Toward a Flexible Metadata Pipeline for Fish Specimen Images

Flexible metadata pipelines are crucial for supporting the FAIR data principles. Despite this need, researchers seldom report their approaches for identifying metadata standards and protocols that support optimal flexibility. This paper reports on an initiative targeting the development of a flexible metadata pipeline for a collection containing over 300,000 digital fish specimen images, harvested from multiple data repositories and fish collections. The images and their associated metadata are being used for AI-related scientific research involving automated species identification, segmentation and trait extraction. The paper provides contextual background, followed by the presentation of a four-phased approach involving: 1. Assessment of the Problem, 2. Investigation of Solutions, 3. Implementation, and 4. Refinement. The work is part of the NSF Harnessing the Data Revolution, Biology Guided Neural Networks (NSF/HDR-BGNN) project and the HDR Imageomics Institute. An RDF graph prototype pipeline is presented, followed by a discussion of research implications and conclusion summarizing the results.Comment: 12 pages. 5 figures. Presented at the 16th International Conference on Metadata and Semantics Research. To be published in the conference proceedings of Metadata and Semantic Research: 16th International Conference, MTSR 2022, London, United Kingdom, November 8-10, 202

Substance Misuse Education for Physicians: Why Older People are Important.

This perspective article focuses on the need for training and education for undergraduate medical students on substance-related disorders, and describes initiatives undertaken in the United Kingdom (UK), Netherlands, United States (US), and Norway to develop the skills, knowledge, and attitudes needed by future doctors to treat patients adequately. In addition, we stress that in postgraduate training, further steps should be taken to develop Addiction Medicine as a specialized and transverse medical domain. Alcohol use disorder is a growing public health problem in the geriatric population, and one that is likely to continue to increase as the baby boomer generation ages. Prescription drug misuse is a major concern, and nicotine misuse remains problematic in a substantial minority. Thus, Addiction Medicine training should address the problems for this specific population. In recent years, several countries have started an Addiction Medicine specialty. Although addiction psychiatry has been a subspecialty in the UK and US for more than 20 years, in most countries it has been a more recent development. Additional courses on addiction should be integrated into the curriculum at both undergraduate and postgraduate levels, as well as form part of the continuous training of other medical specialists. It is recommended that further research and mapping of what is currently taught in medical programs be undertaken, so as to enhance medical education in addiction and improve treatment services

Tight Kernel Bounds for Problems on Graphs with Small Degeneracy

In this paper we consider kernelization for problems on d-degenerate graphs, i.e. graphs such that any subgraph contains a vertex of degree at most $d$. This graph class generalizes many classes of graphs for which effective kernelization is known to exist, e.g. planar graphs, H-minor free graphs, and H-topological-minor free graphs. We show that for several natural problems on d-degenerate graphs the best known kernelization upper bounds are essentially tight.Comment: Full version of ESA 201

Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer

Lung cancer is the leading cause of cancer deaths, because ~84% of cases are diagnosed at an advanced stage. Worldwide in 2008, ~1.5 million people were diagnosed and ~1.3 million died – a survival rate unchanged since 1960. However, patients diagnosed at an early stage and have surgery experience an 86% overall 5-year survival. New diagnostics are therefore needed to identify lung cancer at this stage. Here we present the first large scale clinical use of aptamers to discover blood protein biomarkers in disease with our breakthrough proteomic technology. This multi-center case-control study was conducted in archived samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. We measured >800 proteins in 15uL of serum, identified 44 candidate biomarkers, and developed a 12-protein panel that distinguished NSCLC from controls with 91% sensitivity and 84% specificity in a training set and 89% sensitivity and 83% specificity in a blinded, independent verification set. Performance was similar for early and late stage NSCLC. This is a significant advance in proteomics in an area of high clinical need

