bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards Enhanced Understanding and Experience of Landforms, Geohazards, and Geoheritage through Virtual Reality Technologies in Education: Lessons from the GeoVT Project
Authors: Vandelli Vittoria , Migoń Piotr , Palmgren Ylva , Spyrou Evangelos , Saitis Giannis , Andrikopoulou Maria Eleni , Coratza Paola , Medjkane Mohand , Prieto Carmen , Kalovrektis Konstantinos , Lissak Candide , Papadopoulos Alexandros , Papastamatiou Nikos , Evelpidou Niki , Maquaire Olivier , Psycharis Sarantos , Stroeven Arjen P. , Soldati Mauro
Published: May 2024

Virtual reality is a technological development that, among others, has revolutionized Earth sciences. Its advantages include an opportunity to examine places otherwise difficult or impossible to access and it may also become an important component of education, fostering a better understanding of processes and landforms, geohazard awareness, and an appreciation of geoheritage. This paper reports on the GeoVT project, which aims to create a platform to build and disseminate Virtual Field Trips (VFTs) focused on geomorphology, natural hazards associated with geomorphological processes, and geoheritage sites. To put the GeoVT project in context, an overview of applications of VR in geosciences is provided. This paper subsequently proceeds with a presentation of the project and the GeoVT Authoring application, which is an innovative platform designed to help teachers and students, followed by brief presentations of a number of VFTs developed within the project. They address themes such as fluvial landforms and valley development, coastal landforms, evidence of past glaciation, coastal erosion, wildfire effects, mud volcanoes, and landslides.
Heroic Vulnerability and the Vietnamese Refugee Experience in Thi Bui’s The Best We Could Do
Authors: Porras Sánchez María
Published: May 2024

Autographics illustrating refugee and migrant experiences are frequently published, proof of the power of comics to engage with representations of trauma and vulnerability. Thi Bui’s graphic memoir The Best We Could Do tells the story of the author and her family as “boat people”, before and after migrating from Việt Nam to the US in the so-called second “wave” of refugees (1978–1980). If, as Judith Butler argues, vulnerable lives are more grievable when exposed and acknowledged, then self-representation of vulnerable lives might offer a site of resistance against precarity. Thi Bui’s graphic memoir is no exception, since she deals with common themes in Vietnamese American literature such as PTSD, inherited family trauma or everyday bordering, inscribing herself and her family in the counterhistory of the US regarding the Vietnam War, while also addressing themes and motifs recurrent in Asian American comics. The author follows a thematic concern present in Vietnamese American narratives, which tends to present the refugee experience from a heroic perspective, but this is limited and antagonised by Bui’s personal story, who feels estranged from her parents, their past in Việt Nam and the war. As this article shows, the recording and commemoration of her parents’ memories help her to identify with the family legacy of heroic vulnerability in her role as a mother.
Examining Communicative, Critical Health Literacy and eHealth Literacy among International University Students Residing in Japan
Authors: Ahmad Ishtiaq , Taimur Hira , Shabbir Sameera , Shabbir Chaudhry Ahmed , Ahsan Ali , Ahmad Hafiz Sultan , Masuda Gaku
Published: May 2024

(1) Background: International students with sufficient health literacy are better equipped to respond to public health emergencies and reduce any unintentional harm that may occur during such events. This study aims to assess the current status of health literacy among international students and investigate the factors that influence health literacy. (2) Methods: A cross-sectional study was conducted in Tokyo on international university students using a questionnaire consisting of the Communicative and Critical Health Literacy and eHealth Literacy Scales. The study analyzed 205 valid responses. Descriptive statistics were utilized to assess the level of health literacy, and linear regression was used to identify the association of socio-demographic characteristics and disease status with health and e-health literacy. (3) Results: Health literacy and e-health literacy were low in 48.29% and 47.29% of international students, respectively. The mean scores of CCHL items ranged from 3.13 to 3.26, while the mean scores of eHEALS items ranged from 3.33 to 3.49. Both health literacy and e-health literacy were better with unmarried status (p = 0.015), and e-health literacy was worse with higher age (p = 0.007). (4) Conclusions: Overall, international students’ health literacy and e-health literacy were at intermediate levels, with considerable room for improvement, and affected by certain student attributes.
Perceptions of Tobacco Price Policy among Students from Sapienza University of Rome: Can This Policy Mitigate Smoking Addiction and Its Health Impacts?
Authors: Antinozzi Martina , Caminada Susanna , Amendola Mariano , Cammalleri Vittoria , Dorelli Barbara , Giffi Monica , Giordano Felice , Marani Alessandra , Pocino Roberta Noemi , Renzi Davide , Sindoni Alessandro , Cattaruzza Maria Sofia
Published: May 2024

