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Women, ethnic minority, and less affluent groups are widely underrepresented in chemistry, a problem that is observed at all levels but begins before college matriculation takes place. The importance of representation and humanization of scientists is crucial. Despite limited progress over recent decades, poor visibility of role models from underrepresented groups remains problematic, emphasizing the importance of initiatives to positively introduce them in classroom settings. Through profiles of underrepresented "success stories" from academia and industry, the ChemDiverse project was developed to encourage underrepresented groups to pursue the chemical sciences at higher education levels by providing teachers with an easy and structured way of encouraging Scottish high school students into science, technology, engineering, and mathematics (STEM). Based on survey feedback from teachers at participating schools, it is a well-formulated project that is easy to implement within the context of the Scottish Curriculum for Excellence.

Substantial global attention is focused on how to reduce the risk of future pandemics. Reducing this risk requires investment in prevention, preparedness, and response. Although preparedness and response have received significant focus, prevention, especially the prevention of zoonotic spillover, remains largely absent from global conversations. This oversight is due in part to the lack of a clear definition of prevention and lack of guidance on how to achieve it. To address this gap, we elucidate the mechanisms linking environmental change and zoonotic spillover using spillover of viruses from bats as a case study. We identify ecological interventions that can disrupt these spillover mechanisms and propose policy frameworks for their implementation. Recognizing that pandemics originate in ecological systems, we advocate for integrating ecological approaches alongside biomedical approaches in a comprehensive and balanced pandemic prevention strategy.

Abstract Background Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment. Methods Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing–remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches. Results We identified alterations in peripheral and intrathecal adaptive immunity, mainly affecting the T cell (Tc) but also the B cell (Bc) compartment in ALE, RRMS, and pCNS-tumors compared to controls. ALE, RRMS, and pCNS-tumors featured higher expression of the T cell activation marker HLA-DR, which was even more pronounced in pCNS-tumors than in ALE or RRMS. Glioblastoma patients showed signs of T cell exhaustion that were not visible in RRMS patients. In-depth characterization of the PB revealed differences mainly in the T effector and memory compartment between RRMS and glioblastoma patients and similar alterations in the Bc compartment, including atypical Bc, CD19+CD20− double negative Bc, and plasma cells. PB and CSF mFC together with CSF routine parameters could reliably differentiate ALE and RRMS from pCNS-tumors facilitating early diagnosis and treatment. Conclusions ALE, RRMS, and pCNS-tumors show distinct but partially overlapping changes mainly in HLA-DR+ Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment. Graphical Abstract

The Community Multiscale Air Quality (CMAQ) model has been used for regulatory purposes at the U.S. EPA and in the research community for decades. In 2012, we released the Weather Research and Forecasting (WRF)-CMAQ coupled model that enables aerosol information from CMAQ to affect meteorological processes through direct effects on shortwave radiation. Both CMAQ and WRF-CMAQ are considered limited-area models. Recently, we have extended domain coverage to the global scale by linking the meteorological Model for Prediction Across Scales – Atmosphere (MPAS-A, hereafter referred simply to as MPAS) with CMAQ to form the MPAS-CMAQ global coupled model. To configure these three different models, i.e., CMAQ (offline), WRF-CMAQ, and MPAS-CMAQ, we have developed the Advanced Air Quality Modeling System (AAQMS) for constructing each of them effortlessly. We evaluate this newly built MPAS-CMAQ coupled model using two global configurations: a 120 km uniform mesh and a 92–25 km variable mesh with the finer area over North America. Preliminary computational tests show good scalability and model evaluation, when using a 3-year simulation (2014–2016) for the uniform mesh case and a monthly simulation of January and July 2016 for the variable mesh case, on ozone and PM2.5 and show reasonable performance with respect to observations. The 92–25 km configuration has a high bias in wintertime surface ozone across the United States, and this bias is consistent with the 120 km result. Summertime surface ozone in the 92–25 km configuration is less biased than the 120 km case. The MPAS-CMAQ system reasonably reproduces the daily variability of daily average PM from the Air Quality System (AQS) network.

