Search Results (497)

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Floods are among the most devastating hydrometeorological natural disasters worldwide, causing massive infrastructure and economic loss in low-lying, flood-prone developing countries like Bangladesh. Effective disaster mitigation relies on organized and detailed flood damage information to facilitate emergency evacuation, coordinate relief distribution, and formulate an effective disaster management policy. Nevertheless, the nation confronts considerable obstacles due to insufficient historical flood damage data and the underdevelopment of near-real-time (NRT) flood monitoring systems. This study addresses this issue by developing a replicable methodology for flood damage assessment and NRT monitoring systems. Using the Google Earth Engine (GEE) platform, we analyzed flood events from 2019 to 2023, integrating geospatial layers such as roads, cropland, etc. Analysis of flood events over the five-year period revealed substantial impacts, with 21.60% of the total area experiencing inundation. This flooding affected 6.92% of cropland and 4.16% of the population. Furthermore, 18.10% of the road network, spanning over 21,000 km within the study area, was also affected. This system has the potential to enhance emergency response capabilities during flood events and inform more effective disaster mitigation policies. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier dysfunction, oxidative stress (OS), and neuroinflammation. Current treatments provide symptomatic relief, but do not halt the disease’s progression. OS plays a crucial role in AD pathogenesis by promoting Aβ accumulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the antioxidant response, influencing genes involved in OS mitigation, mitochondrial function, and inflammation. Dysregulation of NRF2 is implicated in AD, making it a promising therapeutic target. Emerging evidence suggests that adherence to a Mediterranean diet (MD), which is particularly rich in polyphenols from extra virgin olive oil (EVOO), is associated with improved cognitive function and a reduced risk of mild cognitive impairment. Polyphenols can activate NRF2, enhancing endogenous antioxidant defenses. This study employs a computational approach to explore the potential of bioactive compounds in EVOO to modulate NRF2-related pathways in AD. We analyzed transcriptomic data from AD and EVOO-treated samples to identify NRF2-associated genes, and used chemical structure-based analysis to compare EVOO’s bioactive compounds with known NRF2 activators. Enrichment analysis was performed to identify common biological functions between NRF2-, EVOO-, and AD-related pathways. Our findings highlight important factors and biological functions that provide new insight into the molecular mechanisms through which EVOO consumption might influence cellular pathways associated with AD via modulation of the NRF2 pathway. The presented approach provides a different perspective in the discovery of compounds that may contribute to neuroprotective mechanisms in the context of AD. Full article

Irritable bowel syndrome (IBS) is a gut–brain axis chronic disorder, characterized by recurrent abdominal pain and altered bowel habits in the absence of organic pathology. Nutrition plays a central role in symptom management, yet no single dietary strategy has demonstrated universal effectiveness. This narrative review critically evaluates current nutritional approaches to IBS. The low-Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAP) diet is the most extensively studied and provides short-term symptom relief, but its long-term effects on microbiota diversity remain concerning. The Mediterranean diet, due to its anti-inflammatory and prebiotic properties, offers a sustainable, microbiota-friendly option; however, it has specific limitations in the context of IBS, particularly due to the adverse effects of certain FODMAP-rich foods. A gluten-free diet may benefit individuals with suspected non-celiac gluten sensitivity, although improvements are often attributed to fructan restriction and placebo and nocebo effects. Lactose-free diets are effective in patients with documented lactose intolerance, while a high-soluble-fiber diet is beneficial for constipation-predominant IBS. IgG-based elimination diets are emerging but remain controversial and require further validation. In this review, we present the 10 dietary commandments for IBS, pragmatic and easily retained recommendations. It advocates a personalized, flexible, and multidisciplinary management approach, avoiding rigidity and standardized protocols, with the aim of optimizing adherence, symptom mitigation, and health-related quality of life. Future research should aim to evaluate, in real-world clinical settings, the impact and applicability of the 10 dietary commandments for IBS in terms of symptom improvement and quality of life Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases. Full article

