Search Results (2,420)

Demand Side Management (DSM) plays a crucial role in modern energy systems, enabling more efficient use of energy resources and contributing to the sustainability of the power grid. This study examines DSM strategies within a multi-environment context encompassing residential, commercial, and industrial sectors, with a focus on diverse appliance types that exhibit distinct operational characteristics and user preferences. Initially, a single-objective optimization approach using Genetic Algorithms (GAs) is employed to minimize the total energy cost under a real Time-of-Use (ToU) pricing scheme. This heuristic method allows for the effective scheduling of appliance operations while factoring in their unique characteristics such as power consumption, usage duration, and user-defined operational flexibility. This study extends the optimization problem to a multi-objective framework that incorporates the minimization of CO₂ emissions under a real annual energy mix while also accounting for user discomfort. The Non-dominated Sorting Genetic Algorithm II (NSGA-II) is utilized for this purpose, providing a Pareto-optimal set of solutions that balances these competing objectives. The inclusion of multiple objectives ensures a comprehensive assessment of DSM strategies, aiming to reduce environmental impact and enhance user satisfaction. Additionally, this study monitors the Peak-to-Average Ratio (PAR) to evaluate the impact of DSM strategies on load balancing and grid stability. It also analyzes the impact of considering different periods of the year with the associated ToU hourly schedule and CO₂ emissions hourly profile. A key innovation of this research is the integration of detailed, category-specific metrics that enable the disaggregation of costs, emissions, and user discomfort across residential, commercial, and industrial appliances. This granularity enables stakeholders to implement tailored strategies that align with specific operational goals and regulatory compliance. Also, the emphasis on a user discomfort indicator allows us to explore the flexibility available in such DSM mechanisms. The results demonstrate the effectiveness of the proposed multi-objective optimization approach in achieving significant cost savings that may reach 20% for industrial applications, while the order of magnitude of the trade-offs involved in terms of emissions reduction, improvement in discomfort, and PAR reduction is quantified for different frameworks. The outcomes not only underscore the efficacy of applying advanced optimization frameworks to real-world problems but also point to pathways for future research in smart energy management. This comprehensive analysis highlights the potential of advanced DSM techniques to enhance the sustainability and resilience of energy systems while also offering valuable policy implications. Full article

Background/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive a first child) and secondary male infertility (which occurs when a man who has already fathered a child faces difficulty conceiving again) remain poorly understood at the genetic level. This study explored the role of single-nucleotide polymorphisms (SNPs) in mitochondrial genes (MT-ND3, MT-ND4L, and MT-ND4) in primary and secondary male infertility. Methods: This study analyzed the genotype distributions of SNPs in 68 infertile males (49 with primary infertility and 19 with secondary infertility) using Sanger sequencing. Results: Key findings revealed that studied SNPs were significantly associated with infertility type. Specifically, rs2857285 (T>C,G) in the ND4 gene showed a significant correlation (p = 0.023) with the TT genotype, which is prominent in primary infertility. Another SNP, rs28358279 (T>A,C) in the ND4L gene, also demonstrated a significant correlation (p = 0.046) with the TT genotype, being more common in primary infertility. In addition, rs869096886 (A>G) in the ND4 gene had a borderline correlation (p = 0.051), indicating a possible association between this SNP and reproductive duration. Conclusions: This study emphasizes the potential relevance of mitochondrial malfunction in male infertility, specifically the effects of studied SNPs on sperm survival and function over time. These findings suggest that certain mitochondrial SNPs might be potential biomarkers for infertility risk. Larger studies are needed to confirm these associations and examine the functional effects of these SNPs. Combining genetic analysis with environmental and lifestyle factors could enhance our understanding of male infertility and improve diagnostic and therapeutic strategies. Full article

Biofilms are structured microbial communities that pose significant challenges to food safety and quality within the food-processing industry. Their formation on equipment and surfaces enables persistent contamination, microbial resistance, and recurring outbreaks of foodborne illness. This review provides a comprehensive synthesis of current knowledge on biofilm formation mechanisms, genetic regulation, and the unique behavior of multi-species biofilms. The review evaluates modern detection and monitoring technologies, including PCR, biosensors, and advanced microscopy, and compares their effectiveness in industrial contexts. Real-world outbreak data and a global economic impact analysis underscore the urgency for more effective regulatory frameworks and sanitation innovations. The findings highlight the critical need for integrated, proactive biofilm management approaches to safeguard food safety, reduce public health risks, and minimize economic losses across global food sectors. Full article

