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A review of a film about 6 contemporary European theologians: Judith Wolfe, Garrick Allen, Ann Loades, David Brown, Perry Schmidt-Leukel and Lieven Boeve sponsored by the Templeton Religion Trust. Beautifully made by Sean Dimond, the film interweaves the interviewees’ theological explorations with elements of their biography and shots of their daily lives and recreations. Despite the very different fields in which they all work: eschatology, the textual history of the Bible, the place of women in church and society, religion and art, interreligious understanding, theology and interruption, common themes begin to emerge, the elusiveness of self-understanding, the sense of the diversity and the constantly developing nature of religious traditions, such that there is always more to be expected and surprised by.

This chapter outlines the history of the Scottish family firm of publishers T&T Clark, which for nearly 200 years made a significant contribution to the development of an historical and critical approach to theological study. This was chiefly effected through a series of publications of mostly German-speaking works of theology and biblical studies. It is suggested that these were principally of a mediating kind, seeking to achieve a complementarity between forms of confessional Protestant belief and theology on the one hand and historical and philosophical studies on the other. This reached a climax in the early twentieth century with the publication of major works by Ritschl and Schleiermacher. Thereafter the firm’s publishing programme became more influenced by confessional forms of theology, particularly through its translation of Karl Barth’s Church Dogmatics. Its legacy, however, remains not only in the form of Barth but of Schleiermacher and historical critical studies of the Bible.

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients, Key Points • Adult patients with hematologic malignancy and COVID-19 found a 34% risk of death, whereas pediatric patients had a 4% risk of death. • Patients on systemic anticancer therapy had a similar risk of death to patients on no treatment (RR, 1.17; 95% CI, 0.83-1.64).

The synthesis of serine from glucose is a key metabolic pathway supporting cellular proliferation in healthy and malignant cells. Despite this, the role that this aspect of metabolism plays in germinal center biology and pathology is not known. Here, we performed a comprehensive characterization of the role of the serine synthesis pathway in germinal center B cells and lymphomas derived from these cells. We demonstrate that upregulation of a functional serine synthesis pathway is a metabolic hallmark of B-cell activation and the germinal center reaction. Inhibition of phosphoglycerate dehydrogenase (PHGDH), the first and rate limiting enzyme in this pathway, leads to defective germinal formation and impaired high-affinity antibody production. In addition, overexpression of enzymes involved in serine synthesis is a characteristic of germinal center B-cell derived lymphomas, with high levels of expression being predictive of reduced overall survival in diffuse large B cell lymphoma. Inhibition of PHGDH induces apoptosis in lymphoma cells reducing disease progression. These findings establish PHGDH as a critical player in humoral immunity and a clinically relevant target in lymphoma.

‘The Bible in the post-colonial world’ describes how colonizers and missionaries used the Bible. During the colonization of Latin America, the narratives of the conquest of Canaan in Joshua and Judges provided support not only for conquest, but also for the merciless killing of those who refused to submit. Nevertheless, Latin America also saw a powerful movement arise to rescue the Bible from its colonial misuse. In Africa too, the Bible could be used as an instrument both of oppression and of liberation. In South Africa, the stories of the Exodus and the entry to the Promised Land played a significant part in the emerging ideology of Afrikanerdom. At the same time, church leaders like Desmond Tutu used the language of the Bible to mount a powerful attack on apartheid.

‘The Bible in politics’ examines the place of the Bible in politics. Martin Luther and the mainstream Reformers used it to justify the power of the sword and to draw a clear line between the laws which were to govern secular society and the teaching of the Sermon on the Mount, which was intended only for Christians. The Quakers in England, like the Anabaptists, interpreted the commandments of the Sermon of the Mount literally and so refused to bear arms or to swear oaths. It is worth considering how the Bible has been a major source of the patriarchy which has marked Christian societies and exploring some feminist critiques of biblical narratives.

