Roxadustat (RXD) is an approved drug substances for the treatment of renal anemia. It has poor aqueous solubility and photochemical stability. This study employs a comprehensive approach to enhance the stability and physicochemical properties RXD through coformer selection and characterization. The investigation integrates delta pKa analysis, molecular complementary assessment, molecular electrostatic potential surface analysis, and machine learning techniques to predict potential co-crystal formation and binding interactions between drug molecules and coformers. The co-crystal screening which lead to in a novel RXD-nicotinamide co-crystal (RXD-NA). Experimental characterization underscores the physical and chemical stability of the co-crystals. To elucidate the supramolecular synthons and understand the intermolecular interactions in the RXD-NA co-crystal, Hirshfeld surfaces analysis, quantum theory of atoms in molecules (QTAIM) analysis and non-covalent interaction (NCI) analysis were performed. Computational analysis of photo-isomer formation aligns with experimental observations, further enhancing our understanding of RXD-coformer interactions. RXD-NA co-crystal was found photo-chemically stable as compared to free base API drug substance. This integrated methodology provides a systematic framework for informed co-crystal design, holding promise for optimizing RXD formulations based on molecular interactions and stability considerations. Consequently, this study contributes valuable insights to the field of rational drug design and formulation optimization.
- MeSH
- Glycine * MeSH
- Solubility MeSH
- Publication type
- Journal Article MeSH
Tapeworms of the genus Proteocephalus Weinland, 1858 (Cestoda: Proteocephalidae) are common and widespread intestinal parasites of whitefish (Coregonus spp., Salmonidae: Coregoninae). Previous taxonomic studies, based solely on morphology and inconsistently fixed specimens, concluded that all salmoniform fish, including whitefish, are parasitised by a single euryxenous and highly polymorphic species, Proteocephalus longicollis (Zeder, 1800). However, recent molecular phylogenetic analyses have revealed the existence of several species specific to individual genera or even species of salmoniform fish. In this study, Proteocephalus fallax La Rue, 1911 is redescribed based on newly collected and genetically characterised specimens from several Coregonus species in Switzerland, the type locality of the species, and in Norway. This cestode was previously synonymised with P. exiguus La Rue, 1911, a parasite of whitefish in North America, but the two species are not closely related. Proteocephalus fallax differs from P. exiguus in its larger body size, wider proglottids, shorter cirrus sac and broader scolex. In addition, the other Proteocephalus species described in whitefish are briefly discussed, with comments on their validity, host range and distribution.
- MeSH
- Cestoda * classification anatomy & histology isolation & purification MeSH
- Cestode Infections * veterinary parasitology MeSH
- Phylogeny * MeSH
- Fish Diseases * parasitology MeSH
- Salmonidae * parasitology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Norway MeSH
- Switzerland MeSH
Well-being and social interaction are among the primary goals to be achieved for the elderly. Intergenerational physical activity (PA) has gained increasing attention due to its potential to encourage PA and social interaction, providing both social and physical benefits to both younger and older individuals. This review aimed to gain a deeper understanding of the potential roles of PA in facilitating intergenerational interactions and provide practical insights. Methods: Following PRISMA guidelines, the systematic review identified specific keywords to search for articles that met the chosen inclusion and exclusion criteria (n. 5 RCT articles, selected between 2009 and 2024), conducted by three independent reviewers. Scopus, PubMed, EBSCOhost, and Web of Science were consulted to identify relevant articles. Risk of bias was assessed using Cochrane RoB 2. For the narrative dissertation, articles were identified across three key areas of focus: types of PA, age groups, and intended goals. Results: Few studies have specifically implemented PA protocols in intergenerational relationships, and most have planned remote activities without monitoring outcomes. The main advantages of intergenerational PA are oriented towards the social and relational sphere rather than simple PA involvement. Conclusions: For the elderly, these programs may help mitigate age-related deficits, while children and adolescents, when adapting to their older counterparts, experience greater effectiveness when provided with clear guidance during shared activities. Considering the characteristics and needs of individuals of different ages, different activities must be proposed to obtain different results. The organization of workshops and preparatory sessions will help in facilitating relationships and interactions among participants.
- Publication type
- Journal Article MeSH
- Review MeSH
The Strengthening the Screening of Lung Cancer in Europe (SOLACE) initiative, supported by Europe's Beating Cancer Plan, is dedicated to advancing lung cancer screening. This initiative brings together the most extensive pan-European network of respiratory and radiology experts, involving 37 partners from 15 countries. SOLACE aims to enhance equitable access to lung cancer screening by developing targeted recruitment strategies for underrepresented and high-risk populations. Through comprehensive work packages, SOLACE integrates scientific research, pilot studies, and sustainability efforts to bolster regional and national screening efforts across EU member states. CRITICAL RELEVANCE STATEMENT: The SOLACE project aims to facilitate the optimization and implementation of equitable lung cancer screening programs across the heterogeneous healthcare landscape in EU member states. KEY POINTS: The effectiveness of lung cancer screening is supported by both scientific evidence and now increasing legislative support. SOLACE aims to develop, test, and disseminate tools to facilitate the realization of lung cancer screening at both a national and regional level. Previously underrepresented populations in lung cancer screening will be targeted by tailored recruitment strategies. SOLACE forms the first pan-European network of experts poised to drive real-world implementation of lung cancer screening.
- Publication type
- Journal Article MeSH
Despite significant improvement in the survival of pediatric patients with cancer, treatment outcomes for high-risk, relapsed, and refractory cancers remain unsatisfactory. Moreover, prolonged survival is frequently associated with long-term adverse effects due to intensive multimodal treatments. Accelerating the progress of pediatric oncology requires both therapeutic advances and strategies to mitigate the long-term cytotoxic side effects, potentially through targeting specific molecular drivers of pediatric malignancies. In this report, we present the results of integrative genomic and transcriptomic profiling of 230 patients with malignant solid tumors (the "primary cohort") and 18 patients with recurrent or otherwise difficult-to-treat nonmalignant conditions (the "secondary cohort"). The integrative workflow for the primary cohort enabled the identification of clinically significant single nucleotide variants, small insertions/deletions, and fusion genes, which were found in 55% and 28% of patients, respectively. For 38% of patients, molecularly informed treatment recommendations were made. In the secondary cohort, known or potentially driving alteration was detected in 89% of cases, including a suspected novel causal gene for patients with inclusion body infantile digital fibromatosis. Furthermore, 47% of findings also brought therapeutic implications for subsequent management. Across both cohorts, changes or refinements to the original histopathological diagnoses were achieved in 4% of cases. Our study demonstrates the efficacy of integrating advanced genomic and transcriptomic analyses to identify therapeutic targets, refine diagnoses, and optimize treatment strategies for challenging pediatric and young adult malignancies and underscores the need for broad implementation of precision oncology in clinical settings.
- MeSH
- Child MeSH
- Genomics * methods MeSH
- Precision Medicine * methods MeSH
- Cohort Studies MeSH
- Infant MeSH
- Medical Oncology methods MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neoplasms * genetics therapy MeSH
- Child, Preschool MeSH
- Gene Expression Profiling MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