Background/Objectives: Tension-type headache (TTH) is the most prevalent form of primary headache. The etiology of TTH is not yet fully understood, although it is associated with the presence of myofascial trigger points (MTPs) in cervical and facial muscles. Dry needling (DN) therapy has emerged as an effective and safe non-pharmacological option for pain relief, but there are a lack of systematic reviews focused on its specific characteristics in TTH. The aim of this paper is to examine the characteristics and methodologies of DN in managing TTH. Methods: A scoping review was conducted with inclusion criteria considering studies that evaluated DN interventions in adults with TTH, reporting target muscles, diagnostic criteria, and technical features. The search was performed using PubMed, Embase, Scopus, and the Web of Science, resulting in the selection of seven studies after a rigorous filtering and evaluation process. Results: The included studies, primarily randomized controlled trials, involved a total of 309 participants. The most frequently treated muscles were the temporalis and trapezius. Identification of MTPs was mainly performed through manual palpation, although diagnostic criteria varied. DN interventions differed in technique. All studies included indicated favorable outcomes with improvements in headache symptoms. No serious adverse effects were reported, suggesting that the technique is safe. However, heterogeneity in protocols and diagnostic criteria limits the comparability of results. Conclusions: The evidence supports the use of DN in key muscles such as the temporalis and trapezius for managing TTH, although the diversity in methodologies and diagnostic criteria highlights the need for standardization. The safety profile of the method is favorable, but further research is necessary to define optimal protocols and improve reproducibility. Implementing objective diagnostic criteria and uniform protocols will facilitate advances in clinical practice and future research, ultimately optimizing outcomes for patients with TTH. Full article

Land cover, topography, precipitation, and socio-economic factors exert both direct and indirect influences on urban land surface temperatures. Within the broader context of global climate change, these influences are magnified by the escalating intensity of the urban heat island effect. However, the interplay and underlying mechanisms of natural and socio-economic determinants of land surface temperatures remain inadequately explored, particularly in the context of cold-region cities located in the northern temperate zone of China. This study focuses on Changchun City, employing multispectral remote sensing imagery to derive and spatially map the distribution of land surface temperatures and topographic attributes. Through comprehensive analysis, the research identifies the principal drivers of temperature variations and delineates their seasonal dynamics. The findings indicate that population density, night-time light intensity, land use, GDP (Gross Domestic Product), relief, and elevation exhibit positive correlations with land surface temperature, whereas slope demonstrates a negative correlation. Among natural factors, the correlations of slope, relief, and elevation with land surface temperature are comparatively weak, with determination coefficients (R²) consistently below 0.15. In contrast, socio-economic factors exert a more pronounced influence, ranked as follows: population density (R² = 0.4316) > GDP (R² = 0.2493) > night-time light intensity (R² = 0.1626). The overall hierarchy of the impact of individual factors on the temperature model, from strongest to weakest, is as follows: population, night-time light intensity, land use, GDP, slope, relief, and elevation. In examining Changchun and analogous cold-region cities within the northern temperate zone, the research underscores that socio-economic factors substantially outweigh natural determinants in shaping urban land surface temperatures. Notably, human activities catalyzed by population growth emerge as the most influential factor, profoundly reshaping the urban thermal landscape. These activities not only directly escalate anthropogenic heat emissions, but also alter land cover compositions, thereby undermining natural cooling mechanisms and exacerbating the urban heat island phenomenon. Full article

This paper proposes a GNSS-compatible method for characterizing the motion of UAV-based navigation enhancement platforms, designed to provide reliable navigation and positioning services in emergency scenarios where GNSS signals are unavailable or severely degraded. The method maps UAV trajectories into standard GNSS navigation messages by establishing a correspondence between ephemeris parameters and platform positions through coordinate transformation and Taylor series expansion. To address modeling inaccuracies, the approach incorporates truncation error analysis and motion-assumption compensation via parameter optimization. This design enables UAV-mounted pseudolite systems to broadcast GNSS-compatible signals without modifying existing receivers, significantly enhancing rapid deployment capabilities in complex or degraded environments. Simulation results confirm precise positional representation in static scenarios and robust error control under dynamic motion through higher-order modeling and optimized broadcast strategies. UAV flight tests demonstrated a theoretical maximum error of 0.4262 m and an actual maximum error of 3.1878 m under real-world disturbances, which is within operational limits. Additional experiments confirmed successful message parsing with standard GNSS receivers. The proposed method offers a lightweight, interoperable solution for integrating UAV platforms into GNSS-enhanced positioning systems, supporting timely and accurate navigation services in emergency and disaster relief operations. Full article

Integrating blockchain into healthcare devices offers the potential for improved data control but faces significant usability and acceptance challenges. This study addresses this gap by evaluating CipherPal, an improved blockchain-enabled Smart Fidget Toy prototype, using a multi-framework approach to understand the interplay between technology, design, and user experience. We synthesized insights from three complementary frameworks: an expert review assessing adherence to Web3 Design Guidelines, a User Acceptance Toolkit assessment with professionals based on UTAUT2, and an extended three-day user testing study. The findings revealed that users valued CipherPal’s satisfying tactile interaction and perceived benefits for well-being, such as stress relief. However, significant usability barriers emerged, primarily related to challenging device–application connectivity and data synchronization. The multi-framework approach proved valuable in revealing these core tensions. While the device was conceptually accepted, the blockchain integration added significant interaction friction that overshadowed its potential benefits during the study. This research underscores the critical need for user-centered design in health-related blockchain applications, emphasizing that seamless usability and abstracting technical complexity are paramount for adoption. Full article

