Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours

Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management. We investigated microRNAs (miRNA) levels in DTs and serum using expression array analysis on two independent cohorts of FAP patients (total, n=24). Each comprised equal numbers of patients who had formed DTs (cases) and those who had not (controls). All controls had absence of DTs confirmed by clinical and radiological assessment over at least three years post- colectomy. Technical qPCR validation was performed using an expanded cohort (29 FAP patients; 16 cases and 13 controls). The most significant elevated serum miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched germline DNA did not detect mutations within the miR-34a-5p transcript sites or 3'-UTR of target genes that would alter functional miRNA activity. In conclusion, miR-34a-5p is a potential circulatory marker and therapy target. A large prospective world-wide multi-centre study is now warranted

Separation of Dual Oxidase 2 and Lactoperoxidase Expression in Intestinal Crypts and Species Differences May Limit Hydrogen Peroxide Scavenging During Mucosal Healing in Mice and Humans.

Background: DUOX2 and DUOXA2 form the predominant H2O2-producing system in human colorectal mucosa. Inflammation, hypoxia, and 5-aminosalicylic acid increase H2O2 production, supporting innate defense and mucosal healing. Thiocyanate reacts with H2O2 in the presence of lactoperoxidase (LPO) to form hypothiocyanate (OSCN-), which acts as a biocide and H2O2 scavenging system to reduce damage during inflammation. We aimed to discover the organization of Duox2, Duoxa2, and Lpo expression in colonic crypts of Lieberkühn (intestinal glands) of mice and how distributions respond to dextran sodium sulfate (DSS)-induced colitis and subsequent mucosal regeneration. Methods: We studied tissue from DSS-exposed mice and human biopsies using in situ hybridization, reverse transcription quantitative polymerase chain reaction, and cDNA microarray analysis. Results: Duox2 mRNA expression was mostly in the upper crypt quintile while Duoxa2 was more apically focused. Most Lpo mRNA was in the basal quintile, where stem cells reside. Duox2 and Duoxa2 mRNA were increased during the induction and resolution of DSS colitis, while Lpo expression did not increase during the acute phase. Patterns of Lpo expression differed from Duox2 in normal, inflamed, and regenerative mouse crypts (P < 0.001). We found no evidence of LPO expression in the human gut. Conclusions: The spatial and temporal separation of H2O2-consuming and -producing enzymes enables a thiocyanate- H2O2 "scavenging" system in murine intestinal crypts to protect the stem/proliferative zones from DNA damage, while still supporting higher H2O2 concentrations apically to aid mucosal healing. The absence of LPO expression in the human gut suggests an alternative mechanism or less protection from DNA damage during H2O2-driven mucosal healing.R.P. was funded by the Monument Trust. M.P.C. was funded by the CARIPLO Foundation (project 2010-0790) and the Italian Ministry of Health. A.R. was supported by an annual fellowship from Fondazione Umberto Veronesi

Labrador retrievers under primary veterinary care in the UK: demography, mortality and disorders

Abstract Background Labrador retrievers are reportedly predisposed to many disorders but accurate prevalence information relating to the general population are lacking. This study aimed to describe demography, mortality and commonly recorded diseases in Labrador retrievers under UK veterinary care. Methods The VetCompass™ programme collects electronic patient record data on dogs attending UK primary-care veterinary practices. Demographic analysis covered all33,320 Labrador retrievers in the VetCompass™ database under veterinary care during 2013 while disorder and mortality data were extracted from a random sample of 2074 (6.2%) of these dogs. Results Of the Labrador retrievers with information available, 15,427 (46.4%) were female and 15,252 (53.6%) were male. Females were more likely to be neutered than males (59.7% versus 54.8%, P <  0.001). The overall mean adult bodyweight was 33.0 kg (SD 6.1). Adult males were heavier (35.2 kg, SD 5.9 kg) than adult females (30.4 kg, SD 5.2 kg) (P <  0.001). The median longevity of Labrador retrievers overall was 12.0 years (IQR 9.9–13.8, range 0.0–16.0). The most common recorded colours were black (44.6%), yellow (27.8%) and liver/chocolate (reported from hereon as chocolate) (23.8%). The median longevity of non-chocolate coloured dogs (n = 139, 12.1 years, IQR 10.2–13.9, range 0.0–16.0) was longer than for chocolate coloured animals (n = 34, 10.7 years, IQR 9.0–12.4, range 3.8–15.5) (P = 0.028). Of a random sample of 2074 (6.2%) Labrador retrievers under care in 2013 that had full disorder data extracted, 1277 (61.6%) had at least one disorder recorded. The total number of dogs who died at any date during the study was 176. The most prevalent disorders recorded were otitis externa (n = 215, prevalence 10.4%, 95% CI: 9.1–11.8), overweight/obesity (183, 8.8%, 95% CI: 7.6–10.1) and degenerative joint disease (115, 5.5%, 95% CI: 4.6–6.6). Overweight/obesity was not statistically significantly associated with neutering in females (8.3% of entire versus 12.5% of neutered, P = 0.065) but was associated with neutering in males (4.1% of entire versus 11.4% of neutered, P < 0.001). The prevalence of otitis externa in black dogs was 12.8%, in yellow dogs it was 17.0% but, in chocolate dogs, it rose to 23.4% (P < 0.001). Similarly, the prevalence of pyo-traumatic dermatitis in black dogs was 1.1%, in yellow dogs it was 1.6% but in chocolate dogs it rose to 4.0% (P = 0.011). Conclusions The current study assists prioritisation of health issues within Labrador retrievers. The most common disorders were overweight/obesity, otitis externa and degenerative joint disease. Males were significantly heavier females. These results can alert prospective owners to potential health issues and inform breed-specific wellness checks