Tobacco use is one of the main risk factors for non-communicable diseases. Avoiding youth initiation and treating addiction are fundamental public health issues to ensure better health. Among tobacco control policies, increasing tobacco price is the single most effective intervention. It reduces tobacco consumption, especially among youths, while representing a government financing source. This study aimed to assess the agreement with the proposal of a one-euro increase in tobacco price earmarked to health issues among students at Sapienza University. Two convenience samples were surveyed, five years apart, on World No Tobacco Days. Smoking habits, agreement with the proposal and reasons for it were collected. Results from the 208 questionnaires (107 in 2014, 101 in 2019) showed 46.6% of agreement with the proposal (53.3% in 2014, 39.2% in 2019, p = 0.044). Main predictive factor for agreement was being a non-smoker (OR = 6.33 p < 0.001), main reason (64.8%) was it could trigger smokers to quit or reduce consumption. Several factors might have influenced this finding, including the introduction of novel tobacco products and their increased advertisement on social media. In 2024, European Union is planning to update the Tobacco Taxation Directive which could greatly contribute to the reduction of non-communicable diseases and premature deaths.
The Psychological Impact on Romanian Women Infected with SARS-CoV-2 during Pregnancy
Authors: Cigăran Ruxandra-Gabriela , Peltecu Gheorghe , Mustață Laura-Mihaela , Botezatu Radu
Published: May 2024

Background: It is well-known that the uncertainty about the COVID-19 pandemic has an indirect negative impact on pregnant women’s mental health, given the fact that pregnant women are more vulnerable emotionally and psychologically than non-pregnant women. The aim of this study was to evaluate the maternal psychological impact on Romanian women who were infected with SARS-CoV-2 during pregnancy and their concerns and to determine which are the best measures to prevent negative outcomes. Methods: A 40-item questionnaire was created for data collection and was shared on social platforms (Facebook and Instagram) and also with obstetric communities between February 2021 and January 2023. Our cross-sectional survey recruited 317 Romanian pregnant women who suffered from SARS-CoV-2 infection. Among general questions about their life and pregnancy during the pandemic, the survey included questions about their SARS-CoV-2 infection during pregnancy, their concerns and how they perceived this period in order to evaluate their emotional status. Results: Of 317 women recruited, 91% of them had a mild to moderate form of COVID-19, and 2% had serious symptoms. Only 9% of women were hospitalized, 4% of women considered that the SARS-CoV-2 infection affected their physical condition to a great extent, and 8% considered to be affected in terms of mental state to a great extent. The main negative feelings of pregnant women during the COVID-19 disease were the fear regarding the possibility of affecting the pregnancy and the concern for their life (51.4%). These increase the risk of developing anxiety or depression. Pregnant women who contracted SARS-CoV-2 infection faced negative feelings, especially those with a severe form of the disease or who recovered with difficulty after the disease. Patients who required hospitalization reported an impairment of the mental state to a great extent and to a very great extent with a frequency of approximately two times and four times higher than non-hospitalized patients, respectively (p < 0.05 and p < 0.001, respectively). Also, giving birth during SARS-CoV-2 and the difficulty of accessing medical services represented a high level of stress. Also, 47% of patients who reported difficulty accessing medical services during the illness evaluated their mental state significantly less favorably. Conclusion: Preventive measures are essential to minimizing the negative psychological impact of COVID-19 disease during pregnancy among pregnant women. The medical treatment of COVID-19 disease during pregnancy should be prioritized, but emotional and mental health support must also be provided.
An Online-Based Survey to Assess Knowledge, Attitudes, and Barriers to Perform First Aid after Road Accidents Conducted among Adult Jordanians
Authors: Al-Qerem Walid , Jarab Anan , Al Bawab Abdel Qader , Hammad Alaa , Eberhardt Judith , Alasmari Fawaz , Kalloush Haneen , Al-Sa’di Lujain , Obidat Raghd
Published: May 2024

(1) Background: First aid administered during road accidents can save millions of lives. However, the knowledge and attitudes of the Jordanian population towards first aid are lacking. This study aimed to examine the knowledge, attitudes, and barriers to performing first aid among the Jordanian population during road accidents. (2) Methods: An online questionnaire was developed and distributed using various Jordanian social media platforms. The questionnaire collected the participants’ sociodemographic details and assessed their first aid knowledge, attitudes toward first aid, and barriers preventing the participants from performing first aid in emergencies. (3) Results: 732 participants participated in this study. The median knowledge score regarding first aid items was 9 (7–10) out of the maximum possible score of 15. The median first aid attitude score was 24 (22–27) out of a maximum possible score of 30. The most commonly reported barrier to performing first aid among the participants was “lack of first aid training” (76.78%), followed by “lack of knowledge about first aid” (75.81%) and “fear of performing first aid” (57.51%). The participants with lower income levels exhibited more negative attitudes towards first aid (4). Conclusions: This study underscores the urgent need for enhanced first aid training and awareness in Jordan. The participants’ first-aid knowledge overall was limited, although positive attitudes toward first-aid delivery were observed. The findings emphasize the need for regular and structured first-aid training courses, addressing barriers such as fear and misinformation and ensuring accessibility across all socioeconomic levels to improve preparedness for road traffic accidents and other emergencies. This comprehensive approach can better equip the Jordanian population to effectively manage emergencies and improve public health outcomes.
Nine-Month Trend of IgG Antibody Persistence and Associated Symptoms Post-SARS-CoV-2 Infection
Authors: Lugo-Trampe Angel , López-Cifuentes Daniel , Mendoza-Pérez Paúl , Tafurt-Cardona Yaliana , Joo-Domínguez Alejandra de Jesús , Rios-Ibarra Clara Patricia , Espinoza-Ruiz Marisol , Chang-Rueda Consuelo , Rodriguez-Sanchez Iram Pablo , Martinez-Fierro Margarita L. , Delgado-Enciso Iván , Trujillo-Murillo Karina del Carmen
Published: May 2024

Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.
Clustering of Cardiovascular Risk Factors and Heart Failure in Older Adults from the Brazilian Far North
Authors: Ribeiro Guilherme José Silva , Moriguchi Emilio Hideyuki , Pinto André Araújo
Published: May 2024

Given the aging global population, identifying heart failure (HF) phenotypes has become crucial, as distinct disease characteristics can influence treatment and prognosis in older adults. This study aimed to analyze the association between clustering of cardiovascular risk factors and HF in older adults. A cross-sectional epidemiological study was conducted with 1322 older adults (55% women, mean age 70.4) seen in primary health care. Diagnosis of HF was performed by a cardiologist based on diagnostic tests and medical history. Cardiovascular risk factors included hypertension, diabetes, hypercholesterolemia, and smoking. Using logistic regression, potential associations were tested. Individual risk factor analysis showed that older adults with hypertension, diabetes, or hypercholesterolemia had up to 7.6 times higher odds to have HF. The cluster where older adults had only one risk factor instead of none increased the odds of HF by 53.0%. Additionally, the odds of older patients having HF ranged from 3.59 times for the two-risk factor cluster to 20.61 times for the simultaneous presence of all four factors. The analysis of clusters substantially increasing HF risk in older adults revealed the importance of individualizing subgroups with distinct HF pathophysiologies. The clinical significance of these clusters can be beneficial in guiding a more personalized therapeutic approach.
The Role of Career Adaptability and Academic Engagement in College Student’s Life Satisfaction
Authors: Oliveira Íris M. , Marques Cátia
Published: May 2024

Career adaptability and academic engagement are important processes in higher education. However, the relationship between these processes and their potential role in students’ life satisfaction still needs to be addressed. The present study aims to explore the role of career adaptability and academic engagement on higher education students’ life satisfaction. This study included 201 participants, 156 women (77.6%) and 45 men (22.4%), aged between 18 and 55 years (M = 21.13, SD = 4.51). Students answered a sociodemographic questionnaire, the Career Adapt-Abilities Scale, the University Student Engagement Inventory, and the Satisfaction with Life Scale. Positive and statistically significant correlations between career adaptability and academic engagement, as well as between these variables and life satisfaction, were found. The results of a hierarchical linear regression analysis suggested that career adaptability and academic engagement statistically significantly contribute to explaining variations in life satisfaction. This study may lead to a better understanding of the relationship between academic, emotional, and career processes. It may also stimulate integrative psychological practices in higher education settings.
Phosphate Uptake and Its Relation to Arsenic Toxicity in Lactobacilli
Authors: Corrales Daniela , Alcántara Cristina , Clemente María Jesús , Vélez Dinoraz , Devesa Vicenta , Monedero Vicente , Zúñiga Manuel
Published: May 2024

The use of probiotic lactobacilli has been proposed as a strategy to mitigate damage associated with exposure to toxic metals. Their protective effect against cationic metal ions, such as those of mercury or lead, is believed to stem from their chelating and accumulating potential. However, their retention of anionic toxic metalloids, such as inorganic arsenic, is generally low. Through the construction of mutants in phosphate transporter genes (pst) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains, coupled with arsenate [As(V)] uptake and toxicity assays, we determined that the incorporation of As(V), which structurally resembles phosphate, is likely facilitated by phosphate transporters. Surprisingly, inactivation in Lc. paracasei of PhoP, the transcriptional regulator of the two-component system PhoPR, a signal transducer involved in phosphate sensing, led to an increased resistance to arsenite [As(III)]. In comparison to the wild type, the phoP strain exhibited no differences in the ability to retain As(III), and there were no observed changes in the oxidation of As(III) to the less toxic As(V). These results reinforce the idea that specific transport, and not unspecific cell retention, plays a role in As(V) biosorption by lactobacilli, while they reveal an unexpected phenotype for the lack of the pleiotropic regulator PhoP.
Polydopamine/SWCNT Ink Functionalization of Silk Fabric to Obtain Electroconductivity at a Low Percolation Threshold
Authors: Baranowska-Korczyc Anna , Kowalczyk Dorota , Cieślak Małgorzata
Published: May 2024

This study presents the functionalization of silk fabric with SWCNT ink. The first step was the formation of a polydopamine (PDA) thin coating on the silk fabric to allow for effective bonding of SWCNTs. PDA formation was carried out directly on the fabric by means of polymerization of dopamine in alkali conditions. The Silk/PDA fabric was functionalized with SWCNT ink of different SWCNT concentrations by using the dip-coating method. IR and Raman analyses show that the dominant β-sheet structure of silk fibroin after the functionalization process remains unchanged. The heat resistance is even slightly improved. The hydrophobic silk fabric becomes hydrophilic after functionalization due to the influence of PDA and the surfactant in SWCNT ink. The ink significantly changes the electrical properties of the silk fabric, from insulating to conductive. The volume resistance changes by nine orders of magnitude, from 2.4 × 1012 Ω to 2.3 × 103 Ω for 0.12 wt.% of SWCNTs. The surface resistance changes by seven orders of magnitude, from 2.1 × 1012 Ω to 2.4 × 105 Ω for 0.17 wt.% of SWCNTs. The volume and surface resistance thresholds are determined to be about 0.05 wt.% and 0.06 wt.%, respectively. The low value of the percolation threshold indicates efficient functionalization, with high-quality ink facilitating the formation of percolation paths through SWCNTs and the influence of the PDA linker.
Pathophysiology and Advances in the Therapy of Cardiomyopathy in Patients with Diabetes Mellitus
Authors: Graczyk Patryk , Dach Aleksandra , Dyrka Kamil , Pawlik Andrzej
Published: May 2024

