A minority of Th1 and Tfh effector cells express survival genes shared by memory cell progeny that require IL-7 or TCR signaling to persist.

It is not clear how CD4 memory T cells are formed from a much larger pool of earlier effector cells. We found that transient systemic bacterial infection rapidly generates several antigen-specific T helper (Th)1 and T follicular helper (Tfh) cell populations with different tissue residence behaviors. Although most cells of all varieties had transcriptomes indicative of cell stress and death at the peak of the response, some had already acquired a memory cell signature characterized by expression of genes involved in cell survival.

Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 × CD3 bispecific antibody) in patients with recurrent ovarian cancer.

Ubamatamab, a Mucin 16 (MUC16) × cluster of differentiation 3 (CD3) bispecific antibody that promotes T-cell-mediated cytotoxicity of MUC16-expressing cells, is being investigated for the treatment of ovarian cancer. Intravenous administration of ubamatamab, with or without the anti-programmed cell death-1 inhibitor cemiplimab, is being evaluated in a first-in-human study in patients with recurrent ovarian cancer. In vitro cytotoxicity and cytokine data and projected ubamatamab human pharmacokinetic (PK) profiles scaled with monkey PK parameters enabled starting-dose selection in humans.

Defining clavicle growth in infancy using chest radiographs.

Background: Despite the critical role of the clavicle in understanding growth and development in early childhood, there remains a notable paucity of comprehensive studies investigating clavicle growth patterns during this crucial period. This hinders our ability to establish normative growth parameters during these early life stages. Our study sought to measure clavicle dimensions and subsequently construct growth curves spanning from preterm infants to toddlers up to the age of 6 years by measuring routine chest radiographs.

A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.

The clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy.

A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants.

The receptor tyrosine kinase FGFR3 is frequently mutated in bladder cancer and is a validated therapeutic target. Although pan-FGFR tyrosine kinase inhibitors (TKI) have shown clinical efficacy, toxicity and acquired resistance limit the benefit of these agents. While antibody-based therapeutics can offer superior selectivity than TKIs, conventional ligand-blocking antibodies are usually ineffective inhibitors of constitutively active receptor tyrosine kinases.

Factors associated with plans for early retirement among Ontario family physicians during the COVID-19 pandemic: a cross-sectional study.

Background: Higher numbers of family physicians (FPs) stopped practicing or retired during the COVID-19 pandemic, worsening the family doctor shortage in Canada. Our study objective was to determine which factors were associated with FPs' plans to retire earlier during the COVID-19 pandemic.

Methods: We administered two cross-sectional online surveys to Ontario FPs asking whether they were "planning to retire earlier" as a result of the pandemic during the first and third COVID-19 pandemic waves (Apr-Jun 2020 and Mar-Jul 2021).

Identifying resource-rational heuristics for risky choice.

Perfectly rational decision making is almost always out of reach for people because their computational resources are limited. Instead, people may rely on computationally frugal heuristics that usually yield good outcomes. Although previous research has identified many such heuristics, discovering good heuristics and predicting when they will be used remains challenging.

Laboratory High-Contrast X-ray Microscopy of Copper Nanostructures Enabled by a Liquid-Metal-Jet X-ray Source.

High-resolution imaging of Cu/low-k on-chip interconnect stacks in advanced microelectronic products is demonstrated using full-field transmission X-ray microscopy (TXM). The comparison of two lens-based laboratory X-ray microscopes that are operated at two different photon energies, 8.0 keV and 9.

Laboratory X-ray Microscopy of 3D Nanostructures in the Hard X-ray Regime Enabled by a Combination of Multilayer X-ray Optics.

High-resolution imaging of buried metal interconnect structures in advanced microelectronic products with full-field X-ray microscopy is demonstrated in the hard X-ray regime, i.e., at photon energies > 10 keV.

Results from the BETTER WISE trial: a pragmatic cluster two arm parallel randomized controlled trial for primary prevention and screening in primary care during the COVID-19 pandemic.

Background: Cancer and chronic diseases are a major cost to the healthcare system and multidisciplinary models with access to prevention and screening resources have demonstrated improvements in chronic disease management and prevention. Research demonstrated that a trained Prevention Practitioner (PP) in multidisciplinary team settings can improve achievement of patient level prevention and screening actions seven months after the intervention.

Methods: We tested the effectiveness of the PP intervention in a pragmatic two-arm cluster randomized controlled trial.

Physician ratings of physician assistant competencies and their experiences and satisfaction working with physician assistants: Results from the supervising physician survey in Ontario, Canada.

Physician Assistants (PAs) are a relatively new addition to the Ontario healthcare system. To understand the impact of the PA role, this study investigated supervising physician satisfaction and perception of PA roles, interprofessional team integration, pandemic supports, and barriers and enablers to PA employment. A web-based survey was conducted of 118 physician supervisors of Ontario PA education program alumni.

Less Time for Health: Parenting, Work, and Time-Intensive Health Behaviors among Married or Cohabiting Men and Women in the United States.

