Evidence-based Ranking Research Articles

E-SERS: An Enhanced Approach to Trust-Based Ranking of Apps

The number of mobile applications (“Apps”) has grown significantly in recent years. App Stores rank/recommend Apps based on factors such as average star ratings and the number of installs. Such rankings do not focus on the internal artifacts of Apps (e.g., security vulnerabilities). If internal artifacts are ignored, users may fail to estimate the potential risks associated with installing Apps. In this research, we present a framework called E-SERS (Enhanced Security-related and Evidence-based Ranking Scheme) for comparing Android Apps that offer similar functionalities. E-SERS uses internal and external artifacts of Apps in the ranking process. E-SERS is a significant enhancement of our past evidence-based ranking framework called SERS. We have evaluated E-SERS on publicly accessible Apps from the Google Play Store and compared our rankings with prevalent ranking techniques. Our experiments demonstrate that E-SERS, leveraging its holistic approach, excels in identifying malicious Apps and consistently outperforms existing alternatives in ranking accuracy. By emphasizing comprehensive assessment, E-SERS empowers users, particularly those less experienced with technology, to make informed decisions and avoid potentially harmful Apps. This contribution addresses a critical gap in current App-ranking methodologies, enhancing the safety and security of today’s technologically dependent society.

Toxicity prediction: An application of alternative testing and computational toxicology in contaminated groundwater sites in Taiwan

Groundwater contamination remains a global threat due to its toxic effects to humans and the environment. The remediation of contaminated groundwater sites can be costly, thus, identifying the priority areas of concern is important to reduce money spent on resources. In this study, we aimed to identify and rank the priority groundwater sites in a contaminated petrochemical district by combining alternative, non-animal approaches – chemical analysis, cell-based high throughput screening (HTS), and Toxicological Priority Index (ToxPi) computational toxicology tool. Groundwater samples collected from ten different sites in a contaminated district showed pollutant levels below the detection limit, however, hepatotoxic bioactivity was demonstrated in human hepatoma HepaRG cells. Integrating the pollutants information (i.e., pollutant characteristics and concentration data) with the bioactivity data of the groundwater samples, an evidence-based ranking of the groundwater sites for future remediation was established using ToxPi analysis. The currently presented combinatorial approach of screening groundwater sites for remediation purposes can further be refined by including relevant parameters, which can boost the utility of this approach for groundwater screening and future remediation.

A manually curated annotation characterises genomic features of P. falciparum lncRNAs

BackgroundImportant regulation occurs at the level of transcription in Plasmodium falciparum and growing evidence suggests that these apicomplexan parasites have complex regulatory networks. Recent studies implicate long noncoding RNAs (lncRNAs) as transcriptional regulators in P. falciparum. However, due to limited research and the lack of necessary experimental tools, our understanding of their role in the malaria-causing parasite remains largely unelucidated. In this work, we address one of these limitations, the lack of an updated and improved lncRNA annotation in P. falciparum.ResultsWe generated long-read RNA sequencing data and integrated information extracted and curated from multiple sources to manually annotate lncRNAs. We identified 1119 novel lncRNAs and validated and refined 1250 existing annotations. Utilising the collated datasets, we generated evidence-based ranking scores for each annotation and characterised the distinct genomic contexts and features of P. falciparum lncRNAs. Certain features indicated subsets with potential biological significance such as 25 lncRNAs containing multiple introns, 335 lncRNAs lacking mutations in piggyBac mutagenic studies and lncRNAs associated with specific biologic processes including two new types of lncRNAs found proximal to var genes.ConclusionsThe insights and the annotation presented in this study will serve as valuable tools for researchers seeking to understand the role of lncRNAs in parasite biology through both bioinformatics and experimental approaches.

