CD70 is upregulated in several malignancies, where it induces cytotoxic effects on B and T lymphocytes leading to immune escape. Novel therapeutic agents targeting CD70 have entered clinical trials. We characterized expression of CD70 protein in RCC specimens of various histologic subtypes and assessed their prognostic value and association with clinical/pathological variables. We employed tissue microarrays containing 330 cases using a novel fluorescent immunohistochemistry-based method of Automated Quantitative Analysis (AQUA) of in situ protein expression. The mean expression of CD70 was almost twice as high in tumors relative to normal tissue (p<0.0001). When broken into subsets, CD70 was higher in sarcomatoid and clear cell tumors (p<0.0001), and variably elevated in oncocytomas and some papillary tumors. No association was found between CD70 expression and stage or grade. High CD70 expression was associated with decreased survival on univariate analysis in the clear cell subset of RCC, however, it did not retain significance on multi-variable analysis. Given the elevated expression of CD70 in clear cell, sarcomatoid, and some papillary tumors, our findings suggest that CD70 might be a good drug target in RCC. Additional studies are warranted to assess the association between expression of CD70 and response to therapy with CD70 targeting drugs in RCC.

Electronic surveys of healthcare workers in humanitarian settings are feasible. Providers in the Syrian humanitarian setting have little experience in TMH; however, they are open to using an S&F service while acknowledging cultural, financial, and technical barriers to the implementation.

The frequency, severity, and forms of symptoms months after coronavirus 2019 are poorly understood, especially in community settings. To better understand and characterize symptoms months after community-based COVID-19, a retrospective cohort analysis was conducted. Three hundred and twentyeight consecutive persons with a positive test for SARS-CoV-2 in the Johns Hopkins Health System, Maryland, March−May 2020, were selected for the study. Symptom occurrence and severity were measured through questionnaires. Of 328 persons evaluated, a median of 242 days (109−478 days) from the initial positive SARS-CoV-2 test, 33.2% reported not being fully recovered and 4.9% reported symptoms that constrained daily activities. Compared to those who reported being fully recovered, those with post-acute sequelae were more likely to report a prior history of heart attack (p < 0.01). Among those reporting long-term symptoms, men and women were equally represented (men = 34.8%, women = 34.6%), but only women reported symptoms that constrained daily activities, and 56% of them were caregivers. The types of new or persistent symptoms varied, and for many, included a deviation from prior COVID-19 health, such as being less able to exercise, walk, concentrate, or breathe. A limitation is that self-report of symptoms might be biased and/or caused by factors other than COVID-19. Overall, even in a community setting, symptoms may persist months after COVID-19 reducing daily activities including caring for dependents.

Shigella is a leading cause of moderate-to-severe diarrhea globally and the causative agent of shigellosis and bacillary dysentery. Associated with 80 to 165 million cases of diarrhea and >13% of diarrheal deaths, in many regions, Shigella exposure is ubiquitous while infection is heterogenous. To characterize host-genetic susceptibility to Shigella-associated diarrhea, we performed two independent genome-wide association studies (GWAS) including Bangladeshi infants from the PROVIDE and CBC birth cohorts in Dhaka, Bangladesh. Cases were infants with Shigella-associated diarrhea (n = 143) and controls were infants with no Shigella-associated diarrhea in the first 13 months of life (n = 446). Shigella-associated diarrhea was identified via quantitative PCR (qPCR) threshold cycle (CT) distributions for the ipaH gene, carried by all four Shigella species and enteroinvasive Escherichia coli. Host GWAS were performed under an additive genetic model. A joint analysis identified protective loci on chromosomes 11 (rs582240, within the KRT18P59 pseudogene; P = 6.40 × 10−8; odds ratio [OR], 0.43) and 8 (rs12550437, within the lincRNA RP11-115J16.1; P = 1.49 × 10−7; OR, 0.48). Conditional analyses identified two previously suggestive loci, a protective locus on chromosome 7 (rs10266841, within the 3′ untranslated region [UTR] of CYTH3; Pconditional = 1.48 × 10−7; OR, 0.44) and a risk-associated locus on chromosome 10 (rs2801847, an intronic variant within MPP7; Pconditional = 8.37 × 10−8; OR, 5.51). These loci have all been indirectly linked to bacterial type 3 secretion system (T3SS) activity, its components, and bacterial effectors delivered into host cells. Host genetic factors that may affect bacterial T3SS activity and are associated with the host response to Shigella-associated diarrhea may provide insight into vaccine and drug development efforts for Shigella-associated diarrheal disease.