Search Results (29,722)

Host innate immunity is crucial for orchestrating a protective response against dangerous pathogens. Herein, we demonstrate that interferon-inducible protein (IFI204), a DNA sensor, is implicated in protection against pulmonary pathogenic Mannheimia haemolytica (M. haemolytica) infection by driving inflammasome signaling activation. Ifi204^−/− mice are more susceptible to pathogenic M. haemolytica infection compared with their wild-type (WT) counterparts, with decreased survival rates, extensive lung architecture destruction, exacerbated inflammatory cells infiltration, and more bacterial colonization. In vivo and in vitro findings elucidate that Ifi204 deficiency leads to a defect in inflammasome signaling activation, and exogenous recombinant IL-18 is sufficient to rescue the susceptibility of Ifi204^−/− mice. Inflammasome signaling downstream of IFI204 facilitates early bacterial killing and clearance. Mechanistically, IFI204 promotes gasdermin D (GSDMD)-dependent inflammasome activation, and GSDMD is required for IFI204-mediated host defense. Notably, IFI204 detects pathogenic M. haemolytica-derived genomic DNA for the inflammasome signaling response. Thus, these data highlight the requirement of IFI204 in host defense response to M. haemolytica infection, and reveal that IFI204 may be a potential therapeutic target for pathogen control. Full article

Background: Little is known about women’s contraceptive use in the United States during the novel coronavirus (“COVID-19”) pandemic and the risk of unintended pregnancy. Methods: We compared the weighted response rates on contraception use for female respondents aged 18–44 from the Behavioral Risk Factor Surveillance System (BRFSS) between 2019 and 2022. Results: Our study reveals a significant increase of 16.1% (CI = 0.145,0.177) in the proportion of women using contraception in 2022 as compared to 2019. The largest increase in the use of non-reversible contraception was seen in the proportion of female sterilization, at 3.0% (CI = 0.017, 0.043), mostly attributed to non-Hispanic Black individuals with a 12% increase (CI = 0.046, 0.198). The largest decrease was seen in the use of condoms, at 7.4% (CI = −0.094, −0.055). This was driven by both non-Hispanic Black and multiracial groups, each experiencing a 19% decrease (CI = −0.251, −0.127; CI = −0.304, −0.068, respectively). The proportion of women at risk of unintended pregnancy increased by 3.7% (CI = 0.010, 0.063). These increases were observed among those with an income of less than USD 15k, showing a 14.9% increase (CI = 0.037, 0.262). Older females and those with Medicaid insurance were more likely to use female sterilization. Hispanics, college graduates, and those with Medicaid insurance were more likely to use condoms. Non-White females and those without annual checkups were more at risk of unintended pregnancy. Conclusions: Contraceptive methods shifted among females with slightly increased sterilization in the years 2019 to 2022. Full article

Background: Ampullary cancer is a rare biliary tract cancer arising from one of the three epithelial tissues in the region. Leveraging a large patient-level genomic database, this study aims to identify, explore, and describe the genetic landscape of ampullary carcinoma and its implications. Methods: A retrospective analysis of ampullary cancer samples was conducted using the AACR Project GENIE database. Analysis of recurrent somatic mutations at large and between patient populations, and co-occurrence and mutual exclusivity of mutations was conducted, with a p-value < 0.05. Results: The most frequent mutations were identified as TP53 (53.2%), KRAS (46.6%), and SMAD4 (16.6%). Mutational differences were noted between sexes, White vs. Non-white groups, and histopathological subtypes. Significant mutual exclusivity was found between KRAS and ERBB2. Co-occurrence was observed in the ARID1A mutation with KMT2D, ERBB2, and PIK3CA; CDKN2A with the SMAD4 and KRAS mutations; TP53 mutation with the CTNNB1 mutation; and KRAS co-occurred with an APC mutation. Reduced survival rates were seen in populations with the TP53 or KRAS mutation. Conclusions: This study provides a detailed descriptive genomic landscape of ampullary carcinoma, highlighting frequent mutations between patient groups and the mutational burden of the DNA damage response pathway in ampullary cancer, laying important groundwork for the development of therapeutic targets and more individualized treatment regimens. Full article

