Search Results (261,208)

Alzheimer’s disease (AD) is primarily recognized for progressive cognitive decline driven by beta-amyloid accumulation and tau pathology. However, many individuals with AD also experience chronic pain and depressive symptoms, which significantly impair daily functioning and quality of life and increase caregiver burden. These non-cognitive features are frequently underrecognized, despite evidence suggesting they share overlapping biological pathways with neurodegeneration. Emerging data highlight the role of neuroinflammation, oxidative stress, hypothalamic–pituitary–adrenal axis dysregulation, and endocannabinoid system alterations in linking AD pathology to disturbances in pain processing and mood regulation. Persistent microglial activation, cytokine imbalance, redox disruption, and chronic stress signaling may simultaneously promote neuronal vulnerability while shaping affective and nociceptive responses. This review synthesizes current preclinical and clinical evidence on the interplay between pain, depression, and AD, emphasizing their shared pathophysiological mechanisms and clinical relevance. Recognizing these symptoms as integral components of disease progression, rather than isolated comorbidities, can inform the development of integrated, multidimensional therapeutic strategies in AD care. Full article

The improper disposal of household pharmaceuticals is a global public health concern, posing risks to both human health and the environment and highlighting the need to raise public awareness. This study aimed to identify individual characteristics associated with the inappropriate disposal of household pharmaceuticals and to determine which individuals may require greater awareness. This cross-sectional study included 310 participants who completed an online questionnaire collecting sociodemographic and clinical information, as well as data regarding the participants’ use, storage, and disposal of medications. Most participants were female (74%), single (57%), had a university degree (81%), and were 34 ± 12 years old; 37% had some non-communicable disease (NCD), 85% used some medication, and 62% disposed of pharmaceuticals inappropriately. Having no undergraduate degree (OR = 4.4; 95%CI = 2.01–9.8), an absence of NCDs (OR = 2.5; 95%CI = 1.1–5.6), a lack of knowledge about reverse logistics (OR = 3.6; 95%CI = 1.7–7.6) or environmental risks (OR = 13.5; 95%CI = 1.5–125), and a lack of guidance from healthcare professionals (OR = 3.6; 95%CI = 1.2–10.6) were associated with inappropriate disposal. Although most respondents (88.6%) were aware of the negative environmental impacts of improper disposal, 69.7% did not know what reverse logistics was or where to find collection points (73.5%). These findings highlight the importance of environmental education for the effective implementation of reverse logistics for household pharmaceuticals. Full article

The date palm (Phoenix dactylifera L.) is a significant perennial crop in arid and semi-arid regions. Understanding the evolution of research on this crop is vital for identifying major research trends, current challenges, and emerging areas for future agricultural innovation and sustainable crop management strategies. This study conducts a comprehensive scientometric analysis of 9062 scientific publications indexed in the Scopus database between 1837 and 2025, spanning nearly two centuries of research on date palm. Using bibliometric tools such as Bibliometrix and ScientoPy, the study examines patterns of scientific production, collaboration networks, institutional participation, thematic evolution, and emerging research trends. The results indicate a marked increase in scientific publications, especially after 2007, with Saudi Arabia, Egypt, and Iran among the most productive countries. The thematic structure of the literature shows a shift from early studies on diseases and oasis cultivation to recent research focusing on biomass valorization, activated carbon production, antioxidant properties, pest management with special emphasis on the red palm weevil (Rhynchophorus ferrugineus), mechanical properties of date palm fibers, and plant biotechnology on methods like micropropagation and somatic embryogenesis. Geographically, research activity is concentrated in the Middle East and North Africa, the primary palm-producing region, with Saudi Arabia leading in institutions, researchers, funding, and international collaborations in date palm research. Emerging trends indicate a rising interest in digital tools, particularly artificial intelligence and advanced analytical tools, which are increasingly being explored to improve crop management. Overall, these findings provide a structured overview of the historical development of date palm research and contribute to a deeper understanding of the evolution and organization of scientific knowledge in this field. Additionally, the identification of key research pathways and emerging trends offers valuable insights for guiding future agronomic innovation, supporting evidence-based crop management strategies, and promoting the sustainable development of date palm production systems. Full article