Piezo1 is a mechanosensitive non-selective cation channel. Genetic alterations of the channel result in a hematologic phenotype named Hereditary Xerocytosis. With Yoda1 and, more recently, Yoda2, compounds to increase the activity of Piezo1 have become available. However, their concrete effect depends on the nano environment of the channel and hence on the cell type. Here we compare the potency of Yoda1 and Yoda2 in red blood cells (RBCs). We investigate the effect of the compounds on direct channel activity using automated patch clamp, as well as the secondary effects of channel activation on signalling molecules and cellular response. In terms of signalling, we investigate the temporal response of the second messenger Ca²⁺, and in terms of cellular response, the activity of the Gárdos channel. The opening of the Gárdos channel leads to a hyperpolarisation of the RBCs, which is measured by the Macey–Bennekou–Egée (MBE) method. Although the interpretation of the data is not straightforward, we discuss the results in a physiological context and provide recommendations for the use of Yoda1 and Yoda2 to investigate RBCs. Full article

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management. Full article

Background: Charcot–Marie–Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals. Methods: A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied. Results: A supervised model showed a clear separation (R²X = 0.3; R²Y = 0.7; Q² = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9–1). Additional altered metabolic pathways were also identified within the disease context. Conclusion: This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers. Full article

Solving competitive facility location problems can optimize market share or operational efficiency in environments where multiple firms compete for customer attention. In such contexts, facility attractiveness is shaped not only by geographic proximity but also by customer preference characteristics. This study presents a novel heuristic framework that integrates multi-view K-means clustering with customer behavior modeling reinforced by a co-regularization mechanism to align clustering results across heterogeneous data views. By jointly exploiting spatial and behavioral information, the framework clusters customers and facilities into meaningful market segments. Within each segment, a bilevel optimization model is applied to represent the sequential decision-making of competing entities—where a leader first selects facility locations, followed by a reactive follower. An empirical evaluation on a real-world dataset from San Francisco demonstrates that the proposed approach, using optimal co-regularization parameters, achieves a total runtime of approximately 4.00 s—representing a 99.34% reduction compared to the full CFLBP-CB model (608.58 s) and a 99.32% reduction compared to a genetic algorithm (585.20 s). Concurrently, it yields an overall profit of 16,104.17, which is an approximate 0.72% increase over the Direct CFLBP-CB profit of 15,988.27 and is only 0.21% lower than the genetic algorithm’s highest profit of 16,137.75. Moreover, comparative analysis reveals that the proposed multi-view clustering with co-regularization outperforms all single-view baselines, including K-means, spectral, and hierarchical methods. This superiority is evidenced by an approximate 5.21% increase in overall profit and a simultaneous reduction in optimization time, thereby demonstrating its effectiveness in capturing complementary spatial and behavioral structures for competitive facility location. Notably, the proposed two-stage approach achieves high-quality solutions with significantly shorter computation times, making it suitable for large-scale or time-sensitive competitive facility planning tasks. Full article

Understanding alpine plants’ survival and reproduction is crucial for their conservation in climate change. Based on 423 valid distribution points, this study utilizes the MaxEnt model to predict the potential habitat and distribution dynamics of Leontopodium nanum under both current and future climate scenarios, while clarifying the key factors that influence its distribution. The primary ecological drivers of distribution are altitude (2886.08 m–5576.14 m) and the mean temperature of the driest quarter (−6.60–1.55 °C). Currently, the suitable habitat area is approximately 520.28 × 10⁴ km², covering about 3.5% of the global land area, concentrated mainly in the Tibetan Plateau, with smaller regions across East and South Asia. Under future climate scenarios, low-emission (SSP126), suitable areas are projected to expand during the 2050s and 2070s. High-emission (SSP585), suitable areas may decrease by 50%, with a 66.07% reduction in highly suitable areas by the 2070s. The greatest losses are expected in the south-eastern Tibetan Plateau. Regarding dynamic habitat changes, by the 2050s, newly suitable areas will account for 51.09% of the current habitat, while 68.26% of existing habitat will become unsuitable. By the 2070s, newly suitable areas will rise to 71.86% of the current total, but the loss of existing areas will exceed these gains, particularly under the high-emission scenario. The centroid of suitable habitats is expected to shift northward, with migration distances ranging from 23.94 km to 342.42 km. The most significant shift is anticipated under the SSP126 scenario by the 2070s. This study offers valuable insights into the distribution dynamics of L. nanum and other alpine species under the context of climate change. From a conservation perspective, it is recommended to prioritize the protection and restoration of vegetation in key habitat patches or potential migration corridors, restrict overgrazing and infrastructure development, and maintain genetic diversity and dispersal capacity through assisted migration and population genetic monitoring when necessary. These measures aim to provide a robust scientific foundation for the comprehensive conservation and sustainable management of the grassland ecosystem on the Qinghai–Tibet Plateau. Full article

