bluuebunny/crossref_metadata_2025 huggingface dataset:
Awareness of Cardiovascular Disease Risk Factors by Community Pharmacists in Saudi Arabia
Authors: Sulaiteen Fahad Mohammad , Al-Zaagi Ibrahim Abdulaziz , Alenazi Majed Sultan , Alotaibi Amani Zaben , Alghamdi Tahani Aali , Yousaf Anum , Ali Sheraz
Published: January 2023

Background: Pharmacists in community settings are recognized as highly accessible healthcare practitioners and demonstrate a crucial role in the primary prevention of cardiovascular disease. Evidence indicates that community pharmacists can make a significant impact on controlling cardiovascular disease risk factors, particularly on hypertension. Objectives: We aimed to assess the knowledge of community pharmacists in Saudi Arabia regarding cardiovascular disease risk factors. Methods: A cross-sectional study involving community pharmacists was conducted. The knowledge of cardiovascular disease risk factors was assessed with the Heart Disease Fact Questionnaire (HDFQ). A web link for an anonymous questionnaire was shared with the licensed community pharmacists in Saudi Arabia using the “Seha” platform of the Ministry of Health. Data analysis was performed with R version 4.0.5. Results: Three hundred seventy-four community pharmacists responded to the questionnaire. Many community pharmacists (94.4%) had satisfactory awareness of cardiovascular disease risk factors. The odds of having satisfactory HDFQ knowledge for community pharmacists seeing more than 20 individuals with diabetes per month were 20 times (AOR = 19.9, 95% CI: 1.73–260, and p = 0.019) more compared to those seeing fewer than 10 individuals with diabetes per month. The age of the community pharmacists and the average number of individuals with diabetes seen per month were found to be factors associated with satisfactory HDFQ knowledge. Conclusion: The practicing pharmacists had a substantial understanding of cardiovascular disease risk factors. In line with counseling and education, the implementation of community pharmacy models for improving the knowledge of pharmacists, particularly the young pharmacists, is needed to effectively assist patients with cardiovascular disease.
Understanding the Experiences of People Living with Stroke Engaging in a Community-Based Physical-Activity Programme
Authors: Smith Matthew , Scott Andrew , Mellish Serena , Faulkner James
Published: January 2023

Research has evidenced that regular exercise can provide physical and physiological benefits for people living with stroke. Our study aims to explore the experiences of people living with stroke when participating in a community physical activity programme. This programme was created to offer targeted physical activity and education interventions following the discharge of patients from the healthcare pathway. This qualitative study involved semi-structured interviews with 16 participants living with stroke who were recruited from individuals who had engaged with the activity programme. A reflexive thematic analysis was conducted on the data, and four overarching themes were developed: (i) Feelings of appreciation, (ii) Interactions with other patients, (iii) Positive contributions of trained instructors, and iv) Personal progress. Generally, participants reported very positive perceptions of the exercise programme, and were very grateful for the opportunity that the exercise classes provided. We hope that these findings will offer practical suggestions for healthcare providers who might develop similar activity programmes for clinical populations.
Fruit Crop Improvement with Genome Editing, In Vitro and Transgenic Approaches
Authors: Penna Suprasanna , Jain Shri Mohan
Published: January 2023

Fruit species contribute to nutritional and health security by providing micronutrients, antioxidants, and bioactive phytoconstituents, and hence fruit-based products are becoming functional foods presently and for the future. Although conventional breeding methods have yielded improved varieties having fruit quality, aroma, antioxidants, yield, and nutritional traits, the threat of climate change and need for improvement in several other traits such as biotic and abiotic stress tolerance and higher nutritional quality has demanded complementary novel strategies. Biotechnological research in fruit crops has offered immense scope for large-scale multiplication of elite clones, in vitro, mutagenesis, and genetic transformation. Advanced molecular methods, such as genome-wide association studies (GWAS), QTLomics, genomic selection for the development of novel germplasm having functional traits for agronomic and nutritional quality, and enrichment of bioactive constituents through metabolic pathway engineering and development of novel products, are now paving the way for trait-based improvement for developing genetically superior varieties in fruit plant species for enhanced nutritional quality and agronomic performance. In this article, we highlight the applications of in vitro and molecular breeding approaches for use in fruit breeding.
Investigation of Growth Factors and Mathematical Modeling of Nutrient Media for the Shoots Multiplication In Vitro of Rare Plants of the Rostov Region
Authors: Chokheli Vasiliy A. , Bakulin Semyon D. , Ermolaeva Olga Yu. , Kozlovsky Boris L. , Dmitriev Pavel A. , Stepanenko Victoriya V. , Kornienko Igor V. , Bushkova Anastasia A. , Rajput Vishnu D. , Varduny Tatiana V.
Published: January 2023

