Search Results (22,791)

Raisins come from dried Vitis vinifera L. grapes. They are consumed worldwide, and their shape, color, texture, and taste largely determine consumer preference and market success. Consumers often select raisins based on visual appeal—namely color—without insight into how this relates to nutritional quality. Therefore, this study evaluated raisins of different colors based on non-targeted metabolomics to reveal the nutritional differences among differently colored raisins and to measure the differences in antioxidant capacity. Compared with green raisins (‘Sultanina’), 377–381 differential metabolites were identified in other colored varieties. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these metabolites were enriched in pathways such as ‘biosynthesis of other secondary metabolites’ and ‘amino acid metabolism’. The comparison of the antioxidant capacity of raisins of different colors shows that the darker the color of the raisins, the stronger their antioxidant capacity. Correlation analysis between total antioxidant capacity and 14 differential metabolites showed a significant positive correlation. Notably, syringetin levels in black raisins (‘Blackcurrant’ and ‘Sweet Sapphire’) were substantially higher—148.31 and 515.94 times greater, respectively—than in green raisins (‘Sultanina’). This elevated syringetin content may significantly contribute to the enhanced antioxidant capacity of black raisins. Furthermore, based on the positive ion mode, the relative contents of 24 and 12 differential metabolites were relatively high in green and red raisins, respectively. The negative ion model identified that 19 and 4 differential metabolites had relatively high contents in green and red raisins. These metabolites may be linked to the unique health benefits of red and green raisins. This study provides valuable insights for consumers selecting raisins based on health needs and for companies developing raisin-based health products. Full article

Background: Wax synthase/diacylglycerol acyltransferases (WS/DGATs), often referred to as WSD proteins, represent a class of key enzymes that catalyze the biosynthesis of wax esters in plants and other organisms. However, the WSD gene family in wheat (Triticum aestivum) has not been systematically characterized. Methods: A comprehensive genome-wide identification and bioinformatic characterization of the WSD gene family were conducted in wheat, followed by an analysis of chromosomal locations, gene structures, conserved motifs, phylogenetic relationships, expression profiles, and cis-element predictions. Results: In this study, a total of 43 TaWSDs were identified through genome-wide analysis in wheat. All identified TaWSD members exhibit highly conserved structural features and contain the core catalytic motif HHXXXDG. Phylogenetic analysis of WSD proteins from 63 species revealed that WSDs in Triticeae, including wheat, were mainly clustered into four distinct clades. Furthermore, sequence divergence among TaWSDs from different clades was primarily localized to the N-terminal region. Notably, expression profile analysis demonstrated that TaWSD genes display organ-specific expression patterns in wheat. Among them, 12 TaWSDs showed the highest expression levels in the leaf lamina joint, implying their potential involvement in the regulation of leaf angle formation. Additionally, 27 transcription factors were computationally predicted as putative regulators of TaWSDs, although their exact roles require further experimental confirmation. Conclusions: Our findings provide novel insights into the biological functions of the wheat WSD gene family and offer new perspectives for elucidating their molecular mechanisms underlying plant architecture regulation. Full article

