the PFC and HIP. Treatment with the combination of BSO + GBR 12909 also decreased BDNF mRNA and its protein in the PFC, but in the HIP, only the level of BDNF protein was decreased. Schizophrenia-like behaviors in rats were assessed at three time points of adolescence (p30, p42–p44, p60–p62) and in early adulthood (p90–p92) using the social interaction test, novel object recognition test, and open field test. Social and cognitive deficits first appeared in the middle adolescence stage and continued to occur into adulthood, both in rats treated with BSO alone or with the BSO + GBR 12909 combination. Behavior corresponding to positive symptoms in humans occurred in the middle adolescence period, only in rats treated with BSO + GBR 12909. Only in the latter group, amphetamine exacerbated the existing positive symptoms in adulthood. Our data show that rats receiving the BSO + GBR 12909 combination in the early postnatal life reproduced virtually all symptoms observed in patients with schizophrenia and, therefore, can be considered a valuable neurodevelopmental model of this disease.
Hypothalamic Astrocytes as a Specialized and Responsive Cell Population in Obesity
Authors: González-García Ismael , García-Cáceres Cristina
Published: June 2021

Astrocytes are a type of glial cell anatomically and functionally integrated into the neuronal regulatory circuits for the neuroendocrine control of metabolism. Being functional integral compounds of synapses, astrocytes are actively involved in the physiological regulatory aspects of metabolic control, but also in the pathological processes that link neuronal dysfunction and obesity. Between brain areas, the hypothalamus harbors specialized functional circuits that seem selectively vulnerable to metabolic damage, undergoing early cellular rearrangements which are thought to be at the core of the pathogenesis of diet-induced obesity. Such changes in the hypothalamic brain region consist of a rise in proinflammatory cytokines, the presence of a reactive phenotype in astrocytes and microglia, alterations in the cytoarchitecture and synaptology of hypothalamic circuits, and angiogenesis, a phenomenon that cannot be found elsewhere in the brain. Increasing evidence points to the direct involvement of hypothalamic astrocytes in such early metabolic disturbances, thus moving the study of these glial cells to the forefront of obesity research. Here we provide a comprehensive review of the most relevant findings of molecular and pathophysiological mechanisms by which hypothalamic astrocytes might be involved in the pathogenesis of obesity.
Mirna Expression in Glaucomatous and TGFβ2 Treated Lamina Cribrosa Cells
Authors: Lopez Navita N. , Rangan Rajiv , Clark Abbot F. , Tovar-Vidales Tara
Published: June 2021

Glaucoma is a group of optic neuropathies that leads to irreversible vision loss. The optic nerve head (ONH) is the site of initial optic nerve damage in glaucoma. ONH-derived lamina cribrosa (LC) cells synthesize extracellular matrix (ECM) proteins; however, these cells are adversely affected in glaucoma and cause detrimental changes to the ONH. LC cells respond to mechanical strain by increasing the profibrotic cytokine transforming growth factor-beta 2 (TGFβ2) and ECM proteins. Moreover, microRNAs (miRNAs or miR) regulate ECM gene expression in different fibrotic diseases, including glaucoma. A delicate homeostatic balance between profibrotic and anti-fibrotic miRNAs may contribute to the remodeling of ONH. This study aimed to determine whether modulation of miRNAs alters the expression of ECM in human LC cells. Primary human normal and glaucoma LC cells were grown to confluency and treated with or without TGFβ2 for 24 h. Differences in expression of miRNAs were analyzed using miRNA qPCR arrays. miRNA PCR arrays showed that the miR-29 family was significantly decreased in glaucomatous LC cell strains compared to age-matched controls. TGFβ2 treatment downregulated the expression of multiple miRNAs, including miR-29c-3p, compared to controls in LC cells. LC cells transfected with miR-29c-3p mimics or inhibitors modulated collagen expression.
Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4–7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia–Reperfusion
Authors: Sudarkina Olga Yu. , Filippenkov Ivan B. , Stavchansky Vasily V. , Denisova Alina E. , Yuzhakov Vadim V. , Sevan’kaeva Larisa E. , Valieva Liya V. , Remizova Julia A. , Dmitrieva Veronika G. , Gubsky Leonid V. , Myasoedov Nikolai F. , Limborska Svetlana A. , Dergunova Lyudmila V.
Published: June 2021