Diabetes mellitus (DM) is known as the first non-communicable global epidemic. It is estimated that 537 million people have DM, but the condition has been properly diagnosed in less than half of these patients. Despite numerous preventive measures, the number of DM cases is steadily increasing. The state of chronic hyperglycaemia in the body leads to numerous complications, including diabetic cardiomyopathy (DCM). A number of pathophysiological mechanisms are behind the development and progression of cardiomyopathy, including increased oxidative stress, chronic inflammation, increased synthesis of advanced glycation products and overexpression of the biosynthetic pathway of certain compounds, such as hexosamine. There is extensive research on the treatment of DCM, and there are a number of therapies that can stop the development of this complication. Among the compounds used to treat DCM are antiglycaemic drugs, hypoglycaemic drugs and drugs used to treat myocardial failure. An important element in combating DCM that should be kept in mind is a healthy lifestyle—a well-balanced diet and physical activity. There is also a group of compounds—including coenzyme Q10, antioxidants and modulators of signalling pathways and inflammatory processes, among others—that are being researched continuously, and their introduction into routine therapies is likely to result in greater control and more effective treatment of DM in the future. This paper summarises the latest recommendations for lifestyle and pharmacological treatment of cardiomyopathy in patients with DM.
Impact of Nebulization on the Physicochemical Properties of Polymer–Lipid Hybrid Nanoparticles for Pulmonary Drug Delivery
Authors: Gonsalves Andrea , Menon Jyothi U.
Published: May 2024

Nanoparticles (NPs) have shown significant potential for pulmonary administration of therapeutics for the treatment of chronic lung diseases in a localized and sustained manner. Nebulization is a suitable method of NP delivery, particularly in patients whose ability to breathe is impaired due to lung diseases. However, there are limited studies evaluating the physicochemical properties of NPs after they are passed through a nebulizer. High shear stress generated during nebulization could potentially affect the surface properties of NPs, resulting in the loss of encapsulated drugs and alteration in the release kinetics. Herein, we thoroughly examined the physicochemical properties as well as the therapeutic effectiveness of Infasurf lung surfactant (IFS)-coated PLGA NPs previously developed by us after passing through a commercial Aeroneb® vibrating-mesh nebulizer. Nebulization did not alter the size, surface charge, IFS coating and bi-phasic release pattern exhibited by the NPs. However, there was a temporary reduction in the initial release of encapsulated therapeutics in the nebulized compared to non-nebulized NPs. This underscores the importance of evaluating the drug release kinetics of NPs using the inhalation method of choice to ensure suitability for the intended medical application. The cellular uptake studies demonstrated that both nebulized and non-nebulized NPs were less readily taken up by alveolar macrophages compared to lung cancer cells, confirming the IFS coating retention. Overall, nebulization did not significantly compromise the physicochemical properties as well as therapeutic efficacy of the prepared nanotherapeutics.
TGF-β2 Induces Ribosome Activity, Alters Ribosome Composition and Inhibits IRES-Mediated Translation in Chondrocytes
Authors: van den Akker Guus G. H. , Chabronova Alzbeta , Housmans Bas A. C. , van der Vloet Laura , Surtel Don A. M. , Cremers Andy , Marchand Virginie , Motorin Yuri , Caron Marjolein M. J. , Peffers Mandy J. , Welting Tim J. M.
Published: May 2024

Alterations in cell fate are often attributed to (epigenetic) regulation of gene expression. An emerging paradigm focuses on specialized ribosomes within a cell. However, little evidence exists for the dynamic regulation of ribosome composition and function. Here, we stimulated a chondrocytic cell line with transforming growth factor beta (TGF-β2) and mapped changes in ribosome function, composition and ribosomal RNA (rRNA) epitranscriptomics. 35S Met/Cys incorporation was used to evaluate ribosome activity. Dual luciferase reporter assays were used to assess ribosomal modus. Ribosomal RNA expression and processing were determined by RT-qPCR, while RiboMethSeq and HydraPsiSeq were used to determine rRNA modification profiles. Label-free protein quantification of total cell lysates, isolated ribosomes and secreted proteins was done by LC-MS/MS. A three-day TGF-β2 stimulation induced total protein synthesis in SW1353 chondrocytic cells and human articular chondrocytes. Specifically, TGF-β2 induced cap-mediated protein synthesis, while IRES-mediated translation was not (P53 IRES) or little affected (CrPv IGR and HCV IRES). Three rRNA post-transcriptional modifications (PTMs) were affected by TGF-β2 stimulation (18S-Gm1447 downregulated, 18S-ψ1177 and 28S-ψ4598 upregulated). Proteomic analysis of isolated ribosomes revealed increased interaction with eIF2 and tRNA ligases and decreased association of eIF4A3 and heterogeneous nuclear ribonucleoprotein (HNRNP)s. In addition, thirteen core ribosomal proteins were more present in ribosomes from TGF-β2 stimulated cells, albeit with a modest fold change. A prolonged stimulation of chondrocytic cells with TGF-β2 induced ribosome activity and changed the mode of translation. These functional changes could be coupled to alterations in accessory proteins in the ribosomal proteome.
Amyloid Beta Leads to Decreased Acetylcholine Levels and Non-Small Cell Lung Cancer Cell Survival via a Mechanism That Involves p38 Mitogen-Activated Protein Kinase and Protein Kinase C in a p53-Dependent and -Independent Manner
Authors: Al Khashali Hind , Ray Ravel , Darweesh Ban , Wozniak Caroline , Haddad Ben , Goel Stuti , Seidu Issah , Khalil Jeneen , Lopo Brooke , Murshed Nayrooz , Guthrie Jeffrey , Heyl Deborah , Evans Hedeel Guy
Published: May 2024

