bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmet Primary Health Care Needs among Nepalese Immigrant Population in Canada
Authors: Bajgain Bishnu Bahadur , Chowdhury Mohammad Z. I. , Dahal Rudra , Bajgain Kalpana Thapa , Adhikari Kamala , Chowdhury Nashit , Turin Tanvir C.
Published: July 2023

Background: Immigrants represent over one-fifth (21.9%) of the Canadian population, which is an increasing trend. Primary care is a gateway to accessing the healthcare system for the majority of Canadians seeking medical services; however, Canada reported a growing shortage of healthcare providers, mainly primary care practitioners. Canadians, including immigrants, encounter many unmet healthcare needs due to various reasons. This study aimed to assess unmet healthcare (UHC) needs and associated factors among Nepalese immigrants residing in Calgary. Methods: A cross-sectional study using a self-administered questionnaire was conducted in 2019. UHC needs were measured based on a single-item question: “During the past 12 months, was there ever a time that you felt you needed medical help, but you did not receive it”. A follow-up question was asked to learn about associated unmet needs factors, and the responses were categorized into availability, accessibility, and acceptability. Descriptive and multivariable logistic regression was employed to assess the association between UHC needs and its predictors by using STATA version 14.2. Results: Of 401 study participants, nearly half of the participants (n = 187; 46.63%) reported UHC needs, which was not significantly different among male and female participants (p = 0.718). UHC needs were nearly two times higher among those aged 26–45 (AOR 1.93) and those ≥56 years (AOR 2.17) compared to those under 25 years of age. The top reasons reported for unmet needs were long waits to access care (67.91%), healthcare costs (57.22%), and lack of knowing where to get help (31.55%). Overall, “services availability when required” was a leading obstacle that accounted for UHC needs (n = 137, 73.26%). Nearly two-thirds (n = 121, 64.71%) of participants reported that “accessibility of services” was a barrier, followed by “acceptability (n = 107, 57.22%). Those who reported UHC needs also reported an impact on their lives personally and economically. The most commonly reported personal impact was mental health impact, including worry, anxiety, and stress (67.38%). The most common economic impact reported due to UHC needs was increased use of over-the-counter drugs (33.16%) and increased healthcare costs (17.20%). Conclusions: UHC needs are presented in the Nepalese immigrant population. Accessibility to healthcare is limited for several reasons: waiting time, cost, distance, and unavailability of services. UHC needs impact individuals’ personal health, daily life activities, and financial capacity. Strategies to improve access to PHC for disadvantaged populations are crucial and need to be tackled effectively.
Time Spent on Mobile Apps Matters: A Latent Class Analysis of Patterns of Smartphone Use among Adolescents
Authors: Fortunato Lucia , Lo Coco Gianluca , Teti Arianna , Bonfanti Rubinia Celeste , Salerno Laura
Published: July 2023

The aims of the present study are: (1) to determine classes of adolescents with homogeneous patterns of smartphone or social media use; and (2) to examine the level of distress across the empirically derived profiles. Three hundred and forty adolescents (Mage = 15.61, SD = 1.19; 38.2% females) participated in a cross-sectional survey. Participants provided objective trace data on time spent on smartphones and applications, as well as self-reported social media addiction, social media use intensity, online social comparison, emotion dysregulation, and psychological distress. Latent class analysis (LCA) with total smartphone use categorized participants into three classes. Participants in Class 3 (19%) showed a more impaired functioning profile, with a tendency towards social media addiction and greater levels of distress. LCAs with the amount of time devoted to specific applications are more heterogeneous, and results showed that heavy use of social media apps was not consistently connected to the most impaired psychosocial profiles. Although the amount of mobile screen time can be a characteristic of problematic users, the link between social media usage and an adolescent’s psychological characteristics is mixed. More research is needed to explore the interplay between mobile screen time and social media usage among adolescents.
The Sustainability of Investing in Cryptocurrencies: A Bibliometric Analysis of Research Trends
Authors: Alqudah Mohammad , Ferruz Luis , Martín Emilio , Qudah Hanan , Hamdan Firas
Published: July 2023

This paper explores the state of the art in the cryptocurrency literature, with a special emphasis on the links between financial dimensions and ESG features. The study uses bibliometric analysis to illustrate the history of cryptocurrency publication activity, focusing on the most popular subjects and research trends. Between 2014 and 2021, 1442 papers on cryptocurrencies were published in the Web of Science core collection, the most authoritative database, although only a tiny percentage evaluated ESG factors. One of the most common criticisms of cryptocurrencies is the pollution derived from energy consumption in their mining process and their use for illicit purposes due to the absence of effective regulation. The study allows us to suggest future research directions that may be beneficial in illustrating the environmental effect, studying financial behavior, identifying the long-term sustainability of cryptocurrencies, and evaluating their financial success. This study provides an in-depth examination of current research trends in the field of cryptocurrencies, identifying prospective future research directions.
C∙∙∙O and Si∙∙∙O Tetrel Bonds: Substituent Effects and Transfer of the SiF3 Group
Authors: Niu Zhihao , Wu Qiaozhuo , Li Qingzhong , Scheiner Steve
Published: July 2023