‘The Bible in the modern world: classic or sacred text?’ provides an overview of how the Bible continues to inform people’s lives in our modern world. Indeed, the Bible is still one of the most influential and widely read books in the world. The chapter introduces some of today’s Bible readers to demonstrate its extraordinary appeal, its ability to speak, negatively or positively, to people of different education, culture, and beliefs. The sheer diversity of the ways in which the Bible has been embodied in Jewish and Christian communities is both fascinating and disturbing. It has been used for purposes which for many are profoundly abhorrent, as well as in the cause of justice and liberation.

‘The Bible and its critics’ explores critical readings, mainly from the Reformation and the Enlightenment, which had radical effects on how the Bible was perceived. For Martin Luther, the Bible speaks about the liberation of men and women from the threat of God’s law and punishment. Thus, the Reformation sought to emancipate men and women from their bondage to the medieval church. To do so, it used the methods of the Renaissance to subject traditional readings of the biblical text to closer scrutiny. Meanwhile, the Enlightenment period saw the rise of the empirical sciences and of rationalist and empiricist philosophies which sought to base human knowledge and the conduct of human affairs on the unaided efforts of human reason. The Deists, in particular, pointed to the existence of inconsistencies and contradictions within the Bible. Out of this emerged a rich tradition of critical scholarship which sought historically to reconstruct the life of Jesus.

The Bible has been the source of great truth, goodness, and beauty at the same time as it has inspired lies, wickedness, and ugliness. What it has not produced is a uniform manner of its reading and interpretation. The very process of canonization is nevertheless part of an attempt to limit diversity and deviance of belief within religious communities. Ultimately, however, there is no controlling the way it is read. It is important therefore to be critically aware of the different kinds of uses to which the Bible may be put and to learn to discriminate among them. Readers need to exercise their own moral and aesthetic judgement over the different readings which have been offered of these texts, not least in their own traditions. At the same time, their own judgement will be influenced by the texts as they engage more closely with them and their reception.

‘Jewish and Christian readings of the Binding of Isaac’ assesses some of the readings of the Bible by believers, both Jews and Christians. It focuses on the Akedah, the story of Abraham’s binding of Isaac in Genesis 22. The Akedah is a story of strange violence and tenderness, of a father ordered by his God to sacrifice ‘his only son’. For Jews, this is a story read in the light of the history of Jewish persecution. Remarkable retellings of the story are to be found from Rabbis in the Rhineland during the Crusades. For Christians, the themes of the Akedah are largely subsumed in their reading of the Passion. Nevertheless, the story has continued to exert its spell, remaining a story which raises profound questions about the nature of faith and suffering. Its use by philosophers (Kierkegaard) and poets (Wilfred Owen) is examined.

‘Galatians through history’ studies the rich reception history of Paul’s letter to the Galatians, which is one of the shorter works in the Bible. At the turn of the 4th century, it helped shape the new worlds which would emerge as the Roman Empire embraced Christianity. At the Reformation, it was one of the central texts for Martin Luther. Luther’s commentary was a key text for John Bunyan and for the Wesleys. It is important to look at how Paul deals in his letter with the central issue of Law observance and consider how later interpreters of his letter used his ideas and images to shape the life of the Churches in their very different situations.

‘The making of the Bible’ discusses the process whereby different books came to be included in the various Bibles (a term first used by the Churches) which are now accepted as authoritative (canonical) by various religious communities, Jewish and Christian. This process is often referred to as the canonization of scripture. It is important to look first at the formation of the Hebrew Bible and its Greek version, the Septuagint. While the Septuagint started life as a translation for Jews living in the Diaspora, it was subsequently taken up by the Christian community as the medium through which the Old Testament was known in the Church. The language of the Septuagint also influenced many of the writers of the Christian New Testament. The authoritative writings of the Christian Church were in the first instance largely identical with the Jewish scriptures. It is valuable to consider the process whereby Christian writings, principally letters and gospels, were collected and recognized as authoritative alongside other Jewish writings.

