Automated Network Assembly of Mechanistic Literature for Informed Evidence Identification to Support Cancer Risk Assessment

Background: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data.Objectives: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated approach that combines machine reading of publications with network visualization tools.Methods: We chose 13 chemicals that were evaluated by the International Agency for Research on Cancer (IARC) Monographs program incorporating the key characteristics of carcinogens (KCCs) approach. Using established literature search terms for KCCs, we retrieved and analyzed literature using Integrated Network and Dynamical Reasoning Assembler (INDRA). INDRA combines large-scale literature processing with pathway databases and extracts relationships between biomolecules, bioprocesses, and chemicals into statements (e.g., “benzene activates DNA damage”). These statements were subsequently assembled into networks and compared with the KCC evaluation by the IARC, to evaluate the informativeness of our approach.Results: We found, in general, larger networks for those chemicals which the IARC has evaluated the evidence to be strong for KCC induction. Larger networks were not directly linked to publication count, given that we retrieved small networks for several chemicals with little support for KCC activation according to the IARC, despite the significant volume of literature for these specific chemicals. In addition, interpreting networks for genotoxicity and DNA repair showed concordance with the IARC KCC evaluation.Discussion: Our method is an automated approach to condense mechanistic literature into searchable and interpretable networks based on an a priori ontology. The approach is no replacement of expert evaluation but, instead, provides an informed structure for experts to quickly identify which statements are made in which papers and how these could connect. We focused on the KCCs because these are supported by well-described search terms. The method needs to be tested in other frameworks as well to demonstrate its generalizability. https://doi.org/10.1289/EHP9112     

3D-printed upper limb prostheses: a review

Goal: This paper aims to provide an overview with quantitative information of existing 3D-printed upper limb prostheses. We will identify the benefits and drawbacks of 3D-printed devices to enable improvement of current devices based on the demands of prostheses users.

Methods: A review was performed using Scopus, Web of Science and websites related to 3D-printing. Quantitative information on the mechanical and kinematic specifications and 3D-printing technology used was extracted from the papers and websites.

Results: The overview (58 devices) provides the general specifications, the mechanical and kinematic specifications of the devices and information regarding the 3D-printing technology used for hands. The overview shows prostheses for all different upper limb amputation levels with different types of control and a maximum material cost of $500.

Conclusion: A large range of various prostheses have been 3D-printed, of which the majority are used by children. Evidence with respect to the user acceptance, functionality and durability of the 3D-printed hands is lacking. Contrary to what is often claimed, 3D-printing is not necessarily cheap, e.g., injection moulding can be cheaper. Conversely, 3D-printing provides a promising possibility for individualization, e.g., personalized socket, colour, shape and size, without the need for adjusting the production machine.

• Implications for rehabilitation

• Upper limb deficiency is a condition in which a part of the upper limb is missing as a result of a congenital limb deficiency of as a result of an amputation.

• A prosthetic hand can restore some of the functions of a missing limb and help the user in performing activities of daily living.

• Using 3D-printing technology is one of the solutions to manufacture hand prostheses.

• This overview provides information about the general, mechanical and kinematic specifications of all the devices and it provides the information about the 3D-printing technology used to print the hands.

     

Epidemiologic and Genomic Analysis of SARS-CoV-2 Delta Variant Superspreading Event in Nightclub,the Netherlands,June 2021

We report a severe acute respiratory syndrome coronavirus 2 superspreading event in the Netherlands after distancing rules were lifted in nightclubs, despite requiring a negative test or vaccination. This occurrence illustrates the potential for rapid dissemination of variants in largely unvaccinated populations under such conditions. We detected subsequent community transmission of this strain.     

Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.

18F-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET. Furthermore, the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated. METHODS: Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT, endoscopic ultrasonography, and ultrasound of the neck. In addition, all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity. RESULTS: 18F-FDG PET was able to detect all esophageal cancers, whereas 18F-FLT PET visualized the tumor in 8 of 10 patients. Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients. 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET, whereas 18F-FDG PET showed uptake in benign lesions in 2 patients. The uptake of 18F-FDG (median standardized uptake value [SUV(mean)], 6.0) was significantly higher than 18F-FLT (median SUV(mean), 3.4). Neither 18F-FDG maximum SUV (SUV(max)) nor 18F-FLT SUV(max) correlated with Ki-67 expression in the linear regression analysis. CONCLUSION: In this study, uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake. 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans. Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation.     

Test‐retest reliability of the default mode network in a multi‐centric fMRI study of healthy elderly: Effects of data‐driven physiological noise correction techniques

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within‐site test‐retest reliability and the across‐site reproducibility consistency of DMN‐derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue‐based regression, PESTICA and FSL‐FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z‐scores and, albeit less markedly, the cluster‐size in the DMN; in particular, FSL‐FIX tended to increase the DMN z‐scores compared to others. Within‐site test‐retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5–11% for DMN z‐scores and cluster‐size reliability. DMN pattern overlap was in the range 60–65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL‐FIX and Tissue‐based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z‐scores relative to NPC. Overall these findings support the use of rPNC methods like tissue‐based or FSL‐FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114–2132, 2016. © 2016 Wiley Periodicals, Inc.     

Review of deprescribing processes and development of an evidence-based,patient-centred deprescribing process

Inappropriate use of medication is widespread, especially in older people, and is associated with risks, including adverse drug reactions, hospitalization and increased mortality. Optimization of appropriate medication use to minimize these harms is an ongoing challenge in healthcare. The term ‘deprescribing’ has been used to describe the complex process that is required for safe and effective cessation of medication. Patients play an important role in their own health and, while they may complain about the number of medications they have to take, they may also be reluctant to cease a medication when given the opportunity to do so. A review of previously proposed deprescribing processes and relevant literature was used to develop the patient-centred deprescribing process, which is a five-step cycle that encompasses gaining a comprehensive medication history, identifying potentially inappropriate medications, determining whether the potentially inappropriate medication can be ceased, planning the withdrawal regimen (e.g. tapering where necessary) and provision of monitoring, support and documentation. This is the first deprescribing process developed using knowledge of the patients'' views of medication cessation; it focuses on engaging patients throughout the process, with the aim of improving long-term health outcomes. Despite a comprehensive review of the literature, there is still a lack in the evidence base on which to conduct deprescribing. The next step in broadening the evidence to support deprescribing will be to test the developed process to determine feasibility in the clinical setting.     

The Delphic oracle: a multidisciplinary defense of the gaseous vent theory

Ancient historical references consistently describe an intoxicating gas, produced by a cavern in the ground, as the source of the power at the oracle of Delphi. These ancient writings are supported by a series of associated geological findings. Chemical analysis of the spring waters and travertine deposits at the site show these gases to be the light hydrocarbon gases methane, ethane, and ethylene. The effects of inhaling ethylene, a major anesthetic gas in the mid-20th century, are similar to those described in the ancient writings. We believe the probable cause of the trancelike state of the Priestess (the Pythia) at the oracle of Delphi during her mantic sessions was produced by inhaling ethylene gas or a mixture of ethylene and ethane from a naturally occurring vent of geological origin.