Yeyong mustard is a mustard vegetable belonging to the Brassicaceae family and the Brassica genus. This study assembled, annotated, and analyzed the chloroplast genome of Brassica juncea L., aiming to clarify its systematic evolutionary relationship with other cruciferous plants. The study used the Illumina NovaSeq 6000 platform to sequence the entire chloroplast genome of leaf mustard, and systematically analyzed its genome structure, repeat sequences, nucleic acid diversity, and codon preferences using bioinformatics methods. At the same time, the phylogenetic relationships were constructed by combining the leaf chloroplast genome sequences of other cruciferous plants. The results showed that the chloroplast genome of leaf mustard had a total length of 153,490 bp and a GC content of 36.36%, exhibiting a typical tetrad structure; a total of 132 coding genes were annotated, including 87 mRNA genes, 37 tRNA genes, and eight rRNA genes, and no pseudogenes were found. Codon preference analysis shows that leucine (Leu) has the highest frequency of use, with 32 codons having a relative synonymous codon usage (RSCU) greater than 1, mostly ending in A or U; there are 37 scattered repetitive sequences and 315 simple repetitive sequences in the genome. Ka/Ks analysis showed that the chloroplast genes of leaf mustard were subjected to purification selection as a whole, while genes such as nadhF and petD showed positive selection, which is speculated to be related to adaptive evolution. The results of the phylogenetic analysis further confirm that the chloroplast genome of leaf mustard has a typical tetrad structure and is relatively conserved. It is most closely related to mustard greens in terms of evolutionary relationship, followed by Brassica plants such as nori and turnip, and is also closely related to Brassica plants such as European rapeseed. This study elucidated the conservative characteristics and evolutionary patterns of the chloroplast genome in mustard leaves, providing theoretical support for the phylogenetic research of the Brassicaceae family and the development and utilization of germplasm resources. Full article

Oral squamous cell carcinoma (OSCC) is a prevalent form of head and neck cancer that typically develops on the lip or within the oral cavity. Although there have been advances in early detection and treatment, the prognosis for patients, particularly those with advanced-stage disease, remains poor. Liquid biopsy, particularly through the analysis of cell-free DNA (cfDNA) in plasma and urine, has emerged as a promising tool for non-invasive cancer detection and monitoring. This study assessed cfDNA concentration dynamics in plasma and urine samples from 32 OSCC patients, with 5 undergoing genomic characterization by targeted next-generation sequencing (NGS). CfDNA levels were higher in patients compared to healthy controls and showed transient increases following treatment initiation, likely reflecting tumor cell death, followed by a gradual return to baseline. However, cfDNA concentrations were not significantly associated with tumor stage, recurrence, or progression-free survival. Targeted NGS analysis revealed a heterogeneous mutational landscape, identifying 76 variants across tumor tissue and initial cfDNA, with 30.3% shared between both sources. Recurrent hotspot mutations were detected in several important genes, including TP53, PIK3CA, KRAS, APC, and FBXW7. Urine cfDNA also captured several mutations absent from plasma or tissue, supporting its complementary value. These findings demonstrate that cfDNA analysis can dynamically reflect treatment response and capture tumor heterogeneity in OSCC. While informative, cfDNA quantification alone offers limited prognostic reliability, reinforcing the need for a multidimensional approach that includes genomic and clinical evaluation. Overall, this study supports the potential of liquid biopsy as a real-time, non-invasive tool for molecular monitoring and personalized management of OSCC patients. Full article

Background:Apocynum venetum L., a saline–alkali-tolerant plant, is a valuable resource for forage, textile, and medicinal purposes. This study aimed to identify the AQP gene family in A. venetum genome-wide and explore their potential functions under abiotic stress. Methods: Gene identification, phylogenetic relationships, structural features, and evolutionary patterns were analyzed, along with gene expression patterns and correlations with physiological traits. Results: Phylogenetic analysis classified the 25 candidate AvAQP genes into five distinct subgroups, with members exhibiting conserved gene structures, motifs, and phosphorylation patterns. Subcellular localization predictions indicate targeting primarily to the plasma membrane or the vacuole, with one isoform (AvTIP5;1) predicted to localize to both. Synteny analysis revealed three intraspecific and multiple interspecific gene pairs (26 with Arabidopsis thaliana and 34 with Medicago truncatula). In silico promoter analysis identified 49 cis-regulatory elements associated with phytohormone response, stress signaling, and development, providing preliminary clues for their possible involvement in diverse biological processes. qPCR profiling under abiotic stress demonstrated tissue-specific expression patterns among AvAQP members under different stress conditions. Correlation analyses between gene expression and physiological indicators (growth- and water-related traits) were predominantly positive, with only a few negative correlations under stress conditions, suggesting that AvAQP expression may be associated with plant physiological status. Conclusions: This study presents a comprehensive analysis of the AQP family in A. venetum providing a foundation for further functional characterization of these genes in response to abiotic stress. Full article

