Social Community Teams' Creation of Service Integration Through Boundary Work and Play with Their Stakeholders.

In many European countries, responsibilities for social care have been shifted to municipalities to enhance accessibility and stimulate integration of care and social services, and to cut costs. Multidisciplinary local Social Community Teams (SCTs) have become increasingly responsible for the provision of these integrated services, requiring them to collaborate with local health and societal organisations. To collaborate and to integrate services the SCTs must work across their own and stakeholders' boundaries (e.

Distinct spatiotemporal dynamics of CD8 T cell-derived cytokines in the tumor microenvironment.

Cells in the tumor microenvironment (TME) influence each other through secretion and sensing of soluble mediators, such as cytokines and chemokines. While signaling of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) is integral to anti-tumor immune responses, our understanding of the spatiotemporal behavior of these cytokines is limited. Here, we describe a single cell transcriptome-based approach to infer which signal(s) an individual cell has received.

Development and validation of a fast and automated DNA identification line.

The importance of DNA evidence for gaining investigative leads demands a fast workflow for forensic DNA profiling performed in large volumes. Therefore, we developed software solutions for automated DNA profile analysis, contamination check, major donor inference, DNA database (DDB) comparison and reporting of the conclusions. This represents the Fast DNA IDentification Line (FIDL) and this study describes its development, validation and implementation in criminal casework at the authors' institute.

High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types.

Background: High tumor mutation burden (TMB-H) has been proposed as a predictive biomarker for response to immune checkpoint blockade (ICB), largely due to the potential for tumor mutations to generate immunogenic neoantigens. Despite recent pan-cancer approval of ICB treatment for any TMB-H tumor, as assessed by the targeted FoundationOne CDx assay in nine tumor types, the utility of this biomarker has not been fully demonstrated across all cancers.

Patients And Methods: Data from over 10 000 patient tumors included in The Cancer Genome Atlas were used to compare approaches to determine TMB and identify the correlation between predicted neoantigen load and CD8 T cells.

Multi-laboratory validation of DNAxs including the statistical library DNAStatistX.

This study describes a multi-laboratory validation of DNAxs, a DNA eXpert System for the data management and probabilistic interpretation of DNA profiles [1], and its statistical library DNAStatistX to which, besides the organising laboratory, four laboratories participated. The software was modified to read multiple data formats and the study was performed prior to the release of the software to the forensic community. The first exercise explored all main functionalities of DNAxs with feedback on user-friendliness, installation and general performance.

In Situ Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy of Nickel-Catalyzed Hydrogenation Reactions.

Synthesis methods to prepare lower transition metal catalysts and specifically Ni for Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy (SHINERS) are explored. Impregnation, colloidal deposition, and spark ablation have been investigated as suitable synthesis routes to prepare SHINERS-active Ni/Au@SiO catalyst/Shell-Isolated Nanoparticles (SHINs). Ni precursors are confirmed to be notoriously difficult to reduce and the temperatures required are generally harsh enough to destroy SHINs, rendering SHINERS experiments on Ni infeasible using this approach.

Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis.

Cancer-associated systemic inflammation is strongly linked to poor disease outcome in patients with cancer. For most human epithelial tumour types, high systemic neutrophil-to-lymphocyte ratios are associated with poor overall survival, and experimental studies have demonstrated a causal relationship between neutrophils and metastasis. However, the cancer-cell-intrinsic mechanisms that dictate the substantial heterogeneity in systemic neutrophilic inflammation between tumour-bearing hosts are largely unresolved.

DNAxs/DNAStatistX: Development and validation of a software suite for the data management and probabilistic interpretation of DNA profiles.

The data management, interpretation and comparison of sets of DNA profiles can be complex, time-consuming and error-prone when performed manually. This, combined with the growing numbers of genetic markers in forensic identification systems calls for expert systems that can automatically compare genotyping results within (large) sets of DNA profiles and assist in profile interpretation. To that aim, we developed a user-friendly software program or DNA eXpert System that is denoted DNAxs.

Publisher Correction: Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.

In the version of this article originally published, there was an error in Fig. 3j. A label on the heatmap read "TGF-α signaling via NF-κB".

Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.

The efficacy of programmed cell death protein 1 (PD-1) blockade in metastatic triple-negative breast cancer (TNBC) is low, highlighting a need for strategies that render the tumor microenvironment more sensitive to PD-1 blockade. Preclinical research has suggested immunomodulatory properties for chemotherapy and irradiation. In the first stage of this adaptive, non-comparative phase 2 trial, 67 patients with metastatic TNBC were randomized to nivolumab (1) without induction or with 2-week low-dose induction, or with (2) irradiation (3 × 8 Gy), (3) cyclophosphamide, (4) cisplatin or (5) doxorubicin, all followed by nivolumab.

Contact-Dependent Killing by Cytotoxic T Lymphocytes Is Insufficient for EL4 Tumor Regression .

Immunotherapies are an emerging strategy for treatment of solid tumors. Improved understanding of the mechanisms employed by cytotoxic T lymphocytes (CTL) to control tumors will aid in the development of immunotherapies. CTLs can directly kill tumor cells in a contact-dependent manner or may exert indirect effects on tumor cells via secretion of cytokines.

Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.

Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites. However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor reactivity of the intratumoral TCR repertoire of CD8 T cells in ovarian and colorectal cancer-two tumor types for which T cell infiltrates form a positive prognostic marker.

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids.

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner.

Identification of CMTM6 and CMTM4 as PD-L1 protein regulators.

The clinical benefit for patients with diverse types of metastatic cancers that has been observed upon blockade of the interaction between PD-1 and PD-L1 has highlighted the importance of this inhibitory axis in the suppression of tumour-specific T-cell responses. Notwithstanding the key role of PD-L1 expression by cells within the tumour micro-environment, our understanding of the regulation of the PD-L1 protein is limited. Here we identify, using a haploid genetic screen, CMTM6, a type-3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein.

Effect of testosterone administration on serum and urine kallikrein concentrations in female-to-male transsexuals.

Background: Concentrations of human tissue kallikreins (hKs), a group of 15 secreted serine proteases found in many tissues, are modulated by steroid hormones in cancer cell lines. To gain insight into in vivo kallikrein regulation we measured kallikrein concentrations in serum and urinary tissue in female-to-male transsexuals before and after testosterone administration.

Methods: We collected blood and urine samples before treatment and after 4 and 12 months from 28 female-to-male transsexuals who received 250 mg of testosterone esters intramuscularly every 2 weeks.

Serum and urine tissue kallikrein concentrations in male-to-female transsexuals treated with antiandrogens and estrogens.

Background: The expression of human tissue kallikrein genes is regulated by steroid hormones, but most studies have been conducted with cancer cell lines. Our purpose was to examine serum and urinary tissue kallikrein concentration changes in male-to-female transsexuals before and after treatment with antiandrogens and estrogens.

Methods: Thirty-five male-to-female transsexuals receiving cyproterone acetate and estrogens (orally or transdermally) were included in this study.

Effects of long-term androgen administration on breast tissue of female-to-male transsexuals.

Our aim was to examine the effects of androgen administration on breast tissue histology of female-to-male transsexuals and to study the immunohistochemical expression of three human tissue kallikreins, hK3 (PSA), hK6, and hK10. We studied 23 female-to-male transsexuals who were treated with injectable testosterone for 18-24 months. We also used 10 control female breast tissues.