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Abstract Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection. Another ISG, IFI27, shows a delayed but sustained response restricted to myeloid cells, attributable to gene and cell-specific epigenetic regulation. These findings are reproducible in experimental and naturally acquired infections with influenza, respiratory syncytial virus and rhinovirus. Blood MX1 expression is superior to IFI27 expression for diagnosis of early infection, as a correlate of viral load and for discrimination of virus culture positivity. Therefore, MX1 expression offers potential to stratify patients for antiviral therapy or infection control interventions. Blood IFI27 expression is superior to MX1 expression for diagnostic accuracy across the time course of symptomatic infection and thereby, offers higher diagnostic yield for respiratory virus infections that incur a delay between transmission and testing.

Abstract Background Larval source management (LSM) is re-emerging as a critical malaria intervention to address challenges associated with core vector control tools, such as insecticide-treated nets (ITNs), and to accelerate progress towards elimination. Presently, LSM is not widely used in rural settings and is instead more commonly applied in urban and arid settings. A systematic entomological assessment was conducted in rural communities of southeastern Tanzania, where insecticide-treated nets (ITNs) are widely used, to explore opportunities for deploying LSM to improve malaria control. Methods Aquatic habitat surveys were conducted in 2022 and 2023 to understand habitat usage by different mosquito vectors, covering five villages during the rainy season and seven villages during the dry season. Additionally, samples of adult mosquitoes were collected to assess the role of various Anopheles species in malaria transmission in the area, and to explore opportunities for species sanitation using targeted LSM. Results Adult mosquito surveys showed that in this area, the total entomological inoculation rates (EIR) for indoor collections were 20.1 and 6.5 infectious bites per person per year for outdoors. Anopheles funestus and Anopheles arabiensis were the only Anopheles vectors identified. Anopheles funestus was responsible for over 97.6% of the malaria transmission indoors and 95.4% outdoors. The concurrent larval surveys found that habitats with late instar An. arabiensis and An. funestus comprised only a small subset of 11.2%–16.5% of all water bodies in the rainy season, and 9.7%–15.2% in the dry season. In terms of size, these habitats covered 66.4%–68.2% of the total habitat areas in the wet season, reducing to 33.9%–40.6% in the dry season. From the rainy season to the dry season, the surface area of habitats occupied by An. arabiensis and An. funestus decreased by 92.0% to 97.5%, while the number of habitats occupied by An. arabiensis and An. funestus decreased by 38.0% to 57.3%. Anopheles funestus preferred large, permanent habitats with clear water and vegetation year-round, while An. arabiensis showed contrasting seasonal preferences, favouring sunlit still waters in the rainy season and larger, opaque habitats in the dry season. Conclusion These findings suggest that An. funestus, which is the dominant malaria vector in the area, mediating over 95% of malaria transmission, preferentially occupies only a small subset of uniquely identifiable aquatic habitats in both wet and dry seasons. This presents an opportunity to expand LSM in rural settings by carefully targeting An. funestus habitats, which might be effective and logistically feasible as a complementary approach alongside existing interventions. Further research should assess the impact of targeted LSM for species sanitation compared to blanket LSM.

Abstract Testicular germ cell tumours (TGCT), which comprise seminoma and non-seminoma subtypes, are the most common cancers in young men. In this study, we present a comprehensive whole genome sequencing analysis of adult TGCTs. Leveraging samples from participants recruited via the UK National Health Service and data from the Genomics England 100,000 Genomes Project, our results provide an extended description of genomic elements underlying TGCT pathogenesis. This catalogue offers a comprehensive, high-resolution map of copy number alterations, structural variation, and key global genome features, including mutational signatures and analysis of extrachromosomal DNA amplification. This study establishes correlations between genomic alterations and histological diversification, revealing divergent evolutionary trajectories among TGCT subtypes. By reconstructing the chronological order of driver events, we identify a subgroup of adult TGCTs undergoing relatively late whole genome duplication. Additionally, we present evidence that human leukocyte antigen loss is a more prevalent mechanism of immune disruption in seminomas. Collectively, our findings provide valuable insights into the developmental and immune modulatory processes implicated in TGCT pathogenesis and progression.