Whole-cell biocatalysis presents a sustainable and efficient approach for the selective reduction in α,β-unsaturated bonds in flavonoid derivatives. This study investigates the capability of yeast strains from the Yarrowia clade to catalyze the chemoselective reduction of 4′-methoxychalcone (1a) to its dihydro derivative. All tested strains exhibited similarly high hydrogenation activity, indicating a broadly conserved enoate reductase function within the clade. Among them, Yarrowia lipolytica KCh 71, previously reported and well characterized in the literature, was selected for preparative-scale transformation of a diverse series of synthetic methoxychalcones bearing additional methoxy groups in positions C-2, C-3, C-4, C-5, and C-6 of ring B. All derivatives were effectively converted into the corresponding dihydrochalcones, with yields ranging from 62% to 92%. Among the tested derivatives, the 2′,4′,6′-trimethoxy chalcone (7a) did not undergo biotransformation under our conditions, whereas mono- and di-methoxy derivatives (2a–6a) were efficiently reduced. These results confirm the broad substrate tolerance, high efficiency, and potential scalability of Y. lipolytica KCh 71, supporting its potential as a whole-cell biocatalyst for the sustainable synthesis of bioactive dihydrochalcones. The consistently high hydrogenation activity observed across 21 tested strains suggests the involvement of evolutionarily conserved enoate reductases. Bioinformatic analysis supports that the Yarrowia clade possesses a robust complement of Old Yellow Enzymes (OYE), providing a reliable enzymatic basis for the observed chemoselective reductions. All Yarrowia tested strains showed the same general transformation type, although the extent and rate of conversion differed among strains, and Y. lipolytica KCh 71 was one of the most tolerant. The broad reduction in α,β-unsaturated chalcones is consistent with the action of flavoenzymatic ene-reductases, particularly Old Yellow Enzyme (OYE)–like reductases. Bioinformatic analysis of Yarrowia genomes reveals putative OYE homologs, supporting this mechanistic interpretation, although the specific enzymes were not identified in this study. Full article

Background: Urothelial bladder cancer (UBC) is a molecularly heterogeneous disease, and most sequencing studies have relied on bladder-specific or solid tumor-restricted panels. Whether broader pan-cancer assays provide additional clinically relevant information remains unclear. Methods: We performed targeted next-generation sequencing using an extended gene panel on tumor samples from 100 patients with UBC treated at a tertiary center. Somatic single-nucleotide variants, small insertions/deletions, copy-number alterations, and gene co-occurrence patterns were analyzed and correlated with clinicopathological features, disease-free survival (DFS), and overall survival (OS). Results: Recurrent alterations were identified in FGFR3 (≈50%), TP53 (≈35%), STAG2 (≈25%), and PIK3CA (≈20%), consistent with established molecular pathways in UBC. Less frequent but potentially actionable alterations, including mutations in BRCA1 and ALK, were also detected, reflecting the extended coverage of the panel. TP53 mutations were independently associated with worse OS, whereas STAG2 alterations were associated with improved OS, particularly in tumors without concurrent TP53 mutations. FGFR3 mutations showed a favorable but non-independent trend. No gene retained independent prognostic significance for DFS. Co-occurrence analysis revealed an FGFR3/PIK3CA-associated pathway and relative mutual exclusivity between FGFR3 and TP53. Copy-number alterations were modest overall. Comparison with TCGA data demonstrated a higher frequency of FGFR3 alterations in our cohort, likely reflecting the larger proportion of non–muscle-invasive tumors. Conclusions: Pan-cancer targeted sequencing provided a comprehensive genomic landscape of UBC, capturing canonical drivers and additional alterations that may be overlooked by bladder-restricted assays. The identification of TP53 and STAG2 as prognostic markers highlights the potential value of broader genomic profiling for biologically informed risk stratification in urothelial bladder cancer. Full article

