Search Results (234)

Background: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair (pMMR) and microsatellite stability (MSS) metastatic colorectal cancer (mCRC). Inhibition of vascular endothelial growth factor (VEGF) or cytotoxic chemotherapy can boost immunogenicity and has the potential to upregulate ICI efficacy. Methods: A comprehensive electronic literature search was conducted up to April 2025 to identify randomized controlled trials comparing cytotoxic chemotherapy plus bevacizumab with or without ICI. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), objective response rate (ORR), and severe adverse events (AEs: grade 3 or more). A meta-analysis was performed using random-effects models to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: Four studies involving 986 patients (With-ICI group, n = 651; Without-ICI group, n = 335) were included. The meta-analysis demonstrated a significant improvement in PFS in the With-ICI group compared with the Without-ICI group, with an HR of 0.82 (95% CI: 0.70–0.96, p = 0.01) without statistical heterogeneity. No significant improvements were observed between the With- and Without-ICI groups in OS and ORR meta-analyses, but the With-ICI group had a favorable trend in OS. A significant increase in serious AEs was not observed in the With-ICI group. Conclusions: This meta-analysis suggests a potential benefit of adding ICIs to chemotherapy plus bevacizumab in pMMR mCRC; however, the evidence remains preliminary and hypothesis-generating, warranting further investigation in biomarker-driven trials and clarification of long-term outcomes. Full article

This paper introduces a theoretical large-scale radio channel model for the downlink in cellular systems, aimed at estimating variations in received signal power at the user terminal as a function of device mobility. This enables applications such as direction-of-arrival (DoA) estimation, estimating power at subsequent points based on received power, and detection of coverage anomalies. The model is validated using real-world measurements from urban and suburban environments, achieving a maximum estimation error of 7.6%. In contrast to conventional models like Okumura–Hata, COST-231, Third Generation Partnership Project (3GPP) stochastic models, or ray-tracing techniques, which estimate average power under static conditions, the proposed model captures power fluctuations induced by terminal movement, a factor often neglected. Although advanced techniques such as wave-domain processing with intelligent metasurfaces can also estimate DoA, this model provides a simpler, geometry-driven approach based on empirical traces. While it does not incorporate infrastructure-specific characteristics or inter-cell interference, it remains a practical solution for scenarios with limited information or computational resources. Full article

The widespread adoption of the Internet of Things (IoT) has driven major advancements in wireless communication, especially in rural and suburban areas where low population density and limited infrastructure pose significant challenges. Accurate Path Loss (PL) prediction is critical for the effective deployment and operation of Wireless Sensor Networks (WSNs) in such environments. This study explores the use of Convolutional Neural Networks (CNNs) for PL modeling, utilizing a comprehensive dataset collected in a smart campus setting that captures the influence of terrain and environmental variations. Several CNN architectures were evaluated based on different combinations of input features—such as distance, elevation, clutter height, and altitude—to assess their predictive accuracy. The findings reveal that CNN-based models outperform traditional propagation models (Free Space Path Loss (FSPL), Okumura–Hata, COST 231, Log-Distance), achieving lower error rates and more precise PL estimations. The best performing CNN configuration, using only distance and elevation, highlights the value of terrain-aware modeling. These results underscore the potential of deep learning techniques to enhance IoT connectivity in sparsely connected regions and support the development of more resilient communication infrastructures. Full article

Accurate path loss prediction is essential for optimizing Long-Range Wide-Area Network (LoRaWAN) performance. Previous studies have employed various Machine Learning (ML) models for path loss prediction. However, environmental factors such as temperature, humidity, barometric pressure, and particulate matter have been largely neglected. This study bridges this gap by evaluating the performance of five boosting ML models—AdaBoost, XGBoost, LightGBM, GentleBoost, and LogitBoost—under dynamic environmental conditions. The models were compared with theoretical models (Log-Distance and Okumura-Hata) and existing studies that employed the same dataset based on metrics such as RMSE, MAE, and R². Furthermore, a detailed performance vs. complexity analysis was conducted using metrics such as training time, inference latency, model size, and energy consumption. Notably, barometric pressure emerged as the most influential environmental factor affecting path loss across all models. Bayesian Optimization was applied to fine-tune hyperparameters to improve model accuracy. Results showed that LightGBM outperformed other models with the lowest RMSE of 0.5166 and the highest R² of 0.7151. LightGBM also offered the best trade-off between accuracy and computational efficiency. The findings show that boosting algorithms, particularly LightGBM, are highly effective for path loss prediction in LoRaWANs. Full article

Mapping methods for loosened rock mass in mountainous areas are useful for risk management of landslide disasters. Depending on the type of aircraft and sensor, there are several different aerial electromagnetic measurement methods for estimating subsurface structures. Helicopter-borne electromagnetic methods are commonly used. Recently, unmanned aerial vehicles (drones) have been used. By understanding the characteristics of each method, it is possible to choose a suitable method for the target of observation. In this study, resistivity from the frequency-domain helicopter-borne electromagnetic (HEM) method and resistivity from the time-domain drone-grounded electrical-source airborne transient electromagnetic (D-GREATEM) method were compared to estimate loosened zones in mountainous areas. The resistivity cross-sectional profiles were largely similar, but differences were observed near the surface in some zones. The comparative analysis of both methods with outcrop observations revealed that D-GREATEM resistivity data can detect both loosened rock mass from the surface to an approximately 30 m depth located above the groundwater and saturated rock mass. It is because D-GREATEM resistivity was obtained by assuming five layers from the surface to a depth of 40 m. This indicates that D-GREATEM is suitable for estimating near-surface loosened rock mass distribution in the valleys. However, D-GREATEM has a limited observation range. Therefore, it was concluded that the D-GREATEM method is suitable for a detailed and localized estimation of landslide susceptibility near the surface, whereas the HEM method is suitable for wide-area analysis. Full article

Recent advances in DNA research have increased the necessity for museums to preserve not only morphological specimens but also their DNA, leading us to maintain tissue samples linked to specimens at −80 °C. DNA analysis has become an essential tool for taxonomic research and biodiversity assessment; however, freezer storage for all samples is impractical due to space limitations and operational costs. This creates a pressing need to develop more widely applicable DNA preservation methods. We investigated the comparative effects of traditional preservation methods versus DESS (DMSO/EDTA/saturated NaCl solution) preservation on both morphology and DNA integrity using museum specimens from various taxonomic groups. Our results demonstrated that DESS preservation maintained high-quality DNA fragments exceeding >15 kb at room temperature across all examined species, with nematode samples maintaining DNA integrity even after 10 years of storage. When preserving whole organisms, the optimal preservation solution conditions for maintaining both morphological features and DNA integrity varied among species. Notably, DNA integrity was maintained even after complete evaporation of the DESS solution. These findings suggest that DESS utilization for specimen DNA preservation is effective across many species, not only for long-term storage in environments without freezer facilities but also for temporary preservation until freezing. Full article

With the increase in prices of correctives and fertilizers, the investigation of the interactions between plants and plant growth-promoting bacteria shows an economically viable and sustainable alternative, and the use of Azospirillum brasilense has shown an increase in efficiency of nitrogen use and increased pasture yield. This study, conducted in the Brazilian Amazon, aimed to evaluate the effect of different inoculation techniques of Azospirillum brasilense associated with the dose of nitrogen topdressing on the productive performance of Brachiaria brizantha cv. Paiaguás is a grass species commonly cultivated in this region. The experiment was conducted in the Experimental Forage Sector of the Federal Rural University of the Amazon, Parauapebas city, Brazil. The experimental design was a randomized block design in a 3 × 3 factorial arrangement, with three inoculation methods (control, seed, and foliar) and three nitrogen fertilization doses (0, 75, and 150 kg ha⁻¹ of N), with four replicates. An effect was observed in interaction between inoculation and nitrogen fertilization (p ≤ 0.05) for the variables total forage green mass, total forage dry mass, dry mass of leaf blade, dry stem mass, and number of tillers m⁻². The dose of 150 kg ha⁻¹ of N promoted a positive effect of N on the total forage dry mass and LAI (leaf area index). Inoculation with Azospirillum brasilense, especially foliar application, efficiently increased Brachiaria brizantha cv. Paiaguás yield, potentially reducing the use of nitrogen fertilizers, promotes greater sustainability in pasture management. Full article

