bluuebunny/crossref_metadata_2025 huggingface dataset:
Fuzzy Fractional Order PID Tuned via PSO for a Pneumatic Actuator with Ball Beam (PABB) System
Authors: Muftah Mohamed Naji , Faudzi Ahmad Athif Mohd , Sahlan Shafishuhaza , Mohamaddan Shahrol
Published: May 2023

This study aims to improve the performance of a pneumatic positioning system by designing a control system based on Fuzzy Fractional Order Proportional Integral Derivative (Fuzzy FOPID) controllers. The pneumatic system’s mathematical model was obtained using a system identification approach, and the Fuzzy FOPID controller was optimized using a PSO algorithm to achieve a balance between performance and robustness. The control system’s performance was compared to that of a Fuzzy PID controller through real-time experimental results, which showed that the former provided better rapidity, stability, and precision. The proposed control system was applied to a pneumatically actuated ball and beam (PABB) system, where a Fuzzy FOPID controller was used for the inner loop and another Fuzzy FOPID controller was used for the outer loop. The results demonstrated that the intelligent pneumatic actuator, when coupled with a Fuzzy FOPID controller, can accurately and robustly control the positioning of the ball and beam system.
A Time-Fractional Schrödinger Equation with Singular Potentials on the Boundary
Authors: Alazman Ibtehal , Jleli Mohamed , Samet Bessem
Published: May 2023

A Schrödinger equation with a time-fractional derivative, posed in (0,∞)×I, where I=]a,b], is investigated in this paper. The equation involves a singular Hardy potential of the form λ(x−a)2, where the parameter λ belongs to a certain range, and a nonlinearity of the form μ(x−a)−ρ|u|p, where ρ≥0. Using some a priori estimates, necessary conditions for the existence of weak solutions are obtained.
Extracellular Polysaccharide Receptor and Receptor-Binding Proteins of the Rhodobacter capsulatus Bacteriophage-like Gene Transfer Agent RcGTA
Authors: Alim Nawshin T. B. , Koppenhöfer Sonja , Lang Andrew S. , Beatty J. Thomas
Published: May 2023

A variety of prokaryotes produce a bacteriophage-like gene transfer agent (GTA), and the alphaproteobacterial Rhodobacter capsulatus RcGTA is a model GTA. Some environmental isolates of R. capsulatus lack the ability to acquire genes transferred by the RcGTA (recipient capability). In this work, we investigated the reason why R. capsulatus strain 37b4 lacks recipient capability. The RcGTA head spike fiber and tail fiber proteins have been proposed to bind extracellular oligosaccharide receptors, and strain 37b4 lacks a capsular polysaccharide (CPS). The reason why strain 37b4 lacks a CPS was unknown, as was whether the provision of a CPS to 37b4 would result in recipient capability. To address these questions, we sequenced and annotated the strain 37b4 genome and used BLAST interrogations of this genome sequence to search for homologs of genes known to be needed for R. capsulatus recipient capability. We also created a cosmid-borne genome library from a wild-type strain, mobilized the library into 37b4, and used the cosmid-complemented strain 37b4 to identify genes needed for a gain of function, allowing for the acquisition of RcGTA-borne genes. The relative presence of CPS around a wild-type strain, 37b4, and cosmid-complemented 37b4 cells was visualized using light microscopy of stained cells. Fluorescently tagged head spike fiber and tail fiber proteins of the RcGTA particle were created and used to measure the relative binding to wild-type and 37b4 cells. We found that strain 37b4 lacks recipient capability because of an inability to bind RcGTA; the reason it is incapable of binding is that it lacks CPS, and the absence of CPS is due to the absence of genes previously shown to be needed for CPS production in another strain. In addition to the head spike fiber, we found that the tail fiber protein also binds to the CPS.
Partial Contribution of Socioeconomic Factors to the Mortality Rate of the Working-Age Population in Russia
Authors: Jakovljevic Mihajlo , Kozlova Olga , Makarova Maria , Neklyudova Natalia , Pyshmintseva Olga
Published: May 2023

This study’s relevance lies in the need to assess the role of socioeconomic, medical, and demographic factors on working-age population mortality in Russia. The purpose of this study is to substantiate the methodological tools for the assessment of the partial contribution of the most important factors that determine the dynamics of the mortality of the working-age population. Our hypothesis is that the factors determining the socioeconomic situation in the country affect the level and dynamics of mortality of the working-age population, but to a different extent in each separate period. To analyse the impact of the factors, we used official Rosstat data for the period from 2005 to 2021. We used the data that reflect the dynamics of socioeconomic and demographic indicators, including the dynamics of mortality of the working-age population in Russia as a whole and in its 85 regions. First, we selected 52 indicators of socioeconomic development and then grouped them into four factor blocks (working conditions, health care, life security, living standards). To reduce the level of statistical noise, we carried out a correlation analysis, which allowed us to narrow down the list to 15 key indicators with the strongest association with the mortality rate of the working-age population. The total period of 2005–2021 was divided into five segments of 3–4 years each, characterising the picture of the socioeconomic state of the country during the period under consideration. The socioeconomic approach used in the study made it possible to assess the extent to which the mortality rate was influenced by the indicators adopted for analysis. The results of this study show that over the whole period, life security (48%) and working conditions (29%) contributed most to the level and dynamics of mortality in the working-age population, while factors determining living standards and the state of the healthcare system accounted for much smaller shares (14% and 9%, respectively). The methodological apparatus of this study is based on the application of methods of machine learning and intelligent data analysis, which allowed us to identify the main factors and their share in the total influence on the mortality rate of the working-age population. The results of this study show the need to monitor the impact of socioeconomic factors on the dynamics and mortality rate of the working-age population in order to improve the effectiveness of social programme. When developing and adjusting government programmes to reduce mortality in the working-age population, the degree of influence of these factors should be taken into account.
Preconception Expanded Carrier Screening: A Discourse Analysis of Dutch Webpages
Authors: Jämterud Sofia , Snoek Anke
Published: May 2023

