Serum CA125 and HE4 as Biomarkers for the Detection of Endometrial Cancer and Associated High-Risk Features

Early detection of endometrial cancer improves survival. Non-invasive diagnostic biomarkers would improve triage of symptomatic women for investigations. This study aimed to determine the diagnostic accuracy of serum Cancer Antigen 125 (CA125) and Human Epididymis 4 (HE4) for endometrial cancer and associated high-risk features. Serum samples from women investigated for gynaecological symptoms or diagnosed with endometrial cancer were analysed for CA125 and HE4. Conventional diagnostic metrics were calculated. In total, 755 women were included; 397 had endometrial cancer. Serum CA125 and HE4 were significantly elevated in cases compared with controls (both p < 0.001), and with pathological markers of disease severity (p < 0.05). A combination of CA125 and HE4 detected endometrial cancer with an area under the curve (AUC) of 0.77 (95% CI: 0.74–0.81). In a model with body mass index (BMI) and parity, HE4 predicted endometrial cancer in pre-menopausal women with an AUC of 0.91 [sensitivity = 84.5%, specificity = 80.9% (p < 0.001)]. In women with abnormal ultrasound, HE4 ≥ 77 pmol/L improved specificity compared with imaging alone [68.6% (95% CI: 75.0–83.6) vs. 34.4% (95% CI: 27.1–42.3), respectively], but at a cost to sensitivity. HE4 ≥ 77 pmol/L improved the detection of myometrial invasion ≥50% in women with stage I disease compared with magnetic resonance imaging (MRI) alone [sensitivity = 100% (95% CI: 54.1–100)]. CA125 ≥ 35 U/mL did not add to imaging. HE4 is a good predictor of poor prognostic features which could assist staging investigations

An in vitro investigation into the effects of 10Hz cyclic loading on tenocyte metabolism

Tendinopathy is a prevalent, highly debilitating condition, with poorly defined aetiology. A wide range of clinical treatments have been proposed, with systematic reviews largely supporting shock wave therapy or eccentric exercise. Characterising these treatments has demonstrated both generate perturbations within tendon at a frequency of approximately 812Hz. Consequently, it is hypothesised that loading in this frequency range initiates increased anabolic tenocyte behaviour, promoting tendon repair. The primary aim of this study is to investigate the effects of 10Hz perturbations on tenocyte metabolism, comparing gene expression in response to a 10Hz and 1Hz loading profile. Tenocytes from healthy and tendinopathic human tendons were seeded into 3D collagen gels and subjected to 15 mins cyclic strain at 10Hz or 1Hz. Tenocytes from healthy tendon showed increased expression of all analysed genes in response to loading, with significantly increased expression of inflammatory and degradative genes with 10Hz, relative to 1Hz loading. By contrast, whilst the response of tenocytes from tendinopathy tendon also increased with 10Hz loading, the overall response profile was more varied and less intense, possibly indicative of an altered healing response. Through inhibition of the pathway, IL1 was shown to be involved in the degradative and catabolic response of cells to high frequency loading, abrogating the loading response. This study has demonstrated for the first time that loading at a frequency of 10Hz may enhance the metabolic response of tenocytes by initiating an immediate degradatory and inflammatory cell response through the IL1 pathway, perhaps as an initial stage of tendon healing

The Juncaceae-Cyperaceae Interface: A Combined Plastid Sequence Analysis

Phylogenetic relationships of Juncaceae and related families of Cyperales were investigated using DNA sequence data from the plastid rps16 intron, trnL intron, and trnL–F intergenic spacer. Results using parsimony analysis of the aligned matrices find Juncaceae and Cyperaceae to be monophyletic families, which form a clade sister to a monophyletic Thurniaceae that includes Prionium (Prioniaceae), all three clades with 100% bootstrap support. Within Juncaceae, the genus Luzula is monophyletic with 100% bootstrap support and sister to the rest of Juncaceae. Further groupings within the family indicate that the genus Juncus may be monophyletic only with the inclusion of the single-flowered genera of Juncaceae (Distichia, Oxychloe, Marsippospermum, and Rostkovia; sequences of Patosia were not included). Major groupings within Juncus are supported by the morphological characters of septate or non-septate leaves and the presence or absence of bracts subtending the flowers, which have been used to define subgenera and sections within Juncus

Wheat Vacuolar Iron Transporter TaVIT2 transports Fe and Mn and is effective for biofortification

Increasing the intrinsic nutritional quality of crops, known as biofortification, is viewed as a sustainable approach to alleviate micronutrient deficiencies. In particular iron deficiency anaemia is a major global health issue, but the iron content of staple crops such as wheat is difficult to change because of genetic complexity and homeostasis mechanisms. To identify target genes for biofortification of wheat (Triticum aestivum), we functionally characterized homologs of the Vacuolar Iron Transporter (VIT). The wheat genome contains two VIT paralogs, TaVIT1 and TaVIT2, which have different expression patterns, but are both low in the endosperm. TaVIT2, but not TaVIT1, was able to rescue growth of a yeast mutant lacking the vacuolar iron transporter. TaVIT2 also complemented a manganese transporter mutant, but not a vacuolar zinc transporter mutant. By over-expressing TaVIT2 under the control of an endosperm-specific promoter, we achieved a > 2-fold increase in iron in white flour fractions, exceeding minimum legal fortification levels in countries such as the UK. The anti-nutrient phytate was not increased and the iron in the white flour fraction was bioavailable in-vitro, suggesting that food products made from the biofortified flour could contribute to improved iron nutrition. The single-gene approach impacted minimally on plant growth and was also effective in barley. Our results show that by enhancing vacuolar iron transport in the endosperm, this essential micronutrient accumulated in this tissue bypassing existing homeostatic mechanisms

