Search Results (3,628)

Understanding how quickly trading liquidity recovers after volatility shocks is central to evaluating market resilience and trading costs in financial markets. The purpose of this study is to examine how quickly trading liquidity recovers after volatility-based stress shocks in an emerging equity market and to evaluate whether recovery horizons vary systematically across shock severity, market fear, downside-risk conditions, and sectors. Using a balanced panel of NIFTY-50 firms over 2018–2024, comprising 91,350 firm-day observations, the analysis employs a non-parametric event-time framework, combined with bootstrap inference and episode-level regression diagnostics, to trace the adjustment in market liquidity following episodes of elevated volatility. Liquidity conditions are measured using the Amihud illiquidity indicator, while stress episodes are identified through firm-specific volatility shocks derived from a standardised realised-volatility measure. The framework introduces duration-based recovery metrics—liquidity half-life and time-to-normalisation—to quantify the persistence of post-shock trading frictions relative to firm-specific pre-stress baselines. Across 602 declustered stress episodes, liquidity deteriorates sharply on the stress day and recovers only gradually thereafter. The estimated mean recovery half-life is slightly above five trading days, while nearly one-third of episodes do not fully normalise within twenty trading days, indicating economically meaningful persistence in post-shock illiquidity. Recovery dynamics also vary systematically across stress severity, market-wide fear conditions (India VIX), downside-risk regimes, and sectors, highlighting that market resilience is state-dependent rather than uniform. The findings provide new evidence on the temporal structure of liquidity adjustment in emerging equity markets and introduce operational recovery-horizon metrics that can inform liquidity risk management, trading execution strategies, and market surveillance during periods of elevated volatility. These recovery-horizon measures have direct practical relevance for portfolio managers and institutional traders because they provide an operational basis for planning execution strategies when market liquidity remains impaired after volatility shocks. They are also useful for exchanges and regulators seeking to complement volatility monitoring with post-shock liquidity surveillance, thereby improving the assessment of market functioning during periods of elevated stress. Full article

Background/Objectives: Sickle cell disease (SCD) is the most prevalent inherited pediatric hematologic disease. Pain is the most common complaint and primary reason for emergency care. Effective coping is critical to improved quality of life for individuals with SCD and other chronic illnesses. Hope, engendered by provision of comprehensive care, may explain the positive impact of effective coping and improved health outcomes. The relevance of effective coping skills and hope’s impact on repeated hospitalizations and/or length of hospitalization stay (LOS) among adolescents with SCD is considered. A regional, comprehensive pediatric sickle cell center (RCPSCC) provided the services. Methods: Patients with SCD, ages 13 through 21 years seen in a university RCPSCC (URCPCC-SCD), completed surveys: a general scale providing a broad range of positive and maladaptive coping-related issues, and KIDCOPE, a standardized scale measuring pediatric coping strategies. Medical records were reviewed for frequency of hospitalization and length of stay (LOS) for the eight months before study entry. Results: Thirty-four URCPCC-SCD outpatients, mean/median age of 16 years, entered the study, and data were analyzed for 33. All reported some sense of future hopefulness, and almost half reported feeling “tense or wound up” most of the time. Use of avoidant or negative coping strategies in response to daily stress correlated positively with increased LOS. Conclusions: Youths with SCD require effective coping strategies to improve self-efficacy and related hope for brighter futures. Individualized, comprehensive treatment and support to families and individuals at risk for sickle cell crisis are uniquely offered in a URCPCC-SCD. Their contributions to service delivery and clinical outcome are expected to enhance hope, mitigate prolonged hospitalizations, and improve adherence to treatment (N = 268). Full article

This paper develops a deep reinforcement learning framework for cryptocurrency portfolio management in which transaction costs are derived from the Riemannian geometry of the underlying volatility model rather than assumed constant. A Proximal Policy Optimisation agent is trained on a reward function grounded in non-equilibrium thermodynamics: we use the free-energy Bellman equation, in which transaction costs are the geodesic slippage on the Fisher information manifold of a maximum-entropy Markov-switching GARCH model, and regime-transition costs are the Wasserstein-2 distance between the calm and turbulent return distributions. A thermodynamic Carnot bound on portfolio efficiency is established and empirically validated. Five hypotheses are tested across Bitcoin, Ethereum, Ripple, Litecoin, and Bitcoin Cash over January 2017 to March 2026. The geometric-cost agent achieves statistically superior Sharpe ratios relative to flat-fee baselines on four of five assets; portfolio turnover is reduced by 56 to 83 percent relative to signal-following; the thermodynamic friction point at which the agent prefers no-trade is asset-specific and ordered by turbulent half-life; a joint topological and geometric circuit breaker reduces Maximum Drawdown by 28 to 38 percent; and ablation confirms that every component of the observation vector contributes a statistically significant performance gain. The framework requires liquid cryptocurrency markets with validated parametric volatility models; transferability to other asset classes requires upstream recalibration. Full article

