In this paper, we introduce a new family of Baskakov-Kantorovich operators that depend on a function ψ. We compare these new ψ-Baskakov-Kantorovich operators with the classical Baskakov-Kantorovich operators to evaluate their approximation results. Our analysis shows that these new operators provide better approximation results across the entire interval [0 ,∞). We demonstrate their uniform convergence in weighted spaces and determine their convergence rates using both first and second-order moduli of continuity. We also prove that these operators preserve shape preserving properties. We support our findings with graphical and numerical examples.

While some studies have suggested that autonomous sensory meridian response (ASMR) can relieves anxiety, whether ASMR relieves anxiety in trait-anxious individuals and its neural mechanisms remains a question worth exploring. We used the self-threatening n-back paradigm to elicit state anxiety and an ASMR video to relieve anxiety. Functional near-infrared spectroscopy(fNIRS) was used to monitor frontal and temporal lobe activity to explore the neurophysiological changes when watching ASRM videos, and then further explore the mechanism of self-reported ”feelings” of ASMR. During the anxiety arousal phase, the hemodynamic responses(HR) of the middle frontal gyrus(MFG) and prefrontal cortex(PFC) were significantly enhanced in participants with high trait anxiety. Those with low trait anxiety had significantly reduced HR of the dorsolateral prefrontal cortex(DLPFC). Compared with the non-ASMR video, the HR of the MFG, PFC, and DLPFC were significantly lower in participants who watched the ASMR video. When the experience of ASMR was reported, the HR of the premotor and auxiliary motor cortices, middle frontal lobe, and DLPFC were significantly reduced. While watching an ASMR video, brain activity is the opposite of when anxiety is elicited in people with high trait anxiety. The activated area when the participants were watching the ASMR video, and when they reported experiencing ASMR, overlapped with the anxiety-related parts of the brain. This provides neurophysiological evidence of how an ASMR video can relieve anxiety.

We depend on the safe, reliable, and timely operation of cyber-physical systems ranging from smart grids to avionics components. Many of them involve time-dependent behaviours and are subject to randomness. Modelling languages and verification tools thus need to support these quantitative aspects. This paper gives an introduction to quantitative verification using the Modest modelling language and the Modest Toolset. It highlights three recent case studies with increasing demands on model expressiveness and tool capabilities: A case of power supply noise in a network-on-chip modelled as a Markov chain; a case of message routing in satellite constellations that needs Markov decision processes with distributed information; and a case of optimising an attack on Bitcoin via Markov automata model checking. For each, we explain the particular conceptual and technical challenges in modelling and verification, and point out open problems for future work.

Działanie adwokata w sprawie-rozważania na gruncie teorii chaosu Teoria chaosu to dziedzina matematyki i nauk przyrodniczych, która bada systemy dynamiczne, w których małe zmiany w warunkach początkowych mogą prowadzić do znacznych i nieprzewidywalnych zmian w rezultatach. Niektóre systemy mogą wydawać się chaotyczne i losowe, mimo że są deterministyczne, co oznacza, że ich zachowanie jest zdefiniowane przez określone równania. Teoria chaosu znalazła zastosowanie w wielu dziedzinach, takich jak meteorologia, biologia, ekonomia, fizyka i inżynieria. Pojęcie chaosu w kontekście matematycznym zaczęło się rozwijać w latach 60. i 70. XX wieku, a kluczową postacią w tym rozwoju był Edward Lorenz, amerykański meteorolog.