Several studies have shown an inverse correlation between the likelihood of developing a neurodegenerative disorder and cancer. We previously reported that the levels of amyloid beta (Aβ), at the center of Alzheimer’s disease pathophysiology, are regulated by acetylcholinesterase (AChE) in non-small cell lung cancer (NSCLC). Here, we examined the effect of Aβ or its fragments on the levels of ACh in A549 (p53 wild-type) and H1299 (p53-null) NSCLC cell media. ACh levels were reduced by cell treatment with Aβ 1–42, Aβ 1–40, Aβ 1–28, and Aβ 25–35. AChE and p53 activities increased upon A549 cell treatment with Aβ, while knockdown of p53 in A549 cells increased ACh levels, decreased AChE activity, and diminished the Aβ effects. Aβ increased the ratio of phospho/total p38 MAPK and decreased the activity of PKC. Inhibiting p38 MAPK reduced the activity of p53 in A549 cells and increased ACh levels in the media of both cell lines, while opposite effects were found upon inhibiting PKC. ACh decreased the activity of p53 in A549 cells, decreased p38 MAPK activity, increased PKC activity, and diminished the effect of Aβ on those activities. Moreover, the negative effect of Aβ on cell viability was diminished by cell co-treatment with ACh.
Exploring the Role of Apigenin in Neuroinflammation: Insights and Implications
Authors: Charrière Karine , Schneider Vincent , Perrignon-Sommet Manon , Lizard Gérard , Benani Alexandre , Jacquin-Piques Agnès , Vejux Anne
Published: May 2024

Neuroinflammation, a hallmark of various central nervous system disorders, is often associated with oxidative stress and neuronal or oligodendrocyte cell death. It is therefore very interesting to target neuroinflammation pharmacologically. One therapeutic option is the use of nutraceuticals, particularly apigenin. Apigenin is present in plants: vegetables (parsley, celery, onions), fruits (oranges), herbs (chamomile, thyme, oregano, basil), and some beverages (tea, beer, and wine). This review explores the potential of apigenin as an anti-inflammatory agent across diverse neurological conditions (multiple sclerosis, Parkinson’s disease, Alzheimer’s disease), cancer, cardiovascular diseases, cognitive and memory disorders, and toxicity related to trace metals and other chemicals. Drawing upon major studies, we summarize apigenin’s multifaceted effects and underlying mechanisms in neuroinflammation. Our review underscores apigenin’s therapeutic promise and calls for further investigation into its clinical applications.
The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples
Authors: Deigin Vladislav , Linkova Natalia , Vinogradova Julia , Vinogradov Dmitrii , Polyakova Victoria , Medvedev Dmitrii , Krasichkov Alexander , Volpina Olga
Published: May 2024

Peptides show high promise in the targeting and intracellular delivery of next-generation biotherapeutics. The main limitation is peptides’ susceptibility to proteolysis in biological systems. Numerous strategies have been developed to overcome this challenge by chemically enhancing the resistance to proteolysis. In nature, amino acids, except glycine, are found in L- and D-enantiomers. The change from one form to the other will change the primary structure of polypeptides and proteins and may affect their function and biological activity. Given the inherent chiral nature of biological systems and their high enantiomeric selectivity, there is rising interest in manipulating the chirality of polypeptides to enhance their biomolecular interactions. In this review, we discuss the first examples of up-and-down homeostasis regulation by two enantiomeric drugs: immunostimulant Thymogen (L-Glu-L-Trp) and immunosuppressor Thymodepressin (D-Glu(D-Trp)). This study shows the perspective of exploring chirality to remove the chiral wall between L- and D-biomolecules. The selected clinical result will be discussed.
Molecular Mechanisms of CBL-CIPK Signaling Pathway in Plant Abiotic Stress Tolerance and Hormone Crosstalk
Authors: Kaya Cengiz , Uğurlar Ferhat , Adamakis Ioannis-Dimosthenis S.
Published: May 2024

