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Competing Interests: Disclosures None of the authors reported any disclosures.

Both the 2022 WHO HAEM5 and the International Consensus Classification of lymphoma have refined the way we now approach high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements moving the previous generation of classification a step forward. The unifying biology of MYC/BCL2 tumours has been clearer and their inferior prognosis confirmed compared to those with morphological similarities but lacking the classifying cytogenetic abnormalities. FISH testing has largely become population based and we have learnt much from this. We can readily define molecular categories and apply these widely to clinical practice. Uncertainty has however been shed upon the place of double MYC/BCL6 translocations in defining a common disease group. We have enhanced knowledge of outcomes and the role of therapy intensification to overcome chemotherapy resistance. For those patients failed by initial induction chemotherapy, immunotherapy approaches, including CAR-T therapies, are improving outcomes. Novel inhibitors, targeting dysregulated oncogenic proteins are being explored at pace. The rare, but difficult, diagnostic classification HGBL (NOS) remains a diagnosis of exclusion with limited data on an optimal clinical approach. The days of talking loosely of double and triple hit lymphoma are numbered as this review synergises the current data on biology, prognosis, and therapies in HGBL., (Copyright © 2024 American Society of Hematology.)

MYC translocation occurs in 8-14% of diffuse large B-cell lymphoma (DLBCL), and may concur with BCL2 and/or BCL6 translocation, known as double-hit (DH) or triple-hit (TH). DLBCL-MYC/BCL2-DH/TH are largely germinal centre B-cell like subtype, but show variable clinical outcome, with IG::MYC fusion significantly associated with inferior survival. While DLBCL-MYC/BCL6-DH are variable in their cell-of-origin subtypes and clinical outcome. Intriguingly, only 40-50% of DLBCL with MYC translocation show high MYC protein expression (>70%). We studied 186 DLBCLs with MYC translocation including 32 MYC/BCL2/BCL6-TH, 75 MYC/BCL2-DH and 26 MYC/BCL6-DH. FISH revealed a MYC/BCL6 fusion in 59% of DLBCL-MYC/BCL2/BCL6-TH and 27% of DLBCL-MYC/BCL6-DH. Targeted NGS showed a similar mutation profile and LymphGen genetic subtype between DLBCL-MYC/BCL2/BCL6-TH and DLBCL-MYC/BCL2-DH, but variable LymphGen subtypes among DLBCL-MYC/BCL6-DH. MYC protein expression is uniformly high in DLBCL with IG::MYC, but variable in those with non-IG::MYC including MYC/BCL6-fusion. Translocation breakpoint analyses of 8 cases by TLC-based NGS showed no obvious genomic configuration that enables MYC transactivation in 3 of the 4 cases with non-IG::MYC, while a typical promoter substitution or IGH super enhancer juxtaposition in the remaining cases. The findings potentially explain variable MYC expression in DLBCL with MYC translocation, and also bear practical implications in its routine assessment., (© 2024. The Author(s).)

The advent of immunotherapy in lymphomas, beginning with Rituximab, have led to paradigm shifting treatments that are increasingly bringing a greater number of affected patients within the ambit of durable disease control and cure. Bispecific antibodies harness the properties of the immunoglobulin antibody structure to design molecules which, apart from engaging with the target tumour associated antigen, engage the host's T-cells to cause tumour cell death. Mosunetuzumab, an anti-CD20 directed bispecific antibody was the first to be approved in follicular lymphoma, this has now been followed by quick approvals of Glofitamab and Epcoritamab in diffuse large B-cell lymphomas. This article reviews contemporary data and ongoing studies evaluating the role of bispecific antibodies in indolent b-cell non Hodgkin lymphomas. This is an area of active research and presents many opportunities in advancing the treatment of indolent lymphomas and potentially forge a chemo-free treatment paradigm in this condition., Competing Interests: AD reports a relationship with the following: F Hoffmann-La Roche Ltd that includes consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement; AbbVie Ltd. that includes consulting or advisory; Genmab BV that includes consulting or advisory; AstraZeneca that includes consulting or advisory and funding grants; Sobi Inc that includes consulting or advisory; Incyte Corporation that includes consulting or advisory; CellCentric Limited that includes funding grants; Bristol Myers Squibb Co that includes consulting or advisory and funding grants; Gilead Sciences Kite HQ that includes consulting or advisory. VR reports a relationship with the following: AbbVie Inc that includes travel reimbursement; Cancer Research UK that includes travel reimbursement; AstraZeneca India Private Limited that includes non-financial support; Pfizer India that includes consulting or advisory; Roche Products India Pvt. Ltd that includes consulting or advisory; European Society for Medical Oncology that includes non-financial support; Intas Pharmaceuticals Ltd that includes non-financial support and travel reimbursement., (Copyright © 2024 Radhakrishnan and Davies.)

Intertidal artificial habitats are proliferating, but are generally simpler in structure and host lower biodiversity than natural rocky reefs. Eco-engineering aims to enhance the biodiversity of coastal infrastructure, often through physical structural modifications that mimic topographic properties of natural shores. Relationships between biotic assemblages and structural properties of natural and artificial reefs have been extensively studied at sampling scales of up to 1 m 2 . But evidence that quantified local structural variation has an appreciable influence on biotic assemblages, at a shore-wide scale across regional environmental gradients, is lacking. Here we addressed this knowledge gap with an observational study at 32 natural and artificial intertidal reef sites in Wales, UK. We used multivariate community analysis and permutation tests to examine associations between local physical structure, regional environmental variables and sessile biotic assemblages. A potential influence of local habitat structure on assemblage composition was evident across regional-scale environmental gradients. Compared to natural sites, artificial reefs had lower taxonomic richness, distinct and more variable assemblage composition, and different physical structure. After removing the effect of habitat (natural or artificial), canonical correspondence analysis showed that environmental variables (wave exposure, sea surface temperature and salinity variation), along with two metrics of physical structure (standard deviation in log-transformed detrended roughness and skewness of surface verticality, both at 0.5 m scale), explained 40 % of the variation in assemblage composition among sites. The two structural metrics independently explained 14.5 % of the variation. Associations identified between individual taxa and environmental variables indicated that sites with a higher proportion of horizontal surfaces hosted more canopy macroalgae, which in turn support other algae and invertebrates. Our findings provide evidence to inform scaling-up of structural eco-engineering interventions from experimental contexts to enhance the biodiversity of coastal infrastructure across regional extents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)