‘How the biblical books were written’ looks at some of the processes of tradition and composition that led to the final form of the biblical books as we know them today. Throughout the period of the composition of the Bible, orality and literacy are closely interrelated. Yet, even though the writings of the Bible have deep roots in an oral culture and tradition, they are also clearly literary works. The writers and compilers of the Bible used a variety of literary forms in which to cast their works. Within the tradition of biblical writing and compilation, such literary forms became influential and constrained and enabled the way in which the books were written

The Bible: A Very Short Introduction explore the material, cultural, and religious history of the Bible. The Bible is both one of the most read and the most influential books in the world. Its stories form the heart of Western civilization, while biblical language is interwoven into literature and everyday speech. As a source of shared Abrahamic beliefs, it has both drawn communities together and given them new life and fuelled bitter disputes. This VSI examines how the books of the Bible have been read and interpreted by different communities across the centuries, including post-colonial and feminist readings of the Bible. It also surveys the Bible’s role in art, music, poetry, and politics.

‘The Bible in high and popular culture’ reflects on how the Bible has had a formative influence on the language, the literature, the art, and the music of all the major European and North American cultures. It continues to influence popular culture in films, novels, and music. From elaborate retellings of the narratives in great novels and in musical representations like Bach’s St Matthew Passion, through Rembrandt’s intimate depictions of biblical scenes and narratives, to echoes of biblical metaphor and motifs in poetry and fiction, there is a huge range of use. Margaret Atwood’s The Handmaid’s Tale (1985) provides a powerful contemporary example. It comments directly on the Bible’s role in the struggle of women.

‘Translation, production, and distribution of the Bible’ examines the translation, production, and distribution of the Bible. For centuries, the religious texts were preserved in Hebrew on scrolls. By the 4th century ce, the whole of the Bible would be found in codex form. Later, the 15th century saw the growth of lay movements based on private prayer and bible reading. It also saw the development of printing using movable type, which made possible the production of cheaper bibles. This prepared the way for the Protestant Reformation with its powerful desire to make the Bible available to all. New methods of producing cheap bibles were developed in the 19th century and led to a remarkably dynamic process of distributing bibles across the world. In this the Bible societies played a vital role.