While carboxymethyl cellulose (CMC)—a biocompatible and water-soluble cellulose derivative—holds promise for biomedical applications, challenges remain in synthesizing CMC-based hydrogels with covalent crosslinking through free radical polymerization without requiring complex, multi-step processes. In this study, we introduce a facile one-pot strategy that combines CMC with acrylamide (AAm) under cryogelation and low-intensity UV irradiation to achieve covalent bonding and a high polymerization yield. The resulting polyacrylamide/carboxymethyl cellulose (PAAm/CMC) porous gels were systematically evaluated for their chemical, physical, thermal, and drug-release properties, with a focus on the effects of AAm concentration and polymerization temperature (frozen vs. room temperature). Notably, the cryogel synthesized with 2.5 M AAm (PC2.5) exhibited significantly enhanced mechanical properties—that is, an 8.4-fold increase in tensile modulus and a 26-fold increase in toughness—compared with the non-cryo gel. Moreover, PC2.5 demonstrated excellent cyclic compression stability in water and phosphate-buffered saline (PBS), with less than 10% reduction in modulus after 100 cycles. These increases in the mechanical properties of PC2.5 are attributed to the formation of macropores with high polymer density and high crosslinking density at the pore walls. PC2.5 also showed slower drug release in PBS and good cytocompatibility. This study presents a simplified and efficient route for fabricating mechanically robust, covalently crosslinked PAAm/CMC cryogels, highlighting their strong potential for biomedical applications in drug delivery systems. Full article

Small Island Developing States (SIDS) face energy security challenges due to reliance on imported fossil fuels and limited land for renewable energy. This study evaluates the techno-economic feasibility of integrating Ocean Thermal Energy Conversion (OTEC) and Seawater Air Conditioning (SWAC) systems as a sustainable solution. The research focuses on (1) developing a scalable onshore OTEC-SWAC system and assessing feasibility across 32 SIDS using 20 years of oceanic and atmospheric data, (2) analyzing key system parameters such as pipeline length, pump sizing, and cooling requirements and their effect on capital cost, and (3) developing a scalable cost estimation model for Levelized Cost of Energy (LCOE) predictions. The techno-economic analysis reveals that 30 of the 32 SIDS are technically feasible for OTEC power generation with a temperature gradient of 20 °C. The proposed system is economically feasible in 23 of the SIDS with a calculated average LCOE of 0.16 USD/kWh, which is 67% lower than the diesel LCOE, which is on average 0.46 USD/kWh, making it a cost-competitive alternative. The developed reduced form of the model enables scalable LCOE calculations based on pipeline length and ocean temperature differentials, aiding policymakers in decision-making. By reducing fossil fuel dependency and supporting green tourism, this study provides actionable insights for sustainable energy adoption in SIDS. Full article

