Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. ...Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited.
We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC).
Cytometric profiling identified an immunologically "hot" cluster with abundant CD8
T cells expressing high levels of PD-1 and TIM-3 and an immunologically "cold" cluster with lower relative abundance of CD8
T cells and expression of inhibitory markers. The "hot" cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the "hot" cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10.
Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer.
The Robert A. and Renée E. Belfer Family Foundation, Expect Miracles Foundation, Starr Cancer Consortium, Stand Up to Cancer Foundation, Conquer Cancer Foundation, International Association for the Study of Lung Cancer, National Cancer Institute (R01 CA205150), and the Damon Runyon Cancer Research Foundation.
The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the ...functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC’s interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers.
ABSTRACT Objective: To analyze whether children and their parents prefer a particular professional coat worn by the dentist and whether these preferences are influenced by their gender or level of ...anxiety. Material and Methods: Standardized images of male and female models dressed with different coats were shown to 400 pairs of 5-12 year-old children and respective parents and they were asked to point their preference. Information about child's dental experience was collected and children's anxiety level was obtained using the Children’s Fear Survey Schedule-Dental Subscale. Results: Both children (55.5%) and parents (76.5%) preferred a female professional over a male one. Children preferred the dentist wearing a white coat, while adults preferred the dentist wearing a colored coat (p<0.05). There was a tendency for the child to choose a dentist with the same gender as theirs, so boys chose more male dentists and girls more female dentists (p<0.05), but there was no difference between the choice of the dentist’s coat between boys and girls (p=0.53). Conclusion: Children have strong preferences in relation to the appearance of their dentists. Children and parents preferred female dentists, but there was a tendency to choose the dentist with the respondent’s gender. Contrary to popular belief, children preferred their dentists wearing the conventional white coat, different from their parents who preferred dentists wearing a colored coat.
The boys love (BL) genre was created for girls and women by
young female manga (comic) artists in early 1970s Japan to
challenge oppressive gender and sexual norms. Over the years, BL
has seen almost ...irrepressible growth in popularity and since the
2000s has become a global media phenomenon, weaving its way into
anime, prose fiction, live-action dramas, video games, audio
dramas, and fan works. BL's male-male romantic and sexual
relationships have found a particularly receptive home in other
parts of Asia, where strong local fan communities and locally
produced BL works have garnered a following throughout the region,
taking on new meanings and engendering widespread cultural effects.
Queer Transfigurations is the first detailed examination of the BL
media explosion across Asia. The book brings together twenty-one
scholars exploring BL media, its fans, and its sociocultural
impacts in a dozen countries in East, Southeast, and South Asia-and
beyond. Contributors draw on their expertise in an array of
disciplines and fields, including anthropology, fan studies, gender
and sexuality studies, history, literature, media studies,
political science, and sociology to shed light on BL media and its
fandoms. Queer Transfigurations reveals the far-reaching influences
of the BL genre, demonstrating that it is truly transnational and
transcultural in diverse cultural contexts. It has also helped
bring about positive changes in the status of LGBT(Q) people and
communities as well as enlighten local understandings of gender and
sexuality throughout Asia. In short, Queer Transfigurations shows
that, some fifty years after the first BL manga appeared in print,
the genre is continuing to reverberate and transform lives.
•Allele frequencies and forensic parameters for 23 STRs were determined.•The sample involved 767 individuals of the State of Pernambuco, Brazil.•The most and less informative markers were SE33 and ...TPOX, respectively.•This panel was very informative for forensic purposes in this population.
Located in the Northeast Region, the Pernambuco State is one of the 27 federative units of Brazil. Here, we determined populational data for 23 short tandem repeat (STR) markers – CSF1PO, FGA, TH01, TPOX, vWA, D1S1656, D2S1338, D2S441, D3S1358, D5S818, D7S820, D8S1179, D10S1248, D12S391, D13S317, D16S539, D18S51, D19S433, D21S11, D22S1045, PENTA D, PENTA E and SE33 — of the Pernambuco population. The sample consisted of 767 healthy, adult, unrelated individuals (437 males, 330 females) born and resident in the State of Pernambuco. STRs were amplified using three multiplex kits, according to the availability: PowerPlex® Fusion 6C System (Promega Corporation), PowerPlex® Fusion System (Promega Corporation) and GlobalFiler™ Express (Thermo Fisher Scientific). Allelic frequencies, forensic parameters and Hardy-Weinberg equilibrium determinations were estimated for all the 23 loci. No deviations from the Hardy-Weinberg equilibrium were observed for any of the markers, after Bonferroni correction. We observed that the most and less informative markers were SE33 and TPOX, respectively. The combined power of discrimination (CPD) was 0.99999999999999999999999999999, and the combined power of exclusion (CPE) was 0.99999999997. The cumulative typical paternity index was 37,919,301,869.3021. Interpopulation analyses (Nei’s genetic distance) based on the expanded CODIS core loci was performed between the Pernambuco sample and other global populations. Pernambuco was the closest Brazilian population to African group and stayed distant from the Native American group. This work contributed to show that a panel of 23 autosomal STR loci is very informative, being able for forensic applications related in this population.
Identifying DNA markers such as Short Tandem Repeats (STR) can be used to investigate genetic diversity based on levels of heterozygosity within and between populations. Allele frequencies and ...forensic data for STRs were obtained from a sample of 384 unrelated individuals living in Bahia, Northeastern Brazil. Thus, the present study aimed to identify the allele frequency distribution, in addition to the forensic and genetic data, of 25 STR loci in the population of Bahia. Buccal swabs or fingertip punctures were utilized to amplify and detect 25 DNA markers. The most polymorphic loci were SE33 (43), D21S11, and FGA (21). The least polymorphic were TH01 (6), TPOX, and D3S1358 (7). Forensic and statistical data were obtained through data analysis, which revealed a large genetic diversity, with an average value of 0.813 for the analyzed population. The present study was more robust than previous STR marker studies and will contribute to future research on population genetics in Brazil and worldwide. The results of this study allowed the establishment of haplotypes found in the forensic samples of Bahia State to serve as a reference in the elucidation of criminal cases and paternity tests, as well as population and evolutionary investigations.
PDF