Introduction: Clinical outcomes for patients with hematologic malignancy and COVID-19 have not been aggregated. We completed a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. Methods: We searched Pubmed and EMBASE up to July 25, 2020, to identify reports of patients with hematologic malignancy and COVID-19 (including papers where the patients with hematologic malignancy were a subset of the total study population). The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included pooled estimates for the risk of ICU admission, mechanical ventilation, and non-invasive ventilation in hospitalized patients. Mortality data were stratified by age, treatment status, and malignancy subtype. For treatment status, "systemic anti-cancer therapy (SACT)" was defined as patients on any anti-cancer therapy. "Cytotoxic SACT" was defined as patients on cytotoxic therapy only. "Not on treatment" was defined as patients on observation or those who were at least 28 days beyond their last active treatment. Sensitivity analyses were conducted on the primary outcomes limiting to studies with low risk of bias, and to studies including both outpatients and hospitalized patients. Due to data limitations, only the primary outcome was assessed for pediatric studies. Pooled prevalence and risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model using MetaXL and Revman 5.4 software. Results: A total of 25 adult studies and 4 pediatric studies comprising 1847 patients from China, Europe, the United Kingdom, and North America were included (Figure 1 and Table 1). The majority of patients were hospitalized (83%). The overall risk of death amongst all patients was 36% (95% CI 31-41, N=1763), and amongst hospitalized patients was 40% (95% CI 36-45, 24 studies with 1295 patients) (Figure 2). Patients aged >60 years had a significantly higher risk of death than patients The risk of ICU admission among hospitalized adult patients was 23% (95% CI 17-29, N=1165); mechanical ventilation 16% (95% CI 12-21, N= 826); and non-invasive ventilation 16% (95% CI 9-26%, N=373). The estimated RR of death among patients on SACT compared to no treatment was 1.22 (95% CI 0.84-1.78; N=457, Figure 3a). The RR of death among patients on cytotoxic SACT versus no treatment was similar at 1.29 (95% CI 0.78-2.15; N=176, Figure 3b). All subgroups of hematologic malignancy had high risks of overall mortality: acquired bone marrow dysfunction syndromes 57% (95% CI 42-72, 11 studies, 42 patients); leukemias 44% (95% CI 31-58, 15 studies, 159 patients), plasma cell dyscrasias 38% (95% CI 29-47, 18 studies, 387 patients); lymphomas (including CLL) 32% (95% CI 26-38, 16 studies, 696 patients); lymphomas (excluding CLL) 32% (95% CI 18-48, 11 studies, 156 patients); CLL 31% (95% CI 24-39, 13 studies, 457 patients); myeloproliferative neoplasms 37% (95% CI 25-49, 9 studies, 62 patients). Sensitivity analysis including only studies with a low risk of bias showed a similar estimate for risk of death among all patients (37% (95% CI 31-42, 20 studies with 1412 patients)) compared to all studies. Sensitivity analysis including only studies reporting on a combination of outpatients and hospitalized patients also showed a similar estimate for risk of death among all patients (38% (95% CI 32-44), 11 studies with 1214 patients) compared to all studies. Conclusion: Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, appear to experience a high risk of dying (pooled risk estimate 36%). Older patients experience higher mortality, and pediatric patients appear to be relatively spared. Importantly, based on the observational data available to date, recent cancer treatment does not appear to significantly increase the risk of dying. These data highlight the need for robust strategies to prevent patients with hematologic malignancy from contracting COVID-19, and may help inform discussions about prevention strategies, treatment, and goals of care. Disclosures Cook: Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; IQVIA: Research Funding; Sanofi: Consultancy; Amgen: Consultancy; Roche: Consultancy; Karyopharm: Consultancy. Zwicker:Dova: Honoraria, Other: Advisory board; Portola: Honoraria, Other: Advisory board; Incyte: Research Funding; Quercegen: Research Funding; Parexel: Consultancy; Sanofi: Consultancy; CSL: Consultancy; Pfizer/BMS: Honoraria, Other: Advisory board. Scarfo:Gilead: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Wood:Pfizer: Research Funding; Best Doctors/Teladoc: Consultancy; Koneksa Health: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Elektra Labs: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ASH Research Collaborative: Honoraria; Genentech: Research Funding. Hicks:Gilead Sciences: Research Funding.

The first cases of coronavirus disease 2019 (COVID-19) were detected in Wuhan, China, in December 2019. Since this time a concerted global effort of research and observational data gathering has meant that a great deal has been learnt about the impact of COVID-19 in patients with lymphoid malignancies. Approximately one-third of patients with lymphoid malignancies who acquire COVID-19 and have it severely enough to require hospital assessment will die from this infection. Major risk factors for a poor outcome are age and co-morbidities, but when these are taken into account lymphoma patients have a slightly greater than 2-fold increased risk compared to the general population. Notably, despite early concerns regarding the particular vulnerability of lymphoma patients due to the immunosuppressive effects of therapy, active treatment, including B-cell depleting agents such as rituximab, do not appear to be associated with an increased risk of a poorer outcome. Indeed, some treatments such as ibrutinib may be beneficial due to their modulation of the potential fatal hyperinflammatory phase of infection. There are risks associated with hemopoietic stem cell transplantation, but the collective experience is that these can be minimized by preventive strategies and that the majority of transplant recipients with COVID-19 infection will survive. Many questions remain including those regarding the outcome of COVID-19 infection in the rarer lymphoid malignancies and the efficacy of COVID-19 vaccines in lymphoma patients. This review aims to discuss these issues and present a summary of the current knowledge of the impact of COVID-19 in lymphoid malignancies.

