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Abstract Background Communication is considered an inherent element of nearly every implementation strategy. Often it is seen as a means for imparting new information between stakeholders, representing a Transaction orientation to communication. From a Process orientation, communication is more than information-exchange and is acknowledged as being shaped by (and shaping) the individuals involved and their relationships with one another. As the field of Implementation Science (IS) works to strengthen theoretical integration, we encourage an interdisciplinary approach that engages communication theory to develop richer understanding of strategies and determinants of practice. Methods We interviewed 28 evaluators, 12 implementors, and 12 administrators from 21 Enterprise-Wide Initiatives funded by the Department of Veteran Affairs Office of Rural Health. Semi-structured interviews focused on experiences with implementation and evaluation strategies. We analyzed the interviews using thematic analysis identifying a range of IS constructs. Then we deductively classified those segments based on a Transaction or Process orientation to communication. Results We organized findings using the two IS constructs most commonly discussed in interviews: Collaboration and Leadership Buy-in. The majority of segments coded as Collaboration (n = 34, 74%) and Leadership Buy-in (n = 31, 70%) discussed communication from a Transaction orientation and referred to communication as synonymous with information exchange, which emphasizes the task over the relationships between the individuals performing the tasks. Conversely, when participants discussed Collaboration and Leadership Buy-in from a Process orientation, they acknowledged both constructs as the result of long-term efforts to develop positive relationships based on trust and respect, and emphasized the time costliness of such strategies. Our findings demonstrate that participants who discussed communication from a Process orientation recognized the nuance and complexity of interpersonal interactions, particularly in the context of IS. Conclusions Efficient, reliable information exchange is a critical but often overemphasized element of implementation. Practitioners and researchers must recognize and incorporate the larger role of communication in IS. Two suggestions for engaging a Process orientation to communication are to: (a) use interview probes to learn how communication is enacted, and (b) use process-oriented communication theories to develop interventions and evaluation tools.

Leaf litter is an important input to freshwater systems. Leaves provide carbon, nutrients, and secondary compounds. We examined the effects of tree leaf species on chlorophyll a concentration—a proxy for phytoplankton biomass. We found that an input of Chinese tallow (Triadica sebiferum, invasive in the southeastern USA) and red maple (Acer rubrum) leaves resulted in lower chlorophyll concentrations than controls and other native species. These leaf species also leached tannins, resulting in a darker water color, and either may have caused the patterns observed. To separate these potential mechanisms (darker water leading to light limitation and tannin toxicity), we conducted a second experiment with a fully factorial design manipulating tannins and water color. We found that darker water resulted in the lowest chlorophyll concentration, suggesting light limitation. In the clear-water treatment, the addition of tannic acid lowered chlorophyll concentrations but also resulted in moderately darker water by the end of the experiment. The tannic acid may have been toxic to the algae, or there may have been some light limitation. Our results suggest that tannins that darken water color may substantially suppress phytoplankton and that tree species composition may influence both phytoplankton and the brownification of freshwater.

Abstract Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically heterogenous. The application of omics technologies—mainly studying nucleic acids—has significantly improved MB classification and stratification, but treatment options are still unsatisfactory. The proteome and their N-glycans hold the potential to discover clinically relevant phenotypes and targetable pathways. We compile a harmonized proteome dataset of 167 MBs and integrate findings with DNA methylome, transcriptome and N-glycome data. We show six proteome MB subtypes, that can be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pG3myc), and synapses/immunological processes (pSHHs, pG3 and pG4). Multiomic analysis reveals different conservation levels of proteome features across MB subtypes at the DNA methylome level. Aggressive pGroup3myc MBs and favorable pWNT MBs are most similar in cluster hierarchies concerning overall proteome patterns but show different protein abundances of the vincristine resistance-associated multiprotein complex TriC/CCT and of N-glycan turnover-associated factors. The N-glycome reflects proteome subtypes and complex-bisecting N-glycans characterize pGroup3myc tumors. Our results shed light on targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures.

Abstract Background Emerging adults aged 18–30 years face challenges during life transitions, with an added burden of navigating the health care system and additional costs associated with diabetes. This stress is compounded by overall low levels of health insurance literacy in this population, as people may not know about available financial and health care resources to minimize suboptimal diabetes outcomes. This study aimed to tailor a financial and health insurance toolkit to emerging adults with type 1 diabetes, including racially, ethnically diverse, and Medicaid-insured individuals, through community-based participatory action research. Methods An academic research team and community members from a national organization held six online community advisory board (CAB) content-creation meetings to understand how to tailor a financial and health insurance Toolkit. The CAB was comprised of six racially and insurance-diverse emerging adults with type 1 diabetes and four content experts (clinical, financial, and insurance). Six 60-minute online CAB meetings were held via University Hospitals (UH)-encrypted Zoom over five months. Pre-reading materials were emailed to CAB members before the meetings. A moderator established the purpose of each meeting and briefly discussed meeting rules before each meeting commenced. During the meetings, the moderator guided the discussions and provided the CAB members opportunities to respond and build on one another’s feedback. A deductive thematic qualitative analysis was utilized. Three researchers independently coded the cross-referenced and de-identified CAB meeting transcripts and then convened to reach a group consensus. Two CAB members performed member-checking. Results The following key themes emerged to tailor the Toolkit: ensuring that content covers empowerment and self-advocacy, including genuine stories and multimedia visuals for aesthetics, addressing clinician bias, acknowledging racial and ethnic disparities in care, incorporating cultural representation, and demystifying Medicaid stigma. Conclusions By successfully partnering with the CAB and a community organization through a community-based participatory action research approach, we will develop a financial and health insurance Toolkit tailored to the needs of racially and ethnically diverse and Medicaid-insured emerging adults with type 1 diabetes.

Abstract Engaging local communities is pivotal for wildlife conservation beyond protected areas, aligning with the 30 × 30 target of the Kunming-Montreal Global Biodiversity Framework. We assessed the effectiveness of 33 offtake indicators, derived from hunter declarations, in monitoring the status and extent of degradation of hunted wildlife sourced from camera trap surveys and faunal composition analysis. The rodents:ungulates ratio in offtake and the mean body mass of total offtake emerged as practical and robust indicators of faunal degradation within hunting systems, with significant potential for broader application in similar tropical forest environments. Our findings provide a blueprint for managing and conserving natural resources in tropical regions through community-based initiatives. Involving local stakeholders ensures sustainable wildlife use and fosters ownership and responsibility. This study advances conservation efforts, bridging scientific rigor with community engagement for effective biodiversity preservation.

Abstract Background Lack of physical activity is a concern for children across diverse backgrounds, particularly affecting those in rural areas who face distinct challenges compared to their urban counterparts. Community-derived interventions are needed that consider the unique context and additional physical activity barriers in under-resourced rural settings. Therefore, a prospective pre-post pilot/feasibility study of Hoosier Sport was conducted over 8-weeks with 6th and 7th grade children in a low-socioeconomic rural middle school setting. The primary objective of the present study was to assess trial- and intervention-related feasibility indicators; and the secondary objective was to collect preliminary assessment data for physical activity levels, fitness, psychological needs satisfaction, and knowledge of physical activity and nutrition among participating youth. Methods This prospective 8-week pilot/feasibility study took place in the rural Midwestern United States where twenty-four middle school students participated in a mixed-methods pre-post intervention during physical education classes. The intervention included elements like sport-based youth development, individualized goal setting, physical activity monitoring, pedometer usage, and health education. Data were collected at baseline (T1) and post-intervention (T3), with intermediate measures during the intervention (T2). Qualitative data were integrated through semi-structured interviews. Analytical methods encompassed descriptive statistics, correlations, repeated measures ANOVA, and thematic analysis. Results Key findings indicate robust feasibility, with intervention-related scores (FIM, AIM, and IAM) consistently surpassing the “good” threshold and 100% retention and recruitment success. Additionally, participants showed significant physical performance improvement, shifting from the 25th to the 50th percentile in the 6-minute walk test (p

The Early Christian churches of the Late Antique hilltop settlement in Lavant (Lienz, Austria) have been investigated for almost a century. In recent years (2017–2021), a large conservation campaign took place within the ruins of the so-called Episcopal Church. During this campaign, it was possible to carry out targeted excavations inside the Early Christian church to understand the consecutive building phases and their dating better. In addition to new insights into the history of the building, several new finds also came from these excavation campaigns, providing further information about the church’s interior. In the following, all objects associated with lighting are presented.