Anthrax is one of the most significant zoonotic diseases in Albania due to its endemic presence in livestock, the potential for occupational exposure, and human cases. Although the implementation of risk-based livestock immunization, animal movement restrictions, and appropriate carcass disposal, the efficacy of targeted management remains limited in certain outbreaks due to insufficient enforcement of these measures. Their efficacy is specifically diminished by insufficient disinfection, the absence of grazing bans in contaminated pastures, and the absence of designated burial sites for the safe disposal of dead animals. District-level data on animal anthrax control programs were collected and analyzed for the period 2021–2025. In addition, a retrospective analysis of national datasets covering the same period was conducted using data from the national surveillance system, alongside a review of the relevant scientific and grey literature and aggregated program and routine surveillance data. Analysis showed that anthrax affected 149 animals in 97 farms, and the average number of animals per infected farm declined from 1.70 to 1.08, indicating a slight reduction within-farm outbreak. Hotspots for human anthrax were aligned with the animal cases and persisted particularly in the southern districts. The peak of outbreaks was in 2023, primarily driven by cattle (n = 32) and sheep (n = 24). Equine cases appeared only in 2024, with small clusters of 3 cases in both 2024 and 2025. Caprine cases remained consistently low throughout the period. Nevertheless, the number of outbreaks and within-herd cases are decreasing due to more rapid identification and response. Targeted surveillance on animal outbreaks provides critical insights into disease spread and links among affected farms in Albania. Therefore, One Health genomic surveillance and antibiotic susceptibility testing of Bacillus anthracis isolates are essential for understanding its epidemiology, transmission routes, and for tracing the sources of infection across humans, animals, and the environment. Full article

Dirofilaria immitis constitutes a significant global veterinary burden and an emerging zoonotic risk. Despite decades of study, the structural evolution of its scientific landscape remains unexplored. This study provides a comprehensive longitudinal analysis of global research on D. immitis to evaluate its trajectory, intellectual structure, and conceptual shifts over the last eight decades. A systematic bibliometric analysis was conducted following PRISMA guidelines adapted for bibliometrics. Data were retrieved from Web of Science Core Collection and Scopus, covering the period from 1945 to 2025. After deduplication and manual screening, a final corpus of 3589 documents was analyzed using performance indicators and science mapping techniques to assess growth patterns, geographic leadership, collaboration networks, and thematic evolution. The field exhibits a mature profile with a sustained mean annual growth rate of 2.39%. Production is geographically polarized, with the United States and Italy acting as the primary research hubs, though international collaboration networks are increasingly integrating endemic regions in the Global South. Thematic analysis reveals a profound paradigm shift: while early research (1945–1980) focused on parasite morphology and clinical description, the 21st century is characterized by a multidisciplinary approach dominated by molecular biology, the study of the endosymbiont Wolbachia, and the genetic mechanisms of macrocyclic lactone resistance. The intellectual structure is currently organized into distinct but interconnected clusters, linking established clinical pathology with emerging genomic and environmental control strategies. Research on D. immitis has evolved from a classical parasitology discipline into a complex biomedical ecosystem aligned with the One Health framework. The persistence of the disease, driven by drug resistance and climate-mediated vector expansion, has catalyzed a transition toward integrative research models. Future control strategies must transcend geographic borders, combining advanced genomic surveillance with ecological modeling to mitigate the impact of this transboundary disease on both animal and human health. Full article