Micropropagation is an effective way to preserve the gene pool of threatened plants. This study is devoted to the mathematical modeling of nutrient media and the study of the effect of mT (meta-topoline) on the multiplication of shoots of Hedysarum grandiflorum, Hyssopus cretaceus, and Matthiola fragrans in vitro in comparison with benzylaminopurine (BAP) and kinetin (KT). Initiation was performed on an MS medium with 0.5 mg/L BAP. For shoots multiplication, MS, B5, and WPM media were used with the addition of mT, BAP, KT. For H. grandiflorum, the multiplication coefficient of shoots was highest on medium B5 with the addition of mT at a concentration of 1 mg/L—2.90 shoots per plant, for H. cretaceus—B5 + 0.5 mg/L mT, and for M. fragrans—B5 + 1 mg/L KT. A positive effect of mT on H. grandiflorum and M. fragrans in vitro was found. The efficiency of using KT for H. cretaceus shoot multiplication is shown. The effectiveness of the B5 nutrient medium for H. grandiflorum and M. fragrans was determined. The positive effect of WPM for H. cretaceus micropropagation has been demonstrated. It is not recommended to use the MS media for micropropagation of these plant species.
Dissecting Seed Proanthocyandin Composition and Accumulation under Different Berry Ripening Process in Wine Grapes
Authors: Liu Aoyi , Wang Jingjing , Yao Xuechen , Xia Nongyu , Sun Qi , Duan Changqing , Pan Qiuhong
Published: January 2023

Grape berry proanthocyandin (PA) mainly exists in the skin and seeds. Its content and composition determine the intensity of bitterness and astringency. Affected by global warming, the world’s wine-producing regions, in particular in dry-hot regions such as western China, are facing the problem of unsynchronized berry ripening and seed ripening. Therefore, it is urgent to understand the influence of berry ripening progression on the composition and accumulation of seed PA, ultimately providing strategies for grape harvest decisions. In this paper, Vitis vinfera L. cv. Cabernet sauvignon and Marselan grapes from four sub-regions with different maturation processes were used as experimental materials to study the changes of soluble and insoluble PA contents as well as differences in their composition and mean degree of polymers (mDP) in seeds. The results showed that compared with ‘Cabernet sauvignon’ seeds, the mDP of soluble and insoluble PA were higher in ‘Marselan’ seeds. Both varieties showed that the grape berry, with the fastest sugar accumulation, had relatively high soluble PA content in seeds and a high content of (-)-epigallocatechin-3-gallate and (-)-epicatechin in the seed PA composition units. In contrast, the ‘Cabernet sauvignon’ grapes from the YQ vineyard exhibited the slowest sugar accumulation speed among the four studied vineyards, and their seed PA had the highest mDP and the lowest proportion of (-)-epigallocatechin-3-gallate in the composition units when commercially harvested. According to the results, it is suggested that a faster maturation process would bring about higher levels of bitterness composition, such as (-)-epigallocatechin-3-gallate in seed PA, which is not conducive to the formation of good-tasting tannins.
Biotechnologies and Strategies for Grapevine Improvement
Authors: Butiuc-Keul Anca , Coste Ana
Published: January 2023

Grapevine (Vitis vinifera subsp. vinifera) is one of the most widespread and economically important perennial fruit crops in the world. Viticulture has changed over the years in response to changing environmental conditions and market demands, triggering the development of new and improved varieties to ensure the crop’s sustainability. The aim of this review is to provide a perspective on the recent developments in biotechnology and molecular biology and to establish the potential of these technologies for the genetic improvement of grapevine. The following aspects are discussed: (i) the importance of molecular marker-based methods for proper cultivar identification and how NGS-based high-throughput technologies have greatly benefited the development of genotyping techniques, trait mapping, and genomic selection; (ii) the recent advances in grapevine regeneration, genetic transformation, and genome editing, such as new breeding technology approaches for enhanced grapevine yield, quality improvement, and the selection of valuable varieties and cultivars. The specific problems and challenges linked to grapevine biotechnology, along with the importance of integrating classical and new technologies, are highlighted.
Risk Assessment of Sea Level Rise for Karasu Coastal Area, Turkey
Authors: Eliawa Ali , Numanoğlu Genç Aslı , Tora Hakan , Maraş Hadi Hakan
Published: January 2023

Sea Level Rise (SLR) due to global warming is becoming a more pressing issue for coastal zones. This paper presents an overall analysis to assess the risk of a low-lying coastal area in Karasu, Turkey. For SLR scenarios of 1 m, 2 m, and 3 m by 2100, inundation levels were visualized using Digital Elevation Model (DEM). The eight-side rule is applied as an algorithm through Geographic Information System (GIS) using ArcMap software with high-resolution DEM data generated by eleven 1:5000 scale topographic maps. The outcomes of GIS-based inundation maps indicated 1.40%, 6.02%, and 29.27% of the total land area by 1 m, 2 m, and 3 m SLR scenarios, respectively. Risk maps have shown that water bodies, low-lying urban areas, arable land, and beach areas have a higher risk at 1 m. In a 2 m scenario, along with the risk of the 1 m scenario, forests become at risk as well. For the 3 m scenario, almost all the territorial features of the Karasu coast are found to be inundated. The effect of SLR scenarios based on population and Gross Domestic Product (GDP) is also analyzed. It is found that the 2 and 3 m scenarios lead to a much higher risk compared to the 1 m scenario. The combined hazard–vulnerability data shows that estuarine areas on the west and east of the Karasu region have a medium vulnerability. These results provide primary assessment data for the Karasu region for the decision-makers to enhance land use policies and coastal management plans.
Overview of Coastal Vulnerability Indices with Reference to Physical Characteristics of the Croatian Coast of Istria
Authors: Šimac Zaviša , Lončar Nina , Faivre Sanja
Published: January 2023