The tetrel bond (TB) between 1,2-benzisothiazol-3-one-2-TF3-1,1-dioxide (T = C, Si) and the O atom of pyridine-1-oxide (PO) and its derivatives (PO-X, X = H, NO2, CN, F, CH3, OH, OCH3, NH2, and Li) is examined by quantum chemical means. The Si∙∙∙O TB is quite strong, with interaction energies approaching a maximum of nearly 70 kcal/mol, while the C∙∙∙O TB is an order of magnitude weaker, with interaction energies between 2.0 and 2.6 kcal/mol. An electron-withdrawing substituent on the Lewis base weakens this TB, while an electron-donating group has the opposite effect. The SiF3 group transfers roughly halfway between the N of the acid and the O of the base without the aid of cooperative effects from a third entity.
Resveratrol Improves Endothelial Function by A PREP1-Mediated Pathway in Mouse Aortic Endothelial Cells
Authors: Cabaro Serena , Agognon Ayewa L. , Nigro Cecilia , Orso Sonia , Prevenzano Immacolata , Leone Alessia , Morelli Cristina , Mormone Federica , Romano Serena , Miele Claudia , Beguinot Francesco , Formisano Pietro , Oriente Francesco
Published: July 2023

PREP1 is a homeodomain transcription factor that impairs metabolism and is involved in age-related aortic thickening. In this study, we evaluated the role of PREP1 on endothelial function. Mouse Aortic Endothelial Cells (MAECs) transiently transfected with a Prep1 cDNA showed a 1.5- and 1.6-fold increase in eNOSThr495 and PKCα phosphorylation, respectively. Proinflammatory cytokines Tnf-α and Il-6 increased by 3.5 and 2.3-fold, respectively, in the presence of Prep1, while the antioxidant genes Sod2 and Atf4 were significantly reduced. Bisindolylmaleimide reverted the effects induced by PREP1, suggesting PKCα to be a mediator of PREP1 action. Interestingly, resveratrol, a phenolic micronutrient compound, reduced the PREP1 levels, eNOSThr495, PKCα phosphorylation, and proinflammatory cytokines and increased Sod2 and Atf4 mRNA levels. The experiments performed on the aorta of 18-month-old Prep1 hypomorphic heterozygous mice (Prep1i/+) expressing low levels of this protein showed a 54 and 60% decrease in PKCα and eNOSThr495 phosphorylation and a 45% reduction in Tnf-α levels, with no change in Il-6, compared to same-age WT mice. However, a significant decrease in Sod2 and Atf4 was observed in Prep1i/+ old mice, indicating the lack of age-induced antioxidant response. These results suggest that Prep1 deficiency partially improved the endothelial function in aged mice and suggested PREP1 as a novel target of resveratrol.
Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa
Authors: Sánchez-Jiménez Ana , Llamas María A. , Marcos-Torres Francisco Javier
Published: July 2023

Pseudomonas aeruginosa is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of virulence factors necessary in different steps of the infection process. This includes factors involved in bacterial motility and attachment, biofilm formation, the production and secretion of extracellular invasive enzymes and exotoxins, the production of toxic secondary metabolites, and the acquisition of iron. Expression of these virulence factors during infection is tightly regulated, which allows their production only when they are needed. This process optimizes host colonization and virulence. In this work, we review the intricate network of transcriptional regulators that control the expression of virulence factors in P. aeruginosa, including one- and two-component systems and σ factors. Because inhibition of virulence holds promise as a target for new antimicrobials, blocking the regulators that trigger the production of virulence determinants in P. aeruginosa is a promising strategy to fight this clinically relevant pathogen.
Dysregulation of Histone Deacetylases Inhibits Trophoblast Growth during Early Placental Development Partially through TFEB-Dependent Autophagy-Lysosomal Pathway
Authors: Wang Peixin , Zhao Chenqiong , Zhou Hanjing , Huang Xiaona , Ying Hanqi , Zhang Songying , Pan Yibin , Zhu Haiyan
Published: July 2023

Dysregulated biological behaviors of trophoblast cells can result in recurrent spontaneous abortion (RSA)—whose underlying etiology still remains insufficient. Autophagy, a conserved intracellular physiological process, is precisely monitored throughout whole pregnancy. Although the exact mechanism or role remains elusive, epigenetic modification has emerged as an important process. Herein, we found that a proportion of RSA patients exhibited higher levels of autophagy in villus tissues compared to controls, accompanied with impaired histone deacetylase (HDAC) expression. The purpose of this study is to explore the connection between HDACs and autophagy in the pathological course of RSA. Mechanistically, using human trophoblast cell models, treatment with HDAC inhibitor (HDACI)-trichostatin A (TSA) can induce autophagy by promoting nuclear translocation and transcriptional activity of the central autophagic regulator transcription factor EB (TFEB). Specifically, overactivated autophagy is involved in the TSA-driven growth inhibition of trophoblast, which can be partially reversed by the autophagy inhibitor chloroquine (CQ) or RNA interference of TFEB. In summary, our results reveal that abnormal acetylation and autophagy levels during early gestation may be associated with RSA and suggest the potential novel molecular target TFEB for RSA treatment.
Alternations of NF-κB Signaling by Natural Compounds in Muscle-Derived Cancers
Authors: Radzka Justyna , Łapińska Zofia , Szwedowicz Urszula , Gajewska-Naryniecka Agnieszka , Gizak Agnieszka , Kulbacka Julita
Published: July 2023

