Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, can prevent pathological mitochondrial fission by inhibiting protein–protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca²⁺ channel-blocking action of cilnidipine, prevent the palmitic acid-induced Drp1–filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high-fat diet-fed mouse livers. These results propose that targeting the Drp1–filamin interaction become a new strategy for the prevention or treatment of fatty liver disease. Full article

We discuss the concept and realization of a heat bath in solid state quantum systems. We demonstrate that, unlike a true resistor, a finite one-dimensional Josephson junction array or analogously a transmission line with non-vanishing frequency spacing, commonly considered as a reservoir of a quantum circuit, does not strictly qualify as a Caldeira–Leggett type dissipative environment. We then consider a set of quantum two-level systems as a bath, which can be realized as a collection of qubits. We show that only a dense and wide distribution of energies of the two-level systems can secure long Poincare recurrence times characteristic of a proper heat bath. An alternative for this bath is a collection of harmonic oscillators, for instance, in the form of superconducting resonators. Full article

The purpose of this study was to develop and validate the Perception of Wisdom Exploratory Rating Scale based on the Polyhedron Model of Wisdom (PMW). A total number of 585 responses from in-service and preservice teachers was collected. In the EFA, the items fit a seven-factor structure, producing the following subscales: knowledge management, self-regulation, moral maturity, openness, tolerance, sound judgment, and creative thinking. CFA was performed to test the construct validity of the scale. The model produced a good fit to the data (χ²/df = 1.67, CFI = 0.92, TLI = 0.91, RMSEA = 0.049, and SRMR = 0.06). With continued testing and revisions, this instrument could be useful for the cross-cultural comparison of perceptions of wisdom and identification of barriers to promoting wisdom instruction. Full article

This paper seeks to deepen the understanding of religious plurality using a range of conceptual lenses and then to draw out some implications for a dialogical approach to religious education in Catholic schools. While what was, until very recent times, seen as conventional religious affiliation has certainly weakened in Australia and elsewhere, this does not necessarily lead to a multiplication of communal beliefs, practices and values. Following Smith, Inglehart and others, what has emerged is a dominant cultural hegemony which has a range of characteristics, but the most pertinent for the discussion here is the loss of the transcendent imperative and the subsequent decline in the knowledge of, and identification with, narratives associated with once-dominant religious communities. An understanding of diversity in the current cultural milieu in Australia needs to consider this hegemony as expressed in a commonality of beliefs, values and practices regardless of expressed affiliation, religious or not. Understanding diversity in this framework establishes a basis for better considering what a dialogical approach to religious education would involve. A dialogical approach to religious education is taken as a settled norm and not one that is heavily contested. A number of the implications of the proposed understanding of diversity for religious education are given. These include following a Vygotskian scaffolded approach to pedagogy and seeing an important place for the articulation of the home religious tradition. Full article

The purpose of this first article is to provide a physical basis for atmospheric Rossby waves at the tropopause to clarify their properties and improve our knowledge of their role in the genesis of extreme precipitation and heat waves. By analogy with the oceanic Rossby waves, the role played by the pycnocline in ocean Rossby waves is replaced here by the interface between the polar jet and the ascending air column at the meeting of the polar and Ferrel cell circulation or between the subtropical jet and the descending air column at the meeting of the Ferrel and Hadley cell circulation. In both cases, the Rossby waves are suitable for being resonantly forced in harmonic modes by tuning their natural period to the forcing period. Here, the forcing period is one year as a result of the variation in insolation due to solar declination. A search for cause-and-effect relationships is performed from the joint representation of the amplitude and phase of (1) the velocity of the cold or warm modulated airflows at 250 mb resulting from Rossby waves, (2) the geopotential height at 500 mb, and (3) the precipitation rate or ground air temperature. This is for the dominant harmonic mode whose period can be 1/16, 1/32, or 1/64 year, which reflects the intra-seasonal variations in the rising and falling air columns at the meeting of the polar, Ferrel, and Hadley cell circulation. Harmonics determine the duration of blocking. Two case studies referring to extreme cold and heat waves are presented. Dual cyclone–anticyclone systems seem to favor extreme events. They are formed by two joint vortices of opposite signs reversing over a period, concomitantly with the involved modulated airflows at the tropopause. A second article will be oriented toward (1) the examination of different case studies in order to ascertain the common characteristics of Rossby wave patterns leading to extreme events and (2) a map of the globe revealing future trends in the occurrence of extreme events. Full article