The second-life application of vehicle batteries is getting attention as millions of battery systems, modules, or cells are going to enter the market in the coming decade. The performance uncertainty with or without historical knowledge of the batteries’ vehicle usage is a concern. Moreover, detailed studies on second-life battery cell behavior is sparse and an improved understanding is required for reuse/repurpose. In this work, two second-life battery packs are dismantled, and the extracted prismatic and pouch Nickel–Manganese–Cobalt (NMC) cells with 141 Ah and 65 Ah, respectively, are extensively investigated to understand the second-life degradation behavior. The one-and-a-half-year-long test campaign has followed dedicated suitable stationary test matrices, generating a valuable dataset. The aging dataset is then filtered with the most correlated features via Pearson correlation analysis (PCA) and used to train different machine learning algorithms, resulting in a root-mean-square-error (RMSE) of 0.065 and 0.109 for prismatic and pouch cells, respectively, with the best-performing ElasticNet model validated against real-life stationary profiles. The developed framework is suitable for edge computation where the SoH could be evaluated online, facilitating state-based performance and lifetime extension. Full article

The Landauer principle motivates the definition of economic temperature as the monetary price of processing a bit irreversibly. No empirical test of this definition exists in transparent fee markets. This paper fills that gap using daily Bitcoin and Ethereum data, constructing canonical thermodynamic state variables and evaluating five diagnostic layers: state variable behavior, Maxwell-type integrability, Carnot-style efficiency bounds, nonlinear regime separation, and structural break sensitivity to protocol events. Bitcoin’s log-temperature behaves as a persistent mean-reverting process with an AR(1) coefficient of 0.97 and a half-life of 21 days; Ethereum is highly persistent, with weaker formal evidence of stationarity than Bitcoin. Maxwell integrability is frequency-dependent: Bitcoin passes all four relations at monthly frequency, whereas Ethereum passes two of four. Carnot-style evidence is the strongest: realized fee extraction efficiency stays well below the implied bound, with daily compliance exceeding 97% on both chains. Structural breaks around Bitcoin ordinals, EIP-1559, the merge, and Shanghai confirm that protocol changes reorganize the temperature relation. The thermodynamic framework provides structure that standard fee market analysis does not, including a first principles efficiency bound and a state space coherence test. The findings provide partial, frequency-dependent, and chain-specific empirical support for a Landauer-based thermodynamic description of blockspace markets. Full article

Ertugliflozin is a sodium-glucose co-transporter-2 inhibitor that has demonstrated promise as a treatment for hyperinsulinaemia in horses. Despite the frequent use of ertugliflozin in equine clinical practice, the pharmacokinetics of this drug in horses has not been established. The aim of the present study was to determine the pharmacokinetics of one supratherapeutic dose (0.25 mg/kg) of ertugliflozin in eight horses. Horses were defined as being healthy by physical examination, haematological, blood biochemical and oral sugar test (OST) results. Plasma concentrations of ertugliflozin were quantified using high-performance liquid chromatography–tandem mass spectrometry 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 14, 18, 24, 30, 36, 48, 60, 72, 96, and 120 h after drug administration enterally. Non-compartmental analysis led to determination of key pharmacokinetic variables, including mean ± SD time to maximum concentration (T_max) of 0.91 ± 0.13 h, maximum measured concentration (C_max) of 267.52 ± 25.37 ng/mL, terminal elimination half-life (T_1/2) of 17.65 ± 3.15 h and apparent oral clearance (CL/F) of 106.95 ± 27.53 mL/h/kg. No clinical signs of adverse effects or blood biochemical abnormalities occurred after drug administration. The results of this study suggest that a single supratherapeutic dose of ertugliflozin in healthy horses is safe. The pharmacokinetics of enterally administered ertugliflozin in horses are similar to pharmacokinetics of the drug in humans and the long T_1/2 makes ertugliflozin suitable for once daily dosing in horses. It is proposed that a starting dose for ertugliflozin in horses be in the range 0.05–0.1 mg/kg. Further pharmacokinetic studies are required to optimise the dose regimen for treating horses with hyperinsulinaemia. Full article