The COVID-19 pandemic caused major disruptions to healthcare services in 2020, delaying cancer diagnosis and treatment. While early-stage thyroid cancer often progresses slowly, it is crucial to determine whether treatment delays associated with the pandemic have impacted the clinical presentation and management of advanced-stage thyroid cancer. The purpose of our study was to determine the impact of the early COVID-19 pandemic on thyroid cancer presentation and treatment times. Utilizing the National Cancer Database, chi-squared tests and regression analyses were performed to compare patient demographic and clinical characteristics over time for 56,011 patients diagnosed with primary thyroid cancer who were treated at the Commission on Cancer-accredited sites in 2019 and 2020. We found that thyroid cancer diagnoses decreased between 2019 and 2020, with the biggest drop among patients with cT1 disease relative to other T stages. We also found that patients diagnosed with thyroid cancer in 2020 had similar treatment times to patients diagnosed in 2019, as measured by both the time between diagnosis and start of treatment and the time between surgery and start of radioactive iodine therapy. Overall, our study suggests that resources during the pandemic were allocated to patients with advanced thyroid disease, despite a decrease in diagnoses.

Abstract Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. In this regard, there is the potential for death. Additionally, the rise in fake Xanax tablets containing etizolam and other counterfeit medications has been exacerbated by the difference in regulations regarding these substances in different countries as well as the illegal drug trade. Healthcare providers may also play a role through the over- or underprescribing of certain medications. Thus, in order to combat the rise in counterfeit medications such as fake Xanax, international cooperation, regulation, and enforcement of laws pertaining to the manufacture, prescription, and distribution of these substances are needed.

Abstract Background Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined. Methods This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy. Results Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher’s Exact). Conclusions Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.

Background and ObjectivesAccurate diagnosis of cardiovascular diseases often relies on the electrocardiogram (ECG). Since the cardiac vector is located within a three-dimensional space and the standard ECG comprises 12 projections or leads derived from it, redundant information is inherently present. This study aims to quantify this redundancy and its impact on classification tasks using Convolutional Neural Networks (CNNs) in cardiovascular diseases.MethodsWe employed signal theory and mutual information to introduce a novel redundancy metric and explored techniques for redundancy augmentation and reduction. This involved lead selection and transformation to evaluate the effects on neural network performance.ResultsOur findings indicate that optimizing input configurations through redundancy reduction techniques can enhance the performance of deep learning models in cardiovascular diagnostics, provided that the information is preserved and minimally distorted.ConclusionFor the first time, this research has quantified the redundancy present in the input by validating various redundancy reduction techniques using a CNN. This discovery paves the way for advancing biomedical signal processing research, simplifying model complexity, and enhancing diagnostic performance in cardiovascular medicine within reduced lead systems, such as Holter monitors or wearables.

Multiple external stressors are known to have adverse impacts on health and development. Certain groups are more vulnerable and/or more likely to be exposed to environmental, psychological, and social stressors simultaneously. Yet, few studies have examined combined exposure to environmental toxicants and psychosocial stress. Here, we integrated environmental chemical exposure data collected using silicone wristbands and self-report social stressor data within the Brain and Early Experience (BEE) perinatal cohort to understand co-exposure to environmental chemicals and social stress. Silicone wristbands were worn for one week by mothers throughout central North Carolina who were 6 months postpartum (n = 97). Exposure to 110 environmental chemicals across eight chemical classes was quantified on silicone wristbands using gas chromatography mass spectrometry. Social stress was evaluated using eight established self-report questionnaires (e.g., Brief Symptom Inventory, Perceived Stress Scale), quantifying experiences such as race-related stress, economic strain, and relationship conflict. Hair cortisol levels were measured as an additional metric of stress. The chemical exposure landscape and associations among chemical exposure, demographic characteristics, and social stress were characterized through individual variable analyses, cluster and data reduction, and compiled scoring approaches to comprehensively evaluate chemical and social stress burdens. We found that chemicals contain co-occurring patterns largely based on chemical class, with phthalates representing the chemical class with highest exposure and polychlorinated biphenyls the lowest. Chemicals showed differential exposure across racial groups, with diethyl phthalate, triphenyl phosphate, and tris(3,5-dimethyl phenyl) phosphate at higher levels in Black participants compared with White participants. Integrating social stressor profiling with chemical exposure data identified one particularly vulnerable subset of participants in which high chemical exposure burden coincided with high experiences of racism and economic stress. These findings demonstrate co-occurring chemical and social stress, warranting further investigation to better understand how these combined stressors may contribute to disparities in maternal and child health.

Abstract Two decades into its tenure as a field, dissemination and implementation (D&I) scientists have begun a process of self-reflection, illuminating a missed opportunity to bridge the gap between research and practice—one of the field’s foundational objectives. In this paper, we, the authors, assert the research-to-practice gap has persisted, in part due to an inadequate characterization of roles, functions, and processes within D&I. We aim to address this issue, and the rising tension between D&I researchers and practitioners, by proposing a community-centered path forward that is grounded in equity. We identify key players within the field and characterize their unique roles using the translational science spectrum, a model originally developed in the biomedical sciences to help streamline the research-to-practice process, as a guide. We argue that the full translational science spectrum, from basic science research, or “T0,” to translation to community, or “T4,” readily applies within D&I and that in using this framework to clarify roles, functions, and processes within the field, we can facilitate greater collaboration and respect across the entire D&I research-to-practice continuum. We also highlight distinct opportunities (e.g., changes to D&I scientific conference structures) to increase regular communication and engagement between individuals whose work sits at different points along the D&I translational science spectrum that can accelerate our efforts to close the research-to-practice gap and achieve the field’s foundational objectives.

Abstract Background The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) simultaneously profiles the RNA transcriptome and the surface protein expression. The surface protein markers in CITE-Seq can be used to identify cell populations similar to the iterative filtration process in flow cytometry, also called “gating”, and is an essential step for downstream analyses and data interpretation. While several packages allow users to interactively gate cells, they often do not process multi-omic sequencing datasets and may require writing redundant code to specify gate boundaries. To streamline the gating process, we developed CITEViz which allows users to interactively gate cells in Seurat-processed CITE-Seq data. CITEViz can also visualize basic quality control (QC) metrics allowing for a rapid and holistic evaluation of CITE-Seq data. Results We applied CITEViz to a peripheral blood mononuclear cell CITE-Seq dataset and gated for several major blood cell populations (CD14 monocytes, CD4 T cells, CD8 T cells, NK cells, B cells, and platelets) using canonical surface protein markers. The visualization features of CITEViz were used to investigate cellular heterogeneity in CD14 and CD16-expressing monocytes and to detect differential numbers of detected antibodies per patient donor. These results highlight the utility of CITEViz to enable the robust classification of single cell populations. Conclusions CITEViz is an R-Shiny app that standardizes the gating workflow in CITE-Seq data for efficient classification of cell populations. Its secondary function is to generate basic feature plots and QC figures specific to multi-omic data. The user interface and internal workflow of CITEViz uniquely work together to produce an organized workflow and sensible data structures for easy data retrieval. This package leverages the strengths of biologists and computational scientists to assess and analyze multi-omic single-cell datasets. In conclusion, CITEViz streamlines the flow cytometry gating workflow in CITE-Seq data to help facilitate novel hypothesis generation.

