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Suratman Suratman,1,2 Kirstin E Ross,1 Kateryna Babina,1 John William Edwards1 1Health and Environment Group, School of the Environment, Faculty of Science and Engineering, Flinders University, Adelaide, SA, Australia; 2School of Public Health, Faculty of Health Sciences, Jenderal Soedirman University, Kampus Karangwangkal, Purwokerto, Indonesia Background: Farmworkers are at risk of exposure to organophosphate pesticides (OPs). Improvements of knowledge and perceptions about organophosphate (OP) exposure may be of benefit for the reduction in OP exposure. Purpose: The purpose of this study was to examine the effectiveness of an educational intervention to improve knowledge and perceptions for reducing OP exposure among Indonesian and South Australian (SA) migrant farmworkers. Methods: This was a quasi-experimental study. The educational intervention used a method of group communication for 30 Indonesian farmworkers and individual communication for seven SA migrant farmworkers. Knowledge and perceptions about OP exposure were measured pre-intervention and 3 months after the intervention. Results: Unadjusted intervention effects at follow-up showed statistically significantly improved scores of knowledge (both adverse effects of OPs and self-protection from OP exposure), perceived susceptibility, and perceived barriers among Indonesian farmworkers compared with SA migrant farmworkers. Furthermore, these four significant variables in the unadjusted model and the two other variables (perceived severity and perceived benefits) were statistically significant after being adjusted for the level of education and years working as a farmworker. In contrast, knowledge about adverse effects of OPs was the only variable that was statistically significantly improved among SA migrant farmworkers. The results of this study suggests educational interventions using a method of group communication could be more effective than using individual intervention. Conclusion: These improvements provide starting points to change health behavior of farmworkers, particularly to reduce OP exposure, both at the workplace and at home. Keywords: group communication, individual communication, organophosphate pesticide exposure, Indonesian farmworkers, South Australian migrant farmworkers

Michael J Taylor, Tara A Garrard, Francis J O'Donahoo, Kirstin E Ross Health and Environment, School of the Environment, Flinders University, Adelaide, SA, Australia Abstract: Strongyloides is a human parasitic nematode that is poorly understood outside a clinical context. This article identifies gaps within the literature, with particular emphasis on gaps that are hindering environmental control of Strongyloides. The prevalence and distribution of Strongyloides is unclear. An estimate of 100–370 million people infected worldwide has been proposed; however, inaccuracy of diagnosis, unreliability of prevalence mapping, and the fact that strongyloidiasis remains a neglected disease suggest that the higher figure of more than 300 million cases is likely to be a more accurate estimate. The complexity of Strongyloides life cycle means that laboratory cultures cannot be maintained outside of a host. This currently limits the range of laboratory-based research, which is vital to controlling Strongyloides through environmental alteration or treatment. Successful clinical treatment with antihelminthic drugs has meant that controlling Strongyloides through environmental control, rather than clinical intervention, has been largely overlooked. These control measures may encompass alteration of the soil environment through physical means, such as desiccation or removal of nutrients, or through chemical or biological agents. Repeated antihelminthic treatment of individuals with recurrent strongyloidiasis has not been observed to result in the selection of resistant strains; however, this has not been explicitly demonstrated, and relying on such assumptions in the long-term may prove to be shortsighted. It is ultimately naive to assume that continued administration of antihelminthics will be without any negative long-term effects. In Australia, strongyloidiasis primarily affects Indigenous communities, including communities from arid central Australia. This suggests that the range of Strongyloides extends beyond the reported tropical/subtropical boundary. Localized conditions that might result in this extended boundary include accumulation of moisture within housing because of malfunctioning health hardware inside and outside the house and the presence of dog fecal matter inside or outside housing areas. Keywords: Strongyloides stercoralis, strongyloidiasis, environmental control, parasitology, nematode

Abstract Background The field of point-of-care ultrasound (POCUS) has advanced in recent decades due to the benefits it holds for medical providers. However, aspiring POCUS practitioners require adequate training. Unfortunately, there remains a paucity of resources to deliver this training, particularly in rural and underserved areas. Despite these barriers, calls for POCUS training in undergraduate medical education are growing, and many medical schools now deliver some form of POCUS education. Our program lacked POCUS training; therefore, we developed and implemented a POCUS curriculum for our first-year medical students. Methods We developed a POCUS curriculum for first year medical students in a rural medically underserved region of the United States. To evaluate our course, we measured learning outcomes, self-reported confidence in a variety of POCUS domains, and gathered feedback on the course with a multi-modal approach: an original written pre- and post-test, survey tool, and semi-structured interview protocol, respectively. Results Student (n=24) knowledge of POCUS significantly increased (pre-test average score = 55%, post-test average score = 79%, P

ABSTRACT Mice that lack the genes for IL-27, or the IL-27 receptor, and infected with Toxoplasma gondii develop T cell-mediated pathology. Here, studies were performed to determine the impact of endogenous IL-27 on the immune response to T. gondii in wild-type (WT) mice. Analysis of infected mice revealed the early production of IL-27p28 by a subset of Ly6Chi, inflammatory monocytes, and sustained IL-27p28 production at sites of acute and chronic infection. Administration of anti-IL-27p28 prior to infection resulted in an early (day 5) increase in levels of macrophage and granulocyte activation, as well as enhanced effector T cell responses, as measured by both cellularity, cytokine production, and transcriptional profiling. This enhanced acute response led to immune pathology, while blockade during the chronic phase of infection resulted in enhanced T cell responses but no systemic pathology. In the absence of IL-27, the enhanced monocyte responses observed at day 10 were a secondary consequence of activated CD4+ T cells. Thus, in WT mice, IL-27 has distinct suppressive effects that impact innate and adaptive immunity during different phases of this infection.IMPORTANCEThe molecule IL-27 is critical in limiting the immune response to the parasite Toxoplasma gondii. In the absence of IL-27, a lethal, overactive immune response develops during infection. However, when exactly in the course of infection this molecule is needed was unclear. By selectively inhibiting IL-27 during this parasitic infection, we discovered that IL-27 was only needed during, but not prior to, infection. Additionally, IL-27 is only needed in the active areas in which the parasite is replicating. Finally, our work found that a previously unstudied cell type, monocytes, was regulated by IL-27, which contributes further to our understanding of the regulatory networks established by this molecule.