Abstract Background Marine sediments represent one of the planet’s largest carbon stores. Bottom trawl fisheries constitute the most widespread physical disturbance to seabed habitats, which exert a large influence over the oceanic carbon dioxide (CO2) sink. Recent research has sparked concern that seabed disturbance from trawling can therefore turn marine sediments into a large source of CO2, but the calculations involved carry a high degree of uncertainty. This is primarily due to a lack of quantitative understanding of how trawling mixes and resuspends sediments, how it alters bioturbation, bioirrigation, and oxygenation rates, and how these processes translate into carbon fluxes into or out of sediments. Methods The primary question addressed by this review protocol is: how does mobile bottom fishing affect benthic carbon processing and storage? This question will be split into the following secondary questions: what is the effect of mobile bottom fishing on: (i) the amount and type of carbon found in benthic sediments; (ii) the magnitude and direction of benthic-pelagic carbon fluxes; (iii) the biogeochemical, biological, and physical parameters that control the fate of benthic carbon; and (iv) the biogeochemical, biological, and physical parameters that control the fate of resuspended carbon. Literature searches will be conducted in Web of Science, SCOPUS, PROQUEST, and a range of grey and specialist sources. An initial scoping search in Web of Science informed the final search string, which has been formulated according to Population Intervention Comparator Outcome (PICO) principles. Eligible studies must contain data concerning a change in a population of interest caused by mobile bottom fishing. Eligible study designs are Before and After, Control and Impact, and Gradient studies. Studies included at full-text screening will be critically appraised, and study findings will be extracted.Extracted data will be stored in an Excel spreadsheet. Results will be reported in narrative and quantitative syntheses using a variety of visual tools including forest plots. Meta-analysis will be conducted where sufficient data exists.

Abstract Fear of Missing Out (FoMO), the concern one is presently absent from a rewarding experience, is an emerging topic in the empirical literature. Though it has been demonstrated that numerous factors including anxiety and depression predict the extent an individual experiences FoMO, more research is needed to understand the inner mechanisms that work between these variables to result in FoMO. One such factor which may mediate the relations of anxiety and depression on FoMO is the need to belong (NTB). The goal of the current research aims to evaluate if NTB mediates the relationship of anxiety and depression with FoMO. In addition, we aimed to detect if attachment anxiety mediates the relationship of anxiety and FoMO. Lastly, the current study evaluated if attachment anxiety mediates the relationship between NTB and FoMO. An effective sample of 397 adults from the United States were recruited to complete multiple questionnaires. Structural Equation Modeling (SEM) was used to test a theoretical model depicting anxiety and depression as predictors of NTB, NTB predicting both attachment anxiety and FoMO, attachment anxiety predicting FoMO, and anxiety predicting attachment anxiety. Our results indicated that NTB was a strong predictor of FoMO, and this effect was mediated by attachment anxiety. Moreover, NTB mediated the influence of depression on FoMO, while attachment anxiety mediated the impact of anxiety on FoMO. The current research outlines that NTB is a key individual difference for why everyone does not uniformly experience FoMO. Limitations and suggestions for future research are outlined.

Abstract To help with preparedness efforts of Canadian public health and safety systems for adaptation to climate change, the humidity index (humidex) and three threshold‐based humidex indices (annual number of days with humidex greater than 30, 35 and 40) were computed for a multi‐model ensemble of climate change projections, over Canada. The ensemble consists of one run from each 19 Coupled Model Intercomparison Project Phase 6 (CMIP6) global climate models and offers historical simulations starting in 1950 and future projections out to 2100 following Shared Socioeconomic Pathways (SSPs): SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5. Each ensemble member was bias‐adjusted and statistically downscaled using the Multivariate bias correction—N‐dimensional probability density function transform (MBCn) with hourly data from ERA5‐Land as the target dataset and following a method proposed by Diaconescu et al. (2023; International Journal of Climatology, 43, 837) to calculate humidex from daily climate model outputs. This paper details the steps for data production including evaluation of the target historical gridded data and selection of downscaling method and presents some of the resulting humidex projections at the end of the century.

Abstract The majority of viruses classified as pandemic threats are enveloped viruses which enter the cell through receptor-mediated endocytosis and take advantage of endosomal acidification to activate their fusion machinery. Here we report that the endosomal fusion of low pH-requiring viruses is highly dependent on TRPM7, a widely expressed TRP channel that is located on the plasma membrane and in intracellular vesicles. Using several viral infection systems expressing the envelope glycoproteins of various viruses, we find that loss of TRPM7 protects cells from infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2. TRPM7 ion channel activity is intrinsically necessary to acidify virus-laden endosomes but is expendable for several other endosomal acidification pathways. We propose a model wherein TRPM7 ion channel activity provides a countercurrent of cations from endosomal lumen to cytosol necessary to sustain the pumping of protons into these virus-laden endosomes. This study demonstrates the possibility of developing a broad-spectrum, TRPM7-targeting antiviral drug to subvert the endosomal fusion of low pH-dependent enveloped viruses.