Cassava brown streak disease (CBSD), caused by cassava brown streak virus (CBSV; Ipomovirus brunusmanihotis) and Ugandan cassava brown streak virus (UCBSV; Ipomovirus manihotis) (family Potyviridae, genus Ipomovirus), is increasingly becoming a threat to cassava production in several parts of Africa, especially in Eastern, Central and Southern Africa. In Kenya, the disease continues to wreak havoc on cassava production leading to a significant reduction in crop yields and economic losses of up to USD 1 billion. Variation in virus populations make the control of CBSD challenging as virus genomic variation can affect the accuracy of diagnostic tests, lead to resistance breaking isolates and jeopardize strategies of breeding for resistance. CBSV and UCBSV populations obtained from cassava fields in Kenya were characterized. In total, 44 new complete sequences of CBSV and UCBSV were assembled and 40 sequences successfully submitted to GenBank. Single Nucleotide Polymorphism (SNP) analysis revealed that the cylindrical inclusion protein (CI) is the most stable region across the genome of CBSV and UCBSV. In contrast, protein 1 (PI) and the coat protein (CP) were the most hypervariable regions. Phylogenetic analysis showed three major geographical groupings for both UCBSV and CBSV isolates, suggesting a continued spread of the viruses through human-mediated movement of infected planting materials. The data obtained in this study can support the development of disease management strategies through improved molecular diagnostic tests and targets for breeding for resistance against CBSD. Full article

The unique ecological gradients of Xinjiang have fostered a rich reservoir of genetic resources in local sheep populations. However, the population genetic structure, adaptive mechanisms to extreme environments, and the genetic basis underlying key economic traits of these breeds remain poorly understood. To address this gap, we performed whole-genome resequencing of 140 individuals from seven indigenous sheep populations—Altay, Bayinbuluke, Kazakh, Kirgiz, Bashibai, Turpan Black, and Yemule White—identifying 18,700,507 high-quality SNPs. Genetic diversity analyses revealed that all populations exhibited comparable levels of genetic diversity, with modest variation across breeds, with Turpan Black sheep exhibiting the highest observed heterozygosity (Ho = 0.3110) and proportion of polymorphic sites, whereas Kirgiz sheep showed comparatively lower values. Population structure analyses consistently indicated that geographic isolation is the primary driver of genetic differentiation, with Kirgiz sheep from the Pamir Plateau in southern Xinjiang displaying the greatest genetic distance relative to northern Xinjiang populations. By integrating multiple selection signature detection methods—including F_ST, π ratio, and XP-CLR—we found that genes under selection in Kirgiz sheep were significantly enriched in biological pathways related to stem cell pluripotency regulation (e.g., BMPR1B), DNA repair (e.g., DDB2), and neural development, thereby elucidating their unique genetic adaptations to high-altitude environments. In contrast, Turpan Black sheep appear to cope with heat stress through mechanisms involving basal transcriptional regulation (e.g., GTF2I), maintenance of protein homeostasis (e.g., DNAJB14), and melanin biosynthesis (e.g., MC1R). Furthermore, comparative analysis of body size identified a suite of candidate genes associated with growth and development (e.g., CUX1, KIT), which are primarily involved in transcriptional regulation, protein kinase activity, and the ubiquitin-mediated proteolytic system, thereby revealing a multi-layered genetic regulatory network governing body conformation. Collectively, this study provides a comprehensive genomic framework for understanding the genetic structure, adaptive evolution, and molecular basis of economically important traits in indigenous sheep breeds from Xinjiang, offering valuable candidate targets for future functional validation and precision breeding programs. 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

Colorectal cancer (CRC) is the third most common cancer globally and the second leading cause of cancer-related deaths. While intestinal microbiota dysbiosis is linked to CRC, the direct role of intratumoral bacteria in metastasis remains poorly understood. In this study, we isolated pathogenic bacteria from CRC tumor tissues, identified as Hungatella hathewayi (H. hathewayi), through the 16S rRNA gene and whole-genome sequencing. We developed specific primers (P48/P52) and polyclonal antibodies for detecting H. hathewayi in samples. Using quantitative real-time PCR (qPCR), we found significant enrichment of H. hathewayi in fecal samples from CRC patients compared to healthy controls, with mean fold changes of 137-fold and 142-fold for primers P48 and P52, respectively. Analysis of tissue samples revealed that H. hathewayi abundance was higher in CRC tumor tissues compared to normal tissues, with mean fold changes of 2.90 for P48 and 3.97 for P52. Fluorescence in situ hybridization (FISH), immunofluorescence (IF), and immunohistochemistry (IHC) confirmed its spatial distribution within tumor tissues. In vitro assays using CRC cell lines demonstrated that H. hathewayi-derived succinate upregulates HIF-1α and SUCNR1 expression and promotes cell metastasis by inducing epithelial–mesenchymal transition (EMT). Collectively, these findings identify H. hathewayi as a novel pro-metastatic bacterium and a potential non-invasive biomarker for CRC diagnosis, providing direct evidence for the role of intratumoral bacteria in CRC progression. Full article