The NF-κB-signaling pathway plays a crucial role in cancer progression, including muscle-derived cancers such as rhabdomyosarcoma or sarcoma. Several natural compounds have been studied for their ability to alter NF-κB signaling in these types of cancers. This review paper summarizes the current knowledge on the effects of natural compounds, including curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, and berberine, on NF-κB signaling in muscle-derived cancers. These compounds have been shown to inhibit NF-κB signaling in rhabdomyosarcoma cells through various mechanisms, such as inhibiting the activation of the IKK complex and the NF-κB transcription factor. These findings suggest that natural compounds could be potential therapeutic agents for muscle-derived cancers. However, further research is needed to fully understand their mechanisms of action and potential clinical applications.
Mitogen-Activated Protein Kinases (MAPKs) and Enteric Bacterial Pathogens: A Complex Interplay
Authors: Nandi Ipsita , Aroeti Benjamin
Published: July 2023

Diverse extracellular and intracellular cues activate mammalian mitogen-activated protein kinases (MAPKs). Canonically, the activation starts at cell surface receptors and continues via intracellular MAPK components, acting in the host cell nucleus as activators of transcriptional programs to regulate various cellular activities, including proinflammatory responses against bacterial pathogens. For instance, binding host pattern recognition receptors (PRRs) on the surface of intestinal epithelial cells to bacterial pathogen external components trigger the MAPK/NF-κB signaling cascade, eliciting cytokine production. This results in an innate immune response that can eliminate the bacterial pathogen. However, enteric bacterial pathogens evolved sophisticated mechanisms that interfere with such a response by delivering virulent proteins, termed effectors, and toxins into the host cells. These proteins act in numerous ways to inactivate or activate critical components of the MAPK signaling cascades and innate immunity. The consequence of such activities could lead to successful bacterial colonization, dissemination, and pathogenicity. This article will review enteric bacterial pathogens’ strategies to modulate MAPKs and host responses. It will also discuss findings attempting to develop anti-microbial treatments by targeting MAPKs.
Study of the Effect of Baicalin from Scutellaria baicalensis on the Gastrointestinal Tract Normoflora and Helicobacter pylori
Authors: Dmitrieva Anastasia , Kozlova Oksana , Atuchin Victor , Milentieva Irina , Vesnina Anna , Ivanova Svetlana , Asyakina Lyudmila , Prosekov Alexander
Published: July 2023

The antimicrobial properties of baicalin against H. pylori and several probiotic cultures were evaluated. Baicalin was isolated from a dry plant extract obtained by extraction with water at 70 °C. For isolation, extraction was carried out with n-butanol and purification on a chromatographic column. The antimicrobial potential was assessed by evaluating changes in the optical density of the bacterial suspension during cultivation; additionally, the disk diffusion method was used. During the study, the baicalin concentrations (0.25, 0.5, and 1 mg/mL) and the pH of the medium in the range of 1.5–8.0 were tested. The test objects were: suspensions of H. pylori, Lactobacillus casei, L. brevis, Bifidobacterium longum, and B. teenis. It was found that the greater the concentration of the substance in the solution, the greater the delay in the growth of the strain zone. Thus, the highest antimicrobial activity against H. pylori was observed at pH 1.5–2.0 and a baicalin concentration of 1.00 mg/mL. In relation to probiotic strains, a stimulating effect of baicalin (1.00 mg/mL) on the growth of L. casei biomass at pH 1.5–2.0 was observed. The results open up the prospects for the use of baicalin and probiotics for the treatment of diseases caused by H. pylori.
Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Modulates Inflammatory Pain in Mice
Authors: Wu Lin , Wu Yujie , Liu Jin , Jiang Jingyao , Zhou Cheng , Zhang Donghang
Published: July 2023

