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Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and their widespread integration as a means of transport remains contentious2-4. Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 BCE, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai around 3500 BCE, a settlement from central Asia associated with corrals and a subsistence economy centred on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines.

BACKGROUND: Reducing malnutrition is a key priority for governments in low- and middle-income countries given its lasting effects on child development, health, income, and economic growth. Strategies to improve recommended infant and young child feeding (IYCF) practices, especially during the first two years of life, are considered among the most effective. METHODS: In this paper, we evaluate the long-run impacts of an innovative education strategy based on interactive play and performing arts implemented in El Alto, Bolivia on caregivers IYCF knowledge and practices. Two thousand and fifteen households were randomly assigned to intervention and control groups. Two rounds of data were collected approximately 30 and 42 months after baseline. We estimate short-term (30 month) and longer-term (42 month) intent-to-treat effects using multivariate linear regression analysis, with and without controlling for covariates. RESULTS: The program significantly increased caregiver IYCF knowledge by 0.13 SDs in the short run, and this effect grew over time. The program also improved adherence to recommended IYCF practices by 0.23 standard deviations (SDs) in the short term, but the effect on practices dissipated over time, and no longer-term impacts were detected. Caregivers with above median baseline knowledge, number of children, and age appear to have benefited most from the program. CONCLUSIONS: Our findings suggest that entertainment-education interventions are a promising model for improving and maintaining IYCF knowledge. However, their ability to sustain more permanent changes in IYCF practices is less certain. Further evidence is needed to identify other avenues for producing long-term, sustainable behavior change, especially among indigenous populations in Latin America, where literature on education and behavior-change interventions related to IYCF practices is limited.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

The goal of this project was to determine whether various measures of mammary development differed between gilts and multiparous sows at the end of gestation. During gestation, Yorkshire × Landrace gilts (n = 19) and sows (second and third gestations, n = 17) were fed one daily meal of a conventional corn-based diet, where the amount fed was based on body weight (BW) and backfat thickness (BF) at mating. On day 110 ± 1 of gestation, a jugular blood sample was obtained from all gilts and sows to measure insulin-like growth factor-1 (IGF-1), glucose, free fatty acids, and urea. On that same day, BW and BF were measured and animals were euthanized. Mammary glands from one side of the udder were dissected for compositional analyses. The fifth gland of the contralateral row of mammary glands was sampled for histology and immunohistochemical localization of Ki67. There was less total parenchyma (1,437.4 vs. 2,004.7 ± 127.1 g; P  0.10), while extraparenchymal tissue weight tended to be less in gilts than sows (P = 0.07). All components within the parenchyma differed by parity (P

Abstract Background Directional vibrotactile biofeedback for balance control can be instructed in the form of Repulsive (to move in the opposite direction of vibrations) or Attractive (to move in the direction of vibrations) stimulus encodings. However, which of these encodings is less cognitively demanding and poses less interference with high-level cognitive processes of conflict resolution remains unresolved. Methods In two between-subject studies with 30 (16 females) and 35 (23 females) healthy young adults, respectively, we investigated the cognitive load of Attractive and Repulsive vibrotactile biofeedback on 1) working memory (Study I) and 2) cognitive conflict resolution (Study II). Both studies also examined the effectiveness of both feedback stimulus encodings on balance control during quiet standing with eyes closed. Results Both Attractive and Repulsive vibrotactile biofeedback increased balance stability (reduced trunk sway variability) in both the working memory and the conflict resolution study (Study I and II, respectively) with a greater increase of stability for the Repulsive encoding during multitasking demanding cognitive conflict resolution (Study II). Cognitive costs, measured in terms of the Linear Integrated Speed-Accuracy Score (LISAS), were greater for the Attractive encoding during multitasking with working memory demands. When cognitive conflict resolution was required as a secondary cognitive task, both stimulus encodings increased cognitive costs equally. Conclusions The effects of instructed Repulsive and Attractive stimulus encodings for the response-related interpretation of vibrotactile biofeedback of body sway were contrasted with respect to cognitive processing demands and balance stabilisation benefits. Both encodings improved balance stability but at certain cognitive costs. Regarding interference with specific high-level cognitive processes, however, a distinction has to be made between both encodings. Repulsive feedback encoding seems to cause less cognitive costs on working memory load and slightly greater stabilisation when cognitive conflict resolution is required. These results are discussed in the context of the known benefits of avoidance actions on cognitive control.