Abstract Given the ongoing environmental degradation from local to global scales, it is fundamental to develop more efficient means of gathering data on species and ecosystems. Local ecological knowledge, in which local communities can consistently provide information on the status of animal species over time, has been shown to be effective. Several studies demonstrate that data gathered using local ecological knowledge (LEK)‐based methods are comparable with data obtained from conventional methods (such as line transects and camera traps). Here, we employ a consensus analysis to validate and evaluate the accuracy of interview data on LEK. Additionally, we investigate the influence of social and bioecological variables on enhancing data quality. We interviewed 323 persons in 19 villages in the Western and Central Amazon to determine the level of consensus on the abundance of hunted and non‐hunted forest species. These villages varied in size, socio‐economic characteristics and in the experience with wildlife of their dwellers. Interviewees estimated the relative abundance of 101 species with a broad spectrum of bioecological characteristics using a four‐point Likert scale. High consensus was found for species population abundance in all sampled villages and for 79.6% of interviewees. The village consensus of all species abundance pooled was negatively correlated with village population size. The consensus level was high regardless of the interviewees' hunting experience. Species that are more frequently hunted or are more apparent had greater consensus values; only two species presented a low consensus level, which are rare and solitary species. We show in our study in the Amazon that information gathered by local peoples, Indigenous as well as non‐Indigenous, can be useful in understanding the status of animal species found within their environment. The high level of cultural consensus we describe likely arises from knowledge sharing and the strong connection between the persons interviewed and the forest. We suggest that consensus analysis can be used to validate LEK‐generated data instead of comparing these types of data with information obtained by conventional methods. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Objective Female representation in the field of otolaryngology is lacking. Residency is the first point at which medical school graduates specialize in a chosen field and thus represents an opportunity to recruit and train more female otolaryngologists. This study sought to identify program factors associated with greater female representation among resident physicians. Methods Departmental websites of all 124 otolaryngology residency programs in the United States and Puerto Rico were examined for a list of residents. For programs with a resident roster available, the genders of residents, faculty, program directors, and chairpersons were recorded. Location and city population for each program was also recorded, as was female resident representation. Programs were compared using Pearson Chi‐squared univariate tests. Results 1,632 residents and 2,605 faculty were included in the analysis of 109 programs. The median female resident representation was 40%. Programs with larger faculty sizes, more female faculty, and urban location were associated with an above‐median female resident representation. Programs with a larger residency cohort approached significance regarding above‐median female resident representation. Higher female faculty representation, program director gender, chairperson gender, and US region were not associated with variation in female resident representation. Conclusions Greater female otolaryngology residency representation was associated with programs having an urban location and greater numbers of female and total faculty. It was also likely that a larger resident cohort size may affect female resident representation. The proportions of female faculty, program director, and chairperson gender, as well as the US region, were not associated with variation in female resident gender representation.

Abstract Background Sinusitis is a common diagnosis that can be erroneously associated with routine weather‐related barometric pressure changes. In actuality, these pressure changes likely exacerbate migraine headaches, which can cause facial pain and pressure rather than true sinus inflammation. Objective The present study sought to characterize the representation of both sinusitis and migraine in association with barometric pressure changes across websites on the Internet. Methods An Internet search for relevant terms was conducted, and content of the resulting pages was assessed for associations between weather‐related pressure changes and either sinusitis or migraine. Variations in reported results across different subtypes of Internet sources were analyzed. The primary outcomes measured were (1) whether a given media source associated barometric weather changes with sinusitis, (2) whether that source associated barometric weather changes with migraine, and (3) treatment options offered by that source. Results Of the 116 included webpages, 36 (31.03%) associated sinusitis and routine barometric pressure changes. Of these, 10 (27.77%) were otolaryngology practice sites. Sixty‐seven webpages (57.76%) associated migraine and routine barometric pressure changes. Of these, nonotolaryngology webpages were more likely to report this link. Conclusions Otolaryngology practice sites were observed to be the most frequent professional medical resource reporting the unsubstantiated claim that routine barometric pressure changes are associated with sinusitis. Nonotolaryngology sources were more likely to link weather‐related pressure changes to migraine. These results suggest that opportunities exist for otolaryngology practice sites to educate patients about nonrhinogenic headache etiologies.

Abstract Floods and droughts are hydrological extremes that impact ecosystems, agriculture, and human well-being. These extremes are expected to intensify in a warmer world, although many regions lack the observations needed to place current trends in the context of long-term variability. Here we present a new multi-century record of tropical rainfall based on a multi-proxy approach from northern Great Barrier Reef coral. The robust calibration with instrumental rainfall allows us to quantitatively estimate summer rainfall in northern Queensland back to 1746 CE. We find that as global climate warmed, wet-season rainfall in this region has increased by ~10% since 1750 and the standard deviation (21-yr 1-σ) of wet-season rainfall more than doubled, as rainy years became much wetter, while dry years remained dry. Reconstructed rainfall correlates with El Niño indices and the link to Pacific temperature variability has strengthened as climate warmed, consistent with expected intensification of La Niña-related rainfall.

Abstract Purpose The significance of regular physical activity (PA) in reducing cardiovascular disease (CVD) risk is widely acknowledged. However, children in rural areas encounter specific barriers to PA compared to their urban counterparts. This study employs human-centered participatory co-design, involving community stakeholders in developing a multi-level PA intervention named Hoosier Sport. The primary hypothesis is the co-design sessions leading to the development of a testable intervention protocol. Methods Two co-design teams, each consisting of six children and six adults, were formed using human-centered participatory co-design facilitated by research faculty and graduate students. The process involved five co-design sessions addressing problem identification, solution generation, solution evaluation, operationalization, and prototype evaluation. Thematic analysis was employed to identify key themes and intervention components. Results Child co-designers (n = 6) ranged from 6th to 8th grade, averaging 12.6 years (SD = 1.8), while adult co-designers (n = 6) averaged 43.3 years (SD = 8.08). Thematic analysis revealed children emphasizing autonomy, the freedom to choose physical and non-physical activities, and the importance of building peer relationships during PA. Adult interviews echoed the importance of autonomy and choice in activities, with a focus on relatedness through positive role modeling. Conclusion The prototype intervention and implementation strategies developed constitute a testable intervention aligned with Phase 1 of the ORBIT model. This testable prototype lays the groundwork for a collaborative campus-community partnership between the university and the local community, ensuring mutual benefits and sustainable impact.

Background Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs. Methods We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae. Results Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast. Conclusions The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in ‘hotspot’ areas.