Background/Objectives: Response inhibition, a core aspect of executive function, is commonly evaluated using the Go/NoGo task. While previous research has demonstrated that short-term practice can influence both behavioral and neural markers of response inhibition, the role of task difficulty—particularly when manipulated through short interstimulus intervals (ISIs)—remains underexplored. This study investigated the effects of short-term repeated practice on behavioral performance and neural activity during a high-difficulty Go/NoGo task with a short ISI. Methods: Fifteen healthy young adults completed a visual Go/NoGo task in four repeated sessions within a single day. The task involved a 600 ms ISI, 100 ms stimulus duration, and a 20% NoGo stimulus frequency. Behavioral outcomes included response time (RT) and error rate (ER). Neural activity was recorded via electroencephalography (EEG), focusing on event-related potentials (ERPs) associated with response inhibition, specifically the NoGo-N2 and NoGo-P3 components. Results: No significant changes were observed in RT or ER across sessions, indicating no improvement in behavioral performance. Similarly, NoGo-N2 amplitudes remained stable. However, a significant reduction in NoGo-P3 amplitude at the Fz electrode was found in later sessions, suggesting decreased frontal cortical engagement in response inhibition. Conclusions: Although short-term repeated practice of a high-difficulty Go/NoGo task did not enhance behavioral performance, it was associated with reduced neural activity related to response inhibition. These findings suggest that neurophysiological adaptations may occur even in the absence of observable behavioral changes, particularly under high task demands. Full article

Cancer survivors (CS) constitute an expanding population with underrecognized cardiometabolic risk. Despite substantial improvements in five-year survival rates, both childhood and adult survivors remain at high risk for premature morbidity and mortality. These risks are particularly pronounced following exposure to anthracyclines and/or chest radiotherapy, typically in a dose-dependent manner. In Chile, the establishment of the National Pediatric Antineoplastic Drug Program (PINDA) in 1998 marked a milestone in improving equitable access to high-quality pediatric oncology care through evidence-based treatment protocols across the public health system; the adult counterpart (PANDA) has developed diagnostic, treatment, and monitoring protocols for hematological neoplasms. Few prospective cohort or mechanistic studies have clarified risk stratification or surveillance strategies in survivor populations. The regulated, short-term activation of inflammation and innate immunity can be an adaptive and protective response to tissue injury, whereas persistent low-grade inflammation may trigger neutrophil extracellular traps formation (NETosis) and other maladaptive pathways that accelerate endothelial injury, thrombosis, and adverse cardiovascular remodeling. NETosis represents a putative immunomodulatory target for therapeutic immunomodulation in heart failure and maladaptive left ventricular remodeling in preclinical models. Concurrently, skeletal muscle-derived and hormonal mediators known as exerkines—together with increased NET activity—may modulate the pathophysiology of chronic cardiometabolic disease and contribute to cancer progression, particularly in the context of obesity, diabetes, and insulin resistance. Structured exercise is a promising non-pharmacological intervention that modulates inflammatory and metabolic pathways and may thereby help prevent non-communicable diseases, including cancer. We synthesize basic and clinical evidence to (1) define how cancer therapies promote low-grade inflammation and NETosis; (2) describe how exerkines and structured exercise influence cardiometabolic biology; and (3) evaluate exercise as a mechanistic and clinically pragmatic strategy to reduce long-term CVD risk in pediatric and adult CS. Full article

Purpose: This study investigates how South Africa’s sectoral stock market performance responds to monetary and fiscal policy shifts across two macroeconomic regimes: the pre-inflation targeting (Pre-IT) and the inflation targeting (IT) periods. Design/methodology/approach: Employing a Markov Switching Dynamic Regression (MS-DR) model, the paper explores non-linear and state-dependent relationships between policy instruments (interest rate, money supply, government expenditure, tax revenue, exchange rate, and inflation) and the performance of the industrial, financial, and resource sectors. Findings: The results reveal regime- and sector-specific heterogeneities. In the Pre-IT era, monetary policy exhibited stronger contractionary effects, while fiscal policy had mixed impacts. Under IT, sectoral responses were moderated, with inflation stability supporting industrial and financial sectors during expansions but dampening resource sector performance in recessions. Practical implications: The findings highlight the need for sector-specific and state-contingent policy designs to enhance macroeconomic stability and inclusive growth. Industrial and resource sectors, being more labour-intensive, require tailored support during downturns. Originality/value: This paper contributes to the literature by providing novel evidence on how structural changes in policy regimes affect the transmission of macroeconomic policies to different stock market sectors in South Africa. Full article