Key Clinical Message

Pancreatic beta (β)-cells secrete insulin in response to a rise in glucose and defective secretion contributes to type 2 diabetes. A rise in β-cell cytosolic Ca2+ triggers insulin exocytosis, and the endoplasmic reticulum (ER) and mitochondria both regulate cytosolic Ca2+ and secretion. Following ER Ca2+ release and reduced ER Ca2+, store-operated calcium entry (SOCE) serves to replete ER Ca2+. To understand the role of SOCE channels in β-cell function, we tested the actions of the SOCE channel blocker YM-58483 (YM) in isolated mouse islets and report that besides inhibiting SOCE activity, YM directly inhibited β-cell metabolism. The implications of these findings are discussed. Experimental Approach: Islets were isolated from mouse, cultured short term and studied using live cell imaging. The acute effects of YM on cytosolic, ER and mitochondrial Ca2+, cytoplasmic ATP/ADP, and KATP channels were monitored. In addition, the effects of YM on the oxygen consumption of isolated cardiac mitochondria were tested. Key Results: YM inhibited islet Ca2+ oscillations, suggesting a role for SOCE in the oscillations. However, YM also reduced ER and mitochondrial Ca2+ and lowered ATP/ADP. After preventing SOCE by removing extracellular calcium, YM still reduced ER, mitochondrial Ca2+ and ATP/ADP. Similar results were found using two other SOCE blockers. YM exposure increased single KATP channel openings, consistent a reduction of cytosolic ATP/ADP. Lastly, applying YM to isolated cardiac mitochondria increased leak flux and reduced ATP, demonstrating that YM directly inhibits mitochondrial OXPHOS.

Kawasaki Disease (KD) is an acute and self-limiting vasculitis of unknown etiology that mainly occurs in infancy and can lead to vascular endothelial injury. Hesperidin (HES) is an economical dietary biological flavonoid with anti-oxidant, anti-inflammatory, and anti-apoptotic pharmacological effects. The main objective of this study was to investigate the protective effects of HES on KD, and try to elucidate the underlying mechanism. The Candida albicans water-soluble fraction (CAWS) was used to induce coronary arteritis of KD mouse model in vivo, and tumor necrosis factor α (TNF-α) was employed to induce human umbilical vein endothelial cell (HUVEC) injury of KD cell model in vitro to investigate the anti-inflammatory and anti-apoptotic effects of HES on KD. Our in vivo results showed that HES significantly reduced coronary artery injury in KD mice by alleviating pericoronary inflammatory infiltration and tissue fibrosis, inhibiting inflammatory cytokines and chemokines expressions, and decreasing vascular endothelial cell apoptosis. Our in vitro study confirmed that HES had the opposite ability of the NF-κB agonist NF-ĸB activator 1 (ACT1) to significantly alleviate the inflammatory response, CellROX level, and apoptosis by decreasing BAX/BCL-2 and Cleaved Caspase-3 levels as well as reducing TUNEL positive cells and the ratio of flow cytometry apoptotic cells in TNF-α induced HUVECs. The further mechanism study based on bioinformatics analysis and western blot demonstrated that HES could protect against vascular inflammation and cell apoptosis of KD through inhibiting the TLR4/IĸBα/NF-ĸB pathway, suggesting that HES may be a promising therapeutic candidate for KD.

Stacked cell culture has emerged as a successful 3D technique in tissue engineering, demonstrated by prototypes developed with various scaffold materials. This study aimed to enhance cell culture by integrating an alginate membrane with a 3D-printed stacking platform composed of PLA material. The platform featured an optimized three-layer structure using L929 cells and was evaluated against MG-63 cells. Cells were seeded on alginate membrane layers comprising a mixture of alginate, agarose, gelatin, and glycerol (1.5:0.25:1:1 %w/v). Increased alginate content resulted in greater weight loss without significantly affecting the degradation rate. In contrast, reducing agarose content accelerated membrane degradation and halved tensile strength (from ~6 to ~3 MPa). Cell viability, Live/Dead staining, and SEM imaging assessed the performance of the stacked culture across layers. The alginate membrane exhibited biocompatibility with L929 cells over 28 days, as verified by Live/Dead staining and SEM imaging on days 7 and 14. The stacked culture maintained over 70% cell viability per layer for both L929 and MG-63 cells compared to single-layer culture. MG-63 cells, representing osteoblastic differentiation, showed enhanced outcomes, with bone-related genes ( RUNX2, OCN, BMP2, COL1A2) exhibiting 1–2-fold increased expression, particularly in the upper layers, compared to general medium. These findings highlight the potential of stacked cell culture to support cell growth and differentiation across layers. This prototype offers promise for tissue engineering applications, with future studies aiming to utilize it for stem cell culture and large-scale 3D tissue development.