Exploring human-guided strategies for reaction network exploration:Interactive molecular dynamics in virtual reality as a tool for citizen scientists

The emerging fields of citizen science and gamification reformulate scientific problems as games or puzzles to be solved. Through engaging the wider non-scientific community, significant breakthroughs may be made by analyzing citizen-gathered data. In parallel, recent advances in virtual reality (VR) technology are increasingly being used within a scientific context and the burgeoning field of interactive molecular dynamics in VR (iMD-VR) allows users to interact with dynamical chemistry simulations in real time. Here, we demonstrate the utility of iMD-VR as a medium for gamification of chemistry research tasks. An iMD-VR "game" was designed to encourage users to explore the reactivity of a particular chemical system, and a cohort of 18 participants was recruited to playtest this game as part of a user study. The reaction game encouraged users to experiment with making chemical reactions between a propyne molecule and an OH radical, and "molecular snapshots" from each game session were then compiled and used to map out reaction pathways. The reaction network generated by users was compared to existing literature networks demonstrating that users in VR capture almost all the important reaction pathways. Further comparisons between humans and an algorithmic method for guiding molecular dynamics show that through using citizen science to explore these kinds of chemical problems, new approaches and strategies start to emerge.</p

DEveloping Tests for Endometrial Cancer deTection (DETECT): protocol for a diagnostic accuracy study of urine and vaginal samples for the detection of endometrial cancer by cytology in women with postmenopausal bleeding.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-28Publication status: PublishedFunder: Wellcome TrustFunder: Department of Health; Grant(s): NIHR300650Funder: Cancer Research UK; Grant(s): C147/A25254IntroductionPostmenopausal bleeding (PMB), the red flag symptom for endometrial cancer, triggers urgent investigation by transvaginal ultrasound scan, hysteroscopy and/or endometrial biopsy. These investigations are costly, invasive and often painful or distressing for women. In a pilot study, we found that voided urine and non-invasive vaginal samples from women with endometrial cancer contain malignant cells that can be identified by cytology. The aim of the DEveloping Tests for Endometrial Cancer deTection (DETECT) Study is to determine the diagnostic test accuracy of urine and vaginal cytology for endometrial cancer detection in women with PMB.Methods and analysisThis is a multicentre diagnostic accuracy study of women referred to secondary care with PMB. Eligible women will be asked to provide a self-collected voided urine sample and a vaginal sample collected with a Delphi screener before routine clinical procedures. Pairs of specialist cytologists, blinded to participant cancer status, will assess and classify samples independently, with differences settled by consensus review or involving a third cytologist. Results will be compared with clinical outcomes from standard diagnostic tests. A sample size of 2000 women will have 80% power to establish a sensitivity of vaginal samples for endometrial cancer detection by cytology of ≥85%±7%, assuming 5% endometrial cancer prevalence. The primary objective is to determine the diagnostic accuracy of urogenital samples for endometrial cancer detection by cytology. Secondary objectives include the acceptability of urine and vaginal sampling to women.Ethics and disseminationThis study has been approved by the North West-Greater Manchester West Research Ethics Committee (16/NW/0660) and the Health Research Authority. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via charity websites.Trial registration numberISRCTN58863784

Northern Hemisphere atmospheric stilling accelerates lake thermal responses to a warming world

Climate change, in particular the increase in air temperature, has been shown to influence lake thermal dynamics, with climatic warming resulting in higher surface temperatures, stronger stratification, and altered mixing regimes. Less-studied is the influence on lake thermal dynamics of atmospheric stilling, the decrease in near-surface wind speed observed in recent decades. Here we use a lake model to assess the influence of atmospheric stilling, on lake thermal dynamics across the Northern Hemisphere. From 1980-2016, lake thermal responses to warming have accelerated as a result of atmospheric stilling. Lake surface temperatures and thermal stability have changed at respective rates of 0.33 and 0.38°C decade-1, with atmospheric stilling contributing 15 and 27% of the calculated changes, respectively. Atmospheric stilling also resulted in a lengthening of stratification, contributing 23% of the calculated changes. Our results demonstrate that atmospheric stilling has influenced lake thermal responses to warming

Pressure-induced superelastic behaviour of isonicotinamide

Dynamic organic crystals have come to the fore as potential lightweight alternatives to inorganic actuators providing high weight-to-force ratios. We have observed pressure-induced superelastic behaviour in Form I of isonicotinamide. The reversible single-crystal to single-crystal transformation exhibited by the system is an important component for functioning actuators. Crucially, our observations have enabled us to propose a mechanism for the molecular movement supported by Pixel energy calculations, that may pave the way for the future design and development of functioning dynamic crystals