The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients

This work was supported by the Broad Medical Research Program of the Broad Foundation [http://www.ccfa.org/science-and-professionals/broad/] (grant no IBD-0289R to Professor Silver and Dr James Lindsay) and Barts and The London Charity [https://bartscharity.org.uk] (grant no MGD0016 to Noor Jawad)

A comparison of two methods for estimating odds ratios: Results from the National Health Survey

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A Decade of SN1993J: Discovery of Wavelength Effects in the Expansion Rate

We have studied the growth of the shell-like radio structure of supernova SN1993J in M81 from September 1993 through October 2003 with very-long-baseline interferometry (VLBI) observations at the wavelengths of 3.6, 6, and 18cm. For this purpose, we have developed a method to accurately determine the outer radius (R) of any circularly symmetric compact radio structure like SN1993J. The source structure of SN1993J remains circularly symmetric (with deviations from circularity under 2%) over almost 4000 days. We characterize the decelerated expansion of SN 1993J through approximately day 1500 after explosion with an expansion parameter $m= 0.845\pm0.005$ ($R \propto t^{m}$). However, from that day onwards the expansion is different when observed at 6 and 18cm. Indeed, at 18cm, the expansion can be well characterized by the same $m$ as before day 1500, while at 6cm the expansion appears more decelerated, and is characterized by another expansion parameter, $m_{6}= 0.788\pm0.015$. Therefore, since about day 1500 on, the radio source size has been progressively smaller at 6cm than at 18cm. These findings are in stark contrast to previous reports by other authors on the details of the expansion. In our interpretation the supernova expands with a single expansion parameter, $m= 0.845\pm0.005$, and the 6cm results beyond day 1500 are due to physical effects, perhaps also coupled to instrumental limitations. Two physical effects may be involved: (a) a changing opacity of the ejecta to the 6cm radiation, and (b) a radial decrease of the magnetic field in the emitting region. (Long abstract cut. Please, read full abstract in manuscript).Comment: 21 pages, 19 figures, accepted in A&

Moving singing for lung health online in response to COVID-19: experience from a randomised controlled trial

Introduction: Singing for lung health (SLH) is a popular arts-in-health activity for people with long-term respiratory conditions. Participants report biopsychosocial benefits, however, research on impact is limited. The ‘SLH: Improving Experiences of Lung Disease trial’, a randomised controlled, single (assessor) blind, trial of 12 weeks SLH versus usual care for people with chronic obstructive pulmonary disease (COPD) (n=120) was setup to help to address this. The first group (n=18, nine singing and nine controls) started face-to-face (five sessions) before changing to online delivery (seven sessions) due to COVID-19-related physical distancing measures. As such, the experience of this group is here reported as a pilot study to inform further research in this area. Methods: We conducted semistructured interviews and thematic analysis regarding barriers, facilitators and key considerations for transitioning from face-to-face to online delivery. Pilot quantitative outcomes include attendance, premeasures and postmeasures of quality of life and disease impact (Short Form 36 Health Survey, COPD Assessment Test score), breathlessness (Medical Research Council breathlessness scale, Dyspnoea-12), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalised Anxiety Disorder-7), balance confidence (Activity specific Balance Confidence, ABC scale) and physical activity (clinical visit PROactive physical activity in COPD tool, combining subjective rating and actigraphy). Results: Attendance was 69% overall, (90% of the face-to-face sessions, 53% online sessions). Analysis of semistructured interviews identified three themes regarding participation in SLH delivered face to face and online, these where (1) perceived benefits; (2) digital barriers (online) and (3) digital facilitators (online). Findings were summarised into key considerations for optimising transitioning singing groups from face-to-face to online delivery. Pilot quantitative data suggested possible improvements in depression (treatment effect −4.78 PHQ-9 points, p<0.05, MCID 5) and balance confidence (treatment effect +17.21 ABC scale points, p=0.04, MCID 14.2). Discussion: This study identifies key considerations regarding the adaptation of SLH from face-to-face to online delivery. Pilot data suggest online group singing for people with COPD may deliver benefits related to reducing depression and improved balance confidence.National Institute for Health Research; Imperial College; Wellcome Trust; UK NIHR