Background/Objectives: Supplementation with nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD⁺) intermediate, exerts anti-aging, anti-obesity, and anti-diabetic effects in animal experiments. However, previous studies have evaluated NMN supplementation using oral administration in drinking water or by intraperitoneal administration. No studies have reported whether NMN exerts beneficial effects when incorporated into the diet. The diet is a multicomponent mixture of many nutrients that may interact with each other, thus weakening the effects of NMN. In the present study, we evaluated whether dietary NMN intake protects obese diabetic db/db mice from obesity-related metabolic disorders, such as dyslipidemia, hepatic steatosis, hyperglycemia, and hyperinsulinemia. Methods: Five-week-old male db/db mice were randomly assigned to two groups and fed for four weeks either a control diet containing 7% corn oil and 0.1% cholesterol (CON group, n = 6) or a diet supplemented with 0.5% NMN (NMN group, n = 5). Results: After 4 weeks of feeding, dietary NMN intake alleviated obesity, hypertriglyceridemia, and hepatic triglyceride accumulation in db/db mice. Respiratory gas analysis indicated that dietary NMN intake significantly enhanced energy expenditure by suppressing carbohydrate oxidation and increasing fat oxidation after 3 weeks of feeding. Additionally, the suppression of the increase in plasma triglyceride (TG) levels by dietary NMN intake was attributable to a reduction in hepatic TG levels through the suppression of fatty acid synthesis and the enhancement of fatty acid β-oxidation in the liver. Furthermore, the improvement in hepatic fatty acid metabolism induced by dietary NMN intake was partially responsible for the significant increase in plasma adiponectin and soluble T-cadherin levels. Conclusions: This is the first report to show that dietary NMN intake but not oral administration in drinking water or intraperitoneal administration alleviates body fat mass and hypertriglyceridemia by enhancing energy expenditure, with preferential promotion of fat oxidation, the enhancement of hepatic lipolysis, and the suppression of hepatic lipogenesis in db/db mice. Full article

Over 150 transthyretin (TTR) mutations have been identified in hereditary transthyretin (ATTRv) amyloidosis, and new TTR variants have recently emerged. However, the pathogenicity of several new variants remains unclear, making it important to elucidate the differences between amyloidogenic and wild-type TTR. In this study, we report a novel TTR variant (V121A) identified in two unrelated amyloidosis patients aged > 60 years who developed cardiomyopathy. We evaluated the detailed biochemical features of this TTR variant to confirm its amyloidogenicity using plasma samples from these patients and recombinant TTR proteins. While the V121A TTR variant has a similar ability to assemble into a tetramer as wild-type TTR, it aggregates more readily over a wide potential hydrogen range than wild-type TTR. Additionally, the V121A variant is highly prone to dissociation and resistant to binding with known TTR tetramer stabilizers. Clinical and biochemical data suggest that this novel variant is clearly pathogenic, is highly prone to dissociation and aggregation, and is associated with the development of late-onset amyloid cardiomyopathy. Interestingly, amyloid fibril formation due to this variant may not be affected by known TTR stabilizers. Full article

Wound healing is a complex, multiphase process crucial for restoring tissue integrity and functionality after injury. Among the emerging therapeutic approaches, antimicrobial peptides (AMPs) have shown substantial promise because of their dual role in microbial defense and cellular modulation. AMP-IBP5, a novel AMP derived from insulin-like growth factor-binding protein 5, exhibits both antimicrobial and wound-healing properties, making it a promising therapeutic candidate. This peptide exhibits robust antimicrobial activity, augments keratinocyte proliferation, increases fibroblast migration, induces angiogenesis, and modulates the immune response. Mechanistically, AMP-IBP5 activates Mas-related G protein-coupled receptors and low-density lipoprotein receptor-related protein 1 (LRP1) in keratinocytes, stimulating IL-8 production and vascular endothelial growth factor expression to accelerate wound healing. This molecule also interacts with LRP1 in fibroblasts to increase cell migration and promote angiogenesis while mitigating inflammatory responses through targeted cytokine modulation. Preclinical studies have demonstrated its remarkable efficacy in promoting tissue repair in diabetic wounds and inflammatory skin conditions, including atopic dermatitis and psoriasis. This review delves into the broad therapeutic potential of AMP-IBP5 across dermatological applications, focusing on its intricate mechanisms of action, comparative advantages, and its path toward clinical and commercial application. Full article