In this systematic review, we examine research from 2009 to 2022 to identify and classify the unintended effects of turnaround in the United States. We develop a conceptual framework classifying three types of side effects--spillover effects, systemic side effects, and internal side effects--and differentiate these side effects from unintended negative intervention effects. We identify four broad categories of side effects within this framework based on the population they impact: communities, school systems, educators, and students. We find that the most prevalent side effects are related to educator experiences, staffing, community reaction, education governance, and the proliferation of external actors. We conclude by calling for future research to explicitly examine common side effects alongside the intended effects of turnaround.

Deploying a Lacanian conceptual framework, this article interrogates the psychoanalytic underpinnings of Paulo Freire's dialogical method of critical pedagogy. The paper advances the claim that the transformative efficacy of Freirean dialogue is rooted in its unique ability to confront and engage the repressed element of trauma, or what Lacan calls the "real." The author suggests that the locus of trauma stands as the elusive, yet central and constitutive axis around which Freire's dialogical engagement turns. Following psychoanalysis' attention to biography, the paper first examines how Freire's personal experience of exile informs his philosophical orientation to being, politics, and education. Turning to a specific classroom event Freire outlines in "Pedagogy of Hope," the paper then develops a new interpretation of Freire's idea of naming, and through Lacanian analysis, extends Freire's insight on the relationship between psyche, ideology, and social antagonism. Pushing the idea of class subjectivity in Freire beyond its familiar determinants (namely as an 'identity'), the paper resituates the notion of radical subjectivity in critical pedagogy as the effect of a traumatic loss or gap in the sociosymbolic order of being. The author argues that the 'naming event' in Freire is formally rooted in an encounter with this unconscious gap. To conclude, the paper offers critical educators some new points of departure for conceptualizing the transformative labor of problem-posing dialogue.

Purpose: Leadership for learning emerged as an integrated leadership framework; however, attempts to establish an empirical measurement model have been limited. Critically, not much is known about how much teachers' beliefs (e.g. self-efficacy) can mediate leadership for learning impact on teacher behaviors. This study establishes a leadership for learning measurement model and examines whether teacher self-efficacy mediates the effect of leadership for learning tasks on teacher collaboration, instructional quality, intention to leave current schools and their confidence in equitable teaching practice. Design/methodology/approach: Drawing on the most recent 2018 Teaching and Learning International Survey (TALIS), the study employed a structural equation modeling mediation approach. Findings: Results suggested that teacher self-efficacy statistically significantly mediated 16 out of 20 of the relationships between leadership for learning task domains and teacher outcomes. Especially, in explaining the variance in instructional quality and teacher confidence in implementing equitable teaching practices, considerable proportions of the predictive power of leadership for learning tasks were accounted for (i.e. mediated) by teacher self-efficacy. Research limitations/implications: School-wide efforts to craft the school vision for learning must be coupled with enhancing teacher self-efficacy. Critically, leadership efforts may fall short of implementing equitable teaching practice and quality instruction without addressing teacher confidence in their ability in instruction, classroom management and student engagement. Originality/value: This study is the first of its kind to evidence teacher self-efficacy mediates leadership for learning practice impact on teacher behaviors.

Highlights Photoelectrochemical CO2 reduction to multicarbon products with high efficiency. Co-design of photoelectrochemical CO2 reduction devices for multicarbon product generation. Optimal semiconductor bandgaps for high multicarbon product selectivity. Limitations in multicarbon product generation from photoelectrochemical CO2 reduction. Optimizing photoelectrochemical CO2 reduction systems for multicarbon product generation.

ObjectiveTo describe the characteristics, management, and functional outcomes of patients with synchronous urethral stricture disease (SUSD) utilizing a multi-institutional cohort.MethodsData were collected and assessed from a prospectively maintained, multi-institutional database. Patients who underwent anterior urethroplasty for urethral stricture disease (USD) were included and stratified by the presence or absence of SUSD. USD location and etiology were classified according to the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System. Anterior urethroplasty techniques were recorded for both strictures. Functional failure was compared between groups.ResultsOne thousand nine hundred eighty-three patients were identified, of whom, 137/1983 (6.9%) had SUSD. The mean primary stricture length for patients with SUSD was 3.5 and 2.6 cm for the secondary stricture. Twelve anterior urethroplasty technique combinations were utilized in treating the 27 different combinations of SUSD. Functional failure was noted in 18/137 (13.1%) patients with SUSD vs 192/1846 (10.4%) patients with solitary USD, P = .3. SUSD was not associated with increased odds of functional failure. S classifications: S1b, P = .003, S2a, P = .001, S2b, P = .01 and S2c, P = .02 and E classifications: E3a, P = .004 and E6, P = .03, were associated with increased odds of functional failure.ConclusionRepair of SUSD in a single setting does not increase the risk of functional failure compared to patients with solitary USD. Increasing S classification, S1b through S2c and E classifications E3a and E6 were associated with increased functional failure. This reinforces the importance of the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System as a necessary tool in large-scale multi-institutional analysis when assessing highly heterogenous patient populations.