The development of student metacognition has the potential to provide some of the greatest learning gains in science education, even outstripping the contribution of general intelligence. While models for metacognition are in broad agreement about their nature, they vary widely in essential elements and the relationships between them, especially between metacognitive knowledge and metacognitive skills. Recent systematic literature reviews have not untangled the concept of metacognition as they are not suited to crafting a synthesised conceptualisation for a controversial topic. This article, then, presents an integrative literature review of metacognition studies that draws together metacognitive knowledge and metacognitive skills into a hierarchical framework. The framework comprises, from the foundational level, metacognitive knowledge, called self-Aware of cognition, then various metacognitive skills; self-Monitor cognition, self-Evaluate cognition, self-Regulate cognition and self-Transfer cognition (AMERT). As a preliminary test of its viability, the AMERT framework is used to analyse interview data in which there was evidence of rich metacognitive thinking by students in the fourth, research-focused, year of a science degree. Rich epitomising statements were found in interviews for each level of the AMERT hierarchy, providing tentative evidence of its viability for understanding metacognitive processes when students learn in science.

Background Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised to be more diverse and malleable than was previously appreciated. Hypoxic signalling pathways are known to regulate important neutrophil behaviours and, as such, are potential therapeutic targets for regulating neutrophil antimicrobial and inflammatory responses. Methods We used a combination of in vivo and ex vivo models, utilising neutrophil and myeloid specific PHD1 or PHD3 deficient mouse lines to investigate the roles of oxygen sensing prolyl hydroxylase enzymes in the regulation of neutrophilic inflammation and immunity. Mass spectrometry and Seahorse metabolic flux assays were used to analyse the role of metabolic shifts in driving the downstream phenotypes. Results We found that PHD1 deficiency drives alterations in neutrophil metabolism and recruitment, in an oxygen dependent fashion. Despite this, PHD1 deficiency did not significantly alter ex vivo neutrophil phenotypes or in vivo outcomes in mouse models of inflammation. Conversely, PHD3 deficiency was found to enhance neutrophil antibacterial properties without excessive inflammatory responses. This was not linked to changes in the abundance of core metabolites but was associated with increased oxygen consumption and increased mitochondrial reactive oxygen species (mROS) production. Conclusions PHD3 deficiency drives a favourable neutrophil phenotype in infection and, as such, is an important potential therapeutic target.

Abstract Substantial global attention is focused on how to reduce the risk of future pandemics. Reducing this risk requires investment in prevention, preparedness, and response. Although preparedness and response have received significant focus, prevention, especially the prevention of zoonotic spillover, remains largely absent from global conversations. This oversight is due in part to the lack of a clear definition of prevention and lack of guidance on how to achieve it. To address this gap, we elucidate the mechanisms linking environmental change and zoonotic spillover using spillover of viruses from bats as a case study. We identify ecological interventions that can disrupt these spillover mechanisms and propose policy frameworks for their implementation. Recognizing that pandemics originate in ecological systems, we advocate for integrating ecological approaches alongside biomedical approaches in a comprehensive and balanced pandemic prevention strategy.

BackgroundInitially developed in the intensive care unit (ICU) at St. Joseph's Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital.MethodsFrom January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively.ResultsFrom March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program.ConclusionsThe formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Because critical thinking is essential for scientific learning, academics and casual staff struggle to effectively develop students' critical thinking. This study examined the integration of the Research Skill Development (RSD) framework into a Biology course in an Indonesian University and tested how it helped academics and casual staff develop students' critical thinking. Specifically, the study focused on the benefits attained by the students and how the use of the RSD framework structured their lab reports. This study employed instruments, i.e., questionnaires, student open-field questions, semi-structured interviews, and a rubric. The results indicated two benefits: self-perception on critical thinking and appropriate student lab reports for the RSD framework.

Introduction and objectiveAutologous hematopoietic stem cell transplantation (aHSCT) is a promising treatment option for persons with multiple sclerosis (pwMS). Patients undergoing aHSCT face unique challenges in all aspects of life. In this study, we explored the lived experiences of pwMS undergoing aHSCT.MethodsSemi-structured interviews of 12 pwMS treated with aHSCT were conducted using a maximum variation sampling strategy. Interviews were transcribed verbatim and analyzed thematically using inductive and deductive categories.ResultsThree major themes were identified: (1) preparing for aHSCT, (2) experiencing the procedure, and (3) post-treatment time. A difficult decision-making process, organizational effort, and funding difficulties characterized the preparation for transplantation. AHSCT was seen as a life-changing event accompanied by both psychological and physical stress, with an associated feeling of regaining control. The transplantation had a lasting positive effect on the lives of the interviewed pwMS. However, the early post-treatment time was characterized by successes and failures alike. Particularly the independently organized medical aftercare was perceived as challenging. Retrospective revaluation has led most pwMS to wish for earlier information provision about the treatment option of aHSCT during their treatment history.ConclusionAHSCT had a clear impact on patients’ physical and psycho-social health, influencing their perception of life and its quality. Assessing and attending to unmet needs of patients before, during, and after transplantation may positively influence their experience of aHSCT.

Triple-negative breast cancer (TNBC), which constitutes 10–20 percent of all breast cancers, is aggressive, has high metastatic potential, and carries a poor prognosis due to limited treatment options. LT-IIc, a member of the type II subfamily of ADP-ribosylating—heat-labile enterotoxins that bind to a distinctive set of cell-surface ganglioside receptors—is cytotoxic toward TNBC cell lines, but has no cytotoxic activity for non-transformed breast epithelial cells. Here, primary TNBC cells, isolated from resected human tumors, showed an enhanced cytotoxic response specifically toward LT-IIc, in contrast to other enterotoxins that were tested. MDA-MB-231 cells, a model for TNBC, were used to evaluate potential mechanisms of cytotoxicity by LT-IIc, which induced elevated intracellular cAMP and stimulated the cAMP response element-binding protein (CREB) signaling pathway. To dissect the role of ADP-ribosylation, cAMP induction, and ganglioside ligation in the cytotoxic response, MDA-MB-231 cells were exposed to wild-type LT-IIc, the recombinant B-pentamer of LT-IIc that lacks the ADP-ribosylating A polypeptide, or mutants of LT-IIc with an enzymatically inactivated A1-domain. These experiments revealed that the ADP-ribosyltransferase activity of LT-IIc was nonessential for inducing the lethality of MDA-MB-231 cells. In contrast, a mutant LT-IIc with an altered ganglioside binding activity failed to trigger a cytotoxic response in MDA-MB-231 cells. Furthermore, the pharmacological inhibition of ganglioside expression protected MDA-MB-231 cells from the cytotoxic effects of LT-IIc. These data establish that ganglioside ligation, but not the induction of cAMP production nor ADP-ribosyltransferase activity, is essential to initiating the LT-IIc-dependent cell death of MDA-MB-231 cells. These experiments unveiled previously unknown properties of LT-IIc and gangliosides in signal transduction, offering the potential for the targeted treatment of TNBC, an option that is desperately needed.

For decades, researchers have used linkable administrative health data for evaluating the health care system, subject to local privacy legislation. In Ontario, Canada, the relevant privacy legislation permits some organizations (prescribed entities) to conduct this kind of research but is silent on their ability to identify and contact individuals in those datasets. Following consultation with the Office of the Information and Privacy Commissioner of Ontario, we developed a pilot study to identify and contact by mail a sample of people at high risk for kidney failure within the next 2 years, based on laboratory and administrative data from provincial datasets held by ICES, to ensure they receive needed kidney care. Before proceeding, we conducted six focus groups to understand the acceptability to the public and people living with chronic kidney disease of direct mail outreach to people at high risk of developing kidney failure. While virtually all participants indicated they would likely participate in the study, most felt strongly that the message should come directly from their primary care provider or whoever ordered the laboratory tests, rather than from an unknown organization. If this is not possible, they felt the health care provider should be made aware of the concern related to their kidney health. Most agreed that, if health authorities could identify people at high risk of a treatable life-threatening illness if caught early enough, there is a social responsibility to notify people. While privacy laws allow for free flow of health information among health care providers who provide direct clinical care, the proposed case-finding and outreach falls outside that model. Enabling this kind of information flow will require greater clarity in existing laws or revisions to these laws. This also requires adequate notification and culture change for health care providers and the public around information uses and flows.

Abstract Expression levels of microRNAs (miRNAs) in single cells are low and conventional miRNA detection methods require amplification that can be complex, time-consuming, costly and may bias results. Single cell microfluidic platforms have been developed; however, current approaches are unable to absolutely quantify single miRNA molecules expressed in single cells. Herein, we present an amplification-free sandwich hybridisation assay to detect single miRNA molecules in single cells using a microfluidic platform that optically traps and lyses individual cells. Absolute quantification of miR-21 and miR-34a molecules was achieved at a single cell level in human cell lines and validated using real-time qPCR. The sensitivity of the assay was demonstrated by quantifying single miRNA molecules in nasal epithelial cells and CD3+ T-cells, as well as nasal fluid collected non-invasively from healthy individuals. This platform requires ~50 cells or ~30 µL biofluid and can be extended for other miRNA targets therefore it could monitor miRNA levels in disease progression or clinical studies.