Background/Objectives: Mental health service utilization gaps remain a persistent global public health challenge. Among the 61.5 million adults with any mental illness in the United States, nearly half went without treatment in the past year, and dropout rates from outpatient services among those who do enter care range from 19.7% to 30.8%. Only 30 to 60% of individuals with lifetime mental illness are in active recovery at any given time. Existing theoretical frameworks, including Andersen’s Behavioral Model, the Health Belief Model, and the COM-B framework, each address isolated phases of the care continuum but offer no unified structure for understanding the complete, sequential journey from first contact through sustained recovery. This article introduces the Access, Initiation, Engagement, Retention, and Recovery (AIERR) model to address this theoretical gap. Methods: A conceptual review was conducted following Hulland’s framework for theory development through narrative synthesis. Literature was identified through targeted searches in PubMed, PsycINFO, and Google Scholar, prioritizing peer-reviewed empirical studies, systematic reviews, and foundational theoretical frameworks. Sources were assigned to AIERR stages using predefined decision rules corresponding to each phase’s defining characteristics. Results: AIERR maps five sequential, interconnected stages: Access (structural, cultural, and systemic conditions enabling service reach), Initiation (the transition from provider identification to first appointment attendance), Engagement (active and meaningful treatment participation), Retention (sustained continuity of care), and Recovery (long-term reclamation of life quality and community belonging). For each stage, the framework identifies individual-level and structural-level barriers, facilitating conditions, and targeted intervention points. Conclusions: AIERR advances mental health services theory by unifying previously siloed frameworks, establishing stage-specificity as a core theoretical principle, and reorienting research and intervention strategy toward the upstream structural conditions that produce downstream utilization failures. These theoretical contributions require empirical testing to confirm. Implications for health equity research, clinical practice, and health systems design are discussed. Full article

Human serum albumin (HSA), as a natural protein carrier, possesses excellent biocompatibility and drug binding capacity. Due to the synergistic effects of the enhanced permeability and retention (EPR) effect and Gp60/SPARC-mediated active targeting, this drug carrier demonstrates favorable tumor selectivity and can be enriched in tumor tissues to achieve long-term therapeutic effects. Particularly, HSA undergoes pH-dependent recycling through the neonatal Fc receptor (FcRn), which significantly prolongs its half-life and enhances its feasibility as a drug delivery platform. In practical clinical applications, the regulation of HSA release rates requires multiple strategies to work synergistically. Additionally, the targeting efficiency of delivery systems due to tumor heterogeneity remains a major bottleneck limiting its universality. This article systematically reviews the unique advantages, clinical applications, challenges, and future perspectives of HSA as a prodrug carrier in tumor therapy. Full article

Metakaolin-based geopolymers modified with ZnO and surface-functionalized ZnO were developed and investigated in terms of structure, morphology, textural properties, and photocatalytic performance. ZnO, ZnO@AS(zinc oxide functionalized with steric acid), and ZnO@PEG(zinc oxide functionalized with polyethylene glycol) were incorporated into the geopolymer matrix and characterized by XRD(X-ray diffraction), ATR–FTIR(Fourier transform infrared spectroscopy in attenuated total reflectance, SEM–EDS( scanning electron microscopy coupled with spectroscopy with energy-dispersive X-ray spectroscopy), and BET(Brunauer–Emmett–Teller) analysis. The results showed that ZnO incorporation did not significantly modify the amorphous aluminosilicate network but affected the morphology and porosity depending on the functionalization method. ZnO@AS induced matrix densification and reduced accessible porosity, while ZnO@PEG improved particle dispersion and preserved the porous structure. Among the ZnO-modified metakaolin-based geopolymers, GP/ZnO@PEG(geopolymer with ZnO@PEG particles) exhibited the highest photocatalytic performance, characterized by a BET surface area of 17.22 m²/g, an apparent kinetic constant of 0.01668 min⁻¹, and a half-life of approximately 41 min, achieving approximately 90% methylene blue removal after 120 min of UV-A irradiation. The study demonstrates that ZnO surface functionalization controls the interfacial interaction with the geopolymer matrix and plays a key role in the performance of geopolymer-based photocatalytic materials. Full article

