Search Results (1,737)

Change points caused by extreme events in global economic markets have been widely studied in the literature. However, existing techniques to identify change points rely on subjective judgments and lack robust methodologies. The objective of this paper is to generalize a novel approach that leverages topological data analysis (TDA) to extract topological features from time series data using persistent homology. In this approach, we use Taken’s embedding and sliding window techniques to transform the initial time series data into a high-dimensional topological space. Then, in this topological space, persistent homology is used to extract topological features which can give important information related to change points. As a case study, we analyzed 26 stocks over the last 12 years by using this method and found that there were two financial market volatility indicators derived from our method, denoted as $L_1$ and $L_2$. They serve as effective indicators of long-term and short-term financial market fluctuations, respectively. Moreover, significant differences are observed across markets in different regions and sectors by using these indicators. By setting a significance threshold of 98 % for the two indicators, we found that the detected change points correspond exactly to four major financial extreme events in the past twelve years: the intensification of the European debt crisis in 2011, Brexit in 2016, the outbreak of the COVID-19 pandemic in 2020, and the energy crisis triggered by the Russia–Ukraine war in 2022. Furthermore, benchmark comparisons with established univariate and multivariate CPD methods confirm that the TDA-based indicators consistently achieve superior F1 scores across different tolerance windows, particularly in capturing widely recognized consensus events. Full article

Dysregulated cytokine responses are a hallmark of severe COVID-19; however, the persistence of these responses following hospital discharge remains inadequately understood. This study aimed to characterize the inflammatory profile of hospitalized COVID-19 patients in Mureș County, Romania, at the point of admission and one month post-discharge. We conducted a prospective observational study involving 68 patients with RT-PCR-confirmed SARS-CoV-2 infection, classified according to disease severity. Blood samples were collected at baseline and after one month. Macrophage migration inhibitory factor (MIF) levels were quantified using ELISA, while other cytokines, including MCP-1, IP-10, IFN-γ, IL-4, IL-10, IL-13, IL-17, and TNF-α, were measured via Luminex multiplex assays. Patients with severe disease exhibited significantly elevated levels of MIF, IFN-γ, IL-17, and TNF-α at admission (p < 0.0001). Although cytokine concentrations generally declined over time, patients with severe disease continued to display persistently elevated MIF (mean 31,035 pg/mL), IFN-γ, and TNF-α, indicative of ongoing inflammatory processes. Clinical parameters such as respiratory rate and oxygen saturation correlated with disease severity. These findings suggest that severe COVID-19 induces a prolonged inflammatory response, with MIF and IFN-γ remaining elevated beyond the acute phase. Cytokine profiling holds potential for improving prognostic assessments and identifying patients at risk of long-term immune dysregulation, with MIF emerging as a potential candidate marker for immune recovery and a possible target for therapy. Full article

Sectoral vulnerability to distinct crisis types in small, open, and geopolitically exposed markets—such as Jordan—remains insufficiently quantified, constraining targeted policy design and portfolio allocation. This study’s primary purpose is to establish a transparent, comparable metric of sector-level market resilience that reveals how crisis typology reorders vulnerabilities and shapes recovery speed. Applying this framework, we assess Jordan’s equity market across three archetypal episodes—the Global Financial Crisis, the Arab Spring, and COVID-19—to clarify how shock channels reconfigure sectoral risk. Using daily Amman Stock Exchange sector indices (2001–2025), we estimate $GARCH\left(\mathrm{1,1}\right)$ models for each sector–crisis window and summarize volatility dynamics by persistence $(\alpha +\beta )$, interpreted as an inverse proxy for resilience; complementary diagnostics include maximum drawdown and days-to-recovery, with nonparametric (Kruskal–Wallis) and rank-based (Spearman, Friedman) tests to evaluate within-crisis differences and cross-crisis reordering. Results show pronounced heterogeneity in every crisis and shifting sectoral rankings: financials—especially banking—display the highest persistence during the GFC; tourism and transportation dominate during COVID-19; and tourism/electric-related industries are most persistent around the Arab Spring. Meanwhile, food & beverages, pharmaceuticals/medical, and education recurrently exhibit lower persistence. Higher persistence aligns with slower post-shock normalization. We conclude that resilience is sector-specific and contingent on crisis characteristics, implying targeted policy and portfolio responses; regulators should prioritize liquidity backstops, timely disclosure, and contingency planning for fragile sectors, while investors can mitigate crisis risk via dynamic sector allocation and volatility-aware risk management in emerging markets. Full article

