Demographic trends in the incidence of malignant appendiceal tumours in England between 1995 and 2016:Population-based analysis

AIMS: Recent data suggest that the incidence of malignant appendiceal tumours is increasing. This study aimed to determine temporal trends in the incidence of malignant appendiceal tumours within England and a possible influence by demographic factors. METHODS: All incident cases of appendiceal tumours in patients aged 20 years and above were identified from the National Cancer Registration and Analysis Service database between 1995 and 2016 using ICD-9/10 codes. Cancers were categorized according to histology. Joinpoint regression analysis was used to investigate changes in age-standardized incidence rates by age, sex, histological subtype and index of multiple deprivation quintiles, based on socioeconomic domains (income, employment, education, health, crime, barriers to housing and services and living environment). Average annual per cent changes (AAPCs) were estimated by performing Monte-Carlo permutation analysis. RESULTS: A total of 7333 tumours were diagnosed and 7056 patients were analysed, comprising 3850 (54.6 per cent) neuroendocrine tumours (NETs), 1892 (26.8 per cent) mucinous adenocarcinomas and 1314 (18.6 per cent) adenocarcinoma (not otherwise specified). The overall incidence of appendiceal tumours increased from 0.3 per 100 000 to 1.6 per 100 000 over the study interval. Incidence rate increases of comparable magnitude were observed across all age groups, but the AAPC was highest among patients aged 20–29 years (15.6 per cent, 95 per cent c.i 12.7–18.6 per cent) and 30–39 years (14.2 per cent, 12.2–16.2 per cent) and lowest among those aged 70–79 years (6.8 per cent, 5.7–8.0 per cent). Similar incidence rate increases were reported across all socioeconomic deprivation quintiles and in both sexes. Analysis by grade of NET showed that grade 1 tumours accounted for 63 per cent between 2010 and 2013, compared with 2 per cent between 2000 and 2003. CONCLUSIONS: The incidence rate of malignant appendiceal tumours has increased significantly since 1995 and is mainly attributed to an increase in NETs. The increased diagnosis of low-grade NETs may in part be due to changes in pathological classification systems

Micro- and nano-fluidics around HAB cells

Have you ever wondered how algae stay so clean? Most flowering-plant leaves also stay clean. Under air, films of water and “dirt” are repelled. Repulsion forces the water into droplets that easily roll off because these leaves are covered in hydrophobic nm- to µm- sized grooves and pillars, producing superhydrophobicity (SH) at the surface. Similarly, most algal cells bear a glycocalyx of organic fibrils that give surface structure, and are often hydrophobic. Glycocalyxes serve many functions, but whether they produce SH is poorly known. SH coatings are being developed to prevent fouling of ships and aquaculture structures without using toxins, so this technology could help understand how algae defeat fouling. Glycocalyxes are composed of exopolymeric secretions (EPS), and algae sometimes make the water more viscous using this tightly and more loosely bound EPS. EPS is also sometimes sticky. SH cuticles on copepods may change ambient fluid microdynamics by allowing slip at their surfaces, and facilitate filter feeding. By managing ambient viscosity and surface properties including slipping and sticking, algae may have the tools to engineer ambient fluidics and stay clean and unfouled

Towards BioDBcore: a community-defined information specification for biological databases

The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological database

THE CASE FOR THE GLOBAL STRATOTYPE SECTION AND POINT(GSSP) FOR THE BASE OF THE NORIAN STAGE

The Norian Stage is the longest stage in the Phanerozoic, and some members of the boundary working group have been evaluating suitable Carnian-Norian boundary sections for roughly two decades. This has identified two possible candidate boundary sections, at Black Bear Ridge (British Columbia, Canada) and Pizzo Mondello (Sicily, Italy). After a formal voting procedure within the working group, ending on the 26th July, 2021, the Pizzo Mondello section was selected as the global stratotype section and point for the base of the Norian. We evaluated the global correlation potential of the two proposed primary markers, the conodont Metapolygnathus parvus and the ‘flat-clam’ Halobia austriaca. Secondary markers were also evaluated around these boundary datums for correlation potential, and the veracity of the proposed sections for GSSP status. Data and arguments for the proposed sections and datums are presented here. Through a two-stage process of option elimination in voting, conforming with ICS guidelines, the working group decided by 60% majority to propose that the first occurrence datum of Halobia austriaca in the Pizzo Mondello section at the base of bed FNP135A should become the ‘golden spike’ for the base of the Norian. A secondary biotic marker for this boundary is the first occurrence of Primatella (Carnepigondolella) gulloae, in sample NA43, ca. 0 m below FNP135A, and the FA of Dimorphites noricus (sample NA42.1) ca. 3.5 m above bed FNP135 (indicating the first subzone of the Jandianus Zone). The best physical secondary marker is the magnetozone PM5n with the proposed boundary ca.40% through the thickness of PM5n. Strengths of the chosen datum are: 1) it also maintains historical priority for ammonoid zonations, which had placed the base Norian near to this level in Europe, North America and probably NE Asia; 2) Halobia austriaca is widely distributed in all paleolatitudes and is a long-established taxon

Co-regulation map of the human proteome enables identification of protein functions

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: All mass spectrometry raw files generated in-house have been deposited in the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository36 with the dataset identifier PXD008888. The co-regulation map is hosted on our website at www.proteomeHD.net, and pair-wise co-regulation scores are available through STRING (https://string-db.org). A network of the top 0.5% co-regulated protein pairs can be explored interactively on NDEx (https://doi.org/10.18119/N9N30Q).Code availability: Data analysis was performed in R 3.5.1. R scripts and input files required to reproduce the results of this manuscript are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/ProteomeHD. R scripts related specifically to the benchmarking of the treeClust algorithm using synthetic data are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/treeClust-benchmarking. The R package data.table was used for fast data processing. Figures were prepared using ggplot2, gridExtra, cowplot and viridis.Note that the title of the AAM is different from the published versionThe annotation of protein function is a longstanding challenge of cell biology that suffers from the sheer magnitude of the task. Here we present ProteomeHD, which documents the response of 10,323 human proteins to 294 biological perturbations, measured by isotope-labelling mass spectrometry. We reveal functional associations between human proteins using the treeClust machine learning algorithm, which we show to improve protein co-regulation analysis due to robust selectivity for close linear relationships. Our co-regulation map identifies a functional context for many uncharacterized proteins, including microproteins that are difficult to study with traditional methods. Co-regulation also captures relationships between proteins which do not physically interact or co-localize. For example, co-regulation of the peroxisomal membrane protein PEX11β with mitochondrial respiration factors led us to discover a novel organelle interface between peroxisomes and mitochondria in mammalian cells. The co-regulation map can be explored at www.proteomeHD.net .Biotechnology & Biological Sciences Research Council (BBSRC)European Commissio

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care