Introduction Emergency medicine (EM) trainees must learn to manage multiple patients simultaneously using task-switching. While prior work has demonstrated that multipatient scenarios can be an effective teaching tool for task-switching, few studies have shown how simulation can be used to assess residents' ability to manage multiple patients effectively. The goal of this curriculum was to provide a formative assessment of core EM skills by employing a series of simulations designed to require frequent task-switching. Methods This exercise consisted of three simulation scenarios running in sequence. The first scenario involved medical resuscitation and advanced cardiac life support, the second required learners to manage two patients involved in a trauma using advanced trauma life support, and the final scenario tested learners' ability to communicate bad news. Faculty observers used scenario-specific checklists to identify gaps in content knowledge, communication skills, and task-switching abilities during reflective debriefs. These checklists were analyzed to identify trends. All participants were sent a postsession evaluation. Items omitted by >50% of participants were flagged for review. Results Flagged items included asking for finger-stick glucose, verbalizing a backup intubation plan, specifying type of blood products, and asking for team input. Nine of 12 participants completed the postsession evaluation, noting that they agreed or strongly agreed the simulation was relevant and promoted reflection on task-switching skills. Discussion This simulation provides educators with a tool to facilitate reflective feedback with senior EM learners regarding their core resuscitation, leadership, and task-switching skills and could be further adapted to promote deliberate practice.

Funded by ADR UK, a new data linking team at the Ministry of Justice set out to link administrative datasets across the justice space, for internal use and sharing with external researchers. To achieve this aim we sought a linkage implementation that was probabilistic, flexible, scalable and ideally open source. Taking into account the tools available at the MoJ, existing open-source software (and paid alternatives) failed to meet our desired criteria. It was decided to develop a software package that builds on FastLink’s implementation in R of an Expectation-Maximisation algorithm to estimate a Fellegi-Sunter linkage model, adding a range of technical improvements, increased functionality and customisation options. Distributed computing offered by Spark could facilitate comparable linkage jobs that run on much larger datasets and much faster. Working with government data, accountability and transparency are vital, so the data and models are made accessible by a range of intuitive visualizations. The Splink python package has been downloaded over 6 million times. This initially used Spark to deliver its superior performance, but Splink v3 caters for various SQL backends and more potential users. As we have made Splink more intuitive, more accessible, and more extensively documented we continue to receive feedback and contributions from around the world, driving further continuous development. Through technical innovation and user-focused development, Splink has improved access to cutting-edge data linkage, and created groundbreaking research opportunities at MoJ and beyond. The team is grateful to ONS and other collaborators for testing and adopting these tools, and we will present some of the latest developments as well as examples of how Splink has been used worldwide.

Collaborative neuroimaging research is often hindered by technological, policy, administrative, and methodological barriers, despite the abundance of available data. COINSTAC (The Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation) is a platform that successfully tackles these challenges through federated analysis, allowing researchers to analyze datasets without publicly sharing their data. This paper presents a significant enhancement to the COINSTAC platform: COINSTAC Vaults (CVs). CVs are designed to further reduce barriers by hosting standardized, persistent, and highly-available datasets, while seamlessly integrating with COINSTAC's federated analysis capabilities. CVs offer a user-friendly interface for self-service analysis, streamlining collaboration, and eliminating the need for manual coordination with data owners. Importantly, CVs can also be used in conjunction with open data as well, by simply creating a CV hosting the open data one would like to include in the analysis, thus filling an important gap in the data sharing ecosystem. We demonstrate the impact of CVs through several functional and structural neuroimaging studies utilizing federated analysis showcasing their potential to improve the reproducibility of research and increase sample sizes in neuroimaging studies.

Abstract Introduction Point-of-care ultrasound (US) is used in clinical practice across many specialties. Ultrasound (US) curricula for medical students are increasingly common. Optimal timing, structure, and effect of ultrasound education during medical school remains poorly understood. This study aims to retrospectively determine the association between participation in a preclinical, longitudinal US curriculum and medical student academic performance. Methods All first-year medical students at a medical school in the Midwest region of the United States were offered a voluntary longitudinal US curriculum. Participants were selected by random lottery. The curriculum consisted of five three-hour hands on-sessions with matching asynchronous content covering anatomy and pathologic findings. Content was paired with organ system blocks in the standard first year curriculum at our medical school. Exam scores between the participating and non-participating students were compared to evaluate the objective impact of US education on performance in an existing curriculum. We hypothesized that there would be an association between participation in the curriculum and improved medical student performance. Secondary outcomes included shelf exam scores for the surgery, internal medicine, neurology clerkships and USMLE Step 1. A multivariable linear regression model was used to evaluate the association of US curriculum participation with student performance. Scores were adjusted for age, gender, MCAT percentile, and science or engineering degree. Results 76 of 178 students applied to participate in the curriculum, of which 51 were accepted. US curriculum students were compared to non-participating students (n = 127) from the same class. The US curriculum students performed better in cardiovascular anatomy (mean score 92.1 vs. 88.7, p = 0.048 after adjustment for multiple comparisons). There were no significant differences in cumulative cardiovascular exam scores, or in anatomy and cumulative exam scores for the gastroenterology and neurology blocks. The effect of US curriculum participation on cardiovascular anatomy scores was estimated to be an improvement of 3.48 points (95% CI 0.78-6.18). No significant differences were observed for USMLE Step 1 or clerkship shelf exams. There were no significant differences in either preclinical, clerkship or Step 1 score for the 25 students who applied and were not accepted and the 102 who did not apply. Conclusions Participation in a preclinical longitudinal US curriculum was associated with improved exam performance in cardiovascular anatomy but not examination of other cardiovascular system concepts. Neither anatomy or comprehensive exam scores for neurology and gastrointestinal organ system blocks were improved.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