This study investigates whether publicly listed cannabis shares provide enough risk-adjusted returns to warrant their incorporation into diversified portfolios. An equally weighted portfolio of cannabis companies is constructed using monthly data from January 2015 to December 2024. Risk-adjusted performance is assessed using the Sharpe, Sortino, and Omega ratios and compared to the Russell 3000 Index and the FTSE All-World ex-US Index. In addition, we estimate both unconditional and conditional Fama–French five-factor model enhanced by momentum. The findings indicate that cannabis stocks persistently underperform U.S. and global benchmarks in both absolute and risk-adjusted metrics. Downside risk is elevated because cannabis portfolios exhibit much higher value at risk (VaR) and conditional value at risk (CVaR) than broad indices, especially after COVID-19. The findings show that cannabis stocks are quite volatile and fail to generate significant returns on a risk-adjusted basis. The study highlights the sector’s structural vulnerabilities and cautions investors, portfolio managers, and regulators against treating cannabis shares as dependable long-term investments. Full article

Background/Objectives: As survival improves in congenital heart defects (CHD), psychosocial support—particularly during crises—has become increasingly important. We examined how concerns of CHD patients and their relatives evolved during the Coronavirus Disease 2019 (COVID-19) pandemic, focusing on the influence of role (patient vs. relative), gender, and CHD complexity. Methods: The German National Register for Congenital Heart Defects (NRCHD) conducted two nationwide online surveys in April 2020 (Survey 1) and April 2021 (Survey 2). Free-text responses were analyzed using Mayring’s summarizing content analysis. Categories were coded per respondent (present/absent) for exploratory comparisons by year, role, sex, and CHD complexity. Analyses were cross-sectional and descriptive (p-values unadjusted). Results: In survey 1, 15.9%, and in survey 2, 19.3% of respondents provided qualitative information. In 2020, dominant themes included general COVID-19 information (37.3%), lack of CHD-specific information (30.4%), worry (24.1%), fear (23.2%), isolation (21.4%), and uncertainty (21.2%). By 2021, concerns shifted toward vaccination (24.1%) and vaccination prioritization (23.4%), while information gaps (21.8%) and fear (21.0%) persisted. Significant year-to-year changes included decreases in general information needs, concern, isolation, and uncertainty, and increases in prioritization (all p < 0.01). Relatives consistently reported higher psychological burden than patients (p ≤ 0.01). Conclusions: Concerns moved from early fear/uncertainty to vaccination and prioritization one year later, with persistent information needs across subgroups. Clear CHD-specific communication, caregiver-inclusive psychosocial support, and crisis-resilient care pathways (including telemedicine) are essential for this vulnerable population. Full article

