Search Results (2,535)

Primary ciliary dyskinesia (PCD) is a rare ciliopathy resulting in chronic oto-sino-pulmonary disease. PCD diagnosis can be achieved by a combination of different diagnostic and adjuvant tools, including high-speed video-microscopy analysis (HSVA). A founder variant has been described in Puerto Rico as the most common cause of PCD in the island. Background/Objectives: In HSVA, objective parameters such as ciliary beat frequency (CBF) and subjective parameters such as ciliary beat pattern (CBP) shed light on the biophysical properties of cilia. However, the subjective nature of CBP creates a gap in knowledge; characteristics such as the length, angle, and bending index of cilia are poorly described. Our goal is to quantify cilia dynamics of the RSPH4A (c.921+3_921+6delAAGT (intronic)) founder variant in Puerto Rico through biophysical properties of cilia. This approach enhances longitudinal patient care by understanding treatment progress through biophysical ciliary function. Methods: We analyzed images from HSVA of six patients with PCD homozygous for the founder variant and six healthy controls (HC) (n = 12). Results: We found that ciliary length (PCD = 7.62 ± 0.95 μm, HC = 8.12 ± 1.36 μm, p = 0.204 ns), orientation vector (PCD = 7.20 ± 0.93 μm, HC = 7.25 ± 1.01 μm, p = 0.883 ns), straight angle (PCD = 1.67 ± 0.27 rad, HC = 1.76 ± 0.29 rad, p = 0.380 ns), and area (PCD = 2.35 ± 0.52 μm², HC = 2.10 ± 0.53 μm², p = 0.264 ns) did not have statistically significant differences between PCD and HC. In contrast, bending index (PCD = 1.06 ± 0.04, HC = 1.12 ± 0.09, p = 0.01), bent angle (PCD = 1.11 ± 0.30 rad, HC = 0.67 ± 0.21 rad, p < 0.0001), net angle (PCD = 0.56 ± 0.26 rad, HC = 1.09 ± 0.35 rad, p < 0.0001), amplitude (PCD = 5.77 ± 1.25 μm, HC = 7.99 ± 1.65 μm, p < 0.0001), and amplitude per second (PCD = 48.83 ± 13.23 A(s), HC = 91.66 ± 27.96 A(s), p < 0.0001) showed significant differences between both groups. Conclusions: Reduced angular excursion and amplitude in PCD demonstrate that the beating pattern of the RSPH4A founder variant is dysfunctional as compared with healthy controls. Our study provides an objective framework to understand the biophysical properties of the RSPH4A founder variant. Full article

The optimization of membrane permeability is a pivotal approach for mitigating late-stage failures in peptide drug development. By leveraging linker chemical diversity, stapled peptides utilize linker engineering to precisely modulate key physicochemical parameters—such as lipophilicity and conformational constraints—to overcome the desolvation energy penalty. This review systematically evaluates linker-based strategies for enhancing the permeability of stapled peptides, categorized into two primary dimensions: (1) high-throughput screening (HTS) compatibility, focusing on the integration of functionalized linkers into mRNA display, phage display, and DNA-encoded libraries (DELs) to identify lead scaffolds with inherent permeability potential during early discovery; and (2) post-screening structural refinement, covering rational design strategies including intramolecular hydrogen-bond (IMHB) shielding, “chameleonic” adaptations, and stimuli-responsive reversible stapling. Furthermore, we analyze the paradigm shift in assessment methodologies from qualitative imaging to quantitative cytosolic delivery assays, which have deepened our understanding of mechanisms such as the charge/lipophilicity threshold balance and metabolism-driven trapping. Overall, linker engineering provides a robust technical roadmap for developing the next generation of cell-permeable stapled peptide therapeutics. Full article

