Fenner

The IQ Transporter Working Group had a rare opportunity to analyse a cross-pharma collation of in vitro data and assay methods for the evaluation of drug transporter substrate and inhibitor potential. Experiments were generally performed in accordance with regulatory guidelines. Discrepancies, such as not considering the impact of pre-incubation for inhibition and free or measured in vitro drug concentrations, may be due to the retrospective nature of the dataset and analysis. Lipophilicity was a frequent indicator of cross-transport inhibition (P-gp, BCRP, OATP1B and OCT1) with high molecular weight ({greater than or equal to}500 Da) also common for OATP1B and BCRP inhibitors...

Polatuzumab Vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in DLBCL. To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B. Our results reveal the striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity...

BACKGROUND: Using a multiple-measurement approach, we examined the real-world effectiveness of portable HEPA air filtration devices (air cleaners) in a school setting. METHODS: We collected data over 7 weeks during winter 2022/2023 in 2 Swiss secondary school classes: environmental (CO2 , particle concentrations), epidemiologic (absences related to respiratory infections), audio (coughing), and molecular (bioaerosol and saliva samples). Using a crossover design, we compared particle concentrations, coughing, and risk of infection with and without air cleaners...

When chemical pollutants enter the environment, they can undergo diverse transformation processes, forming a wide range of transformation products (TPs), some of them benign and others more harmful than their precursors. To date, the majority of TPs remain largely unrecognized and unregulated, particularly as TPs are generally not part of routine chemical risk or hazard assessment. Since many TPs formed from oxidative processes are more polar than their precursors, they may be especially relevant in the context of persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances, which are two new hazard classes that have recently been established on a European level...

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against prototype and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5, and XBB.1.5) in human serum. For the prototype strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity...

Organic contaminants enter aquatic ecosystems from various sources, including wastewater treatment plant effluent. Freshwater biofilms play a major role in the removal of organic contaminants from receiving water bodies, but knowledge of the molecular mechanisms driving contaminant biotransformations in complex stream biofilm (periphyton) communities remains limited. Previously, we demonstrated that biofilms in experimental flume systems grown at higher ratios of treated wastewater (WW) to stream water displayed an increased biotransformation potential for a number of organic contaminants...

As I reflect on my 30 years in academic medicine, my professional journey is uniquely intertwined with the growth and development of the field of urogynecology and the ultimate subspecialty recognition by the American Board of Obstetrics and Gynecology (ABOG), the Association of American Medical Colleges (AAMC), and the American Board of Medical Specialties (ABMS). In this article, I will retrace that journey from personal memories and notes, conversations with the leaders in the room, and documents and minutes generously provided by ABOG and the American Urogynecologic Society (AUGS)...

BACKGROUND: Given their high-risk resident population, nursing homes were critical institutions in the COVID-19 pandemic, calling for continued monitoring and vaccine administration to healthcare workers and residents. Here, we studied long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in vaccinated and unvaccinated healthcare workers and residents of a nursing home in Switzerland between February 2021 and June 2022. METHODS: Our study comprised 45 participants, of which 39 were healthcare workers and six were residents...

PURPOSE: To describe healthcare experiences and health outcomes among rural LGBTQ + individuals. DESIGN: 2022 cross-sectional survey. SETTING: Southern Illinois. SAMPLE: 85 individuals. MEASURES: Demographics, sexual orientation and gender identity, healthcare experiences, health outcomes. ANALYSIS: Experiences and outcomes were assessed vs orientation and identity. Distribution comparison was by t -test and chi-square, risk prediction by logistic regression, and significance assumed at P < ...

Biodegradation plays a key role in the fate of chemicals in the environment. The variability of biodegradation in time can cause uncertainty in evaluating the environmental persistence and risk of chemicals. However, the seasonality of biodegradation in rivers has not yet been the subject of environmentally relevant testing and systematic investigation for large numbers of chemicals. In this work, we studied the biodegradation of 96 compounds during four seasons at four locations (up- and downstream of WWTPs located on two Swedish rivers)...