Demonstration of an aggregated biomarker response approach to assess the impact of point and diffuse contaminant sources in feral fish in a small river case study

The assessment of the exposure of aquatic wildlife to complex environmental mixtures of chemicals originating from both point and diffuse sources and evaluating the potential impact thereof constitutes a significant step towards mitigating toxic pressure and the improvement of ecological status. In the current proof-of-concept study, we demonstrate the potential of a novel Aggregated Biomarker Response (ABR) approach involving a comprehensive set of biomarkers to identify complex exposure and impacts on wild brown trout (Salmo trutta fario). Our scenario used a small lowland river in Germany (Holtemme river in the Elbe river catchment) impacted by two wastewater treatment plants (WWTP) and diffuse agricultural runoff as a case study. The trout were collected along a pollution gradient (characterised in a parallel study) in the river. Compared to fish from the reference site upstream of the first WWTP, the trout collected downstream of the WWTPs showed a significant increase in micronucleus formation, phase I and II enzyme activities, and oxidative stress parameters in agreement with increasing exposure to various chemicals. By integrating single biomarker responses into an aggregated biomarker response, the two WWTPs' contribution to the observed toxicity could be clearly differentiated. The ABR results were supported by chemical analyses and whole transcriptome data, which revealed alterations of steroid biosynthesis and associated pathways, including an anti-androgenic effect, as some of the key drivers of the observed toxicity. Overall, this combined approach of in situ biomarker responses complemented with molecular pathway analysis allowed for a comprehensive ecotoxicological assessment of fish along the river. This study provides evidence for specific hazard potentials caused by mixtures of agricultural and WWTP derived chemicals at sublethal concentrations. Using aggregated biomarker responses combined with chemical analyses enabled an evidence-based ranking of sites with different degrees of pollution according to toxic stress and observed effects.

Abstract 5707: A standard operating procedure for the interpretation of oncogenicity/pathogenicity of somatic mutations

Abstract Somatic variants in cancer-relevant genes are interpreted from multiple partially overlapping perspectives. When considered in discovery and translational research endeavors, it is important to determine if a particular variant observed in a gene of interest is oncogenic/pathogenic or not, as such knowledge provides the foundation on which targeted cancer treatment research is based. In contrast, clinical applications are dominated by diagnostic, prognostic, or therapeutic interpretations which in part also depends on underlying variant oncogenicity/pathogenicity. The Association for Molecular Pathology, the American Society of Clinical Oncology, and the College of American Pathologists (AMP/ASCO/CAP) have published structured somatic variant clinical interpretation guidelines which specifically address diagnostic, prognostic, and therapeutic implications. These guidelines have been well-received by the oncology community. Many variant knowledgebases, clinical laboratories/centers have adopted or are in the process of adopting these guidelines. The AMP/ASCO/CAP guidelines also describe different data types which are used to determine oncogenicity/pathogenicity of a variant, such as: population frequency, functional data, computational predictions, segregation, and somatic frequency. A second collaborative effort created the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets to provide a harmonized vocabulary that provides an evidence-based ranking system of molecular targets that supports their value as clinical targets. However, neither of these clinical guideline systems provide systematic and comprehensive procedures for aggregating population frequency, functional data, computational predictions, segregation, and somatic frequency to consistently interpret variant oncogenicity/pathogenicity, as has been published in the ACMG/AMP guidelines for interpretation of pathogenicity of germline variants. In order to address this unmet need for somatic variant oncogenicity/pathogenicity interpretation procedures, the Variant Interpretation for Cancer Consortium (VICC, a GA4GH driver project) Knowledge Curation and Interpretation Standards (KCIS) working group (WG) has developed a Standard Operating Procedure (SOP) with contributions from members of ClinGen Somatic Clinical Domain WG, and ClinGen Somatic/Germline variant curation WG using an approach similar to the ACMG/AMP germline pathogenicity guidelines to categorize evidence of oncogenicity/pathogenicity as very strong, strong, moderate or supporting. This SOP enables consistent and comprehensive assessment of oncogenicity/pathogenicity of somatic variants and latest version of an SOP can be found at https://cancervariants.org/wg/kcis/. Citation Format: Peter Horak, Malachi Griffith, Arpad Danos, Beth A. Pitel, Subha Madhavan, Xuelu Liu, Jennifer Lee, Gordana Raca, Shirley Li, Alex H. Wagner, Shashikant Kulkarni, Obi L. Griffith, Debyani Chakravarty, Dmitriy Sonkin. A standard operating procedure for the interpretation of oncogenicity/pathogenicity of somatic mutations [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5707.