Reception studies in audiovisual translation seek to explore how translation choices affect the audience’s comprehension, emotional engagement, enjoyment, and overall viewing experience of audiovisual materials. This study focuses on the subtitling product and analyzes the acceptability of swear words translated through different stimuli: subtitles with softened, maintained, and intensified swearing, along with standard Netflix subtitles (control). Employing a multi-method approach, the study collected data through a survey, using questionnaires with a Likert scale and interviews, following the user-centered translation model to understand how participants receive and perceive swear words in subtitling. The results indicate that the control group had the highest acceptability of the participants, while the group with softened swear words presented the lowest acceptability rate. The analysis shows that participants across all groups reported that discomfort does not arise from reading the swear word in the subtitle but from perceiving a deliberate change in its offensive load—usually softened. The findings demonstrate that this change can lead to a breach of the contract of illusion in subtitling, as participants are exposed to the original dialogue and the translated subtitle simultaneously. In conclusion, when perceived, the change in the offensive load can redirect the viewer’s focus from the video to the subtitles, negatively affecting the enjoyment of the audiovisual experience. Full article

4-(tris(4-methyl-1H-pyrazol-1-yl)methyl)aniline was prepared in a 63% yield utilizing a C–F activation strategy from a mixture of 4-(trifluoromethyl)aniline, 4-methylpyrazole, and KOH in dimethylsulfoxide (DMSO). The identity of the product was confirmed by nuclear magnetic resonance spectroscopy, infrared spectroscopy, mass spectrometry, and single-crystal analysis. An analysis of crystals grown from the layering method (CH₂Cl₂/acetone/pentane) indicated two distinct polymorphs of the title compound. Moreover, density functional theory calculations utilizing the MN15L density functional and the def2-TZVP basis set indicated that 4-(tris(4-methyl-1H-pyrazol-1-yl)methyl)aniline forms with similar energetics to the previously reported unmethylated analog. Full article

This paper presents empirical evidence to support the so-called syntactization of discourse, that is, the projection of relevant pragmatic features in the narrow syntax. In particular, it analyses deictic inversion in English, a construction which is used by the speaker to point at a proximal or distal location and bring the addressee’s attention to an entity related to that location (e.g., Here comes the bus). It offers a novel account of this construction, which takes it to be an evidential strategy in a language that does not have standard evidential markers; this evidential status explains its main differences with locative inversion, a construction with which it is pragmatically and structurally related. Deictic inversion therefore receives a natural explanation in a framework that maps syntax with the speech act and introduces in the derivation pragmatic information about the participants in the communicative exchange and about the source of the information for the proposition asserted. Full article

Background: new-onset atrial fibrillation remains a common complication in critical care settings, often necessitating treatment when the correction of triggers is insufficient to restore hemodynamics. The treatment strategy includes electric cardioversion in cases of hemodynamic instability and either rhythm control or rate control in the absence of instability. Landiolol, an ultrashort beta-blocker, effectively controls heart rate with the potential to regulate rhythm. Objectives This review aims to compare the efficacy of landiolol in controlling heart rate and converting to sinus rhythm in the critical care setting. Methods: We conducted a comprehensive review of the published literature from 2000 to 2022 describing the use of landiolol to treat atrial fibrillation in critical care settings, excluding both cardiac surgery and medical cardiac care settings. The primary outcome assessed was sinus conversion following landiolol treatment. Results: Our analysis identified 17 publications detailing the use of landiolol for the treatment of 324 critical care patients. While the quality of the data was generally low, primarily comprising non-comparative studies, landiolol consistently demonstrated similar efficacy in controlling heart rate and facilitating conversion to sinus rhythm in both non-surgical (75.7%) and surgical (70.1%) settings. The incidence of hypotension associated with landiolol use was 13%. Conclusions: The use of landiolol in critical care patients with new-onset atrial fibrillation exhibited comparable efficacy and tolerance in both non-surgical and surgical settings. Despite these promising results, further validation through randomized controlled trials is necessary. Full article

Background: Accurate malaria diagnosis constitutes a challenging task, necessitating the need for the implementation of targeted and effective diagnostic tools. The purpose of the current study was to evaluate the effectiveness of two different molecular methodologies in terms of sensitivity for the detection of External Quality Assessment (EQA) Plasmodium samples. Methods: A total of 104 lyophilized blood samples from 14 different UK-NEQAS (National External Quality Assessment Site) (2016–2021) and eight WHO-NEQAS distributions (2017–2020) were analyzed. An in-house multiplex PCR protocol, followed by single target real-time PCR protocols for all five Plasmodium species, was implemented. Results: The multiplex PCR had a success rate of 10/16 and 20/28 for P. vivax and P. falciparum species, respectively. On the other hand, the respective results for real-time PCR had a success rate of 13/16 (P. vivax), 28/28 (P. falciparum), 5/8 (P. malariae), 8/10 (P. ovale), and 10/14 (P. knowlesi). Plasmodium falciparum samples displayed the highest sensitivity of detection, 0.02 parasites/μL. Plasmodium vivax samples displayed a 0.1 parasites/μL cutoff value, greater than the respective value for whole blood samples, while P. ovale species displayed a respective cutoff value of 0.05 parasites/μL. Due to the limited number of tested samples, data obtained for P. malariae and P. knowlesi species samples were inconclusive. Conclusions: Real-time PCR comprises a credible molecular methodology in terms of sensitivity assessment and detection of low parasitemia levels of Plasmodium sp. in EQA lyophilized blood samples. Full article

Marshes are an important ecosystem, acting as a biodiversity hotspot, a carbon sink and a bioremediation site, breaking down anthropogenic waste such as antibiotics, metals and fertilizers. Due to their participation in these metabolic activities and their capability to contribute to primary productivity, the microorganisms in such habitats have become of interest to investigate. Since Proteobacteria were previously found to be abundant and the waters are well aerated and organic-rich, this study on the presence of anoxygenic phototrophic bacteria, purple non-sulfur bacteria and aerobic anoxygenic phototrophs in marshes was initiated. One sample was collected at each of the seven Manitoban sites, and anoxygenic phototrophs were cultivated and enumerated. A group of 14 strains, which represented the phylogenetic diversity of the isolates, was physiologically investigated further. Aerobic anoxygenic phototrophs and purple non-sulfur bacteria were present at each location, and they belonged to the α- and β-Proteobacteria subphyla. Some were closely related to known heavy metal reducers (Brevundimonas) and xenobiotic decomposers (Novosphingobium and Sphingomonas). All were able to synthesize the photosynthetic complexes aerobically. This research highlights the diversity of and the potential contributions that anoxygenic phototrophs make to the essential functions taking place in wetlands. Full article