Patients with Liver Hepatocellular carcinoma (LIHC) have a poor prognosis due to late-stage diagnosis and the limited efficacy of drug treatments. Dysregulation of nuclear pore complex (NPC) components, particularly nucleoporins (NUPs), may play a role in tumor progression. However, the specific role of NUP205 in LIHC has not been comprehensively investigated. We evaluated the expression, prognostic significance, epigenetic regulation, microRNA(miRNA) interactions, drug sensitivity, and biological functions of NUP205 in LIHC. Comprehensive bioinformatics analyses were performed using publicly available databases and web-based analysis platforms, including The Cancer Genome Atlas (TCGA), UALCAN, and the Kaplan–Meier Plotter (KM Plotter), among others. In vitro validation was performed using small interfering RNA (siRNA)-mediated knockdown of NUP205 in HepG2 cells, followed by quantitative reverse transcription PCR (RT-qPCR), apoptosis assay and wound-healing assay. NUP205 expression was significantly elevated in patients with LIHC and was associated with advanced clinicopathological features and poor prognosis. Promoter hypomethylation and miRNAs were identified as regulatory mechanisms influencing NUP205 expression. Increased NUP205 levels were associated with resistance to multiple chemotherapeutic agents. NUP205 knockdown significantly reduced messenger RNA (mRNA) expression in HepG2 and PLC/PRF/5 cells, and also reduced the expression of Transmembrane protein 209 (TMEM209) in HepG2 cells and improved sensitivity to doxorubicin. NUP205 expression was consistently associated with adverse clinicopathological features, poor prognosis, and altered drug sensitivity in LIHC. Integrative analyses suggest that NUP205 dysregulation may be linked to epigenetic and miRNA-associated regulatory mechanisms. These findings support NUP205 as a candidate prognostic biomarker and a potential regulatory factor in LIHC, warranting further mechanistic and protein-level validation. Further research is necessary to fully elucidate its underlying mechanisms and potential clinical applications. Full article

Limosilactobacillus fermentum KUB-D18 is a probiotic strain with significant potential in food fermentation and health promotion, yet the systems-level mechanisms underlying its physiological robustness remain elusive. To elucidate the metabolic remodeling strategies operating across growth phases, we developed an integrated framework combining genome-scale metabolic modeling (GSMM) with transcriptomics. A high-quality metabolic model for L. fermentum KUB-D18, designated iYH640 and comprising 640 genes, 1530 metabolites, and 1922 reactions, was constructed and validated against experimental growth data. Specifically, in vitro assays measuring biomass and glucose concentrations showed a maximum specific growth rate of 0.2696 h⁻¹ and a glucose uptake rate of 11.75 mmol gDCW⁻¹ h⁻¹, providing physiological constraints for the model. Using transcriptome-regulated flux balance analysis (TR-FBA), gene expression profiles from the logarithmic phase (L-phase) and stationary phase (S-phase) were integrated to quantify growth phase-specific metabolic flux distributions. These simulations revealed a distinct transcription-driven metabolic shift, in which the organism moves from a proliferation-oriented metabolic state with active central carbon metabolism and macromolecule synthesis to a maintenance-oriented state. This S-phase is characterized by reduced flux through anabolic pathways together with the selective preservation of redox balance and nucleotide homeostasis. Collectively, these results provide a quantitative explanation of how L. fermentum KUB-D18 balances growth and maintenance, offering a mechanistic basis for improving its stability and functional performance in industrial probiotic applications. Full article