Elevated excitability of glutamatergic neurons in the lateral parabrachial nucleus (PBL) is associated with the pathogenesis of inflammatory pain, but the underlying molecular mechanisms are not fully understood. Sodium leak channel (NALCN) is widely expressed in the central nervous system and regulates neuronal excitability. In this study, chemogenetic manipulation was used to explore the association between the activity of PBL glutamatergic neurons and pain thresholds. Complete Freund’s adjuvant (CFA) was used to construct an inflammatory pain model in mice. Pain behaviour was tested using von Frey filaments and Hargreaves tests. Local field potential (LFP) was used to record the activity of PBL glutamatergic neurons. Gene knockdown techniques were used to investigate the role of NALCN in inflammatory pain. We further explored the downstream projections of PBL using cis-trans-synaptic tracer virus. The results showed that chemogenetic inhibition of PBL glutamatergic neurons increased pain thresholds in mice, whereas chemogenetic activation produced the opposite results. CFA plantar modelling increased the number of C-Fos protein and NALCN expression in PBL glutamatergic neurons. Knockdown of NALCN in PBL glutamatergic neurons alleviated CFA-induced pain. CFA injection induced C-Fos protein expression in central nucleus amygdala (CeA) neurons, which was suppressed by NALCN knockdown in PBL glutamatergic neurons. Therefore, elevated expression of NALCN in PBL glutamatergic neurons contributes to the development of inflammatory pain via PBL-CeA projections.
Comparison of Intermolecular Halogen...Halogen Distances in Organic and Organometallic Crystals
Authors: Grineva Olga V.
Published: July 2023

Statistical analysis of halogen...halogen intermolecular distances was performed for three sets of homomolecular crystals under normal conditions: C–Hal1...Hal2–C distances in crystals consisting of: (i) organic compounds (set Org); (ii) organometallic compounds (set Orgmet); and (iii) distances M1–Hal1...Hal2–M2 (set MHal) (in all cases Hal1 = Hal2, and in MHal M1 = M2, M is any metal). When analyzing C–Hal...Hal–C distances, a new method for estimating the values of van der Waals radii is proposed, based on the use of two subsets of distances: (i) the shortest distances from each substance less than a threshold; and (ii) all C–Hal...Hal–C distances less than the same threshold. As initial approximations for these thresholds for different Hal, the Ragg values previously introduced in investigations with the participation of the author were used (Ragg values make it possible to perform a statistical assessment of the presence of halogen aggregates in crystals). The following values are recommended in this work to be used as universal values for crystals of organic and organometallic compounds: RF = 1.57, RCl = 1.90, RBr = 1.99, and RI = 2.15 Å. They are in excellent agreement with the results of some other works but significantly (by 0.10–0.17 Å) greater than the commonly used values. For the Orgmet set, slightly lower values for RI (2.11–2.09 Å) were obtained, but number of the C–I...I–C distances available for analysis was significantly smaller than in the other subgroups, which may be the reason for the discrepancy with value for the Org set (2.15 Å). Statistical analysis of the M–Hal...Hal–M distances was performed for the first time. A Hal-aggregation coefficient for M–Hal bonds is proposed, which allows one to estimate the propensity of M–Hal groups with certain M and Hal to participate in Hal-aggregates formed by M–Hal...Hal–M contacts. In particular, it was found that, for the Hg–Hal groups (Hal = Cl, Br, I), there is a high probability that the crystals have Hg–Hal...Hal–Hg distances with length ≤ Ragg.
Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone
Authors: Zară-Dănceanu Camelia Mihaela , Stavilă Cristina , Minuti Anca Emanuela , Lăbușcă Luminiţa , Nastasa Valentin , Herea Dumitru-Daniel , Malancus Răzvan-Nicolae , Ghercă Daniel , Pasca Sorin-Aurelian , Chiriac Horia , Mares Mihai , Lupu Nicoleta
Published: July 2023

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP’s role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.
ROS and Abiotic Stress in Plants 2.0
Authors: Petrov Veselin , Gechev Tsanko
Published: July 2023

Climate insecurity and extreme weather events have stimulated efforts to enhance plant resilience and productivity in adverse environmental conditions [...]
Opportunities and Challenges of In Vitro Tissue Culture Systems in the Era of Crop Genome Editing
Authors: Bekalu Zelalem Eshetu , Panting Michael , Bæksted Holme Inger , Brinch-Pedersen Henrik
Published: July 2023

Currently, the development of genome editing (GE) tools has provided a wide platform for targeted modification of plant genomes. However, the lack of versatile DNA delivery systems for a large variety of crop species has been the main bottleneck for improving crops with beneficial traits. Currently, the generation of plants with heritable mutations induced by GE tools mostly goes through tissue culture. Unfortunately, current tissue culture systems restrict successful results to only a limited number of plant species and genotypes. In order to release the full potential of the GE tools, procedures need to be species and genotype independent. This review provides an in-depth summary and insights into the various in vitro tissue culture systems used for GE in the economically important crops barley, wheat, rice, sorghum, soybean, maize, potatoes, cassava, and millet and uncovers new opportunities and challenges of already-established tissue culture platforms for GE in the crops.
The Role of Aquaporins in Epileptogenesis—A Systematic Review
Authors: Bonosi Lapo , Benigno Umberto Emanuele , Musso Sofia , Giardina Kevin , Gerardi Rosa Maria , Brunasso Lara , Costanzo Roberta , Paolini Federica , Buscemi Felice , Avallone Chiara , Gulino Vincenzo , Iacopino Domenico Gerardo , Maugeri Rosario
Published: July 2023

Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Molecular Mechanism of m6A Methylation Modification Genes METTL3 and FTO in Regulating Heat Stress in Sheep
Authors: Chen Bowen , Yuan Chao , Guo Tingting , Liu Jianbin , Yang Bohui , Lu Zengkui
Published: July 2023