Coastal areas are dynamic and complex systems exposed to waves, high tides, and storm surges. Often, these areas are densely populated and have essential socio-economic values for the region and country. Any changes or disruptions can cause a tremendous social burden. Coastal Vulnerability Index (CVI) is one of the most used and straightforward methods to assess coastal vulnerability. This paper aims to analyse and summarise the current state of published coastal vulnerability indices. The analysis seeks to develop a regional vulnerability index for the eastern Adriatic coast, specifically for the Istrian peninsula. A total of 18 published papers were reviewed. A detailed survey was performed on three groups of variables that represent (a) the physical features of the coast, (b) the amount of influence of wave energy on the coast, and (c) exposed socio-economic factors. While choosing Physical and ecological variables is relatively straightforward, choosing Socio-economic variables is particularly challenging. The number of variables differs significantly from one author to another. As a result of the huge variety of global coastal characteristics and different research approaches, there is no universal CVI. Therefore, analysed indices are not suited for the calculation of the vulnerability of the Istrian coast without modification. A 5 × 5 m cell dimension was proposed as the most suitable for analysing the physical vulnerability of the Croatian coast of Istria.
Barriers to Optimal Child Sleep among Families with Low Income: A Mixed-Methods Study to Inform Intervention Development
Authors: Adams Elizabeth L. , Edgar Amanda , Mosher Peyton , Armstrong Bridget , Burkart Sarah , Weaver R. Glenn , Beets Michael W. , Siceloff E. Rebekah , Prinz Ronald J.
Published: January 2023

This study gathered formative data on barriers to optimal child sleep to inform the development of a sleep intervention for parents of preschool-aged children in low-income households. Parents (n = 15, age: 34 ± 8 years, household income: $30,000 ± 17,845/year) reporting difficulties with their child’s sleep participated in this study. Mixed methods included an online survey and semi-structured phone interview. Items assessed barriers/facilitators to optimal child sleep and intervention preferences. Interview transcripts were coded using inductive analyses and constant-comparison methods to generate themes. Derived themes were then mapped onto the Theoretical Domains Framework to contextualize barriers and inform future intervention strategies. Themes that emerged included: stimulating bedtime activities, child behavior challenges, variability in children’s structure, parent work responsibilities, sleep-hindering environment, and parent’s emotional capacity. Parent’s intervention preferences included virtual delivery (preferred by 60% of parents) to reduce barriers and provide flexibility. Mixed preferences were observed for the group (47%) vs. individual (53%) intervention sessions. Parents felt motivated to try new intervention strategies given current frustrations, the potential for tangible results, and knowing others were in a similar situation. Future work will map perceived barriers to behavior change strategies using the Behavior Change Wheel framework to develop a parenting sleep intervention.
The Impact of Wearable Devices on Physical Activity for Chronic Disease Patients: Findings from the 2019 Health Information National Trends Survey
Authors: Yu Shiyuan , Chen Zhifeng , Wu Xiang
Published: January 2023

Background: Wearable devices are shown to be an advanced tool for chronic disease management, but their impacts on physical activity remain uninvestigated. This study aims to examine the effect of wearable devices on physical activity in general people and chronic patients. Methods: Our sample was from the third cycle of the fifth iteration of the Health Information National Trends Survey (HINTS), which includes a total of 5438 residents. Genetic matching was used to evaluate the effect of wearable devices on physical activity in different populations. Results: (1) Both using wearable devices and using them with high frequency will improve physical activity for the whole population. (2) Wearable devices may have greater positive effects on physical activity for chronic patients. (3) Especially in patients with hypertension, high-frequency use of wearable devices can significantly improve the duration and frequency of physical activity. Conclusions: Wearable devices lead to more physical activity, and the benefit is more noticeable for chronic patients, particularly those with hypertension.
Safe, Efficient, and Comfortable Autonomous Driving Based on Cooperative Vehicle Infrastructure System
Authors: Chen Jing , Zhao Cong , Jiang Shengchuan , Zhang Xinyuan , Li Zhongxin , Du Yuchuan
Published: January 2023