Background: The purpose of this study was to evaluate the effects of a structured barefoot walking program on menopausal symptoms, sleep quality, stress, and quality of life in middle-aged women experiencing menopausal symptoms. Methods: A quasi-experimental design with a nonequivalent control group and pretest-posttest was used. Community-dwelling women aged 45 to 65 years residing in Wonju, Republic of Korea, were recruited and assigned to either an experimental (n = 29) or control group (n = 31). The intervention consisted of 12 weeks of barefoot walking (three times per week, 60 min per session). Outcome measures included the Menopause Rating Scale (MRS), Verran and Snyder–Halpern Sleep Scale, Stress Response Inventory, and WHOQOL-BREF. In addition, changes in participants’ body composition before and after the intervention were assessed using a bioelectrical impedance analyzer (InBody 770). Data were analyzed using the Mann–Whitney U test, repeated measures ANOVA, ANCOVA, and other relevant statistical methods, with the level of significance set at p < 0.05. Results: Compared with the control group, the experimental group showed significant improvements in menopausal symptoms (z = −5.59, p < 0.001), stress (z = −3.58, p < 0.001), and quality of life (z = −3.47, p = 0.001). A significant time-by-group interaction effect was observed for sleep quality (F = 7.53, p = 0.008). No significant changes were found in body composition. Conclusion: Barefoot walking represents a promising, low-cost, community-based intervention for alleviating menopausal symptoms, enhancing sleep quality, reducing stress and improving quality of life in middle-aged women experiencing menopausal symptoms. Further randomized controlled trials are warranted to confirm these findings. Full article

The wound healing (WH) process is often severely hindered by bacterial infections and prolonged inflammatory responses. To address this problem, we developed a novel injectable nanocomposite DPB-ODQ hydrogel, which comprises polydopamine-modified Prussian blue nanoparticles (PB@PDA, also called DPB) and an oxidized dextran/quaternized chitosan (QCS)-based Schiff-base network. This hydrogel possesses a highly interconnected porous structure, an excellent swelling rate (730%), rapid gelling speed (45 s), a high mass retention rate over a three-day period (73.20%), and exceptional self-healing properties. Based on the presence of PDA and the Schiff base, it also exhibited good adhesive strength (13.5 kPa). In addition, under near-infrared irradiation at 1.0 W/cm², temperatures increased by more than 35 °C within 5 min, indicating excellent photothermal (PT) performance. The PT performance of DPB, synergized with the inherent antibacterial properties of QCS, endowed it with a bactericidal rate exceeding 96% against both Staphylococcus aureus and Escherichia coli. In vitro cell experiments have shown that it significantly promoted fibroblast proliferation and migration. In experiments involving mice infected with S. aureus, DPB-ODQ demonstrated an impressive WH rate of 92.82%, greatly promoting collagen deposition. Full article

Some special volatile organic compounds (VOCs) that significantly induce female oviposition preferences may be utilized to disrupt oviposition behavior and to enhance trapping strategies; such approaches offer a promising avenue for reducing insect infestations in stored commodities. Based on the significant differences in the oviposition preference of P. interpunctella among six normal-oleic varieties (NOPs), the key VOCs involved were further explored. Seventeen VOCs that may contribute the oviposition preference and that exhibited a high content in the peanut varieties were measured through electroantennogram (EAG) response measurements of female moths. The VOCs that produced significant EAG responses by the females were further assayed for behavioral responses by the Y-tube olfactometer method, wind tunnel tests, and a multiple-choice device for female oviposition. Heptanal, acetophenone, nonanal, hexanal, benzaldehyde, octanal, hexanoic acid, decanal, phenylacetaldehyde, and 1-octen-3-ol from peanuts elicited strong antennal EAG responses. These VOCs (especially heptanal, nonanal, hexanal, octanal, and decanal) attracted more females in both Y-tube olfactometer and wind tunnel assays and increased oviposition rates in oviposition tests. The results indicate that heptanal, decanal, octanal, nonanal, and hexanal may be utilized to develop oviposition attractants for female moths further. Full article