Objectives—Metallic elements and fibrin clot properties have been linked to stroke. We examined metallic and nonmetallic elements, fibrin clot lysis time (CLT), and maximum absorbance (Abs_max) in relation to ischemic stroke. Design—A case–control study of ischemic stroke patients vs. healthy individuals. Subjects and Methods—Plasma and serum were collected from 260 ischemic stroke patients (45.0% women; age, 68 ± 12 years) and 291 healthy controls (59.7% women; age, 50 ± 17 years). Fibrin CLT and Abs_max were measured using a validated turbidimetric assay. Serum elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). Data were analyzed by bivariate correlations and multiple or logistic regression. Results—In female stroke patients, copper, lithium, and aluminum were significantly lower compared with controls; in male stroke patients, potassium was lower, and beryllium was elevated. In female and male stroke patients, iron, zinc, nickel, calcium, magnesium, sodium, and silicon were significantly lower, while strontium was elevated. Positive correlations between fibrin clot properties and metals, observed in healthy controls, were lost in ischemic stroke patients. In multivariate regression analysis, fibrin CLT and/or Abs_max was associated with zinc, calcium, potassium, beryllium, and silicon in stroke patients and with sodium, potassium, beryllium, and aluminum in controls. In logistic regression analysis, stroke was independently associated with lithium, nickel, beryllium, strontium, boron, and silicon and with sodium, potassium, calcium, and aluminum but not with fibrin CLT/Abs_max. Conclusions—Various elements were associated with fibrin clot properties and the risk of ischemic stroke. Lithium, sodium, calcium, and aluminum abrogated the association of fibrin clot properties with ischemic stroke. Full article

Immune cell migration is required for the development of an effective and robust immune response. This elegant process is regulated by both cellular and environmental factors, with variables such as immune cell state, anatomical location, and disease state that govern differences in migration patterns. In all cases, a major factor is the expression of cell surface receptors and their cognate ligands. Rapid adaptation to environmental conditions partly depends on intrinsic cellular immune factors that affect a cell’s ability to adjust to new environment. In this review, we discuss both myeloid and lymphoid cells and outline key determinants that govern immune cell migration, including molecules required for immune cell adhesion, modes of migration, chemotaxis, and specific chemokine signaling. Furthermore, we summarize tumor-specific elements that contribute to immune cell trafficking to cancer, while also exploring microenvironment factors that can alter these cellular dynamics within the tumor in both a pro and antitumor fashion. Specifically, we highlight the importance of the secretome in these later aspects. This review considers a myriad of factors that impact immune cell trajectory in cancer. We aim to highlight the immunotherapeutic targets that can be harnessed to achieve controlled immune trafficking to and within tumors. Full article

The purpose of this mixed-method study was to (1) examine the effect of an adapted physical activity program, Fitness Access McGill (FAM), on leisure-time physical activity (LTPA), autonomous and controlled motivation, and the basic psychological needs of self-determination theory among university students/staff with a physical disability and/or chronic conditions, and (2) explore participants’ experiences after completing FAM. Nineteen participants completed validated questionnaires for all study outcomes pre- and post-FAM. Nine participants partook in a 30–60 min semi-structured interview conducted within three months of completing FAM. Quantitative data were analyzed using repeated measures effect size calculations. Qualitative data were analyzed using directed content analysis. Participants reported an increase in total LTPA (dRMpooled = 0.58), with the greatest positive change on strenuous intensity (dRMpooled = 0.81). Large effects were found for changes in autonomous motivation (dRMpooled = 0.52), autonomy (dRMpooled = 0.79), competence (dRMpooled = 0.79), and relatedness (dRMpooled = 0.89). Participants reported FAM being supportive towards their psychological needs, the development of a LTPA routine, and enhanced overall well-being. Future research can be built upon this study to develop a robust understanding as to how need-supportive, adapted LTPA programs could be implemented within community settings or out-patient rehabilitation to support exercise engagement, physical health and overall well-being among adults with disabilities. Full article

To clarify the hydrodynamic interference characteristics of flows around multiple cylinders under the wall effect, the two-dimensional (2D) flows around the near-wall single, two tandem and parallel cylinders are simulated under different gap ratios (0.15 ≤ G/D ≤ 3.0) and spacing ratios (1.5 ≤ T/D ≤ 4.0) at a Reynolds number of Re = 6300. We also examine the wake patterns, the force coefficients, and the vortex-shedding frequency with emphases on the wall effect and effects of the two-cylinder interference. A critical wall gap of G/D = 0.6 is identified in the single-cylinder case where the wall can exert significant influences. The two near-wall tandem cylinders exhibit three wake states: stretching mode, attachment mode, and impinging mode. The force coefficients on the upstream cylinder are significantly affected by the wall for G/D ≤ 0.6. The downstream cylinder is mainly influenced by the upstream cylinder. For G/D > 0.6, the force coefficients on the two cylinders exhibit a similar variation trend. In the parallel arrangement, the two cylinders exhibit four wake states in different G/D and T/D ranges: double stretching mode, hetero-vortex scale mode, unilateral vortex mode, and free vortex mode. Moreover, the two parallel cylinders in the hetero-vortex scale or free vortex mode have two states: synchronous in-phase state and synchronous out-of-phase state. The mean drag coefficients on the two cylinders decrease, while the mean lift coefficients exhibit opposite variation trends, as the T/D grows. Full article