Abiotic stressors, including drought, salt, cold, and heat, profoundly impact plant growth and development, forcing elaborate cellular responses for adaptation and resilience. Among the crucial orchestrators of these responses is the CBL-CIPK pathway, comprising calcineurin B-like proteins (CBLs) and CBL-interacting protein kinases (CIPKs). While CIPKs act as serine/threonine protein kinases, transmitting calcium signals, CBLs function as calcium sensors, influencing the plant’s response to abiotic stress. This review explores the intricate interactions between the CBL-CIPK pathway and plant hormones such as ABA, auxin, ethylene, and jasmonic acid (JA). It highlights their role in fine-tuning stress responses for optimal survival and acclimatization. Building on previous studies that demonstrated the enhanced stress tolerance achieved by upregulating CBL and CIPK genes, we explore the regulatory mechanisms involving post-translational modifications and protein–protein interactions. Despite significant contributions from prior research, gaps persist in understanding the nuanced interplay between the CBL-CIPK system and plant hormone signaling under diverse abiotic stress conditions. In contrast to broader perspectives, our review focuses on the interaction of the pathway with crucial plant hormones and its implications for genetic engineering interventions to enhance crop stress resilience. This specialized perspective aims to contribute novel insights to advance our understanding of the potential of the CBL-CIPK pathway to mitigate crops’ abiotic stress.
Emerging Roles of Vitamin B12 in Aging and Inflammation
Authors: Simonenko Sergey Yu. , Bogdanova Daria A. , Kuldyushev Nikita A.
Published: May 2024

Vitamin B12 (cobalamin) is an essential nutrient for humans and animals. Metabolically active forms of B12-methylcobalamin and 5-deoxyadenosylcobalamin are cofactors for the enzymes methionine synthase and mitochondrial methylmalonyl-CoA mutase. Malfunction of these enzymes due to a scarcity of vitamin B12 leads to disturbance of one-carbon metabolism and impaired mitochondrial function. A significant fraction of the population (up to 20%) is deficient in vitamin B12, with a higher rate of deficiency among elderly people. B12 deficiency is associated with numerous hallmarks of aging at the cellular and organismal levels. Cellular senescence is characterized by high levels of DNA damage by metabolic abnormalities, increased mitochondrial dysfunction, and disturbance of epigenetic regulation. B12 deficiency could be responsible for or play a crucial part in these disorders. In this review, we focus on a comprehensive analysis of molecular mechanisms through which vitamin B12 influences aging. We review new data about how deficiency in vitamin B12 may accelerate cellular aging. Despite indications that vitamin B12 has an important role in health and healthy aging, knowledge of the influence of vitamin B12 on aging is still limited and requires further research.
Prognostic Value of B7H4 Expression in Patients with Solid Cancers: A Systematic Review and Meta-Analysis
Authors: Dawidowicz Miriam , Kula Agnieszka , Mielcarska Sylwia , Świętochowska Elżbieta , Waniczek Dariusz
Published: May 2024

V-set domain-containing T-cell activation inhibitor 1 (aliases VTCN1, B7H4) participates in tumour immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the B7H4 prognostic value in solid cancers. Three databases were searched for relevant articles. The main endpoints were overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Appropriate hazard ratios (HRs) were pooled. The R studio software (version 4.0.3) was used for data analysis. Thirty-one studies met the inclusion criteria. High expression of B7H4 was associated with worse OS (HR = 1.52, 95% CI: 1.37–1.68) but not with DSS (HR = 1.14, 95% CI: 0.49–2.63), RFS (HR = 1.77, 95% CI: 0.75–4.18), DFS (HR = 1.29, 95% CI: 0.8–2.09), or PFS (HR = 1.71, 95% CI: 0.91–3.2) in patients with solid cancers. High expression of B7H4 is associated with a poorer prognosis in patients with solid cancers. B7H4 is a promising prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumourigenesis.
Natural Compounds for Bone Remodeling: A Computational and Experimental Approach Targeting Bone Metabolism-Related Proteins
Authors: Loukas Alexandros-Timotheos , Papadourakis Michail , Panagiotopoulos Vasilis , Zarmpala Apostolia , Chontzopoulou Eleni , Christodoulou Stephanos , Katsila Theodora , Zoumpoulakis Panagiotis , Matsoukas Minos-Timotheos
Published: May 2024

Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults and postmenopausal women. The disruption of the balance between bone-forming osteoblasts and bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium and vitamin D supplementation and specific drugs that either inhibit osteoclasts or stimulate osteoblasts. However, these treatments have limitations, including side effects and compliance issues. Natural products have emerged as potential osteoporosis therapeutics, but their mechanisms of action remain poorly understood. In this study, we investigate the efficacy of natural compounds in modulating molecular targets relevant to osteoporosis, focusing on the Mitogen-Activated Protein Kinase (MAPK) pathway and the gut microbiome’s influence on bone homeostasis. Using an in silico and in vitro methodology, we have identified quercetin as a promising candidate in modulating MAPK activity, offering a potential therapeutic perspective for osteoporosis treatment.
KiSS-1 Modulation by Epigenetic Agents Improves the Cisplatin Sensitivity of Lung Cancer Cells
Authors: Beretta Giovanni Luca , Alampi Desirè , Corno Cristina , Carenini Nives , Corna Elisabetta , Perego Paola
Published: May 2024