Background/Objectives: Understanding the durability of immunity induced by mRNA COVID-19 vaccines, especially in individuals with chronic health conditions, remains essential for guiding booster strategies. We conducted a longitudinal study to evaluate humoral and cellular immune responses up to 21 months after a primary two-dose BNT162b2 vaccination followed by a booster, either homologous (BNT162b2) or heterologous (mRNA-1273). Methods: Twenty-eight adults, mostly with chronic conditions, were assessed at approximately 9, 12 and 21 months post-primary vaccination. Serum anti-trimeric Spike IgG levels were quantified, and peripheral blood mononuclear cells were analyzed at 21 months for Spike-specific memory B-cell and T-cell responses by flow cytometry. Results: Participants were stratified by booster type, prior SARS-CoV-2 infection and health status. Anti-Spike IgG persisted in all participants but declined over time. The heterologous mRNA-1273 booster induced higher antibody titers at 9 months, while the homologous BNT162b2 booster led to more sustained antibody levels and higher frequencies of Spike-specific memory B cells at 21 months. Prior infection significantly enhanced antibody titers, particularly in homologous booster recipients. Surprisingly, individuals with chronic health conditions exhibited equal or higher antibody levels compared to healthy participants at all time points. At 21 months, robust Spike-specific class-switched memory B cells and polyfunctional CD4⁺ and CD8⁺ T-cell responses were detected. Conclusions: These findings demonstrate that BNT162b2 vaccination elicits durable, multi-layered immunity lasting nearly two years, even in individuals with chronic conditions, and support the use of both homologous and heterologous mRNA boosters to sustain protection in diverse populations. Full article

COVID-19 infection is often accompanied by psychological symptoms, which may persist long after the end of the infection (long COVID). The symptoms include fatigue, cognitive impairment, and anxiety. The reason for these long-term effects is currently unclear. Therapeutic approaches have included cognitive rehabilitation therapy, physical activity, and serotonin reuptake inhibitors (SSRIs) if depression co-exists. The neuropsychological evaluation of subjects with suspected cognitive issues is essential for the correct diagnosis. Most of the COVID-19 studies used the Montreal Cognitive Assessment (MoCA) or the Mini Mental State Examination (MMSE). However, MoCA scores can be confusing if not interpreted correctly. For this reason, we have developed an original technique to map cognitive domains and motor performance on various brain areas in COVID-19 patients aiming at improving the follow-up of long-COVID-19 symptoms. To this end, we retrospectively reanalyzed data from a cohort of 40 patients hospitalized for COVID-19 without requiring intubation or hemodialysis. Cognitive function was tested during hospitalization and six months after. Global cognitive function and cognitive domains were retrieved using MoCA tests. Laboratory data were retrieved regarding kidney function, electrolytes, acid–base, blood pressure, TC score, and P/F ratio. The dimensionality of cognitive functions was represented over cortical brain structures using a transformation matrix derived from fMRI data from the literature and the Cerebroviz mapping tool. Memory function was linearly dependent on the P/F ratio. We also used the UMAP method to reduce the dimensionality of the data and represent them in low-dimensional space. Six months after hospitalization, no cases of severe cognitive deficit persisted, and the number of moderate cognitive deficits reduced from 14% to 4%. Most cognitive domains (visuospatial abilities, executive functions, attention, working memory, spatial–temporal orientation) improved over time, except for long-term memory and language skills, which remained reduced or slightly decreased. The Cerebroviz algorithm helps to visualize which brain regions might be involved in the process. Many patients with COVID-19 continue to suffer from a subclinical cognitive deficit, particularly in the memory and language domains. Cerebroviz’s representation of the results provides a new tool for visually representing the data. Full article

Background: Elevated serum IgE has been reported in severe COVID-19, suggesting that mast cell activation, allergic-like responses, and possible viral immune evasion occur. Objective: This study aimed to assess serum IgE, IgG, eosinophils, basophils, IL-10, and IL-33 in COVID-19 patients, and evaluate the infiltration of mast cells, basophils, and plasma cells in fatal cases. Methods: This retrospective study included 21 patients with severe COVID-19 or related respiratory conditions hospitalized in Plovdiv, Bulgaria (February 2020–May 2022). Serum immunoglobulins were quantified via immunoassays; IL-10 and IL-33 were also measured. Lung tissues from 30 autopsies were examined histologically and immunohistochemically using CD117 (mast cells) and CD138 (plasma cells). Results: Elevated IgE (>100 IU/mL) occurred in 10/21 patients, with two patients exhibiting levels exceeding 1000 IU/mL. High IgE correlated with reduced eosinophils and basophils, except in post-COVID lobar pneumonia. IL-10 was significantly increased, while IL-33 was reduced in acute and long COVID. Lung histology showed the accumulation of mast cells and plasma cells (5–20/field) during the diffuse alveolar damage and acute respiratory distress syndrome (ARDS) phases, but not in later fibrotic stages. Basophils are located near capillary basement membranes and the endothelium. Conclusions: SARS-CoV-2 may induce IgE-driven allergic-like mechanisms that contribute to severity. Monitoring IgE and mast cell activity may provide prognostic and therapeutic value, while elevated IgG4 could mitigate the effects of IgE. Full article