Background: Disease-related malnutrition is highly prevalent among hospitalized patients and is associated with increased mortality, complications, and prolonged hospital stays. Early identification of patients at nutritional risk is therefore essential to improve clinical outcomes. The Controlling Nutritional Status (CONUT) score is an objective prognostic immunometabolic marker derived from serum albumin, total cholesterol, and lymphocyte count. This study aimed to evaluate the prognostic value of the CONUT score for in-hospital mortality and length of hospital stay (LOS) in hospitalized patients with moderate-to-severe nutritional risk and to determine whether incorporating CONUT improves the predictive performance of a clinical model based on routine admission variables. Methods: A retrospective observational cohort study was conducted, including 671 adult patients admitted to a tertiary university hospital with CONUT ≥ 6. Multivariable logistic regression was used to assess predictors of in-hospital mortality, while LOS was analyzed using multivariable linear regression. Model discrimination was evaluated using receiver operating characteristic (ROC) curve analysis and comparison of the area under the curve (AUC). Results: Higher CONUT scores were independently associated with increased in-hospital mortality. Each one-point increase in CONUT was associated with 28% higher odds of death (OR 1.28; 95% CI 1.13–1.46; p < 0.001). Patients with a severe CONUT score had significantly higher mortality compared with those with a moderate CONUT score (OR 1.77; 95% CI 1.12–2.81; p = 0.004). Incorporating CONUT into the clinical prediction model significantly improved discrimination, increasing the AUC from 0.728 to 0.753 (DeLong p = 0.035). Higher CONUT values were also associated with longer hospital stays: each additional point corresponded to a 5.4% increase in LOS (p = 0.009), and a severe CONUT score was associated with a 17.6% longer stay (p = 0.027). Conclusions: the CONUT score is independently associated with in-hospital mortality and prolonged hospitalization. While its incremental discriminative improvement is modest, its automated calculation from routine laboratory data makes it a practical and scalable tool for early risk stratification. Full article

Introduction: Liver transplantation has re-emerged as a potential therapeutic option for patients with unresectable colorectal liver metastases after failure of standard treatments. This systematic review and meta-analysis evaluated survival outcomes, recurrence patterns, and prognostic factors associated with this approach. Materials and Methods: A systematic review was conducted according to PRISMA 2020 guidelines and registered in PROSPERO. Electronic databases were searched for studies published between November 2015 and November 2025, that assessed liver transplantation in the context of unresectable colorectal liver metastases. Random-effect meta-analyses were conducted to estimate the pooled overall survival, disease-free survival and recurrence rates. Heterogeneity was assessed using I² statistics. Results: Twenty-three studies involving patients with unresectable liver-only colorectal metastases were included. Pooled overall survival after liver transplantation was 96.6% at 1 year (95% CI 93.9–99.4; I² = 44.3%), 73.4% at 3 years (95% CI 62.9–83.9; I² = 95.4%), and 49.4% at 5 years (95% CI 35.4–63.3; I² = 90.5%). Ten-year overall survival was approximately 27%. The pooled recurrence rate was 63.5% (95% CI 52.5–76.8), and the type of recurrence was mainly extrahepatic, most commonly pulmonary. Disease-free survival was 64.1% (95% CI 47.5–80.7) with substantial heterogeneity (I² = 95.6%). Biological risk factors, including carcinoembryonic antigen levels, metabolic tumor volume, and composite risk scores, consistently influenced survival outcomes. Conclusions: In highly selected patients with unresectable colorectal liver metastases, liver transplantation is associated with favorable long-term survival despite frequent recurrence. Outcomes appear to be primarily driven by tumor biology rather than tumor burden, supporting the cautious use within specialized centers under structured selection protocols. Full article

