Gene-expression of metastasized versus non-metastasized primary head and neck squamous cell carcinomas: A pathway-based analysis

Background: Regional lymph node metastasis is an important prognostic factor in head and neck squamous cell carcinoma (HNSCC) and plays a decisive role in the choice of treatment. Here, we present an independent gene expression validation study of metastasized versus non-metastasized HNSCC. Methods: We used a dataset recently published by Roepman et al. as reference dataset and an independent gene expression dataset of 11 metastasized and 11 non-metastasized HNSCC tumors as validation dataset. Reference and validation studies were performed on different microarray platforms with different probe sets and probe content. In addition to a supervised gene-based analysis, a supervised pathway-based analysis was performed, evaluating differences in gene expression for predefined tumorigenesis- and metastasis related gene sets. Results: The gene-based analysis showed 26 significant differentially expressed genes in the reference dataset, 21 of which were present on the microarray platform used in the validation study. 7 of these genes appeared to be significantly expressed in the validation dataset, but failed to pass the correction for multiple testing. The pathway-based analysis revealed 23 significant differentially expressed gene sets, 7 of which were statistically validated. These gene sets are involved in extracellular matrix remodeling (MMPs, MMP regulating pathways and the uPA system), hypoxia and angiogenesis (HIF1α regulated angiogenic factors and HIF1α regulated invasion). Conclusion: Pathways that are differentially expressed between metastasized and non-metastasized HNSCC are involved in the processes of extracellular matrix remodeling, hypoxia and angiogenesis. A supervised pathway-based analysis enhances the understanding of the biological context of the results, the comparability of results across different microarray studies, and reduces multiple testing problems by focusing on a limited number of pathways of interest instead of analyzing the large number of probes available on the microarray

ATBF1 and NQO1 as candidate targets for allelic loss at chromosome arm 16q in breast cancer: Absence of somatic ATBF1 mutations and no role for the C609T NQO1 polymorphism

<p>Abstract</p> <p>Background</p> <p>Loss of heterozygosity (LOH) at chromosome arm 16q is frequently observed in human breast cancer, suggesting that one or more target tumor suppressor genes (TSGs) are located there. However, detailed mapping of the smallest region of LOH has not yet resulted in the identification of a TSG at 16q. Therefore, the present study attempted to identify TSGs using an approach based on mRNA expression.</p> <p>Methods</p> <p>A cDNA microarray for the 16q region was constructed and analyzed using RNA samples from 39 breast tumors with known LOH status at 16q.</p> <p>Results</p> <p>Five genes were identified to show lower expression in tumors with LOH at 16q compared to tumors without LOH. The genes for NAD(P)H dehydrogenase quinone (<it>NQO1</it>) and AT-binding transcription factor 1 (<it>ATBF1</it>) were further investigated given their functions as potential TSGs. <it>NQO1 </it>has been implicated in carcinogenesis due to its role in quinone detoxification and in stabilization of p53. One inactive polymorphic variant of <it>NQO1 </it>encodes a product showing reduced enzymatic activity. However, we did not find preferential targeting of the active <it>NQO1 </it>allele in tumors with LOH at 16q. Immunohistochemical analysis of 354 invasive breast tumors revealed that NQO1 protein expression in a subset of breast tumors is higher than in normal epithelium, which contradicts its proposed role as a tumor suppressor gene.</p> <p><it>ATBF1 </it>has been suggested as a target for LOH at 16q in prostate cancer. We analyzed the entire coding sequence in 48 breast tumors, but did not identify somatic sequence changes. We did find several in-frame insertions and deletions, two variants of which were reported to be somatic pathogenic mutations in prostate cancer. Here, we show that these variants are also present in the germline in 2.5% of 550 breast cancer patients and 2.9% of 175 healthy controls. This indicates that the frequency of these variants is not increased in breast cancer patients. Moreover, there is no preferential LOH of the wildtype allele in breast tumors.</p> <p>Conclusion</p> <p>Two likely candidate TSGs at 16q in breast cancer, <it>NQO1 </it>and <it>ATBF1</it>, were identified here as showing reduced expression in tumors with 16q LOH, but further analysis indicated that they are not target genes of LOH. Furthermore, our results call into question the validity of the previously reported pathogenic variants of the <it>ATBF1 </it>gene.</p

The LOFT mission concept: a status update

The Large Observatory For x-ray Timing (LOFT) is a mission concept which was proposed to ESA as M3 and M4 candidate in the framework of the Cosmic Vision 2015-2025 program. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument and the uniquely large field of view of its wide field monitor, LOFT will be able to study the behaviour of matter in extreme conditions such as the strong gravitational field in the innermost regions close to black holes and neutron stars and the supra-nuclear densities in the interiors of neutron stars. The science payload is based on a Large Area Detector (LAD, >8m2 effective area, 2-30 keV, 240 eV spectral resolution, 1 degree collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g., GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the current technical and programmatic status of the mission