The KELT Follow-Up Network And Transit False-Positive Catalog: Pre-Vetted False Positives For TESS

The Kilodegree Extremely Little Telescope (KELT) project has been conducting a photometric survey of transiting planets orbiting bright stars for over 10 years. The KELT images have a pixel scale of ~23\u27\u27 pixel⁻¹—very similar to that of NASA\u27s Transiting Exoplanet Survey Satellite (TESS)—as well as a large point-spread function, and the KELT reduction pipeline uses a weighted photometric aperture with radius 3\u27. At this angular scale, multiple stars are typically blended in the photometric apertures. In order to identify false positives and confirm transiting exoplanets, we have assembled a follow-up network (KELT-FUN) to conduct imaging with spatial resolution, cadence, and photometric precision higher than the KELT telescopes, as well as spectroscopic observations of the candidate host stars. The KELT-FUN team has followed-up over 1600 planet candidates since 2011, resulting in more than 20 planet discoveries. Excluding ~450 false alarms of non-astrophysical origin (i.e., instrumental noise or systematics), we present an all-sky catalog of the 1128 bright stars (6 \u3c V \u3c 13) that show transit-like features in the KELT light curves, but which were subsequently determined to be astrophysical false positives (FPs) after photometric and/or spectroscopic follow-up observations. The KELT-FUN team continues to pursue KELT and other planet candidates and will eventually follow up certain classes of TESS candidates. The KELT FP catalog will help minimize the duplication of follow-up observations by current and future transit surveys such as TESS

Hydrogen and helium traces in type Ib-c supernovae

The spectroscopic properties of a selected optical photospheric spectra of core collapse supernovae (CCSNe) are investigated.Special attention is devoted to traces of hydrogen at early phases. The generated spectra are found to match the observed ones reasonably well, including a list of only 23 candidate ions. Guided by SN Ib 1990I, the observed trough near 6300\AA is attributed to H$\alpha$ in almost all Type Ib events, although in some objects it becomes too weak to be discernible, especially at later phases. Alternative line identifications are discussed. Differences in the way hydrogen manifests its presence within CCSNe are highlighted. In Type Ib SNe, the H$\alpha$ contrast velocity (i.e. line velocity minus the photospheric velocity) seems to increase with time at early epochs, reaching values as high as 8000 km s$^{-1}$ around 15-20 days after maximum and then remains almost constant. The derived photospheric velocities, indicate a lower velocity for Type II SNe 1987A and 1999em as compared to SN Ic 1994I and SN IIb 1993J, while Type Ib events display a somewhat larger variation. The scatter, around day 20, is measured to be $\sim$5000 km s$^{-1}$. Following two simple approaches, rough estimates of ejecta and hydrogen masses are given. A mass of hydrogen of approximately 0.02 $M_\odot$ is obtained for SN 1990I, while SNe 1983N and 2000H ejected $\sim$0.008 $M_\odot$ and $\sim$0.08 $M_\odot$ of hydrogen, respectively. SN 1993J has a higher hydrogen mass, $\sim 0.7$ $M_\odot$ with a large uncertainty. A low mass and thin hydrogen layer with very high ejection velocities above the helium shell, is thus the most likely scenario for Type Ib SNe. Some interesting and curious issues relating to oxygen lines suggest future investigations.Comment: 26 pages, 37 figures, 2 tables. Published in Astronomy and Astrophysics (Volume 450, Page 305); Title change

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche

Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps