Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states.

In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury.

The Positive School Safety Program (PSSP) for School Officers: Implementation Processes and Outcomes.

Approximately 50% of U.S. students attend a school with a school officer.

Cutting Edge: Retinoic Acid Promotes Brain-homing of CD8+ T Cells during Congenital Cytomegalovirus Infection.

The most common congenital viral infection is CMV, which leads to numerous neurologic disabilities. Using a mouse model of congenital CMV, we previously determined that Ag-specific CD8+ T cells traffic to the brain in a CCR9-dependent manner. The mechanism by which these CD8+ T cells acquire a CCR9-dependent "brain-tropic" phenotype remains unclear.

Gene Regulatory Programs that Specify Age-Related Differences during Thymocyte Development.

T cell development is fundamental to immune system establishment, yet how this development changes with age remains poorly understood. Here, we construct a transcriptional and epigenetic atlas of T cell developmental programs in neonatal and adult mice, revealing the ontogeny of divergent gene regulatory programs and their link to age-related differences in phenotype and function. Specifically, we identify a gene module that diverges with age from the earliest stages of genesis and includes programs that govern effector response and cell cycle regulation.

Functionalized nanowires for miRNA-mediated therapeutic programming of naïve T cells.

Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic-polymer-functionalized nanowires were used to pre-program the fate of primary naïve CD8 T cells to achieve a therapeutic response in vivo.

The gene regulatory basis of bystander activation in CD8 T cells.

CD8 T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced CD8 T cells can respond to innate cytokines alone in the absence of cognate T cell receptor stimulation, a phenomenon referred to as bystander activation. Here, we demonstrate that neonatal CD8 T cells undergo a robust and diverse program of bystander activation, which corresponds to enhanced innate-like protection against unrelated pathogens.

Neonatal CD8+ T Cells Resist Exhaustion during Chronic Infection.

Chronic viral infections, such as HIV and hepatitis C virus, represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections, the underlying mechanisms remain unknown. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (lymphocytic choriomeningitis virus clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host.

Adaptive immune cells are necessary for SARS-CoV-2-induced pathology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic associated with morbidity and mortality in humans. Although disease severity correlates with immune dysregulation, the cellular mechanisms of inflammation and pathogenesis of COVID-19 remain relatively poorly understood. Here, we used mouse-adapted SARS-CoV-2 strain MA10 to investigate the role of adaptive immune cells in disease.

The application of implementation science methods in correctional health intervention research: a systematic review.

Background: Improving access to high-quality healthcare for individuals in correctional settings is critical to advancing health equity in the United States. Compared to the general population, criminal-legal involved individuals experience higher rates of chronic health conditions and poorer health outcomes. Implementation science frameworks and strategies offer useful tools to integrate health interventions into criminal-legal settings and to improve care.

Implementing trauma-focused cognitive behavioral therapy in Philadelphia: A 10-year evaluation.

In 2012, Philadelphia's Department of Behavioral Health and Intellectual disAbility Services (DBHIDS) developed an initiative to implement an evidence-based treatment for posttraumatic stress disorder (PTSD), trauma-focused cognitive behavioral therapy (TF-CBT), across the city's behavioral health system. This report evaluates the initiative's 10-year implementation and effectiveness outcomes. The Exploration, Preparation, Implementation, and Sustainment framework guided our implementation evaluation.

Single-cell transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states associated with senescence.

Skeletal muscle regeneration is driven by the interaction of myogenic and non-myogenic cells. In aging, regeneration is impaired due to dysfunctions of myogenic and non-myogenic cells, but this is not understood comprehensively. We collected an integrated atlas of 273,923 single-cell transcriptomes from muscles of young, old, and geriatric mice (~5, 20, 26 months-old) at six time-points following myotoxin injury.

Ccr2+ Monocyte-Derived Macrophages Influence Trajectories of Acquired Therapy Resistance in Braf-Mutant Melanoma.

Unlabelled: Therapies targeting oncogene addiction have had a tremendous impact on tumor growth and patient outcome, but drug resistance continues to be problematic. One approach to deal with the challenge of resistance entails extending anticancer treatments beyond targeting cancer cells by additionally altering the tumor microenvironment. Understanding how the tumor microenvironment contributes to the evolution of diverse resistance pathways could aid in the design of sequential treatments that can elicit and take advantage of a predictable resistance trajectory.

Measuring recovery in participants with a schizophrenia spectrum disorder: validation of the Individual Recovery Outcomes Counter (I.ROC).

Background: To improve recovery in mental health, validated instruments are needed.