Since being identified in China in December 2019, coronavirus disease 2019 (Covid‐19) has rapidly evolved into a global pandemic with over 4 million cases and more than 270,000 deaths.(1) Following the first reported cases in the United Kingdom (UK) in late January 2020, numbers have continued to rise with 223,060 cases and 32,065 deaths reported as of 11th May 2020.(2) Initial reports from China have indicated that Covid‐19 has an overall mortality rate of 1.4%. However, the prognosis varies widely between groups, with age over 60 years and underlying conditions including hypertension, diabetes, cardiovascular disease and cancer identified as risk factors for severe disease and death.(3) The initial reports from China show that patients with cancer are over‐represented among individuals who develop severe Covid‐19 after contracting the virus.(4) Patients with haematological malignancies are expected to be at increased risk of adverse outcomes from this viral infection, due being immunosuppressed as a consequence of the underlying cancer, and from the effects of therapy.

The fields of cancer- and immuno-metabolism have re-emerged as areas of significant translational potential. Even though the upregulation of glycolysis by proliferating lymphocytes is the basis for widely used clinical tests such as FDG-PET, little is known about which metabolic pathways are involved in the utilization of glucose to support B-cell proliferation. The synthesis of serine from glucose has been demonstrated to be a key metabolic pathway supporting cellular proliferation in some healthy and malignant cell types. Importantly, this pathway is regulated by MYC, which is known to be essential for germinal centre formation and is commonly dysregulated in lymphoma. Despite this, the role that the serine synthesis pathway (SSP) plays in germinal center biology and pathology has not been previously investigated. We performed a comprehensive characterization of the role of the SSP in germinal center B cells and lymphomas derived from these cells. We demonstrate that upregulation of a functional SSP is a metabolic hallmark of B-cell activation and the germinal center reaction. We show that both human and murine resting naïve B cells lack expression of the first two enzymes in this pathway, phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) enzymes. However, B-cell activation, predominantly through the B-cell receptor, robustly induces the expression of these enzymes in vitro, resulting in an acquired ability to synthesize serine, glycine and the purine nucleotides adenosine and guanosine from glucose. This is reflected in striking expression of PHGDH and PSAT1 within germinal centers but not in marginal zones confirming that this upregulation is occurring in germinal B cells activated in vivo. We then proceeded to investigate the impact of inhibiting PHGDH on germinal center formation and high-affinity antibody production in vivo. This was done both genetically, using a conditional B-cell knockout mouse model, and pharmacologically using a specific inhibitor of PHGDH, PH-755. Importantly, we show that PHGDH inhibition impairs germinal center formation with a resultant reduction in high-affinity antibody production. Mechanistic experiments demonstrate that PHGDH inhibition effectively blocks cells from synthesising serine and glycine from glucose, making them unable to proliferate in environments that lack these amino acids. We then investigated role of PHDGH and PSAT1 in Burkitt Lymphoma (BL), Diffuse Large B Cell Lymphoma (DLBCL) and Chronic Lymphocytic Leukemia (CLL). Notably, very high expression of these two proteins was observed in BL, with intermediate-to-high expression in DLBCL and relatively low expression in CLL, where expression was restricted to proliferation centers. Given the heterogeneity of expression in DLBCL patients, we next interrogated a published GSE database (Lenz et al. NEJM 2008) to investigate the impact on outcome. Notably high expression of PSAT1 was significantly associated with a poorer overall survival rate in DLBCL. We then investigated whether the SSP could be a therapeutic target in lymphoma. We demonstrate that PHGDH inhibition effectively inhibits de novo serine, glycine and purine nucleotide synthesis from glucose, resulting in impaired proliferation and increased apoptosis in a panel of human BL cell lines in vitro. We then analyzed the impact of PHGDH inhibition on lymphoma development in vivo using Eµ-myc mice, which harbour Myc coupled to the IgH enhancer characteristic of BL. Importantly we confirm the role of MYC by demonstrating that Eµ-Myc B-cells show significantly higher expression of PHGDH and PSAT1 expression resulting in increased serine and glycine synthesis when compared to control cells. We demonstrate that pharmacological inhibition of PHGDH using PH-755 impairs lymphoma progression in this model. We confirm the importance of PHGDH by showing that genetic ablation of Phgdh in Eµ-myc cells in a tamoxifen inducible system (using Eµ-myc/+;Rosa26-CreER T2/+;Phgdh fl/fl mice) also results in a significant reduction in lymphoma progression. Taken together, this work represents the first report of the role of the SSP in the biology of the germinal centre response and lymphomas derived from these cells. These findings establish PHGDH as a critical player in humoral immunity and a clinically relevant target in MYC-driven lymphoma, which is an area of significant unmet need. Disclosures Gribben: Abbvie: Honoraria; AZ: Honoraria, Research Funding; BMS: Honoraria; Gilead/Kite: Honoraria; Janssen: Honoraria, Research Funding; Morphosys: Honoraria; Novartis: Honoraria; Takeda: Honoraria; TG Therapeutis: Honoraria. Calado: Myricx Pharma: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Patents & Royalties: Cancer Treatments. WO patent WO 2020/128475 A1 (2020).