The gradual shift to online modes of learning in higher education institutions over the past 2 decades accelerated drastically on a global scale between 2020 and 2022. Students and educators, who have initially grappled with the shift, have now become accustomed to online teaching; however, there are concerns about the quality of learning that has resulted. To enable a sustainable and effective online pedagogy, educators may need to learn about fostering higher-order thinking skills, which can be challenging even for experienced educators. To conceptualise effective online pedagogy, the community of inquiry (CoI) framework emphasises cognitive presence (CP), which focuses on the higher-order thinking process. The CoI is the most widely researched framework in online pedagogy, yet contemporary CoI literature lacks collective evidence of factors that influence CP. This scoping review of the CoI literature explores the factors that influence the higher-order thinking that is indicative of CP. Inclusion criteria included evidence of CP in online learning contexts and published between January 2000 and March 2022, providing a total of 121 studies. Results suggest that teaching presence, structure of learning activities and student characteristics all influence CP.

Informal physics programs bring physicists together with youth and adults from local communities to engage with physics content outside of classroom settings. These public engagement or "physics outreach" programs are a significant endeavor of the physics community; however, we lack a systemic documentation of these efforts, which makes it difficult to situate physics education research on individual informal physics programs into a broader narrative. Additionally, informal physics programs have many formats and vary in terms of their audience, content, activities, and resources. It is important to understand these aspects of programs if we want them to be more equitable and inclusive. This work shows our early steps of a large project aiming to map the landscape of informal physics programs in the United States. Drawing from organizational theory, and using data collected from a national sample of programs, we have created and validated a survey for lead facilitators to capture the who, what, where, when, and why for their informal programs. After validation, we completed targeted data collection within one state as a test case for broader implementation. Our analysis of the sample (n = 18 programs at 6 institutions) shows that there are many different factors other than common presentation-style labels that are relevant, such as geographic reach, audience demographics, funding, and involvement of physics students. One notable finding is that university physics students play a big role in the operation of these programs, making them rich environments for the attention of physics education researchers and administrators at academic institutions.

The Research Skill Development (RSD) framework was devised in 2006 to articulate what educators do when they facilitate student learning through active exploration in ways that enable their skills to grow in sophistication and rigour. This special issue of JUTLP comprises eight articles that focus on the critique, adaptation and application of the RSD. This article introduces the special issue and presents the 2018 version of the RSD, in response to 12 years of feedback on the framework. Changes in the RSD include improvements in articulation of the facets of research, better delineation of autonomy, and the addition of the affective domain and guiding questions. Of the other seven articles, five are set in the undergraduate years and two in master's, with contexts including biology, education, engineering, humanities and interdisciplinary studies. The articles are based across diverse settings, including laboratory, online, language and workplace learning. Of these seven, one critiques the RSD, three focus on curriculum design and three connect the RSD to enduring issues of current concern by adapting the framework for academic literacy, work skills and problem solving. These three adaptations are examples of numerous emerging models that modify RSD terminology and shape, within its broad parameters, and are introduced in this issue as the Models of Engaged Learning and Teaching (MELT).

Abstract Background Initially developed in the intensive care unit (ICU) at St. Joseph’s Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital. Methods From January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively. Results From March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program. Conclusions The formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Abstract Background The medical care of patients with myositis is a great challenge in clinical practice. This is due to the rarity of these disease, the complexity of diagnosis and management as well as the lack of systematic analyses. Objectives Therefore, the aim of this project was to obtain an overview of the current care of myositis patients in Germany and to evaluate epidemiological trends in recent years. Methods In collaboration with BARMER Insurance, retrospective analysis of outpatient and inpatient data from an average of approximately 8.7 million insured patients between January 2005 and December 2019 was performed using ICD-10 codes for myositis for identification of relevant data. In addition, a comparative analysis was performed between myositis patients and an age-matched comparison group from other populations insured by BARMER. Results 45,800 BARMER-insured individuals received a diagnosis of myositis during the observation period, with a relatively stable prevalence throughout. With regard to comorbidities, a significantly higher rate of cardiovascular disease as well as neoplasm was observed compared to the control group within the BARMER-insured population. In addition, myositis patients suffer more frequently from psychiatric disorders, such as depression and somatoform disorders. However, the ICD-10 catalogue only includes the specific coding of “dermatomyositis” and “polymyositis” and thus does not allow for a sufficient analysis of all idiopathic inflammatory myopathies subtypes. Conclusion The current data provide a comprehensive epidemiological analysis of myositis in Germany, highlighting the multimorbidity of myositis patients. This underlines the need for multidisciplinary management. However, the ICD-10 codes currently still in use do not allow for specific analysis of the subtypes of myositis. The upcoming ICD-11 coding may improve future analyses in this regard.

Abstract Background Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing–remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape. Methods We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions. Results Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy. Conclusion Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.