Aim: The rationale for combining various extracorporeal blood purification techniques to improve patient outcomes is currently being discussed extensively. The combined use of CytoSorb^®, with high capacity for cytokine removal, and Oxiris^®, which adsorbs endotoxins and smaller cytokines, may enhance the efficacy of blood purification in sepsis. Study Design: Retrospective analysis of efficacy and safety of simultaneous use of CytoSorb^® and Oxiris^® in 12 consecutive critically ill patients with COVID-19, who developed secondary bacterial sepsis and persistent hemodynamic instability. Results: Most of the patients (n = 8) treated with combination of the Oxiris^® and CytoSorb^® had a significant decrease in vasopressor requirement. Pre- and post-haemoadsorption data were analysed in 9 patients, who completed a 24 h course of treatment. A significant decrease in mean SOFA score (16.3 ± 1.7 to 15.0 ± 2.0 points), median vasopressor requirement (0.56 ± 0.29 to 0.11 ± 0.21 µg/kg/min), median procalcitonin levels (6.5 ± 27.0 to 1.6 ± 6.0 ng/mL), median IL-6 levels (584 ± 6279 to 107 ± 571 pg/mL), and mean leucocyte count (36.0 ± 20.6 to 20.9 ± 10.1 × 10³/mL) was observed. Furthermore, there was significant increase in PaO₂/FiO₂ ratio (108 ± 30 to 185 ± 55). We did not observe any device-associated adverse events or technical problems. A 27.5% drop in platelet count (269 ± 116 to 195 ± 82 × 10⁶/mL) and an 11.8% drop in haemoglobin level (10.7 ± 2.9 to 9.5 ± 2.0 g/dL) was noted. Conclusions: Our data suggests that combined use of Oxiris^® and CytoSorb^® for simultaneous cytokine and endotoxin removal in patients with underlying viral infection may be a promising therapeutic option. Our findings may serve as a guide for future research and provide directions for further development in this field. Full article

Background/Objectives: The post-COVID-19 condition frequently includes dysphonia. We aimed to assess objective and subjective voice disorders and short-term responses to multimodal therapy in patients with isolated post-COVID-19 dysphonia. Methods: This retrospective, single-center pre–post study screened 244 post-COVID-19 patients; a subset of 14 with isolated dysphonia underwent standardized assessment at baseline and at 1-month follow-up. Patient-reported outcomes (Voice Handicap Index, VHI; Voice-Related Quality of Life, V-RQOL) and endoscopic evaluation were performed using videolaryngostroboscopy (LVS) and high-speed videoendoscopy (HSV) with kymographic analysis to quantify parameters describing vocal fold oscillations. The treatment included short-term systemic corticosteroids, inhaled corticosteroids, hyaluronic-acid inhalations, and structured voice therapy. Results: At baseline, HSV revealed signs of glottal insufficiency—irregular and asymmetric vocal fold motion, reduced amplitude and pliability, a disrupted mucosal wave, and an increased open quotient. At follow-up, HSV showed increased oscillation, amplitude, and cycle regularity with reduced left–right asymmetry and phase differences; phonovibrograms displayed clearer and more structured patterns. Perturbation indices decreased across jitter and shimmer measures, and the mean fundamental frequency was lower. Improvements in instrumental measures aligned with better VHI and V-RQOL scores. Conclusions: In patients with persistent dysphonia after acute SARS-CoV-2 infection, comprehensive ENT evaluation with instrumental laryngeal assessment is warranted. Short-term multimodal management was associated with improvements in both HSV-derived measures and patient-reported outcomes; confirmation in controlled studies is needed. Full article