Pulmonary tuberculosis (TB) remains a global health threat, with individual genetic determinants like Toll-like receptor 2 (TLR2) gene variations potentially modulating immune responses to Mycobacterium tuberculosis. This systematic review evaluates the role of TLR2 polymorphisms in influencing susceptibility to and clinical manifestations of pulmonary TB. Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, and ScienceDirect was conducted through July 2024 for observational studies investigating TLR2 single-nucleotide polymorphisms (SNPs) and active TB. Risk of bias was assessed using the Newcastle–Ottawa Scale. Of 8878 identified articles, 32 studies met the inclusion criteria. The most frequently investigated variants, Arg753Gln (rs5743708), −196 to −174 del, and rs3804099, were consistently associated with increased TB susceptibility, particularly in Asian and African populations. Furthermore, specific polymorphisms correlated with greater disease severity, including cavitary lesions and aggressive clinical progression. In conclusion, TLR2 genetic polymorphisms significantly increase the risk of developing pulmonary TB and contribute to more severe clinical outcomes. These findings emphasize the potential of genetic profiling in enhancing TB control strategies and developing personalized diagnostic or therapeutic approaches. Full article

Inherited cardiomyopathies represent a major cause of ventricular arrhythmias (VA) and sudden cardiac death (SCD), frequently occurring in the absence of advanced systolic dysfunction. Traditional strategies for the primary prevention of SCD have relied predominantly on left ventricular ejection fraction (LVEF), an approach that fails to capture the substantial biological and clinical heterogeneity of non-ischemic cardiomyopathies. Over the past decade, advances in cardiac genetics and cardiac magnetic resonance imaging have identified specific genotypes associated with a disproportionate arrhythmic risk, which often precedes overt ventricular remodeling. The 2023 European Society of Cardiology (ESC) Guidelines on cardiomyopathies formalize this paradigm shift by integrating etiology, myocardial substrate, and electrical phenotype into contemporary risk stratification. In this narrative review, we focus on cardiomyopathy-associated genotypes consistently linked to high arrhythmic risk—LMNA, truncating variants in FLNC, RBM20, PLN p.Arg14del, and desmosomal genes—and examine their molecular mechanisms, phenotypic trajectories, and arrhythmogenic profiles. We discuss how genotype-specific patterns of myocardial fibrosis, conduction disease, and VA inform implantable cardioverter-defibrillator (ICD) decision-making beyond LVEF-based thresholds. By synthesizing genetic, imaging, and clinical evidence in light of ESC 2023 recommendations, this review highlights the evolving role of genotype-informed strategies in the personalized prevention of SCD and underscores remaining gaps in evidence and risk prediction. Full article

Pinus oocarpa Schiede ex Schltdl. is the most important resin-producing conifer in Mexico, yet its morphological variation and seed transfer guidelines remain poorly defined for the Sierra Madre del Sur (SMS). This study evaluated variation in cone, seed, fascicle sheath, and needle traits, analyzed their associations with geographic and climatic factors, and delineated altitudinal seed zones and assisted migration distances. Most variation occurred among individual trees, with smaller but significant components among populations and provenances. All traits differed significantly among populations, provenances, and trees (p ≤ 0.0325), except for cone length, which showed no significant differences among populations (p = 0.0714). Multivariate analyses at both tree and provenance levels identified two differentiated population groups within the SMS. Several traits, including needle thickness, seed size, cone length, and seed weight, showed significant associations with environmental gradients. To realign provenances with projected climates for the 2030s, 2060s, and 2090s, upward altitudinal shifts of 165, 255, and 400 m are required. These findings support the implementation of a modified climate-adjusted provenancing strategy to reduce maladaptation risks and enhance climate resilience in reforestation and restoration programs. Full article