Traffic crashes, heavy congestion, and discomfort often occur on rough pavements due to human drivers’ imperfect decision-making for vehicle control. Autonomous vehicles (AVs) will flood onto urban roads to replace human drivers and improve driving performance in the near future. With the development of the cooperative vehicle infrastructure system (CVIS), multi-source road and traffic information can be collected by onboard or roadside sensors and integrated into a cloud. The information is updated and used for decision-making in real-time. This study proposes an intelligent speed control approach for AVs in CVISs using deep reinforcement learning (DRL) to improve safety, efficiency, and ride comfort. First, the irregular and fluctuating road profiles of rough pavements are represented by maximum comfortable speeds on segments via vertical comfort evaluation. A DRL-based speed control model is then designed to learn safe, efficient, and comfortable car-following behavior based on road and traffic information. Specifically, the model is trained and tested in a stochastic environment using data sampled from 1341 car-following events collected in California and 110 rough pavements detected in Shanghai. The experimental results show that the DRL-based speed control model can improve computational efficiency, driving efficiency, longitudinal comfort, and vertical comfort in cars by 93.47%, 26.99%, 58.33%, and 6.05%, respectively, compared to a model predictive control-based adaptive cruise control. The results indicate that the proposed intelligent speed control approach for AVs is effective on rough pavements and has excellent potential for practical application.
Adaptive Goal Processes and Underlying Motives That Sustain Mental Wellbeing and New Year Exercise Resolutions
Authors: Dickson Joanne M. , Hart Amelia , Fox-Harding Caitlin , Huntley Christopher D.
Published: January 2023

Exercise resolutions are the most common goals people set each New Year. However, research has rarely examined adaptive goal processes and motives that may maintain wellbeing and resolution pursuit. We therefore investigated if (1) personal goal flexibility and tenacity maintain mental wellbeing and adherence to New Year exercise resolutions and if (2) underlying intrinsic and extrinsic motives maintain wellbeing and sustained exercise resolution adherence. A community sample (N = 297) completed an online longitudinal study. At baseline, participants listed their most important exercise-related New Year resolution. Participants then completed measures to assess goal flexibility and tenacity, resolution motives, and mental wellbeing at baseline. At three follow-up surveys over a two-month period, participants completed self-report measures of wellbeing and adherence to their exercise resolution. As predicted, goal flexibility and tenacity each independently predicted wellbeing across time. Counter to prediction, neither goal flexibility nor tenacity predicted sustained exercise adherence. Notably, underlying intrinsic motives (but not extrinsic motives) maintained mental wellbeing and exercise adherence across time. Our findings indicate that goal flexibility and tenacity are beneficial in maintaining mental wellbeing and that pursuing resolutions for internalised motives is beneficial for one’s mental wellbeing and exercise adherence.
An Examination of Barriers to Accessing Mental Health Care, and Their Association with Depression, Stress, Suicidal Ideation, and Wellness in a Bangladeshi University Student Sample
Authors: Sifat Munjireen , Huq Maisha , Baig Mirza , Tasnim Naima , Green Kerry M.
Published: January 2023

Background: The mental health burden is high and rising among Bangladeshi university students. Understanding barriers to mental healthcare and how barriers impact mental health outcomes may inform the development of targeted interventions to decrease barriers and improve access to care. Aims: This study identifies barriers to mental healthcare and their association with mental health outcomes in a Bangladeshi university student sample. Methods: We conducted a cross-sectional survey (n = 350) on stigma-related, attitudinal, and instrumental barriers to accessing mental healthcare among Bangladeshi university students. We examined the association between stigma and non-stigma (i.e., attitudinal and instrumental) barriers with four mental health outcomes: suicidal ideation, depression, high perceived stress, and wellness. Results: Attitudinal barriers were the most reported barriers. Stigma-related barriers were significant for individuals who had experienced suicidal ideation (aOR = 2.97, p = 0.001), not for individuals with depression. Non-stigma-related barriers were significant for individuals who had experienced depression (aOR = 2.80, p = 0.011). Conclusions: The current work advances our understanding of how to improve access to mental healthcare among university students in Bangladesh. Stigma-related barriers were particularly salient for individuals who experienced suicidal ideation. Further study is needed on how stigma may impact access to care distinctly for different mental health problems among Bangladeshi university students.
Contribution of Genetic Polymorphisms in Human Health
Authors: Chiarella Pieranna , Capone Pasquale , Sisto Renata
Published: January 2023

Human health is influenced by various factors; these include genetic inheritance, behavioral lifestyle, socioeconomic and environmental conditions, and public access to care and therapies in case of illness, with the support of the national health system. All these factors represent the starting point for the prevention and promotion of a healthy lifestyle. However, it is not yet clear to what extent these factors may actually affect the health of an entire population. The exposures to environmental and occupational factors are several, most of which might be poorly known, contributing to influencing individual health. Personal habits, including diet, smoking, alcohol, and drug consumption, together with unhealthy behaviors, may inevitably lead people to the development of chronic diseases, contributing to increasing aging and decreasing life expectancy. In this article, we highlight the role of susceptibility biomarkers, i.e., the genetic polymorphisms of individuals of different ethnicities, with particular attention to the risk factors in the response to specific exposures of Europeans. Moreover, we discuss the role of precision medicine which is representing a new way of treating and preventing diseases, taking into account the genetic variability of the individual with each own clinical history and lifestyle.
The Mediating Effect of Presenteeism on the Relationship between Emotional Labor and Work Engagement of Coaches for Disability Sports
Authors: Seo Eun-Chul , Sim Young-Kyun , Kim Inwoo , Seo Jae-Pil , Ha Min-Seong , Kim Song-Eun
Published: January 2023