Abstract Background Antibiotic overuse at hospital discharge is common, costly, and harmful. While discharge-specific antibiotic stewardship interventions are effective, they are resource-intensive and often infeasible for hospitals with resource constraints. This weakness impacts generalizability of stewardship interventions and has health equity implications as not all patients have access to the benefits of stewardship based on where they receive care. There may be different pathways to improve discharge antibiotic prescribing that vary widely in feasibility. Supporting hospitals in selecting interventions tailored to their context may be an effective approach to feasibly reduce antibiotic overuse at discharge across diverse hospitals. The objective of this study is to evaluate the effectiveness of the Reducing Overuse of Antibiotics at Discharge Home multicomponent implementation strategy (“ROAD Home”) on antibiotic overuse at discharge for community-acquired pneumonia and urinary tract infection. Methods This 4-year two-arm parallel cluster-randomized trial will include three phases: baseline (23 months), intervention (12 months), and postintervention (12 months). Forty hospitals recruited from the Michigan Hospital Medicine Safety Consortium will undergo covariate-constrained randomization with half randomized to the ROAD Home implementation strategy and half to a “stewardship as usual” control. ROAD Home is informed by the integrated-Promoting Action on Research Implementation in Health Services Framework and includes (1) a baseline needs assessment to create a tailored suite of potential stewardship interventions, (2) supported decision-making in selecting interventions to implement, and (3) external facilitation following an implementation blueprint. The primary outcome is baseline-adjusted days of antibiotic overuse at discharge. Secondary outcomes include 30-day patient outcomes and antibiotic-associated adverse events. A mixed-methods concurrent process evaluation will identify contextual factors influencing the implementation of tailored interventions, and assess implementation outcomes including acceptability, feasibility, fidelity, and sustainment. Discussion Reducing antibiotic overuse at discharge across hospitals with varied resources requires tailoring of interventions. This trial will assess whether a multicomponent implementation strategy that supports hospitals in selecting evidence-based stewardship interventions tailored to local context leads to reduced overuse of antibiotics at discharge. Knowledge gained during this study could inform future efforts to implement stewardship in diverse hospitals and promote equity in access to the benefits of quality improvement initiatives. Trial registration Clinicaltrials.gov NCT06106204 on 10/30/23

Abstract Parkinson’s disease (PD) is a common age-related neurodegenerative disorder characterized by the aggregation of α-Synuclein (αSYN) building up intraneuronal inclusions termed Lewy pathology. Mounting evidence suggests that neuron-released αSYN aggregates could be central to microglial activation, which in turn mounts and orchestrates neuroinflammatory processes potentially harmful to neurons. Therefore, understanding the mechanisms that drive microglial cell activation, polarization and function in PD might have important therapeutic implications. Here, using primary microglia, we investigated the inflammatory potential of pure αSYN fibrils derived from PD patients. We further explored and characterized microglial cell responses to a chronic-type inflammatory stimulation combining PD patient-derived αSYN fibrils (FPD), Tumor necrosis factor-α (TNFα) and prostaglandin E2 (PGE2) (TPFPD). We showed that FPD hold stronger inflammatory potency than pure αSYN fibrils generated de novo. When combined with TNFα and PGE2, FPD polarizes microglia toward a particular functional phenotype departing from FPD-treated cells and featuring lower inflammatory cytokine and higher glutamate release. Whereas metabolomic studies showed that TPFPD-exposed microglia were closely related to classically activated M1 proinflammatory cells, notably with similar tricarboxylic acid cycle disruption, transcriptomic analysis revealed that TPFPD-activated microglia assume a unique molecular signature highlighting upregulation of genes involved in glutathione and iron metabolisms. In particular, TPFPD-specific upregulation of Slc7a11 (which encodes the cystine-glutamate antiporter xCT) was consistent with the increased glutamate response and cytotoxic activity of these cells toward midbrain dopaminergic neurons in vitro. Together, these data further extend the structure–pathological relationship of αSYN fibrillar polymorphs to their innate immune properties and demonstrate that PD-derived αSYN fibrils, TNFα and PGE2 act in concert to drive microglial cell activation toward a specific and highly neurotoxic chronic-type inflammatory phenotype characterized by robust glutamate release and iron retention.

Introduction: Antifungal prophylaxis is an important preventative strategy for high-risk pediatric oncology patients. When triazoles are contraindicated, micafungin is an alternative to polyenes, due to improved tolerability and limited drug-drug interactions. An intermittent dosing schedule is advantageous for outpatient parenteral antimicrobial therapy (OPAT), but studies assessing safety in pediatric patients are limited. Methods: This single-centre, retrospective, observational study compared the safety and tolerability of daily (1 mg/kg) and intermittent (3 mg/kg) dosing of amphotericin B liposomal (AmB) and micafungin in children under 18 years, with high-risk leukemia. ResultsOf 51 patients, with 76 individual dosing schedules, hepatoxicity and nephrotoxicity were comparable across all four dosing schedules. Severity of hypokalemia was significantly higher amongst patients receiving AmB (p = 0.041), with higher rates of intravenous electrolyte supplementation required. Infusion-related reactions occurred only in the AmB group (22 %). Intermittent administration and dosing of micafungin was well tolerated, with similar effects on liver function and reduced rates of hypokalemia. Conclusion: This study supports the positive safety profile of intermittent micafungin compared with AmB and describes successful OPAT implementation. Prospective studies assessing efficacy are needed to validate these findings.

ABSTRACTEmerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14–60 days and 121–180 days was 52.7% (46.9–57.8%) and 35.5% (−2.8–59.5%) for infection, and 59.3% (49.7–67.0%) and 33.2% (−28.2–68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9–85.1%) and 52.0% (−1.2–77.3%) at 14–60 days and 61–120 days, respectively. rVE against XBB at 14–60 days and 121–180 days was 48.8% (33.4–60.7%) and −3.9% (−18.1–11.3%) for infection, 70.7% (52.4–82.0%) and 15.7% (−6.0–33.2%) for ED/UC encounters, and 87.9% (43.8–97.4%) and 57.1% (17.0–77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

ABSTRACT Hematophagous Stomoxys (stable) fly populations in dairy barns are sustained by a constant availability of cattle hosts and manure, which serve as major reservoirs of both zoonotic and opportunistic bacterial pathogens. However, the composition of the Stomoxys fly microbiota, the mechanisms by which flies acquire their microbiome, and the ability of potentially pathogenic bacteria to colonize and persist in fly hosts remain to be investigated. Here, we longitudinally collected fly and manure samples from two connected dairy facilities. High throughput 16S rRNA gene amplicon sequencing was then used to characterize and compare bacterial communities present on or within flies and in manure collected from the same facility, while culture-dependent methods were used to verify the viability of clinically relevant bacteria. Bacterial alpha diversity was overall higher in manure samples as compared to fly samples, with manure-associated bacterial communities being dominated by members of the Bacteroidales, Eubacteriales, and Oscillospirales. In contrast, flies harbored relatively low-complexity communities dominated by members of the Enterobacterales, Staphylococcales, and Lactobacillales. Clinically relevant bacterial strains, including Escherichia spp. and other taxa associated with mastitic cows housed in the same facilities, were detected in paired fly and manure samples but exhibited dramatically elevated abundances in fly samples as compared to manure samples. Viable colonies of Escherichia, Klebsiella, and Staphylococcus spp. were also readily isolated from fly samples, confirming that flies harbor culturable mastitis-associated bacteria. This study identifies biting flies as bona fide carriers of opportunistically pathogenic bacterial taxa on dairy farms.IMPORTANCEDisease prevention on dairy farms has significant implications for cattle health, food security, and zoonosis. Of particular importance is the control of bovine mastitis, which can be caused by diverse bacteria, including Klebsiella, Escherichia coli, Streptococcus, and Staphylococcus spp. Despite being one of the most significant and costly cattle diseases worldwide, the epidemiology of bovine mastitis is not well understood. This study provides parallel culture-independent and culture-dependent evidence to support the carriage of opportunistically pathogenic bacteria by Stomoxys flies on dairy farms. We further show that the fly microbiota is enriched in clinically relevant taxa—the vast majority of which can be traced to the manure habitats in which flies breed. Altogether, our results identify biting flies as underrecognized carriers of bacterial taxa associated with environmental bovine mastitis and other opportunistic infections in vertebrates and offer important insights into mechanisms of microbial acquisition by these and other medically important insects.

