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Myelodysplastic syndromes and acute myeloid leukemia with TP53 mutations are characterized by frequent relapses, poor or short responses, and poor survival with the currently available therapies including chemotherapy and 5-azacitidine (AZA). PRIMA-1Met(APR-246,APR) is a methylated derivative of PRIMA-1, which induces apoptosis in human tumor cells through restoration of the transcriptional transactivation function of mutant p53. Here we show that low doses of APR on its own or in combination with AZA reactivate the p53 pathway and induce an apoptosis program. Functionally, we demonstrate that APR exerts these activities on its own and that it synergizes with AZA in TP53-mutated myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) cell lines and in TP53-mutated primary cells from MDS/AML patients. Low doses of APR on its own or in combination with AZA also show significant efficacy in vivo Lastly, using transcriptomic analysis, we found that the APR + AZA synergy was mediated by downregulation of the FLT3 pathway in drug-treated cells. Activation of the FLT3 pathway by FLT3 ligand reversed the inhibition of cell proliferation by APR + AZA. These data suggest that TP53-mutated MDS/AML may be better targeted by the addition of APR-246 to conventional treatments.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and non-cancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer, 89% COVID-19+), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Chronic viral RNA carriers exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of non-conventional monocytes and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T helper cells, and non-naive Granzyme B+ FasL+, EomehighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

Violent groups sometimes invest significant resources in social work, notably in the form of charities and NGOs. The present paper models a terrorist group's charities as a means to advertise its cause in order to raise popular support. The analysis explains how different types of organizations arise in equilibrium, depending on government policies. Then, the interaction between a purely terrorist group and an independent local NGO is examined. It is shown that a purely terrorist group always invests in more attacks than an integrated terrorist-charity organization. Furthermore, the latter may have more NGO activity than a separate local NGO.

Peer to peer (P2P) microfinance connects philanthropic citizens with poor entrepreneurs in the developing world. Although its popularity has grown exponentially with the creation of several competing online platforms, very little is known about how individual lenders behave and whether their priorities differ from those of traditional development practitioners. This paper presents evidence on how individual lenders choose between borrowers, and how lenders' preferences relate to the objectives of the microfinance sector. Using data from Kiva.org, we present estimates of the impact of publicly visible project characteristics on funding speed. Results suggest that Kiva lenders rationally consider indicators of the likelihood of repayment as well as borrowers' need. Smaller loans, groups and women get funded faster as do loans to sectors of activity with low entry costs. Meanwhile, loans requested to finance education and health projects or those advertised by NGOs with better risk ratings, and lower default and delinquency rates, fund faster. The results imply that policy makers and practitioners who seek to use microfinance as a poverty alleviation tool should invest in the P2P approach.

This paper investigates the effect of competition between NGO projects on their ability to raise funds, using the case of Kiva, an online peer-to-peer (P2P) microlending website. Although NGO behavior in competitive environments is often subject to controversy, there is little formal empirical evidence to illustrate theoretical findings and inform policy. We find that competition has a sizable negative impact on projects' funding speed and that the effect is stronger between close substitutes. These results illustrate several key findings in the theoretical literature and suggest that regulating the entry of projects on charitable P2P platforms may sometimes improve welfare. Furthermore, we find that increases in the lender side of the market generated by media exposure improve funding speed and relax the impact of competition. Our findings shed light on the way media exposure affects NGOs' fundraising success.

Non Governmental Organizations (NGOs) have various sources of income and expenditure. They have donated and commercial incomes, and they spend them on both charitable and non-charitable expenditure. Standard economic theory implies that different sources of income are fungible, which means that income elasticities should be the same across income and expenditure categories. This paper seeks to test that assumption using panel data on 74 UK-based international NGOs. I find that changes in donated income primarily affect charitable expenditures, while changes in commercial income sources seem to affect mostly expenditures that relate less to the NGO's charitable mission. These findings suggest that income is not fungible but that NGOs have mental accounts.