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease and end-stage renal disease worldwide and results from the long-term effects of hypertension on renal structure and function. The pathogenesis of HN is complex and involves haemodynamic disturbances, renal vascular injury, oxidative stress, chronic inflammation, and progressive interstitial fibrosis. In recent years, increasing attention has focused on the role of non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—as key regulators of gene expression involved in these processes. This review summarises the current understanding of the molecular mechanisms underlying HN, with particular emphasis on the roles of oxidative stress, activation of the renin–angiotensin–aldosterone system, transforming growth factor beta signalling, and inflammatory and fibrogenic pathways. The contribution of dysregulated ncRNAs to endothelial dysfunction, inflammatory responses, apoptosis, angiogenesis, and renal remodelling and fibrosis is also discussed. Particular attention is given to miRNAs and lncRNAs as mediators of disease progression and potential biomarkers, as well as to the emerging role of circRNAs in hypertensive kidney injury, including their involvement in the regulation of redox balance and intercellular communication. Collectively, available evidence indicates that ncRNAs represent a critical link between haemodynamic stimuli and persistent molecular alterations in renal tissue, highlighting their potential as diagnostic markers and therapeutic targets in HN. Full article

S. Tomé and Principe (STP) islands have been studied in recent years for their wide range of medicinal plants which exhibit several biological activities of great medicinal interest for some diseases. Experimental design for optimization of several parameters was carried out by a full-factorial test of two levels of three factors for secondary metabolite extraction from Rauvolfia caffra leaves. The best conditions for highest extraction of phenolic compounds (i.e., 89.90 μmoles gallic acid equivalent/g leaves) were obtained at 25 °C in H₂O and at 5 days of incubation. Several phytochemical assays were performed for characterization of these plant extracts, and the highest levels of TFC, DPPH and reducing power were obtained with aqueous plant extraction at 25 °C and for 5 days of incubation, whereas leaf extraction with water at 40 °C for 5 days of incubation revealed the highest levels of ABTS scavenging activity. The levels of SOD and superoxide radical scavenging activities were highest in plant extraction, with hexane at 25 and 40 °C for 5 days of incubation, respectively. The present report consists of a novel and intrinsic synchronous fluorescence and phosphorescence characterization of secondary metabolites from this plant extract. Intrinsic and non-destructive synchronous fluorescence was carried out in the range of 250 to 750 nm with a Δλ range of 5–30 nm, which exhibited several fluorescence peaks in hexane and aqueous plant extracts. On the other hand, intrinsic and non-destructive synchronous phosphorescence was also performed which also exhibited several peaks in aqueous and hexane extracts. 3D spectra of secondary metabolites confirmed the fluorescence peaks observed in SFS in plant extracts. FTIR spectroscopy was selected to investigate the structural properties of secondary metabolites in these plant extracts. Therefore, the present work describes a novel characterization of secondary metabolites by a non-destructive and intrinsic synchronous fluorescence technique for plant extracts. Full article

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications. Full article

The disproportionately severe disease course of diabetic patients with SARS-CoV-2 infection was repeatedly observed by clinicians during the COVID-19 pandemic. The overlap between metabolic impairment, viral pathophysiology, and chronic inflammation created a pattern that urged deeper examination. The aim of this paper was to review and synthesize evidence regarding the interaction between diabetes mellitus and COVID-19. We synthesized evidence across mechanistic pathways (immune dysregulation, chronic inflammation, ACE2/DPP-4-related signaling, endothelial dysfunction, and pancreatic involvement) and key clinical outcomes (severity, intensive care unit (ICU) admission, mortality, dysglycaemia/new-onset diabetes, and DKA). This systematic search was conducted in PubMed, Clinical Key, and Google Scholar. The eligibility criteria included papers on adults (≥18 years) with pre-existing diabetes mellitus (type 1 or type 2) or newly diagnosed diabetes/hyperglycemia and confirmed SARS-CoV-2 infection, published between January 2020 and October 2025, in English language. The PRISMA guidelines were used for data extraction. We identified 412 articles, out of which only 30 met all the inclusion criteria. Diabetes was consistently evoked as a major risk factor for severe COVID-19, being associated with higher susceptibility to pneumonia, respiratory failure, ICU admission, and mortality. The explanation lies in the impaired immune system, endothelial dysfunction, and metabolic repercussions imposed by hyperglycemia. Several antidiabetic drugs appeared protective in multiple cohorts. In conclusion, the accumulated evidence underscores the tight interplay between metabolic disease and COVID-19. Essentially, the clinical management of these patients would be a thoughtful selection of antidiabetic therapy and close metabolic monitoring. Full article