ObjectiveTo clinically validate a previously developed adult-acquired buried penis (AABP) classification system that is based on a standardized preoperative physical examination that subtypes patients by their penile skin/escutcheon complex (P), abdominal pannus (A), and scrotal skin (S).MethodsThe Trauma and Urologic Reconstruction Network of Surgeons (TURNS) database was used to create an AABP cohort. Patients were retrospectively classified using the previously described PAS classification system. The frequency of subtypes, surgical methods utilized for AABP repair, and correlations between PAS classification and surgery subtypes were analyzed.ResultsThe final cohort consisted of 101 patients from 10 institutions. Interrater reliability between two reviewers was excellent (κ = 0.95). The most common subtypes were P2c (contributory escutcheon+insufficient penile skin; 27%) and P2a (contributory escutcheon+sufficient penile skin; 21%) for penile subtypes, A0 (no pannus; 41%) and A1 (noncontributory pannus; 39%) for abdominal subtypes, and S0 (normal scrotal skin with preserved scrotal sulcus; 71%) for scrotal subtypes. AABP repair procedures included escutcheonectomy (n = 59, 55%), scrotoplasty (n = 51, 48%), split-thickness skin grafting (n = 50, 47%), penile skin excision (n = 47, 44%) and panniculectomy (n = 7, 7%). P, A, and S subtypes were strongly associated with specific AABP surgical techniques.ConclusionThe PAS classification schema adequately describes AABP heterogeneity, is reproducible among observers, and correlates well with AABP surgery types. Future work will focus on how PAS subtypes affect both surgical and patient-centered outcomes.

ObjectiveMicrotubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free functional magnetic resonance imaging (fMRI) mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers.MethodsWe compared cross-sectional fMRI data between 17 symptomatic and 39 presymptomatic carriers and 81 controls with (1) seed-based analyses to examine connectivity within networks associated with the 4 most common MAPT-associated clinical syndromes (ie, salience, corticobasal syndrome, progressive supranuclear palsy syndrome, and default mode networks) and (2) whole-brain connectivity analyses. We applied K-means clustering to explore connectivity heterogeneity in presymptomatic carriers at baseline. Neuropsychological measures, plasma neurofilament light chain, and gray matter volume were compared at baseline and longitudinally between the presymptomatic subgroups defined by their baseline whole-brain connectivity profiles.ResultsSymptomatic and presymptomatic carriers had connectivity disruptions within MAPT-syndromic networks. Compared to controls, presymptomatic carriers showed regions of connectivity alterations with age. Two presymptomatic subgroups were identified by clustering analysis, exhibiting predominantly either whole-brain hypoconnectivity or hyperconnectivity at baseline. At baseline, these two presymptomatic subgroups did not differ in neuropsychological measures, although the hypoconnectivity subgroup had greater plasma neurofilament light chain levels than controls. Longitudinally, both subgroups showed visual memory decline (vs controls), yet the subgroup with baseline hypoconnectivity also had worsening verbal memory and neuropsychiatric symptoms, and extensive bilateral mesial temporal gray matter decline.InterpretationNetwork connectivity alterations arise as early as the presymptomatic phase. Future studies will determine whether presymptomatic carriers' baseline connectivity profiles predict symptomatic conversion. ANN NEUROL 2023;94:632-646.

