Ex vivo T-lymphopoiesis assays assisting corrective treatment choice for genetically undefined T-lymphocytopaenia

Persistent selective T-lymphocytopenia is found both in SCID and congenital athymia. Without molecular diagnosis, it is challenging to determine whether HCT or thymus transplantation ought to be performed. Ex vivo T-lymphopoiesis assays have been proposed to assist clinical decision-making for genetically undefined patients. We investigated 20 T-lymphocytopenic patients, including 13 patients awaiting first-line treatment and 7 patients with failed immune reconstitution after previous HCT or thymus transplantation. Whilst developmental blocks in ex vivo T-lymphopoiesis indicated hematopoietic cell-intrinsic defects, successful T-lymphocyte differentiation required careful interpretation, in conjunction with clinical status, immunophenotyping, and genetic investigations. Of the 20 patients, 13 proceeded to treatment, with successful immune reconstitution observed in 4 of the 6 patients post-HCT and 4 of the 7 patients after thymus transplantation, the latter including two patients who had previously undergone HCT. Whilst further validation and standardization are required, we conclude that assessing ex vivo T-lymphopoiesis during the diagnostic pathway for genetically undefined T-lymphocytopenia improves patient outcomes by facilitating corrective treatment choice

Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control

The polarized glandular organization of epithelial cells is frequently lost during development of carcinoma. However, the specific oncogene targets responsible for polarity disruption have not been identified. Here, we demonstrate that activation of ErbB2 disrupts apical-basal polarity by associating with Par6-aPKC, components of the Par polarity complex. Inhibition of interaction between Par6 and aPKC blocked the ability of ErbB2 to disrupt the acinar organization of breast epithelia and to protect cells from apoptosis but was not required for cell proliferation. Therefore, oncogenes target polarity proteins to disrupt glandular organization and protect cells from apoptotic death during development of carcinoma

Comparing Human-Only, AI-Assisted, and AI-Led Teams on Assessing Research Reproducibility in Quantitative Social Science

This study evaluates the effectiveness of varying levels of human and artificial intelligence (AI) integration in reproducibility assessments of quantitative social science research. We computationally reproduced quantitative results from published articles in the social sciences with 288 researchers, randomly assigned to 103 teams across three groups - human-only teams, AI-assisted teams and teams whose task was to minimally guide an AI to conduct reproducibility checks (the "AI-led" approach). Findings reveal that when working independently, human teams matched the reproducibility success rates of teams using AI assistance, while both groups substantially outperformed AI-led approaches (with human teams achieving 57 percentage points higher success rates than AI-led teams, ﹤ 0.001). Human teams were particularly effective at identifying serious problems in the analysis: they found significantly more major errors compared to both AI-assisted teams (0.7 more errors per team, = 0.017) and AI-led teams (1.1 more errors per team, ﹤ 0.001). AI-assisted teams demonstrated an advantage over more automated approaches, detecting 0.4 more major errors per team than AI-led teams ( = 0.029), though still significantly fewer than human-only teams. Finally, both human and AI-assisted teams significantly outperformed AIled approaches in both proposing (25 percentage points difference, = 0.017) and implementing (33 percentage points difference, = 0.005) comprehensive robustness checks. These results underscore both the strengths and limitations of AI assistance in research reproduction and suggest that despite impressive advancements in AI capability, key aspects of the research publication process still require human substantial human involvement