Abstract Background Spinal muscular atrophy is a rare neurodegenerative disorder in children which leads untreated to muscle wasting, respiratory impairments, and a shortened life expectancy. Parents as primary caregivers are often physically and psychologically burdened. In recent years, new and promising treatment options have been approved, but it remains unclear if they have an impact on the psychosocial situation of affected families. Objectives The aim of this study was to explore the views and experiences of parents as informal caregivers of children with SMA in the course of the disease against the background of new treatment options (Spinraza® or Zolgensma®). Methods We conducted qualitative interviews with 27 parents of children with SMA treated with Spinraza® and Zolgensma® from April to September 2020. The analysis was done using thematic analysis and reported according to the COREQ criteria. Results The data analysis resulted in three main themes: a) caregiver burden and negative consequences for families, b) resources and protective aspects, c) psychosocial care needs. The results are discussed against the background of new treatment options and previous models of supportive care needs. Parental caregivers of affected children face multiple burdens in different stages of the child’s disease progression. Conclusion Although new treatment options for SMA showed observable effects for most parents, the main caregiver burden and reported symptoms were attributable to the overburdening care tasks. To unburden families, more screening for unmet needs, family-centered help services, professional caregivers, childcare, and sufficient financial support are needed.

Abstract Background 46,XX testicular disorder/difference of sex development (46,XX DSD) is a rare congenital condition, characterized by a combination of the typical female sex chromosome constitution, 46,XX, and a variable male phenotype. In the majority of individuals with 46,XX DSD, a Y chromosome segment containing the sex-determining region gene (SRY) has been translocated to the paternal X chromosome. However, the precise genomic content of the translocated segment and the genome-wide effects remain elusive. Methods We performed long-read DNA sequencing, RNA sequencing and DNA methylation analyses on blood samples from 46,XX DSD (n = 11), male controls (46,XY; variable cohort sizes) and female controls (46,XX; variable cohort sizes), in addition to RNA sequencing and DNA methylation analysis on blood samples from males with Klinefelter syndrome (47,XXY, n = 22). We also performed clinical measurements on all 46,XX DSD and a subset of 46,XY (n = 10). Results We identified variation in the translocated Y chromosome segments, enabling subcategorization into 46,XX DSD (1) lacking Y chromosome material (n = 1), (2) with short Yp arms (breakpoint at 2.7–2.8 Mb, n = 2), (3) with medium Yp arms (breakpoint at 7.3 Mb, n = 1), and (4) with long Yp arms (n = 7), including deletions of AMELY, TBLY1 and in some cases PRKY. We also identified variable expression of the X-Y homologues PRKY and PRKX. The Y-chromosomal transcriptome and methylome reflected the Y chromosome segment lengths, while changes to autosomal and X-chromosomal regions indicated global effects. Furthermore, transcriptional changes tentatively correlated with phenotypic traits of 46,XX DSD, including reduced height, lean mass and testicular size. Conclusion This study refines our understanding of the genetic composition in 46,XX DSD, describing the translocated Y chromosome segment in more detail than previously and linking variability herein to genome-wide changes in the transcriptome and methylome.

Abstract Background The introduction of newborn screening (NBS) for spinal muscular atrophy (SMA) has increased the early diagnosis of 5q-associated SMA in presymptomatic and symptomatic preterm infants. National and international recommendations for treating preterms and newborns

Abstract Background The risk assessment of dental erosion among children and adolescents is an important aspect of dental care, as dental erosion constitutes a rapidly growing, global problem. Dental professionals rely solely on their own perception, as the current risk assessment process is not completely automatized, which affects the risk assessment reliability. Aim To explore dental professionals’ experiences with risk assessment of dental erosion among children and adolescents. Method In-depth interview was used as data collection method. A total of 11 dental professionals were interviewed. The interviews were analyzed using qualitative content analysis. Results The findings were summarized in the categories Professionals’ responsibility, Systematic approach , and Collaboration and communication. Dental staff perceived that their basic knowledge regarding erosion should be improved, and skills development was desired to reduce the knowledge gaps around the risk assessment of dental erosion. They alleged that the systematic approach could be improved by reducing workplace stress, implementing a universal dental erosion index, improving the existing risk assessment software, and automating the risk assessment of the condition. Dental professionals also experienced a need to calibrate and collaborate with each other and with other healthcare professionals to improve patient care. Conclusion Dental professionals experienced their basic knowledge of dental erosion and their risk assessment as good, but a more advanced skill development was required. Furthermore, they experienced the risk assessment software as a good tool that should be improved to compile more objective risk assessment. A universal erosion index was also requested.