Earthquakes are sudden and highly destructive events that severely disrupt infrastructure and logistics systems, making accurate and timely emergency material demand forecasting a critical challenge in disaster response. However, the scarcity of reliable data during the early stages of an earthquake limits the effectiveness of traditional forecasting methods. To address this issue, this study proposes a hybrid forecasting framework that integrates the Grey Model (GM(1,1)) with Bayesian Dynamic Linear Models (BDLMs), aiming to improve both the accuracy and adaptability of demand predictions. The approach operates in two phases: first, GM(1,1) generates preliminary forecasts using limited initial observations; second, BDLMs dynamically update these forecasts in real time as new data become available. The model is validated through a case study of the 2010 M7.1 Yushu earthquake in Qinghai Province, China. The results indicate that the hybrid method produces reliable forecasts even at the earliest stages of the disaster, with increasing accuracy as more observational data are incorporated. Our case study demonstrates that the integrated GM(1,1)-BDLM framework substantially reduces prediction errors compared to standalone GM(1,1). Using the first five days’ data to forecast fatalities and emergency material demand for days 6–10, the hybrid model achieves a 4.01% error rate—a 19.62 percentage point improvement over GM(1,1)’s 23.63% error rate. This adaptive forecasting mechanism offers robust support for evidence-based decision-making in emergency material allocation, enhancing the efficiency and responsiveness of post-disaster relief operations. Full article

As part of the post-conflict reconstruction and recovery, the development of Kabul New City aims to bring relief to the existing capital city, Kabul, which has experienced exponential population growth, putting heavy pressure on its existing resources. Kabul New City is divided into four subsectors, and each of them is being developed and is expected to reach a target population by 2025, as defined by the master plan. The study’s objective is to determine which of the four zones are in demand and need to be prioritized for development, as per the model results. The data collection involves an online questionnaire, and the responses are collected from residents of Kabul and Herat. Agent-based modeling (ABM) is an emerging method of simulating urban dynamics. Cities are evolving continuously and are forming unique spatial patterns that result from the movement of residents in search of new locations that accommodate their needs and preferences. An agent-based model is developed using the weighted random selection process based on household size and income levels. The agents are the residents of Kabul and Herat, and the environment is the land use classification image using the Sentinel 2 image of Kabul New City. The barren class is treated as the developable area and is divided into four sub-sectors. The model simulates three alternative growth rate scenarios, i.e., ambitious, moderate, and steady. The results of the simulation reveal that the sub-sector Dehsabz South, being closer to Kabul city, is in higher demand. Barikab is another sub-sector high in demand, which has connectivity through the highway and is an upcoming industrial hub. Full article

Menopause is characterized by a decline in estrogen levels, leading to symptoms such as vasomotor instability, osteoporosis, and increased cardiovascular and cognitive risk. Hormone replacement therapy (HRT) remains the gold standard for managing menopausal symptoms; however, concerns regarding its long-term safety, including elevated risks of cancer and cardiovascular events, have prompted interest in alternative therapies. Phytoestrogens, particularly the isoflavones daidzein and genistein, are plant-derived compounds structurally similar to 17β-estradiol (E2) and capable of binding estrogen receptors. Found abundantly in soybeans and red clover, these compounds exhibit selective estrogen receptor modulator (SERM)-like activity, favoring ERβ over ERα, which underlies their tissue-specific effects. In vitro, in silico, and in vivo studies demonstrate their ability to modulate estrogenic pathways, inhibit oxidative stress, and influence reproductive and neurological function. Clinical trials show that daidzein and genistein, especially in equol-producing individuals, can reduce vasomotor symptoms such as hot flashes and night sweats. While results across studies vary, consistent findings support their safety and modest efficacy, particularly for women unable or unwilling to use HRT. Pharmacokinetic studies reveal moderate bioavailability and interindividual variability due to gut microbiota metabolism. At dietary levels, these compounds are generally safe, although high-dose supplementation is discouraged in individuals with hormone-sensitive cancers. Emerging evidence suggests lifelong consumption of soy-based foods may reduce cancer risk. In conclusion, daidzein and genistein represent promising, well-tolerated natural alternatives to conventional HRT, offering symptom relief and additional health benefits. Further research is warranted to optimize dosing, improve clinical outcomes, and clarify long-term safety in diverse populations, particularly with genetic variations in isoflavone metabolism. Full article