Background and Objectives: This systematic review aimed to analyze published peer-reviewed studies on the effects of exergaming (EXG) compared to conventional physical exercise (CPE) interventions on health status in older people with Parkinson’s disease (PD) according to training dose. Materials and Methods: Using six generic databases: PubMed, EBSCO, Medline, CINAHL Complete, Scopus, and Web of Science, the PRISMA, TESTEX, RoB 2, and GRADE tools assessed methodological quality and certainty. The protocol was registered in PROSPERO (code: CRD42024575969). Results: Out of 805 records, 14 randomized controlled trials with 406 older people with PD were included. Seven overall meta-analyses showed significant improvements (p < 0.01) in favor of EXG in the Berg Balance Scale (BBS, ES = 0.90), Dynamic Gait Index (DGI, ES = 0.77) and quality of life questionnaire (PDQ-39, ES = 0.52), without significant improvements (p > 0.05) in the Unified PD Rating Scale, Montreal Cognitive Assessment, Timed Up-and-Go and Falls Efficacy Scale-International. Four subgroup meta-analyses, according to training schedules, showed that there were significant improvements (p < 0.05) in BBS in favor of EXG at >8 weeks of training (ES = 1.38), >3 weeks per week (ES = 1.18), <45 min duration (ES = 0.99), and with >20 total sessions (ES = 1.31). Both weeks and total sessions were predictors of BBS performance in EXG interventions in older people with PD. Conclusions: EXG is an innovative alternative to improve the health status in balance, gait, and quality of life variables in older people with PD, with a high potential for clinical practice in this population. The training dose is a determinant (weeks and total sessions) that varies the response to intervention in the BBS. Full article

Background: The COVID-19 pandemic disrupted healthcare systems, disproportionately affecting individuals with rare diseases. This study explores the health-related quality of life and financial burden in the post-pandemic context among children with Duchenne Muscular Dystrophy and their families in Greece, providing insights into health system performance. Methods: A multicenter, cross-sectional study was conducted in two neuromuscular clinics in Greece. Fifty families (response rate 67%) completed standardized quality of life instruments (PedsQL™ 4.0 Generic Core Scale; PedsQL™ 3.0 DMD Module) and a socioeconomic questionnaire. Descriptive and correlation analyses assessed associations between functional status, financial strain, and psychosocial indicators. Results: Children with Duchenne Muscular Dystrophy reported moderate-to-severe reductions in physical and emotional well-being, and substantial out-of-pocket expenditures. Families with greater financial strain or wheelchair-dependent children had significantly lower health-related quality of life scores. Insurance coverage was positively associated with emotional and psychosocial functioning. Conclusions: Greek families living with Duchenne Muscular Dystrophy continue to face significant financial and psychosocial challenges in the post-pandemic period. While the cross-sectional design does not allow causal attribute to COVID-19 pandemic, the results underscore the need to strengthen financial protection, coordinated multidisciplinary care, and equitable access to support services for rare disease management. Full article

This work presents a mixed reality application for drum learning that combines the PocketDrum virtual drumming device with the Meta Quest 3 headset, integrating hand tracking to provide an immersive, responsive experience without the need for a physical drum set. The system features a modular architecture for real-time strike detection, visual guidance synchronized with music, spatial calibration, and audio rendering. The system additionally makes use of the headset’s color Passthrough during the calibration stage to align the virtual drum kit with the player’s position. To evaluate the system’s performance, a technical analysis was conducted to measure latency, jitter, and sampling rate across the technologies involved. Additionally, a functional validation experiment assessed how spatial hand tracking from Meta Quest 3 improved PocketDrum’s classification accuracy. Results showed that the fused system corrected 19.1% of drum assignment errors made by the inertial-only setup, enhancing consistency in complex rhythmic patterns. These findings demonstrate the effectiveness of sensor fusion for immersive percussion training and support its potential use in accessible, feedback-rich musical learning environments. Full article