Background and aimsSYNGAP1-related disorder (SYNGAP1-RD) is a prevalent genetic form of Autism Spectrum Disorder and Intellectual Disability (ASD/ID) and is caused by de novo or inherited mutations in one copy of the SYNGAP1 gene. In addition to ASD/ID, SYNGAP1 disorder is associated with comorbid symptoms including treatment-resistant-epilepsy, sleep disturbances, and gastrointestinal distress. Mechanistic links between these diverse symptoms and SYNGAP1 variants remain obscure, therefore, our goal was to generate a zebrafish model in which this range of symptoms can be studied.MethodsWe used CRISPR/Cas9 to introduce frameshift mutations in the syngap1a and syngap1b zebrafish duplicates (syngap1ab) and validated these stable models for Syngap1 loss-of-function. Because SYNGAP1 is extensively spliced, we mapped splice variants to the two zebrafish syngap1a and b genes and identified mammalian-like isoforms. We then quantified locomotory behaviors in zebrafish syngap1ab larvae under three conditions that normally evoke different arousal states in wild-type larvae: aversive, high-arousal acoustic, medium-arousal dark, and low-arousal light stimuli.ResultsWe show that CRISPR/Cas9 indels in zebrafish syngap1a and syngap1b produced loss-of-function alleles at RNA and protein levels. Our analyses of zebrafish Syngap1 isoforms showed that, as in mammals, zebrafish Syngap1 N- and C-termini are extensively spliced. We identified a zebrafish syngap1 α1-like variant that maps exclusively to the syngap1b gene. Quantifying locomotor behaviors showed that syngap1ab mutant larvae are hyperactive compared to wild-type but to differing degrees depending on the stimulus. Hyperactivity was most pronounced in low arousal settings, and hyperactivity was proportional to the number of mutant syngap1 alleles.LimitationsSyngap1 loss-of-function mutations produce relatively subtle phenotypes in zebrafish compared to mammals. For example, while mouse Syngap1 homozygotes die at birth, zebrafish syngap1ab−/− survive to adulthood and are fertile, thus some aspects of symptoms in people with SYNGAP1-Related Disorder are not likely to be reflected in zebrafish.ConclusionOur data support mutations in zebrafish syngap1ab as causal for hyperactivity associated with elevated arousal that is especially pronounced in low-arousal environments.

ABSTRACT Clorobiocin is a well-known, highly effective inhibitor of DNA gyrase belonging to the aminocoumarin antibiotics. To identify potentially novel derivatives of this natural product, we conducted an untargeted investigation of clorobiocin biosynthesis in the known producer Streptomyces roseochromogenes DS 12.976 using LC-MSE, molecular networking, and analysis of fragmentation spectra. Previously undescribed clorobiocin derivatives uncovered in this study include bromobiocin, a variant halogenated with bromine instead of chlorine, hydroxylated clorobiocin, carrying an additional hydroxyl group on its 5-methyl-pyrrole 2-carboxyl moiety, and two other derivatives with modifications on their 3-dimethylallyl 4-hydroxybenzoate moieties. Furthermore, we identified several compounds not previously considered clorobiocin pathway products, which provide new insights into the clorobiocin biosynthetic pathway. By supplementing the medium with different concentrations of potassium bromide, we confirmed that the clorobiocin halogenase can utilize bromine instead of chlorine. The reaction, however, is impeded such that non-halogenated clorobiocin derivatives accumulate. Preliminary assays indicate that the antibacterial activity of bromobioin against Bacillus subtilis and efflux-impaired Escherichia coli matches that of clorobiocin. Our findings emphasize that yet unexplored compounds can be discovered from established strains and biosynthetic gene clusters by means of metabolomics analysis and highlight the utility of LC-MSE-based methods to contribute to unraveling natural product biosynthetic pathways.IMPORTANCEThe aminocoumarin clorobiocin is a well-known gyrase inhibitor produced by the gram-positive bacterium Streptomyces roseochromogenes DS 12.976. To gain a deeper understanding of the biosynthetic pathway of this complex composite of three chemically distinct entities and the product spectrum, we chose a metabolite-centric approach. Employing high-resolution LC-MSE analysis, we investigated the pathway products in extracted culture supernatants of the natural producer. Novel pathway products were identified that expand our understanding of three aspects of the biosynthetic pathway, namely the modification of the noviose, transfer and methylation of the pyrrole 2-carboxyl moiety, and halogenation. For the first time, brominated products were detected. Their levels and the levels of non-halogenated products increased in medium supplemented with KBr. Based on the presented data, we propose that the enzyme promiscuity contributes to a broad product spectrum.

The modernization and intensification of fishing practices have raised the threat to sea turtles, with escalating unintentional captures endangering turtles of all life stages. In this study, we examined the impact of artisanal fishing on sea turtles in two coastal regions of Angola, southern Africa. Between August 2015 - March 2016, through participatory monitoring (n = 8) and interviews with fishers (n= 41), we documented unintentional turtle captures occurring year-round during fishing activities. A total of 405 turtles, 403 olive ridley (Lepidochelys olivacea) and 2 green (Chelonia mydas), were caught in gillnets by fishers engaged in participatory monitoring. Net characteristics, including length and proximity to the shoreline, as reported by the interviewed fishers, correlated with those used by the monitoring group. We estimated approximately 1219 turtles captured by the 41 interviewed fishers over the 8-month study period. Most captures occurred within 100 m from the shoreline. The likelihood of accidental turtle captures increased significantly with proximity to the beach, larger mesh sizes, and greater net lengths and number of hauls. We calculated a survival rate of 41%, and a mortality rate of 59% for captured turtles. Number of turtles caught as bycatch varied throughout the year, with the highest Catch Per Unit Effort (CPUE) reported for Oct. – Dec. Since this period aligns with the nesting season, most captured turtles are likely to be females. The high mortality rate reported in this study emphasizes the immediate threat posed by accidental captures to sea turtle populations, underscoring the critical importance of conservation efforts, particularly in artisanal gillnet fisheries.

Background: Autoimmune diseases have been linked to an increased risk of pregnancy-related complications. A family history of autoimmune diseases may be related to the risk of childhood cancer based on similar histocompatibility antigens. We utilized data from national registries in Denmark to examine associations between maternal autoimmune disease and cancer in their offspring. Methods: We linked data from several national registries in Denmark to identify childhood cancer cases in children

Abstract Animal movement is increasingly affected by human alterations to habitat and climate change. In wetland systems, widespread hydrologic alterations from agriculture have changed the shape, function, and stability of shallow streams and wetland habitats. These changes in habitat quality and quantity may be especially consequential for freshwater fishes such as Grass Pickerel (Esox americanus vermiculatus), a small predatory fish found in disjunct populations across southern Ontario and listed as Special Concern under Canada’s Species at Risk Act. To characterize Grass Pickerel movement response to stream-channel alterations, Fisheries and Oceans Canada implemented a tracking study to monitor the movements of a Grass Pickerel population in an agricultural drain on the Niagara Peninsula (Ontario, Canada). From 2009 to 2013, 2007 Grass Pickerel were tagged and tracked in the 37.3 km2 Beaver Creek watershed using a combination of mark-recapture surveys and eight fully automated passive integrated transponder tag antennas. Most individuals moved within 500 m (i.e., stationary fish) while 16% of the fish moved > 500 m (i.e., mobile fish), with a maximum median movement distance of 1.89 km and a maximum movement distance of 13.5 km (a long-tail distribution). Most movements occurred near the largest confluence where only a few were long-distance upstream or downstream movements. Mobile fish were larger than their stationary counterparts. Grass Pickerel in sites with higher abundance had more mobile fish, implying potential density dependence. Our results highlight that, while a long-distance dispersal ability exists in extant Grass Pickerel populations, the current conditions of riverscapes may prevent these dispersals from occurring. For declining Grass Pickerel populations, limitations to their movement ecology may substantially increase the likelihood of local extirpations.

