Institutional barriers to clinical trial exploration experienced by the Latinx community.

This study evaluated two types of barriers that the authors deemed important to resolve during the early stage of cancer clinical trial exploration by Latinx community members. One was the accessibility of information provided on cancer centers' websites. The other was the telephone responders' clinical trial knowledge and their conveyance of a warm welcome to Latinx callers inquiring about the centers' clinical trials. Simulated clinical trial inquiry calls were made to 17 National Cancer Institute-designated centers in this study. The centers were located in cities where the Latinx community accounted for at least 25% of the population, thereby justifying center-wide efforts to encourage the Latinx community to explore clinical trial participation. A rubric was developed to determine and quantify a Total Score that was partially composed of the accessibility of clinical trial information displayed on each cancer center's website. A research assistant gathered information by posing as a person calling the cancer center to inquire about clinical trials on behalf of a family member with limited English proficiency and evaluated their response using a "mystery shopper" method of data collection. The warmth and sense of welcome conveyed by the telephone responder was also quantified and included in the rubric's Total Score. A perfect Total Score reflected the likely existence of an environment that would encourage Latinx community members to continue exploring clinical trials, i.e., removed or diminished possible barriers. Welcoming characteristics, such as those elements included in the scoring rubric, can be monitored regularly to assure that centers are consistently conveying an optimal sense of welcome to the Latinx community, while also providing accessible clinical trial information. Among the 17 cancer centers, no correlation was found between the size of the Latinx population served and each center's Total Score.

Nucleolar stress in C9orf72 and sporadic ALS spinal motor neurons precedes TDP-43 mislocalization.

Nucleolar stress has been implicated in the pathology and disease pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) from repeat expansions of GGGGCC in C9orf72 (C9-ALS/FTLD) but not in sporadic ALS (SALS). Previously we reported that antisense RNA transcripts are unique in C9-ALS because of their nucleolar localization in spinal motor neurons and correlation with TDP-43 mislocalization, the hallmark proteinopathy of ALS and FTLD. Here we report our further studies of 11 SALS, 11 C9-ALS and 11 control spinal cords. We find that nucleolar stress manifests specifically as shrinkage in nucleoli of C9-ALS spinal motor neurons. Nucleolar size reduction is greatest in similarly sized alpha motor neurons from C9-ALS cases and results are not skewed by the number of surviving neurons from each ALS spinal cord. Surprisingly, nucleolar shrinkage occurs before main pathological hallmarks-TDP-43 mislocalization or antisense RNA foci-appear and this suggest that nucleolar stress can precede pathology in C9-ALS, findings previously identified in C9-FTLD using sense RNA foci and dipeptide repeat proteins as pathological markers. Importantly, these observations are also seen in SALS motor neurons and thus nucleolar stress appears to be a significant and probably upstream problem in sporadic disease.