Background: Limited real-world data (RWD) may provide important information regarding diagnostic and treatment patterns in patients (pts) with AL Amyloidosis. The aim was to analyze the characteristics, treatment approach and clinical outcome of patients in the real-world settings. Materials and Methods: RWD of 60 pts diagnosed with AL amyloidosis were analyzed. Advanced cardiac involvement, Mayo Clinical Stage (CS) IIIa and IIIb, and Revised-Mayo CS III and IV, has been found in 26.7%, and 16.7%, or 33.3% and 16.7%, respectively. Bortezomib (Bz)-based regimens were applied in 36 pts (60%), and alkylating-based regimens in 24 pts (40%). In 8 pts (13.3%) treated initially with CyBorD induction, high-dose therapy with Melphalan and autologous stem cell transplantation (HDT + ASCT) was applied as the first line of treatment. Results: The overall response rate (ORR, ≥partial response) was achieved in 40 pts (70%). Patients treated with Bz-based induction followed by HDT + ASCT achieved significantly better hematologic (p = 0.001), cardiac (p = 0.004) and renal response rates (p = 0.002) in comparison to CyBorD or Alk-based regimens alone. There was no difference in PFS between those groups (p = 0.733), but patients treated with CyBorD + HDT + ASCT had significantly durable OS (p = 0.039). Univariate analysis pointed out the predictive influence of cardiac involvement (Mayo CS and Revised Mayo CS), ASCT eligibility, and hematologic, cardiac, renal and composite response rates. Conclusions: Advanced cardiac involvement and cardiac and hematologic response still retain adverse prognostic impact on the clinical outcome. Bz-based combinations significantly improved the survival of patients with AL amyloidosis, regardless of HDT + ASCT treatment. Full article

The curative management of localized esophageal and esophagogastric junction (EGJ) cancers has undergone major changes over the past decade, shaped by multimodal strategies integrating chemotherapy, chemoradiotherapy, surgery, and more recently, immunotherapy. For esophageal squamous cell carcinoma (SCC), neoadjuvant or definitive chemoradiotherapy remains the standard of care in Western countries. In contrast, for adenocarcinoma (AC) of the esophagus and EGJ, perioperative chemotherapy has emerged as the preferred strategy. Despite these advances, long-term outcomes remain suboptimal, and recurrence continues to pose a major challenge, highlighting the need to optimize patient selection and treatment sequencing. The integration of immunotherapy in the perioperative or adjuvant setting has recently led to improvements in surrogate endpoints yet overall survival benefit remains under investigation. For patients with tumors harboring microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), checkpoint inhibitors show exceptional activity, and non-operative management may be feasible in select cases. Conversely, human epidermal growth receptor 2 (HER2)-targeted strategies, although effective in metastatic disease, have not yet translated into practice-changing benefit in the curative setting. The role of circulating tumor deoxyribo nucleic acid (DNA) and functional imaging as real-time tools to assess response and guide treatment adaptation is also being actively explored. This review provides a comprehensive overview of current standards, ongoing developments, and future directions for the treatment of localized esophageal and EGJ cancers, with a focus on emerging personalization strategies and biomarker-driven approaches aimed at improving cure rates and minimizing treatment-related morbidity. Full article

Background/Objectives: Proficiency in moral reasoning is essential for healthcare providers to successfully navigate ethically challenging decision-making. It is critical that student dentists about to enter practice have well-developed moral reasoning skills to ensure optimal patient care. The aim of the present study was to investigate the moral reasoning ability of students undertaking their final year of the undergraduate Bachelor of Dental Surgery (BDS) programme at the University of Adelaide (UofA) in Australia. Methods: Sixty-six final-year BDS students were invited to participate in an e-survey which included the Defined Issues Test 2 (DIT-2), a validated instrument for measuring moral reasoning. Calculated DIT-2 scores incorporatedthe postconventional (P) score and N2 score. Data analysis of demographic details and scores related to the DIT-2 included the use of t-tests, Mann–Whitney and the Spearman rank correlation coefficient tests. Results: A response rate of 45.5% (n = 30) was recorded. The mean (95% CI) P and N2 scores were 37.80 (32.04, 43.56) and 42.12 (37.72, 46.53), respectively. Scores for females and for those who had undertaken the majority of their pre-BDS studies outside of Australia and New Zealand were higher, but the differences were not statistically significant (p > 0.05). A Spearman Correlation Coefficient test indicated that age was moderately associated (r = 0.41; 95% CI: 0.01, 0.65; p = 0.04) with N2 scores. Conclusions: Moral reasoning scores were comparable to studies among similar cohorts conducted in other countries but were less than the scores considered optimal for a healthcare provider to proficiently manage challenges to ethical decision-making. Consideration should be given to the introduction of appropriate formal training in ethics to better manage these challenges. Full article