Traditional palliative care education may limit the development of clinical competencies and attitudes required to alleviate suffering and improve quality of life. Gamification has been proposed as an alternative educational strategy in this field. Background/Objectives: This study aimed to assess the association between gamification-based intervention and palliative care knowledge among nursing students at a public university. Methods: This single-group, pre–post-intervention study was conducted in the Nursing Program of the Universidad Técnica del Norte, Ecuador, including 136 students from the accessible population. Palliative care knowledge was assessed before and after the intervention using the validated Palliative Care Quiz for Nursing (PCQN-SV). Student satisfaction and Moodle usability were assessed using a 10-item Likert-type questionnaire. The gamified educational intervention was delivered online over 60 h. Data were analyzed using descriptive statistics and Wilcoxon signed-rank tests for paired comparisons, and exploratory logistic regression analyses were conducted to evaluate contextual differences across hospitals. Statistical significance was set at α = 0.05. Results: The mean age was 22.9 years (SD = 1.89), and 73.5% were female. Knowledge scores increased significantly after the intervention (Wilcoxon signed-rank test, p < 0.001; r = 0.35). The proportion of students achieving sufficient knowledge (≥13 correct responses) increased from 27.2% (37/136) at baseline to 49.3% (67/136) post-intervention. Contextual analysis indicated variability across clinical training sites, with Lago Agrio showing higher odds of sufficient knowledge (aOR = 3.25; 95% CI [1.26–8.41]; p = 0.015). Conclusions: The gamified intervention was associated with increased palliative care knowledge among nursing students. Heterogeneity across hospitals suggests that contextual factors may influence the magnitude of change. Full article

Sex determination in teleost fishes exhibits remarkable evolutionary plasticity; however, the underlying mechanisms remain largely elusive for many species of high economic importance. Herein, we provide the first genome-wide investigation of the genetic basis of sex determination in the European anchovy (Engraulis encrasicolus), an ecologically and commercially vital clupeiform fish. Using low-pass whole-genome resequencing of 100 sexually mature individuals (50 females and 50 males), we conducted a genome-wide association study (GWAS) and F_ST scans to identify sex-linked loci and characterize sex-determining regions (SDRs). Our analyses revealed two major candidate SDRs located on chromosomes 14 and 18, encompassing multiple sex-associated single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). Among these, the amhr2 (anti-Müllerian hormone type 2 receptor) gene on Chr14 displayed the strongest and most consistent association with phenotypic sex, marked by several male-specific missense SNPs and InDel variants. Comparative and transcriptomic analyses confirmed sex-biased expression of amhr2 and other SDR-linked genes, potentially indicating a male heterogametic (XY-like) genetic sex determination system. These results provide the first molecular evidence for a candidate SDR in E. encrasicolus, raise the possibility of involvement of amhr2 and additional loci in sex determination, and highlight rapid sex chromosome turnover within Clupeiformes. Our findings not only expand the understanding of teleost sex determination evolution but also establish a genomic foundation for developing molecular tools for sex identification and population management in anchovy fisheries. Full article

Oyamel forest, Abies religiosa (Kunth) Schltdl. et Cham., is a high-mountain ecosystem that contains abundant biodiversity, contributes to supporting traditional medicine, and represents a reservoir of medicinal plants. Despite this medicinal relevance, the potential of the flora of the Mexican Oyamel forest from Santuario del Agua Presa Corral de Piedra (SAPCP), Mexico, has been scarcely studied. This review focused on identifying the flora of the SAPCP which has been reported as medicinal resource in the literature through the recovery of ethnomedicinal uses and their proven pharmacological effects. In addition, phytochemical reports of the SAPCP medicinal flora and their pharmacological activities were integrated and analyzed to estimate their medicinal potential. The results showed that the SAPCP forest represents an important source of medicinal plants, with 39% of the total species reporting at least one ethnomedicinal use belonging to different taxonomic families, but mainly included Asteraceae, Lamiaceae, Rosaceae, and Solanaceae. The most commonly observed ethnomedicinal uses among all the species were against inflammation, infections, diarrhea, and diabetes, while antioxidant, antidiabetic, and anti-inflammatory effects were predominantly proven as pharmacological effects. The phytochemical results revealed a great diversity of secondary metabolites, although flavonoids, phenolic acids, and triterpenes were observed in a major number of species, many of which have been proven to exert anti-inflammatory, antidiabetic, and antibacterial effects through several action mechanisms. In conclusion, these results highlight the importance of sustainable management and the conservation of forest species, as they provide a reservoir of medicinal species that produce bioactive metabolites. Full article