A document by Kidus Yohannes. Click on the document to view its contents.

Loneliness and social isolation are pressing societal concerns with many downstream ramifications on mental and physical health. The prevalence and burden of these issues have become even more intense in the wake of the COVID-19 pandemic, elevating them to the status of a public health epidemic as declared by Dr. Vivek Murthy, U.S. Surgeon General. While the consequences are now well-established, understanding how social isolation and loneliness translate into ill health requires an integrated view of central and peripheral physiological mechanisms. The present review looks across allostatic systems to identify psychophysiological mechanisms through which loneliness and social increase health risk, framing them within the context of Allostatic Theory. Specifically, we discuss neurobiological, neuroendocrinological, immunological, and cardiovascular responses as well as interactions among these pathways and future directions in this space. Neurobiological correlates span structure, function, and neuropeptides, notably in regions such as the prefrontal cortex and limbic areas, and networks including the attentional, visual, and default mode networks. These neurobiological changes interweave with dysregulated hormonal responses such as elevated cortisol, and weakened immune function marked by heightened inflammatory markers. Cardiovascular responses, including increased blood pressure and arterial stiffness, further compound the impact of loneliness and social isolation on physiology. The interplay among these allostatic systems collectively drives the progression of chronic illnesses and contributes to heightened morbidity and mortality. By synthesizing evidence across these domains, this integrative review highlights the need for a comprehensive understanding of the molecular mechanisms linking loneliness and social isolation to various psychophysiological bases, as well as the development of targeted interventions to address the adverse effects of social stress on health.

A document by MD. Deluwar Hussen. Click on the document to view its contents.

Facial nerve injuries lead to significant functional impairments and psychological distress for affected patients. Effective repair of these injuries remains a challenge. For longer nerve gaps, the regeneration outcomes after nerve grafting remain suboptimal due to limited sources and postoperative immune responses. Tissue engineering techniques are conventional methods for repairing peripheral nerve defects. This study explores the potential of dental pulp stem cells (DPSCs) combined with stem cell factor (SCF) to enhance neurogenic differentiation and improve facial nerve regeneration. DPSCs were isolated from rabbit dental pulp, characterized for their multipotency. In vivo experiments involved injuring the buccal branch of the facial nerve in New Zealand white rabbits, followed by treatment with PBS, DPSCs, SCF, or SCF + DPSCs. Functional recovery was assessed over 12 weeks, with SCF + DPSCs demonstrating the most significant improvement in whisker movement scores. Histomorphological evaluations revealed enhanced myelinated fiber density and axonal morphology in the SCF + DPSCs group. RNA sequencing identified 608 differentially expressed genes, with enrichment in the TGF-β signaling pathway. In in vitro experiments, we demonstrated from multiple angles using Western blot analysis, Real-time quantitative polymerase chain reaction (QPCR) analysis, and immunofluorescence staining that SCF can promote the neurogenic differentiation of DPSCs through the TGF-β1 signaling pathway. Our findings indicate that the combination of SCF and DPSCs offers a promising strategy for enhancing facial nerve repair.

A rare case of syphilitic abdominal aortic aneurysm: A case report from EthiopiaFeryat L.2, Beka A.1, Sebhatleab T.2Elias T. 2 Eskedar G.3Nephrology Unit , Department of Internal Medicine, School of Health Sciences, Addis Ababa University, Addis Ababa.Department of Internal Medicine, School of Health Sciences, Addis Ababa University, Addis Ababa.Infectious disease unit, Department of Internal Medicine, School of Health Sciences, Addis Ababa University, Addis Ababa.

