The risk and benefit profiles of US eligible lung cancer screening attendees vs. non-attendees.

BACKGROUND: The United States Preventive Services Task Force (USPSTF) recommend lung-cancer screening for individuals aged 50-80 with ≥20 pack-years and ≤15 quit-years, but uptake is low. The risk and benefit profiles of screening attendees are unknown; consequently, the impact and lost opportunity of ongoing lung-cancer screening in the US remains unclear. METHODS: We estimated lung-cancer death risk (using the Lung Cancer Death Risk Assessment Tool) and life gained from screening (using the LYFS-CT model) for individuals 50-79 who ever-smoked in the US-representative 2022 Behavioral Risk Factor Surveillance System. We compared lung-cancer death risk and life-gained among USPSTF-eligible individuals by screening status (self-reported screened vs not screened in past year), and estimated the number of lung-cancer deaths averted and life-years gained under current screening levels and if everyone eligible was screened. RESULTS: USPSTF-eligibility was 33.7% (95%CI:33.1-34.4%), of whom 17.9% (95%CI : 17.0-18.8%) self-reported screening. Screening uptake increased with increasing lung-cancer death risk quintile (Q1 = 5.2% (95%CI : 3.0%-8.8%); Q5 = 21.8% (95%CI : 20.3%-23.3%)) and life-gain from screening quintile (Q1 = 6.2% (95%CI : 3.8%-9.9%); Q5 = 20.8% (95%CI : 19.5%-22.2%)). Screened individuals had higher lung-cancer death risk (Risk Ratio [RR]=1.35, 95%CI : 1.26-1.46) and life-years gained (RR = 1.19, 95%CI : 1.12-1.25) than unscreened individuals. Currently screening averts 19,306 lung-cancer deaths and gains 237,564 life-years; screening everyone eligible would additionally avert 56,956 lung-cancer deaths and gain 751,850 life-years. Two-thirds of USPSTF-lung-eligible women were up-to-date with breast-cancer screening, but only 17.3% attended lung screening in the past year. CONCLUSIONS: Eligible screening attendees had higher lung-cancer death risk and benefit from screening. Higher rates of screening could substantially increase the number of lung-cancer deaths prevented.

Influence of an extreme event-the COVID-19 pandemic-On establishment of and data collection by a citizen science project.

The recent rising incidence of extreme natural events may significantly influence the implementation of citizen science projects, including the success of outreach strategies and the quality and scope of data collection. The MassMammals Watch and subsidiary MassBears citizen science projects, initiated during the height of the pandemic, recruit volunteers to submit sightings of black bears and other mammals. In this study, we evaluated the methods we employed for engaging and retaining community volunteers during a period of intense social restrictions, and we assessed whether such conditions were associated with spatial biases in our collected data. Newspaper features were more likely to recruit volunteers who engaged with the project multiple times, but social media and internet presence were important for reaching a larger audience. Bear sighting submissions peaked in number and were more likely to be in forested areas during 2020, the height of the pandemic, compared to later years, a pattern which we suggest stems from an increased desire to participate in outdoor activities in light of social distancing measures during that year. Such shifts in patterns of data collection are likely to continue, particularly in response to increasing extreme weather events associated with climate change. Here, we both make recommendations on optimal outreach strategies for others initiating citizen science programs and illustrate the importance of assessing potential biases in data collection imposed by extreme circumstances.

Rickettsia africae infections in sub-Saharan Africa: A systematic literature review of epidemiological studies and summary of case reports.

Rickettsia africae is a tick-borne bacteria known to cause African tick bite fever (ATBF). While the disease was first described more than 100 years ago, knowledge of transmission risk factors and disease burden remain poorly described. To better understand the burden of R. africae, this article reviewed and summarized the published literature related to ATBF epidemiology and clinical management. Using a systematic approach, consistent with the PRISMA guidelines, we identified more than 100 eligible articles, including 65 epidemiological studies and 41 case reports. Most reports described R. africae in ticks and livestock, while human studies were less common. Human disease case reports were exclusively among returning travellers from non-endemic areas, which limits our disease knowledge among at-risk populations: people living in endemic regions. Substantial efforts to elucidate the ATBF risk factors and clinical manifestations among local populations are needed to develop effective preventative strategies and facilitate appropriate and timely diagnosis.

Molecular characterization of metaplastic breast carcinoma via next-generation sequencing.

Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer with variable morphology. MBC is more often triple negative (ER-, PR-, HER2-) and is associated with poorer clinical outcome when compared with infiltrating ductal carcinoma. The purpose of our study is to identify molecular alterations in MBC using next-generation sequencing (NGS), which may aid chemotherapy selection and use of targeted therapy. A cohort of 18 patients with MBC yielded adequate DNA from microdissected formalin-fixed and paraffin-embedded tumor blocks. NGS was performed using the Ion AmpliSeq cancer hotspot mutation panel version 2 kit, which targets hotspot regions in 50 genes. Immunohistochemical stains for androgen receptor (AR), and programmed cell death ligand-1 were performed. A total of 23 genetic alterations were identified in 15 (83.3%) of 18 patients. Eleven genetic alterations in the PI3K signaling pathway were identified in 9 (50.0%) of 18 patients, including 7 PIK3CA mutations (38.9%), 3 PTEN genetic alterations (16.7%), and 1 AKT1 mutation (5.6%). Ten (55.6%) of 18 patients each harbored 1 TP53 genetic alteration. Additional genetic alterations identified were 1 HRAS mutation and 1 ATM mutation. AR immunoreactivity was identified in 2 (11.1%) of 18 patients. Programmed cell death ligand-1 was negative in all patients. NGS analysis demonstrated that PI3K pathway-related genetic alterations were detected in a high percentage of MBCs, suggesting that targeting the PI3K/mTOR pathway may be promising in patients with MBC. In addition, patients with AR expressing MBC may benefit from androgen antagonist treatment.

GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells.

GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine production. However, this model is largely based on studies of disruption of the GADS/SLP-76 interaction and murine T cell differentiation in GADS deficient mice. The role of GADS in mediating TCR-induced signals in human CD4+ T cells has not been thoroughly investigated. In this study, we have suppressed the expression of GADS in human CD4+ HuT78 T cells. GADS deficient HuT78 T cells displayed similar levels of TCR-induced SLP-76 and PLC-γ1 phosphorylation but exhibited substantial decrease in TCR-induced IL-2 and IFN-γ release. The defect in cytokine production occurred because of impaired calcium mobilization due to reduced recruitment of SLP-76 and PLC-γ1 to the LAT complex. Surprisingly, both GADS deficient HuT78 and GADS deficient primary murine CD8+ T cells had similar TCR-induced adhesion when compared to control T cells. Overall, our results show that GADS is required for calcium influx and cytokine production, but not cellular adhesion, in human CD4+ T cells, suggesting that the current model for T cell regulation by GADS is incomplete.