Preconception expanded carrier screening (PECS) informs prospective parents about the risk of conceiving a child with a heritable genetic condition. PECS will also, for many, become an important screening test, and websites will likely play a vital role in providing information on this practice. The aim of this article is to examine rationalities in the information on PECS on Dutch websites. The method used is multimodal critical discourse analysis. This method allows an examination of norms and assumptions in the descriptions, as well as of the positions that are discursively made available. The data consist of publicly available material on websites from two genetics departments in the Netherlands. In the results, we present the three main discourses and subject positions that were identified: risk and the couple as possible mediators of severe conditions; the focus on scientific facts and rational conceivers; and severity of the conditions and the responsible couple. In this study, we highlight the importance of acknowledging the interrelation between epistemology and ethics in the discourse on PECS. Finally, it is claimed that the focus on scientific facts in information on PECS risks making existential and ethical dilemmas and choices invisible.
Regional Differences in Self-Reported Health, Physical Activity and Physical Fitness of Urban Senior Citizens in Austria
Authors: Jungreitmayr Sonja , Venek Verena , Ring-Dimitriou Susanne
Published: May 2023

The aim of this study is to compare data on the health status, self-reported exercise and non-exercise physical activity as well as fitness parameters, such as grip strength, of people in retirement in two cities that are both considered urban centres according to the statistical office of the European Union (EUROSTAT), but differ by geographic location. Self-reported physical activity questionnaires and objective assessments of physical fitness indicators collected by sports scientists were used and examined for differences. A total of 210 people (66.3 years ± 2.3) in Salzburg (n = 90) and Vienna (n = 120) was analysed. While no differences were found in self-reported health, there were differences in self-reported exposure to self-reported exercise and non-exercise physical activity, with the Viennese population being more inactive than their more western comparison group. In addition, the objective indicators for muscle strength, balance and flexibility of the lower extremities differed significantly in favour of the more western Austrian population. We recommend assessing the situation of older people in Austria regarding their physical activity and fitness on a regional basis, even if they live in cities of the same category. Future projects should therefore aim to consider specific regional needs during development and incorporate both subjective and objective indicators when monitoring the success of such programs.
Real World Evidence on the Effectiveness of Nusinersen within the National Program to Treat Spinal Muscular Atrophy in Poland
Authors: Krupa Dominika , Czech Marcin , Chudzyńska Ewa , Koń Beata , Kostera-Pruszczyk Anna
Published: May 2023

Background: Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease resulting in children’s mortality and disability. Nusinersen is available to all SMA patients in Poland since 2019. Aim: To compare mortality or disease progression to mechanical ventilation in two patient cohorts before and after the program’s introduction. Additionally, to describe the patient population treated with nusinersen and costs incurred by the public payer. Methods: We used the National Health Fund (NHF) database to identify patients born in either 2014 or 2019, who received at least two health services with an ICD10 G12 diagnosis. Outcomes were time to event: death or first mechanical ventilation. We identified all benefits received by nusinersen-treated patients, between 1 January 2019 and 31 May 2022. Results: Children with SMA born in 2019 had significantly lower mortality in the first years of their lives than children born in 2014. Approximately 875 patients (all age groups) were treated with nusinersen in the analysis period. The cost of causal drugs in this period amounted to €51.4 million. The cost of healthcare benefits amounted to €14.9 million. Conclusions: The drug program to treat SMA improved patient care in Poland. The NHF database was a reliable source to monitor resource-intensive therapies’ costs, demography, and selected patient outcomes.
Effectiveness of the Therapeutic Community Model in Addiction Treatment: A Retrospective Pilot Study in French Prisons
Authors: Vinais Théodore , Lacroix Aurélie , Gelle Thibaut , Nubukpo Philippe
Published: May 2023

