Reactive arthritis

This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of reactive arthritis

Screening Mammography for Reducing Breast Cancer Mortality

Screening mammography reduces breast cancer mortality in women 40 to 49 years of age who have an average risk of breast cancer. (Strength of Recommendation: A, based on eight randomized controlled trials [RCTs].) The relative risk reduction in this age group is 15 percent, similar to that of women 50 years and older (14 percent). To prevent one breast cancer death, 1,904 women 40 to 49 years of age must be screened annually for 10 years, compared with 1,339 women 50 to 59 years of age. Although both age groups appear to have a similar relative risk reduction from routine screening, women 40 to 49 years of age have a smaller absolute risk reduction and may experience greater harms from screening compared with older women. These potential harms include false-positive results, diagnosis and treatment for cancer that would not have become clinically evident during the woman's lifetime, false-negative results (i.e., false reassurance), radiation exposure, biopsies, and anxiety

Translating science fiction in a CAT tool:machine translation and segmentation settings

There is increasing interest in machine assistance for literary translation, but research on how computer-assisted translation (CAT) tools and machine translation (MT) combine in the translation of literature is still incipient, especially for non-Europeanlanguages. This article presents two exploratory studies where English-to-Chinese translators used neural MT to translate science fiction short stories in Trados Studio. One of the studies compares post-editing with a ‘no MT’ condition. The other examinestwo ways of presenting the texts on screen for post-editing, namely by segmenting them into paragraphs or into sentences. We collected the data with the Qualititivity plugin for Trados Studio and describe a method for analysing data collected with this plugin through the translation process research database of the Center for Research in Translation and Translation Technology (CRITT). While post-editing required less technical effort, we did not find MT to be appreciably timesaving. Paragraph segmentation was associated with less post-editing effort on average, though with high translator variability. We discuss the results in the light of broader concepts, such as status-quo bias, and call for more research on the different ways in which MT may assist literary translation, including its use for comparison purposes or, as mentioned by a participant, for ‘inspiration’

Low-level expression of HER2 and CK19 in normal peripheral blood mononuclear cells: relevance for detection of circulating tumor cells

<p>Abstract</p> <p>Background</p> <p>Detection of circulating tumor cells (CTC) in the blood of cancer patients may have prognostic and predictive significance. However, background expression of 'tumor specific markers' in peripheral blood mononuclear cells (PBMC) may confound these studies. The goal of this study was to identify the origin of Cytokeratin 19 (CK19) and HER-2 signal in PBMC and suggest an approach to enhance techniques involved in detection of CTC in breast cancer patients.</p> <p>Methods</p> <p>PBMC from healthy donors were isolated and fractionated into monocytes, lymphocytes, natural killer cells/granulocytes and epithelial populations using immunomagnetic selection and fluorescent cell-sorting for each cell type. RNA isolated from each fraction was analyzed for CK19, HER2 and Beta 2 microglobulin (B2M) using real-time qRT-PCR. Positive selection for epithelial cells and negative selection for NK/granulocytes were used in an attempt to reduce background expression of CK19 and HER2 markers.</p> <p>Results</p> <p>In normal PBMC, CK19 was expressed in the lymphocyte population while HER-2 expression was highest in the NK/granulocyte population. Immunomagnetic selection for epithelial cells reduced background CK19 signal to a frequency of <5% in normal donors. Using negative selection, the majority (74–98%) of HER2 signal could be removed from PBMC. Positive selection methods are variably effective at reducing these background signals.</p> <p>Conclusion</p> <p>We present a novel method to improve the specificity of the traditional method of detecting CTC by identifying the source of the background signals and reducing them by negative immunoselection. Further studies are warranted to improve sensitivity and specificity of methods of detecting CTC will prove to be useful tools for clinicians in determining prognosis and monitoring treatment responses of breast cancer patients.</p

Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception

BackgroundThyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.MethodsWe conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.ResultsThe follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P=0.74; absolute difference, −0.4 percentage points; 95% CI, −6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P=0.14).ConclusionsThe use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.

