Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer.

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies.

Bluetongue virus serotype 12 in sheep and cattle in the Netherlands in 2024 - A BTV serotype reported in Europe for the first time.

Bluetongue (BT) is a viral vector borne disease primarily affecting ruminants such as sheep, cattle, and goats. On 3 September 2023, the Netherlands reported the first case of bluetongue virus serotype 3 (BTV-3/NET2023)), after being BTV free for eleven years. Vaccination with inactivated BT vaccines for serotype 3 has been applied in the Netherlands since May 2024.

Agricultural subsoil microbiomes and functions exhibit lower resistance to global change than topsoils in Chinese agroecosystems.

Soils play a critical role in supporting agricultural production. Subsoils, below 20 cm, underpin fundamental agroecosystem sustainability traits including soil carbon storage, climate regulation and water provision. However, little is known about the ecological stability of subsoils in response to global change.

Visualizing motions within the cochlea's organ of Corti and illuminating cochlear mechanics with optical coherence tomography.

Beginning in 2006, optical coherence tomography (OCT) has been adapted for use as a vibrometer for hearing research. The application of OCT in this field, particularly for studying cochlear mechanics, represents a revolutionary advance over previous technologies. OCT provides detailed evidence of the motions of components within the organ of Corti, extending beyond the first-encountered surface of observation.

More Than a Small Brain: The Importance of Studying Neural Function during Development.

The nervous system contains complex circuits comprising thousands of cell types and trillions of connections. Here, we discuss how the field of "developmental systems neuroscience" combines the molecular and genetic perspectives of developmental neuroscience with the (typically adult-focused) functional perspective of systems neuroscience. This combination of approaches is critical to understanding how a handful of cells eventually produce the wide range of behaviors necessary for survival.

Molecular heterogeneity in urothelial carcinoma and determinants of clinical benefit to PD-L1 blockade.

Checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have revolutionized cancer therapy across many indications including urothelial carcinoma (UC). Because many patients do not benefit, a better understanding of the molecular mechanisms underlying response and resistance is needed to improve outcomes. We profiled tumors from 2,803 UC patients from four late-stage randomized clinical trials evaluating the PD-L1 inhibitor atezolizumab by RNA sequencing (RNA-seq), a targeted DNA panel, immunohistochemistry, and digital pathology.

Long-term survival following anti-PD-(L)1 monotherapy in advanced urothelial cancer and an assessment of potential prognostic clinical factors: a multicentre observational study.

Background: Anti-PD-(L)1 agent are approved as first- and second-line treatment options in advanced urothelial cancer (UC), but information about long-term survival is scarce. There is a need for prognostic factors, as these may help in the decision-making concerning anti-PD-(L)1 in patients with UC. Here, we examined long-term survival following anti-PD-(L)1 in advanced UC and assessed clinical factors for their correlation with survival.

FGFR Inhibition in Urothelial Carcinoma.

Background And Objective: The 2024 US Food and Drug Administration approval of erdafitinib for the treatment of metastatic urothelial carcinoma (mUC) with FGFR3 alterations ushered in the era of targeted therapy for bladder cancer. In this review, we summarize the effects of FGFR pathway alterations in oncogenesis, clinical data supporting FGFR inhibitors in the management of bladder cancer, and the challenges that remain.

Methods: Original articles relevant to FGFR inhibitors in urothelial cancer between 1995 and 2024 were systematically identified in the PubMed and MEDLINE databases using the search terms "FGFR" and "bladder cancer".

Microbial genetic potential differs among cryospheric habitats of the Damma glacier.

Climate warming has led to glacier retreat worldwide. Studies on the taxonomy and functions of glacier microbiomes help us better predict their response to glacier melting. Here, we used shotgun metagenomic sequencing to study the microbial functional potential in different cryospheric habitats, i.

Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.

Background: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes.

Methods: In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group).

Specialized protist communities on mycorrhizal fungal hyphae.

Arbuscular mycorrhizal (AM) fungi not only play a crucial role in acquiring nutrients for plants but also serve as a habitat for soil microbes. Recent studies observed that AM fungal hyphae are colonized by specific bacterial communities. However, so far it has not been explored whether fungal hyphae and mycorrhizal networks also harbor specific communities of protists, a key group of microbes in the soil microbiome.

Quantifying concentration distributions in redox flow batteries with neutron radiography.

The continued advancement of electrochemical technologies requires an increasingly detailed understanding of the microscopic processes that control their performance, inspiring the development of new multi-modal diagnostic techniques. Here, we introduce a neutron imaging approach to enable the quantification of spatial and temporal variations in species concentrations within an operating redox flow cell. Specifically, we leverage the high attenuation of redox-active organic materials (high hydrogen content) and supporting electrolytes (boron-containing) in solution and perform subtractive neutron imaging of active species and supporting electrolyte.

The role of halophyte-induced saline fertile islands in soil microbial biogeochemical cycling across arid ecosystems.

Halophyte shrubs, prevalent in arid regions globally, create saline fertile islands under their canopy. This study investigates the soil microbial communities and their energy utilization strategies associated with tamarisk shrubs in arid ecosystems. Shotgun sequencing revealed that high salinity in tamarisk islands reduces functional gene alpha-diversity and relative abundance compared to bare soils.

Advancements in the front-line treatment of metastatic urothelial carcinoma.

Both the CheckMate-901 (gemcitabine-cisplatin plus nivolumab) trial and the EV-302 (enfortumab-vedotin plus pembrolizumab; EV+P) trial have shown a significant improvement in OS over standard (cis)platinum-based chemotherapy. The effect size, as well as the broader eligibility criteria for EV+P position this regimen as a compelling preferred candidate for the new standard of care in front-line mUC treatment.

Integrated noninvasive diagnostics for prediction of survival in immunotherapy.

Background: Integrating complementary diagnostic data sources promises enhanced robustness in the predictive performance of artificial intelligence (AI) models, a crucial requirement for future clinical validation/implementation. In this study, we investigate the potential value of integrating data from noninvasive diagnostic modalities, including chest computed tomography (CT) imaging, routine laboratory blood tests, and clinical parameters, to retrospectively predict 1-year survival in a cohort of patients with advanced non-small-cell lung cancer, melanoma, and urothelial cancer treated with immunotherapy.

Patients And Methods: The study included 475 patients, of whom 444 had longitudinal CT scans and 475 had longitudinal laboratory data.

Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study.

Background: Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1.

Platinum-Based Chemotherapy Induces Opposing Effects on Immunotherapy Response-Related Spatial and Stromal Biomarkers in the Bladder Cancer Microenvironment.

Purpose: Platinum-based chemotherapy and immune checkpoint inhibitors are key components of systemic treatment for muscle-invasive and advanced urothelial cancer. The ideal integration of these two treatment modalities remains unclear as clinical trials have led to inconsistent results. Modulation of the tumor-immune microenvironment by chemotherapy is poorly characterized.