Discoveries of new species often depend on one or a few specimens, leading to delays as researchers wait for additional context, sometimes for decades. There is currently little professional incentive for a single expert to publish a stand-alone species description. Additionally, while many journals accept taxonomic descriptions, even specialist journals expect insights beyond the descriptive work itself. The combination of these factors exacerbates the issue that only a small fraction of marine species are known and new discoveries are described at a slow pace, while they face increasing threats from accelerating global change. To tackle this challenge, this first compilation of Ocean Species Discoveries (OSD) presents a new collaborative framework to accelerate the description and naming of marine invertebrate taxa that can be extended across all phyla. Through a mode of publication that can be speedy, taxonomy-focused and generate higher citation rates, OSD aims to create an attractive home for single species descriptions. This Senckenberg Ocean Species Alliance (SOSA) approach emphasises thorough, but compact species descriptions and diagnoses, with supporting illustrations and with molecular data when available. Even basic species descriptions carry key data for distributions and ecological interactions (e.g., host-parasite relationships) besides universally valid species names; these are essential for downstream uses, such as conservation assessments and communicating biodiversity to the broader public.This paper presents thirteen marine invertebrate taxa, comprising one new genus, eleven new species and one re-description and reinstatement, covering wide taxonomic, geographic, bathymetric and ecological ranges. The taxa addressed herein span three phyla (Mollusca, Arthropoda, Echinodermata), five classes, eight orders and twelve families. Apart from the new genus, an updated generic diagnosis is provided for four other genera. The newly-described species of the phylum Mollusca are Placiphorella methanophila Vončina, sp. nov. (Polyplacophora, Mopaliidae), Lepetodrilus marianae Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Lepetodrilidae), Shinkailepas gigas Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Phenacolepadidae) and Lyonsiella illaesa Machado & Sigwart, sp. nov. (Bivalvia, Lyonsiellidae). The new taxa of the phylum Arthropoda are all members of the subphylum Crustacea: Lepechinella naces Lörz & Engel, sp. nov. (Amphipoda, Lepechinellidae), Cuniculomaera grata Tandberg & Jażdżewska, gen. et sp. nov. (Amphipoda, Maeridae), Pseudionella pumulaensis Williams & Landschoff, sp. nov. (Isopoda, Bopyridae), Mastigoniscus minimus Wenz, Knauber & Riehl, sp. nov. (Isopoda, Haploniscidae), Macrostylis papandreas Jonannsen, Riehl & Brandt, sp. nov. (Isopoda, Macrostylidae), Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. (Isopoda, Nannoniscidae) and Apseudopsis daria Esquete & Tato, sp. nov. (Tanaidacea, Apseudidae). In the phylum Echinodermata, the reinstated species is Psychropotes buglossa E. Perrier, 1886 (Holothuroidea, Psychropotidae).The study areas span the North and Central Atlantic Ocean, the Indian Ocean and the North, East and West Pacific Ocean and depths from 5.2 m to 7081 m. Specimens of eleven free-living and one parasite species were collected from habitats ranging from an estuary to deep-sea trenches. The species were illustrated with photographs, line drawings, micro-computed tomography, confocal laser scanning microscopy and scanning electron microscopy images. Molecular data are included for nine species and four species include a molecular diagnosis in addition to their morphological diagnosis.The five new geographic and bathymetric distribution records comprise Lepechinella naces Lörz & Engel, sp. nov., Cuniculomaera grata Tandberg & Jażdżewska, sp. nov., Pseudionella pumulaensis Williams & Landschoff, sp. nov., Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. and Psychropotes buglossa E. Perrier, 1886, with the novelty spanning from the species to the family level. The new parasite record is Pseudionella pumulaensis Williams & Landschoff, sp. nov., found in association with the hermit crab Pagurus fraserorum Landschoff & Komai, 2018.