Aims: The aim of this phase 1 trial was to assess the pharmacokinetics, safety, and tolerability of balcinrenone (previously AZD9977) in participants with severe renal impairment versus those with normal renal function. Methods: Participants with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) not on dialysis were compared with group-matched control participants with eGFR ≥90 mL/min/1.73 m2. Eligible participants received a single oral dose of 150 mg balcinrenone, and blood and urine samples were collected for analysis. Results: The total apparent balcinrenone clearance was 50% lower in the severe renal impairment group, resulting in a ~two-fold higher area under the curve (AUC) and a 1.4-fold higher maximum observed plasma concentration in the severe renal impairment group versus the control group. The terminal half-life and plasma protein binding were similar in both groups. Balcinrenone was safe and well tolerated in all participants. All adverse events reported were of mild-to-moderate severity and not considered related to balcinrenone. Conclusions: Balcinrenone exposure was approximately two-fold higher in participants with severe renal impairment compared with the group-matched control participants. Based on obtained results, the AUC exposure is predicted to be <50% higher in patients with an eGFR of 20 mL/min/1.73 m2 compared with those with an eGFR of 60 mL/min/1.73 m2. In light of these findings, no dose adjustment based on eGFR is needed in two ongoing studies that target these patients (MIRO-CKD [NCT06350123] and BalanceD-HF [NCT06307652]).

A Case of Hypoxic-Ischemic Brain Injury Initially Suggesting a Persistent Vegetative State but Resulting in Near-Complete Recovery

Ultrahigh-frequency ultrasound sonographic features of

To investigate the histologic effects of topiramate (TPM), lamotrigine (LTG), levetiracetam (LEV), lacosamide (LCM), clobazam (CLB), and zonisamide (ZNS) on rat bone. Seventy male Wistar-Albino rats (aged 21-24 days, weighing 46.4-55.3 g) were divided into 7 experimental groups with 10 rats each:(i) Control group, (ii) TPM group (40 mg/kg/day), (iii) LTG group (10 mg/kg/day), (iv) LEV group (200 mg/kg/day), (v) LCM group (30 mg/kg/day), (vi) CLB group (50 mg/kg/day), and (vii) ZNS group (100 mg/kg/day). All the drugs were administered by gavage for 90 days.The specimens were analyzed using apoptosis (TUNEL) and immunohistochemical staining. The number of osteoblasts and the thickness of femoral compact bone decreased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups. In osteoblasts, there was local atrophy in TPM, LEV, and LCM groups, while intense atrophy was observed in LTG, CLB, and ZNS groups. In all experimental groups, there were abnormally prominent enlargements in the Havers and Volkmann canals. The number of TUNEL-positive cells was higher in all experimental groups compared to the control group, and this difference was statistically significant in CLB and ZNS groups ( p<0.001 for both). The HSCORE increased significantly for C-3, C-9, and BAX immunohistochemical staining ( p<0.001) and increased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups ( p<0.001).

Unconfined compressive strength (UCS) and California Bearing Ratio (CBR) are critical for assessing soil strength under vertical loading, especially in fine-grained soils, which often fail to meet the required standards for road and embankment projects. This study examines the effects of cement and fly ash on improving UCS and CBR through soil stabilization. The results showed an increase in both UCS and CBR with the incorporation of these materials, though the improvements were asymmetrical depending on the dosage of cement and fly ash. The variation is attributed to changes in the soil-cement or soil-fly ash matrix due to chemical oxides like silica, alumina, and calcium. The study modeled UCS and CBR using three mathematical models: pure quadratic (PQ), interaction (IA), and full quadratic (FQ), based on 130 fly ash-treated, 31 cement-treated, and 50 untreated soil datasets. The FQ model best predicted UCS (R 2 = 0.88) and CBR (R 2 = 0.95). Calcium oxide and curing time were the most influential factors for UCS while curing time and optimum moisture content were key for CBR. This study suggests a high-calcium oxide soil-additive matrix to enhance UCS and CBR in fine-grained soils.