BackgroundThere is an urgent need for harmonization between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology platforms and assays prior to defining appropriate correlates of protection and as well inform the development of new rapid diagnostic tests that can be used for serosurveillance as new variants of concern (VOC) emerge. We compared multiple SARS-CoV-2 serology reference materials to the WHO International Standard (WHO IS) to determine their utility as secondary standards, using an international network of laboratories with high-throughput quantitative serology assays. This enabled the comparison of quantitative results between multiple serology platforms.MethodsBetween April and December 2020, 13 well-characterized and validated SARS-CoV-2 serology reference materials were recruited from six different providers to qualify as secondary standards to the WHO IS. All the samples were tested in parallel with the National Institute for Biological Standards and Control (NIBSC) 20/136 and parallel-line assays were used to calculate the relevant potency and binding antibody units.ResultsAll the samples saw varying levels of concordance between diagnostic methods at specific antigen–antibody combinations. Seven of the 12 candidate materials had high concordance for the spike-immunoglobulin G (IgG) analyte [percent coefficient of variation (%CV) between 5 and 44%].ConclusionDespite some concordance between laboratories, qualification of secondary materials to the WHO IS using arbitrary international units or binding antibody units per milliliter (BAU/ml) does not provide any benefit to the reference materials overall, due to the lack of consistent agreeable international unit (IU) or BAU/ml conversions between laboratories. Secondary standards should be qualified to well-characterized reference materials, such as the WHO IS, using serology assays that are similar to the ones used for the original characterization of the WHO IS.

Clinical and communication skills involved in managing patient death are essential for medical practitioners, yet these skills are often neglected in undergraduate medical education. We aim to review current reported evidence of simulation-based education on medical students' preparedness and performance toward patient death. A narrative review of the literature on simulation-based education for medical students on patient death was conducted. Data on study design, simulation dimension, evaluation tool, and outcome were collected and summarized. Eleven prospective studies were included for narrative review. Simulation modalities included mannequins, standardized patients, and online virtual reality. Heterogeneity in the evaluation tool of simulation-based education was demonstrated. Ninety percent of studies concluded positive outcome of simulation on improving medical students' preparedness in patient death. No negative or adverse learner reaction was reported. Simulation-based education may safely improve medical students' competence in handling patient death. Current data and evaluation tools of education outcomes are sparse and heterogeneous. Future research is encouraged to explore this under-researched topic, amid increasing interest in the use of simulation in medical education.

Abstract Renal colic encounters are common; in the United States alone, they represent greater than one million annual emergency department (ED) visits. Most of these stones are managed conservatively with a trial of passage. However, some lead to repeat colic episodes, secondary ED visits, increased anxiety, and increased cost. Of the 5%–10% of symptomatic stones that become lodged at the ureteropelvic junction and are larger than 5 mm, most require operative intervention. In the process of executing a NASA‐funded study of ultrasonic repositioning of kidney stones, the subject was administered fluid to dilate the collecting system, placed in Trendelenburg bed positioning, and rolled to both sides. During this process a symptomatic, obstructing 9‐mm ureteropelvic junction stone moved back into the kidney's lower pole/infundibulum and symptoms were immediately resolved. The patient remained asymptomatic for a period of 5 weeks at which point elective intervention was scheduled. This case demonstrates that ureteropelvic junction stones may be repositioned in a non‐invasive manner, turning a stone that requires urgent intervention into one that can be managed electively.

Abstract Background The secretion of recombinant disulfide-bond containing proteins into the periplasm of Gram-negative bacterial hosts, such as E. coli, has many advantages that can facilitate product isolation, quality and activity. However, the secretion machinery of E. coli has a limited capacity and can become overloaded, leading to cytoplasmic retention of product; which can negatively impact cell viability and biomass accumulation. Fine control over recombinant gene expression offers the potential to avoid this overload by matching expression levels to the host secretion capacity. Results Here we report the application of the RiboTite gene expression control system to achieve this by finely controlling cellular expression levels. The level of control afforded by this system allows cell viability to be maintained, permitting production of high-quality, active product with enhanced volumetric titres. Conclusions The methods and systems reported expand the tools available for the production of disulfide-bond containing proteins, including antibody fragments, in bacterial hosts.

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

Abstract Background This study aims to compare the increased time needed to perform advanced focused cardiac measurements in the emergency department, including diastolic heart failure evaluation via E/E′, and cardiac output with LVOT/VTI. Patients with pertinent cardiopulmonary symptoms in the emergency department had a focused cardiac ultrasound performed by the emergency department ultrasound team. The ability to obtain basic cardiac windows, evaluate for effusion, systolic ejection fraction, and right-sided heart pressures were recorded. Advanced measurements, along with time to obtain all images and the training level of the provider, were recorded. Results Fifty-three patients were enrolled. Basic focused cardiac windows were able to be obtained in 80% of patients. The average 4-window focused cardiac ultrasound took 4 min and 49 s to perform. Diastolic measurements were able to be obtained in 51% of patients, taking an average of 3 min and 17 s. Cardiac output measurements were able to be obtained in 53% of patients, taking an average of 3 min and 8 s. Conclusion The ability to obtain these images improved with increasing level of training. Performing both cardiac output and diastolic measurements increased the time with bedside ultrasound by 6 min and 25 s, and were able to be obtained in slightly over half of all ED patients.

Introduction: Medical students’ ability to learn clinical procedures and competently apply these skills is an essential component of medical education. Complex skills with limited opportunity for practice have been shown to degrade without continued refresher training. To our knowledge there is no evidence that objectively evaluates temporal degradation of clinical skills in undergraduate medical education. The purpose of this study was to evaluate temporal retention of clinical skills among third year medical students. Methods: This was a cross-sectional study conducted at four separate time intervals in the cadaver laboratory at a public medical school. Forty-five novice third year medical students were evaluated for retention of skills in the following three procedures: pigtail thoracostomy, femoral line placement, and endotracheal intubation. Prior to the start of third-year medical clerkships, medical students participated in a two-hour didactic session designed to teach clinically relevant materials including the procedures. Prior to the start of their respective surgery clerkships, students were asked to perform the same three procedures and were evaluated by trained emergency medicine and surgery faculty for retention rates, using three validated checklists. Students were then reassessed at six week intervals in four separate groups based on the start date of their respective surgical clerkships. We compared the evaluation results between students tested one week after training and those tested at three later dates for statistically significant differences in score distribution using a one-tailed Wilcoxon Mann-Whitney U-test for non-parametric rank-sum analysis. Results: Retention rates were shown to have a statistically significant decline between six and 12 weeks for all three procedural skills. Conclusion: In the instruction of medical students, skill degradation should be considered when teaching complex technical skills. Based on the statistically significant decline in procedural skills noted in our investigation, instructors should consider administering a refresher course between six and twelve weeks from initial training.