Background: Remote cardiac rehabilitation (RCR) is emerging alternative to outpatient rehabilitation. However, evidence related to its effect on health-related quality of life (HRQOL) is limited. Methods: This is a sub-analysis of the RecRCR study, a multi-center, nonrandomized trial evaluating the efficacy and safety of RCR with real-time telemonitoring in patients with CVD, after discharge. The Short-Form Health Survey-8 was employed to evaluate the HRQOL before and 2–3 months after RCR. Based on the improvement of exercise tolerance, the patients were divided into I group (>10% improvement) and NI group (≤10% improvement). Results: Of 57 patients who completed RCR, 31 patients were included for analysis of HRQOL, including 15 (I group) and 16 patients (NI group). The physical (PCS) (45.5 ± 8.0 to 52.5 ± 4.0, p < 0.001) and mental (MCS) component scores (47.5 ± 7.9 to 51.0 ± 5.6, p = 0.005) improved significantly in all populations following RCR. The PCS improved significantly in the I and NI groups, respectively. By contrast, only in the I group, the MCS improved. However, the change in PCS or MCS was not significantly different between the two groups. The increases of MCS significantly associated with days from admission to the beginning of RCR (rs = −0.51, p = 0.007). Conclusions: In multifaced contents of HRQOL, the scores in PCS or MCS changed differently from the change in exercise capacity. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma is a lethal malignancy, necessitating an understanding of its molecular mechanisms for the development of new therapeutic strategies. The tight junction protein claudin-1, known to influence cellular functions in various cancers and is considered a therapeutic target, remains unclear in pancreatic cancer. Methods: This study assessed claudin-1 expression in resected pancreatic cancer samples, public databases, and pancreatic cancer cell lines. Claudin-1 knockout with CRISPR/Cas9 on poorly differentiated pancreatic cancer cell lines and a proteome analysis were performed to investigate the intracellular mechanisms of claudin-1. Results: Claudin-1 was markedly overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia compared to normal ducts, and high claudin-1 levels were an independent predictor of poor prognosis. Claudin-1 knockout diminished cell proliferation, migration, invasion, and chemoresistance in pancreatic ductal adenocarcinoma. Proteome analysis revealed the significant downregulation of aldo-keto reductase family proteins (AKR1C2, AKR1C3, and AKR1B1) in claudin-1 knockout cells, which are linked to metabolic pathways. Aldo-keto reductase knockdown reduced chemoresistance, proliferation, and invasion in these cell lines. Conclusions: These findings indicate that the abnormal expression of claudin-1 promotes tumor progression and drug resistance through its interaction with aldo-keto reductase proteins, highlighting claudin-1 and aldo-keto reductase family proteins as potential biomarkers and therapeutic targets for pancreatic cancer. Full article

It is well known that existing empirical models cannot fit perfectly into environments other than those they were formulated in due to differences in terrain and climate. The Okumura–Hata family of models are gaining acceptability over the VHF/UHF channels. However, it is imperative to investigate their reliability and to use the one most suited to each environment. This study investigated the reliability of the Okumura–Hata, COST-231, ECC-33, and Ericsson models over digital UHF channels in Ikorodu and Akure, Southwestern Nigeria. The drive test protocol was used for data collection at intervals of 1 km along different routes from the experimental stations up to maximums of 10 and 16 km in Ikorodu and Akure, respectively. This was carried out for both wet and dry season months using a digital Satlink meter with a spectrum (WS-6936), GPS Map 78s and a field vehicle. The uniqueness of this study is that it used real-world data with a seasonal scope, and the mean values were employed in the analysis to strengthen the reliability of the results. The measured path loss (MPL) and predicted path loss (PPLM) were computed, with error margin analysis carried out between them. The results reveal a mean MPL of 110.42 dB in Ikorodu, while the PPLMs were 121.90, 123.55, 158.42, and 291.01 dB for the Hata, COST-231, Ericsson, and ECC-33 models, respectively. In Akure, the mean MPL was 123.157 dB, while the PPLMs were 121.922, 130.179, 198.979, and 313.494 dB. The results further indicate that the Hata model had the best performance with the lowest RMSE of 10.812 in Ikorodu, while COST-231 had the best performance in Akure, with the lowest RMSE of 9.877. The optimized Hata and COST-231 models were developed with improved RMSEs of 5.895 and 7.815 for the Ikorodu and Akure environments, respectively. The optimized models had higher degrees of reliability and will provide a valuable approach to wireless communication planning in tropical urban and suburban environments for achieving quality of transmission and reception (QoTnR) over UHF channels in Nigeria and similar environments in Africa. Full article