The aim of present study was to examine the mediating effect of presenteeism on the relationship between emotional labor and work engagement of coaches for disability sports. A total of 198 coaches in Korea participated in this study. Participants responded a survey measuring emotional labor, presenteeism, and work engagement. After analyzing the correlation between each variable, the mediation model was verified through structural equation model analysis. The results reveal that emotional labor of coaches for disability sports positively predicted their work engagement, but negatively predicted presenteeism. In addition, the participants’ presenteeism can have a negative effect on their work engagement. Moreover, completing work in presenteeism was found to mediate the relationship between the deep acting and surface acting in emotional labor and work engagement of disability sports coaches.
Fatal Motor Vehicle Crashes in Upstate and Long Island New York: The Impact of High Visibility Seat Belt Enforcement on Multiple Risky Driving Behaviors
Authors: Pressley Joyce C. , Puri Nirajan , He Tianhui
Published: January 2023

Despite an observed daytime front-seat seat belt use that exceeds 90%, nearly half of motor vehicle occupants who die in New York State (NYS) each year are not wearing a seat belt. Crash outcomes were examined by occupant, vehicle, environmental and traffic enforcement patterns related to the annual Click It or Ticket high visibility seat belt enforcement campaign. Three periods of enforcement were examined: pre-enforcement, peri-enforcement (during/immediately after), and post-enforcement. Of the 14.4 million traffic citations, 713,990 (5.0%) were seat belt violations. Relative risk with 95% CI was assessed using deaths from the Fatality Analysis Reporting System (FARS) and SAS Glimmix 9.4 software. Mortality was lower peri-enforcement (32.9%) compared to pre- (40.9%) or post-enforcement (37.1%) (p < 0.001) and tended to be elevated in low enforcement response areas (43.6%). Fatalities were 30% lower (0.7, 95% CI 0.6–0.9) during peri-enforcement in models adjusted for demographics, law coverage, enforcement response, rural, weekend, impairment, speeding, and vehicle type. Adjusted mortality was higher in rural (1.9, 1.6–2.6), alcohol-involved (1.8, 1.4–2.9), and speeding-involved (2.0, 1.7–2.5) crashes. Peri-enforcement alcohol- and speed-involved fatalities tended to be lower in restrained, unrestrained and occupants missing belt status. The finding of lower mortality in both belted and unbelted occupant’s peri-enforcement—in the context of fewer fatal speed and alcohol-involved crashes—suggests that the mechanism(s) through which high visibility seat belt enforcement lowers mortality is through impacting multiple risky driving behaviors.
Neighborhood Socioeconomic Status and Women’s Mental Health: A Longitudinal Study of Hurricane Katrina Survivors, 2005–2015
Authors: Nguyen Angela-Maithy , Kim Yeerae , Abramson David M.
Published: January 2023

There is limited knowledge on the relationship between neighborhood factors and mental health among displaced disaster survivors, particularly among women. Hurricane Katrina (Katrina) was the largest internal displacement in the United States (U.S.), which presented itself as a natural experiment. We examined the association between neighborhood socioeconomic status (SES) and mental health among women up to 10 years following Katrina (N = 394). We also investigated whether this association was modified by move status, comparing women who were permanently displaced to those who had returned to their pre-Katrina residence. We used hierarchical linear models to measure this association, using data from the American Community Survey and the Gulf Coast Child and Family Health study. Neighborhood SES was created as an index which represented social and economic characteristics of participants’ neighborhoods. Mental health was measured using mental component summary (MCS) scores. Increased neighborhood SES was positively associated with mental health after controlling for age, race/ethnicity, economic positioning, time, and move status (19.6, 95% Confidence Interval: 5.8, 33.7). Neighborhood SES and mental health was also modified by move status. These findings underscore the need to better understand the impacts of socioeconomic conditions and health outcomes among women affected by natural disasters.
Silver Nanoparticles Modified by Carbosilane Dendrons and PEG as Delivery Vectors of Small Interfering RNA
Authors: Abashkin Viktar , Pędziwiatr-Werbicka Elżbieta , Horodecka Katarzyna , Zhogla Victoriya , Ulashchik Egor , Shmanai Vadim , Shcharbin Dzmitry , Bryszewska Maria
Published: January 2023

The fact that cancer is one of the leading causes of death requires researchers to create new systems of effective treatment for malignant tumors. One promising area is genetic therapy that uses small interfering RNA (siRNA). These molecules are capable of blocking mutant proteins in cells, but require specific systems that will deliver RNA to target cells and successfully release them into the cytoplasm. Dendronized and PEGylated silver nanoparticles as potential vectors for proapoptotic siRNA (siMCL-1) were used here. Using the methods of one-dimensional gel electrophoresis, the zeta potential, dynamic light scattering, and circular dichroism, stable siRNA and AgNP complexes were obtained. Data gathered using multicolor flow cytometry showed that AgNPs are able to deliver (up to 90%) siRNAs efficiently to some types of tumor cells, depending on the degree of PEGylation. Analysis of cell death showed that complexes of some AgNP variations with siMCL-1 lead to ~70% cell death in the populations that uptake these complexes due to apoptosis.
Hepatotoxicity of Drugs Used in Multiple Sclerosis, Diagnostic Challenge, and the Role of HLA Genotype Susceptibility
Authors: Meunier Lucy , Larrey Dominique
Published: January 2023