The growth of proteomics-based methods in archaeology prompted an investigation of the survival of non-collagenous proteins, specifically immunoglobulin G (IgG), in archaeological human bone and dentine. Over a decade ago reports were published on extracted, immunoreactive archaeological IgG, and the variable yields of IgG molecules detected by Western blots of 1D and 2D SDS-PAGE gels. If IgG can indeed be recovered from archaeological skeletal material, it offers remarkable opportunities for exploring the history of disease - for example in applying functional anti-malarial IgGs to study past patterns of malaria. More recently, the field has seen a move away from immunological approaches and towards the use of shotgun proteomics via mass spectrometry. Using previously published techniques, this study attempted to extract and characterize archaeological IgG proteins. In only one extraction method were immunoglobulin derived peptides identified, and these displayed extensive evidence of degradation. The failure to extract immunoglobulins by all but one method, along with observed patterns of protein degradation, suggests that IgG may be an unsuitable target for detecting disease-associated antigens. This research highlights the importance of revisiting previously ‘successful’ biomolecular methodologies using emerging technologies.

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In the era of Big Data, sharing neuroimaging data across multiple sites has become increasingly important. However, researchers who want to engage in centralized, large-scale data sharing and analysis must often contend with problems such as high database cost, long data transfer time, extensive manual effort, and privacy issues for sensitive data. To remove these barriers to enable easier data sharing and analysis, we introduced a new, decentralized, privacy-enabled infrastructure model for brain imaging data called COINSTAC in 2016. We have continued development of COINSTAC since this model was first introduced. One of the challenges with such a model is adapting the required algorithms to function within a decentralized framework. In this paper, we report on how we are solving this problem, along with our progress on several fronts, including additional decentralized algorithms implementation, user interface enhancement, decentralized regression statistic calculation, and complete pipeline specifications.

A recently proposed water retention model has been further developed for the application on unsaturated deformable soils. The physical mechanisms underpinning the water retention characteristic of soils was at first described in terms of traditional theories of capillarity and interfacial physical chemistry at pore level. Then upscaling to macroscopic level of material scale in terms of average volume theorem produces an analytical formula for the water retention characteristic. The methodology produces an explicit form of the water retention curve as a function of three state parameters: the suction, the degree-of-water-saturation and the void-ratio. At last, the model has been tested using experimental measurements.

Abstract Background During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. Methods A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Results Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. Conclusions The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study. Please see Commentary: http://www.biomedcentral.com/1741-7015/9/13/abstract.

Abstract Background The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1) the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2) a suitable cell-line representative of naive T cells. Results Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes.

Legionella is an opportunistic waterborne pathogen that causes Legionnaires' disease. It poses a significant public health risk, especially to vulnerable populations in health care facilities. It is ubiquitous in manufactured water systems and is transmitted via inhalation or aspiration of aerosols/water droplets generated from water fixtures (e.g., showers and hand basins). As such, the effective management of premise plumbing systems (building water systems) in health care facilities is essential for reducing the risk of Legionnaires' disease. Chemical disinfection is a commonly used control method and chlorine-based disinfectants, including chlorine, chloramine, and chlorine dioxide, have been used for over a century. However, the effectiveness of these disinfectants in premise plumbing systems is affected by various interconnected factors that can make it challenging to maintain effective disinfection. This systematic literature review identifies all studies that have examined the factors impacting the efficacy and decay of chlorine-based disinfectant within premise plumbing systems. A total of 117 field and laboratory-based studies were identified and included in this review. A total of 20 studies directly compared the effectiveness of the different chlorine-based disinfectants. The findings from these studies ranked the typical effectiveness as follows: chloramine > chlorine dioxide > chlorine. A total of 26 factors were identified across 117 studies as influencing the efficacy and decay of disinfectants in premise plumbing systems. These factors were sorted into categories of operational factors that are changed by the operation of water devices and fixtures (such as stagnation, temperature, water velocity), evolving factors which are changed in-directly (such as disinfectant concentration, Legionella disinfectant resistance, Legionella growth, season, biofilm and microbe, protozoa, nitrification, total organic carbon(TOC), pH, dissolved oxygen(DO), hardness, ammonia, and sediment and pipe deposit) and stable factors that are not often changed(such as disinfectant type, pipe material, pipe size, pipe age, water recirculating, softener, corrosion inhibitor, automatic sensor tap, building floor, and construction activity). A factor-effect map of each of these factors and whether they have a positive or negative association with disinfection efficacy against Legionella in premise plumbing systems is presented. It was also found that evaluating the effectiveness of chlorine disinfection as a water risk management strategy is further complicated by varying disinfection resistance of Legionella species and the form of Legionella (culturable/viable but non culturable, free living/biofilm associated, intracellular replication within amoeba hosts). Future research is needed that utilises sensors and other approaches to measure these key factors (such as pH, temperature, stagnation, water age and disinfection residual) in real time throughout premise plumbing systems. This information will support the development of improved models to predict disinfection within premise plumbing systems. The findings from this study will inform the use of chlorine-based disinfection within premise plumbing systems to reduce the risk of Legionnaires disease., Competing Interests: Declaration of competing interest Hao Xi and Jason Hinds work for Enware Pty Ltd, Caringbah, NSW, Australia, a manufacturer of specialist plumbing and safety products. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Increasingly, hospital handwashing basins have been identified as a source of healthcare-associated infections. Biofilms formed on the faucet and drains of handbasins can potentially harbour pathogenic microbes and promote the dissemination of antimicrobial resistance. However, little is known about the diversity of these biofilm communities and the routes of contamination., Aim: The aim of this paper was to use 16S rRNA gene amplicon sequencing to investigate the diversity of prokaryote communities present in faucet and drain biofilm samples taken from hospital and residential handbasins., Findings: The biofilm prokaryotes communities were diverse, with high abundances of potentially corrosive, biofilm forming and pathogenic genera, including those that are not typically waterborne. The β-diversity showed statistically significant differences in the variation of bacterial communities on the basis on building type (hospital vs residential p = 0.0415). However, there was no statistically significant clustering based on sampling site (faucet vs drain p = 0.46). When examining the β-diversity between individual factors, there was a significant difference between drain biofilms of different buildings (hospital drain vs residential drain p = 0.0338)., Conclusion: This study demonstrated that biofilms from hospital and residential handbasins contain complex and diverse microbial communities that differ significantly by building type. It also showed biofilms formed on the faucet and drain of a hospital's handbasins were not significantly different. Future research is needed to understand the potential mechanisms of transfer between drains and faucets of hospital handbasins. This information will inform improved infection control guidelines to control this underrecognized source of infections., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Claire Hayward reports financial support was provided by Enware Australia Pty Ltd. Jason Hinds reports a relationship with Enware Australia Pty Ltd. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Legionella is the causative agent of Legionnaires' disease, and its prevalence in potable water is a significant public health issue. Water stagnation within buildings increases the risk of Legionella. However, there are limited studies investigating how stagnation arising through intermittent usage affects Legionella proliferation and the studies that are available do not consider viable but non culturable (VBNC) Legionella . This study used a model plumbing system to examine how intermittent water stagnation affects both VBNC and culturable Legionella . The model plumbing system contained a water tank supplying two biofilm reactors. The model was initially left stagnant for ≈5 months (147 days), after which one reactor was flushed daily, and the other weekly. Biofilm coupons, and water samples were collected for analysis at days 0, 14 and 28. These samples were analysed for culturable and VBNC Legionella , free-living amoebae, and heterotrophic bacteria. After 28 days, once-a-day flushing significantly ( p  < 0.001) reduced the amount of biofilm-associated culturable Legionella (1.5 log 10 reduction) compared with weekly flushing. However, higher counts of biofilm-associated VBNC Legionella (1 log 10 higher) were recovered from the reactor with once-a-day flushing compared with weekly flushing. Likewise, once-a-day flushing increased the population of biofilm-associated Vermamoeba vermiformis (approximately 3 log 10 higher) compared with weekly flushing, which indicated a positive relationship between VBNC Legionella and V. vermiformis . This is the first study to investigate the influence of stagnation on VBNC Legionella under environmental conditions. Overall, this study showed that a reduction in water stagnation decreased culturable Legionella but not VBNC Legionella ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Methamphetamine contamination of residential properties remains a serious public health concern for members of the public. External stakeholders including Environmental Health Officers (EHOs) and testing and remediation technicians are engaged on investigating whether contamination has occurred from manufacturing or smoking processes. More specifically, local council EHOs are responsible for managing clandestine drug laboratories when notified by police and also for responding to public enquiries. However, the full scope of these contaminated properties is not seen by any single stakeholder, making it very challenging to quantify these situations. To evaluate the prevalence of methamphetamine related enquiries from the general public to EHOs, this study surveyed and interviewed officers from around Australia. It was found that public enquiries were infrequent with only 6% of respondents having received enquiries in the last month, which indicates that people are seeking information from other sources. Interestingly, there were case study scenarios that also mentioned issues with awareness and the flow of information. Concerns regarding difficult cases, police notifications, and site visits were also highlighted. The results of this study provide a benchmark of how methamphetamine related cases are managed and highlight the need for trustworthy information that is available to EHOs, governments, industry members, and the public in a unified location.