Computational Thinking (CT) is an emerging topic in school curricula. Different tools exist to support the learning of CT, namely visual programming languages and tangible development platforms (TDP), which are widely used in extra-curricular activities. To date, few tools have been developed that consider both teachers' needs and the school context. We designed the Kniwwelino Classroom Kit (KCK) in order to support the teaching of CT in classrooms. This paper presents the results of a pilot study, in which the KCK was used in three primary and three secondary schools in Luxembourg. The KCK is based on Kniwwelino, a creative environment designed for children from 8 years old to learn about programming and electronics. The study explored the suitability of the KCK for teaching CT in primary and secondary schools, focusing on three research questions: (1) how the KCK supports teachers' pedagogical practices, (2) how the KCK fulfils the pedagogical objectives set by teachers, and (3) the user experience of the KCK (for teachers and pupils). To assess how the KCK meets the three above-mentioned objectives, we used a mixed method approach, combining semi-guided interviews, logbooks, and several questionnaires. We learned that the KCK is versatile enough to adapt to different environments, objectives, and pedagogical approaches, which responds to the first two research questions, and thus offers a great deal of freedom to teachers. The fun and tangible approach of the KCK introduces programming and enables pupils to develop both CT and soft skills such as communication and collaboration. Teachers' feedback on their user experience was positive, particularly concerning stimulation, novelty, and attractiveness. KCK was evaluated as interesting, valuable, and good, but it was noted that some improvements needed to be made to make it easier, more predictable, and faster. The pupils also rated their user experience positively, with values that were generally on a par with previous studies reported in the state of the art regarding the use of Scratch and BBC Micro:bit in school-based experiments for learning CT. Drawing from these learnings, we list several recommendations for the development of other similar TDP tools to support the teaching of CT in a classroom setting. These recommendations concern the material, programming interface, connection, educational material, and the creation of a community.

Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17-34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling.

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.

Abstract Cryopyrin-associated periodic syndromes (CAPS) are orphan hereditary auto-inflammatory diseases with various phenotypes, including chronic kidney disease (CKD). Current therapies inhibit interleukin-1 (IL-1) to achieve clinical and serological remission; however, the effect on kidney involvement remains unclear. The objective of this study was to investigate the long-term efficacy of anti-IL-1 treatment with special emphasis on renal outcome. We retrospectively analysed clinical, genetic and laboratory data of patients with CAPS under anti-IL-1 therapy from a single-centre university outpatient clinic. Patients with CAPS (n = 28) were followed for a median of 11 (IQR 8.5–13) years. Four patients at various ages (19%), bearing the most common CAPS mutation R260W, had significant CKD at presentation. All affected patients were related; however, other family members with the same genetic variant did not develop CKD. While anti-IL-1 therapy was effective in lowering symptom burden and inflammatory parameters in all CAPS patients, two of the four individuals with significant CKD had persistent proteinuria and worsening kidney function. None of the patients without renal affection at therapy initiation developed relevant CKD in the follow-up period. We showed that in patients with CAPS: (1) CKD is a common complication; (2) renal involvement shows familial predisposition beyond the mutational status and is independent of age; (3) anti-IL-1 therapy results in sustained improvement of inflammatory parameters and symptom load and (4) may prevent development of CAPS-associated CKD but not affect kidney involvement when already present. Overall, early therapy initiation might sufficiently prevent renal disease manifestation and attenuate progression.

In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59) , P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.

Abstract Urbanization is a key driver of global environmental change and is adversely impacting wildlife populations. Human tolerance for wildlife is critical to wildlife conservation in urban areas. Using metropolitan Atlanta, Georgia, United States, as a case study, we investigated human tolerance for a range of different wildlife species. Almost half of the human–wildlife interactions that are reported to the state wildlife agency originate from metropolitan Atlanta, which is one of the fastest growing metropolises in the United States. We surveyed a representative sample of 1006 residents of metropolitan Atlanta in 2022. We found heterogeneity in respondents' tolerance for various species, although most respondents were intolerant of bobcats, coyotes, opossums and snakes. Respondents' tolerance for different species largely depended on their attitudes and emotions towards species, and their basic beliefs pertaining to wildlife and the relationships between humans and wildlife. We found some evidence that tolerance also depended on people's prior interactions with wildlife, their beliefs that they can mitigate conflicts with wildlife and their demographic characteristics. Our results suggest that communication that improves urban residents' attitudes towards wildlife and/or reinforces positive emotions towards wildlife may increase wildlife tolerance in urban areas. Read the free Plain Language Summary for this article on the Journal blog.

Summary: Epstein-Barr virus (EBV) is a ubiquitous oncogenic virus associated with multiple cancers and autoimmune diseases. Unlike most herpesviruses, EBV reactivation from latency occurs asymptomatically, allowing it to spread efficiently to other hosts. However, available models are limited by the inefficient and asynchronous reactivation from latency into lytic replication. To address this problem, we develop a dual-fluorescent lytic reporter (DFLR) EBV that specifically labels cells in the early and late stages of replication. Using lymphoblastoid cell lines transformed by DFLR EBV as a model for EBV reactivation in B cells, we observe extensive reprogramming of the host cell transcriptome during lytic cycle progression. This includes widespread shutoff of host gene expression and disruption of mRNA processing. Unexpectedly, host shutoff remains extensive even in cells infected with DFLR EBV deleted for the BGLF5 nuclease. These findings implicate BGLF5-independent mechanisms as the primary drivers of host transcriptome remodeling during EBV lytic replication.