Mountain regions across Europe face demographic decline and institutional fragmentation that hinder sustainable tourism development. This study analyzes the territorial governance system of the Val Canale and Canal del Ferro valleys (Italian Alps) with the aim of designing a stakeholder-based Organizational Model (OM) to strengthen sustainable tourism coordination in a peripheral mountain context. A qualitative single-case study approach integrates Stakeholder Analysis, Actor-Linkage Matrix, Appreciative Inquiry, and spatial contextualization to examine relational, institutional, and territorial dynamics. The findings reveal a territory rich in environmental and cultural assets—characterized by protected areas and extensive trail networks—yet constrained by fragmented inter-municipal cooperation and limited supra-municipal coordination. Governance fragmentation, rather than resource scarcity, emerges as the primary barrier to coherent territorial development. In response, the proposed multi-level Organizational Model introduces a valley-level coordination unit designed to institutionalize collaborative governance, enhance administrative capacity, and align local initiatives with regional strategies. By operationalizing stakeholder theory within a structured territorial framework, the study contributes to place-based governance literature and offers transferable insights for peripheral mountain regions facing similar coordination challenges. Full article

In the study of eggplant (Solanum melongena L.), a cross between the green peel line 19143 and the white peel line 19147 produced E4957 F₁ hybrids with a purple–brown peel. Self-fertilization of the F₁ hybrids yielded E4957 F₂ offspring with a segregation ratio of 27:9:21:7 among individuals with purple–brown, purple–red, green, and white peel colors, respectively, which was consistent with a genetic model controlled by reciprocal recessive epistasis between D and P, and Gv1 likely acting as a modifying factor. The green peel line 19143 exhibited higher chlorophyll but lower anthocyanin levels than the white peel line 19147, which contained low levels of both pigments, while the E4957 F₁ hybrids had elevated levels of both pigments. Two epistatic genes, D and P, associated with anthocyanin synthesis, were mapped on chromosomes 10 and 8, respectively. The putative modifying locus Gf, involved in chlorophyll accumulation in the flesh, was mapped on chromosome 8, and the localization interval was close to the previously reported Gv1 locus associated with chlorophyll synthesis in the peel. DNA markers (InDel22522, InDel5531, InDel-APRR2) were developed to genotype 237 F₂ individuals and correlate genotypes with phenotypes. Sequence analysis revealed a 6 bp deletion in the SmMYB1 (D) gene and a large deletion in the SmAPRR2-Like (Gv1) gene in the white peel line 19147, as well as a T to A mutation in the SmANS (P) gene in the green line 19143. This study provided evidence for inheritance between loci involved in anthocyanin and chlorophyll pathways contributing to eggplant peel color variation and provides molecular markers that may facilitate the breeding of eggplant varieties with diverse peel colors. Full article

Background/Objectives: Paediatric cataract is among the most common treatable causes of childhood blindness, caused by a genetically diverse disorder with variable clinical features. Although genetic factors significantly contribute to the development of paediatric cataracts, recent data on their genetic makeup and genotype–phenotype relationships in Saudi Arabia is limited. This study aims to investigate the genetic spectrum, inheritance patterns, and genotype–phenotype correlations of paediatric cataract in a Saudi population over twenty years. Methods: We conducted a retrospective cohort study of children diagnosed with congenital or juvenile cataracts between 2000 and 2019 at two major referral centres in Riyadh. Clinical, ocular, and systemic data were collected through multidisciplinary evaluations. Genetic analysis involved whole-exome and whole-genome sequencing performed at College of American Pathologists (CAP)-accredited laboratories. Variant interpretation was supported by bioinformatic and Artificial Intelligence (AI) prediction tools. Genotype–phenotype relationships were systematically analysed. Results: The study included 28 cases of genetically confirmed paediatric cataracts. Variants classified as pathogenic or likely pathogenic were identified in 13 genes. Autosomal recessive inheritance was predominant, with many patients exhibiting homozygous variants, often due to consanguinity. Two novel variants were identified in the Collagen Type XVIII Alpha 1 Chain (COL18A1) and the RAB3 GTPase-activating protein catalytic subunit 2 (RAB3GAP2) genes. Considerable phenotypic variability was observed, even among patients with the same mutation, particularly those with the recurrent CRYBB1 c.171del (p.Asn58fs) mutation. Syndromic cataracts were more frequently associated with loss-of-function variants and multisystem features. Conclusions: This study offers updated insights into the genetics and clinical presentation of paediatric cataract in Saudi Arabia. It highlights high genetic diversity, unique inheritance patterns, and notable genotype–phenotype variability, emphasising the importance of early genetic testing and multidisciplinary assessment for improved diagnosis, management, and counselling. Full article

Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m² per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. Full article

Microplastics impact coral reefs due to their presence in the water column. This is the case of Ingeniero Reef, which borders the Veracruz-Boca del Rio metropolitan area. The objective of this study was to determine the presence of microplastics in the feeding zone adjacent to the corals located on Ingeniero Reef. Two sampling periods were conducted (dry and rainy seasons, 2023), obtaining water samples from the area adjacent to the corals and from the water column, with 20 per sampling period. In the laboratory, the microplastics were separated and classified by type, size, and color. A one-way ANOVA was performed to compare microplastic concentration between the two seasons and average size in corals and the water column, and the Bray–Curtis index was applied. A new technique for obtaining microplastics from coral reefs was developed. The concentration of microplastics varies according to the climatic season, with fibers being the dominant type. The size of microplastics can be a determining factor for corals. The development and application of standardized protocols for studying microplastics will allow for more reliable monitoring programs, yielding comparable results that will enable the assessment of the impact of this emerging pollutant. Full article

Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and primarily affects the respiratory, digestive, and reproductive systems. Globally, CF is most prevalent among European ancestry, with an incidence rate of approximately 1/2500 to 1/3500. In China, the incidence is about 1/128,000. However, CF is not extremely rare in the Chinese population; rather, its prevalence is significantly underestimated. The CFTR mutation spectrum in China is highly unique, characterized by an extremely low frequency of p.Phe508del. Instead, region-specific mutations such as p.Gly970Asp, p.Ile1023Arg, and p.Arg553Ter predominate, alongside a high proportion of splicing variants and complex rearrangements. A significant proportion of Chinese CF patients primarily present with CF-like phenotypes within the CF-related disease spectrum (such as congenital bilateral absence of the vas deferens and pseudo-Bartter syndrome), exhibiting overlapping features with classic CF but lacking typical respiratory-dominant symptoms. This review examines how these atypical symptoms deviate from the diagnostic pathways established in Western countries. Establishing localised data and functional platforms is a prerequisite for achieving precision medicine. Achieving a transition from symptom-focused care to defect-correcting therapy will require coordinated multicenter collaboration and sustained infrastructure development. Full article

In traditional wind turbine (WT) operation and maintenance, fault diagnosis and repair have long been relied on, yet the demand for continuous operation under faults persists. To address this, this study proposes a triggered fault-tolerant control framework for wind turbines with zonotope-based interval estimation. The method enhances safety from point to range estimation of FDI, reduces network traffic load via a WT load region-based adaptive event-triggered mechanism, and enables fast, robust fault diagnosis/isolation using interval residuals. A damage equivalent load (DEL)-sensitive cost term balances structural fatigue suppression while ensuring power tracking and safety constraints. Theoretically, Linear Matrix Inequality (LMI) conditions based on common quadratic Lyapunov ensure closed-loop stability and bounded observation errors, with proven interval residual fault sensitivity and triggering reliability. Numerically, on the standard NREL 5-MW WT model under multi-conditions (turbulence, faulty communication), it achieves an average power tracking accuracy of 95.56%, 28.68% fatigue suppression, and 67.40% bandwidth saving. Overall, it synergistically optimizes robust estimation, economical communication, and fatigue-aware control, providing a theoretically rigorous and experimentally validated technical framework for engineering-scale WT reliability improvement and lifespan extension. Full article