Background: Aberrant protein kinase regulation leading to abnormal substrate phosphorylation is associated with several human diseases. Despite the promise of therapies targeting kinases, many human kinases remain understudied. Most existing computational tools predicting phosphorylation cover less than 50% of known human kinases. They utilize local feature selection based on protein sequences, motifs, domains, structures, and/or functions, and do not consider the heterogeneous relationships of the proteins. In this work, we present KSFinder, a tool that predicts kinase-substrate links by capturing the inherent association of proteins in a network comprising 85% of the known human kinases. We also postulate the potential role of two understudied kinases based on their substrate predictions from KSFinder., Methods: KSFinder learns the semantic relationships in a phosphoproteome knowledge graph using a knowledge graph embedding algorithm and represents the nodes in low-dimensional vectors. A multilayer perceptron (MLP) classifier is trained to discern kinase-substrate links using the embedded vectors. KSFinder uses a strategic negative generation approach that eliminates biases in entity representation and combines data from experimentally validated non-interacting protein pairs, proteins from different subcellular locations, and random sampling. We assess KSFinder's generalization capability on four different datasets and compare its performance with other state-of-the-art prediction models. We employ KSFinder to predict substrates of 68 "dark" kinases considered understudied by the Illuminating the Druggable Genome program and use our text-mining tool, RLIMS-P along with manual curation, to search for literature evidence for the predictions. In a case study, we performed functional enrichment analysis for two dark kinases - HIPK3 and CAMKK1 using their predicted substrates., Results: KSFinder shows improved performance over other kinase-substrate prediction models and generalized prediction ability on different datasets. We identified literature evidence for 17 novel predictions involving an understudied kinase. All of these 17 predictions had a probability score ≥0.7 (nine at >0.9, six at 0.8-0.9, and two at 0.7-0.8). The evaluation of 93,593 negative predictions (probability ≤0.3) identified four false negatives. The top enriched biological processes of HIPK3 substrates relate to the regulation of extracellular matrix and epigenetic gene expression, while CAMKK1 substrates include lipid storage regulation and glucose homeostasis., Conclusions: KSFinder outperforms the current kinase-substrate prediction tools with higher kinase coverage. The strategically developed negatives provide a superior generalization ability for KSFinder. We predicted substrates of 432 kinases, 68 of which are understudied, and hypothesized the potential functions of two dark kinases using their predicted substrates., Competing Interests: The authors declare there are no competing interests., (©2023 Anandakrishnan et al.)