Mpox Illness Narratives: Stigmatising Care and Recovery During and After an Emergency Outbreak

In May 2022, a global outbreak of mpox (formerly monkeypox virus) affected thousands of mainly gay and bisexual men. Mpox is usually a time-limited illness that can involve fever, pain, and skin lesions, but may require hospitalisation. There is scant research into the firsthand experiences of people affected by mpox, including experiences of symptoms, healthcare, and recovery. This study considers the different illness narratives of people who experienced mpox in Australia in 2022. In-depth interviews and 6-month follow-up interviews were conducted with 16 people, including 13 people diagnosed with mpox and three close contacts. All participants were cisgender gay or bisexual men living in Australia. Participants’ accounts described minor to severe periods of sickness, negative and stigmatising experiences engaging with healthcare, and some participants experienced long-term effects on their sexual well-being and complications from mpox. The emergency outbreak context meant that mpox was highly distressing, making it difficult to manage and producing varying forms of disruption to everyday life. Mpox was narrated as disruptive in different ways: as a minor interruption to holiday plans, a prolonged period of poor health, or a biographically disruptive event prompting a re-evaluation of sexual values and health. This analysis demonstrates that an unfamiliar emergent disease outbreak related to sexual practices and sociality can reconfigure personal life and sexual well-being, suggesting a need to focus on providing quality patient care in outbreaks of mpox and other infectious diseases

Concordance of gonorrhoea of the rectum, pharynx and urethra in same-sex male partnerships attending a sexual health service in Melbourne, Australia

Abstract Background We aimed to describe anatomic site-specific concordance of gonococcal infections in partnerships of men who have sex with men (MSM). Methods We conducted a cross-sectional analysis of data from MSM partnerships attending Melbourne Sexual Health Centre between March 2011 and February 2015. Logistic regression models (random effect) were used to examine the association between gonococcal infections of the urethra, rectum and pharynx. Gonococci were detected by culture at all anatomic sites. Results The analysis included 495 partnerships. Of the men with urethral gonorrhoea, 33% (95% CI 18–52) had partners with pharyngeal gonorrhoea and 67% (95% CI 48–82) had partners with rectal gonorrhoea. The adjusted odds of having urethral gonorrhoea was 4.6 (95% CI 1.2–17.1) for a man whose partner had pharyngeal gonorrhoea, and 48.1 (95% CI 18.3–126.7) for a man whose partner had rectal gonorrhoea. Of the men with rectal gonorrhoea, 46% (95% CI 31–61) had a partner with urethral gonorrhoea and 23% (95% CI 12–37) had a partner with pharyngeal gonorrhoea. The adjusted odds of having rectal gonorrhoea was 63.9 (95% CI 24.7–165.6) for a man whose partner had urethral gonorrhoea. Of the men with pharyngeal gonorrhoea, 42% (95% CI 23–63) had a partner with rectal gonorrhoea and 23% (95% CI 9–44) had a partner with had a partner with pharyngeal gonorrhoea. The adjusted odds of having pharyngeal gonorrhoea was 8.9 (95% CI 3.2–24.6) for a man whose partner had rectal gonorrhoea. The crude odds of having pharyngeal gonorrhoea was 14.2 (95% CI 5.1–39.0) for a man whose partner had pharyngeal gonorrhoea. Conclusions These data provide the first estimates of concordance of anatomic site-specific gonococcal infections in MSM partnerships, and confirm that urethral gonorrhoea is contracted from both rectal and pharyngeal sites, and suggest that gonococci transmit between the rectum and pharynx. However, due to use of culture rather than NAAT, our analysis was not adequately powered to assess pharynx-to-pharynx transmission of gonococci

Non-consensual condom removal, reported by patients at a sexual health clinic in Melbourne, Australia.

BackgroundNon-consensual removal of condoms, colloquially referred to as 'stealthing', is the removal of a condom during sex by a sexual partner when consent has been given for sex with a condom only.MethodsWe conducted a cross-sectional survey to determine how commonly women and men who have sex with men (MSM) attending Melbourne Sexual Health Centre had experienced stealthing, and analysed situational factors associated with the event. Responses were linked to demographic information extracted from patient files.Results1189 of 2883 women (41.2%), and 1063 of 3439 MSM (30.9%) attending the clinic during the study period completed the survey. Thirty-two percent of women (95% CI: 29%,35%) and 19% of MSM (95% CI: 17%,22%) reported having ever experienced stealthing. Women who had been stealthed were more likely to be a current sex worker (Adjusted Odds Ratio [AOR] 2.87, 95% CI: 2.01,4.11, p ConclusionsA high proportion of women and MSM attending a sexual health service reported having experienced stealthing. While further investigation is needed into the prevalence of stealthing in the general community, clinicians should be aware of this practice and consider integrating this question into their sexual health consultation. Understanding situational factors would assist in the development of preventive strategies, particularly female sex workers and MSM