Background: In France, addiction care in prison usually consists of nurses’ interventions, medical care and socio-educational programs, but new alternatives have arisen, namely the therapeutic community (TC) model. This pilot study aims to evaluate the effectiveness of this prison-based TC in comparison with classic and socio-educational care offered in French prisons. Methods: To compare these three types of prison-based care, two detention centers’ files were screened for use of multiple drugs, willingness to participate and absence of psychiatric comorbidities incompatible with group therapy. A custom questionnaire was built based on the fifth version of the Addiction Severity Index. It investigates medical status, employment and support, primary addiction status, legal status, social/familial status and psychiatric status through various items. Results: Our sample only consisted of male repeat offenders with a mean age of 37.7 ± (9.1) years. Primary addiction status improvement was observed for all care studied but was more important in TC than in classic care. Self-esteem and social/familial status saw significant improvement throughout TC care. Conclusions: The TC model represents an alternative to classic and socio-educational care in French prisons. More studies are needed to assess the extent of the benefits provided on both the medical side and economic side.
Reliability and Validity of the Korean Version of Lung Cancer Screening Health Belief Scale
Authors: Cho Mi-Kyoung , Cho Yoon-Hee
Published: May 2023

The purpose of this study was to verify the validity and reliability of the LCSHBS-K. This was a methodological study. The participants were adults aged between 50 and 74 years old, according to the selection criteria for lung cancer screening presented by the Comprehensive Cancer Network clinical practice guidelines in oncology recommendations. This study included 204 high-risk individuals who had not been diagnosed with lung cancer. The collected data were analyzed using the IBM SPSS Statistics software 26.0 version (IBM, New York, NY, USA). The reliability was analyzed by Cronbach’s α for internal consistency, and the concurrent validity was analyzed by Pearson’s correlation coefficients to identify the correlations with the health belief scale for Korean adults. To test the convergent validity, the average variance extracted (AVE) and composite reliability (CR) were calculated using confirmatory factor analysis. In addition, the model fit for a tool was CMIN (χ2/df), SRMR, RMSEA, GFI, and CFI as a comparative fit index. The discriminant validity was tested based on AVE > r2. The average age of the participants was 55.49 (SD = 5.07), the average smoking history was 29.55 (SD = 8.12) years, and the average number of cigarettes smoked per day was 12.18 (SD = 7.77). The goodness of fit met the criteria with GFI = 0.81 (criteria > 0.9), CMIN = 1.69 (criteria < 2), SRMR = 0.06 (criteria < 0.08), RMSEA = 0.058 (criteria < 0.06), and CFI = 0.91 (criteria > 0.9). The LCSHBS-K showed a statistically significant positive correlation with the HBS (r = 0.32 (p < 0.001)). Cronbach’s α was 0.80 for all the items in the LCSHBS-K. Therefore, the validity and reliability of the LCSHBS-K tool were confirmed. Based on the results of this study, the Korean version of the LCSHBS tool was found to be suitable for screening lung cancer in high-risk groups in Korea.
Conditions for Social Exclusion Leading to Distress Change in Chinese Lesbian, Gay, and Bisexual (LGB) People
Authors: Cheung Chau-kiu , Tsang Eileen Yuk-ha
Published: May 2023

Lesbian, gay, and bisexual (LGB) people are likely to be at risk of distress because of social exclusion, including the feelings of resentment, resistance, and rejection they might experience from society. Nevertheless, the conditions for social exclusion leading to changes in distress are empirically unclear, especially in Chinese LGB people. To examine these conditions, this study surveyed 303 Chinese LGB people in Taiwan, Hong Kong, and various places in Mainland China. For comparability with other LGB studies, the study did not explicitly identify asexual, demisexual, or pansexual people in the LGB group. Results show that the retrospective reporting of social exclusion in 2016 did not significantly and unconditionally predict levels of distress in 2017. However, the reporting of exclusion significantly predicted current distress when the retrospective report of distress in 2016 was high. These results from the stress–vulnerability model indicate that prior distress is a vulnerability condition that allows social exclusion to exert its stressful effect. This study implies the need to prevent the social exclusion of highly distressed LGB people.
Interventions to Strengthen Environmental Sustainability of School Food Systems: Narrative Scoping Review
Authors: Gardner Grace , Burton Wendy , Sinclair Maddie , Bryant Maria
Published: May 2023

School food systems play a role in the wider food system, but there is a scarcity of literature exploring interventions that aim to improve the environmental sustainability of school food systems. The present review aimed to understand and describe the types of interventions that have previously been explored to strengthen the sustainability of school food systems along with their impact. We applied a scoping review methodology guided by Arksey and O’Malley, which included a review of the online database Scopus and the grey literature. Information relating to intervention design, study population, evaluation method and impact were extracted. In total, 6016 records were screened for eligibility, 24 of which were eligible for inclusion. The most common types of interventions were school lunch menus designed to be more sustainable; school food waste reduction; sustainable food system education using school gardens; and dietary interventions with added environmental components. This review highlights a range of interventions which could positively influence the environmental sustainability of school food systems. Further research is needed to explore the effectiveness of such interventions.
Self-Reported Cognitive Aging and Well-Being among Older Middle Eastern/Arab American Immigrants during the COVID-19 Pandemic
Authors: Sayed Linda , Alanazi Mohammed , Ajrouch Kristine J.
Published: May 2023