Time spent working or caring for children may reduce the time available for undertaking time-intensive health behaviors. We test competing perspectives about how work hours and the number of children of specific ages will be associated with married or cohabiting men's and women's sleep duration and physical activity. We use data from the 2004 to 2017 waves of the National Health Interview Survey (N = 154,580).

Nongynecologic healthcare screening in women.

The primary care physician is bombarded with recommendations regarding health screening and preventive services. Often, these recommendations and guidelines are in conflict. This article will not settle these debates; however, it will provide an overview of recommendations for screening in nongynecologic areas and a framework on how to evaluate conflicting recommendations to give reasonable guidance to patients.

Excess Deaths in the United States Compared to 18 Other High-Income Countries.

Unlabelled: The U.S. is exceptional among high-income countries for poor survival outcomes.

Whole-body diffusion magnetic resonance imaging with simultaneous multi-slice excitation in children and adolescents.

Background: Whole-body magnetic resonance imaging (WB-MRI) is an increasingly used guideline-based imaging modality for oncological and non-oncological pathologies during childhood and adolescence. While diffusion-weighted imaging (DWI), a part of WB-MRI, enhances image interpretation and improves sensitivity, it also requires the longest acquisition time during a typical WB-MRI scan protocol. Interleaved short tau inversion recovery (STIR) DWI with simultaneous multi-slice (SMS) acquisition is an effective way to speed up examinations.

Cost-effectiveness Analysis in Diagnostic Musculoskeletal Radiology: A Systematic Review.

Diagnostic musculoskeletal imaging represents a large economic expenditure within the health care system. Cost-effectiveness analysis can identify the most efficient use of imaging resources, but the literature is not well summarized. The purpose of this study was to summarize the existing literature on this topic and identify areas for future research.

A computational process-tracing method for measuring people's planning strategies and how they change over time.

One of the most unique and impressive feats of the human mind is its ability to discover and continuously refine its own cognitive strategies. Elucidating the underlying learning and adaptation mechanisms is very difficult because changes in cognitive strategies are not directly observable. One important domain in which strategies and mechanisms are studied is planning.

Immune tolerance of food is mediated by layers of CD4 T cell dysfunction.

Gastrointestinal health depends on the adaptive immune system tolerating the foreign proteins in food. This tolerance is paradoxical because the immune system normally attacks foreign substances by generating inflammation. Here we addressed this conundrum by using a sensitive cell enrichment method to show that polyclonal CD4 T cells responded to food peptides, including a natural one from gliadin, by proliferating weakly in secondary lymphoid organs of the gut-liver axis owing to the action of regulatory T cells.

Vectored jets power arms-first and tail-first turns differently in brief squid with assistance from fins and keeled arms.

Squids maneuver to capture prey, elude predators, navigate complex habitats and deny rivals access to mates. Despite the ecological importance of this essential locomotive function, limited quantitative data on turning performance and wake dynamics of squids are available. To better understand the contribution of the jet, fins and arms to turns, the role of orientation (i.

Rheology of particulate suspensions with non-Newtonian fluids in capillaries.

Particulate suspensions occur in situations from blood flow to slurries in drilling applications. Existing investigations of these suspensions generally concentrate on the impact of particle volume fraction for suspensions in Newtonian fluids under free-flow conditions. Recently, particulate-polymer composites have been used in additive manufacturing (AM).

Boosting corrects a memory B cell defect in SARS-CoV-2 mRNA-vaccinated patients with inflammatory bowel disease.

Immunosuppressed patients with inflammatory bowel disease (IBD) generate lower amounts of SARS-CoV-2 spike antibodies after mRNA vaccination than healthy controls. We assessed SARS-CoV-2 spike S1 receptor binding domain-specific (S1-RBD-specific) B lymphocytes to identify the underlying cellular defects. Patients with IBD produced fewer anti-S1-RBD antibody-secreting B cells than controls after the first mRNA vaccination and lower amounts of total and neutralizing antibodies after the second.

Rational use of cognitive resources in human planning.

Making good decisions requires thinking ahead, but the huge number of actions and outcomes one could consider makes exhaustive planning infeasible for computationally constrained agents, such as humans. How people are nevertheless able to solve novel problems when their actions have long-reaching consequences is thus a long-standing question in cognitive science. To address this question, we propose a model of resource-constrained planning that allows us to derive optimal planning strategies.

Avoiding N-nitrosodimethylamine formation in metformin pharmaceuticals by limiting dimethylamine and nitrite.

Since late 2019, concerns regarding trace levels of the probable human carcinogen N-dimethylnitrosamine (NDMA) in Metformin-containing pharmaceuticals have been an issue if they exceeded the maximum allowable intake of 96 ng/day for a medicine with long-term intake. Here, we report results from an extensive analysis of NDMA content along the active pharmaceutical ingredient (API) manufacturing process as well as two different drug product manufacturing processes. Our findings confirm that Metformin API is not a significant source of NDMA found in Metformin pharmaceuticals and that NDMA is created at those steps of the drug product manufacturing that introduce heat and nitrite.