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Simple Summary: We retrospectively evaluated the clinical outcomes and prognostic factors of 127 patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from the initiation of ARSI were assessed. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS varied among patients treated with enzalutamide, abiraterone acetate, apalutamide, and darolutamide (27.0, 20.0, 10.0, and 14.0 months, respectively; p = 0.33). Multivariate analysis indicated that a baseline PSA level of ≥3.67 ng/mL (p = 0.002) was significantly associated with poorer OS prognosis. ARSI demonstrated favorable efficacy in nmCRPC patients, with no significant differences in clinical outcomes among different types of ARSI. High baseline PSA of ARSI was found to have a significantly poor prognosis associated with OS. We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from ARSI initiation were assessed using the Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥ 3.67 ng/mL at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BC) in adolescents and young adults (AYA) has unique biological qualities, but the details of these features remain unclear, and treatment options are comparable to those of other age groups. In this study, we identified a gene that demonstrates a strong association with patient prognosis solely in AYA patients, despite the fact that its expression does not differ by age group. Although this gene, GALNT1, has no prognostic significance in whole BC, when examined in AYA BC, high GALNT1 was significantly associated with worse survival. Furthermore, high GALNT1 expression was found to be an independent factor for survival among several clinical features of AYA patients. Finally, high GALNT1 BC is associated with increased EMT, angiogenesis, and protein secretion in AYA patients, but not in the elderly. We report the clinical relevance of the GALNT1 gene in AYA BC. It is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance of GALNT1 expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of GALNT1 expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest GALNT1 expression compared to ER-positive/HER2-negative BC, GALNT1 levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high-GALNT1 expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in GALNT1 expression levels among AYAs and older patients. However, high GALNT1 expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high GALNT1 expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with high GALNT1 expression demonstrated low levels of CD8+ T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of GALNT1 BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that GALNT1 expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Multilevel societies are the most complex social structures in animals. They are social structures with nested levels of social organization, where stable "core units" gather to form higher-level groups. Such multiple-unit groups usually become very large (usually 100–1000 individuals), making it difficult to conduct observations. Most previous studies lack numerical definitions and descriptions; thus, it is largely unknown how and why animals, including humans, form multilevel societies. Aerial observation from unmanned aerial vehicles (drones) is a powerful method of capturing the spatial structures and movements of large animal groups. Recent advances in drone technology and its application have led to new discoveries, such as the spatial structure of multiunit groups and the underlying mechanisms of collective behavior. We review how previous studies have utilized drones and how drone applications have contributed to the understanding of multilevel societies. We will further discuss the potential opportunities and challenges with regard to drone observations in future studies. Unmanned aerial vehicles (drones) have recently been used in various behavioral ecology studies. However, their application has been limited to single groups, and most studies have not implemented individual identification. A multilevel society refers to a social structure in which small stable "core units" gather and make a larger, multiple-unit group. Here, we introduce recent applications of drone technology and individual identification to complex social structures involving multiple groups, such as multilevel societies. Drones made it possible to obtain the identification, accurate positioning, or movement of more than a hundred individuals in a multilevel social group. In addition, in multilevel social groups, drones facilitate the observation of heterogeneous spatial positioning patterns and mechanisms of behavioral propagation, which are different from those in a single-level group. Such findings may contribute to the quantitative definition and assessment of multilevel societies and enhance our understanding of mechanisms of multiple group aggregation. The application of drones to various species may resolve various questions related to multilevel societies. [ABSTRACT FROM AUTHOR]

Simple Summary: Cats (Felis silvestris catus) live with humans as domesticated animals. However, it is not clear how they have evolved from African wildcats (Felis silvestris lybica) through domestication. In this study, we compared the facial morphology of cats and wildcats to determine how the facial morphology of cats has changed in relation to their interactions with humans. Cats kept by humans had a smaller nose length and a lower eye angle compared with wildcats and feral cats, and these changes were found to influence cuteness ratings. The facial morphology of feral cats not living with humans was not significantly different from that of wildcats, suggesting that this change is due to the process of feralization. We aimed to clarify the changes in facial morphology of cats in relation to their interactions with humans. In Study 1, we compared the facial morphology of cats (feral mixed breed, owned domestic mixed breed, and owned domestic purebreds) with that of African wildcats. After collecting 3295 photos, we found that owned domestic cats' noses were significantly shorter than those of African wildcats and feral mixed breed, and there were no significant differences between the latter two. The eye angles were significantly more gradual in owned domestic purebreds than in the other groups. In Study 2, we examined the correlation between facial morphology and years with the owner, and found that the former is not affected by the latter. This suggests that changes in facial morphology are possibly transgenerational changes. The difference in facial morphology between wildcats and owned cats might be caused by domestication, and that between feral cats and owned cats might be due to feralization. In Study 3, we investigated whether cats' facial features affect cuteness ratings. We asked human participants to evaluate the cuteness of cats' face images and found that faces with shorter nose lengths were considered cuter. This suggests that owned domestic cats' facial morphology is preferred by humans. [ABSTRACT FROM AUTHOR]

Notch signaling plays various roles in cell-fate specification through direct cell–cell interactions. Notch receptors are evolutionarily conserved transmembrane proteins with multiple epidermal growth factor (EGF)-like repeats. Drosophila Notch has 36 EGF-like repeats, and while some play a role in Notch signaling, the specific functions of most remain unclear. To investigate the role of each EGF-like repeat, we used 19 previously identified missense mutations of Notch with unique amino acid substitutions in various EGF-like repeats and a transmembrane domain; 17 of these were identified through a single genetic screen. We assessed these mutants' phenotypes in the nervous system and hindgut during embryogenesis, and found that 10 of the 19 Notch mutants had defects in both lateral inhibition and inductive Notch signaling, showing context dependency. Of these 10 mutants, six accumulated Notch in the endoplasmic reticulum (ER), and these six were located in EGF-like repeats 8–10 or 25. Mutations with cysteine substitutions were not always coupled with ER accumulation. This suggests that certain EGF-like repeats may be particularly susceptible to structural perturbation, resulting in a misfolded and inactive Notch product that accumulates in the ER. Thus, we propose that these EGF-like repeats may be integral to Notch folding. [ABSTRACT FROM AUTHOR]

Yamaguchi et al. summarized pioneering studies using I Drosophila i models that linked ALS and CMT to epigenetic regulation associated with post-translational histone modifications and noncoding RNAs [[8]]. Indeed, the authors discuss that genetic approaches using I Drosophila i models identified several epigenetic regulators as important modifiers of phenotypes seen in ALS and CMT model flies. Further characterization of these factors in relation to these diseases would be an important future direction, not only for ALS and CMT research but also for studies related to other types of neurological and neurodegenerative disorders. The fruit fly I Drosophila melanogaster i is a highly tractable animal model to study various human diseases [[1]]. [Extracted from the article]