Background: The COVID-19 pandemic posed new challenges for cognitive aging since it brought interruptions in family relations for older adults in immigrant communities. This study examines the consequences of COVID-19 for the familial and social support systems of aging Middle Eastern/Arab immigrants in Michigan, the largest concentration in the United States. We conducted six focus groups with 45 participants aged 60 and older to explore participant descriptions of changes and difficulties faced during the pandemic relating to their cognitive health, familial and social support systems, and medical care. The findings indicate challenges around social distancing for older Middle Eastern/Arab American immigrants, which generated three overarching themes: fear, mental health, and social relationships. These themes provide unique insights into the lived experiences of older Middle Eastern/Arab American adults during the pandemic and bring to light culturally embedded risks to cognitive health and well-being. A focus on the well-being of older Middle Eastern/Arab American immigrants during COVID-19 advances understanding of how environmental contexts inform immigrant health disparities and the sociocultural factors that shape minority aging.
Perceptions and Intentions around Uptake of the COVID-19 Vaccination among Older People: A Mixed-Methods Study in Phuket Province, Thailand
Authors: Luevanich Chayanit , Kane Ros , Naklong Aimon , Surachetkomson Prapaipim
Published: May 2023

Background: A 70% vaccination rate against COVID-19 in the general population was required for re-opening Phuket tourist industry. However, prior to this research, 39.61% of older people remained unvaccinated. This study aimed to examine perceptions and intentions around COVID-19 vaccination amongst older people and to explore the reasons and factors influencing their decisions to receive or refuse vaccination. Methods: This was a mixed-methods approach with a sequential explanatory design. We conducted an online survey and semi-structured qualitative interview with a subsample. Multinomial logistic regression was applied and thematic content analysis was conducted. Results: 92.4% of participants reported intention to receive the vaccine. Multinomial regression analysis revealed that perceived barriers (AdjOR = 0.032; 95% CI: 0.17–0.59), perceived benefit (AdjOR = 2.65; 95% CI: 1.49–4.71), good health (AdjOR = 3.51; 95% CI: 1.01–12.12) and health not good (AdjOR = 0.10; 95% CI: 0.02–0.49) were predictors of vaccine uptake. In the qualitative interviews, four key influences on up-take for the 28 vaccinated participants were: prevention and protection, convenience, fear of death from COVID-19, and trust in the vaccine. Four key influences on refusal of vaccination in the eight unvaccinated participants were: rarely leaving the house, fear of vaccine side-effects, fear of death after getting the vaccine, and not enough information for decision-making. Conclusion: Intervention and campaigns addressing COVID-19 vaccination should employ strategies, including the widespread use of social and other popular media to increase older people’s perceived benefit of vaccination on their current and future health status, while decreasing perceived barriers to receiving the vaccine.
Connecting Circuits with Networks in Addiction Neuroscience: A Salience Network Perspective
Authors: Cushnie Adriana K. , Tang Wei , Heilbronner Sarah R.
Published: May 2023

Human neuroimaging has demonstrated the existence of large-scale functional networks in the cerebral cortex consisting of topographically distant brain regions with functionally correlated activity. The salience network (SN), which is involved in detecting salient stimuli and mediating inter-network communication, is a crucial functional network that is disrupted in addiction. Individuals with addiction display dysfunctional structural and functional connectivity of the SN. Furthermore, while there is a growing body of evidence regarding the SN, addiction, and the relationship between the two, there are still many unknowns, and there are fundamental limitations to human neuroimaging studies. At the same time, advances in molecular and systems neuroscience techniques allow researchers to manipulate neural circuits in nonhuman animals with increasing precision. Here, we describe attempts to translate human functional networks to nonhuman animals to uncover circuit-level mechanisms. To do this, we review the structural and functional connections of the salience network and its homology across species. We then describe the existing literature in which circuit-specific perturbation of the SN sheds light on how functional cortical networks operate, both within and outside the context of addiction. Finally, we highlight key outstanding opportunities for mechanistic studies of the SN.
Serum microRNA Levels as a Biomarker for Diagnosing Non-Alcoholic Fatty Liver Disease in Chinese Colorectal Polyp Patients
Authors: Ng Lui , Sin Ryan Wai-Yan , Cheung David Him , Leung Wai-Keung , Man Abraham Tak-Ka , Lo Oswens Siu-Hung , Law Wai-Lun , Foo Dominic Chi-Chung
Published: May 2023

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374, p = 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978, p = 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081, p = 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582, p = 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (p = 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (p < 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.
Stability of Human Telomeric G-Quadruplexes Complexed with Photosensitive Ligands and Irradiated with Visible Light
Authors: Libera Valeria , Ripanti Francesca , Petrillo Caterina , Sacchetti Francesco , Ramos-Soriano Javier , Galan Maria Carmen , Schirò Giorgio , Paciaroni Alessandro , Comez Lucia
Published: May 2023

