Discovery of ERD-12310A as an Exceptionally Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα).

Inhibition of estrogen receptor alpha (ERα) signaling is an established therapeutic approach for the treatment of ER-positive (ER+) breast cancers, but new therapeutic strategies are urgently needed to overcome clinical resistance. In the present study, we describe the discovery and extensive evaluation of ERD-12310A as an exceptionally potent and orally efficacious PROTAC degrader of ERα. ERD-12310A achieved a DC value of 47 pM and is 10 times more potent than ARV-471.

Reconstruction of Composite Mandible Defects Using a Cellular Bone Allograft and Soft Tissue Free Flap Coverage.

Study Design: Retrospective case series.

Objective: Cellular bone allografts (CBAs) contain the components of a successful bone graft with no autologous component and have been used extensively outside the head and neck. Descriptions of their utilization for mandible reconstruction are limited.

Going Paperless: Using Electronic Questionnaires to Improve the Quality of Well-Child Checkups.

Objective: At our large, university-affiliated primary care clinic, we aimed to enhance the quality of well-child checkups (WCCs) to align with Bright Futures/American Academy of Pediatrics recommendations. Our primary goal was to increase the rate of complete WCCs from 45.6% to 80% by April 2024.

Opportunities for carbon sequestration from removing or intensifying pasture-based beef production.

Pastures, on which ruminant livestock graze, occupy one third of the earth's surface. Removing livestock from pastures can support climate change mitigation through carbon sequestration in regrowing vegetation and recovering soils, particularly in potentially forested areas. However, this would also decrease food and fiber production, generating a tradeoff with pasture productivity and the ruminant meat production pastures support.

Iterative Catalyst-Controlled Diastereoselective Matteson Homologations Enable the Selective Synthesis of Benzestrol Isomers.

We report the development of an iterative Matteson homologation reaction with catalyst-controlled diastereoselectivity through the design of a new catalyst. This reaction was applied to the selective synthesis of each stereoisomer of benzestrol, a bioactive compound with estrogenic activity featuring three contiguous stereocenters. The different stereoisomers were assayed to determine their binding affinity for the estrogen receptor α (ERα), and the absolute configuration of the compound having uniquely high activity was determined.

Which Environmental Pollutants Are Toxic to Our Ears?-Evidence of the Ototoxicity of Common Substances.

Ototoxicity refers to the adverse effects of substances on auditory or vestibular functions. This study examines the evidence of ototoxicity's association with exposure to common environmental pollutants, as documented in toxicological profiles by the Agency for Toxic Substances and Disease Registry. Our aim was to evaluate whether the evidence supports modifying the charting of ototoxic effects in the summary tables of these toxicological profiles and providing a guide for scientists to access these data.

Microbial urea-nitrogen recycling in arctic ground squirrels: the effect of ambient temperature of hibernation.

Energy conservation associated with hibernation is maximized at the intersection of low body temperature (T), long torpor bouts, and few interbout arousals. In the arctic ground squirrel (Urocitellus parryii), energy conservation during hibernation is best achieved at ambient temperatures (T) around 0 °C; however, they spend the majority of hibernation at considerably lower T. Because arctic ground squirrels switch to mixed fuel metabolism, including protein catabolism, at extreme low T of hibernation, we sought to investigate how microbial urea-nitrogen recycling is used under different thermal conditions.

Challenges and Opportunities in Developing an Oncology Clinical Trial Network in the United States Veterans Affairs Health Care System: The VA STARPORT Experience.

The United States Veterans Affairs (VA) Health Care System has a strong history of conducting impactful oncology randomized clinical trials (RCTs). We developed a phase II/III RCT to test the use of metastasis-directed therapy in Veterans with oligometastatic prostate cancer (OMPC)-the first VA RCT in OMPC that leverages novel imaging and advanced radiotherapy techniques. To accomplish this, we developed a clinical trial network to conduct the study.

BEAM or cyclophosphamide in autologous haematopoietic stem cell transplantation for relapsing-remitting multiple sclerosis.

The most widely used conditioning regimens in autologous haematopoietic stem cell transplantation (ASCT) for multiple sclerosis (MS) are BEAM with anti-thymocyte globulin (ATG) and high-dose cyclophosphamide with ATG (Cy/ATG). In this retrospective study, we compare efficacy and safety of these regimens when used for relapsing-remitting MS. We assessed 231 patients treated in Sweden before January 1, 2020.

Lifetime Psychotropic Medication Use Among Service Members and Veterans With and Without History of Mild Traumatic Brain Injury: A Pilot Study.

Introduction: Military Service Members, Veterans, and other patient populations who experience traumatic brain injury (TBI) may have increased risk of early neurodegenerative diseases relative to those without TBI history. Some evidence suggests that exposure to psychotropic medications may play a role in this association. The Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) prospective longitudinal study provides an ideal setting to examine the effects of psychotropic medication exposure on long-term neurological health of those with and without mild TBI history.

Positive and negative controls in rheumatology research.

Observational research from large population databases may be affected by unmeasured confounding and time-related biases, such as immortal time bias. Modern causal inference practice applies propensity score-based methods, new-user designs, and other strategies to mitigate bias. The degree to which these methodologic approaches adequately address bias for any particular study may be difficult to measure.

Investigation of the diversity, equity, inclusion, and belonging within the undergraduate student population within the Department of Animal Science at Iowa State University.

Iowa State University (ISU) provides resources for diversity, equity, inclusion, and belonging (DEI-B) to provide students with a comfortable academic home regardless of their demographics or prior experiences. The objective of this study was to investigate undergraduate students' DEI-B perspectives in the Department of Animal Science at ISU. One survey instrument was developed containing 14 questions that covered demographics, feelings of inclusion, comfort-seeking tools, and ways to improve DEI-B.

Do environmental attitudes and personal characteristics influence how people perceive their exposure to green spaces?

Background: This study explores the relationship between perceived and objective greenspace exposure, and how sociodemographic traits and environmental attitudes influence peoples' perceptions of greenspace.

Methods: We leveraged a cross-sectional survey on greenspace exposure among residents of Denver, CO that ran from November 2019 through April 2021. We measured objective greenspace using the average NDVI (normalized difference vegetation index), average percent vegetation, and median GVI (green view index) within 300, 500, and 1,000 m of participants' residences, and in participant-drawn polygons representing their neighborhoods.