In recent years, the frequency of nosocomial infections has increased. Hospital water systems support the growth of microbes, especially opportunistic premise plumbing pathogens. In this study, planktonic prokaryotic communities present in water samples taken from hospital showers and hand basins, collected over three different sampling phases, were characterized by 16S rRNA gene amplicon sequencing. Significant differences in the abundance of various prokaryotic taxa were found through univariate and multivariate analysis. Overall, the prokaryotic communities of hospital water were taxonomically diverse and dominated by biofilm forming, corrosion causing, and potentially pathogenic bacteria. The phyla Proteobacteria, Actinobacteriota, Bacteroidota, Planctomycetota, Firmicutes, and Cyanobacteria made up 96% of the relative abundance. The α-diversity measurements of prokaryotic communities showed no difference in taxa evenness and richness based on sampling sites (shower or hand basins), sampling phases (months), and presence or absence of Vermamoeba vermiformis. However, β-diversity measurements showed significant clustering of prokaryotic communities based on sampling phases, with the greatest difference observed between the samples collected in phase 1 vs phase 2/3. Importantly, significant difference was observed in prokaryotic communities based on flow dynamics of the incoming water. The Pielou's evenness diversity index revealed a significant difference (Kruskal Wallis, p < 0.05) and showed higher species richness in low flow regime (< 13 minutes water flushing per week and ≤ 765 flushing events per six months). Similarly, Bray-Curtis dissimilarity index found significant differences (PERMANOVA, p < 0.05) in the prokaryotic communities of low vs medium/high flow regimes. Furthermore, linear discriminant analysis effect size showed that several biofilm forming (e.g., Pseudomonadales), corrosion causing (e.g., Desulfobacterales), extremely environmental stress resistant (e.g., Deinococcales), and potentially pathogenic (e.g., Pseudomonas) bacterial taxa were in higher amounts under low flow regime conditions. This study demonstrated that a hospital building water system consists of a complex microbiome that is shaped by incoming water quality and the building flow dynamics arising through usage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Climate change is the most urgent and significant public health risk facing the globe. In Australia, it has been identified that Environmental Health Officers/Practitioners (EHOs/EHPs, hereafter EHOs) are a currently underutilized source of knowledge and skills that can contribute to climate change adaptation planning at the local government level. The ability of local government EHOs to utilize their local knowledge and skills in human health risk assessment during a public health emergency was demonstrated through their role in the response to COVID-19. This study used a survey and follow up interviews to examine the roles and responsibilities of EHOs during the COVID-19 pandemic and used the results to examine the potential of the workforce to tackle climate change and health related issues. What worked well, what regulatory tools were helpful, how interagency collaboration worked and what barriers or hindering factors existed were also explored. A workforce review of EHOs in South Australia was also undertaken to identify current and future challenges facing EHOs and their capacity to assist in climate change preparedness. The findings demonstrated that the workforce was used in the response to COVID-19 for varying roles by councils, including in education and communication (both internally and externally) as well as monitoring and reporting compliance with directions. Notably, half the workforce believed they could have been better utilized, and the other half thought they were well utilized. The South Australian Local Government Functional Support Group (LGFSG) was praised by the workforce for a successful approach in coordinating multiagency responses and communicating directions in a timely fashion. These lessons learnt from the COVID-19 pandemic should be incorporated into climate change adaptation planning. To ensure consistent messaging and a consolidated information repository, a centralized group should be used to coordinate local government climate change adaptation plans in relation to environmental health and be included in all future emergency management response plans. The surveyed EHOs identified environmental health issues associated with climate change as the most significant future challenge; however, concerningly, participants believe that a lack of adequate resourcing, leading to workforce shortages, increasing workloads and a lack of support, is negatively impacting the workforce's preparedness to deal with these emerging issues. It was suggested that the misperception of environmental health and a failure to recognize its value has resulted in a unique dilemma where EHOs and their councils find themselves caught between managing current workload demands and issues, and endeavouring to prepare, as a priority, for emerging environmental health issues associated with climate change and insufficient resources.

The UK online puppy trade has rapidly outgrown the current legislation, aided by the anonymity provided by classified advertisement platforms. In an effort to meet increased demand, some unregulated and regulated breeders may have employed practices that negatively impact canine welfare. A paucity of up-to-date empirical data, necessary to characterise the scale and nature of this industry, makes intervention challenging. This study quantifies the online puppy trade via web-scraped online classified advertisements, providing empirical data that reveal market trends, along with spatial and temporal patterns. A total of 17,389 unique dog advertisements were collated and analysed over a 2-year period (1 June 2018 to 31 May 2020). The second year included the COVID-19 Lockdown (23 March 2020 to 31 May 2020). Statistical comparisons between dependent and independent variables were performed by linear regression. In the case of a single continuous variable, a one sample t -test was used. Of these advertisements, 57.2% were sourced from a pet-specific classified advertisement website (Pets4Homes, n = 9948), and the remaining 42.8% from two general classified advertisement websites (Gumtree, n = 7149, 41.1%; Preloved, n = 292, 1.7%, respectively). England exhibited the greatest number of advertisements (n = 10,493), followed by Wales (n = 1566), Scotland (n = 975), and Northern Ireland (NI; n = 344). Scaled for estimated human population density, Wales possessed as many advertisements per million inhabitants (489.4) as the other three combined (England = 186.4, Scotland = 177.3, and NI = 181.1). Across both years, 559 unique breeds were advertised, yet 66% of all advertisements focused on 20 breeds, and 48% advertisements focused on only 10 breeds. Regional breed popularity was suggested, with French Bulldog as the most advertised breed in England (7.3%), Scotland (6.8%), and Wales (6.8%), but Schnauzers were most popular within Northern Ireland (6.83%). Within the 559 unique breeds advertised, only 3.4% had links to conformational disorders CD); however, these breeds were among the most commonly advertised, totalling 46.9% of all ads. Across all regions, price density peaked between GBP 300 and GBP 1000, with Bulldogs presenting the greatest cost (mean = GBP 1461.38, SD = GBP 940.56), followed closely by French Bulldog (mean = GBP 1279.44, SD = GBP 664.76) and Cavapoo (mean = GBP 1064.56, SD = GBP 509.17). CD breeds were found to be GBP 208.07 more expensive, on average, than non-CD breeds. Our results represent a buoyant online market with regional and seasonal fluctuations in price, advertised breed frequency and total counts. This suggests a market influenced by consumer trends, with a particular focus on breed preference, despite links to illness/disease associated with conformation. Our findings highlight the value of utilising online classified advertisement data for long-term monitoring, in order to assist with evidence-based regulatory reform, impact measurement of targeted campaigns, and legislative enforcement.