Guanine-rich DNA sequences can fold into non-canonical nucleic acid structures called G-quadruplexes (G4s). These nanostructures have strong implications in many fields, from medical science to bottom-up nanotechnologies. As a result, ligands interacting with G4s have attracted great attention as candidates in medical therapies, molecular probe applications, and biosensing. In recent years, the use of G4-ligand complexes as photopharmacological targets has shown significant promise for developing novel therapeutic strategies and nanodevices. Here, we studied the possibility of manipulating the secondary structure of a human telomeric G4 sequence through the interaction with two photosensitive ligands, DTE and TMPyP4, whose response to visible light is different. The effect of these two ligands on G4 thermal unfolding was also considered, revealing the occurrence of peculiar multi-step melting pathways and the different attitudes of the two molecules on the quadruplex stabilization.
Markers of Restenosis after Percutaneous Transluminal Balloon Angioplasty in Patients with Critical Limb Ischemia
Authors: Sobolevskaya Elvira V. , Shumkov Oleg A. , Smagin Mikhail A. , Guskov Andrey E. , Malysheva Alexandra V. , Atuchin Victor V. , Nimaev Vadim V.
Published: May 2023

Among cardiovascular diseases, chronic obliterating lesions of the arteries of lower extremities, which are one of the important problems of modern healthcare, are distinguished. In most cases, the cause of damage to the arteries of lower extremities is atherosclerosis. The most severe form is chronic ischemia, characterized by pain at rest and ischemic ulcers, ultimately increasing the risk of limb loss and cardiovascular mortality. Therefore, patients with critical limb ischemia need limb revascularization. Percutaneous transluminal balloon angioplasty is one of the least invasive and safe approaches, with advantages for patients with comorbidities. However, after this procedure, restenosis is still possible. Early detection of changes in the composition of some molecules as markers of restenosis will help screen patients at the risk of restenosis, as well as find ways to apply efforts for further directions of inhibition of this process. The purpose of this review is to provide the most important and up-to-date information on the mechanisms of restenosis development, as well as possible predictors of their occurrence. The information collected in this publication may be useful in predicting outcomes after surgical treatment and will also find new ways for the target implication to the mechanisms of development of restenosis and atherosclerosis.
Plasmatic MicroRNAs and Treatment Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer: A Hospital-Based Cohort Study and In Silico Analysis
Authors: Silva Jani , Tavares Valéria , Afonso Ana , Garcia Juliana , Cerqueira Fátima , Medeiros Rui
Published: May 2023

Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Inevitably, all advanced PCa patients develop metastatic castration-resistant prostate cancer (mCRPC), an aggressive phase of the disease. Treating mCRPC is challenging, and prognostic tools are needed for disease management. MicroRNA (miRNA) deregulation has been reported in PCa, constituting potential non-invasive prognostic biomarkers. As such, this study aimed to evaluate the prognostic potential of nine miRNAs in the liquid biopsies (plasma) of mCRPC patients treated with second-generation androgen receptor axis-targeted (ARAT) agents, abiraterone acetate (AbA) and enzalutamide (ENZ). Low expression levels of miR-16-5p and miR-145-5p in mCRPC patients treated with AbA were significantly associated with lower progression-free survival (PFS). The two miRNAs were the only predictors of the risk of disease progression in AbA-stratified analyses. Low miR-20a-5p levels in mCRPC patients with Gleason scores of <8 were associated with worse overall survival (OS). The transcript seems to predict the risk of death regardless of the ARAT agent. According to the in silico analyses, miR-16-5p, miR-145-5p, and miR-20a-5p seem to be implicated in several processes, namely, cell cycle, proliferation, migration, survival, metabolism, and angiogenesis, suggesting an epigenetic mechanism related to treatment outcome. These miRNAs may represent attractive prognostic tools to be used in mCRPC management, as well as a step further in the identification of new potential therapeutic targets, to use in combination with ARAT for an improved treatment outcome. Despite the promising results, real-world validation is necessary.
Design, Synthesis, Antiproliferative Actions, and DFT Studies of New Bis–Pyrazoline Derivatives as Dual EGFR/BRAFV600E Inhibitors
Authors: Al-Wahaibi Lamya H. , Abou-Zied Hesham A. , Beshr Eman A. M. , Youssif Bahaa G. M. , Hayallah Alaa M. , Abdel-Aziz Mohamed
Published: May 2023

