ABSTRACT
Despite improvements in cancer outcomes over time, significant disparities remain between Black and White cancer survivors. Medical care is estimated to account for 10-20% of health outcomes, while other modifiable factors explain as much as 80-90% of outcomes. These disparities may thus be driven by multiple factors including social determinants of health, differences in treatment or follow up, or attitudes and behaviors of care teams. As part of a larger project, we conducted a qualitative study to understand cancer survivor preferences for and experiences with social needs screening and referrals. The results of this assessment will inform the delivery of social risk screening for breast and prostate cancer survivors in the multi-site study. Semi-structured interviews were conducted in English between March and April 2022 with breast and prostate cancer survivors from two cancer institutes in Washington DC. Patients were purposively recruited to ensure diversity in age, race, and cancer stage (I-III). Each interview lasted 60 minutes. Transcripts were reviewed for consensus and preferences for social needs screening. Thirteen survivors participated in the interviews. Participants were mostly breast cancer survivors (n=10), African American (n=6), were equal in stages I and II at time of diagnosis (n=5), and ranged in age from 34 to 81 with a median age of 64. Most patients (n=7) did not report social needs screening during their treatment, though all patients welcomed having these conversations with their care team. The majority of patients (n=9) desired face-to-face conversations as opposed to on paper (n=1) or through the patient portal (n=1). Similarly, most patients (n=7) did not mind who on their care team held the conversations. There was difference in opinion on how often social needs should be discussed, with four participants suggesting every appointment to another patient suggesting once at diagnosis. When asked about the needs patients experienced during treatment, food insecurity and nutrition were most cited (n=6), followed by transportation (n=4) and emotional resources (n=4). Only one patient reported not desiring social needs referrals during treatment. Other avenues for seeking out social resources included self-initiated research online or through books (n=2), and another patient described utilizing their local church (n=1). Finally, patients also spoke about challenges in receiving treatment and transitioning to survivorship due to the COVID-19 pandemic, including hospital staff turnover and care team inconsistency (n=1), bringing loved ones to appointments (n=1), and transportation challenges for individuals who relied on public transport to and from the clinic (n=1). This research reveals important insight to the perspective on social needs screening among a group of breast and prostate cancer survivors in the Washington DC region and highlights the ways in which patients have experienced and desire screening for social needs. In future work we will expand the number of interviews and apply these findings into practice.
ABSTRACT
The coronavirus nucleocapsid protein (N) is a structural protein that regulates the transcription and replication of the viral genome and promotes the packaging of RNA into viral particles. The N protein has a complex domain structure and undergoes multipoint phosphorylation in the central unstructured region after entering the cell. According to the literature data, phosphorylation of homologous N protein from the SARS-CoV coronavirus leads to its retention in the cytoplasm due to direct binding with cellular regulatory proteins of the 14-3-3 family. Human 14-3-3 proteins are represented by seven isoforms that are highly expressed in tissues susceptible to SARS-CoV-2 infection. Through interaction with N 14-3-3 proteins may play an important role in the life cycle of the coronavirus. In this work, we dissected the molecular mechanism of the interaction between SARS-CoV-2 N and human 14-3-3 proteins. The phosphorylated form of N (pN) was obtained in a special system of co-expression with protein kinase A in E. coli, which led to phosphorylation of more than 20 sites in N. We have shown that only pN interacts with all isoforms of human 14-3-3 with micromolar affinity and the stoichiometry 2:2. Through the series of truncated mutants of N, it was shown that the presence of pS197 residue is necessary for the binding of 14-3-3 proteins. Utilizing the genetic code expansion allowing for the site-specific, translational incorporation of phosphoserine residues into proteins of interest we confirmed that S197 phosphorylation is sufficient for binding to 14- 3-3 proteins. It is noteworthy that this 14-3-3-binding site is quite conserved among N proteins from various coronaviruses. So, the proposed molecular mechanism for the formation of the 14-3-3/ pN complex could be universal and useful in the development of new therapeutic approaches for fighting coronavirus infections.