Background: This study aimed to systematically review case reports documenting rare adverse events in patients with small cell lung cancer (SCLC) following the administration of immune checkpoint inhibitors (ICIs). Methods: A systematic literature review was conducted to identify case reports detailing previously unreported adverse drug reactions to ICIs in patients with SCLC. The scope of the literature reviewed was restricted to case studies on SCLC published up to 31 December 2023. Results: We analyzed twenty-four studies on ICI use for patients with SCLC. There were six reports on atezolizumab, four on durvalumab, and three on adverse events from monotherapy with nivolumab. Reports involving combination treatments were the most frequent, with a total of six, predominantly involving using nivolumab in combination with ipilimumab. Additionally, there was one report each on using pembrolizumab, nofazinilimab, sintilimab, tislelizumab, and toripalimab. We collected detailed information on the clinical course, including patient and disease characteristics, symptoms, treatment for each adverse event, and recovery status. Among the patients included in the case reports, 21 out of 24 (87.5%) had extensive-stage SCLC when initiating ICI therapy, with only 1 patient diagnosed with limited-stage SCLC. Respiratory system adverse events were most common, with seven cases, followed by neurological, endocrinological, and gastroenterological events. Three case reports documented adverse events across multiple systems in a single patient. In most cases, patients showed symptom improvement; however, four studies reported cases where patients either expired without symptom improvement or experienced sequelae. Conclusions: Efforts to develop reliable biomarkers for predicting irAEs continue, with ongoing research to enhance predictive precision. Immunotherapy presents diverse and unpredictable adverse events, underscoring the need for advanced diagnostic tools and a multidisciplinary approach to improve patient management. Full article

Background: Chronic obstructive pulmonary disease (COPD) has significant systemic manifestations, including cardiovascular morbidity. The main aim of our study was to evaluate the effect of short-term COPD treatment with tiotropium/olodaterol (TIO/OLO) 5/5 μg on cardiac function and autonomic integrity. Methods: Twenty-nine patients with newly diagnosed moderate-to-severe COPD were enrolled. We performed pulmonary function tests, cardiac magnetic resonance, cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging and analysis of blood biomarkers on our study subjects. The correlations between the tests’ results were evaluated at baseline. The changes in pulmonary and cardiac parameters from baseline through 12 weeks were assessed. Results: Significant associations between pulmonary function tests’ results and high-sensitivity C-reactive protein (hs-CRP), as well as interleukin-22 (IL-22), were observed at baseline. Treatment with TIO/OLO significantly improved lung function as measured by spirometry and body plethysmography. Moreover, we found that the cardiac index increased from 2.89 (interquartile range (IQR) 1.09) to 3.21 L/min/m² (IQR 0.78) (p = 0.013; N = 18) and the late heart-to-mediastinum ratio improved from 1.88 (IQR 0.37) to 2 (IQR 0.41) (p = 0.026; N = 16) after 12 weeks of treatment. Conclusions: Treatment with TIO/OLO improves lung function and positively impacts cardiac function and autonomic integrity, suggesting that dual bronchodilation might have a potential in decreasing the risk for cardiac events in COPD. Hs-CRP and IL-22 might be beneficial in determining the intensity of systemic inflammation in COPD. Further research with a larger cohort is needed to enhance the initial results of this study. Full article