The effect of occupational exposure to solar ultraviolet radiation on malignant skin melanoma and non- melanoma skin cancer: a systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

A systematic review and meta-analysis of studies were conducted reporting on the association between occupational exposure to solar ultraviolet radiation (UVR) and both malignant skin melanoma (melanoma) and non-melanoma skin cancer (NMSC), with the aim of enabling the estimation of the numbers of deaths and disability-adjusted life years from melanoma and NMSC attributable to occupational exposure to solar UVR, for the development of the World Health Organization (WHO)/International Labour Organization (ILO) Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). A protocol was developed and published, applying the Navigation Guide as an organizing systematic review framework where feasible. Electronic bibliographic databases were searched for potentially relevant records; electronic grey literature databases and organizational websites were also searched, reference lists of previous systematic reviews and included study records were hand-searched, and additional experts were consulted. Randomized controlled trials and cohort, case–control and other non-randomized studies were included that estimated the effect of any occupational exposure to solar UVR, compared with no occupational exposure to solar UVR, on melanoma (excluding melanoma of the lip or eye) or NMSC prevalence, incidence or mortality. At least two reviewers independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage. Adjusted relative risks were combined using random-effects meta-analysis. Two or more reviewers assessed the risk of bias, quality of evidence and strength of evidence. Fifty-three (48 case–control, three case–case and two cohort) eligible studies were found, published in 62 study records, including over 457 000 participants in 26 countries of three WHO regions (Region of the Americas, European Region and Western Pacific Region), reporting on the effect on melanoma or NMSC incidence or mortality. No studies on the prevalence of melanoma or NMSC were found. In most studies, exposure was self-reported in questionnaires during interviews and the health outcome was assessed via physician diagnosis based on biopsy and histopathological confirmation. The risk of bias of the body of evidence was judged to be generally “probably low”, although there were some concerns regarding risks of exposure misclassification bias, detection bias and confounding. The main meta-analyses of relevant case–control studies revealed a relative risk (RR) of melanoma and NMSC incidence of 1.45 (95% confidence interval (CI): 1.08–1.94; I2 = 81%) and 1.60 (95% CI: 1.21–2.11; I2 = 91%), respectively. No statistically significant differences in risk of melanoma and NMSC incidence were found when conducting subgroup analyses by WHO region, and no differences in risk of NMSC incidence in a subgroup analysis by sex. However, in a subgroup analysis by NMSC subtype, the increased risk of basal cell carcinoma (RR: 1.50; 95% CI: 1.10–2.04; 15 studies) was probably lower (P = 0.05 for subgroup differences) than the increased risk for squamous cell carcinoma (RR: 2.42; 95% CI: 1.66–3.53; 6 studies). The sensitivity analyses found that effect estimates of NMSC incidence were significantly higher in studies with any risk of bias domain rated as “high” or “probably high” compared with studies with only a “low” or “probably low” risk of bias, and in studies not reporting the health outcome by International Statistical Classification of Diseases and Related Health Problems (ICD) code compared with the two studies reporting ICD codes. The quality of available evidence of the effect of any occupational exposure to solar UVR on melanoma incidence and mortality and on NMSC mortality was rated as “low”, and the quality of evidence for NMSC incidence was rated as “moderate”. The strength of the existing bodies of evidence reporting on occupational exposure to solar UVR was judged as “inadequate evidence for harmfulness” for melanoma mortality and NMSC mortality. For the health outcome of melanoma incidence, the strength of evidence was judged as “limited evidence for harmfulness”, that is, a positive relationship was observed between exposure and outcome where chance, bias and confounding cannot be ruled out with reasonable confidence. For the health outcome of NMSC incidence, the strength of evidence was judged as “sufficient evidence of harmfulness”, that is, a positive relationship is observed between exposure and outcome where chance, bias and confounding can be ruled out with reasonable confidence. The 2009 International Agency for Research on Cancer classification of solar UVR as a Group 1 carcinogen that causes cutaneous melanoma and NMSC is a compelling attribute for the strength of evidence on occupational exposure to solar UVR and skin cancer incidence. Producing estimates for the burden of NMSC attributable to occupational exposure to solar UVR appears evidence-based (while acknowledging the limitations of the bodies of evidence), and the pooled effect estimates can be used as input data for the WHO/ILO Joint Estimates

Spider-Venom Peptides as Therapeutics

Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Archives of Virology (2021) 166:3567–3579. https://doi.org/10.1007/s00705-021-05266-wIn March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This work was also supported in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. 75N91019D00024, Task Order No. 75N91019F00130 to I.C., who was supported by the Clinical Monitoring Research Program Directorate, Frederick National Lab for Cancer Research. This work was also funded in part by Contract No. HSHQDC-15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges partial support from the Special Research Initiative of Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University, and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494. Part of this work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001030), the UK Medical Research Council (FC001030), and the Wellcome Trust (FC001030).S

CropPol: a dynamic, open and global database on crop pollination

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved