Immune checkpoint blockade (ICB) has revolutionized cancer therapy, but varying response rates illustrate the need for biomarkers of response. Studies in mice have identified a subset of CD8 T cells that is essential for response to PD-1 ICB. These CD8 T cells co-express CXCR5, PD-1 and Tcf1, and provide effector T cells upon PD-1 ICB.  https://www.selleckchem.com/products/bay-1000394.html  It is unknown whether similar T cells play a role in PD-1 ICB in humans. We studied human peripheral blood and lymph nodes (LNs) for the frequency, phenotype, and functionality of CXCR5+ PD-1+ CD8 T cells. We find that CXCR5+ PD-1+ CD8 T cells are memory-like cells, express Tcf1, and lack expression of effector molecules. CXCR5+ PD-1+ CD8 T cells produce cytokines upon stimulation, but have limited proliferative capacity. We studied patients with hematologic malignancies with varying response rates to PD-1 ICB. Specifically in chronic lymphocytic leukemia, in which PD-1 ICB does not induce clinical responses, CXCR5+ PD-1+ CD8 T cells show loss of the memory phenotype and increased effector differentiation. In conclusion, we identified CXCR5+ PD-1+ CD8 T cells in human peripheral blood and LN, which could play a similar role during PD-1 ICB. Future studies should analyze CXCR5+ PD-1+ CD8 T cells during PD-1 ICB and their importance for therapeutic response.
  This practice-based evidence study examined trajectories of God representations and psychological distress among Christians participating in spiritually integrated psychotherapies (SIPs).
 
  In total, 17 clinicians practicing SIPs in a mid-sized city on the US Gulf Coast implemented session-to-session assessments of these outcomes with 158 clients over a 4-month period and also reported their use of specific spiritual interventions after each session (e.g., affirmed client's divine worth).
 
  Multivariate growth modeling revealed clients' psychological distress decreased over the study period whereas authoritarian God representations increased and benevolent God representations remained stable. In addition, clients who increased in benevolent representations of God had a greater likelihood of experiencing alleviation of psychological distress.
 
  These findings affirm the potential efficacy of SIPs and cultural importance of belief in a benevolent deity as a source of strength, identity, and potential healing among Christians clients who prefer a spiritually integrated approach in psychotherapy.
 These findings affirm the potential efficacy of SIPs and cultural importance of belief in a benevolent deity as a source of strength, identity, and potential healing among Christians clients who prefer a spiritually integrated approach in psychotherapy.
  Exploring a wide range of factors associated with flourishing and with the absence of depressive symptoms among postpartum women.
 
  A sample of 661 postpartum women completed a set of questionnaires assessing sociodemographicand infant-related data, flourishing, psychological flexibility, self-compassion, resilience, and maternal confidence.
 
  Younger infant age, higher levels of maternal confidence, and resilience increased the likelihood of flourishing. In turn, higher income, fewer problems with an infant's sleep, perceiving an infant's temperament as easy, and higher psychological flexibility increased the likelihood of not having depressive symptoms. Appraising the support received by others as good and having higher self-compassion increased the likelihood of both outcomes.
 
  Our results support positive mental health and mental illness being related but distinct dimensions. Promoting positive mental health in the postpartum period should be an additional goal in public health care as it may efficiently complement the prevention of psychopathology.
 Our results support positive mental health and mental illness being related but distinct dimensions. Promoting positive mental health in the postpartum period should be an additional goal in public health care as it may efficiently complement the prevention of psychopathology.Plant carbon isotope discrimination is complex, and could be driven by climate, evolution and/or edaphic factors. We tested the climate drivers of carbon isotope discrimination in modern and historical plant chemistry, and focus in particular on the relationship between rising [CO2 ] over Industrialization and carbon isotope discrimination. We generated temporal records of plant carbon isotopes from museum specimens collected over a climo-sequence to test plant responses to climate and atmospheric change over the past 200 yr (including Pinus strobus, Platycladus orientalis, Populus tremuloides, Thuja koraiensis, Thuja occidentalis, Thuja plicata, Thuja standishii and Thuja sutchuenensis). We aggregated our results with a meta-analysis of a wide range of C3 plants to make a comprehensive study of the distribution of carbon isotope discrimination and values among different plant types. We show that climate variables (e.g. mean annual precipitation, temperature and, key to this study, CO2 in the atmosphere) do not drive carbon isotope discrimination. Plant isotope discrimination is intrinsic to each taxon, and could link phylogenetic relationships and adaptation to climate quantitatively and over ecological to geological time scales.Allergic diseases are characterized by overactive type 2 immune responses to allergens and immunoglobulin E (IgE)-mediated hypersensitivity. Emerging evidence suggests that follicular helper T (TFH ) cells, rather than type 2 T-helper (TH 2) cells, play a crucial role in controlling IgE production. However, follicular regulatory T (TFR ) cells, a specialized subset of regulatory T (TREG ) cells resident in B-cell follicles, restricts TFH cell-mediated help in extrafollicular antibody production, germinal center (GC) formation, immunoglobulin affinity maturation, and long-lived, high-affinity plasma and memory B-cell differentiation. In mouse models of allergic asthma and food allergy, CXCR5+ TFH cells, not CXCR5- conventional TH 2 cells, are needed to support IgE production, otherwise exacerbated by CXCR5+ TFR cell deletion. Upregulation of TFH cell activities, including a skewing toward type 2 TFH (TFH 2) and IL-13 producing TFH (TFH 13) phenotypes, and defects in TFR cells have been identified in patients with allergic diseases.