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Introduction Suicide is a multifaceted subject that encompasses a broad spectrum of perspectives, spanning philosophy, the arts, social sciences, neuroscience, neuropsychiatry, and public health. The history of suicide is intricately intertwined with the history of humanity itself, and examining the shifting attitudes towards suicide holds significant implications for the field of suicide prevention. Objectives The objective of this paper is to offer a timeline of the social perspectives about suicidal behavior throughout history in order to showcase the influence of cultural and contextual factors. Methods This poster is based on the Massive Open Online Course (MOOC) “Focus on Suicidal Behaviour” provided by the European Psychiatric Association. We performed a brief overview of the chapter on history of suicide and updated data on this topic with recent literature findings. Results In antiquity, suicide was sometimes regarded as justifiable, whether to preserve honor or protest injustices. However, during the Middle Ages, suicide was primarily seen as a criminal act, violating the rules of the Christian religion. The Renaissance brought about a shift in the perception of suicide, as it began to be depicted in art as a heroic or philosophical act. Moving into the Romantic period, suicide took on a tragic and noble connotation, often seen as an escape from unbearable suffering. The 19th century marked a significant turning point when the social context started being recognized as a crucial factor in the development of suicidal behavior. In the 20th century, suicide was increasingly considered a public health problem. In the 21st century, the discourse on suicide has become multifaceted. On one hand, network analysis has enabled the development of an integrated model of suicide, emphasizing the complex interactions among various risk and protective factors. On the other hand, ethical and moral debates persist regarding assisted suicide and its indications. This summary primarily centers on the historical context of suicide within Europe. However, attitudes toward suicide vary significantly across cultures. For instance, in China, suicide rates are higher for women than for men, while Japan has historically displayed a relatively tolerant attitude toward suicide, particularly within the military. In contrast, Islamic countries consider suicide a major sin and implicitly associate it with stigma. Conclusions The understanding of suicide evolves over time and is deeply influenced by cultural contexts. Familiarizing ourselves with the historical perspectives on suicide is essential for comprehending this complex social and personal phenomenon. Such knowledge forms the foundation for the creation of effective prevention strategies. Disclosure of Interest None Declared

Lactate levels in humans reveal intensity and duration of exertion and provide a critical readout for the severity of life-threatening illnesses such as pediatric sepsis. Using the lactate oxidase enzyme (Lox) from Aerococcus viridians, we demonstrated its functionality for lactate electrochemical sensing in physiological fluids in a lab setting. The structure and dynamics of LOx were validated by crystallography, X-ray scattering, and hydroxyl radical protein footprinting. This provided a validated protein template for understanding and designing an enzyme-based electrochemical sensing elements. Using this template, LOx enzyme variants were generated and compared. Comparison of the variants demonstrates that one exhibits effective lactate sensing at significantly reduced operating voltages. Additionally, we demonstrate that the four hexahistidine-tags on each enzyme tetramer are sufficient for immobilization to create a durable, functional sensor, with no need for a covalent attachment, enabling self-immobilization and eliminating the need for additional immobilization steps. The functionality of the LOx enzyme variants was verified at physiological lactate concentrations in both human serum (0–4 mM) and artificial sweat (0–100 mM) using 3-electrode setups for analysis of the three variants in parallel. Accuracy of measurement in both artificial sweat and human serum were high. Employing a microfluidic flow cell, we successfully monitored varying lactate levels in physiological fluids continuously over a 2h period. Overall, this optimized LOx enzyme, which self-immobilizes onto gold sensing electrodes, facilitates efficient and reliable lactate detection and continuous monitoring at reduced operating voltages suitable for further development towards commercial use.

Alveolar macrophages (AM) perform a primary defense mechanism in the lung through phagocytosis of inhaled particles and microorganisms. AM are known to be relatively immunosuppressive consistent with the aim to limit alveolar inflammation and maintain effective gas exchange in the face of these constant challenges. How AM respond to T cell derived cytokine signals, which are critical to the defense against inhaled pathogens, is less well understood. For example, successful containment of Mycobacterium tuberculosis (Mtb) in lung macrophages is highly dependent on IFN-γ secreted by Th-1 lymphocytes, however, the proteomic IFN-γ response profile in AM remains mostly unknown. In this study, we measured IFN-γ induced protein abundance changes in human AM and autologous blood monocytes (MN). AM cells were activated by IFN-γ stimulation resulting in STAT1 phosphorylation and production of MIG/CXCL9 chemokine. However, the global proteomic response to IFN-γ in AM was dramatically limited in comparison to that of MN (9 AM vs 89 MN differentially abundant proteins). AM hypo-responsiveness was not explained by reduced JAK-STAT1 signaling nor increased SOCS1 expression. These findings suggest that AM have a tightly regulated response to IFN-γ which may prevent excessive pulmonary inflammation but may also provide a niche for the initial survival and growth of Mtb and other intracellular pathogens in the lung.

