A Prospective Non-interventional Real-World Study of cabozantinib in Pretreated Patients With Advanced Renal Cell Carcinoma Refractory to Vascular Endothelial Growth Factor-Targeted Therapy (CASSIOPE).

Background: There is a lack of published data on real-world cabozantinib use in patients with advanced renal cell carcinoma after prior vascular endothelial growth factor (VEGF)-targeted therapy.

Methods: CASSIOPE was a real-world, prospective, multicenter, non-interventional postauthorization safety study of cabozantinib in adult patients with advanced renal cell carcinoma in Europe following prior VEGF-targeted treatment (NCT03419572). Endpoints included cabozantinib utilization (dose modifications due to adverse events [AEs; primary endpoint], dose, dose modifications, and treatment duration), safety, effectiveness (progression-free survival [PFS], overall survival [OS], best overall response [BOR]), and healthcare resource utilization.

Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial.

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off).

Potentially toxic elements (PTEs) in seabirds foraging across a heterogeneous landscape: Cross-species bioaccumulation patterns.

Seabirds are particularly susceptible to potentially toxic elements (PTEs) due to the tendency of biomagnification of some elements, thus serving as potential bioindicators for assessing environmental health. In this study, we analyzed As, Cd, Cu and Zn concentrations in liver samples from nine seabird species (51 specimens) collected along the Southwestern Atlantic Ocean. Results revealed substantial variations in PTE concentrations among species, with taxonomic orders influencing accumulation patterns.

Discovery of ART0380, a Potent and Selective ATR Kinase Inhibitor Undergoing Phase 2 Clinical Studies for the Treatment of Advanced or Metastatic Solid Cancers.

One of the hallmarks of cancer is high levels of DNA replication stress and defects in the DNA damage response (DDR) pathways, which are critical for maintaining genomic integrity. Ataxia telangiectasia and Rad3-related protein (ATR) is a key regulator of the DDR machinery and an attractive therapeutic target, with multiple ATR inhibitors holding significant promise in ongoing clinical studies. Herein, we describe the discovery and characterization of ART0380 (), a potent and selective ATR inhibitor with a compelling in vitro and in vivo pharmacological profile currently undergoing Phase 2 clinical studies in patients with advanced or metastatic solid tumors as monotherapy and in combination with DNA-damaging agents (NCT04657068 and NCT05798611).

POLE-Mutated Uterine Carcinosarcomas: A Clinicopathologic and Molecular Study of 11 Cases.

Uterine carcinosarcomas (UCS) are high-grade biphasic neoplasms with generally poor outcomes. Based on The Cancer Genome Atlas molecular classification of endometrial carcinomas, the majority of UCS are classified as copy-number high/serous-like (p53-abnormal); however, a small subset represent other molecular subtypes, including those that harbor POLE mutations. We identified 11 POLE-mutated (POLEmut) UCS across 3 institutions and assessed the clinical, histopathologic, immunohistochemical, and molecular features of these tumors.

Microbial communities in slow sand filters for drinking water treatment adapt to organic matter altered by ozonation.

Changing natural organic matter quality from anthropogenic activity and stricter requirements for micropollutant removal challenges existing systems for drinking water production. Ozonation of water followed by biofiltration, such as passage through a slow sand filter (SSF), is a partial solution. Biofiltration relies on biofilms (microbial communities within extracellular matrices).

Assessment of pathogenicity in goats: implications for transmission dynamics and host resistant.

, commonly associated with ovine babesiosis, poses a significant threat to sheep health, often resulting in severe clinical manifestations and high mortality rates. However, the impact of on goats has remained uncertain, prompting us to investigate its pathogenicity in caprine hosts. Experimental infections using -infected blood inoculation and infected tick infestation, were conducted on spleen-intact (n=5) and splenectomized (n=5) goats.

The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against In Vitro.

Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome 1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as spp.

Evaluation of perforation-mediated modified atmosphere packaging for the commercialization of bulk purple passion fruit under refrigeration.

Modified atmosphere packaging (MAP) is widely used to preserve fresh fruits. In the case of exporting products in bulk formats (2-5 kg), perforated MAP can help extend shelf life if appropriately configured to reach suitable gas levels. This study evaluated the configuration of a perforated MAP system for purple passion (Passiflora edulis Sims) fruits based on modeling and simulation of changes in gas levels within the package headspace and experimental data on the respiration and transpiration of the fruits.

Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and report.

Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period.

Long-Term Impacts of COVID-19 on Thyroid Health: Insights From Clinical Studies.

Background: COVID-19 emerged in December 2019 and rapidly became a global pandemic. It has since been associated with the progression of various endocrine disorders, including thyroid disease. The long-term effects of this interplay have yet to be explored.

Total synthesis of (-)-cylindrocyclophane A facilitated by C-H functionalization.

(-)-Cylindrocyclophane A is a 22-membered C-symmetric [7.7]paracyclophane that bears bis-resorcinol functionality and six stereocenters. We report a synthetic strategy for (-)-cylindrocyclophane A that uses 10 C-H functionalization reactions, resulting in a streamlined route with high enantioselectivity and efficiency (17 steps).

Safety and Effectiveness of Oral Anticoagulants in Atrial Fibrillation: Real-World Insights Using Natural Language Processing and Machine Learning.

We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. This is a retrospective study in 15 Spanish hospitals (2014-2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs).

Types, behaviour and therapeutic requirements of inflammatory pouch disorders: Results from the RESERVO study of GETECCU.

Background And Aims: Inflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied.

Methods: This retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term.

Immunopeptidomics of Serovar -Infected Pig Macrophages Genotyped for Class II Molecules.

Salmonellosis is a zoonotic infection that has a major impact on human health; consuming contaminated pork products is the main source of such infection. Vaccination responses to classic vaccines have been unsatisfactory; that is why peptide subunit-based vaccines represent an excellent alternative. Immunopeptidomics was used in this study as a novel approach for identifying antigens coupled to major histocompatibility complex class II molecules.

Microbial acidification by N, S, Fe and Mn oxidation as a key mechanism for deterioration of subsea tunnel sprayed concrete.

The deterioration of fibre-reinforced sprayed concrete was studied in the Oslofjord subsea tunnel (Norway). At sites with intrusion of saline groundwater resulting in biofilm growth, the concrete exhibited significant concrete deterioration and steel fibre corrosion. Using amplicon sequencing and shotgun metagenomics, the microbial taxa and surveyed potential microbial mechanisms of concrete degradation at two sites over five years were identified.

Bioethanol production by immobilized co-culture of Saccharomyces cerevisiae and Scheffersomyces stipitis in a novel continuous 3D printing microbioreactor.

Biorefineries require low-cost production processes, low waste generation and equipment that can be used not only for a single process, but for the manufacture of several products. In this context, in this research a continuous 3D printing microbioreactor coupled to an Arduino-controlled automatic feeding system was developed for the intensification of the ethanol production process from xylose/xylulose (3:1), using a new biocatalyst containing the co-culture of Scheffersomyces stipitis and Saccharomyces cerevisiae (50/50). Initially, batch fermentations of monocultures of S.