Photocatalytic two-electron oxygen reduction for hydrogen peroxide (H2O2) production represents a cost-effective and sustainable synthetic approach that has garnered significant attention. Inexpensive graphite-like carbon nitride (g-C3N4) features a tunable bandgap and impressive photocatalytic performance in the 2e- oxygen reduction reaction (ORR), facilitating H2O2 synthesis. This study presents the design of a defect vacancy ring-opening g-C3N4 that introduces specific C-OH sites at the edges of the ring openings. The g-C3N4 is covalently bonded to anthraquinone (AQ) via ester C-O-C=O oxygen bridges, resulting in a CN-O-AQ catalyst characterized by a silk-like, ordered stacked layer structure. The incorporation of specialized oxygen bridge bonds alters charge transport dynamics, establishing rapid charge diffusion pathways that enhance electron migration to the surface during the photoactivated oxygen reduction reaction. The synergistic effects of optimizing the (100) crystal plane crystallinity and introducing dual O/Cl element doping promote the development of new light absorption centers and lower oxygen adsorption energy while creating suitable electron vacancies. This combination significantly boosts the catalyst’s direct two-electron oxygen reduction capability for H2O2 formation. The CN-O-AQ catalyst achieved an impressive H2O2 yield of 626 mmol L-1, which is 14.9 times higher than that of pure CN (42 mmol L-1). This work elucidates the dual impact of modulating both crystal and electronic structures on photocatalytic performance, offering valuable insights for designing defect sites and doping strategies in organic conjugated structure catalysts.

Identification of individuals within a species is vital for monitoring population dynamics and determining appropriate conservation efforts. Traditional methods for marking individual lizards include toe-clipping, branding, tattooing, and passive integrated transponder (PIT) tags. However, some of these methods can potentially cause stress, affect performance and survival, and raise concerns about the ethical treatment of animals. We conducted a long-term study on the urban ecology of Texas horned lizards living in two small towns in south Texas, USA. Our study was in the unique position of possessing a dataset of individuals that were PIT tagged, genotyped, and photographed which allowed us to validate genotyping and natural markings for individual identification. Our genotyping had low error rates and high power to identify individuals, additionally, individual spot patterns were unique and stable across years. We used HotSpotter software to match photographs and had a success rate of 94%. This could be increased to almost 100% by looking at the top 10 picture matches by eye to validate the matching. Using pictures of ventral spots is an easy way to identify individuals, avoids potential rare instances of infection or mortality, and is inexpensive relative to PIT tags and genotyping.

As climate change increasingly affects biodiversity and ecosystem services, a key challenge in ecology is accurate attribution of these impacts. Though experimental studies have greatly advanced our understanding of climate change impacts on ecological systems, experimental results are difficult to generalize to real-world scenarios. To better capture realized impacts, ecologists can use observational data. Disentangling cause and effect using observational data, however, requires careful research design. Here we describe advances in causal inference that can improve climate change attribution in observational settings. Our framework includes five steps: 1) describe the theoretical foundation, 2) choose appropriate observational data sets, 3) design a causal inference analysis, 4) estimate a counterfactual scenario, and 5) evaluate assumptions and results using robustness checks. We then demonstrate this framework using a case study focused on detecting climate change impacts on whitebark pine growth in California’s Sierra Nevada. We conclude with a discussion of challenges and frontiers in ecological climate change attribution. Our aim is to provide an accessible foundation for applying observational causal inference to climate change attribution in ecology.