Heat stress is an important environmental factor affecting livestock production worldwide. Primary hepatocytes and preadipocytes derived from Hu sheep were used to establish a heat stress model. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that heat induction significantly increased the expression levels of heat stress protein (HSP) genes and the N6-methyladenosine (m6A) methylation modification genes: methyltransferase-like protein 3 (METTL3), methyltransferase-like protein 14 (METTL14), and fat mass and obesity associated protein (FTO). Heat stress simultaneously promoted cell apoptosis. Transcriptome sequencing identified 3980 upregulated genes and 2420 downregulated genes related to heat stress. A pathway enrichment analysis of these genes revealed significant enrichment in fatty acid biosynthesis, degradation, and the PI3K-Akt and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Overexpression of METTL3 in primary hepatocytes led to significant downregulation of HSP60, HSP70, and HSP110, and significantly increased mRNA m6A methylation; FTO interference generated the opposite results. Primary adipocytes showed similar results. Transcriptome analysis of cells under METTL3 (or FTO) inference and overexpression revealed differentially expressed genes enriched in the mitogen-activated protein kinase (MAPK) signaling pathways, as well as the PI3K-Akt and Ras signaling pathways. We speculate that METTL3 may increase the level of m6A methylation to inhibit fat deposition and/or inhibit the expression of HSP genes to enhance the body’s resistance to heat stress, while the FTO gene generated the opposite molecular mechanism. This study provides a scientific basis and theoretical support for sheep feeding and management practices during heat stress.
Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer
Authors: Anderson Ronald , Rapoport Bernardo L. , Steel Helen C. , Theron Annette J.
Published: July 2023

Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling evidence in this context has been derived from the notable association of elevated circulating platelet counts with the onset and prognosis of various human malignancies, particularly lung cancer, which represents the primary focus of the current review. Key topics include an overview of the association of lung cancer with the circulating platelet count, as well as the mechanisms of platelet-mediated, pro-tumorigenic immunosuppression, particularly the role of transforming growth factor beta 1. These issues are followed by a discussion regarding the pro-tumorigenic role of platelet-derived microparticles (PMPs), the most abundant type of microparticles (MPs) in human blood. In this context, the presence of increased levels of PMPs in the blood of lung cancer patients has been associated with tumor growth, invasion, angiogenesis and metastasis, which correlate with disease progression and decreased survival times. The final section of the review addresses, firstly, the role of cancer-related platelet activation and thrombosis in the pathogenesis of secondary cardiovascular disorders and the associated mortality, particularly in lung cancer, which is second only to disease progression; secondly, the review addresses the potential role of antiplatelet agents in the adjunctive therapy of cancer.
JAK3 Y841 Autophosphorylation Is Critical for STAT5B Activation, Kinase Domain Stability and Dimer Formation
Authors: Rodriguez Georgialina , Martinez George Steven , Negrete Omar Daniel , Sun Shengjie , Guo Wenhan , Xie Yixin , Li Lin , Xiao Chuan , Ross Jeremy Aaron , Kirken Robert Arthur
Published: July 2023

Janus tyrosine kinase 3 (JAK3) is primarily expressed in immune cells and is needed for signaling by the common gamma chain (γc) family of cytokines. Abnormal JAK3 signal transduction can manifest as hematological disorders, e.g., leukemia, severe combined immunodeficiency (SCID) and autoimmune disease states. While regulatory JAK3 phosphosites have been well studied, here a functional proteomics approach coupling a JAK3 autokinase assay to mass spectrometry revealed ten previously unreported autophosphorylation sites (Y105, Y190, Y238, Y399, Y633, Y637, Y738, Y762, Y824, and Y841). Of interest, Y841 was determined to be evolutionarily conserved across multiple species and JAK family members, suggesting a broader role for this residue. Phospho-substitution mutants confirmed that Y841 is also required for STAT5 tyrosine phosphorylation. The homologous JAK1 residue Y894 elicited a similar response to mutagenesis, indicating the shared importance for this site in JAK family members. Phospho-specific Y841-JAK3 antibodies recognized activated kinase from various T-cell lines and transforming JAK3 mutants. Computational biophysics analysis linked Y841 phosphorylation to enhanced JAK3 JH1 domain stability across pH environments, as well as to facilitated complementary electrostatic JH1 dimer formation. Interestingly, Y841 is not limited to tyrosine kinases, suggesting it represents a conserved ubiquitous enzymatic function that may hold therapeutic potential across multiple kinase families.
Development of Cryopreservation Technique for Meristems of Syringa vulgaris L. Cultivars
Authors: Koroleva Olga Vasilevna , Molkanova Olga Ivanovna , Vysotskaya Olga Nikolaevna
Published: July 2023