Aims: This study evaluates psychometric properties of the Individual Recovery Outcomes Counter (I.ROC) in a Dutch population of participants with a schizophrenia spectrum disorder (SSD).

Building a new regional home for implementation science: Annual Midwest Clinical & Translational Research Meetings.

The vision of the Central Society for Clinical and Translational Research (CSCTR) is to "promote a vibrant, supportive community of multidisciplinary, clinical, and translational medical research to benefit humanity." Together with the Midwestern Section of the American Federation for Medical Research, CSCTR hosts an Annual Midwest Clinical & Translational Research Meeting, a regional multispecialty meeting that provides the opportunity for trainees and early-stage investigators to present their research to leaders in their fields. There is an increasing national and global interest in implementation science (IS), the systematic study of activities (or strategies) to facilitate the successful uptake of evidence-based health interventions in clinical and community settings.

Shaping immunity for life: Layered development of CD8 T cells.

Historically, the immune system was believed to develop along a linear axis of maturity from fetal life to adulthood. Now, it is clear that distinct layers of immune cells are generated from unique waves of hematopoietic progenitors during different windows of development. This model, known as the layered immune model, has provided a useful framework for understanding why distinct lineages of B cells and γδ T cells arise in succession and display unique functions in adulthood.

Cutting Edge: CCR9 Promotes CD8+ T Cell Recruitment to the Brain during Congenital Cytomegalovirus Infection.

CD8+ T lymphocytes infiltrate the brain during congenital CMV infection and promote viral clearance. However, the mechanisms by which CD8+ T cells are recruited to the brain remain unclear. Using a mouse model of congenital CMV, we found a gut-homing chemokine receptor (CCR9) was preferentially expressed in CD8+ T cells localized in the brain postinfection.

Evaluation of court-initiated randomized controlled trial of online parent programs for divorcing and separating parents.

We conducted an evaluation of a court-initiated randomized controlled trial comparing outcomes for parents assigned to either a no-program control group or one of two online parenting programs-Two Families Now (TFN) or Children in Between (CIB)-among 221 parents in initial divorce or separation court cases. We gathered parent report measures of family functioning at study entry, completion of program, and 1-year following study entry. We also gathered and coded court records to capture the content of the document resolving issues and occurrence of relitigation in the following year.

Lessons for a COVID-19 era: Barriers and facilitators to court ordered online parenting programs for divorcing and separating parents.

Family courts are increasingly interested in online parenting programs for divorcing and separating parents, particularly during the COVID-19 pandemic. To our knowledge, no previous study has evaluated the barriers to and facilitators of parent participation in these programs for family law cases. We interviewed 61 parents in the midst of family law cases regarding their perspectives.

Fate-mapping mice: new tools and technology for immune discovery.

The fate-mapping mouse has become an essential tool in the immunologist's toolbox. Although traditionally used by developmental biologists to trace the origins of cells, immunologists are turning to fate-mapping to better understand the development and function of immune cells. Thus, an expansion in the variety of fate-mapping mouse models has occurred to answer fundamental questions about the immune system.

Measuring personal recovery in a low-intensity community mental healthcare setting: validation of the Dutch version of the individual recovery outcomes counter (I.ROC).

Background: Measuring progress in treatment is essential for systematic evaluation by service users and their care providers. In low-intensity community mental healthcare, a questionnaire to measure progress in treatment should be aimed at personal recovery and should require little effort to complete.

Methods: The Individual Recovery Outcome Counter (I.

Understanding therapists' perceived determinants of trauma narrative use.

Background: Trauma narratives are a critical, exposure-based component of trauma-focused cognitive-behavioral therapy, yet community therapists rarely use them. Given evidence that intentions to deliver elements of cognitive behavioral therapy vary by component, and that intentions to deliver exposure are the weakest, this study focused specifically on trauma narratives. We drew on a social psychology causal theory (Theory of Planned Behavior (TPB)) and an implementation science framework (the Consolidated Framework for Implementation Research (CFIR)) to glean insight into multilevel influences on trauma narrative use.

MicroRNA-29 specifies age-related differences in the CD8+ T cell immune response.

MicroRNAs (miRNAs) have emerged as critical regulators of cell fate in the CD8+ T cell response to infection. Although there are several examples of miRNAs acting on effector CD8+ T cells after infection, it is unclear whether differential expression of one or more miRNAs in the naive state is consequential in altering their long-term trajectory. To answer this question, we examine the role of miR-29 in neonatal and adult CD8+ T cells, which express different amounts of miR-29 only prior to infection and adopt profoundly different fates after immune challenge.