In this paper, we discussed a new subclass ${\mathcal{J}\mathcal{Q}}_{⅁,A}^B\left(q\right)$ of bi-univalent functions in the unit disk $\mathbb{U}$ using q-generalized Janowski function and q-derivative. Additionally, certain properties were examined and effectively demonstrated, such as the second Hankel determinant, Fekete–Szegö estimates, and Coefficients Bounds. Each of these bounds were precise and were confirmed by finding the extremal function for the new class. Furthermore, there are in-depth conversations available regarding certain intriguing specific cases of the outcomes achieved. Full article

Reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR) is a commonly used tool for gene expression analysis. The selection of stably expressed reference genes is required for accurate normalization. The aim of this study was to identify the optimal reference genes for RT-qPCR normalization in various brain regions of rats at different stages of the lithium–pilocarpine model of acquired epilepsy. We tested the expression stability of nine housekeeping genes commonly used as reference genes in brain research: Actb, Gapdh, B2m, Rpl13a, Sdha, Ppia, Hprt1, Pgk1, and Ywhaz. Based on four standard algorithms (geNorm, NormFinder, BestKeeper, and comparative delta-Ct), we found that after pilocarpine-induced status epilepticus, the stability of the tested reference genes varied significantly between brain regions and depended on time after epileptogenesis induction (3 and 7 days in the latent phase, and 2 months in the chronic phase of the model). Pgk1 and Ywhaz were the most stable, while Actb, Sdha, and B2m demonstrated the lowest stability in the analyzed brain areas. We revealed time- and region-specific changes in the mRNA expression of the housekeeping genes B2m, Actb, Sdha, Rpl13a, Gapdh, Hprt1, and Sdha. These changes were more pronounced in the hippocampal region during the latent phase of the model and are thought to be related to epileptogenesis. Thus, RT-qPCR analysis of mRNA expression in acquired epilepsy models requires careful selection of reference genes depending on the brain region and time of analysis. For the time course study of epileptogenesis in the rat lithium–pilocarpine model, we recommend the use of the Pgk1 and Ywhaz genes. Full article

Recently, community detection has emerged as a prominent research area in the analysis of complex network structures. Community detection models based on non-negative matrix factorization (NMF) are shallow and fail to fully discover the internal structure of complex networks. Thus, this article introduces a novel constrained symmetric non-negative matrix factorization with deep autoencoders (CSDNMF) as a solution to this issue. The model possesses the following advantages: (1) By integrating a deep autoencoder to discern the latent attributes bridging the original network and community assignments, it adeptly captures hierarchical information. (2) Introducing a graph regularizer facilitates a thorough comprehension of the community structure inherent within the target network. (3) By integrating a symmetry regularizer, the model’s capacity to learn undirected networks is augmented, thereby facilitating the precise detection of symmetry within the target network. The proposed CSDNMF model exhibits superior performance in community detection when compared to state-of-the-art models, as demonstrated by eight experimental results conducted on real-world networks. Full article

This paper explores the development of a smart Structural Health Monitoring (SHM) platform tailored for long-span bridge monitoring, using the Forth Road Bridge (FRB) as a case study. It discusses the selection of smart sensors available for real-time monitoring, the formulation of an effective data strategy encompassing the collection, processing, management, analysis, and visualization of monitoring data sets to support decision-making, and the establishment of a cost-effective and intelligent sensor network aligned with the objectives set through comprehensive communication with asset owners. Due to the high data rates and dense sensor installations, conventional processing techniques are inadequate for fulfilling monitoring functionalities and ensuring security. Cloud-computing emerges as a widely adopted solution for processing and storing vast monitoring data sets. Drawing from the authors’ experience in implementing long-span bridge monitoring systems in the UK and China, this paper compares the advantages and limitations of employing cloud- computing for long-span bridge monitoring. Furthermore, it explores strategies for developing a robust data strategy and leveraging artificial intelligence (AI) and digital twin (DT) technologies to extract relevant information or patterns regarding asset health conditions. This information is then visualized through the interaction between physical and virtual worlds, facilitating timely and informed decision-making in managing critical road transport infrastructure. Full article