Gotthold Ephraim Lessing’s publication of Fragments of an Unknown Wolfenbüttel Author in the 1770s unleashed a storm of debate and controversy, which ended with censor stepping in and forbidding further contributions. The Fragmentenstreit, the ‘Battle of the Fragments’, as it came to be known, was a critical point in the development of German theology. For Schweitzer, as is made clear by the full title of his survey of historical Jesus studies ( The Quest of the Historical Jesus: A Critical Study of its Progress from Reimarus to Wrede), the publication of the fragment ‘On the purpose of Jesus and his disciples’ marks the true beginnings of an historical engagement with the Gospel stories about Jesus. For Lessing, Reimarus’ text certainly raised questions about the interpretative methods and categories which are most properly applied to the Gospels; it also raised issues about the relationship between reason and revelation, the place of the Bible, the canon, in the development of Christian faith, and indeed of the very nature of faith itself. We will look briefly at some of these questions. There is, too, a much wider and more demanding question: what influence did this debate have on the subsequent history of German theology which, in the 150 years which followed, saw the rise of both liberal and more confessionally oriented theologies, the prominence of figures like Schleiermacher, Hegel, Ritschl, Barth, and Bultmann? We can offer no more than a few pointers to the beginnings of such developments.

In response to antigen challenge, B cells clonally expand, undergo selection and differentiate to produce mature B cell subsets and high affinity antibodies. However, the interplay between dynamic B cell states and their antibody-based selection is challenging to decipher in primary human tissue. We have applied an integrated analysis of bulk and single-cell antibody repertoires paired with single-cell transcriptomics of human B cells undergoing affinity maturation. We define unique gene expression and antibody repertoires of known and novel B cell states, including a pre-germinal centre state primed to undergo class switch recombination. We dissect antibody class-dependent gene expression of germinal centre and memory B cells to find that class switching prior to germinal centre entry dictates the capacity of B cells to undergo antibody-based selection and differentiate. Together, our analyses provide unprecedented resolution into the gene expression and selection dynamics that shape B cell-mediated immunity.

This chapter outlines the history of the Scottish family firm of publishers T&T Clark, which for nearly 200 years made a significant contribution to the development of an historical and critical approach to theological study. This was chiefly effected through a series of publications of mostly German-speaking works of theology and biblical studies. It is suggested that these were principally of a mediating kind, seeking to achieve a complementarity between forms of confessional Protestant belief and theology on the one hand and historical and philosophical studies on the other. This reached a climax in the early twentieth century with the publication of major works by Ritschl and Schleiermacher. Thereafter the firm’s publishing programme became more influenced by confessional forms of theology, particularly through its translation of Karl Barth’s Church Dogmatics. Its legacy, however, remains not only in the form of Barth but of Schleiermacher and historical critical studies of the Bible.