Sarcopenia is increasingly recognized as a key extracardiac manifestation of heart failure (HF), contributing to functional impairment, reduced quality of life, and adverse clinical outcomes. Characterized by progressive loss of skeletal muscle mass, strength, and physical performance, it affects more than half of hospitalized HF patients. It is independently associated with increased mortality and reduced exercise capacity. The pathophysiology of sarcopenia in HF is multifactorial and closely linked to metabolic and nutritional disturbances. Chronic inflammation, neurohormonal activation, oxidative stress, endothelial dysfunction, and anabolic resistance contribute to muscle catabolism and impaired protein synthesis. These alterations are further exacerbated by inadequate dietary protein intake and micronutrient deficiencies, promoting progressive muscle wasting and functional decline. Sarcopenia may also represent an early and potentially modifiable stage in the continuum toward cardiac cachexia. This narrative review provides a comprehensive synthesis of current evidence on the epidemiology, pathophysiological mechanisms, and management of sarcopenia in HF, with particular emphasis on nutritional and metabolic determinants. Emerging data support a multimodal therapeutic approach integrating exercise training with targeted nutritional strategies, including adequate protein intake, essential amino acid supplementation, and correction of micronutrient deficiencies. However, evidence from large, well-designed trials remains limited. In summary, improved recognition and integrated management of sarcopenia in HF are essential. Future research should focus on the development of effective, nutrition-centered therapeutic strategies. Full article

Background: Dyspareunia is a common female sexual pain disorder that significantly impairs quality of life. Despite the availability of evidence-based treatments, including multimodal pelvic floor physiotherapy and psychosexual interventions, patient awareness of these options remains insufficiently characterized. This study aimed to assess knowledge of dyspareunia management among affected women and to identify independent predictors of awareness. Methods: A cross-sectional survey was conducted in 2023 at the Central Clinical Hospital of the Medical University of Lodz, Poland, among 72 women with physician-confirmed dyspareunia. An 82-item questionnaire administered via structured face-to-face interviews assessed sociodemographic characteristics, clinical features including intercourse positions, penetration depth, and partner-related factors, and knowledge of pelvic floor therapy. Responses to 18 knowledge items were aggregated into a synthetic awareness variable (range 0–24 points). Internal consistency was evaluated using Cronbach’s alpha. Statistical analysis included item-level scoring, multiple linear regression, Mann–Whitney U test, Kruskal–Wallis test, and Spearman’s rank correlation. Effect sizes are reported as Cohen’s d for parametric comparisons and rank-biserial correlation for nonparametric comparisons. Results: The mean awareness score was 10.9 ± 6.1 out of 24 points. The awareness scale demonstrated good internal consistency (standardized Cronbach’s α = 0.880). Item-level analysis revealed critical knowledge gaps: biofeedback was recognized by only 15.3% of participants, and only 6.2% could correctly estimate the number of pelvic floor muscles. In multiple linear regression (R² = 0.224, adjusted R² = 0.153, p = 0.009), age (β = −0.305, p = 0.009) and current urogynecological physiotherapy use (β = 0.332, p = 0.019) were independent predictors of awareness. Physiotherapy users scored on average 5.6 points higher than non-users (16.0 ± 4.9 vs. 10.4 ± 6.0; p = 0.027; rank-biserial r = 0.51), although this finding should be interpreted with caution given the small number of physiotherapy users (n = 7) and the wide confidence interval. More than half of participants (55.6%) reported positional dependency of dyspareunia; in exploratory analyses, none of the assessed dyspareunia characteristics showed a statistically significant association with awareness. Younger women (≤24 years) demonstrated significantly higher awareness than older participants (12.1 ± 5.6 vs. 9.1 ± 6.5; p = 0.039; Cohen’s d = 0.51). Conclusions: Women with dyspareunia demonstrate modest and heterogeneous awareness of evidence-based treatments, with the largest deficits in knowledge of specific physiotherapeutic modalities. These findings highlight the need for targeted educational interventions and improved referral pathways to pelvic floor physiotherapy. This study establishes a conceptual framework for assessing patient awareness of dyspareunia treatments, which warrants validation in larger, multi-center studies. Full article

Nanoparticles (interchangeably called ultrafine particles) constitute one of the growing risks encountered in everyday life. Both short- and long-term exposure to them, as well as to particulate matter in general, may pose serious health risks. In this study, we focus on monitoring of particle concentration in urban air for 200 days, with special attention to nanoparticles. The overall data coverage exceeded 80%, reaching over 97% in three selected months. Measurements were carried out at 25.5 m height in southern Warsaw, in close vicinity to residential blocks with apartments also at the same level. Data were collected from January to first half of August 2025 using a Grimm MINI-WRAS portable wide-range aerosol spectrometer and a thermo-hygro-barometer. Over the 8-month period, significant variations between months and days in both nanoparticle and all particulate matter concentrations were observed. Winter months were almost four times more polluted with particles (both nanoparticles and those above 100 nm) than spring and summer periods. Although nanoparticle concentration in colder months was higher, the percentage of nanoparticles was lower. An important aspect of these investigations was comparing the obtained results with publicly available air pollution data from urban air quality monitoring stations, which represent ground-level measurements. At rooftop altitude, PM_2.5/PM₁₀ ratios were significantly higher than those measured at ground level. Full article