Cryopreservation is considered to be one of the most effective methods for long-term storage of plant genetic resources, particularly for ornamental species. However, there is a very little research on cryopreservation of lilacs. In this study, for the first time the cryopreservation protocol (a variation of a pregrowth-dehydration method) was successfully applied to two cultivars of Syringa vulgaris: ‘Aucubaefolia’ and ‘Polina Osipenko’. Explants of both cultivars were able to withstand the different steps of the protocol, and high survival and regrowth percentages were obtained after exposure to liquid nitrogen (67–100% and 63–88%, respectively). The current study is mainly focused on the preculture conditions of the applied method. Based on our results, we propose the use of paclobutrazol (PBZ) with the combination of 6-benzylaminopurine (BAP) and thidiazuron (TDZ) in the preculture medium for increasing explant tolerance to subsequent dehydration and freezing. During post-LN recovery, the explants appeared morphologically normal, and after 12–16 weeks after thawing, they were propagated and cultured as normal plantlets. Therefore, the reported method is effective for long-term storage of lilac meristems and could be used to create a cryobank of achievements in lilac breeding.
Investigating the Impact of Irrigation Water Quality on Secondary Metabolites and Chemical Profile of Mentha piperita Essential Oil: Analytical Profiling, Characterization, and Potential Pharmacological Applications
Authors: Haddou Mounir , Taibi Mohamed , Elbouzidi Amine , Loukili El Hassania , Yahyaoui Meryem Idrissi , Ou-Yahia Douaae , Mehane Lamyae , Addi Mohamed , Asehraou Abdeslam , Chaabane Khalid , Bellaouchi Reda , El Guerrouj Bouchra
Published: July 2023

This study examines the impact of irrigation water quality on the synthesis of secondary metabolites and the chemical composition of Mentha piperita essential oil (MPEO). Three essential oils from Mentha piperita plants, irrigated with different water sources commonly used for mint irrigation in Morocco’s Oriental region, were analyzed. The water sources were characterized based on various parameters, such as nitrites, nitrates, orthophosphates, chemical oxygen demand (COD), biological oxygen demand (BOD5), pH, and electrical conductivity. The essential oils were extracted using hydrodistillation, and their chemical composition was determined using gas chromatography coupled with mass spectrometry (GC/MS), revealing notable variations among the compositions of the three essential oils. In this study, in silico tests using the Prediction of Activity Spectra for Substances (PASS) algorithm; the absorption, distribution, metabolism, and excretion (ADME) model; and Pro-Tox II were conducted to evaluate the drug-likeness, pharmacokinetic properties, expected safety profile upon ingestion, and potential pharmacological activity of the identified compounds in MPEO. The antioxidant activity of the MPEOs was assessed through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and the total antioxidant activity (TAC) method. Additionally, the antimicrobial effectiveness of the essential oils was tested against four bacterial strains (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Pseudomonas aeruginosa) and four fungal strains (Candida glabrata, Rhodotorula glutinis, Penicillium digitatum, Aspergillus niger), demonstrating moderate to strong activities against the tested strains. This study concludes that regulating irrigation water quality can enhance the production of specific metabolites, making them potentially valuable as antioxidants and antimicrobial agents.
Gender and Age Differences in Outcomes after Mild Traumatic Brain Injury
Authors: Wågberg Sophia , Stålnacke Britt-Marie , Magnusson Beatrice M.
Published: July 2023

Many people who suffer traumatic brain injury (TBI) have long-term residual symptoms. This study evaluates post-TBI symptoms and disabilities seven to eight years after mild TBI (mTBI), with specific aims to evaluate gender and age differences, and whether repeated TBI leads to the deterioration of symptoms and function. Telephone interviews with 595 patients were conducted using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) to assess post-TBI symptoms, and the Glasgow Outcome Scale Extended (GOSE) was used to assess disability. Thirty-four percent reported post-concussion symptoms (40% of females and 29% of males). The symptom burden was higher in women than in men, and higher in patients with repeated TBI. The distribution of symptoms was similar for women and men. Women reported a significantly higher level of disability on GOSE; 31% had not returned fully to daily life, compared with 17% of men (p < 0.001), the biggest difference being in the age group of 25–49 years. Patients with repeated mTBI reported significantly lower scores on GOSE; 31% had not returned fully to daily life, compared with 21% of the single-TBI patients (p < 0.05). After mild TBI, one of three patients reported at least one post-TBI symptom. Women and individuals with repeated TBI presented a worse GOSE outcome. These findings have implications for clinical practice and research and should be taken into consideration when planning the rehabilitation and follow-up of mTBI patients. This also emphasises the importance of informing patients about post-concussion symptoms and when to seek healthcare.
Near-Infrared Spectroscopy-Guided, Individualized Arterial Blood Pressure Management for Carotid Endarterectomy under General Anesthesia: A Randomized, Controlled Trial
Authors: Tomić Mahečić Tina , Malojčić Branko , Tonković Dinko , Mažar Mirabel , Baronica Robert , Juren Meaški Snježana , Crkvenac Gregorek Andrea , Meier Jens , Dünser Martin W.
Published: July 2023

