Publications by authors named "Simon Lacey"

Sound symbolism occurs when the sound of a word alone can convey its meaning, e.g. 'balloon' and 'spike' sound rounded and pointed, respectively.

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Sound symbolism, the idea that the sound of a word alone can convey its meaning, is often studied using auditory pseudowords. For example, people reliably assign the auditory pseudowords "bouba" and "kiki" to rounded and pointed shapes, respectively. Previously we showed that representational dissimilarity matrices (RDMs) of the shape ratings of auditory pseudowords correlated significantly with RDMs of acoustic parameters reflecting spectro-temporal variations; the ratings also correlated significantly with voice quality features.

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Both multisensory and lexical information are known to influence the perception of speech. However, an open question remains: is either source more fundamental to perceiving speech? In this perspective, we review the literature and argue that multisensory information plays a more fundamental role in speech perception than lexical information. Three sets of findings support this conclusion: first, reaction times and electroencephalographic signal latencies indicate that the effects of multisensory information on speech processing seem to occur earlier than the effects of lexical information.

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Non-arbitrary mapping between the sound of a word and its meaning, termed sound symbolism, is commonly studied through crossmodal correspondences between sounds and visual shapes, e.g., auditory pseudowords, like 'mohloh' and 'kehteh', are matched to rounded and pointed visual shapes, respectively.

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Unlabelled: Non-arbitrary mapping between the sound of a word and its meaning, termed sound symbolism, is commonly studied through crossmodal correspondences between sounds and visual shapes, e.g., auditory pseudowords, like 'mohloh' and 'kehteh', are matched to rounded and pointed visual shapes, respectively.

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Physical activity is known to positively impact brain structure and function, but its effects on resting-state functional connectivity (rsFC) and its relationship with complex tasks as a function of age remain unclear. Here, we address these issues in a large population-based sample (N = 540) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository. We relate levels of physical activity to rsFC patterns in magnetoencephalographic (MEG) and functional magnetic resonance imaging (fMRI) data, and to measures of executive function and visuomotor adaptation, across the lifespan.

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Purpose: Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET.

Experimental Design: Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy.

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Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and characterized a potent, fully human anti-MSLN CAR.

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Article Synopsis
  • Studies highlight the role of gut microbes in enhancing T cell function during cancer checkpoint immunotherapy.
  • This research indicates that vancomycin-induced changes in gut microbiota improve the effectiveness of CAR T cell therapy in mice with lymphoma and melanoma.
  • Clinical observations reveal that leukemia patients receiving CART-19 therapy while on vancomycin had a stronger therapeutic response, suggesting gut microbiota modulation could enhance CAR T cell treatment outcomes across different cancers.
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Unlabelled: We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)-negative complete response/stringent complete response.

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The sensory systems responsible for perceptions of touch, vision, hearing, etc. have traditionally been regarded as mostly separate, only converging at late stages of processing. Contrary to this dogma, recent work has shown that interactions between the senses are robust and abundant.

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Chimeric antigen receptor (CAR) T cells have not induced meaningful clinical responses in solid tumors. Loss of T cell stemness, poor expansion capacity, and exhaustion during prolonged tumor antigen exposure are major causes of CAR T cell therapeutic resistance. Single-cell RNA-sequencing analysis of CAR T cells from a first-in-human trial in metastatic prostate cancer identified two independently validated cell states associated with antitumor potency or lack of efficacy.

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Synesthetes can be distinguished from nonsynesthetes on a variety of experimental tasks because their concurrent synesthetic experiences can affect task performance if these experiences match or conflict with some aspect of the stimulus. Here, we tested grapheme-color synesthetes and nonsynesthetic control participants using a novel perceptual similarity task to assess whether synesthetes' concurrent color experiences influence perceived grapheme similarity. Participants iteratively arranged graphemes and, separately, their associated synesthetic colors in a display, such that similar items were placed close together and dissimilar items further apart.

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Unlabelled: Chimeric antigen-receptor (CAR) T cells lead to high response rates in myeloma, but most patients experience recurrent disease. We combined several high-dimensional approaches to study tumor/immune cells in the tumor microenvironment (TME) of myeloma patients pre- and post-B-cell maturation antigen (BCMA)-specific CAR T therapy. Lower diversity of pretherapy T-cell receptor (TCR) repertoire, presence of hyperexpanded clones with exhaustion phenotype, and BAFF+PD-L1+ myeloid cells in the marrow correlated with shorter progression-free survival (PFS) following CAR T therapy.

