Temporal context effects on suboptimal choice.

Choice can be driven both by rewards and stimuli that signal those rewards. Under certain conditions, pigeons will prefer options that lead to less probable reward when the reward is signaled. A recently quantified model, the Signal for Good News (SiGN) model, assumes that in the context of uncertainty, signals for a reduced delay to reward reinforce choice.

ABBV-319: a CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Glucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone.

Gut microbiota regulate maturation and mitochondrial function of the nutrient-sensing enteroendocrine cell.

Enteroendocrine cells (EECs) are crucial for sensing ingested nutrients and regulating feeding behavior. How gut microbiota regulate the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis demonstrates that commensal microbiota colonization significantly increases the expression of many genes associated with mitochondrial function.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2024 Update.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management.

Reflections on co-production: Developing a dementia research funding application with a diverse lived experience group.

Published work on dementia research co-production focuses on developing health and social care interventions. Less is written about practicalities and experiences of co-producing dementia research funding applications. UK public contributors are typically from white middle class populations.

Alpha-Emitting Radionuclides: Current Status and Future Perspectives.

The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress.

Gut microbiota promotes enteroendocrine cell maturation and mitochondrial function.

The enteroendocrine cells (EECs) in the intestine are crucial for sensing ingested nutrients and regulating feeding behavior. The means by which gut microbiota regulates the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis of the EECs from germ-free (GF) and conventionalized (CV) zebrafish revealed that commensal microbiota colonization significantly increased the expression of many genes that are associated with mitochondrial function.

Engineering CAR-T cells for radiohapten capture in imaging and radioimmunotherapy applications.

The dynamics of CAR-T cells remain incompletely understood. Novel methods are urgently needed to longitudinally monitor transferred cells non-invasively for biodistribution, functionality, proliferation, and persistence and for improving their cytotoxic potency in case of treatment failure. Here we engineered CD19 CAR-T cells ("Thor"-cells) to express a membrane-bound scFv, huC825, that binds DOTA-haptens with picomolar affinity suitable for labeling with imaging or therapeutic radionuclides.

Short-term effects of the "I Spy Feelings" program on emotion regulation in 5- to 6-year-old children.

Introduction: Mental health difficulties in early childhood can have a debilitating and ongoing impact throughout an individual's life; emotion regulation can serve as a protective factor. Therefore, evidence-based prevention programs that teach children effective skills and strategies for emotion regulation are needed.

Methods: As part of the Aussie Optimism pilot study evaluating the "I Spy Feelings" program, this study aims to assess the short-term effects of the program on emotion regulation in pre-primary aged children after 2 months via a longitudinal cluster randomized controlled trial.

Efficacy of HER2-Targeted Intraperitoneal Ac α-Pretargeted Radioimmunotherapy for Small-Volume Ovarian Peritoneal Carcinomatosis.

Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally considered to be surgically incurable. Targeted α-therapy with the α-particle-emitting radionuclide Ac (half-life, 9.92 d) is a high-linear-energy-transfer treatment approach effective for small-volume disease and even single cells.

Suboptimal choice: A review and quantification of the signal for good news (SiGN) model.

As first reported several decades ago, pigeons () sometimes choose options that provide less food over options that provide more food. This behavior has been variously referred to as suboptimal, maladaptive, or paradoxical because it lowers overall food intake. A great deal of research has been directed at understanding the conditions under which animals and people make suboptimal choices and the mechanisms that drive this behavior.

Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response.

Unlabelled: Noninvasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer therapies. AR is a critical driver and mediator of resistance of prostate cancer but currently available noninvasive prostate cancer biomarkers to monitor AR activity are discordant with downstream AR pathway activity. External beam radiotherapy (EBRT) remains a common treatment for all stages of prostate cancer, and DNA damage induced by EBRT upregulates AR pathway activity to promote therapeutic resistance.

[F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response.

The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways-such as those induced by irradiation.

Forced-exposure trials increase suboptimal choice.

The influence of single option or forced-exposure (FE) trials was studied in the suboptimal choice task. Pigeons chose between an optimal alternative that led to food half of the time and a suboptimal alternative that led to food 20% of the time. Choice of the suboptimal alternative was compared across groups of subjects that received different numbers of FE trials during training.

Treatment of Patients with Acute Myeloid Leukemia with the Targeted Alpha-Particle Nanogenerator Actinium-225-Lintuzumab.

Purpose: The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab.

Couples Therapy Delivered Through Videoconferencing: Effects on Relationship Outcomes, Mental Health and the Therapeutic Alliance.

Changing technology, and the pervasive demand created by a greater need in the population for access to mental health interventions, has led to the development of technologies that are shifting the traditional way in which therapy is provided. This study investigated the efficacy of a behavioral couples therapy program conducted videoconferencing, as compared to face-to-face. There were 60 participants, in couples, ranging in age from 21 to 69 years old.

Good news is better than bad news, but bad news is not worse than no news.

Under certain conditions, pigeons will reliably prefer an alternative that leads to a lower probability of food over an alternative that leads to a higher probability of food (i.e., demonstrate suboptimal choice).

Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function.

Deficiency of the serine hydrolase prolyl endopeptidase-like (PREPL) causes a recessive metabolic disorder characterized by neonatal hypotonia, feeding difficulties, and growth hormone deficiency. The pathophysiology of PREPL deficiency and the physiological substrates of PREPL remain largely unknown. In this study, we connect PREPL with mitochondrial gene expression and oxidative phosphorylation by analyzing its protein interactors.

Prevention of Mental Health Difficulties for Children Aged 0-3 Years: A Review.

The period of infancy and early childhood is a critical time for interventions to prevent future mental health problems. The first signs of mental health difficulties can be manifest in infancy, emphasizing the importance of understanding and identifying both protective and risk factors in pregnancy and the early postnatal period. Parents are at a higher risk of developing mental health problems during the perinatal period.

Radiation Safety Considerations and Clinical Advantages of α-Emitting Therapy Radionuclides.

For CE credit, you can access the test for this article, as well as additional CE tests, online at https://www.snmmilearningcenter.org Complete the test online no later than March 2025.

The Impact of the Aussie Optimism Program on the Emotional Coping of 5- to 6-Year-Old Children.

Research indicates that mental health disorders can occur in children as young as 4 years of age, prompting the need for prevention programs for young children. The ability to use healthy strategies to cope with emotions is a protective factor against mental health disorders that can be effectively taught to children from an early age. The current study used a pre-test post-test cluster randomized controlled trial to test the efficacy of the new Aussie Optimism: I Spy Feelings Program.

Engineered Cells as a Test Platform for Radiohaptens in Pretargeted Imaging and Radioimmunotherapy Applications.

Pretargeted imaging and radioimmunotherapy approaches are designed to have superior targeting properties over directly targeted antibodies but impose more complex pharmacology, which hinders efforts to optimize the ligands prior to human applications. Human embryonic kidney 293T cells expressing the humanized single-chain variable fragment (scFv) C825 (huC825) with high-affinity for DOTA-haptens (293T-huC825) in a transmembrane-anchored format eliminated the requirement to use other pretargeting reagents and provided a simplified, accelerated assay of radiohapten capture while offering normalized cell surface expression of the molecular target of interest. Using binding assays, biodistribution, and imaging, we demonstrated that radiohaptens based on benzyl-DOTA and a second generation "Proteus" DOTA-platform effectively and specifically engaged membrane-bound huC825, achieving favorable tumor-to-normal tissue uptake ratios in mice.