We analyzed large-scale post-translational modification (PTM) data to outline cell signaling pathways affected by tyrosine kinase inhibitors (TKIs) in ten lung cancer cell lines. Tyrosine phosphorylated, lysine ubiquitinated, and lysine acetylated proteins were concomitantly identified using sequential enrichment of post translational modification (SEPTM) proteomics. Machine learning was used to identify PTM clusters that represent functional modules that respond to TKIs. To model lung cancer signaling at the protein level, PTM clusters were used to create a co-cluster correlation network (CCCN) and select protein-protein interactions (PPIs) from a large network of curated PPIs to create a cluster-filtered network (CFN). Next, we constructed a Pathway Crosstalk Network (PCN) by connecting pathways from NCATS BioPlanet whose member proteins have PTMs that co-cluster. Interrogating the CCCN, CFN, and PCN individually and in combination yields insights into the response of lung cancer cells to TKIs. We highlight examples where cell signaling pathways involving EGFR and ALK exhibit crosstalk with BioPlanet pathways: Transmembrane transport of small molecules; and Glycolysis and gluconeogenesis. These data identify known and previously unappreciated connections between receptor tyrosine kinase (RTK) signal transduction and oncogenic metabolic reprogramming in lung cancer. Comparison to a CFN generated from a previous multi-PTM analysis of lung cancer cell lines reveals a common core of PPIs involving heat shock/chaperone proteins, metabolic enzymes, cytoskeletal components, and RNA-binding proteins. Elucidation of points of crosstalk among signaling pathways employing different PTMs reveals new potential drug targets and candidates for synergistic attack through combination drug therapy., Competing Interests: JK was funded in part by a sponsored research agreement with Bristol Myers Squibb unrelated to this work., (Copyright: © 2023 Ross et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Legionella pneumophila is a waterborne pathogen and, as the causative agent of Legionnaires' disease, a significant public health concern. Exposure to environmental stresses, and disinfection treatments, promotes the formation of resistant and potentially infectious viable but non-culturable (VBNC) Legionella . The management of engineered water systems to prevent Legionnaires' disease is hindered by the presence of VBNC Legionella that cannot be detected using the standard culture (ISO11731:2017-05) and quantitative polymerase reaction (ISO/TS12869:2019) methods. This study describes a novel method to quantify VBNC Legionella from environmental water samples using a "viability based flow cytometry-cell sorting and qPCR" (VFC + qPCR) assay. This protocol was then validated by quantifying the VBNC Legionella genomic load from hospital water samples. The VBNC cells were unable to be cultured on Buffered Charcoal Yeast Extract (BCYE) agar; however, their viability was confirmed through their ATP activity and ability to infect amoeba hosts. Subsequently, an assessment of the ISO11731:2017-05 pre-treatment procedure demonstrated that acid or heat treatment cause underestimation of alive Legionella population. Our results showed that these pre-treatment procedures induce culturable cells to enter a VBNC state. This may explain the observed insensitivity and lack of reproducibility often observed with the Legionella culture method. This study represents the first time that flow cytometry-cell sorting in conjunction with a qPCR assay has been used as a rapid and direct method to quantify VBNC Legionella from environmental sources. This will significantly improve future research evaluating Legionella risk management approaches for the control of Legionnaires' disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nisar, Ross, Brown, Bentham, Best and Whiley.)

Climate change is the greatest global health threat of the 21st century, with numerous direct and indirect human health consequences. Local governments play a critical role in communities' response to climate change, both through strategies to reduce emissions and adaption plans to respond to changing climate and extreme weather events. Australian local government environmental health officers (EHOs) have the relevant skills and expertise to inform and develop adaptation plans for health protection in the context of climate change. This study used an online survey followed by phone interviews of local government management to determine the extent to which EHOs are involved in adaptation planning in health protection climate change plans. Questions were also asked to determine whether local councils are aware of EHOs' capability to contribute and to gauge the willingness of management to provide EHOs with the workload capacity to do so. The findings demonstrated that although climate adaptation and mitigation planning is occurring in local government, it is not including or considering the public health impacts on the community. Primarily, it was found that this oversight was due to a lack of awareness of the health impacts of climate change outside of a disaster or emergency scenario. Currently, EHOs are an untapped source of knowledge and skills that can contribute to climate change adaption planning. To support this, a framework of local environmental health practice was developed to assist the reconceptualization of the scope of practice required for the planning and response to climate change.

Methamphetamine manufacture, use, and the resulting contamination is a significant issue that affects public health, the environment, and the economy. Third-hand exposure to methamphetamine can result in adverse health risks for individuals and first responders. Such exposures can result from the inhalation of airborne residues or from contact with contaminated objects. This review was conducted to determine the current methods used for methamphetamine extraction from indoor air and porous fabric materials. Dynamic solid phase microextraction (SPME) and sorbent sampling tubes have been applied to extract airborne methamphetamine residues from contaminated properties. SPME and solvent extraction have been applied to sample clothing and textiles for methamphetamine detection. This review demonstrates that there is limited literature on the detection of methamphetamine from indoor air and clothing. Supplementary and consistent methods to detect methamphetamine from air and porous surfaces should be developed and published to allow better assessment of the environmental risk to public health caused by third-hand exposure to methamphetamine.