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Article Synopsis
  • Chimeric antigen receptor T-cell (CART) immunotherapy shows promise for treating B-cell non-Hodgkin lymphoma (NHL), but around two-thirds of patients do not respond effectively.
  • A study found that chromosomal alterations in the BCL-2 gene, which helps cancer cells resist apoptosis, are linked to decreased survival rates in patients treated with anti-CD19 CART.
  • To improve efficacy, researchers created venetoclax-resistant CART cells by modifying BCL-2 and found that this approach, combined with venetoclax, enhanced anti-tumor activity, suggesting new strategies for improving CART therapy in resistant lymphoma cases.
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Purpose: To study the biology and identify markers of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in children after chimeric antigen receptor T-cell (CAR T) treatment.

Experimental Design: We used comprehensive proteomic profiling to measure over 1,400 serum proteins at multiple serial timepoints in a cohort of patients with B-cell acute lymphoblastic leukemia treated with the CD19-targeted CAR T CTL019 on two clinical trials.

Results: We identified fms-like tyrosine kinase 3 (FLT3) and mast cell immunoglobulin-like receptor 1 (MILR1) as preinfusion predictive biomarkers of severe CRS.

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The epidermal growth factor receptor variant III (EGFRvIII) has been investigated as a therapeutic target for chimeric antigen receptor (CAR) T cell therapy in glioblastoma. Earlier research demonstrated that phenotypic and genotypic characteristics in T cells and CAR T product predicted therapeutic success in hematologic malignancies, to date no determinants for clinical response in solid tumors have been identified. We analyzed apheresis and infusion products from the first-in-human trial of EGFRvIII-directed CAR T for recurrent glioblastoma (NCT02209376) by flow cytometry.

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In chronic lymphocytic leukemia (CLL) patients who achieve a complete remission (CR) to anti-CD19 chimeric antigen receptor T cells (CART-19), remissions are remarkably durable. Preclinical data suggesting synergy between CART-19 and the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib prompted us to conduct a prospective single-center phase 2 trial in which we added autologous anti-CD19 humanized binding domain T cells (huCART-19) to ibrutinib in patients with CLL not in CR despite ≥6 months of ibrutinib. The primary endpoints were safety, feasibility, and achievement of a CR within 3 months.

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Chimeric antigen receptor (CAR) T cells have demonstrated promising efficacy, particularly in hematologic malignancies. One challenge regarding CAR T cells in solid tumors is the immunosuppressive tumor microenvironment (TME), characterized by high levels of multiple inhibitory factors, including transforming growth factor (TGF)-β. We report results from an in-human phase 1 trial of castration-resistant, prostate cancer-directed CAR T cells armored with a dominant-negative TGF-β receptor (NCT03089203).

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The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers. However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia who achieved a complete remission in 2010.

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Objective: Heterogeneity has hampered sepsis trials, and sub-phenotyping may assist with enrichment strategies. However, biomarker-based strategies are difficult to operationalize. Four sub-phenotypes defined by distinct temperature trajectories in the first 72 h have been reported in adult sepsis.

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Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematological malignancies but remains ineffective in solid tumors, due in part to CAR T cell exhaustion in the solid tumor microenvironment. To study dysfunction of mesothelin-redirected CAR T cells in pancreatic cancer, we establish a robust model of continuous antigen exposure that recapitulates hallmark features of T cell exhaustion and discover, both in vitro and in CAR T cell patients, that CAR dysregulation is associated with a CD8+ T-to-NK-like T cell transition. Furthermore, we identify a gene signature defining CAR and TCR dysregulation and transcription factors, including SOX4 and ID3 as key regulators of CAR T cell exhaustion.

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Purpose: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cells (CART-BCMA) are a promising treatment for relapsed/refractory multiple myeloma (r/rMM). We evaluated the safety and feasibility of bridging radiation (RT) in subjects treated on a phase I trial of CART-BCMA.

Experimental Design: Twenty-five r/rMM subjects were treated in three cohorts with two doses of CART-BCMA cells ± cyclophosphamide.

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Synopsis of recent research by authors named "Simon Lacey"

  • - Simon Lacey's recent research emphasizes the concept of
  • sound symbolism
  • , exploring how the sounds of words influence perceived meanings, as seen in his articles discussing phonetic underpinnings and auditory pseudowords that align with specific shapes.
  • - His studies highlight the
  • neural and perceptual aspects
  • of sound symbolism, investigating how auditory and visual information interact, particularly in the experiment where sounds are associated with physical shapes, indicating significant neural correlates.
  • - Additionally, Lacey's work extends beyond linguistics to explore
  • multisensory integration
  • in speech perception, suggesting that multisensory information plays a more crucial role than lexical information in processing speech signals as indicated by reaction times and EEG data from his review.

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