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and the association with other autoimmune diseases is well-documented. There are many therapeutic options for the treatment of MS. Most of the available drugs cause drug-induced liver injury (DILI) to variable extents with heterogeneous clinical and biological manifestations, including liver injury with or without signs of hypersensitivity and autoimmunity. The diagnosis of DILI may be particularly difficult because MS is frequently associated with idiopathic autoimmune hepatitis. Recent advances suggest that MS and immune-mediated DILI could be promoted by genetic factors, including HLA genotype. In addition, some of these drugs may promote hepatitis B virus reactivation. This review explores the potential hepatotoxicity of drugs used to treat MS and the criteria to distinguish DILI from idiopathic autoimmune hepatitis associated with MS. The role of susceptible genes both promoting MS and causing the hepatotoxicity of the drug used for MS treatment is also discussed.
The Inhibitory Properties of a Novel, Selective LMTK3 Kinase Inhibitor
Authors: Agnarelli Alessandro , Lauer Betrán Andrea , Papakyriakou Athanasios , Vella Viviana , Samuels Mark , Papanastasopoulos Panagiotis , Giamas Christina , Mancini Erika J. , Stebbing Justin , Spencer John , Cilibrasi Chiara , Ditsiou Angeliki , Giamas Georgios
Published: January 2023

Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical analyses, we identify a highly selective small molecule LMTK3 inhibitor, namely C36. Biochemical/biophysical and cellular studies revealed that C36 displays a high in vitro selectivity profile and provides notable therapeutic effect when tested in the National Cancer Institute (NCI)-60 cancer cell line panel. We also report the binding affinity between LMTK3 and C36 as demonstrated via microscale thermophoresis (MST). In addition, C36 exhibits a mixed-type inhibition against LMTK3, consistent with the inhibitor overlapping with both the adenosine 5′-triphosphate (ATP)- and substrate-binding sites. Treatment of different breast cancer cell lines with C36 led to decreased proliferation and increased apoptosis, further reinforcing the prospective value of LMTK3 inhibitors for cancer therapy.
Exploring the Potential Energy Surface of Pt6 Sub-Nano Clusters Deposited over Graphene
Authors: Barrena-Espés Daniel , Boneta Sergio , Polo Victor , Munárriz Julen
Published: January 2023

Catalytic systems based on sub-nanoclusters deposited over different supports are promising for very relevant chemical transformations such as many electrocatalytic processes as the ORR. These systems have been demonstrated to be very fluxional, as they are able to change shape and interconvert between each other either alone or in the presence of adsorbates. In addition, an accurate representation of their catalytic activity requires the consideration of ensemble effects and not a single structure alone. In this sense, a reliable theoretical methodology should assure an accurate and extensive exploration of the potential energy surface to include all the relevant structures and with correct relative energies. In this context, we applied DFT in conjunction with global optimization techniques to obtain and analyze the characteristics of the many local minima of Pt6 sub-nanoclusters over a carbon-based support (graphene)—a system with electrocatalytic relevance. We also analyzed the magnetism and the charge transfer between the clusters and the support and paid special attention to the dependence of dispersion effects on the ensemble characteristics. We found that the ensembles computed with and without dispersion corrections are qualitatively similar, especially for the lowest-in-energy clusters, which we attribute to a (mainly) covalent binding to the surface. However, there are some significant variations in the relative stability of some clusters, which would significantly affect their population in the ensemble composition.
Conjugated Linoleic Acids Have Anti-Inflammatory Effects in Cultured Endothelial Cells
Authors: Valenzuela Carina A. , Baker Ella J. , Miles Elizabeth A. , Calder Philip C.
Published: January 2023

Conjugated linoleic acid (CLA) isomers may have a role in preventing atherosclerosis through the modulation of inflammation, particularly of the endothelium. However, whether low concentrations of CLAs are able to affect basal unstimulated endothelial cell (EC) responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the basal inflammatory responses by ECs. EA.hy926 cells (HUVEC lineage) were cultured under standard conditions and exposed to individual CLAs for 48 h. Both CLAs were incorporated into ECs in a dose-dependent manner. CLA9,11 (1 μM) significantly decreased concentrations of MCP-1 (p < 0.05), IL-6 (p < 0.05), IL-8 (p < 0.01) and RANTES (p < 0.05) in the culture medium. CLA10,12 (10 μM) decreased the concentrations of MCP-1 (p < 0.05) and RANTES (p < 0.05) but increased the concentration of IL-6 (p < 0.001). At 10 μM both CLAs increased the relative expression of the NFκβ subunit 1 gene (p < 0.01 and p < 0.05, respectively), while decreasing the relative expression of PPARα (p < 0.0001), COX-2 (p < 0.0001) and IL-6 (p < 0.0001) genes. CLA10,12 increased the relative expression of the gene encoding IκK-β at 10 μM compared with CLA9,11 (p < 0.05) and increased the relative expression of the gene encoding IκBα at 1 and 10 μM compared with linoleic acid (both p < 0.05). Neither CLA affected the adhesion of monocytes to ECs. These results suggest that low concentrations of both CLA9,11 and CLA10,12 have modest anti-inflammatory effects in ECs. Thus, CLAs may influence endothelial function and the risk of vascular disease. Nevertheless, at these low CLA concentrations some pro-inflammatory genes are upregulated while others are downregulated, suggesting complex effects of CLAs on inflammatory pathways.
iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs
Authors: Lee Hae-Ri , Kim Soo , Shin Sungho , Jeong Seon-Yeong , Lee Dae-Won , Lim Sun-Ung , Kang Ji Yeon , Son Mi-Young , Lee Cheolju , Yu Kyung-Rok , Kim Myungshin , Oh Il-Hoan
Published: January 2023

Mesenchymal stromal cells derived from induced pluripotent stem cells (iMSCs) have been proposed as alternative sources of primary MSCs with various advantages for cell therapeutic trials. However, precise evaluation of the differences between iMSCs and primary MSCs is lacking due to individual variations in the donor cells, which obscure direct comparisons between the two. In this study, we generated donor-matched iMSCs from individual bone marrow-derived MSCs and directly compared their cell-autonomous and paracrine therapeutic effects. We found that the transition from primary MSCs to iMSCs is accompanied by a functional shift towards higher proliferative activity, with variations in differentiation potential in a donor cell-dependent manner. The transition from MSCs to iMSCs was associated with common changes in transcriptomic and proteomic profiles beyond the variations of their individual donors, revealing expression patterns unique for the iMSCs. These iMSC-specific patterns were characterized by a shift in cell fate towards a pericyte-like state and enhanced secretion of paracrine cytokine/growth factors. Accordingly, iMSCs exhibited higher support for the self-renewing expansion of primitive hematopoietic progenitors and more potent immune suppression of allogenic immune responses than MSCs. Our study suggests that iMSCs represent a separate entity of MSCs with unique therapeutic potential distinct from their parental MSCs, but points to the need for iMSC characterization in the individual basis.
The Prolonged Treatment of Salmonella enterica Strains with Human Serum Effects in Phenotype Related to Virulence
Authors: Futoma-Kołoch Bożena , Małaszczuk Michał , Korzekwa Kamila , Steczkiewicz Małgorzata , Gamian Andrzej , Bugla-Płoskońska Gabriela
Published: January 2023

Salmonella enterica as common pathogens of humans and animals are good model organisms to conduct research on bacterial biology. Because these bacteria can multiply in both the external environments and in the living hosts, they prove their wide adaptability. It has been previously demonstrated that prolonged exposition of Salmonella serotype O48 cells to normal human serum led to an increase in resistance to sera in connection with the synthesis of very long O-antigen. In this work, we have studied the phenotype connected to virulence of Salmonella enterica strains that were subjected to consecutive passages in 50% human serum from platelet-poor plasma (SPPP). We found that eight passages in SPPP may not be enough for the bacteria to become serum-resistant (S. Typhimurium ATCC 14028, S. Senftenberg). Moreover, C1q and C3c complement components bound to Salmonellae (S. Typhimurium ATCC 14028, S. Hammonia) membrane proteins, which composition has been changed after passaging in sera. Interestingly, passages in SPPP generated genetic changes within gene fljB, which translated to cells’ motility (S. Typhimurium ATCC 14028, S. Erlangen). One strain, S. Hammonia exposed to a serum developed a multi-drug resistance (MDR) phenotype and two S. Isaszeg and S. Erlangen tolerance to disinfectants containing quaternary ammonium salts (QAS). Furthermore, colonial morphotypes of the serum adaptants were similar to those produced by starter cultures. These observations suggest that overcoming stressful conditions is manifested on many levels. Despite great phenotypic diversity occurring after prolonged exposition to SPPP, morphotypes of colonies remained unchanged in basic media. This work is an example in which stable morphotypes distinguished by altered virulence can be confusing during laboratory work with life-threatening strains.
Diagnostic and Prognostic Role of Extracellular Vesicles in Pancreatic Cancer: Current Evidence and Future Perspectives
Authors: Nicoletti Alberto , Negri Marcantonio , Paratore Mattia , Vitale Federica , Ainora Maria Elena , Nista Enrico Celestino , Gasbarrini Antonio , Zocco Maria Assunta , Zileri Dal Verme Lorenzo
Published: January 2023

Pancreatic cancer is one of the most aggressive tumors, with a dismal prognosis due to poor detection rates at early stages, rapid progression, post-surgical complications, and limited effectiveness of conventional oncologic therapies. There are no consistently reliable biomarkers or imaging modalities to accurately diagnose, classify, and predict the biological behavior of this tumor. Therefore, it is imperative to develop new and improved strategies to detect pancreatic lesions in the early stages of cancerization with greater sensitivity and specificity. Extracellular vesicles, including exosome and microvesicles, are membrane-coated cellular products that are released in the outer environment. All cells produce extracellular vesicles; however, this process is enhanced by inflammation and tumorigenesis. Based on accumulating evidence, extracellular vesicles play a crucial role in pancreatic cancer progression and chemoresistance. Moreover, they may represent potential biomarkers and promising therapy targets. The aim of the present review is to review the current evidence on the role of extracellular vesicles in pancreatic cancer.
Bioprinting Technologies and Bioinks for Vascular Model Establishment
Authors: Kong Zhiyuan , Wang Xiaohong
Published: January 2023