Background and Objective: Benign prostatic hyperplasia (BPH) and urethral stricture (US) are common causes of lower urinary tract symptoms in ageing men, often requiring repeated interventions. Conventional treatments of US, such as urethrotomy and mechanical dilation, have high recurrence rates. The Optilume drug-coated balloon catheter system, which combines mechanical dilation with paclitaxel delivery, has emerged as a minimally invasive alternative. This systematic review assesses its efficacy and safety in the management of BPH and US. Methods: A systematic search of PubMed was conducted for studies published between August 2020 and October 2023. Eligible studies included randomised controlled trials (RCTs), cohort studies, and case reports evaluating Optilume’s therapeutic effects. Key outcomes analysed included symptom relief, urinary flow improvement, recurrence rates, and adverse events. Results: Seven studies met the inclusion criteria, including five on US and two on BPH. The ROBUST trial series demonstrated sustained improvements in urinary flow rates and symptom scores in US patients over follow-up periods of up to four years. The EVEREST-1 and PINNACLE trials reported significant symptom relief and preserved sexual function in BPH patients, with a favourable safety profile and minimal complications. Conclusions: Optilume appears to be a promising alternative to conventional endoscopic treatments for US and BPH, offering durable symptom relief with a low complication rate. Further long-term studies are required to confirm its efficacy and cost-effectiveness in routine clinical practice. Full article

Neuropathic pain is a significant global clinical issue that poses substantial challenges to both public health and the economy due to its complex underlying mechanisms. It has emerged as a serious health concern worldwide. Recent studies involving dorsal root ganglion (DRG) stimulation have provided strong evidence supporting its effectiveness in alleviating chronic pain and its potential for sustaining long-term pain relief. In addition to that, there has been ongoing research with clinical evidence relating to the role of small non-coding ribonucleic acids known as microRNAs in regulating gene expressions affecting pain signals. The signal pathway involves alterations in neuronal excitation, synaptic transmission, dysregulated signaling, and subsequent pro-inflammatory response activation and pain development. When microRNAs are dysregulated in the dorsal root ganglia neurons, they polarize macrophages from anti-inflammatory M2 to inflammatory M1 macrophages causing pain signal generation. By reversing this polarization, a therapeutic activity can be induced. However, the direct delivery of these nucleotides has been challenging due to limitations such as rapid clearance, degradation, and reduction in half-life. Therefore, safe and efficient carrier vehicles are fundamental for microRNA delivery. Here, we present a comprehensive analysis of miRNA-based nano-systems for chronic neuropathic pain, focusing on their impact in dorsal root ganglia. This review provides a critical evaluation of various delivery platforms, including viral, polymeric, lipid-based, and inorganic nanocarriers, emphasizing their therapeutic potential as well as their limitations in the treatment of chronic neuropathic pain. Innovative strategies such as hybrid nanocarriers and stimulus-responsive systems are also proposed to enhance the prospects for clinical translation. Serving as a roadmap for future research, this review aims to guide the development and optimization of miRNA-based therapies for effective and sustained neuropathic pain management. Full article

In both scientific and industrial fields, there has been a notable increase in attention toward High-Altitude Pseudo-Satellites (HAPSs) in recent years. This surge is driven by their distinct advantages over traditional satellites and Remotely Piloted Aircraft Systems (RPASs). These benefits are particularly evident in critical areas such as intelligent transportation systems, surveillance, remote sensing, traffic and environmental monitoring, emergency communications, disaster relief efforts, and the facilitation of large-scale temporary events. This review provides an overview of key aspects related to the propellers and propulsion systems of HAPSs. To date, propellers remain the most efficient means of propulsion for high-altitude applications. However, due to the unique operational conditions at stratospheric altitudes, propeller design necessitates specific approaches that differ from those applied in conventional applications. After a brief overview of the propulsion systems proposed in the literature or employed by HAPSs, focusing on both the technical challenges and advancements in this emerging field, this review integrates theoretical foundations, historical design approaches, and the latest multi-fidelity optimization techniques to provide a comprehensive comparison of propeller design methods for HAPSs. It identifies key trends, including the growing use of CFD-based simulations methodologies, which contribute to notable performance improvements. Additionally, the review includes a critical assessment of experimental methods for performance evaluation. These developments have enabled the design of propellers with efficiencies exceeding 85%, offering valuable insights for the next generation of high-endurance, high-altitude platforms. Full article