Understanding perceived availability and importance of tobacco control interventions to inform European adoption of a UK economic model: a cross-sectional study

BackgroundThe evidence on the extent to which stakeholders in different European countries agree with availability and importance of tobacco-control interventions is limited. This study assessed and compared stakeholders’ views from five European countries and compared the perceived ranking of interventions with evidence-based ranking using cost-effectiveness data.MethodsAn interview survey (face-to-face, by phone or Skype) was conducted between April and July 2014 with five categories of stakeholders - decision makers, service purchasers, service providers, evidence generators and health promotion advocates - from Germany, Hungary, the Netherlands, Spain, and the United Kingdom. A list of potential stakeholders drawn from the research team’s contacts and snowballing served as the sampling frame. An email invitation was sent to all stakeholders in this list and recruitment was based on positive replies. Respondents were asked to rate availability and importance of 30 tobacco control interventions. Kappa coefficients assessed agreement of stakeholders’ views. A mean importance score for each intervention was used to rank the interventions. This ranking was compared with the ranking based on cost-effectiveness data from a published review.ResultsNinety-three stakeholders (55.7% response rate) completed the survey: 18.3% were from Germany, 17.2% from Hungary, 30.1% from the Netherlands, 19.4% from Spain, and 15.1% from the UK. Of those, 31.2% were decision makers, 26.9% evidence generators, 19.4% service providers, 15.1% health-promotion advocates, and 7.5% purchasers of services/pharmaceutical products. Smoking restrictions in public areas were rated as the most important intervention (mean score = 1.89). The agreement on availability of interventions between the stakeholders was very low (kappa = 0.098; 95% CI = [0.085, 0.111] but the agreement on the importance of the interventions was fair (kappa = 0.239; 95% CI = [0.208, 0.253]). A correlation was found between availability and importance rankings for stage-based interventions. The importance ranking was not statistically concordant with the ranking based on published cost-effectiveness data (Kendall rank correlation coefficient = 0.40; p-value = 0.11; 95% CI = [− 0.09, 0.89]).ConclusionsThe intrinsic differences in stakeholder views must be addressed while transferring economic evidence Europe-wide. Strong engagement with stakeholders, focussing on better communication, has a potential to mitigate this challenge.

Selection of embryos for transfer in IVF: ranking embryos based on their implantation potential using morphological scoring

The selection of embryos based on morphology is still the core of daily laboratory practice in IVF/intracytoplasmic sperm injection. At present, the selection of embryos is primarily based on experience and local protocols. Since an evidence-based ranking strategy for embryos on day 3 is currently lacking, this work constructed a multivariable prediction model to rank embryos according to their implantation potential. A total of 6021 fresh embryo transfers between January 2004 and July 2009 were included, eight potential predictive factors were evaluated and a prediction model was developed using multivariable logistic regression. The model was externally validated with data from couples treated between August 2009 and September 2011 in the same clinic. Five factors were included in the final prediction model: early cleavage, number of blastomeres on days 2 and 3 and morphological score and presence of morula on day 3. With validation, the model showed moderate discriminative capacity (c-statistic 0.70) and calibrated well and was able to distinguish embryos with high ongoing implantation potential from embryos with moderate or low ongoing implantation potential. The model can be used by embryologists as an objective tool to rank embryos according to implantation potential, thereby aiding the selection of embryos for transfer.

FDA perspectives on health claims for food labels

The U.S. Food and Drug Administration's regulatory authority over health claims was clarified in 1990 legislation known as the Nutrition Labeling and Education Act (NLEA). This law established mandatory nutrition labeling for most foods and placed restrictions on the use of food label claims characterizing the levels or health benefits of nutrients in foods. NLEA set a high threshold for the scientific standard under which the U.S. Food and Drug Administration (FDA) may authorize health claims, this standard is known as the significant scientific agreement (SSA) standard. Subsequent legislation known as the Food and Drug Administration Modernization Act (FDAMA) provided an alternative to FDA review of the health claim where an U.S. government scientific body other than FDA concluded that there is SSA for a substance/disease relationship. Courts have since extended the scope of health claims to include qualified health claims (QHC) that are health claims not substantiated on evidence that meets the level of SSA standard, but include a qualifying statement intended to convey to the consumer the level of evidence for the claim. FDA has responded by developing an evidence-based ranking system for scientific data to determine the level of evidence substantiating a health claim. The following is an overview of FDA's regulations and evidence-based method for evaluating health claims.