Some new Bis-pyrazoline hybrids 8–17 with dual EGFR and BRAFV600E inhibitors have been developed. The target compounds were synthesized and tested in vitro against four cancer cell lines. Compounds 12, 15, and 17 demonstrated strong antiproliferative activity with GI50 values of 1.05 µM, 1.50 µM, and 1.20 µM, respectively. Hybrids showed dual inhibition of EGFR and BRAFV600E. Compounds 12, 15, and 17 inhibited EGFR-like erlotinib and exhibited promising anticancer activity. Compound 12 is the most potent inhibitor of cancer cell proliferation and BRAFV600E. Compounds 12 and 17 induced apoptosis by increasing caspase 3, 8, and Bax levels, and resulted in the downregulation of the antiapoptotic Bcl2. The molecular docking studies verified that compounds 12, 15, and 17 have the potential to be dual EGFR/BRAFV600E inhibitors. Additionally, in silico ADMET prediction revealed that most synthesized bis-pyrazoline hybrids have low toxicity and adverse effects. DFT studies for the two most active compounds, 12 and 15, were also carried out. The values of the HOMO and LUMO energies, as well as softness and hardness, were computationally investigated using the DFT method. These findings agreed well with those of the in vitro research and molecular docking study.
An Optimized Flow Cytometric Method to Demonstrate the Differentiation Stage-Dependent Ca2+ Flux Responses of Peripheral Human B Cells
Authors: Bajnok Anna , Serény-Litvai Timea , Temesfői Viktória , Nörenberg Jasper , Herczeg Róbert , Kaposi Ambrus , Berki Timea , Mezosi Emese
Published: May 2023

Calcium (Ca2+) flux acts as a central signaling pathway in B cells, and its alterations are associated with autoimmune dysregulation and B-cell malignancies. We standardized a flow-cytometry-based method using various stimuli to investigate the Ca2+ flux characteristics of circulating human B lymphocytes from healthy individuals. We found that different activating agents trigger distinct Ca2+ flux responses and that B-cell subsets show specific developmental-stage dependent Ca2+ flux response patterns. Naive B cells responded with a more substantial Ca2+ flux to B cell receptor (BCR) stimulation than memory B cells. Non-switched memory cells responded to anti-IgD stimulation with a naive-like Ca2+ flux pattern, whereas their anti-IgM response was memory-like. Peripheral antibody-secreting cells retained their IgG responsivity but showed reduced Ca2+ responses upon activation, indicating their loss of dependence on Ca2+ signaling. Ca2+ flux is a relevant functional test for B cells, and its alterations could provide insight into pathological B-cell activation development.
The Role of Integrin Receptor’s α and β Subunits of Mouse Mesenchymal Stem Cells on the Interaction of Marine-Derived Blacktip Reef Shark (Carcharhinus melanopterus) Skin Collagen
Authors: Ge Baolin , Wei Mingjun , Bao Bin , Pan Zhilin , Elango Jeevithan , Wu Wenhui
Published: May 2023

Marine collagen (MC) has recently attracted more attention in tissue engineering as a biomaterial substitute due to its significant role in cellular signaling mechanisms, especially in mesenchymal stem cells (MSCs). However, the actual signaling mechanism of MC in MSC growth, which is highly influenced by their molecular pattern, is poorly understood. Hence, we investigated the integrin receptors (α1β1, α2β1, α10β1, and α11β1) binding mechanism and proliferation of MCs (blacktip reef shark collagen (BSC) and blue shark collagen (SC)) compared to bovine collagen (BC) on MSCs behavior through functionalized collagen molecule probing for the first time. The results showed that BSC and SC had higher proliferation rates and accelerated scratch wound healing by increasing migratory rates of MSCs. Cell adhesion and spreading results demonstrated that MC had a better capacity to anchor MSCs and maintain cell morphology than controls. Living cell observations showed that BSC was gradually assembled by cells into the ECM network within 24 h. Interestingly, qRT-PCR and ELISA revealed that the proliferative effect of MC was triggered by interacting with specific integrin receptors such as α2β1, α10β1, and α11β1 of MSCs. Accordingly, BSC accelerated MSCs’ growth, adhesion, shape, and spreading by interacting with specific integrin subunits (α2 and β1) and thereby triggering further signaling cascade mechanisms.
Short-Term Irisin Treatment Enhanced Neurotrophin Expression Differently in the Hippocampus and the Prefrontal Cortex of Young Mice
Authors: Dicarlo Manuela , Pignataro Patrizia , Zerlotin Roberta , Suriano Clelia , Zecca Chiara , Dell’Abate Maria Teresa , Storlino Giuseppina , Oranger Angela , Sanesi Lorenzo , Mori Giorgio , Grano Maria , Colaianni Graziana , Colucci Silvia
Published: May 2023

As a result of physical exercise, muscle releases multiple exerkines, such as “irisin”, which is thought to induce pro-cognitive and antidepressant effects. We recently demonstrated in young healthy mice the mitigation of depressive behaviors induced by consecutive 5 day irisin administration. To understand which molecular mechanisms might be involved in such effect, we here studied, in a group of mice previously submitted to a behavioral test of depression, the gene expression of neurotrophins and cytokines in the hippocampus and prefrontal cortex (PFC), two brain areas frequently investigated in the depression pathogenesis. We found significantly increased mRNA levels of nerve growth factor (NGF) and fibroblast growth factor 2 (FGF-2) in the hippocampus and brain-derived growth factor (BDNF) in the PFC. We did not detect a difference in the mRNA levels of interleukin 6 (IL-6) and IL-1β in both brain regions. Except for BDNF in the PFC, two-way ANOVA analysis did not reveal sex differences in the expression of the tested genes. Overall, our data evidenced a site-specific cerebral modulation of neurotrophins induced by irisin treatment in the hippocampus and the PFC, contributing to the search for new antidepressant treatments targeted at single depressive events with short-term protocols.
NOVAprep-miR-Cervix: New Method for Evaluation of Cervical Dysplasia Severity Based on Analysis of Six miRNAs
Authors: Kniazeva Margarita , Zabegina Lidia , Shalaev Andrey , Smirnova Olga , Lavrinovich Olga , Berlev Igor , Malek Anastasia
Published: May 2023

Cervical cancer is one of the most common gynecological malignancies and it is preventable through the yearly diagnosis and management of pre-cancerous cervical disease. The profile of miRNA expression in cervical epithelium cells is altered with cervical dysplasia development and further progression. The NOVAprep-miR-CERVIX is a new approach for the assessment of cervical dysplasia through the analysis of six marker miRNAs. This study aims to evaluate theperformance and diagnostic potency of the new method. Cytological smears from 226 women (NILM, n.114; HSIL, n.112) were included in the study. A VPH test was performed with RealBest DNAHPV HR screen Kit, six marker miRNAs (miR-21, -29b, -145, -451a, -1246, -1290) were assayed using NOVAprep-miR-CERVIX kit. Obtained data were analyzed using the Delta Ct method and random forest machine learning algorithm. The results of the quantitative analysis of six microRNAs were expressed as a miR-CERVIX parameter, which ranged from 0 to 1, where “0” corresponded to the healthy cervical epithelium, while “1” corresponded to high-grade squamous intraepithelial dysplasia. The average value of miR-CERVIX differed in groups of NILM and HSIL samples (0.34 vs. 0.72; p < 0.000005). An estimation of miR-CERVIX allowed for the differentiation between healthy and pre-cancerous samples with sensitivity of 0.79 and specificity of 0.79, as well as to confirm HSIL with specificity of 0.98. Interestingly, the HSIL group included HPV(+) and HPV(−) samples, which were statistically significantly different in terms of miR-CERVIX value. Analysis of CC-associated miRNAs in material of cervical smear might serve as an additional method for the evaluation of cervical dysplasia severity.
Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study
Authors: Åberg Daniel , Gadd Gustaf , Jood Katarina , Redfors Petra , Stanne Tara M. , Isgaard Jörgen , Blennow Kaj , Zetterberg Henrik , Jern Christina , Åberg N. David , Svensson Johan
Published: May 2023

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4–8.5 and OR 5.7, 95% CI: 2.5–12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1–3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.
Specific Signal Transduction of Constitutively Activating (D576G) and Inactivating (R476H) Mutants of Agonist-Stimulated Luteinizing Hormone Receptor in Eel
Authors: Choi Seung-Hee , Byambaragchaa Munkhzaya , Kim Dae-Jung , Lee Jong-Hyuk , Kang Myung-Hwa , Min Kwan-Sik
Published: May 2023

We investigated the mechanism of signal transduction using inactivating (R476H) and activating (D576G) mutants of luteinizing hormone receptor (LHR) of eel at the conserved regions of intracellular loops II and III, respectively, naturally occurring in mammalian LHR. The expression of D576G and R476H mutants was approximately 58% and 59%, respectively, on the cell surface compared to those of eel LHR-wild type (wt). In eel LHR-wt, cAMP production increased upon agonist stimulation. Cells expressing eel LHR-D576G, a highly conserved aspartic acid residue, exhibited a 5.8-fold increase in basal cAMP response; however, the maximal cAMP response by high-agonist stimulation was approximately 0.62-fold. Mutation of a highly conserved arginine residue in the second intracellular loop of eel LHR (LHR-R476H) completely impaired the cAMP response. The rate of loss in cell-surface expression of eel LHR-wt and D576G mutant was similar to the agonist recombinant (rec)-eel LH after 30 min. However, the mutants presented rates of loss higher than eel LHR-wt did upon rec-eCG treatment. Therefore, the activating mutant constitutively induced cAMP signaling. The inactivating mutation resulted in the loss of LHR expression on the cell surface and no cAMP signaling. These data provide valuable information regarding the structure–function relationship of LHR–LH complexes.
Chemerin as an Inducer of β Cell Proliferation Mediates Mitochondrial Homeostasis and Promotes β Cell Mass Expansion
Authors: Li Min , Zhang Ruifan , Ge Qian , Yue Lingzhi , Ma Dan , Khattab Firas , Xie Wenhua , Cui Yewei , Gilon Patrick , Zhao Xueya , Li Xi , Cheng Rui
Published: May 2023

Loss of the β cell population is a crucial feature of type 2 diabetes. Restoring the β cell mass by stimulating β cell proliferation and preventing its apoptosis was proposed as a therapeutic approach to treating diabetes. Therefore, researchers have been increasingly interested in identifying exogenous factors that can stimulate β cell proliferation in situ and in vitro. Adipokine chemerin, which is secreted from adipose tissue and the liver, has been identified as a chemokine that plays a critical role in the regulation of metabolism. In this study, we demonstrate that chemerin as a circulating adipokine promotes β cell proliferation in vivo and in vitro. Chemerin serum levels and the expression of the main receptors within islets are highly regulated under a variety of challenging conditions, including obesity and type 2 diabetes. As compared to their littermates, mice overexpressing chemerin had a larger islet area and increased β cell mass with both a normal and high-fat diet. Moreover, in chemerin-overexpressed mice, we observed improved mitochondrial homeostasis and increased insulin synthesis. In summary, our findings confirm the potential role of chemerin as an inducer of β cell proliferation, and they provide novel insights into the helpful strategy to expand β cell population.
Integrated Multi-Omics Reveals Significant Roles of Non-Additively Expressed Small RNAs in Heterosis for Maize Plant Height
Authors: Zhang Jie , Xie Yuxin , Zhang Hongwei , He Cheng , Wang Xiaoli , Cui Yu , Heng Yanfang , Lin Yingchao , Gu Riliang , Wang Jianhua , Fu Junjie
Published: May 2023

Heterosis is a complex biological phenomenon regulated by genetic variations and epigenetic changes. However, the roles of small RNAs (sRNAs), an important epigenetic regulatory element, on plant heterosis are still poorly understood. Here, an integrative analysis was performed with sequencing data from multi-omics layers of maize hybrids and their two homologous parental lines to explore the potential underlying mechanisms of sRNAs in plant height (PH) heterosis. sRNAome analysis revealed that 59 (18.61%) microRNAs (miRNAs) and 64,534 (54.00%) 24-nt small interfering RNAs (siRNAs) clusters were non-additively expressed in hybrids. Transcriptome profiles showed that these non-additively expressed miRNAs regulated PH heterosis through activating genes involved in vegetative growth-related pathways while suppressing those related to reproductive and stress response pathways. DNA methylome profiles showed that non-additive methylation events were more likely to be induced by non-additively expressed siRNA clusters. Genes associated with low-parental expression (LPE) siRNAs and trans-chromosomal demethylation (TCdM) events were enriched in developmental processes as well as nutrients and energy metabolism, whereas genes associated with high-parental expression (HPE) siRNAs and trans-chromosomal methylation (TCM) events were gathered in stress response and organelle organization pathways. Our results provide insights into the expression and regulation patterns of sRNAs in hybrids and help to elucidate their potential targeting pathways contributing to PH heterosis.
Circadian Activity and Clock Genes in Pachycrepoideus vindemmiae: Implications for Field Applications and Circadian Clock Mechanisms of Parasitoid Wasps
Authors: Teng Ziwen , Huo Mengran , Zhou Yanan , Zhou Yuqi , Liu Yunjie , Lin Yan , Zhang Qi , Zhang Zhiqi , Wan Fanghao , Zhou Hongxu
Published: May 2023

Despite the importance of circadian rhythms in insect behavior, our understanding of circadian activity and the molecular oscillatory mechanism in parasitoid wasp circadian clocks is limited. In this study, behavioral activities expected to be under the control of the endogenous circadian system were characterized in an ectoparasitoid wasp, Pachycrepoideus vindemmiae. Most adults exhibited emergence between late night and early morning, while mating only occurred during the daytime, with a peak at midday. Oviposition had three peaks in the early morning, late day, or early night and late night. Additionally, we identified eight putative clock genes from P. vindemmiae. The quantitative PCR (qPCR) results indicate that most clock genes showed significant rhythmic expressions. Our comparative analysis of clock genes in P. vindemmiae and 43 other parasitoid wasps revealed that none of the wasps possessed the timeless and cry1 genes commonly found in some other insect species, suggesting that the circadian clock system in parasitoid wasps is distinct from that in other non-Hymenoptera insects such as Drosophila. Thus, this study attempted to build the first hypothetical circadian clock model for a parasitoid wasp, thus generating hypotheses and providing a platform for the future functional characterization of P. vindemmiae clock genes as well as those of other parasitoid wasps. Finally, these findings on P. vindemmiae circadian activity will aid the development of effective field release programs for biological control, which can be tested under field conditions.
Manipulating Pixels in Computer Graphics by Converting Raster Elements to Vector Shapes as a Function of Hue
Authors: Koren Ivančević Tajana , Stanić Loknar Nikolina , Rudolf Maja , Bratić Diana
Published: May 2023

This paper proposes a method for changing pixel shape by converting a CMYK raster image (pixel) to an HSB vector image, replacing the square cells of the CMYK pixels with different vector shapes. The replacement of a pixel by the selected vector shape is done depending on the detected color values for each pixel. The CMYK values are first converted to the corresponding RGB values and then to the HSB system, and the vector shape is selected based on the obtained hue values. The vector shape is drawn in the defined space, according to the row and column matrix of the pixels of the original CMYK image. Twenty-one vector shapes are introduced to replace the pixels depending on the hue. The pixels of each hue are replaced by a different shape. The application of this conversion has its greatest value in the creation of security graphics for printed documents and the individualization of digital artwork by creating structured patterns based on the hue.