The constant pursuit of efficient and cost-effective methods for analyzing human samples drives ongoing innovation in biomedical research. Introduced in 2014, Volumetric Absorptive Microsampling (VAMS) technology ensures fixed blood volume absorption and enhanced sample uniformity. Our study aims to enhance VAMS functionality by integrating sample preparation onto the device primarily used for sample collection. This involves the adsorption of antibodies onto VAMS tips, enabling instant sample clean-up at the time of sample collection. Using human chorionic gonadotropin (hCG) as a model analyte, we evaluated the qualitative and quantitative performance of Affinity-VAMS. First, we showed that adsorbing and covalently binding monoclonal antibodies to VAMS tips results in capturing of the target analyte in comparison to unmodified VAMS. Due to the ease of preparation, we moved forward using antibody adsorption to VAMS tip and optimized the procedure. Optimization of the procedure involved fine-tuning the antibody coupling step, washing process, and determining the optimal amount of antibody required, leading to a streamlined process with significant time savings up to two days. Recovery experiments demonstrate successful capture of the target analyte by the Affinity-VAMS, while matrix effects and stability assessments indicate no negative effects from serum matrix or storage conditions. Finally, quantitative analysis shows promising performance of the Affinity-VAMS in detecting different concentrations of the target analyte in the concentration range between 7.5 - 25 ng·mL−1. The calculated correlation factor was R2 of 0.9988 and limit of detection 2.5 ng·mL−1. The precision lays within the ICH guidelines for bioanalytical method validation. While this report is focused on the proof of concept of the Affinity-VAMS, our findings demonstrate the potential for the usage of modified VAMS in remote sampling and integrated sample processing, enhancing biomarker analysis in clinical and research settings.

BACKGROUND: Recent 3-dimensional optical (3DO) imaging advancements have provided more accessible, affordable, and self-operating opportunities for assessing body composition. 3DO is accurate and precise in clinical measures made by DXA. However, the sensitivity for monitoring body composition change over time with 3DO body shape imaging is unknown. OBJECTIVES: This study aimed to evaluate the ability of 3DO in monitoring body composition changes across multiple intervention studies. METHODS: A retrospective analysis was performed using intervention studies on healthy adults that were complimentary to the cross-sectional study, Shape Up! Adults. Each participant received a DXA (Hologic Discovery/A system) and 3DO (Fit3D ProScanner) scan at the baseline and follow-up. 3DO meshes were digitally registered and reposed using Meshcapade to standardize the vertices and pose. Using an established statistical shape model, each 3DO mesh was transformed into principal components, which were used to predict whole-body and regional body composition values using published equations. Body composition changes (follow-up minus the baseline) were compared with those of DXA using a linear regression analysis. RESULTS: The analysis included 133 participants (45 females) in 6 studies. The mean (SD) length of follow-up was 13 (5) wk (range: 3-23 wk). Agreement between 3DO and DXA (R2) for changes in total FM, total FFM, and appendicular lean mass were 0.86, 0.73, and 0.70, with root mean squared errors (RMSEs) of 1.98 kg, 1.58 kg, and 0.37 kg, in females and 0.75, 0.75, and 0.52 with RMSEs of 2.31 kg, 1.77 kg, and 0.52 kg, in males, respectively. Further adjustment with demographic descriptors improved the 3DO change agreement to changes observed with DXA. CONCLUSIONS: Compared with DXA, 3DO was highly sensitive in detecting body shape changes over time. The 3DO method was sensitive enough to detect even small changes in body composition during intervention studies. The safety and accessibility of 3DO allows users to self-monitor on a frequent basis throughout interventions. This trial was registered at clinicaltrials.gov as NCT03637855 (Shape Up! Adults; https://clinicaltrials.gov/ct2/show/NCT03637855); NCT03394664 (Macronutrients and Body Fat Accumulation: A Mechanistic Feeding Study; https://clinicaltrials.gov/ct2/show/NCT03394664); NCT03771417 (Resistance Exercise and Low-Intensity Physical Activity Breaks in Sedentary Time to Improve Muscle and Cardiometabolic Health; https://clinicaltrials.gov/ct2/show/NCT03771417); NCT03393195 (Time Restricted Eating on Weight Loss; https://clinicaltrials.gov/ct2/show/NCT03393195), and NCT04120363 (Trial of Testosterone Undecanoate for Optimizing Performance During Military Operations; https://clinicaltrials.gov/ct2/show/NCT04120363).