• Research data close
• Collection close

Predicting the future can bring enormous advantages. Across the ages, reliance on supernatural foreseeing was substituted by the opinion of expert forecasters, and now by collective intelligence approaches which draw on many non-expert forecasters. Yet all of these approaches continue to see individual forecasts as the key unit on which accuracy is determined. Here, we hypothesize that compromise forecasts, defined as the average prediction in a group, represent a better way to harness collective predictive intelligence. We test this by analysing 5 years of data from the Good Judgement Project and comparing the accuracy of individual versus compromise forecasts. Furthermore, given that an accurate forecast is only useful if timely, we analyze how the accuracy changes through time as the events approach. We found that compromise forecasts are more accurate, and that this advantage persists through time, though accuracy varies through time. Contrary to what was expected (i.e. a monotonous increase in forecasting accuracy as time passes), forecasting error for individuals and for team compromise starts its decline around two months prior to the event. Overall, we offer a method of aggregating forecasts to improve accuracy, which can be straightforwardly applied in noisy real-world settings.

Intimate partner violence (IPV) is among the most common acts of violence against women worldwide, making it a major global threat to women’s health and safety. The assessment and management of IPV offenders are therefore vital tasks in criminal justice systems. The current study examined whether the DRAOR, a general case management tool, was useful for supervising 112 male IPV offenders in Iowa, United States. Several risk factors emerged as potentially important treatment targets for partner-violent men, including poor attachment with others, substance abuse, anger/hostility, opportunity/access to victims, and problematic interpersonal relationships. While further research is needed to improve the utility of the DRAOR for predicting IPV recidivism, it assesses several factors that are relevant for supervising IPV cases (e.g., substance abuse, anger/hostility, victim access). This suggests the DRAOR could potentially be used to guide case management in the presence of a validated IPV tool that focuses on static risk factors, such as the ODARA. The use of the DRAOR with IPV offenders may also be warranted if they are found to be generally violent/antisocial rather than as family only offenders.

Abstract Background Recently discovered drugs that target epigenetic modifying complexes are providing new treatment options for a range of cancers that affect patients of reproductive age. Although these drugs provide new therapies, it is likely that they will also affect epigenetic programming in sperm and oocytes. A promising target is Enhancer of Zeste 2 (EZH2), which establishes the essential epigenetic modification, H3K27me3, during development. Results In this study, we demonstrate that inhibition of EZH1/2 with the clinically relevant drug, tazemetostat, severely depletes H3K27me3 in growing oocytes of adult female mice. Moreover, EZH2 inhibition depleted H3K27me3 in primary oocytes and in fetal oocytes undergoing epigenetic reprogramming. Surprisingly, once depleted, H3K27me3 failed to recover in growing oocytes or in fetal oocytes. Conclusion Together, these data demonstrate that drugs targeting EZH2 significantly affect the germline epigenome and, based on genetic models with oocyte-specific loss of EZH2 function, are likely to affect outcomes in offspring.

Abstract Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like). IL-11 + iCAF were spatially associated with inflammatory monocytes and regulated in vitro through synergistic activation of canonical NF-κB signalling by IL-1β and TNF-α. FRC-like were enriched in immune-hot HPV+ve tumours, associated with CD4 + T-cells and B-cells in tertiary lymphoid structures and regulated through non-canonical NF-κB signalling via lymphotoxin. Pan-cancer analysis revealed several ‘iCAF’ subgroups present in both normal and cancer tissues; IL11 + iCAF were found in cancers from the gastrointestinal (GI) tract and transcriptomically distinct from iCAFs previously described in pancreatic and breast cancers with greater inflammatory properties; FRC-like fibroblasts were present at low frequencies in all tumour types, and were associated with significantly better survival in patients receiving checkpoint immunotherapy. This work clarifies and expands current literature on immunomodulatory CAFs, highlighting links with important immunological niches.

Abstract Improving the growth status of Aspergillus oryzae is an efficient way to enhance L-malate production. However, the growth mechanism of filamentous fungi is relatively complex, which limits A. oryzae as a cell factory to produce L-malate industrially. This study determined the relationship between growth status and L-malate production. The optimal ranges of colony diameter, percentage of vegetative mycelia, and pellet number of A. oryzae were determined to be 26–30 mm, 35–40%, and 220–240/mL, respectively. To achieve this optimum range, adaptive evolution was used to obtain the evolved strain Z07 with 132.54 g/L L-malate and a productivity of 1.1 g/L/h. Finally, a combination of transcriptome analysis and morphological characterization was used to identify the relevant pathway genes that affect the growth mechanism of A. oryzae. The strategies used in this study and the growth mechanism provide a good basis for efficient L-malate production by filamentous fungi. Graphical Abstract