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This article examines the impact of the Ottoman Empire's battle against legal imperialism on the status of Central Asians in its domains, specifically after the promulgation of a nationality law in 1869 that classified them as foreigners. It traces how the threat of Muslim colonial subjects attaining European consular protections led to the emergence of a “Central Asian protection question”: whether Afghans, Bukharans, and Chinese Muslims had legitimate claims to European legal nationality and, by extension, capitulatory privileges. Through a number of case studies, the article shows how the Ottoman Foreign Ministry fused international legal norms and pan-Islamic claims to arrive at the position that Central Asians from informally colonized lands were not “real” subjects of European empires, and that they were under the exclusive protection of the caliphate. This strategy, I argue, undermined the creation of an Ottoman citizenship boundary and opened up a complex field of inter- and intraimperial contestation about who was a foreigner. In contrast to positive associations with legal pluralism in this period, Central Asian migrants and pilgrims who were protected by the caliph but not recognized as Ottomans or European subjects found that they could not benefit from practices such as forum shopping and affiliation switching. And while the notion of foreignness remained subject to multiple and conflicting interpretations across the empire, I argue that nationality as a legal category was incontrovertibly becoming a defining feature of these foreign Muslims' rights and status in the sultan's domains.

The role of Sufi networks in facilitating trans-imperial travel and the concomitant social and political connections associated with the pilgrimage to Mecca is often mentioned in the literature on Ottoman-Central Asian relations, yet very little is known about how these networks operated or the people who patronized them. This paper focuses on the Sultantepe Özbekler Tekkesi, a Naqshbandi lodge in Istanbul that was a primary locus of Ottoman state interactions with Central Asians and a major hub of Central Asian diasporic networks. It departs from an exclusive focus on the experiences of elites, to which much of the conventional historiography on Ottoman-Central Asian relations has confined itself, and examines the butchers and bakers, craftsmen and students who set out on the hajj to Mecca in the late nineteenth and early twentieth centuries. Drawing on sources from the private archive of this lodge, the paper reconstructs the experiences of a diverse range of remarkably mobile actors and explores the myriad ways in which this Ottoman-administered institution facilitated their travel to and from Mecca. Through its focus on the conduits and mediators, the structures and buildings—the actual sites—where connections were forged, the paper sheds light on the role that such state-administered Sufi lodges played in delivering on the paternalistic rhetoric and system of sultanic charity that was an integral part of late Ottoman politics and society.

Identification of immune phenotypes linked to durable graft-versus-leukemia (GVL) response following donor lymphocyte infusions (DLI) is of high clinical relevance. In this prospective observational study of 13 AML relapse patients receiving therapeutic DLI, we longitudinally investigated changes in differentiation stages and exhaustion markers of T cell subsets using cluster analysis of 30-color spectral flow cytometry during 24 months follow-up. DLI cell products and patient samples after DLI were analyzed and correlated to the clinical outcome. Analysis of DLI cell products revealed heterogeneity in the proportions of naïve and antigen experienced T cells. Cell products containing lower levels of effector memory (eff/m) cells and higher amounts of naïve CD4 + and CD8 + T cells were associated with long-term remission. Furthermore, investigation of patient blood samples early after DLI showed that patients relapsing during the study period, had higher levels of CD4 + eff/m T cells and expressed a mosaic of surface molecules implying an exhausted functional state. Of note, this observation preceded the clinical diagnosis of relapse by five months. On the other hand, patients with continuous remission retained lower levels of exhausted CD4 + eff/m T cells more than four months post DLI. Moreover, lower frequencies of exhausted CD8 + eff/m T cells as well as higher amounts of CD4 + temra CD45RO + T cells were present in this group. These results imply the formation of functional long-term memory pool of T cells. Finally, unbiased sample analysis showed that DLI cell products with low levels of eff/m cells both in CD4 + and CD8 + T cell subpopulations associate with a lower relapse incidence. Additionally, competing risk analysis of patient samples taken early after DLI revealed that patients with high amounts of exhausted CD4 + eff/m T cells in their blood exhibited significantly higher rates of relapse. In conclusion, differentially activated T cell clusters, both in the DLI product and in patients post infusion, were associated with AML relapse after DLI. Our study suggests that differences in DLI cell product composition might influence GVL. In-depth monitoring of T cell dynamics post DLI might increase safety and efficacy of this immunotherapy, while further studies are needed to assess the functionality of T cells found in the DLI.

Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19 + B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity. Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy.

As organizations search for better solutions to their everyday problems, many are encouraging employees to use their experiences to develop new ideas and play a more active role in the innovation process. Companies including AT&T Inc., Google Inc., and Deutsche Telekom AG have turned to what's known as internal crowdsourcing. Although external crowdsourcing, which solicits ideas from consumers, suppliers, and anyone who wants to participate, has been widely studied, internal crowdsourcing, which seeks to channel the ideas and expertise of the company's own employees, is less well-understood. However, as the authors point out, harnessing the cognitive diversity within organizations can open up rich new sources of innovation while at the same time engaging younger employees and people working on the front lines. In this article, the authors examine the benefits of internal crowdsourcing and the common roadblocks to participation, collaboration, and implementation; they draw on their research at a number of companies, including a health care company, a telecommunications company, and fashion and retail company Li & Fung Ltd. The authors present a set of action steps to help executives make their internal crowdsourcing efforts more effective. Those steps include: (1) keeping the focus broadly on long-term innovation rather than short-term problem-solving; (2) giving employees slack time to participate; (3) allowing for anonymous participation; and (4) making sure experts within the company don't exert too much influence. The authors also recommend that companies encourage collaboration, use technology platforms that connect individuals with ideas from other participants, and have well-defined procedures for how ideas will be handled after the crowdsourcing event. \"Although companies are accustomed to giving recognition to teams who submit winning solutions, they don't always offer clear criteria to guide the process or take the time to follow up with employees who don't win,\" the authors write. \"But these efforts can pay big dividends in terms of driving future participation and generating better solutions later on.\"

Evaluating long-term protection against SARS-CoV-2 variants of concern in convalescing individuals is of high clinical relevance. In this prospective study of a cohort of 46 SARS-CoV-2 patients infected with the Wuhan strain of SARS-CoV-2 we longitudinally analyzed changes in humoral and cellular immunity upon early and late convalescence. Antibody neutralization capacity was measured by surrogate virus neutralization test and cellular responses were investigated with 31-colour spectral flow cytometry. Spike-specific, isotype-switched B cells developed already during the disease phase, showed a memory phenotype and did not decrease in numbers even during late convalescence. Otherwise, no long-lasting perturbations of the immune compartment following COVID-19 clearance were observed. During convalescence anti-Spike (S1) IgG antibodies strongly decreased in all patients. We detected neutralizing antibodies against the Wuhan strain as well as the Alpha and Delta but not against the Beta, Gamma or Omicron variants for up to 7 months post COVID-19. Furthermore, correlation analysis revealed a strong association between sera anti-S1 IgG titers and their neutralization capacity against the Wuhan strain as well as Alpha and Delta. Overall, our data suggest that even 7 month after the clearance of COVID-19 many patients possess a protective layer of immunity, indicated by the persistence of Spike-specific memory B cells and by the presence of neutralizing antibodies against the Alpha and Delta variants. However, lack of neutralizing antibodies against the Beta, Gamma and Omicron variants even during the peak response is of major concern as this indicates viral evasion of the humoral immune response.