Background/Objectives: Chronic metabolic acidosis (CMA) is a mild, persistent acid–base imbalance characterized by low serum bicarbonate and urinary pH and is common in chronic illness, aging, and metabolic disorders such as type 2 diabetes (T2D). This review highlights the critical, yet often overlooked, role of CMA in T2D (CMAD) and its contribution to disease pathophysiology. Methods: We conducted a comprehensive review of the systemic impacts of CMA, from molecular mechanisms to organ-specific dysfunction. The analysis covers physiological pH dynamics in intracellular (IC) and extracellular (EC) fluids and explores their effects on cellular processes, including the cell cycle and apoptosis. Results: At the molecular level, acidosis significantly alters enzyme kinetics, macromolecule metabolism, and ion conductance. Cell-level analysis shows that pH shifts impact proliferation and programmed cell death. Systemically, the manifestations of CMA align closely with T2D features in vital organs, including the pancreas, liver, skeletal muscle, adipose tissue, and the renal, nervous, and immune systems. Our findings indicate that the pathophysiological landscape of T2D largely mirrors the biological effects of chronic acidosis. Conclusions: The alignment between the effects of CMA and the clinical features of T2D suggests that T2D pathophysiology is worth revisiting through the lens of CMAD. This perspective is further supported by therapeutic interventions showing preliminary efficacy signals in limited studies of acid-neutralization in managing T2D symptoms and progression. Full article

Background/Objectives: To identify major dietary patterns among adults aged ≥45 years and examine their associations with metabolic health–obesity phenotypes. Materials and Methods: We analyzed 32,091 adults aged ≥45 years from the 2015 China Adults National Chronic Disease and Nutrition Surveillance. Diet was assessed using three consecutive 24 h dietary recalls, with household condiment weighing used to improve estimation of cooking oil and salt intake. Dietary patterns were derived using principal component analysis and categorized into quartiles. Multinomial logistic regression adjusted for energy intake and key sociodemographic/lifestyle factors to estimate odds of metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) versus metabolically healthy non-obesity (MHNO). Results: Four patterns with geographic variation were identified: (1) the Rice–Vegetable–Pork pattern; (2) the Fruit–Egg–Dairy pattern; (3) the Red Meat–Offal–Snack pattern; and (4) the Soybeans–Tubers–Grains pattern. Compared with Q1, Q4 of Pattern 1 was associated with lower odds of MHO (OR = 0.42, 95% CI: 0.38–0.46) and MUO (OR = 0.40, 95% CI: 0.36–0.44). Pattern 2 and Pattern 3 were associated with higher odds of MHO (Q4 vs. Q1: OR = 1.42 and 1.21) and MUO (OR = 1.36 and 1.14, all p < 0.001). Pattern 4 was inversely associated with MHO (OR = 0.85, 95% CI: 0.79–0.92) but positively associated with MUNO (OR = 1.16, 95% CI: 1.08–1.24). Conclusions: The Rice–Vegetable–Pork pattern was associated with more favorable obesity-related metabolic phenotypes, whereas energy-dense, animal-derived patterns were associated with higher odds of obesity phenotypes; the Soybeans–Tubers–Grains pattern showed mixed associations. Full article