Regulation of Ras proteins by reactive nitrogen species

Ras GTPases have been a subject of intense investigation since the early-80’s, when single point mutations in Ras were shown to cause deregulated cell growth control. Subsequently, Ras was identified as the most prevalent oncogene found in human cancer. Ras proteins regulate a host of pathways involved in cell growth, differentiation, and apoptosis by cycling between inactive GDP-bound and active GTP-bound states. Regulation of Ras activity is controlled by cellular factors that alter guanine nucleotide cycling. Oncogenic mutations prevent protein regulatory factors from down-regulating Ras activity, thereby maintaining Ras in a chronically activated state. The central dogma in the field is that protein modulatory factors are the primary regulators of Ras activity. Since the mid-90’s, however, evidence has accumulated that small molecule reactive nitrogen species (RNS) can also influence Ras guanine nucleotide cycling. Herein, we review the basic chemistry behind RNS formation and discuss the mechanism through which various RNS enhance nucleotide exchange in Ras proteins. In addition, we present studies that demonstrate the physiological relevance of RNS-mediated Ras activation within the context of immune system function, brain function, and cancer development. We also highlight future directions and experimental methods that may enhance our ability to detect RNS-mediated activation in cell cultures and in vivo. The development of such methods may ultimately pave new directions for detecting and elucidating how Ras proteins are regulated by redox species, as well as for targeting redox-activated Ras in cancer and other disease states

Crystal structure of an HD-GYP domain cyclic-di-GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre

Bis-(3′,5′) cyclic di-guanylate (c-di-GMP) is a key bacterial second messenger that is implicated in the regulation of many crucial processes that include biofilm formation, motility and virulence. Cellular levels of c-di-GMP are controlled through synthesis by GGDEF domain diguanylate cyclases and degradation by two classes of phosphodiesterase with EAL or HD-GYP domains. Here, we have determined the structure of an enzymatically active HD-GYP domain protein from Persephonella marina (PmGH) alone, in complex with substrate (c-di-GMP) and final reaction product (GMP). The structures reveal a novel trinuclear iron binding site, which is implicated in catalysis and identify residues involved in recognition of c-di-GMP. This structure completes the picture of all domains involved in c-di-GMP metabolism and reveals that the HD-GYP family splits into two distinct subgroups containing bi- and trinuclear metal centres.</p

The Development of the Vulnerability Index (VI) using Principal Component Analysis (PCA)

Climate change elevates the rate of emergence of urban heat islands (UHIs), especially in the tropics. UHIs severely affect human comfort and health. Many studies have suggested that urban areas should be properly mitigated or planned. To cope with this, it is best to present the issue using easy-to-understand approaches to allow for better decision-making, especially during urban planning. Based on the information, adaptations and mitigation strategies can be suggested in order to reduce the impact. Hence, this research was aimed at determining the heat vulnerability index (HVI) of urban areas. This study was conducted in Malaysia in the Klang Valley, a tropical city with a complex urban morphology. Remote sensing techniques were employed to extract and derive the spatial index values for exposure, sensitivity, and adaptive capacity. A principal component analysis (PCA) was used to estimate the vulnerability as well as to generate the HVI. The most vulnerable districts were found to be Petaling (1.00), Kuala Lumpur (0.99), and Putrajaya (0.95). Kuala Lumpur had a level of exposure that was high (0.56), a level of sensitivity that was high (0.84), and capacity to adapt that was low (0.54), while Petaling had a high exposure value (0.56), very high sensitivity (1), and high adaptive capacity (0.72). A Pearson’s correlation (r) test also revealed that the variables used were highly correlated. From the preliminary findings, the vulnerability of the population to high temperatures in the Klang Valley can be identified to help develop adaptative plans that are targeted as a response to rapid warming in the future in Malaysia

Multidisciplinary consensus statement on the clinical management of patients with pancreatic cancer

Pancreatic cancer (PC) remains one of the most aggressive tumors with an increasing incidence rate and reduced survival. Although surgical resection is the only potentially curative treatment for PC, only 15-20% of patients are resectable at diagnosis. To select the most appropriate treatment and thus improve outcomes, the diagnostic and therapeutic strategy for each patient with PC should be discussed within a multidisciplinary expert team. Clinical decision-making should be evidence-based, considering the staging of the tumor, the performance status and preferences of the patient. The aim of this guideline is to provide practical and evidence-based recommendations for the management of PC