Epigenetic alterations my play a role in the aggressive behavior of Non-Small Cell Lung Cancer (NSCLC). Treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) has been reported to interfere with the proliferative and invasive potential of NSCLC cells. In addition, the DNA methyltransferase inhibitor azacytidine (AZA, vidaza) can modulate the levels of the metastasis suppressor KiSS-1. Thus, since cisplatin is still clinically available for NSCLC therapy, the aim of this study was to evaluate drug combinations between cisplatin and SAHA as well as AZA using cisplatin-sensitive H460 and -resistant H460/Pt NSCLC cells in relation to KiSS-1 modulation. An analysis of drug interaction according to the Combination-Index values indicated a more marked synergistic effect when the exposure to SAHA or AZA preceded cisplatin treatment with respect to a simultaneous schedule. A modulation of proteins involved in apoptosis (p53, Bax) was found in both sensitive and resistant cells, and compared to the treatment with epigenetic agents alone, the combination of cisplatin and SAHA or AZA increased apoptosis induction. The epigenetic treatments, both as single agents and in combination, increased the release of KiSS-1. Finally, the exposure of cisplatin-sensitive and -resistant cells to the kisspeptin KP10 enhanced cisplatin induced cell death. The efficacy of the combination of SAHA and cisplatin was tested in vivo after subcutaneous inoculum of parental and resistant cells in immunodeficient mice. A significant tumor volume inhibition was found when mice bearing advanced tumors were treated with the combination of SAHA and cisplatin according to the best schedule identified in cellular studies. These results, together with the available literature, support that epigenetic drugs are amenable for the combination treatment of NSCLC, including patients bearing cisplatin-resistant tumors.
Anti-Biofilm Activity of Oleacein and Oleocanthal from Extra-Virgin Olive Oil toward Pseudomonas aeruginosa
Authors: Di Pietro Marisa , Filardo Simone , Mattioli Roberto , Bozzuto Giuseppina , Raponi Giammarco , Mosca Luciana , Sessa Rosa
Published: May 2024

New antimicrobial molecules effective against Pseudomonas aeruginosa, known as an antibiotic-resistant “high-priority pathogen”, are urgently required because of its ability to develop biofilms related to healthcare-acquired infections. In this study, for the first time, the anti-biofilm and anti-virulence activities of a polyphenolic extract of extra-virgin olive oil as well as purified oleocanthal and oleacein, toward P. aeruginosa clinical isolates were investigated. The main result of our study was the anti-virulence activity of the mixture of oleacein and oleocanthal toward multidrug-resistant and intermediately resistant strains of P. aeruginosa isolated from patients with ventilator-associated pneumonia or surgical site infection. Specifically, the mixture of oleacein (2.5 mM)/oleocanthal (2.5 mM) significantly inhibited biofilm formation, alginate and pyocyanin production, and motility in both P. aeruginosa strains (p < 0.05); scanning electron microscopy analysis further evidenced its ability to inhibit bacterial cell adhesion as well as the production of the extracellular matrix. In conclusion, our results suggest the potential application of the oleacein/oleocanthal mixture in the management of healthcare-associated P. aeruginosa infections, particularly in the era of increasing antimicrobial resistance.
Elucidating the Structural Features of Bis(arylimino)acenaphthene (Aryl-BIAN) Bismuth Complexes: A Combined Single-Crystal X-ray Diffraction and Hirshfeld Analysis Approach
Authors: Machado Beatriz P. , Celador-Garcia Maria , Rosa Vitor , Gomes Clara S. B.
Published: May 2024

Dimeric bismuth(III) complexes bearing bis(aryl-imino)acenaphthene (Aryl-BIAN) donor ligands of the general formulae [(Dipp-BIAN)BiCl3]2 2, [(o-iPr-BIAN)BiCl3]2 3, and [(p-iPr-BIAN)BiCl3]2 4, where Dipp = diisopropyl, o-iPr = ortho-isopropyl and p-iPr = para-isopropyl, were prepared by reaction of the corresponding neutral BIAN ligand with BiCl3, under inert atmosphere conditions. X-ray studies were performed, and their molecular structures were determined. The individual contributions of intermolecular interactions to crystal packing have been quantified by means of Hirsfeld surface analysis.
Incidence of the El Niño–Southern Oscillation Cycle on the Existing Fundamental Niche and Establishment Risk of Some Anastrepha Species (Diptera-Tephritidae) of Horticultural Importance in the Neotropics and Panama
Authors: Degracia Arturo Batista , Ávila Jiménez Julián , Alvarado Anovel Barba , Valdespino Randy Atencio , Altamiranda-Saavedra Mariano
Published: May 2024