The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes. Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke. At 24 h after tMCAO, we observed the upregulation of active CREB in subcortical structures, including the focus of the ischemic damage; downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex; and downregulation of active JNK in both tissues under the action of Semax. Moreover, a regulatory network was constructed. In conclusion, the suppression of inflammatory and cell death processes and the activation of recovery may contribute to the neuroprotective action of Semax at both the transcriptome and protein levels.
EVA1A Plays an Important Role by Regulating Autophagy in Physiological and Pathological Processes
Authors: Zhao Shizhen , Wang Honggang
Published: June 2021

Eva-1 homolog A (EVA1A) is regarded as TMEM166 (transmembrane protein 166) or FAM176A (family with sequence similarity 176) and a lysosome and endoplasmic reticulum-associated protein involved in regulating autophagy and apoptosis. EVA1A regulates embryonic neurogenesis, cardiac remodeling, islet alpha-cell functions, acute liver failure, and hepatitis B virus replication. However, the related mechanisms are not fully clear. Autophagy is a process in which cells transfer pathogens, abnormal proteins and organelles to lysosomes for degradation. It plays an important role in various physiological and pathological processes, including cancer, aging, neurodegeneration, infection, heart disease, development, cell differentiation and nutritional starvation. Recently, there are many studies on the important role of EVA1A in many physiological and pathological processes by regulating autophagy. However, the related molecular mechanisms need further study. Therefore, we summarize the above-mentioned researches about the role of EVA1A in physiological and pathological processes through regulating autophagy in order to provide theoretical basis for future researches.
Bioinformatics Accelerates the Major Tetrad: A Real Boost for the Pharmaceutical Industry
Authors: Behl Tapan , Kaur Ishnoor , Sehgal Aayush , Singh Sukhbir , Bhatia Saurabh , Al-Harrasi Ahmed , Zengin Gokhan , Babes Elena Emilia , Brisc Ciprian , Stoicescu Manuela , Toma Mirela Marioara , Sava Cristian , Bungau Simona Gabriela
Published: June 2021

With advanced technology and its development, bioinformatics is one of the avant-garde fields that has managed to make amazing progress in the pharmaceutical–medical field by modeling the infrastructural dimensions of healthcare and integrating computing tools in drug innovation, facilitating prevention, detection/more accurate diagnosis, and treatment of disorders, while saving time and money. By association, bioinformatics and pharmacovigilance promoted both sample analyzes and interpretation of drug side effects, also focusing on drug discovery and development (DDD), in which systems biology, a personalized approach, and drug repositioning were considered together with translational medicine. The role of bioinformatics has been highlighted in DDD, proteomics, genetics, modeling, miRNA discovery and assessment, and clinical genome sequencing. The authors have collated significant data from the most known online databases and publishers, also narrowing the diversified applications, in order to target four major areas (tetrad): DDD, anti-microbial research, genomic sequencing, and miRNA research and its significance in the management of current pandemic context. Our analysis aims to provide optimal data in the field by stratification of the information related to the published data in key sectors and to capture the attention of researchers interested in bioinformatics, a field that has succeeded in advancing the healthcare paradigm by introducing developing techniques and multiple database platforms, addressed in the manuscript.
Magnetically Controlled Carbonate Nanocomposite with Ciprofloxacin for Biofilm Eradication
Authors: Rumyantceva Viktoriya , Rumyantceva Valeriya , Andreeva Yulia , Tsvetikova Sofia , Radaev Anton , Vishnevskaya Maria , Vinogradov Vladimir , Drozdov Andrey S. , Koshel Elena
Published: June 2021

Biofilms are the reason for a vast majority of chronic inflammation cases and most acute inflammation. The treatment of biofilms still is a complicated task due to the low efficiency of drug delivery and high resistivity of the involved bacteria to harmful factors. Here we describe a magnetically controlled nanocomposite with a stimuli-responsive release profile based on calcium carbonate and magnetite with an encapsulated antibiotic (ciprofloxacin) that can be used to solve this problem. The material magnetic properties allowed targeted delivery, accumulation, and penetration of the composite in the biofilm, as well as the rapid triggered release of the entrapped antibiotic. Under the influence of an RF magnetic field with a frequency of 210 kHz, the composite underwent a phase transition from vaterite into calcite and promoted the release of ciprofloxacin. The effectiveness of the composite was tested against formed biofilms of E. coli and S. aureus and showed a 71% reduction in E. coli biofilm biomass and an 85% reduction in S. aureus biofilms. The efficiency of the composite with entrapped ciprofloxacin was higher than for the free antibiotic in the same concentration, up to 72%. The developed composite is a promising material for the treatment of biofilm-associated inflammations.
Symptom Severity, Infection Progression and Plant Responses in Solanum Plants Caused by Three Pospiviroids Vary with the Inoculation Procedure
Authors: Vázquez Prol Francisco , Márquez-Molins Joan , Rodrigo Ismael , López-Gresa María Pilar , Bellés José María , Gómez Gustavo , Pallás Vicente , Lisón Purificación
Published: June 2021