Background In this secondary analysis of the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST‐D) study we used antidepressant response trajectories to assess the association of treatment and multiple clinical/demographic factors with the probability of response. Methods Using data from VAST‐D, a multi‐site, randomized, single‐blind trial with parallel‐assignment to one of three treatment interventions in 1522 Veterans whose major depressive disorder was unresponsive to at least one antidepressant trial, we evaluated response patterns using group‐based trajectory modeling (GBTM). A weighted multinomial logistic regression analysis with backward elimination and additional exploratory analyses were performed to evaluate the association of multiple clinical/demographic factors with the probability of inclusion into specific trajectories. Additional exploratory analyses were used to identify factors associated with trajectory group membership that could have been missed in the primary analysis. Results GBTM showed the best fit for depression symptom change was comprised of six trajectories, with some trajectories demonstrating minimal improvement and others showing a high probability of remission. High baseline depression and anxiety severity scores decreased, and early improvement increased, the likelihood of inclusion into the most responsive trajectory in both the GBTM and exploratory analyses. Conclusion While multiple factors influence responsiveness, the probability of inclusion into a specific depression symptom trajectory is most strongly influenced by three factors: baseline depression, baseline anxiety, and the presence of early improvement.

Plastic pollution is ubiquitous, and the Arctic is no exception. One important step to understand the extent of the problem, and to monitor its impact is to have repeatable, comparable, and relevant measures across time and space that allow for the detection of marine litter trends. Arctic shorelines are a critical part of monitoring efforts. Pan-Arctic monitoring of litter on shorelines is also an essential component to examine global trends. Based on previous work examining litter in some regions of the Arctic, we suggest steps towards more harmonized protocols that include community-based monitoring, crowdsourced science programs, and science team-based surveys that are specific for the Arctic. Specifically, we recommend that shoreline survey sites for long-term monitoring be established where possible and be at least 50 m and surveys carried out at regular intervals of at least twice a year by any type of research team. Criteria for the selection of sites should be grounded in Indigenous and other local community and regional priorities, and should result in representation of both remote shorelines impacted by distant-source marine litter and shorelines impacted by more local sources. Results of any Arctic shoreline litter surveys should be made regularly available either through publications which include data sets, and/or accessible databases to promote regional comparisons and trend analysis across the pan-Arctic.

Abstract Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by cell-type-specific tau lesions in neurons and glia. Prior work uncovered transcriptome changes in human PSP brains, although their cell-specificity is unknown. Further, systematic data integration and experimental validation platforms to prioritize brain transcriptional perturbations as therapeutic targets in PSP are currently lacking. In this study, we combine bulk tissue (n = 408) and single nucleus RNAseq (n = 34) data from PSP and control brains with transcriptome data from a mouse tauopathy and experimental validations in Drosophila tau models for systematic discovery of high-confidence expression changes in PSP with therapeutic potential. We discover, replicate, and annotate thousands of differentially expressed genes in PSP, many of which reside in glia-enriched co-expression modules and cells. We prioritize DDR2, STOM, and KANK2 as promising therapeutic targets in PSP with striking cross-species validations. We share our findings and data via our interactive application tool PSP RNAseq Atlas ( https://rtools.mayo.edu/PSP_RNAseq_Atlas/ ). Our findings reveal robust glial transcriptome changes in PSP, provide a cross-species systems biology approach, and a tool for therapeutic target discoveries in PSP with potential application in other neurodegenerative diseases.

Abstract Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53 Fl/Fl ::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.

Calcium (Ca2+) functions as a universal signal messenger in eukaryotes but in bacteria, the physiological roles for Ca2+ are limited. Here, we examine the role of Ca2+ in Streptococcus pneumoniae during manganese (Mn2+) intoxication. S. pneumoniae mntE mutants, lacking the Mn2+ efflux transporter, exhibit impaired growth due to accumulation of Mn2+ when exposed to elevated exogenous Mn2+. This Mn2+-sensitive growth defect is restored to wild-type growth level by exogenous Ca2+, in a Ca2+-dependent manner. Despite growth restoration of the mntE mutant to wild-type levels, cellular Mn2+ remains elevated in this strain. Bacterial capsule production is also increased for the mntE mutant, resulting in reduced adherence capacity to surfaces and poor biofilm formation, which is consistent with it experiencing Mn2+ intoxication. Ca2+ presence did not significantly impact bacterial capsule production or biofilm formation. Further analysis of the cell morphology demonstrates that Ca2+ contributes to cell division and reduces cell chain lengths. Together, these data describe the first role of Ca in S. pneumoniae that has potential implications in bacterial virulence since Ca affects cell division and likely Mn2+-associated cellular processes.

Medicinal plants take a fundamental place in people's livelihoods. They seem to be a palliative therapeutic option for health problems. The knowledge of traditional uses of plants for healing held by indigenous people is an asset to the valorization of traditional medicine, which is increasingly solicited for the treatment of many diseases. The aim of this research is to improve know-how on plant species employed in the traditional pharmacopoeia practiced by the Baka people, recognized as great healers. Data were collected between 2018 and 2019 from 75 households distributed in five villages in the Mintom subdivision, Southern Region of Cameroon. The so-called popular ethnobotanical survey method was used. One thousand six hundred and thirty-five (1 635) citations and six hundred and five (605) recipes were recorded, involving 210 plant species, distributed in 183 genera and 75 families. A total of 69 health problems were identified and distinguished in 13 groups of diseases. Results reveal that for the same diseases, each village uses its own list of plants. The study area is highly diverse in terms both flora and uses. This paper can therefore be seen as a continuation of the research and development of plants-based medicines. It is also in the line with the import-substitution policy for valorization of Cameroonian.

Background and purpose: Magnetic Resonance Imaging (MRI) guided stereotactic body radiotherapy (SBRT) of liver metastases is an upcoming high-precision non-invasive treatment. Interobserver variation (IOV) in tumor delineation, however, remains a relevant uncertainty for planning target volume (PTV) margins. The aims of this study were to quantify IOV in MRI-based delineation of the gross tumor volume (GTV) of liver metastases and to detect patient-specific factors influencing IOV. Materials and methods: A total of 22 patients with liver metastases from three primary tumor origins were selected (colorectal(8), breast(6), lung(8)). Delineation guidelines and planning MRI-scans were provided to eight radiation oncologists who delineated all GTVs. All delineations were centrally peer reviewed to identify outliers not meeting the guidelines. Analyses were performed both in- and excluding outliers. IOV was quantified as the standard deviation (SD) of the perpendicular distance of each observer’s delineation towards the median delineation. The correlation of IOV with shape regularity, tumor origin and volume was determined. Results: Including all delineations, average IOV was 1.6 mm (range 0.6–3.3 mm). From 160 delineations, in total fourteen single delineations were marked as outliers after peer review. After excluding outliers, the average IOV was 1.3 mm (range 0.6–2.3 mm). There was no significant correlation between IOV and tumor origin or volume. However, there was a significant correlation between IOV and regularity (Spearman’s ρs = -0.66; p = 0.002). Conclusion: MRI-based IOV in tumor delineation of liver metastases was 1.3–1.6 mm, from which PTV margins for IOV can be calculated. Tumor regularity and IOV were significantly correlated, potentially allowing for patient-specific margin calculation.

