Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging. However, immunotherapy responses are uniquely challenging to ...interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation. We hypothesized that monitoring tumor cell death in real time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy.
We compared longitudinal changes in ctDNA levels with changes in radiographic tumor size and with survival outcomes in 28 patients with metastatic non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor therapy. CtDNA was quantified by determining the allele fraction of cancer-associated somatic mutations in plasma using a multigene next-generation sequencing assay. We defined a ctDNA response as a >50% decrease in mutant allele fraction from baseline, with a second confirmatory measurement.
Strong agreement was observed between ctDNA response and radiographic response (Cohen's kappa, 0.753). Median time to initial response among patients who achieved responses in both categories was 24.5 days by ctDNA versus 72.5 days by imaging. Time on treatment was significantly longer for ctDNA responders versus nonresponders (median, 205.5 vs. 69 days;
< 0.001). A ctDNA response was associated with superior progression-free survival hazard ratio (HR), 0.29; 95% CI, 0.09-0.89;
= 0.03, and superior overall survival (HR, 0.17; 95% CI, 0.05-0.62;
= 0.007).
A drop in ctDNA level is an early marker of therapeutic efficacy and predicts prolonged survival in patients treated with immune checkpoint inhibitors for NSCLC.
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We sought to evaluate the frequency of anxiety, depression, PTSD, and any experiences of violence in women who had undergone Female Genital Mutilation/Cutting (FGM/C) and were seeking asylum in the ...United States. We undertook a retrospective qualitative descriptive study of FGM/C cases seen in an asylum clinic over a 2-year period. Standardized questionnaires provided quantitative scores for anxiety, depression and PTSD. Clients’ personal and physician medical affidavits were analyzed for experiences of violence. Of the 13 cases, anxiety and depression were exhibited by 92 and 100% of women, while all seven women screened for PTSD had symptoms. Qualitative analysis revealed extensive violence perpetrated against these women, demonstrating that FGM/C is only part of the trauma experienced. The high level of mental health disorders and endured violence has implications for providers working with FGM/C survivors and indicates the need for accessible mental health services and trauma-informed care.
Background
Despite lower incidence rates among black women and a national decline in breast cancer (BC) deaths, there is a widening gap in BC mortality rates between black and white women in the ...United States. A previous study evaluating data from 1992 to 1999 found a racial disparity in the receipt of surveillance mammography. We sought to evaluate whether this disparity persists between black and white women diagnosed with BC between 2000 and 2011.
Methods
Using the SEER-Medicare registry, we conducted an analysis of women ≥ 66 years diagnosed with early-stage (0–III) BC between 2000 and 2011 who underwent BC surgery. The primary outcome was receipt of surveillance mammography within 12 months of surgery. Chi square analyses were used to compare characteristics between black and white women. Multivariate logistic regression was used to assess receipt of surveillance mammography after controlling for potential confounders.
Results
There were 3353 black and 40,564 white women in the final cohort. After adjusting for confounders, black women were still 24% less likely than white women to receive surveillance mammography (Odds ratio 0.76, 95% CI 0.70–0.0.82). Those who were married, younger, in the highest income quartile, diagnosed at earlier stages, had a lower comorbidity score, or who resided in metropolitan areas were more likely to receive surveillance mammography (
p
< 0.05).
Conclusion(s)
We found that older black BC survivors continue to experience lower rates of surveillance mammography, even after adjusting for multiple potential confounders. There remains a need to investigate which individual and systemic factors affect disparities in breast cancer care.
•In the United States, there is limited screening of women aged 65 years or more for osteoporosis.•Significant racial/ethnic disparities exist in the diagnosis and treatment of osteoporosis; ...systems-, provider-, and patient-level factors contribute to these disparities.•The current fracture risk calculators were primarily validated in white populations, making their generalizability to racial/ethnic minority populations unclear.
Osteoporosis and fragility fractures result in significant morbidity and mortality and contribute to substantial healthcare costs. Despite being a treatable disease, osteoporosis remains both underdiagnosed and undertreated in the US general population, with significant disparities in care between non-White and White women. These disparities are evident from screening to post-fracture treatment. Non-White women are less likely to be screened for osteoporosis, to be prescribed pharmacotherapy, or to receive treatment post-fracture; furthermore, the mortality rate after fracture is higher in non-White women. Given existing diagnostic and treatment disparities, additional studies and interventions are needed to optimize the bone health of Asian, Black, Hispanic, and Native American women, and to reduce morbidity and mortality from osteoporosis and fragility fractures.
In the original publication of the article, under the Methods section, second paragraph, the sentence that reads as “We excluded 3047 patients … surgical treatment (see Fig. 1)” should read as “We ...excluded 3047 patients who did not identify as black or white, 5395 who were not initially diagnosed with stage 0–III cancer or were missing stage or residence data, 2573 patients who passed away within 18 months of diagnosis, and 4716 patients who did not undergo primary surgical treatment (see Fig. 1)”.
Search vectors composed primary of Gly, Ala, Arg, and Pro residues (GARP) distributed across the entire protein sequence retrieve 98% of each of the ribosomal proteins in bacterial species with no ...false “hits”. Different combinations of G, A, R and P and insertions or deletions differentiate each ribosomal protein from all others. We are able to identify site mutations that subdivide each ribosomal protein ensemble into the individual classes of bacteria. For example, four fold variation in a single sequence position in S4 separates 490 gram‐positive bacteria that have Y and F in this position and 717 gram‐negative bacteria that have W in this position from 68 cyanobacteria and 601 chloroplasts that have an H in this position. Detection of co‐evolution of amino acids in four sequence positions makes it possible to divide the 1876 ribosomal proteins into 25 classes. Further subdivision into orders, families, genus, and species is trivial. While there are significant differences between the sequences of the ribosomal proteins in different classes of bacteria, within each class the amino acid sequences have remained highly conserved for millions of years. We have found that the total GARP content of the ribosomal proteins of each class is a marker of the order of evolution and that the last universal common ancestor (LUCA) appears to have been an Actinobacteria.
The 32 Codon World of A. dehalogenans Duax, William L; Huether, Robert; Pletnev, Vladimir ...
The FASEB journal,
04/2009, Letnik:
23, Številka:
S1
Journal Article
Recenzirano
Abstract only
The genome of the soil bacteria
Anaeromyxobacter dehalogenans
(Adhal) is reported to have 4346 coding sequences composed of 1,521,374 codons, a GC content of 74.82% and GC occupancy of ...the third base position of 97.07%. Over 50% of the proteins in Adhal are annotated as having uncertain or unknown function. Over 1000 have two or less Met residues and Val and Leu residues are often identified as start codes. Examination of the sequences indicates that over 80% of them have 3 open reading frames. The presence of multiple open reading frames and ambiguity of start and stop code identification has resulted in misidentification of hundreds of nonsense sequences as hypothetical proteins. Significant differences in codon use between functionally characterized and hypothetical proteins, errors in coding frame selection, and in start and stop code identifications indicate that most (and possibly all) of the sixteen codons that have A or T bases in the first and third position are nonsense codes (de facto stops). These patterns present in many bacterial genomes suggest that the modern genetic code evolved from a coding system in which just the 32 codons that end in G or C define all 20 amino acids. The DNA in which this code evolved was stabilized by the presence of three hydrogen bonds linking the GC pairs present in every third base pair of the DNA encoding proteins.
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