Infectious viroid clones consist of dimeric cDNAs used to generate transcripts which mimic the longer-than-unit replication intermediates. These transcripts can be either generated in vitro or produced in vivo by agro-inoculation. We have designed a new plasmid, which allows both inoculation methods, and we have compared them by infecting Solanum lycopersicum and Solanum melongena with clones of Citrus exocortis virod (CEVd), Tomato chlorotic dwarf viroid (TCDVd), and Potato spindle tuber viroid (PSTVd). Our results showed more uniform and severe symptoms in agro-inoculated plants. Viroid accumulation and the proportion of circular and linear forms were different depending on the host and the inoculation method and did not correlate with the symptoms, which correlated with an increase in PR1 induction, accumulation of the defensive signal molecules salicylic (SA) and gentisic (GA) acids, and ribosomal stress in tomato plants. The alteration in ribosome biogenesis was evidenced by both the upregulation of the tomato ribosomal stress marker SlNAC082 and the impairment in 18S rRNA processing, pointing out ribosomal stress as a novel signature of the pathogenesis of nuclear-replicating viroids. In conclusion, this updated binary vector has turned out to be an efficient and reproducible method that will facilitate the studies of viroid–host interactions.
The Role of Anthocyanins, Deoxyanthocyanins and Pyranoanthocyanins on the Modulation of Tyrosinase Activity: An In Vitro and In Silico Approach
Authors: Correia Patrícia , Oliveira Hélder , Araújo Paula , Brás Natércia F. , Pereira Ana Rita , Moreira Joana , de Freitas Victor , Mateus Nuno , Oliveira Joana , Fernandes Iva
Published: June 2021

Tyrosinase is the central enzyme involved in the highly complex process of melanin formation, catalyzing the rate-limiting steps of this biosynthetic pathway. Due to such a preponderant role, it has become a major target in the treatment of undesired skin pigmentation conditions and also in the prevention of enzymatic food browning. Numerous phenolic-based structures from natural sources have been pointed out as potential tyrosinase inhibitors, including anthocyanins. The aim of the present study was to individually assess the tyrosinase inhibitory activity of eight purified compounds with a variable degree of structural complexity: native anthocyanins, deoxyanthocyanins, and pyranoanthocyanins. The latter two, the groups of anthocyanin-related compounds with enhanced stability, were tested for the first time. Compounds 1 to 4 (luteolinidin, deoxymalvidin, cyanidin-, and malvidin-3-O-glucoside) revealed to be the most effective inhibitors, and further kinetic studies suggested their inhibition mechanism to be of a competitive nature. Structure–activity relationships were proposed based on molecular docking studies conducted with mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (hTYRP1) crystal structures, providing information about the binding affinity and the different types of interactions established with the enzyme’s active center which corroborated the findings of the inhibition and kinetic studies. Overall, these results support the applicability of these compounds as pigmentation modulators.
Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats
Authors: Aqil Farrukh , Jeyabalan Jeyaprakash , Munagala Radha , Ahmad Iqbal , Schultz David J. , Gupta Ramesh C.
Published: June 2021

Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm3) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC.
Improper Remodeling of Organelles Deputed to Ca2+ Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing
Authors: Protasi Feliciano , Pietrangelo Laura , Boncompagni Simona
Published: June 2021