Pitahaya (Hylocereus spp.) production is increasingly affected by climatic factors, as well as by phytopathogens and abiotic stress, leading to delays in agronomic interventions and reduced productivity. The objective was to design, implement, and validate a multimodal system (CARYPAR) that enables early disease detection and agile decision-making, characterized by low latency and reduced dependence on cloud connectivity. The methodology integrates climate reanalysis from NASA POWER, biophysical remote sensing variables derived from Sentinel-1/2, and proximal computer vision captured via mobile devices using a late fusion architecture and an optimized convolutional neural network, EfficientNet-V2B0, which discriminates between optimal and pathological conditions in vegetative tissues and fruit. The results of the experimental validation carried out in 160 georeferenced units achieved an overall accuracy of 80.0% and an F1 score of 0.8645 for Bad Fruit. The McNemar test and the operational agreement with agro-industrial experts yielded a Cohen’s Kappa index of κ = 0.6831, with an inference latency reduced to 22.00 ms. It is concluded that the multimodal integration of satellite bio-environmental data with edge computer vision achieves substantial agreement with agronomic expert judgment under heterogeneous field conditions (Cohen’s κ = 0.6831), supporting its role as a decision-support tool rather than a replacement for expert assessment. Therefore, its adoption can enhance real-time irrigation management and crop protection, while contributing to traceability and sustainable resource management in agricultural regions with limited connectivity. Full article

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and remains a leading cause of cancer-related mortality worldwide. Advances in molecular characterization and tumor biology have driven the development of antibody-based therapies targeting immune checkpoints, angiogenesis, and oncogenic signaling pathways critical for tumor growth and progression. Among these agents, Ramucirumab, Atezolizumab, and Amivantamab have demonstrated significant clinical efficacy in selected NSCLC populations. This review summarizes the mechanisms of action, pivotal clinical trials, and current clinical evidence supporting the use of ramucirumab, atezolizumab, and amivantamab in the management of advanced NSCLC. Relevant literature was identified through searches of PubMed, clinical trial registries, and recent international conference proceedings, with an emphasis on therapeutic efficacy, safety profiles, and rational combination strategies. Ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor-2 (VEGFR-2), has shown a survival benefit when combined with docetaxel in patients with previously treated advanced NSCLC. Atezolizumab, a programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor (ICI), has become a cornerstone of NSCLC treatment across multiple disease stages, both as monotherapy and in combination with chemotherapy. Amivantamab, a bispecific antibody targeting both epidermal growth factor receptor (EGFR) and mesenchymal–epithelial transition factor (MET), has demonstrated robust and durable clinical activity in patients with EGFR exon 20 insertion–mutated NSCLC. Collectively, these agents highlight the expanding role of antibody-based therapies in NSCLC and underscore the importance of biomarker-driven patient selection and treatment personalization. Ongoing research into resistance mechanisms, predictive biomarkers, and combination approaches is expected to further refine the integration of antibody-based strategies in precision oncology for NSCLC. Full article

Pharmacological inhibition of the nucleoside transporter hENT1 is a promising therapeutic target across a range of diseases, including cardiovascular disorders, neurodegenerative conditions, and cancer. However, current inhibitors lack drug-like properties, necessitating the development of new inhibitors with improved pharmacological profiles. We employed a dual-pharmacophore virtual screening protocol to identify putative hENT1 inhibitors from a library of over 2 million compounds, followed by structure-based molecular docking. To validate the inhibition effect of the lead compounds, we established a functional assay using gemcitabine (GEM)-induced cytotoxicity as a readout of hENT transport activity using eight cancer cell lines. H292 was the optimal cancer cell line for the validation assay based on its high GEM sensitivity (IC50 = 28 nM) and the concentration-dependent cytotoxicity inhibition of the reference inhibitor NBTI, a hENT1 inhibitor. Of the 19 candidate compounds, two leads (compounds 2 and 3) demonstrated potency comparable to NBTI, increasing GEM IC50 values by 2.2- and 2.9-fold at 5 µM, respectively. Both compounds were non-cytotoxic to normal fibroblasts, exhibited favorable ADME properties, displayed superior docking scores of −12.63 and −12.49 kcal/mol compared to NBTI (−9.06 kcal/mol), and displayed a novel vertical binding orientation within the hENT1 binding pocket distinct from NBTI’s horizontal mode. This study established a validated non-radioactive, gemcitabine-based functional assay for hENT inhibitor discovery and identified two putative inhibitors with therapeutic potential for cancer chemosensitization, pain management, and cardio- and neuroprotection. The non-radioactive functional assay overcomes the limitations of traditional radiolabeled methods, enabling scalable, broader screening applications. Full article