Robust SARS-CoV-2 T cell responses with common TCR?? motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%–75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response

From Romantic Gothic to Victorian Medievalism: 1817 and 1877

"The Cambridge History of the Gothic was conceived in 2015, when Linda Bree, then Editorial Director at Cambridge University Press, first suggested the idea to us

Venetoclax Initiation in Chronic Lymphocytic Leukemia: International Insights and Innovative Approaches for Optimal Patient Care

Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated-TP53 and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death. Venetoclax ramp-up involves gradual, stepwise increases in daily venetoclax dosing from 20 mg to 400 mg (target dose) over 5 weeks; adherence to on-label scheduling provides a tumor debulking phase, reducing the risk of TLS. The key components of safe venetoclax therapy involve assessment (radiographic evaluation and baseline blood chemistry), preparation (adequate hydration), and initiation (blood chemistry monitoring). In addition to summarizing the evidence for venetoclax’s efficacy and safety, this review uses hypothetical patient scenarios based on risk level for TLS (high, medium, low) to share the authors’ clinical experience with venetoclax initiation and present global approaches utilized in various treatment settings. These hypothetical scenarios highlight the importance of a multidisciplinary approach and shared decision-making, outlining best practices for venetoclax initiation and overall optimal treatment strategies in patients with CLL

Prospective comprehensive profiling of immune responses to COVID‐19 vaccination in patients on zanubrutinib therapy

Abstract Zanubrutinib‐treated and treatment‐naïve patients with chronic lymphocytic leukaemia (CLL) or Waldenstrom's macroglobulinaemia were recruited in this prospective study to comprehensively profile humoral and cellular immune responses to COVID‐19 vaccination. Overall, 45 patients (median 72 years old) were recruited; the majority were male (71%), had CLL (76%) and were on zanubrutinib (78%). Seroconversion rates were 65% and 77% following two and three doses, respectively. CD4+ and CD8+ T‐cell response rates increased with third dose. In zanubrutinib‐treated patients, 86% developed either a humoral or cellular response. Patients on zanubrutinib developed substantial immune responses following two COVID‐19 vaccine doses, which further improved following a third dose

The Theatrical Gothic in the Nineteenth Century

Despite its seeming defeat at the hands of the new melodrama and, later, the emerging stage realism, the Gothic continued to stalk the stage long into the nineteenth century. Shape-shifting and refusing to die outright, the Gothic mode would inform melodrama, domestic drama, sensation drama and even the emerging realist dramas to the end of the century. Moreover, whilst according to hegemonic narratives of theatre history, the new modes of realism would claim a victorious precedence over the drama of the shudder, this chapter argues that as the fin de siècle loomed, attempts to repress the Gothic on stage were met with an increasingly Gothic representation of the theatre itself within the wider popular and literary imagination

The Gothic in Nineteenth-Century Italy

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The Genesis of the Victorian Ghost Story

The Victorian culture of mourning and fascination with death is only partly responsible for the rise of the ghost story as a distinct genre in the period. More fundamentally, it can be contextualized in relation to an array of interleaving discourses of the unseen: the perceived invisibility of money and the financial markets; the advent of new, invisible technologies (telegraphy, telephony) that constituted a form of modern supernatural; spiritualism and the pseudo-scientific investigation of the paranormal. Many ghost story writers explored, even embraced, the spectral effects of modernity and the ghost story flourished in an historical moment when scientific and technological progress was shadowed by the occult. For women writers, the ghost story is a tale of increasing visibility and opportunity: in a climate of social and political reform, women occupied a prominent role in the genre, exploiting the growing appetite for popular and marketable writing, particularly in shorter forms, afforded by a burgeoning periodical culture. The chapter will conclude by considering the impact of this changing publication context on the development of the ghost story, including the institution of the Christmas ghost tale, networks of writers and ghost story cycles. The main writers to be discussed will be Charles Dickens, Amelia Edwards, Sheridan Le Fanu, Elizabeth Gaskell, Henry James, M. R. James, Vernon Lee, Edith Nesbit, Margaret Oliphant and Charlotte Riddell