The Coronavirus disease 2019 (COVID-19) pandemic had a profound global impact, yet children exhibited distinct clinical and epidemiological patterns compared to adults. Pediatric cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were generally characterized by milder disease, lower hospitalization rates, and few long-term sequelae. However, a subset of children developed severe complications such as multisystem inflammatory syndrome in children (MIS-C), highlighting the heterogeneity in disease presentation. Differences in immune system maturity and comorbidities likely contribute to the age-dependent manifestation of SARS-CoV-2 and other respiratory viruses. Persistent SARS-CoV-2 infection, particularly in immunocompromised individuals, has been implicated in the emergence of new viral variants with immune escape characteristics due to ongoing viral replication in the presence of selective pressure. While SARS-CoV-2 evolution in persistently infected adults has been well-documented, it is less clear how the virus evolves during persistent infection in the pediatric population. To address this question, we performed viral whole genome sequencing of longitudinal specimens collected from immunocompetent and immunocompromised pediatric COVID-19 patients. Similarly to what has been observed in adult cohorts, mutations associated with enhanced viral fitness and immune escape arose intra-host over time. Intra-host diversity accumulated at similar rates in immunocompetent and immunocompromised children, though more mutations overall were observed in the immunocompromised cohort due to the longer infection time courses. Overall, we identified similar viral evolutionary trends over the course of infection despite clinical differences in pediatric COVID-19 manifestation and severity. This similarity suggests that persistent infection in children may be an additional, but not unique, source of ongoing viral diversification. Full article

Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments (“brain fog”), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4⁺ and CD8⁺ T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC. Full article

Türkiye’s role in the global lemon trade was evaluated using the Constant Market Share (CMS) method to assess changes in export competitiveness across major destination markets. The CMS framework decomposes export performance into three components—market share effect, commodity composition effect, and commodity adaptation effect—which, respectively, represent competitiveness, product–market alignment, and structural responsiveness. Trade data for the ten largest importing countries, representing over 80% of Türkiye’s lemon exports, were analyzed to identify the drivers of export growth and structural change. Results show a sharp decline in competitiveness during the COVID-19 disruption, followed by a partial recovery in markets such as Iraq, Poland, Russia, and Azerbaijan. Persistent structural rigidities were identified in several Eastern European and Gulf markets, indicating limited responsiveness to shifting import demand. The findings highlight the need for flexible production systems, improved alignment of export structures with market requirements, and strategic partnerships to sustain long-term competitiveness in the global citrus sector. Full article

The importance of policy coordination between fiscal and monetary policy authorities has become more apparent, in the face of unexpected economic shocks and persistent macroeconomic challenges. In this paper, we employ the Set-Theoretic Approach (STA) to explicitly measure the presence of coordination between fiscal and monetary policies from 1990 to 2023 in South Africa. In addition, the model measures policy shocks theoretically and structurally using a structural vector autoregressive (SVAR) model. The results indicate a weak level of policy coordination estimated at 24% where shocks are measured theoretically. Where shocks are measured structurally, the results still present weak policy coordination estimated at 33%. These results underscore the need for stronger policy coordination in South Africa, particularly during periods of economic strain such as the Global Financial Crisis and the COVID-19 pandemic, when conflicting fiscal and monetary stances weakened policy effectiveness. In the South African case, limited coordination contributed to procyclical fiscal tightening alongside contractionary monetary policy, which constrained growth and delayed recovery. Full article