To compare the environmental space of four Anastrepha species in different ENSO episodes (El Niño, El Neutro and La Niña), we built ecological niche models with NicheA software. We analysed the fundamental niche and the combined establishment risk maps of these species developed with the ArcGisPro combine geoprocess. A comparison of the ellipsoids that represent the fundamental niche existing for the species showed changes in the El Niño, El Neutro and La Niña episodes. For A. grandis in the El Niño vs. El Neutro episodes, there was a Jaccard index of 0.3841, while the comparison between the La Niña vs. El Neutro episodes presented a Jaccard index of 0.6192. A. serpentina in the El Niño vs. El Neutro and La Niña vs. El Neutro episodes presented Jaccard indices of 0.3281 and 0.6328, respectively. For A. obliqua, the comparison between the El Niño vs. El Neutro and La Niña vs. El Neutro episodes presented Jaccard indices of 0.3518 and 0.7472, respectively. For A. striata, comparisons between the episodes of El Niño vs. El Neutro and La Niña vs. El Neutro presented Jaccard indices of 0.3325 and 0.6022, respectively. When studying the comparison between Anastrepha species and the different ENSO climatic episodes, we found that in the El Niño episode, the comparisons with the best environmental similarity were A. obliqua vs. A. striata and A. obliqua vs. A. serpentina, with higher Jaccard indices (0.6064 and 0.6316, respectively). In the El Neutro episode, the comparisons with the best environmental similarity were A. serpentina vs. A. striata and A. obliqua vs. A. striata, which presented higher Jaccard indices (0.4616 and 0.6411, respectively). In the La Niña episode, the comparisons that presented the best environmental similarity were A. obliqua vs. A. serpentina and A. obliqua vs. A. striata, with higher Jaccard indices (0.5982 and 0.6228, respectively). Likewise, our results present the risk maps for the establishment of these species throughout the Neotropics, allowing us to predict the level of risk in order to develop integrated pest management plans.
Migration Activity of Spodoptera litura (Lepidoptera: Noctuidae) between China and the South-Southeast Asian Region
Authors: Song Yifei , Cang Xinzhu , He Wei , Zhang Haowen , Wu Kongming
Published: May 2024

The common cutworm, Spodoptera litura (F.), feeds on a wide variety of food and cash crops and is one of the most widespread and destructive agricultural pests worldwide. Migration is the biological basis of its regional population outbreaks but the seasonal movement of this pest between east and south Asia regions remains unknown. In this study, searchlight traps were used to monitor the seasonal migration of S. litura from 2019 to 2023 in Ruili City (Yunnan, China), located along the insect migratory route between China and the south Asia region. The results showed that migratory activity could occur throughout the year, with the main periods found in spring (April–May) and autumn (October–December). The ovarian development and mating status of the trapped females indicated that most individuals were in the middle or late stages of migration and that Ruili City was located in the transit area of the long-distance migration of the pest. In the migration trajectory simulation, populations of S. litura moved from northeast India, Bangladesh, and northern Myanmar to southwestern China along the southern margin of the Himalayas in spring and returned to the south Asia region in autumn. Our findings clarify the seasonal migration patterns of S. litura in China and South Asia and facilitate the development of regional cross-border monitoring and management systems for this pest.
The sFlt-1/PlGF Ratio at 12, 24, and 32 Weeks Gestation in Twin Pregnancies as a Predictor of Late Preterm Birth and Perinatal Event Secondary to Prematurity
Authors: Satorres-Pérez Elena , Martínez-Varea Alicia , Novillo-Del Álamo Blanca , Morales-Roselló José , Diago-Almela Vicente
Published: May 2024

Background: Preterm birth impacts 60% of twin pregnancies, with the subsequent risk of complications in both newborns secondary to the immaturity of organs. This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting late preterm birth and adverse perinatal outcomes related to prematurity in twin pregnancies. Methods: This is a prospective cohort study developed at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks’ gestation. Results: Seventy patients were included, from which 54.3% suffered late preterm birth. Results revealed a significant difference in sFlt-1/PlGF ratio at week 32 between term and preterm groups, with a one-unit increase associated with a 1.11-fold increase in the probability of preterm birth. The sFlt-1/PlGF ratio at week 32 alone presented considerable predictive capacities (sensitivity of 71%, specificity of 72%, a PPV of 75%, and an NPV of 68%. Similarly, at week 24, a one-unit increase in sFlt-1/PlGF ratio was associated with a 1.24-fold increase in the probability of adverse perinatal events due to prematurity. Combining parity, maternal age, conception method, BMI, and chorionicity, the model yielded better predictive capacities (sensitivity of 82%, specificity of 80%, PPV of 58%, NPV of 93%). Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for preterm birth and adverse perinatal outcomes secondary to prematurity in twin pregnancies is underscored.
A Systematic Literature Review of Predictors of Erythropoiesis-Stimulating Agent Failure in Lower-Risk Myelodysplastic Syndromes
Authors: Boccia Ralph , Xiao Hong , von Wilamowitz-Moellendorff Caroline , Raorane Renuka , Deshpande Sohan , Klijn Sven L. , Yucel Aylin
Published: May 2024

Erythropoiesis-stimulating agents (ESAs) are the first-line treatment option for anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS). A systematic literature review was conducted to identify evidence of the association between prognostic factors and ESA response/failure in LR-MDS. MEDLINE, Embase, and relevant conferences were searched systematically for studies assessing the association between prognostic factors and ESA response/failure in adult patients. Of 1566 citations identified, 38 were included. Patient risk status in studies published from 2000 onwards was commonly assessed using the International Prognostic Scoring System (IPSS) or revised IPSS. ESA response was generally assessed using the International Working Group MDS criteria. Among the included studies, statistically significant relationships were found, in both univariate and multivariate analyses, between ESA response and the following prognostic factors: higher hemoglobin levels, lower serum erythropoietin levels, and transfusion independence. Furthermore, other prognostic factors such as age, bone marrow blasts, serum ferritin level, IPSS risk status, and karyotype status did not demonstrate statistically significant relationships with ESA response. This systematic literature review has confirmed prognostic factors of ESA response/failure. Guidance to correctly identify patients with these characteristics could be helpful for clinicians to provide optimal treatment.