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients undergoing either primary debulking surgery followed by adjuvant chemotherapy (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT). Genetic analysis was performed on 43 primary HGSOC tumor samples using targeted massive parallel sequencing via next-generation sequencing (NGS). Clinical and molecular data were evaluated collectively and through subgroup comparisons between PDS and NACT cohorts. All analyzed samples harbored genetic alterations. Univariate survival analysis revealed that the total number of mutations (p = 0.0035), as well as mutations in HRAS (p = 0.044), FLT3 (p = 0.023), TP53 (p = 0.03), and ERBB4 (p = 0.007), were significantly associated with poorer OS. Multivariate Cox regression integrating clinical and molecular data confirmed that ERBB4 mutations are independently associated with adverse outcomes. These findings reveal a distinctive mutational landscape between the PDS and NACT groups and suggest that ERBB4 alterations may define a particularly aggressive tumor phenotype. This study contributes to a deeper understanding of HGSOC biology and may support the development of novel therapeutic targets and personalized treatment strategies in the context of precision oncology. Full article

Coffee beverage quality is determined by a complex interaction of genetic and environmental factors, including specific biochemical characteristics. In this context, the present study aimed to estimate the genetic parameters of elite irrigated Conilon coffee genotypes in the Cerrado over two consecutive years based on the biochemical characteristics of the beans, assessed by near-infrared spectroscopy (NIRS). The research was conducted at the Embrapa Cerrados experimental field, using the unit’s elite collection. Levels of chlorogenic acid (5-ACQ), caffeine, sucrose, citric acid and trigonelline were analyzed in the raw beans of 18 genotypes harvested in two consecutive years. Data were subjected to analysis of variance in a time-subdivided plot design, considering genotypes as plots and years as subplots, with means grouped by the Scott-Knott test at 5% significance. Results showed significant genetic variability for caffeine, sucrose and trigonelline, while chlorogenic and citric acid levels did not differ significantly among genotypes. A significant genotype × year interaction was observed for caffeine, sucrose, and 5-ACQ. Estimated heritabilities were high for caffeine (85.5%), trigonelline (80.1%), sucrose (62%) and citric acid (60%). Selection gains were positive for sucrose (5.58%), citric acid (10.01%) and trigonelline (8.27%), and negative for caffeine (−6.87%) and 5-ACQ (−0.47%). It is concluded that among the compounds evaluated, caffeine shows the greatest potential for selection, enabling effective gains in raw bean composition, while sucrose and trigonelline present moderate potential for genetic improvement. Full article

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders. Full article

Aging is a well-known, complex physiological process characterized by progressive functional decline and increased susceptibility to disease, particularly in the cardiovascular and nervous systems. While genetic and environmental factors can shape its advancement, molecular regulators such as vascular endothelial growth factor (VEGF) and dopamine signaling have emerged as critical factors in maintaining vascular and neural health. VEGF promotes angiogenesis and tissue repair, while dopamine, primarily recognized for its neuromodulatory roles, regulates vascular tone and appears to modulate VEGF activity. Despite substantial research on their roles in cardiovascular and neurodegenerative diseases, little is known about how VEGF and dopamine interact in the aging process, particularly in healthy versus unhealthy aging contexts. This review describes existing evidence on the independent and potentially complementary roles of VEGF and dopamine in aging, emphasizing their influence on maintaining or improving neurovascular health. It also explores how lifestyle interventions may be beneficial in modulating VEGF and dopamine signaling pathways in the aging population. By addressing the current knowledge gap surrounding VEGF–dopamine crosstalk, this review highlights the need for further investigation into their combined effects and targeting molecular interaction to unlock new research avenues for innovative strategies for healthy aging and the potential treatment of age-related diseases. Full article

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Background/Objectives: Impulsivity is a key psychological construct implicated in the onset and maintenance of behavioural addictions. Dysregulation of impulsivity is central to behavioural addictions, yet its genetic basis remains unclear. This study examined the association between the DAT1 variable number tandem repeat polymorphism and impulsivity in individuals with behavioural addictions. Methods: A total of 328 males (128 with behavioural addictions and 200 controls) completed the Barratt Impulsiveness Scale. DAT1 genotyping was performed via PCR and gel electrophoresis. Statistical analyses included chi-square tests, Mann–Whitney U-tests, and two-way ANOVA. Results: No differences in DAT1 genotype frequencies were found between groups. However, a significant interaction emerged for attentional impulsivity: individuals with behavioural addictions and the 9/9 genotype had the highest BIS-AI scores (F_{2, 322} = 5.48; p = 0.0046). Conclusions: The DAT1 9/9 genotype may increase vulnerability to attentional impulsivity, but only in the context of behavioural addictions. These findings highlight a gene–environment interaction and support the role of dopaminergic mechanisms in cognitive dysregulation. Future studies should validate these findings using longitudinal designs and neurobiological methods. Full article