Abstract Background: An important part of biomedical research is the translation of discoveries into clinical or community applications that impact patient health. For a vast majority of clinical applications and sustainable community interventions, a time-tested way to get innovations to patients is through licensing of the technology and commercial development, often through startups. While biomedical scientists and trainees are schooled in discovery research, the processes of commercialization are foreign or intimidating. Further, many trainees will not aspire to a faculty position, and other avenues of advancement are desirable. Methods: At Case Western Reserve University, we developed and launched a Translational Fellows Program to provide such training for the community, focusing specifically on graduate students and postdoctoral fellows. The goals of this program include familiarizing our trainees with the principles of entrepreneurship, product development, and startups. This is accomplished through study of their laboratory’s technology to identify points of translational focus and to increase awareness to potentially move ideas and products toward societal impact. This program leverages much of our existing infrastructure and provides a mechanism for the prioritization of the translation of the technology as well as “release-time” to promote effort. Results: Launched in summer 2020, our first cohort had 3 of the 12 fellows launching startups based on their technology and submitting an National Institutes of Health Small Business Innovation Research (SBIR) proposal. At least 80% reported increased knowledge and confidence in five of six key translational competencies. Conclusion: We are now continuing and improving the program and searching for sustainable support to stabilize the program for a long-term productive future.

Background: There is increasing recognition that social determinants of health (SDOH) profoundly affect health outcomes. Frontline nurses must grasp how SDOH shape health disparities and inequities., Purpose: This paper describes an innovative pedagogical approach that leverages didactic, experiential, and reflective methods, specifically a "small moments" writing activity, to enhance students' understanding of SDOH., Methods: Nursing students (n = 135) from a southeastern U.S. university participated in the activity, and 72 provided consent for inclusion in this analysis. Themes related to students' understanding of SDOH were identified, and implications for nursing practice were considered., Results: This integrative approach deepened students' understanding of SDOH. Narratives highlighted economic instability, cultural barriers, and systemic inequities as drivers of health disparities. Students described greater awareness, empathy, and culturally competent care., Conclusion: Student narratives showed evidence of critical thinking, empathy, and advocacy, crucial skills for addressing health disparities., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Addressing threats to the nursing and public health workforce, while also strengthening the skills of current and future workers, requires programmatic solutions. Training programs should be guided by frameworks, which leverage nursing expertise and leadership, partnerships, and integrate ongoing evaluation., Purpose Statement: This article provides a replicable framework to grow, bolster, and diversify the nursing and public health workforces, known as the Nurse-led Equitable Learning (NEL) Framework for Training Programs. The framework has been applied by several multipronged, federally funded training programs led by investigators embedded in an academic nursing institution., Methods: The NEL framework focuses on: (1) increasing equitable access to the knowledge, skills, and competencies needed to prepare a diverse workforce to deliver effective interventions; (2) fostering academic-practice linkages and community partnerships to facilitate the deployment of newly gained knowledge and skills to address ongoing and emerging challenges in care delivery; and (3) continuously evaluating and disseminating findings to inform expansion and replication of programs., Results: Ten programs using this framework have successfully leveraged $18.3 million in extramural funding to support over 1000 public health professionals and trainees. Longitudinal evaluation efforts indicate that public health workers, including nurses, are benefiting from the programs' workplace trainings, future clinicians are being rigorously trained to identify and address determinants of health to improve patient and community well-being, and educators are engaging in novel pedagogical opportunities to enhance their ability to deliver high quality public health education., Conclusions: Training programs may apply the NEL framework to ensure that the nursing and public health workforces achieve equitable, sustainable growth and deliver high quality evidence-based care., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Single-cell transcriptome sequencing (scRNA-Seq) has allowed new types of investigations at unprecedented levels of resolution. Among the primary goals of scRNA-Seq is the classification of cells into distinct types. Many approaches build on existing clustering literature to develop tools specific to single-cell. However, almost all of these methods rely on heuristics or user-supplied parameters to control the number of clusters. This affects both the resolution of the clusters within the original dataset as well as their replicability across datasets. While many recommendations exist, in general, there is little assurance that any given set of parameters will represent an optimal choice in the trade-off between cluster resolution and replicability. For instance, another set of parameters may result in more clusters that are also more replicable., Results: Here, we propose Dune, a new method for optimizing the trade-off between the resolution of the clusters and their replicability. Our method takes as input a set of clustering results-or partitions-on a single dataset and iteratively merges clusters within each partitions in order to maximize their concordance between partitions. As demonstrated on multiple datasets from different platforms, Dune outperforms existing techniques, that rely on hierarchical merging for reducing the number of clusters, in terms of replicability of the resultant merged clusters as well as concordance with ground truth. Dune is available as an R package on Bioconductor: https://www.bioconductor.org/packages/release/bioc/html/Dune.html ., Conclusions: Cluster refinement by Dune helps improve the robustness of any clustering analysis and reduces the reliance on tuning parameters. This method provides an objective approach for borrowing information across multiple clusterings to generate replicable clusters most likely to represent common biological features across multiple datasets., (© 2024. The Author(s).)