Clinically, large diameter artery defects (diameter larger than 6 mm) can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene. There are many problems in the construction of small diameter blood vessels (diameter between 1 and 3 mm) and microvessels (diameter less than 1 mm), especially in the establishment of complex vascular models with multi-scale branched networks. Throughout history, the vascularization strategies have been divided into three major groups, including self-generated capillaries from implantation, pre-constructed vascular channels, and three-dimensional (3D) printed cell-laden hydrogels. The first group is based on the spontaneous angiogenesis behaviour of cells in the host tissues, which also lays the foundation of capillary angiogenesis in tissue engineering scaffolds. The second group is to vascularize the polymeric vessels (or scaffolds) with endothelial cells. It is hoped that the pre-constructed vessels can be connected with the vascular networks of host tissues with rapid blood perfusion. With the development of bioprinting technologies, various fabrication methods have been achieved to build hierarchical vascular networks with high-precision 3D control. In this review, the latest advances in 3D bioprinting of vascularized tissues/organs are discussed, including new printing techniques and researches on bioinks for promoting angiogenesis, especially coaxial printing, freeform reversible embedded in suspended hydrogel printing, and acoustic assisted printing technologies, and freeform reversible embedded in suspended hydrogel (flash) technology.
Introduction from Guest Editors to Special Issue “Magnetism in Chemistry”
Authors: Fianchini Mauro , Gracia Jose , Mikhailov Oleg V.
Published: January 2023

Magnetism in a chemical compound is the macroscopic result of the couplings of the spins of electrons within in it [...]
Immunogenicity and Safety of the BNT162b2 COVID-19 Vaccine in Patients with Cystic Fibrosis with or without Lung Transplantation
Authors: Lucca Francesca , Bezzerri Valentino , Danese Elisa , Olioso Debora , Peserico Denise , Boni Christian , Cucchetto Giulia , Montagnana Martina , Tridello Gloria , Meneghelli Ilaria , Ros Mirco , Lippi Giuseppe , Cipolli Marco
Published: January 2023

Cystic fibrosis (CF) is characterized by a progressive decline in lung function, which may be further impaired by viral infections. CF is therefore considered a comorbidity of coronavirus disease 2019 (COVID-19), and SARS-CoV-2 vaccine prioritization has been proposed for patients with (pw)CF. Poor outcomes have been reported in lung transplant recipients (LTR) after SARS-CoV-2 infections. LTR have also displayed poor immunization against SARS-CoV-2 after mRNA-based BNT162b2 vaccination, especially in those undergoing immunosuppressive treatment, mostly those receiving mycophenolate mofetil (MMF) therapy. We aimed to determine here the immunogenicity and safety of the BNT162b2 vaccine in our cohort of 260 pwCF, including 18 LTR. Serum levels of neutralizing anti-SARS-CoV-2 IgG and IgA antibodies were quantified after the administration of two doses. PwCF displayed a vaccine-induced IgG and IgA antiviral response comparable with that seen in the general population. We also observed that the immunogenicity of the BNT162b2 vaccine was significantly impaired in the LTR subcohort, especially in patients undergoing MMF therapy. The BNT162b2 vaccine also caused minor adverse events as in the general population, mostly after administration of the second dose. Overall, our results justify the use of the BNT162b2 vaccine in pwCF and highlight the importance of a longitudinal assessment of the anti-SARS-CoV-2 IgG and IgA neutralizing antibody response to COVID-19 vaccination.
Emerging Hallmarks of Metabolic Reprogramming in Prostate Cancer
Authors: Lasorsa Francesco , di Meo Nicola Antonio , Rutigliano Monica , Ferro Matteo , Terracciano Daniela , Tataru Octavian Sabin , Battaglia Michele , Ditonno Pasquale , Lucarelli Giuseppe
Published: January 2023

Prostate cancer (PCa) is the most common male malignancy and the fifth leading cause of cancer death in men worldwide. Prostate cancer cells are characterized by a hybrid glycolytic/oxidative phosphorylation phenotype determined by androgen receptor signaling. An increased lipogenesis and cholesterogenesis have been described in PCa cells. Many studies have shown that enzymes involved in these pathways are overexpressed in PCa. Glutamine becomes an essential amino acid for PCa cells, and its metabolism is thought to become an attractive therapeutic target. A crosstalk between cancer and stromal cells occurs in the tumor microenvironment because of the release of different cytokines and growth factors and due to changes in the extracellular matrix. A deeper insight into the metabolic changes may be obtained by a multi-omic approach integrating genomics, transcriptomics, metabolomics, lipidomics, and radiomics data.
Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number
Authors: López-Armas Gabriela del Carmen , Ramos-Márquez Martha Eloisa , Navarro-Meza Mónica , Macías-Islas Miguel Ángel , Saldaña-Cruz Ana Miriam , Zepeda-Moreno Abraham , Siller-López Fernando , Cruz-Ramos José Alfonso
Published: January 2023

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.