Reptiles are the largest clade of terrestrial vertebrates, yet the microbiome of reptiles is one of the least studied of any vertebrate group, despite the known presence of various pathogens impacting multiple species declines across the globe. One of these pathogens is the dermatophyte fungus Ophidiomyces ophiodiicola, the causal agent of Snake Fungal Disease (SFD). SFD has been linked to population declines in multiple snake species, including the Timber Rattlesnake (Crotalus horridus) and the Common Watersnake (Nerodia sipedon) in North America and the Grass Snake (Natrix natrix) and the Little Filesnake (Acrochordus granulatus) in Europe and Asia. However, the full phylogenetic and geographic extent of snake species impacted by SFD has not been formally quantified. Here we perform a systematic literature review following Preferred Reporting Items for Systematic reviews and Meta-Analyses in Ecology and Evolution (PRISMA-EcoEvo) guidelines and quantitatively compile snake species being infected by SFD, their taxonomic distribution, if infected snakes were wild or captive and the known geographic distribution of SFD cases. We show that while the most studied cases of SFD are found within wild populations of Viperidae, and that Colubridae is the family of snakes with the most prevalence of SFD infections. Additionally, we show a geographic bias in SFD studies, with 85% of the known cases being found in the United States. This study will inform future research regarding emergent disease, One Health principles, and host-microbiome interactions and spans fields from ecology and evolutionary biology to conservation.

The oxidation stability of edible oils decreases when exposed to high temperatures. This is an area of interest due to related health concerns it presents and food security. The study used kinetic and thermodynamics to assess the oxidative stability of palm, sunflower, and corn oil when exposed to frying temperatures of 180 °C and 200 °C. Rancimat and quality parameters were used to evaluate both oxidative stability and temperature influence on the oil. The Arrhenius equation and complex activated theory reaction calculated activation energy, rate constant, activation enthalpy, and entropy. From the results, the activation energy for palm ranges (from 90.8 to 100) Kj/mol; for corn (80.6 to 83.9) Kj/mol; and for sunflower oil (77.1 to 82.4) Kj/mol, depending on the frying cycles. This indicates that palm oil is comparatively the most resistant to thermal-oxidative stress since it requires the most energy for the oxidative reaction, followed by corn oil and sunflower. Thermodynamic parameters further supported this; the activation enthalpy for palm oil was (94.2 to 103.4) Kj/mol, corn oil (83.8 to 87.1) Kj/mol, and sunflower (80.3 to 85.6) Kj/mol. The reaction was found to be endothermic since the Gibbs free energies were all positive. The entropy values were all negative, indicating that the reaction favours the formation of the products more. The study observed that the rancidity rate is inversely proportional to activation energy and directly proportional to temperature and unsaturation of oils.

The transition of immunotherapy administration from intravenous infusion to subcutaneous (SC) administration for oncology patients has garnered significant interest. SC administration offers multiple benefits, including at-home administration, enhanced patient compliance, reduced hospital congestion, lowered health care costs, and improved sustainability by reducing drug wastage and minimizing environmental impact. However, for many biologics, the shift to SC administration requires the development of ultra-high–concentration monoclonal antibody products (ultra-HCmAP) due to the need for large dose volumes. Here we explore the impact of the COVID-19 pandemic on immunotherapy administration and the imperative of adopting SC administration. We discuss challenges encountered throughout the manufacturing, shipping, storage and delivery of ultra-HCmAP. A central hurdle identified involves the physical instability and the exponential increase in viscosity of these biologics due to increased protein concentration. Both issues stem from molecular crowding that leads to elevated protein-protein interactions. The main excipients reported to reduce viscosity are salts and amino acids, with Arg-HCl demonstrating particularly improved formulation viscosity in ultra-HCmAP. However, excipients with viscosity-lowering effects can also impact protein stability. The journey to discover suitable excipient strategies remains ongoing, combined with emerging approaches such as molecular engineering and computational techniques, with the ultimate aim of facilitating the successful integration of SC administration for economic savings, environmental sustainability and social equity.