Proper skeletal muscle function is controlled by intracellular Ca2+ concentration and by efficient production of energy (ATP), which, in turn, depend on: (a) the release and re-uptake of Ca2+ from sarcoplasmic-reticulum (SR) during excitation–contraction (EC) coupling, which controls the contraction and relaxation of sarcomeres; (b) the uptake of Ca2+ into the mitochondrial matrix, which stimulates aerobic ATP production; and finally (c) the entry of Ca2+ from the extracellular space via store-operated Ca2+ entry (SOCE), a mechanism that is important to limit/delay muscle fatigue. Abnormalities in Ca2+ handling underlie many physio-pathological conditions, including dysfunction in ageing. The specific focus of this review is to discuss the importance of the proper architecture of organelles and membrane systems involved in the mechanisms introduced above for the correct skeletal muscle function. We reviewed the existing literature about EC coupling, mitochondrial Ca2+ uptake, SOCE and about the structural membranes and organelles deputed to those functions and finally, we summarized the data collected in different, but complementary, projects studying changes caused by denervation and ageing to the structure and positioning of those organelles: a. denervation of muscle fibers—an event that contributes, to some degree, to muscle loss in ageing (known as sarcopenia)—causes misplacement and damage: (i) of membrane structures involved in EC coupling (calcium release units, CRUs) and (ii) of the mitochondrial network; b. sedentary ageing causes partial disarray/damage of CRUs and of calcium entry units (CEUs, structures involved in SOCE) and loss/misplacement of mitochondria; c. functional electrical stimulation (FES) and regular exercise promote the rescue/maintenance of the proper architecture of CRUs, CEUs, and of mitochondria in both denervation and ageing. All these structural changes were accompanied by related functional changes, i.e., loss/decay in function caused by denervation and ageing, and improved function following FES or exercise. These data suggest that the integrity and proper disposition of intracellular organelles deputed to Ca2+ handling and aerobic generation of ATP is challenged by inactivity (or reduced activity); modifications in the architecture of these intracellular membrane systems may contribute to muscle dysfunction in ageing and sarcopenia.
Genetic Dissection of Vps13 Regulation in Yeast Using Disease Mutations from Human Orthologs
Authors: Park Jae-Sook , Hollingsworth Nancy M. , Neiman Aaron M.
Published: June 2021

The VPS13 family of proteins have emerged as key players in intracellular lipid transport and human health. Humans have four different VPS13 orthologs, the dysfunction of which leads to different diseases. Yeast has a single VPS13 gene, which encodes a protein that localizes to multiple different membrane contact sites. The yeast vps13Δ mutant is pleiotropic, exhibiting defects in sporulation, protein trafficking, endoplasmic reticulum (ER)-phagy and mitochondrial function. Non-null alleles resulting from missense mutations can be useful reagents for understanding the multiple functions of a gene. The exceptionally large size of Vps13 makes the identification of key residues challenging. As a means to identify critical residues in yeast Vps13, amino acid substitution mutations from VPS13A, B, C and D, associated with human disease, were introduced at the cognate positions of yeast VPS13, some of which created separation-of-function alleles. Phenotypic analyses of these mutants have revealed that the promotion of ER-phagy is a fourth, genetically separable role of VPS13 and provide evidence that co-adaptors at the endosome mediate the activity of VPS13 in vacuolar sorting.
TRPV1 Hyperfunction Contributes to Renal Inflammation in Oxalate Nephropathy
Authors: Lu Chien-Lin , Teng Te-Yi , Liao Min-Tser , Ma Ming-Chieh
Published: June 2021

Inflammation worsens oxalate nephropathy by exacerbating tubular damage. The transient receptor potential vanilloid 1 (TRPV1) channel is present in kidney and has a polymodal sensing ability. Here, we tested whether TRPV1 plays a role in hyperoxaluria-induced renal inflammation. In TRPV1-expressed proximal tubular cells LLC-PK1, oxalate could induce cell damage in a time- and dose-dependent manner; this was associated with increased arachidonate 12-lipoxygenase (ALOX12) expression and synthesis of endovanilloid 12(S)-hydroxyeicosatetraenoic acid for TRPV1 activation. Inhibition of ALOX12 or TRPV1 attenuated oxalate-mediated cell damage. We further showed that increases in intracellular Ca2+ and protein kinase C α activation are downstream of TRPV1 for NADPH oxidase 4 upregulation and reactive oxygen species formation. These trigger tubular cell inflammation via increased NLR family pyrin domain-containing 3 expression, caspase-1 activation, and interleukin (IL)-1β release, and were alleviated by TRPV1 inhibition. Male hyperoxaluric rats demonstrated urinary supersaturation, tubular damage, and oxidative stress in a time-dependent manner. Chronic TRPV1 inhibition did not affect hyperoxaluria and urinary supersaturation, but markedly reduced tubular damage and calcium oxalate crystal deposition by lowering oxidative stress and inflammatory signaling. Taking all these results together, we conclude that TRPV1 hyperfunction contributes to oxalate-induced renal inflammation. Blunting TRPV1 function attenuates hyperoxaluric nephropathy.
Antibacterial Photodynamic Inactivation of Fagopyrin F from Tartary Buckwheat (Fagopyrum tataricum) Flower against Streptococcus mutans and Its Biofilm
Authors: Kim Jaecheol , Kim Suna , Lee Kiuk , Kim Ryun Hee , Hwang Keum Taek
Published: June 2021