Societal Impact Statement Grapevine leaves are emblematic of the strong visual associations people make with plants. Leaf shape is immediately recognizable at a glance, and therefore, this is used to distinguish grape varieties. In an era of computationally enabled machine learning‐derived representations of reality, we can revisit how we view and use the shapes and forms that plants display to understand our relationship with them. Using computational approaches combined with time‐honored methods, we can predict theoretical leaves that are possible, enabling us to understand the genetics, development, and environmental responses of plants in new ways. Summary Grapevine leaves are a model morphometric system. Sampling over 10,000 leaves using dozens of landmarks, the genetic, developmental, and environmental basis of leaf shape has been studied and a morphospace for the genus Vitis predicted. Yet, these representations of leaf shape fail to capture the exquisite features of leaves at high resolution. We measure the shapes of 139 grapevine leaves using 1672 pseudo‐landmarks derived from 90 homologous landmarks with Procrustean approaches. From hand traces of the vasculature and blade, we have derived a method to automatically detect landmarks and place pseudo‐landmarks that results in a high‐resolution representation of grapevine leaf shape. Using polynomial models, we create continuous representations of leaf development in 10 Vitis spp. We visualize a high‐resolution morphospace in which genetic and developmental sources of leaf shape variance are orthogonal to each other. Using classifiers, Vitis vinifera, Vitis spp., rootstock and dissected leaf varieties as well as developmental stages are accurately predicted. Theoretical eigenleaf representations sampled from across the morphospace that we call synthetic leaves can be classified using models. By predicting a high‐resolution morphospace and delimiting the boundaries of leaf shapes that can plausibly be produced within the genus Vitis, we can sample synthetic leaves with realistic qualities. From an ampelographic perspective, larger numbers of leaves sampled at lower resolution can be projected onto this high‐resolution space, or, synthetic leaves can be used to increase the robustness and accuracy of machine learning classifiers.

Prairie dogs (Cynomys sp.) are recognized as keystone species because their colonies provide habitat heterogeneity and are inhabited by specialized plant and animal communities. While many studies have demonstrated the unique ecological properties of prairie dog colonies and their effects on local grassland bird communities, few have examined how their presence influences bird diversity at a landscape scale. We collected species diversity data across 192 points within 64 80-ha sampling cells. With 11 of those 64 cells containing an active prairie dog town, we tested if the presence of black-tailed prairie dog (Cynomys ludovicianus) colonies would result in higher landscape-scale avian biodiversity in a mixed-grass prairie and sagebrush steppe ecosystem in north-central Montana. Utilizing permutational multivariate analysis of variance, we observed significant dissimilarities between avian communities with and without prairie dog colonics, and colony presence explained a moderate proportion of variance in avian diversity. Indicator species analysis found 5 species significantly associated with colony cells: Homed Lark (Eremophila alpestris), Marbled Godwit (Limosa fedoa), Brewer's Blackbird (Euphagus cyanocephalus), Killdeer (Charadrius vociferus), and Burrowing Owl (Athene cunicularia). These findings suggest prairie dogs play an important role in maintaining high avian biodiversity at a landscape scale within grassland ecosystems. Further, our results emphasize the importance of incorporating prairie dogs into conservation efforts for grassland birds. Received 14 August 2023. Accepted 8 March 2024. Key words: conservation, Great Plains, keystone species, Montana, songbirds. (Spanish)--Los perritos de las praderas (Cynomys sp.) se reconocen como especies clave ya que sus colonias brindan heterogeneidad al habitat y son habitadas por comunidades animales y vegetales especializadas. Mientras muchos estudios han demostrado las propiedades unicas de las colonias de perritos de las praderas y sus efectos en comunidades locales de aves de praderas, pocos han examinado como su presencia influye en la diversidad de aves a escala del paisaje. Colectamos datos de diversidad de especie en 192 puntos con celdas de muestreo de 64-80 ha. Con 11 de esas 64 celdas que contenian poblaciones activas de perritos de las praderas, analizamos si la presencia de colonias de perrito de la pradera de cola negra (Cynomys ludovicianus) resultan en una mayor biodiversidad de aves a escala del paisaje en una pradera de pastos mixtos y ecosistema de estepa de artemisa en la parte central del norte de Montana. Utilizando analisis de varianza multivariado permutacional, observamos disimilitudes significativas entre comunidades de aves con y sin colonias de perritos de la pradera y la presencia de colonias explico en proporcion moderada la varianza de la diversidad aviar. Analisis de especies indicadoras encontro 5 especies significativamente asociadas con celdas de colonias: alondra Eremophila alpeslris, aguja Limosa fedoa, tordo Euphagus cyanocephalus, chorlito Charadrius vociferus, y el tecolote Athene cunicularia. Estos hallazgos sugieren que los perritos de la pradera juegan un papel importante en mantener una alta biodiversidad de aves a escala de paisaje dentro de ecosistemas de pradera. Ademas, nuestros resultados enfatizan en la importancia de incorporar a los perritos de pradera en esfuerzos de conservacion de aves de pradera. Palabras clave: aves canoras, conservacion, especies clave, Great Plains, Montana., Grassland bird communities coevolved with frequent and large-scale ecological disturbances such as grazing and fire that create a mosaic of habitat within grasslands (Knopf 1996, Smith and Lomolino 2004, Fuhlendorf [...]