Background: Differences in blood pressure can influence the risk of brain ischemia, perioperative complications, and postoperative neurocognitive function in patients undergoing carotid endarterectomy (CEA). Methods: In this single-center trial, patients scheduled for CEA under general anesthesia were randomized into an intervention group receiving near-infrared spectroscopy (NIRS)-guided blood pressure management during carotid cross-clamping and a control group receiving standard care. The primary endpoint was postoperative neurocognitive function assessed before surgery, on postoperative days 1 and 7, and eight weeks after surgery. Perioperative complications and cerebral autoregulatory capacity were secondary endpoints. Results: Systolic blood pressure (p < 0.001) and norepinephrine doses (89 (54–122) vs. 147 (116–242) µg; p < 0.001) during carotid cross-clamping were lower in the intervention group. No group differences in postoperative neurocognitive function were observed. The rate of perioperative complications was lower in the intervention group than in the control group (3.3 vs. 26.7%, p = 0.03). The breath-holding index did not differ between groups. Conclusions: Postoperative neurocognitive function was comparable between CEA patients undergoing general anesthesia in whom arterial blood pressure during carotid cross-clamping was guided using NIRS and subjects receiving standard care. NIRS-guided, individualized arterial blood pressure management resulted in less vasopressor exposition and a lower rate of perioperative complications.
Global Health Resource Utilization and Cost-Effectiveness of Therapeutics and Diagnostics in Immune Thrombotic Thrombocytopenic Purpura (TTP)
Authors: Butt Ayesha , Allen Cecily , Purcell Adriana , Ito Satoko , Goshua George
Published: July 2023

In this review, we examine the current landscape of health resource utilization and cost-effectiveness data in the care of patient populations with immune thrombotic thrombocytopenic purpura. We focus on the therapeutic (therapeutic plasma exchange, glucocorticoids, rituximab, caplacizumab) and diagnostic (ADAMTS13 assay) health technologies employed in the care of patients with this rare disease. Health resource utilization and cost-effectiveness data are limited to the high-income country context. Measurement of TTP-specific utility weights in the high-income country context and collection of health resource utilization data in the low- and middle-income country settings would enable an evaluation of country-specific quality-adjusted life expectancy and cost-effectiveness of these therapeutic and diagnostic health technologies. This quantification of value is one way to mitigate cost concerns where they exist.
Microcirculation in Hypertension: A Therapeutic Target to Prevent Cardiovascular Disease?
Authors: Rizzoni Damiano , Agabiti-Rosei Claudia , Boari Gianluca E. M. , Muiesan Maria Lorenza , De Ciuceis Carolina
Published: July 2023

Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases, as well as microvascular eye diseases. Established hypertension leads to the chronic vasoconstriction of small arteries as well as to a decreased lumen diameter and the thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was firstly demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alterations in small resistance arteries; however, microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair the organ flow reserve, playing a crucial role in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage and related cardiovascular events, thus possessing a relevant prognostic relevance. New non-invasive techniques, such as scanning laser Doppler flowmetry or adaptive optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in terms of cardio- and cerebrovascular events. A rarefaction of the capillary network has also been reported in hypertension, which may contribute to flow reduction in and impairment of oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might contribute to microvascular angina, stroke, and renal dysfunction. In addition, they can be markers useful in monitoring the beneficial effects of antihypertensive treatment. Additionally, conductance arteries may be affected by a remodeling process in hypertension, and an interrelationship is present in the structural changes in small and large conductance arteries. The review addresses the possible relations between structural microvascular alterations and hypertension-mediated organ damage, and their potential improvement with antihypertensive treatment.
Impact of a VA–ECMO in Combination with an Extracorporeal Cytokine Hemadsorption System in Critically Ill Patients with Cardiogenic Shock–Design and Rationale of the ECMOsorb Trial
Authors: Haertel Franz , Lehmann Thomas , Heller Tabitha , Fritzenwanger Michael , Pfeifer Ruediger , Kretzschmar Daniel , Otto Sylvia , Bogoviku Jurgen , Westphal Julian , Bruening Christiane , Gecks Thomas , Kaluza Mirko , Moebius-Winkler Sven , Schulze P. Christian
Published: July 2023

