Rational design of a SOCS1-edited tumor-infiltrating lymphocyte therapy using CRISPR/Cas9 screens.

Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the antitumor activity of T cell therapies, large-scale in vitro and in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, with the SOCS1 gene identified as a top T cell-enhancing target. In murine CD8+ T cell-therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of central memory T cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cells (Texprog) in tumors.

Detecting Anosognosia from the Prodromal Stage of Alzheimer's Disease.

Background: Though not originally developed for this purpose, the Healthy Aging Brain Care Monitor (HABC-M) seems a valuable instrument for assessing anosognosia in Alzheimer's disease (AD).

Objectives: Our study aimed at 1) investigating the validity of the HABC-M (31 items), and its cognitive, psychological, and functional subscales, in discriminating AD patients from controls; 2) exploring whether the HABC-M discrepancy scores between the self-reports of patients/controls in these different domains and the respective ratings provided by their caregivers/informants correlate with an online measure of self-awareness; 3) determining whether the caregiver burden level, also derived from the HABC-M, could add additional support for detecting anosognosia.

Methods: The HABC-M was administered to 30 AD patients and 30 healthy controls, and to their caregivers/informants.

Inoperative Love and Social Well-Being in the Face of Oppression: A Psychoanalytic-Agambenian Developmental Perspective and Its Implications for Psychoanalytic Therapy.

The author depicts, relying on several of Giorgio Agamben's philosophical concepts as well as a psychoanalytic developmental perspective, the origins and features of inoperative love and spaces, especially as they pertain to oppressive situations wherein social, political, and economic apparatuses undermine the psychosocial well-being of individuals, families, and communities. In addition, the author conceptualizes psychoanalytic therapy as an inoperative space wherein patients actualize their capacity for impotentiality and experience singularity and rapport.

Novel and Engineered Type II CRISPR Systems from Uncultivated Microbes with Broad Genome Editing Capability.

Type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 nucleases have been extensively used in biotechnology and therapeutics. However, many applications are not possible owing to the size, targetability, and potential off-target effects associated with currently known systems. In this study, we identified thousands of CRISPR type II effectors by mining an extensive, genome-resolved metagenomics database encompassing hundreds of thousands of microbial genomes.

Designing a Dyad-Based Digital Health Intervention to Reduce Sedentary Time in Black Breast Cancer Survivors and Their First-degree Relatives: Human-Centered Design Study.

Background: Breast cancer, the most commonly diagnosed cancer and second leading cause of cancer-related death in women in the United States, disproportionately affects women from minoritized or low socioeconomic backgrounds. The average woman has an approximately 12% lifetime risk of developing breast cancer. Lifetime risk nearly doubles if a woman has a first-degree relative with breast cancer, and the risk increases as multiple family members are affected.