Wildfire events are becoming increasingly common across many areas of the United States, including North Carolina (NC). Wildfires can cause immediate damage to properties, and wildfire smoke conditions can harm the overall health of exposed communities. It is critical to identify communities at increased risk of wildfire events, particularly in areas with that have sociodemographic disparities and low socioeconomic status (SES) that may exacerbate incurred impacts of wildfire events. This study set out to: (1) characterize the distribution of wildfire risk across NC; (2) implement integrative cluster analyses to identify regions that contain communities with increased vulnerability to the impacts of wildfire events due to sociodemographic characteristics; (3) provide summary-level statistics of populations with highest wildfire risk, highlighting SES and housing cost factors; and (4) disseminate wildfire risk information via our online web application, ENVIROSCAN. Wildfire hazard potential (WHP) indices were organized at the census tract-level, and distributions were analyzed for spatial autocorrelation via global and local Moran’s tests. Sociodemographic characteristics were analyzed via k-means analysis to identify clusters with distinct SES patterns to characterize regions of similar sociodemographic/socioeconomic disparities. These SES groupings were overlayed with housing and wildfire risk profiles to establish patterns of risk across NC. Resulting geospatial analyses identified areas largely in Southeastern NC with high risk of wildfires that were significantly correlated with neighboring regions with high WHP, highlighting adjacent regions of high risk for future wildfire events. Cluster-based analysis of SES factors resulted in three groups of regions categorized through distinct SES profiling; two of these clusters (Clusters 2 and 3) contained indicators of high SES vulnerability. Cluster 2 contained a higher percentage of younger (

Abstract Nucleation of H2O vapor bubbles in magma requires surpassing a chemical supersaturation threshold via decompression. The threshold is minimized in the presence of a nucleation substrate (heterogeneous nucleation, 100 MPa). The existence of explosively erupted aphyric rhyolite magma staged from shallow (

Abstract We document the presence, composition, and number density (TND) of titanomagnetite nanolites and ultra‐nanolites in aphyric rhyolitic pumice, obsidian, and vesicular obsidian from the 1060 CE Glass Mountain volcanic eruption of Medicine Lake Volcano, California, using magnetic methods. Curie temperatures indicate compositions of Fe2.40Ti0.60O4 to Fe3O4. Rock‐magnetic parameters sensitive to domain state, which is dependent on grain volume, indicate a range of particle sizes spanning superparamagnetic (10 μm) particles. Cylindrical cores drilled from the centers of individual pumice clasts display anisotropy of magnetic susceptibility with prolate fabrics, with the highest degree of anisotropy coinciding with the highest vesicularity. Fabrics within a pumice clast require particle alignment within a fluid, and are interpreted to result from the upward transport of magma driven by vesiculation, ensuing bubble growth, and shearing in the conduit. Titanomagnetite number density (TND) is calculated from titanomagnetite volume fraction, which is determined from ferromagnetic susceptibility. TND estimates for monospecific assemblages of 1,000 nm–10 nm cubes predict 1012 to 1020 m−3 of solid material, respectively. TND estimates derived using a power law distribution of grain sizes predict 1018 to 1019 m−3. These ranges agree well with TND determinations of 1018 to 1020 m−3 made by McCartney et al. (2024), and are several orders of magnitude larger than the number density of bubbles in these materials. These observations are consistent with the hypothesis that titanomagnetite crystals already existed in extremely high number‐abundance at the time of magma ascent and bubble nucleation.

Abstract New results that employ Zr‐in‐rutile thermometry (ZiR) and quartz‐inclusion‐in‐garnet (QuiG) barometry constrain the P–T conditions of garnet formation in blueschists and eclogites from the island of Syros, Greece. QuiG barometry reveals that garnet from different regions across the island formed at pressures ranging from 1.1 to 1.8 GPa and ZiR thermometry on rutile inclusions in garnet constrains the minimum temperature of garnet formation to have been 475–550°C. Most importantly, there is no systematic difference in the conditions of garnet formation from different regions across the island and these results are nearly identical to those obtained from the islands of Sifnos and Ios, Greece. A model is proposed whereby the rocks from all three islands were initially metamorphosed along a relatively shallow geotherm of around 11°C/km to a depth of around 45 km and were then subjected to metamorphism along a geotherm of around 7–8°C/km, which could have been caused by either an increase in the dip of the subduction zone or an increase in the rate of subduction. Garnet formed along this steeper geotherm was accompanied by the release of significant H2O from the breakdown of chlorite over a duration of 1 Ma or less based on thermal and diffusion modeling. It is concluded that rocks from Syros, Sifnos and Ios all followed a similar, roughly counter‐clockwise prograde P–T path and that the present outcrop configuration is largely due to a complex exhumation history.

BackgroundThe Department of Veterans Affairs (VA) Office of Rural Health (ORH) supports national VA program offices' efforts to expand health care to rural Veterans through its Enterprise-Wide Initiatives (EWIs) program. In 2017, ORH selected Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM), an implementation science framework, to structure the EWI evaluation and reporting process. As part of its mandate to improve EWI program evaluation, the Center for the Evaluation of Enterprise-Wide Initiatives conducted a qualitative evaluation to better understand EWI team' perceptions of, and barriers and facilitators to, the EWI evaluation process.MethodsWe conducted 43 semi-structured interviews with 48 team members (e.g., evaluators, program office leads, and field-based leads) representing 21 EWIs from April-December 2020. Questions focused on participants' experiences using strategies targeting each RE-AIM dimension. Interviews were inductively analyzed in MAXQDA. We also systematically reviewed 51 FY19-FY20 EWI annual reports to identify trends in misapplications of RE-AIM.ResultsParticipants had differing levels of experience with RE-AIM. While participants understood ORH's rationale for selecting a common framework to structure evaluations, the perceived misalignment between RE-AIM and EWIs' work emerged as an important theme. Concerns centered around 3 sub-themes: (1) (Mis)Alignment with RE-AIM Dimensions, (2) (Mis)Alignment between RE-AIM and the EWI, and (3) (Mis)Alignment with RE-AIM vs. other Theories, Models, or Frameworks. Participants described challenges differentiating between and operationalizing dimensions in unique contexts. Participants also had misconceptions about RE-AIM and its relevance to their work, e.g., that it was meant for established programs and did not capture aspects of initiative planning, adaptations, or sustainability. Less commonly, participants shared alternative models or frameworks to RE-AIM. Despite criticisms, many participants found RE-AIM useful, cited training as important to understanding its application, and identified additional training as a future need.DiscussionThe selection of a shared implementation science framework can be beneficial, but also challenging when applied to diverse initiatives or contexts. Our findings suggest that establishing a common understanding, operationalizing framework dimensions for specific programs, and assessing training needs may better equip partners to integrate a shared framework into their evaluations.