Background: Cardiogenic shock and arrest present as critical, life-threatening emergencies characterized by severely compromised tissue perfusion and inadequate oxygen supply. Veno–arterial extracorporeal membrane oxygenation (VA–ECMO) serves as a mechanical support system for patients suffering shock refractory to conventional resuscitation. Despite the utilization of VA–ECMO, clinical deterioration due to systemic inflammatory response syndrome (SIRS) resulting from the underlying shock and exposure of blood cells to the artificial surfaces of the ECMO circuit may occur. To address this issue, cytokine adsorbers offer a valuable solution by eliminating blood proteins, thereby controlling SIRS and potentially improving hemodynamics. Consequently, a prospective, randomized, blinded clinical trial will be carried out with ECMOsorb. Methods and Study Design: ECMOsorb is a single-center, controlled, randomized, triple-blinded trial that will compare the hemodynamic effects of treatment with a VA–ECMO in combination with a cytokine adsorber (CytoSorb®, intervention) to treatment with VA–ECMO only (control) in patients with cardiogenic shock (with or without prior cardiopulmonary resuscitation (CPR)) requiring extracorporeal, hemodynamic support. Fifty-four patients will be randomized in a 1:1 fashion to the intervention or control group over a 36-month period. The primary endpoint of ECMOsorb is the improvement of the Inotropic Score (IS) 72 h after the intervention. Prognostic indicators, including mortality rates, hemodynamic parameters, laboratory findings, echocardiographic assessments, quality of life measurements, and clinical parameters, will serve as secondary outcome measures. The safety evaluation encompasses endpoints such as air embolisms, allergic reactions, peripheral ischemic complications, vascular complications, bleeding incidents, and stroke occurrences. Conclusions: The ECMOsorb trial seeks to assess the efficacy of a cytokine adsorber (CytoSorb®; CytoSorbents Europe GmbH, Berlin, Germany) in reducing SIRS and improving hemodynamics in patients with cardiogenic shock who are receiving VA–ECMO. We hypothesize that a reduction in cytokine levels can lead to faster weaning from inotropic and mechanical circulatory support, and ultimately to improved recovery.
On the Virtues of “Team Medicine”—A City of Hope Perspective
Authors: Kulkarni Prakash , Salgia Ravi
Published: July 2023

Our first Special Issue of the Journal of Clinical Medicine, entitled ‘Integrating Clinical and Translational Research Networks—Building Team Medicine,’ highlighted the collective experience of the City of Hope and was a tremendous success [...]
Quality of Life after Brain Injury in Children and Adolescents (QOLIBRI-KID/ADO)—The First Disease-Specific Self-Report Questionnaire after Traumatic Brain Injury
Authors: Von Steinbuechel Nicole , Zeldovich Marina , Greving Sven , Olabarrieta-Landa Laiene , Krenz Ugne , Timmermann Dagmar , Koerte Inga K. , Bonfert Michaela Veronika , Berweck Steffen , Kieslich Matthias , Brockmann Knut , Roediger Maike , Lendt Michael , Staebler Michael , Schmidt Silke , Muehlan Holger , Cunitz Katrin
Published: July 2023

The subjective impact of the consequences of pediatric traumatic brain injury (pTBI) on different life dimensions should be assessed multidimensionally and as sensitively as possible using a disease-specific health-related quality of life (HRQoL) instrument. The development and psychometrics of the first such self-report questionnaire for children and adolescents after TBI are reported here. Focus group interviews with children, adolescents, and their parents, cognitive debriefing, item pool generation and reduction using Delphi expert panels were performed. The resulting version was psychometrically tested on 300 individuals aged 8–17 years. After item reduction based on factor analyses, differential item functioning, reliability, and validity were investigated. The final 35 items were associated with six scales (Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, Physical Problems). Internal consistency and construct validity were satisfactory. Health-related Quality of life (HRQoL) was significantly lower in older and in female participants, as well as those with cognitive disabilities, anxiety, depression and post-concussion symptoms, than in comparative groups. The new QOLIBRI-KID/ADO is a comprehensive, multidimensional, reliable, and valid instrument, comparable in content and items to the QOLIBRI adult version. Therefore, disease-specific HRQoL can now be measured across the lifespan and may support the amelioration of treatment, care, rehabilitation, and daily life of children and adolescents after TBI.
Prospective of Pancreatic Cancer Diagnosis Using Cardiac Sensing
Authors: Singh Mansunderbir , Anvekar Priyanka , Baraskar Bhavana , Pallipamu Namratha , Gadam Srikanth , Cherukuri Akhila Sai Sree , Damani Devanshi N. , Kulkarni Kanchan , Arunachalam Shivaram P.
Published: July 2023

Pancreatic carcinoma (Ca Pancreas) is the third leading cause of cancer-related deaths in the world. The malignancies of the pancreas can be diagnosed with the help of various imaging modalities. An endoscopic ultrasound with a tissue biopsy is so far considered to be the gold standard in terms of the detection of Ca Pancreas, especially for lesions <2 mm. However, other methods, like computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), are also conventionally used. Moreover, newer techniques, like proteomics, radiomics, metabolomics, and artificial intelligence (AI), are slowly being introduced for diagnosing pancreatic cancer. Regardless, it is still a challenge to diagnose pancreatic carcinoma non-invasively at an early stage due to its delayed presentation. Similarly, this also makes it difficult to demonstrate an association between Ca Pancreas and other vital organs of the body, such as the heart. A number of studies have proven a correlation between the heart and pancreatic cancer. The tumor of the pancreas affects the heart at the physiological, as well as the molecular, level. An overexpression of the SMAD4 gene; a disruption in biomolecules, such as IGF, MAPK, and ApoE; and increased CA19-9 markers are a few of the many factors that are noted to affect cardiovascular systems with pancreatic malignancies. A comprehensive review of this correlation will aid researchers in conducting studies to help establish a definite relation between the two organs and discover ways to use it for the early detection of Ca Pancreas.