Monoclonal antibody biologics have significantly transformed the therapeutic landscape within the biopharmaceutical industry, partly due to the utilisation of discovery technologies such as the hybridoma method and phage display. While these established platforms have streamlined the development process to date, their reliance on cell transformation for antibody identification faces limitations related to library diversification and the constraints of host cell physiology. Cell-free systems like ribosome display offer a complementary approach, enabling antibody selection in a completely in vitro setting while harnessing enriched cellular molecular machinery. This review aims to provide an overview of the fundamental principles underlying the ribosome display method and its potential for advancing antibody discovery and development.

Background: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear., Objective: To report COVID-19 rates in pwMS according to vaccine serology., Methods: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included. Logistic regression was performed to examine whether seroconversion following vaccination predicted risk of subsequent COVID-19 infection after adjusting for potential confounders. Rates of severe COVID-19 (requiring hospitalisation) were also calculated., Results: A total of 647 pwMS were included (mean age 48 years, 500 (77%) female, median Expanded Disability Status Scale (EDSS) 3.5% and 524 (81%) exposed to DMT at the time of vaccine 1). Overall, 472 out of 588 (73%) were seropositive after vaccines 1 and 2 and 222 out of 305 (73%) after vaccine 3. Seronegative status after vaccine 2 was associated with significantly higher odds of subsequent COVID-19 infection (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.34-4.12, p  = 0.0029), whereas seronegative status after vaccine 3 was not (OR: 1.05, 95% CI: 0.57-1.91). Five people (0.8%) experienced severe COVID-19, all of whom were seronegative after most recent vaccination., Conclusion: Attenuated humoral response to initial COVID-19 vaccination predicts increased risk of COVID-19 in pwMS, but overall low rates of severe COVID-19 were seen.

The behaviour and distribution of iodine in the environment are of significant interest in a range of scientific disciplines, from health, as iodine is an essential element for humans and animals, to climate and air quality, to geochemistry. Aquatic environments are the reservoir for iodine, where it exists in low concentrations as iodide, iodate and dissolved organic iodine and in which it undergoes redox reactions. The current measurement techniques for iodine species are typically time-consuming, subject to relatively poor precision and require specialist instrumentation including those that require mercury as an electrode. We present a new method for measuring iodine species, that is tailored towards lower dissolved organic carbon waters, such as seawater, rainwater and snow, using ion exchange chromatography (IC) with direct ultra-violet spectrophotometric detection of iodide and without the need for sample pre-concentration. Simple chemical amendments to the sample allow for the quantification of both iodate and dissolved organic iodine in addition to iodide. The developed IC method, which takes 16 min, was applied to contrasting samples that encompass a wide range of aqueous environments, from Arctic sea-ice snow (low concentrations) to coastal seawater (complex sample matrix). Linear calibrations are demonstrated for all matrices, using gravimetrically prepared potassium iodide standards. The detection limit for the iodide ion is 0.12 nM based on the standard deviation of the blank, while sample reproducibility is typically <2% at >8 nM and ∼4% at <8 nM. Since there is no environmental certified reference material for iodine species, the measurements made on seawater samples using this IC method were compared to those obtained using established analytical techniques; iodide voltammetry and iodate spectrophotometry. We calculated recoveries of 102 ± 16% (n = 107) for iodide and 116 ± 9% (n = 103) for iodate, the latter difference may be due to an underestimation of iodate by the spectrophotometric method. We further compared a chemical oxidation and reduction of the sample to an ultra-violet digestion to establish the total dissolved iodine content, the average recovery following chemical amendments was 98 ± 4% (n = 92). The new method represents a simple, efficient, green, precise and sensitive method for measuring dissolved speciated iodine in complex matrices., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Particulate nitrate ([Formula: see text]) has long been considered a permanent sink for NO x (NO and NO 2 ), removing a gaseous pollutant that is central to air quality and that influences the global self-cleansing capacity of the atmosphere. Evidence is emerging that photolysis of [Formula: see text] can recycle HONO and NO x back to the gas phase with potentially important implications for tropospheric ozone and OH budgets; however, there are substantial discrepancies in "renoxification" photolysis rate constants. Using aircraft and ground-based HONO observations in the remote Atlantic troposphere, we show evidence for renoxification occurring on mixed marine aerosols with an efficiency that increases with relative humidity and decreases with the concentration of [Formula: see text], thus largely reconciling the very large discrepancies in renoxification photolysis rate constants found across multiple laboratory and field studies. Active release of HONO from aerosol has important implications for atmospheric oxidants such as OH and O 3 in both polluted and clean environments.

Background: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group., Methods: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured., Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There was no association between laboratory evidence of prior COVID-19 and seroconversion following vaccine 3., Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine., (Copyright © 2022. Published by Elsevier B.V.)

Objective: The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines in people with multiple sclerosis (MS)., Methods: Four hundred seventy-three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID-19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV-2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS-CoV-2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response., Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01-0.06, p < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01-0.12) were associated with lower seroconversion following the SARS-CoV-2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Preliminary data on cellular T-cell immunity showed 40% of seronegative subjects had measurable anti-SARS-CoV-2 T cell responses., Interpretation: Some disease modifying therapies convey risk of attenuated serological response to SARS-CoV-2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 20219999:n/a-n/a., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)