The objective of this study was to determine reactive oxygen species (ROS) produced by fagopyrin F-rich fraction (FFF) separated from Tartary buckwheat flower extract exposed to lights and to investigate its antibacterial photodynamic inactivation (PDI) against Streptococcus mutans and its biofilm. ROS producing mechanisms involving FFF with light exposure were determined using a spectrophotometer and a fluorometer. S. mutans and its biofilm inactivation after PDI treatment of FFF using blue light (BL; 450 nm) were determined by plate count method and crystal violet assay, respectively. The biofilm destruction by ROS produced from FFF after exposure to BL was visualized using confocal laser scanning microscopy (CLSM) and field emission scanning electron microscope (FE-SEM). BL among 3 light sources produced type 1 ROS the most when applying FFF as a photosensitizer. FFF exposed to BL (5 and 10 J/cm2) significantly more inhibited S. mutans viability and biofilm formation than FFF without the light exposure (p < 0.05). In the PDI of FFF exposed to BL (10 J/cm2), an apparent destruction of S. mutans and its biofilm were observed by the CLSM and FE-SEM. Antibacterial PDI effect of FFF was determined for the first time in this study.
Clusters, Assemblies and Aggregates of Tumor Cells in the Blood of Breast Cancer Patients; Composition, Mode of Action, Detection and Impact on Metastasis and Survival
Authors: Smietanka Urszula , Szostakowska-Rodzos Małgorzata , Tabor Sylwia , Fabisiewicz Anna , Grzybowska Ewa A.
Published: June 2021

Circulating tumor cells (CTCs) are gaining momentum as a diagnostic tool and therapeutic target. CTC clusters are more metastatic, but harder to study and characterize, because they are rare and the methods of isolation are mostly focused on single CTCs. This review highlights the recent advances to our understanding of tumor cell clusters with the emphasis on their composition, origin, biology, methods of detection, and impact on metastasis and survival. New approaches to therapy, based on cluster characteristics are also described.
A Graph Database Representation of Portuguese Criminal-Related Documents
Authors: Carnaz Gonçalo , Nogueira Vitor Beires , Antunes Mário
Published: June 2021

Organizations have been challenged by the need to process an increasing amount of data, both structured and unstructured, retrieved from heterogeneous sources. Criminal investigation police are among these organizations, as they have to manually process a vast number of criminal reports, news articles related to crimes, occurrence and evidence reports, and other unstructured documents. Automatic extraction and representation of data and knowledge in such documents is an essential task to reduce the manual analysis burden and to automate the discovering of names and entities relationships that may exist in a case. This paper presents SEMCrime, a framework used to extract and classify named-entities and relations in Portuguese criminal reports and documents, and represent the data retrieved into a graph database. A 5WH1 (Who, What, Why, Where, When, and How) information extraction method was applied, and a graph database representation was used to store and visualize the relations extracted from the documents. Promising results were obtained with a prototype developed to evaluate the framework, namely a name-entity recognition with an F-Measure of 0.73, and a 5W1H information extraction performance with an F-Measure of 0.65.
Effects of Essential Oils from 24 Plant Species on Sitophilus zeamais Motsch (Coleoptera, Curculionidae)
Authors: Patiño-Bayona William R. , Nagles Galeano Leidy J. , Bustos Cortes Jenifer J. , Delgado Ávila Wilman A. , Herrera Daza Eddy , Suárez Luis E. Cuca , Prieto-Rodríguez Juliet A. , Patiño-Ladino Oscar J.
Published: June 2021

Chemical control of the maize weevil (Sitophilus zeamais) has been ineffective and presents serious collateral damage. Among plant-derived insecticides, essential oils (EOs) are suitable candidates to control this stored products pest. In this work, the insecticidal activities of 45 natural EOs against S. zeamais adults were screened, and the most promising ones (24 EOs) were characterized by GC–MS. The repellent and toxic effects (contact and fumigant) of these 24 EOs were determined, and by a cluster analysis they were classified into two groups considering its fumigant activity and contact toxicity. For the EOs with the highest fumigant potential (14 oils) and their main active constituents (17 compounds), lethal concentrations were determined. The most active EOs were those obtained from L. stoechas and L. alba, with LC50 values of 303.4 and 254.1 µL/L air and characterized by a high content of monoterpenes. Regarding the major compounds, the oxygenated monoterpenes R-(+)-pulegone (LC50 = 0.580 mg/L air), S-(-)-pulegone (LC50 = 0.971 mg/L air) and R-(-)-carvone (LC50 = 1.423 mg/L air) were the most active, as few variations in their concentrations significantly increased insect mortality.