Public reason and food policy

Ten-year trend of rituximab use for hematological malignancies: a multiregional real-world study using the Italian VALORE distributed database network

To assess the use of rituximab in non-Hodgkin lymphoma (nHL) and chronic lymphocytic leukemia (CLL) in light of the evolving regulatory landscape, including the introduction of subcutaneous and biosimilar formulations in the past decade. A retrospective cohort study was conducted using the VALORE distributed database network covering nine Italian regions (2012–2022). Patients with at least one rituximab dispensing and a previous nHL or CLL diagnosis were included. Annual prevalence rates (per 10,000 inhabitants) were estimated for intravenous originator, biosimilar, and subcutaneous formulations. Switch rates between originator and biosimilar were assessed by index year at 1 year of follow-up. We selected 73,870 prevalent rituximab users. Prevalence peaked in 2019 (4.6/10,000) and declined in 2022 (3.4/10,000), with originator use dropping from 4.2 to 0.2/10,000. Among 24,258 incident users (nHL: 21,001; CLL: 3,257), originator-to-biosimilar switch rates rose from 12.5% (2017) to 33.3% (2022) in nHL ( p  < 0.05) and from 10.3% (2017) to 78.3% (2020) in CLL ( p  < 0.05). Biosimilar-to-originator switches were rare in CLL (3.8%) but more frequent in nHL (15.3%), due to subcutaneous switch. These findings show a shift from originator to biosimilar rituximab in Italy, alongside a recent decline in its use, likely driven by COVID-19 pandemic and new treatment strategies.

Antigenic drift in SARS-CoV-2: diminished vaccine protection in pediatric populations against Omicron and its JN.1 subvariant

The COVID-19 vaccination campaign for children in Brazil evolved gradually from 2021 to the present, adapting to regulatory framework from the Brazilian Health Regulatory Agency (ANVISA). However, while adults received updated vaccines targeting newer variants, children and adolescents continued to receive vaccines based on the original wild-type strain. This study evaluates the vaccine-induced protective immunity, measured by serum antibody and neutralization responses, in vaccinated ( n  = 61) and unvaccinated ( n  = 13) pediatric populations against the wild-type (WT), Omicron BA.1, and JN.1 SARS-CoV-2 variants. Vaccinated children exhibited significantly higher antibody levels and neutralization titers against WT compared to unvaccinated peers ( p  ≤ 0.0001). However, responses to BA.1 were drastically reduced, and JN.1 subvariant neutralization was limited in both groups. Immunoinformatic analysis revealed a marked decline in conserved neutralizing antibody-targeting epitopes within the Spike protein: from 465 in WT to 49 in BA.1 and 41 in JN.1. This substantial antigenic drift underscores the immunological gap created by vaccinating children with outdated formulations. Our findings highlight the urgent need for updating pediatric vaccines to include antigens from circulating virus variants in order to increase immune protection and reduce susceptibility to infection and controlling community transmission.

Establishing a pediatric solid tumor PDX biobank for precision oncology research

Developing advanced preclinical models and targeted therapies is essential for reducing cancer-related deaths in children with solid tumors. Patient-derived xenografts (PDX) have the potential to replicate key elements of the original tumor, including morphology, genetic alterations, and microenvironment, making them valuable tools for studying tumor biology and drug response. We implanted 124 pediatric solid tumor samples, collected for 1 y, into NOD/SCID/IL2Rg (NSG) mice. Tumor fragments were placed subcutaneously, and the animals were monitored for up to 1 y. Histopathology, Short Tandem Repeat (STR) profiling, RT-PCR and/or RNA-sequencing were performed to confirm tumor identity and detect driver fusions. Fifty-five xenografts were successfully established (44.35% of implanted samples), representing 19 tumor types. Sarcomas, notably osteosarcoma, Ewing sarcoma, synovial sarcoma, and rhabdomyosarcoma, displayed first-generation engraftment rates above 55%. Central nervous system tumors had lower success, reflecting unique microenvironmental requirements. Histopathology and STR concordances were 85.45% and 81.1%, respectively, while 92.6% of sarcoma PDXs retained original fusion genes. Second-generation xenografts showed faster growth, suggesting adaptation to the murine host. Sporadic discrepancies, such as new fusions or lymphoproliferative expansions, indicated the need for ongoing molecular validation parallel to other techniques. A pediatric PDX biobank can effectively capture key tumor features while facilitating the study of therapeutic responses and tumor evolution. Our models confirm the feasibility of achieving stable histological and molecular profiles, offering a valuable resource for precision oncology research. Ultimately, these pediatric PDXs could accelerate the discovery of targeted therapy and significantly improve treatment outcomes.

Just Care: Messy Entanglements of Disability, Dependency, and Desire by Akemi Nishida, USA, Temple University Press, 2022, 264 pp., $110.50 USD (hardcover), EAN 9781439919897, $34.95 USD (paperback), EAN 9781439919903, $34.95 USD (eBook), EAN 9781439919910

Green-reinforced clay sandy soil with natural fibers

Several studies focus on enhancing soil strength through the incorporation of natural or synthetic fibers. However, there is limited published data on the effectiveness of rice husk in soil reinforcement. The use of rice husk as a reinforcing material is supported by the fact that rice is one of the most produced and consumed cereals globally. In this article, we analyze the behavior of a clayey soil from southern Brazil with the addition of 0.5, 0.75, and 1% rice husk (RH), comparing it to coconut coir (CC) and curauá fibers (CU). In unconfined compressive strength tests (UCS), increases in soil strength of 20, 40, and 140% were observed for RH, CC, and CU, respectively, compared to pure soil. From consolidated undrained triaxial compression tests, both unreinforced soil and soil reinforced with 1% RH, CC, and CU were examined. The triaxial tests revealed an increase in the internal friction angle of 72 and 98%, alongside a decrease in cohesion of 57 and 94% due to the addition of CC and CU, respectively, in terms of effective stress. In contrast, RH did not significantly enhance the soil’s behavior, likely due to its shorter fiber length.

Preface to the Special Issue on the IFMIF-DONES fusion neutron source

DONES performance, experimental capabilities and perspectives

Extended pharmacological thromboprophylaxis and clinically relevant venous thromboembolism after major abdominal and pelvic surgery: international, prospective, propensity score-weighted cohort study

Differential motor neuron activity in rats during successful and failed grasping

A substantial body of literature has focused on neural signals evoked by errors emerging during the execution of goal-directed actions. It is still unclear how motor cortex activity during movement execution relates to feedback error processing. To investigate this, we recorded primary motor cortex (M1) single-unit activity in rats during a grasping task. About half of the recorded neurons showed modulation of their firing activity that did not depend on success or failure, which we termed outcome-independent neurons. Other neurons showed a difference in their discharge profile when comparing successful and unsuccessful trials, which we called outcome-dependent neurons. Among both outcome-dependent and -independent neurons, we further distinguished neurons presenting their maximum firing rate in specific epochs as defined by the task. We compared the cortical distribution of outcome-independent and outcome-dependent neurons to cortical maps of complex forelimb movements evoked by intracortical microstimulation in additional animals. The majority of outcome-independent neurons was localized within the limb extension and paw open-closure movement representations. Outcome-dependent neurons were not clearly associated to particular motor representations. Cortical arrangement of neurons, both outcome-independent and outcome-dependent, and their correlation with distinct movement representations, can serve as indicator for anticipating potential outcomes before the conclusion of an action.