Free-living amoebae are ubiquitous in the environment and cause both opportunistic and non-opportunistic infections in humans. Some genera of amoebae are natural reservoirs of opportunistic plumbing pathogens, such as Legionella pneumophila. In this study, the presence of free-living amoebae and Legionella was investigated in 140 water and biofilm samples collected from Australian domestic (n = 68) and hospital water systems (n = 72). Each sample was screened in parallel using molecular and culture-based methods. Direct quantitative polymerase chain reaction (qPCR) assays showed that 41% samples were positive for Legionella, 33% for L. pneumophila, 11% for Acanthamoeba, and 55% for Vermamoeba vermiformis gene markers. Only 7% of samples contained culturable L. pneumophila serogroup (sg)1, L. pneumophila sg2-14, and non-pneumophila Legionella. In total, 69% of samples were positive for free-living amoebae using any method. Standard culturing found that 41% of the samples were positive for amoeba (either Acanthamoeba, Allovahlkampfia, Stenamoeba, or V. vermiformis). V. vermiformis showed the highest overall frequency of occurrence. Acanthamoeba and V. vermiformis isolates demonstrated high thermotolerance and osmotolerance and strong broad spectrum bacteriogenic activity against Gram-negative and Gram-positive bacteria. Importantly, all Legionella positive samples were also positive for amoeba, and this co-occurrence was statistically significant (p < 0.05). According to qPCR and fluorescence in situ hybridization, V. vermiformis and Allovahlkampfia harboured intracellular L. pneumophila. To our knowledge, this is the first time Allovahlkampfia and Stenamoeba have been demonstrated as hosts of L. pneumophila in potable water. These results demonstrate the importance of amoebae in engineered water systems, both as a pathogen and as a reservoir of Legionella. The high frequency of gymnamoebae detected in this study from Australian engineered water systems identifies an issue of significant public health concern. Future water management protocols should incorporate treatments strategies to control amoebae to reduce the risk to end users., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jason Hinds reports equipment, drugs, or supplies was provided by Enware Australia Pty Ltd. Jason Hinds reports a relationship with Enware Australia Pty Ltd that includes: employment., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has compelled biomedical researchers to communicate data in real time to establish more effective medical treatments and public health policies. Nontraditional sources such as preprint publications, i.e. articles not yet validated by peer review, have become crucial hubs for the dissemination of scientific results. Natural language processing (NLP) systems have been recently developed to extract and organize COVID-19 data in reasoning systems. Given this scenario, the BioCreative COVID-19 text mining tool interactive demonstration track was created to assess the landscape of the available tools and to gauge user interest, thereby providing a two-way communication channel between NLP system developers and potential end users. The goal was to inform system designers about the performance and usability of their products and to suggest new additional features. Considering the exploratory nature of this track, the call for participation solicited teams to apply for the track, based on their system's ability to perform COVID-19-related tasks and interest in receiving user feedback. We also recruited volunteer users to test systems. Seven teams registered systems for the track, and &gt;30 individuals volunteered as test users; these volunteer users covered a broad range of specialties, including bench scientists, bioinformaticians and biocurators. The users, who had the option to participate anonymously, were provided with written and video documentation to familiarize themselves with the NLP tools and completed a survey to record their evaluation. Additional feedback was also provided by NLP system developers. The track was well received as shown by the overall positive feedback from the participating teams and the users. Database URL: https://biocreative.bioinformatics.udel.edu/tasks/biocreative-vii/track-4/., (© The Author(s) 2022. Published by Oxford University Press.)

The popularity of tattooing has increased significantly over recent years. This has raised concerns about the safety of tattoo inks and their metabolites/degradation products. The photolytic and metabolic degradation of tattoo pigments may result in the formation of toxic compounds, with unforeseen health risks. A systematic literature review was undertaken to determine the current state of knowledge of tattoo pigments' degradation products when irradiated with sunlight, laser light or metabolised. The review demonstrates that there is a lack of knowledge regarding tattoo pigment degradation/metabolism, with only eleven articles found pertaining to the photolysis of tattoo pigments and two articles on the metabolism of tattoo pigments. The limited research indicates that the photolysis of tattoo pigments could result in many toxic degradation products, including hydrogen cyanide and carcinogenic aromatic amines., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

iPTMnet is a resource that combines rich information about protein post-translational modifications (PTM) from curated databases as well as text mining tools. Researchers can use the iPTMnet website to query, analyze and download the PTM data. In this chapter we describe the iPTMnet RESTful API which provides a way to streamline the integration of iPTMnet data into an automated data analysis workflow. In the first section, we give an overview of the architecture of the API. In the second section, we describe various function defined by the API and provide detailed examples of using these functions., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Summary: The global response to the COVID-19 pandemic has led to a rapid increase of scientific literature on this deadly disease. Extracting knowledge from biomedical literature and integrating it with relevant information from curated biological databases is essential to gain insight into COVID-19 etiology, diagnosis and treatment. We used Semantic Web technology RDF to integrate COVID-19 knowledge mined from literature by iTextMine, PubTator and SemRep with relevant biological databases and formalized the knowledge in a standardized and computable COVID-19 Knowledge Graph (KG). We published the COVID-19 KG via a SPARQL endpoint to support federated queries on the Semantic Web and developed a knowledge portal with browsing and searching interfaces. We also developed a RESTful API to support programmatic access and provided RDF dumps for download., Availability and Implementation: The COVID-19 Knowledge Graph is publicly available under CC-BY 4.0 license at https://research.bioinformatics.udel.edu/covid19kg/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To better protect public health from third-hand exposure to methamphetamine, it is important to understand the techniques and current practices used within the methamphetamine testing and decontamination industry in Australia. A survey was conducted focusing on business owners that advertised testing and/or remediation services online. They were also invited to participate in a follow-up phone interview upon completion. The survey demonstrated that testing and decontamination methods were highly varied, which was expected for an industry with no regulation. Most companies offered methamphetamine testing and remediation which could be a conflict of interest. Participants also shared personal experiences, including the conduct of other industry members, demonstrating both poor practice and/or the competitive nature of the business. Participating business owners were following Australian guidelines to the best of their ability, and many are advocates for regulation to be implemented within the industry. This would address the inconsistencies between companies and establish trust for industry members and the public. It would also provide significant public health protection, which is currently lacking. A more consistent approach to the testing and remediation of methamphetamine contamination, aided by regulation, would address the significant risk to public health caused by third-hand exposure to methamphetamine.

Lung cancer is the leading cause of cancer mortality worldwide. The treatment of patients with lung cancer harboring mutant EGFR with orally administered EGFR tyrosine kinase inhibitors (TKI) has been a paradigm shift. Osimertinib and rociletinib are third-generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard of care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here we characterized the proteome and phosphoproteome of a series of isogenic EGFR-mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs, comprising the most comprehensive proteomic dataset resource to date to investigate third generation EGFR TKI resistance in lung adenocarcinoma. Unbiased global quantitative mass spectrometry uncovered alterations in signaling pathways, revealed a proteomic signature of epithelial-mesenchymal transition, and identified kinases and phosphatases with altered expression and phosphorylation in TKI-resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition, resulting in subsequent inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Anticorrelation analyses of this phosphoproteomic dataset with published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures program predicted drugs with the potential to overcome EGFR TKI resistance. The PI3K/MTOR inhibitor dactolisib in combination with osimertinib overcame resistance both in vitro and in vivo . Taken together, this study reveals global proteomic alterations upon third generation EGFR TKI resistance and highlights potential novel approaches to overcome resistance. SIGNIFICANCE: Global quantitative proteomics reveals changes in the proteome and phosphoproteome in lung cancer cells resistant to third generation EGFR TKIs, identifying the PI3K/mTOR inhibitor dactolisib as a potential approach to overcome resistance., (©2021 American Association for Cancer Research.)