Bioequivalence (BE) studies are essential to file an abbreviated new drug application (ANDA) against an innovator drug product. Conventional BE studies can be complex, time-consuming, and operationally challenging, particularly for products with long half-life drugs, high variability, or formulation complexity. Advances in quantitative modeling and simulation have expanded the role of model-generated information in generic drug development from a supportive role toward providing critical regulatory evidence. Model-Integrated Bioequivalence (MIBE) represents a focused application of this paradigm in which mechanistic or empirical models are used to directly support BE determination. While physiologically based pharmacokinetic (PBPK) and physiologically based biopharmaceutics modeling (PBBM) approaches have been widely discussed in the literature, increasing attention is being directed toward population pharmacokinetic (POP-PK) modeling for MIBE implementation, particularly when mechanistic assumptions are uncertain or extensive in vitro characterization is impractical. This review provides a contemporary overview of MIBE in generic drug development, with a specific emphasis on POP-PK-based approaches. Key quantitative modeling frameworks are discussed along with evolving regulatory perspectives that support the integration of model-based evidence for BE assessment. We illustrate six diverse hypothetical case examples covering different formulations, a variety of BE scenarios and using MIBE to answer specific regulatory questions on BE. Collectively, this manuscript addresses an important topic of MIBE for complex and non-complex generic formulations and may provoke thinking among the generic companies to use such approaches in the regulatory context to enable faster and timely approval to bring the necessary medicines to the market at a rapid pace. Full article

The rise in antimicrobial resistance represents a significant challenge to global health. The reason partially lies in an inappropriate use of conventional antibiotics and the subsequent rapid spread of multidrug-resistant pathogen strains. This emergency requires an urgent search for conceptually new antimicrobial agents. A viable alternative to conventional antibiotics is antimicrobial peptides (AMPs), which are ribosomally synthesized molecules with considerable potential as next-generation anti-infectious therapeutics. Previously, we have reported on the β-hairpin peptide Ap9, an analog of abarenicin from the marine polychaeta Abarenicola pacifica, with potent activity against key Gram-negative pathogens. Here, it is shown that Ap9 acts in a manner resembling polymyxin B, namely via interaction with lipopolysaccharide (LPS), and retains its activity against polymyxin-resistant isolates without observed cross-resistance, and causes insignificant damage in cytoplasmic membrane at bactericidal concentrations. NMR spectroscopy reveals that LPS binding induces a conformational rearrangement of Ap9, its dimer formation, and local structural remodeling of the peptide region (residues 8–12) into 3₁₀-helix. Bacterial resistance to Ap9 was found to be relatively low with a reduced susceptibility associated with infrequent genetic alterations, such as the mutation in lptD or the deletion in mlaA. Furthermore, Ap9 demonstrates a favorable tolerability, a wider therapeutic window than that of polymyxin B, and a sufficiently long half-life through the systemic use, as well as in vivo efficacy in murine models of Gram-negative infections, including sepsis caused by the mcr-1-harboring Escherichia coli strain. The obtained results point to Ap9 as a promising candidate for further preclinical studies aimed at development of an alternative to polymyxins. Full article

We synthesized two vitamin D₃ analogues, 3 and 4, which have a shortened or elongated fluoro-side-chain based on 24,24-difluoro-25-hydroxyvitamin D₃ (5) using an efficient convergent approach and studied their preliminary biological activity. Both analogues exhibited greater resistance to CYP24A1-mediated metabolism than the natural 25-hydroxyvitamin D₃ (6), although their stability was lower than that of 5. Analogue 3 showed an approximately 100-fold lower human vitamin D receptor (hVDR)-binding affinity compared with 5 and 6. Despite this marked reduction in VDR-binding affinity, it demonstrated an approximately 1.5-fold increase in VDR-ligand binding domain (LBD) transcriptional activation of the natural ligand 6. In contrast, analogue 4 displayed moderate VDR-binding affinity and VDR-LBD transactivation compared with 5 and 6. We found that compound 3 is a unique vitamin D analogue with a fluorinated and shortened side-chain, exhibiting low binding affinity for hVDR but potent transcriptional activity through VDR-LBD with its long half-life; thus, 3 may serve as a basic structural skeleton for advancing medicinal chemistry and drug discovery. Full article