Ecological forecasts are becoming increasingly valuable tools for conservation and management. However, there are few examples of near-real-time forecasting systems that account for the wide range of ecological complexities. We developed a new coral disease ecological forecasting system that explores a suite of ecological relationships and their uncertainty and investigates how forecast skill changes with shorter lead times. The Multi-Factor Coral Disease Risk product introduced here uses a combination of ecological and marine environmental conditions to predict the risk of white syndromes and growth anomalies across reefs in the central and western Pacific and along the east coast of Australia and is available through the US National Oceanic and Atmospheric Administration Coral Reef Watch program...

Dyadic interviews were conducted with 32 youth ages 13-21 and their self-identified key adult supports to illuminate how adult supports help protect youth in communities impacted by high levels of violence. Interview transcripts were analyzed using thematic content analysis. Youth described choosing social interactions carefully, avoiding high-violence areas, and keeping busy with activities. Many youths discussed the necessity of minimizing contact with peers to avoid violence, resulting in isolation from friends and increased engagement with family at home...

OBJECTIVES: To compare the prevalence of SARS-CoV-2 and other respiratory viruses in saliva and bioaerosols between two winters and to model the probability of virus detection in classroom air for different viruses. METHODS: We analysed saliva, air, and air cleaner filter samples from studies conducted in two Swiss secondary schools (students aged 14-17 years) over 7 weeks during the winters of 2021/22 and 2022/23. Two bioaerosol sampling devices and high efficiency particulate air (HEPA) filters from air cleaners were used to collect airborne virus particles in four classrooms...

OBJECTIVES: The aim of the study was to describe clinical examination and thoracic CT (TCT) findings in cats after trauma, and to identify physical examination findings associated with both abnormalities on TCT and the need for therapeutic interventions. METHODS: A multicentre, retrospective, observational study was conducted. Cats admitted to the participating hospitals with a history of blunt trauma and that underwent TCT were eligible. Data were collected on signalment, history, physical examination, TCT findings and subsequent interventions...

Agonistic behaviours are often directed at other animals for self-defence or to increase distance from valued resources, such as food. Examples include aggression and counter-predator behaviours. Contemporary diets may boost the value of food as a resource and create unanticipated associations with the humans who deliver it. At the same time the domestic horse is asked to carry the weight of riders and perform manoeuvres that, ethologically, are out-of-context and may be associated with instances of pain, confusion, or fear...

No abstract text is available yet for this article.

A highly enantioselective organocatalytic aza-Michael addition of 4-nitro-pyrazole to ethyl ( E )-2,2-difluoro-5-oxopent-3-enoate has been developed. This reaction enabled a concise, four-step, stereoselective synthesis of highly functionalized 3,3-difluoro-4-pyrazolo-piperidine GSK3901383A, a key intermediate for the synthesis of a leucine-rich repeat kinase 2 inhibitor API. Computational analysis provided insight into the steric requirements of the catalytic system, enabling rational selection of a highly selective catalyst...

Clozapine is the only licensed medication for treatment-resistant schizophrenia (TRS). Few predictors for variation in response to clozapine have been identified, but clozapine metabolism is known to influence therapeutic response and adverse side effects. Here, we expand on genome-wide studies of clozapine metabolism, previously focused on common genetic variation, by analysing whole-exome sequencing data from 2062 individuals with schizophrenia taking clozapine in the UK. We investigated whether rare genomic variation in genes and gene sets involved in the clozapine metabolism pathway influences plasma concentrations of clozapine metabolites, assessed through the longitudinal analysis of 6585 pharmacokinetic assays...

PURPOSE: To investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution. DESIGN: Retrospective, single institution, cohort review. SUBJECTS: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4. METHODS: DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing...

This paper reports the first examples of ground state radical-mediated intramolecular C-H amination to afford 1-methyl-1,2,3,4-tetrahydroquinolines from N -2,4-dinitrophenoxy derivatives of arylpropylamines. Whereas the photoactivation of N -2,4-dinitrophenoxyamines for intermolecular reactions has been established, ground state chemistry provides the desired cyclization products in moderate to excellent yields using Ru(bpy)3 Cl2 (42-95% yields) under acidic conditions under an air atmosphere.