Maria José

Department of Biochemistry, Federal University of Santa Catarina, Florianopolis 88040-900, Brazil

IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain

Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, 15706 Santiago de Compostela, Spain

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.

Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Diogo de Botelho nº 1327, 4169-005 Porto, Portugal

Purpose: This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC). Patients and Methods: Part 1 determined the recommended dose for expansion (RDE) of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate (cORR) by independent central review. Results: Seven patients with mBC were enrolled in part 1 and received T-DXd 3.2 mg/kg (4 patients) or 5.4 mg/kg (3 patients) plus nivolumab. The RDE for T-DXd was 5.4 mg/kg plus nivolumab 360 mg intravenously/3 weeks. In part 2, 32 patients with HER2-positive mBC (cohort 1; inclusive of 3 administered 5.4 mg/kg in part 1), 16 with HER2-low mBC (cohort 2), 30 with HER2-high mUC (cohort 3), and 4 with HER2-low mUC (cohort 4) were enrolled. At data cutoff (July 22, 2021), the cORR (95% CI) for cohorts 1-4 was 65.6% (46.8%-81.4%), 50.0% (24.7%-75.3%), 36.7% (19.9%-56.1%), and not assessed due to small sample size, respectively. Median treatment duration (range) with T-DXd in cohorts 1-4 was 8.9 (1-23), 6.9 (1-21), 3.9 (1-21) months, and not assessed; most common treatment-emergent adverse event was nausea (55.2%, 62.5%, 73.3%, 75.0%). Adjudicated drug-related ILD/pneumonitis rates (cohorts 1-3) were 20.7%, 0%, and 20.0% (1 grade 5 each, cohorts 1 and 3). Conclusion: T-DXd plus nivolumab demonstrated promising antitumor activity in HER2-expressing mBC or mUC and safety consistent with the known profile of T‑DXd. ILD/pneumonitis is an important risk and requires careful monitoring and prompt intervention.

Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, 08041 Barcelona, Spain

We conducted semi structured in-person interviews with 36 dairy farmers in a dairy producing region in southern Brazil undergoing intensification. Thematic analysis revealed that farmers' perceptions of cow welfare were closely tied to their production environment. Farmers in pasture-based systems emphasized the importance of outdoor access and grazing, associating these with the cows' intrinsic needs and longevity. Conversely, farmers operating confined systems, or those with positive attitudes towards transitioning to confinement, linked cow welfare to practices that aim at minimizing environmental stressors, enhancing comfort, and boosting productivity. Despite these differing views, empathetic concerns towards the cows were evident in both groups and influenced decisions such as improving farm infrastructure or using anesthetics in invasive procedures. However, the transition to confined systems was associated with a more instrumental view of animals, as seen in the abandonment of naming cows and in a greater focus on productive performance. All things considered, this study suggests that working structures may influence farmers' perceptions of animal care, indicating that farm animal welfare likely depends not only on farmers' attitudes but also on global and local policies that shape agricultural practices through incentives and constraints.

Abstract Background Obesity is a complex, multifactorial disease with rising global prevalence.

Postgraduate Program in Clean Technologies, Cesumar University—UNICESUMAR, Maringa 87050-390, PR, Brazil