Background: A personal history of video gaming has been associated with improved laparoscopic skills acquisition in some but not all studies. The impact of playing a musical instrument on laparoscopic or robotic proficiency is less investigated. Methods: This study evaluates the impact of video gaming, playing a musical instrument, and other demographic parameters on robotic simulator proficiency in a cohort of 27 participants. Candidates performed 3 standardized exercises on a virtual reality robotic training platform, resulting in a proficiency score. After completing a detailed survey, participants repeated the standardized exercises to obtain a basic learning curve. Gaming history, playing a musical instrument, surgical experience, and demographic parameters were correlated with overall robotic proficiency and improvement during the experimental session. Results: Participants with previous gaming history had 33 % higher overall robotic performance scores (p = 0.02). There was no difference in performance between surgical trainees and attending physicians with high volume laparoscopic surgery experience (average of 77 laparoscopic procedures). In this small cohort, playing an instrument had no influence overall (p = 0.2), but we found a trend towards increased proficiency in those playing the piano, yielding 30 % higher scores (p = 0.14). Participants performed up to 22 % better in the second run of the ''Suture Sponge'' exercises (p = 0.08), indicating a steep learning curve of simulated robotic surgery. Conclusions: A history of video gaming and playing the piano is associated with improved performance on a virtual-reality robotic surgical simulator. The steep learning curve underlines the benefit of virtual robotic surgical training before performing robotic procedures on patients.

Background: Increasing chronic diseases challenges the health systems of low- and middle-income countries, including Cameroon. Type 1 diabetes (T1D), among the most common chronic diseases in children, poses particular care delivery challenges. Aim: We examined social representations of patients’ roles and implementation of T1D care among political decision-makers, healthcare providers and patients within families. Setting: The study was conducted in Yaoundé, Cameroon. Methods: Eighty-two individuals were included in the study. The authors conducted semi-structured interviews with policy makers (n = 5), healthcare professionals (n = 7) and patients ’parents (n = 20). Questionnaires were administered to paediatric patients with T1D (n = 50). The authors also observed care delivery at a referral hospital and at a T1D-focused non-governmental organisation over 15 days. Data were analysed using thematic content analysis and descriptive statistics. Results: Cameroonian health policy portrays patients with T1D as passive recipients of care. While many practitioners recognised the complex social and economic determinants of adherence to T1D care, in practice interactions focused on specific biomedical issues and offered brief guidance. Cultural barriers and policy implementation challenges prevent patients and their families from being fully active participants in care. Parents and children prefer an ongoing relationship with a single clinician and interactions with other patients and families. Conclusion: Patients and families mobilise experience and lay knowledge to complement biomedical knowledge, but top-down policy and clinical practice limit their active engagement in T1D care. Contribution: Children with T1D and their families, policy makers, healthcare professionals, and civil society have new opportunities to contribute to person-centred care, as advocated by the Sustainable Development Goals.

Background: Galectins (Gal’s) are a family of carbohydrate-binding proteins that are known to support the tumour microenvironment through their immunosuppressive activity and ability to promote metastasis. As such they are attractive therapeutic targets, but little is known about the cellular expression pattern of galectins within the tumour and its neighbouring stromal microenvironment. Here we investigated the cellular expression pattern of Gals within pancreatic ductal adenocarcinoma (PDAC). Methods: Galectin gene and protein expression were analysed by scRNAseq (n=4) and immunofluorescence imaging (n=19) in fibroblasts and epithelial cells of pancreatic biopsies from PDAC patients. Galectin surface expression was also assessed on tumour adjacent normal fibroblasts and cancer associated primary fibroblasts from PDAC biopsies using flow cytometry. Results: scRNAseq revealed higher Gal-1 expression in fibroblasts and higher Gal-3 and −4 expression in epithelial cells. Both podoplanin (PDPN+, stromal/fibroblast) cells and EpCAM+ epithelial cells expressed Gal-1 protein, with highest expression seen in the stromal compartment. By contrast, significantly more Gal-3 and −4 protein was expressed in ductal cells expressing either EpCAM or PDPN, when compared to the stroma. Ductal Gal-4 cellular expression negatively correlated with ductal Gal-1, but not Gal-3 expression. Higher ductal cellular expression of Gal-1 correlated with smaller tumour size and better patient survival. Conclusions: In summary, the intricate interplay and cell-specific expression patterns of galectins within the PDAC tissue, particularly the inverse correlation between Gal-1 and Gal-4 in ducts and its significant association with patient survival, highlights the complex molecular landscape underlying PDAC and provides valuable insights for future therapeutic interventions.

IntroductionBK virus-associated hemorrhagic cystitis (BK-HC) is a debilitating and poorly understood complication of hematopoietic stem cell transplantation (SCT). Hematuria, dysuria, and other symptoms associated with BK-HC are common in the immediate post-SCT period, making BK-HC difficult to distinguish from other conditions presenting with these symptoms. Despite published criteria for diagnosis, the degree to which these criteria are consistently applied to either clinical diagnosis or to studies informing BK-HC management is unclear. We present a case of BK-HC in a pediatric SCT recipient, and discuss the challenges associated with treatment in the absence of rigorous data to inform clinical management.MethodsWe reviewed all cases of BK viruria at our center in patients undergoing SCT between January 2015 and December 2019. We then performed a scoping review of publications in PubMed addressing BK-HC, specifically focusing on how BK-HC was defined. Publications using the keywords “BK polyomavirus” and “hemorrhagic cystitis” were included if they involved a clinical study of SCT recipients and a full-text article was available in English. Case reports were excluded. Analysis focused on whether BK-HC was explicitly defined and whether the definition incorporated elements of diagnostic criteria published by European Conference on Infections in Leukemia (ECIL).ResultsA total of 30 studies published between January 2018 and 30 June 2021 met criteria for review, including 4 clinical trials, 7 prospective observational studies, and 19 retrospective observational studies. Fifteen of these studies included pediatric patients (7 pediatric only, 8 combined adult and pediatric). Of the 30 publications, 19 included a definition of either BK-HC or BK cystitis, with only five using ECIL criteria, all of which were observational studies. Multiple interventions are described for treatment of BK-HC, including cidofovir, leflunomide, quinolones, hyperbaric oxygen, keratinocyte growth factor, and BK-specific cytotoxic T lymphocytes. However, evidence to support efficacy for any of these interventions is lacking.DiscussionAlthough BK-HC is a well-known complication of SCT, evidence to support available treatment options is limited. Well-controlled studies that incorporate clear diagnostic criteria are needed to better define the risk factors, natural history, and ideal interventions.

Abstract Background Prenatal exposure to metals in private well water may increase the risk of preterm birth (PTB) (delivery 25% of tests exceeded the MCL for lead (aOR 1.10, 95%CI 1.02,1.18) or cadmium (aOR 1.11, 95% CI 1.00,1.23) had an increased odds of PTB. Conversely, those residing in areas with > 25% MCL for zinc (aOR 0.77 (95% CI: 0.56,1.02) and copper (aOR 0.53 (95% CI: 0.13,1.34)) had a reduced odds of PTB. A quartile increase in the concentrations of a mixture of lead, cadmium, and chromium was associated with a small increased odds for PTB (aOR 1.02, 95% CI 1.01, 1.03). This metal mixture effect was most pronounced among American Indian individuals (aOR per quartile increase in all metals: 1.19 (95% CI 1.06,1.34)). Conclusions In a large study population of over one million births, lead and cadmium were found to increase the risk of PTB individually and in a mixture, with additional mixtures-related impacts estimated from co-exposure with chromium. This study highlights critical racial and ethnic health disparities in relation to private well water thereby emphasizing the urgent need for improved private well water quality to protect vulnerable populations.

Abstract Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development.