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The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the studys core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition protocol for all 27 HBCD Study recruitment sites to measure brain structure, function, microstructure, and metabolites. Acquisition parameters of individual modalities have been matched across MRI scanner platforms for harmonized acquisitions and state-of-the-art technologies are employed to enable faster and motion-robust imaging. Here, we provide an overview of the HBCD MRI protocol, including decisions of individual modalities and preliminary data. The result will be an unparalleled resource for examining early neurodevelopment which enables the larger scientific community to assess normative trajectories from birth through childhood and to examine the genetic, biological, and environmental factors that help shape the developing brain.

CASE SUMMARY: This report describes the diagnostic findings, natural history and genetic analysis of the candidate gene Forkhead Box F1 (FOXF1) in a young cat with developmental lung disease and high probability of pulmonary hypertension. A 1-year-old male entire Chartreux cat was referred for cardiac murmur investigation and exercise intolerance. Echocardiography identified a high-velocity tricuspid regurgitant jet with right-sided cardiac changes, supporting a high probability of pulmonary hypertension. No congenital cardiac shunts or left-sided cardiac changes were found to support a primary cardiac cause of pulmonary hypertension. Extensive laboratory work, thoracic radiographs and CT were performed. Histopathological characterisation (lung biopsy and later post mortem) was necessary to reach the final diagnosis. Eight months after diagnosis, the cat developed right-sided congestive heart failure, eventually leading to euthanasia. Survival from diagnosis to death was 12 months. RELEVANCE AND NOVEL INFORMATION: Developmental lung disease belongs to a group of diffuse lung diseases in humans associated with pulmonary hypertension. The veterinary literature describing lung growth disorders in cats is sparse, and the present report provides information on clinical presentation and progression alongside a thorough diagnostic workup, which may aid clinicians in identifying this condition. Lung biopsy was pivotal in reaching the final diagnosis. No causal variants in FOXF1 were identified.

Abstract The goal of the study was to apply a musculoskeletal knee model that considers individual tibiofemoral alignment (TFA) and to investigate its effect on knee contact force (KCF) during gait in mechanically (MA) and kinematically aligned (KA) total knee arthroplasty (TKA) patients. Total, medial, and lateral KCF was estimated from pre- and postoperative gait data of TKA patients (MA: n = 26, KA: n = 22). Preoperative KCF was compared between the generic and the adapted model using t-tests and statistical parametric mapping (SPM). The TFA-adapted model was then used to analyze pre- to postoperative differences in MA and KA patients. The factor of TFA increased estimates of KCF during the stance phase and led to higher peak contact forces (3–5%, p

This perspective piece explores the transformative potential and associated challenges of large language models (LLMs) in education and how those challenges might be addressed utilizing playful and game-based learning. While providing many opportunities, the stochastic elements incorporated in how present LLMs process text, requires domain expertise for a critical evaluation and responsible use of the generated output. Yet, due to their low opportunity cost, LLMs in education may pose some risk of over-reliance, potentially and unintendedly limiting the development of such expertise. Education is thus faced with the challenge of preserving reliable expertise development while not losing out on emergent opportunities. To address this challenge, we first propose a playful approach focusing on skill practice and human judgment. Drawing from game-based learning research, we then go beyond this playful account by reflecting on the potential of well-designed games to foster a willingness to practice, and thus nurturing domain-specific expertise. We finally give some perspective on how a new pedagogy of learning with AI might utilize LLMs for learning by generating games and gamifying learning materials, leveraging the full potential of human-AI interaction in education.

Abstract Yersinia pestis has been infecting humans since the Late Neolithic (LN). Whether those early infections were isolated zoonoses or initiators of a pandemic remains unclear. We report Y. pestis infections in two individuals (of 133) from the LN necropolis at Warburg (Germany, 5300–4900 cal BP). Our analyses show that the two genomes belong to distinct strains and reflect independent infection events. All LN genomes known today (n = 4) are basal in the phylogeny and represent separate lineages that probably originated in different animal hosts. In the LN, an opening of the landscape resulted in the introduction of new rodent species, which may have acted as Y. pestis reservoirs. Coincidentally, the number of dogs increased, possibly leading to Y. pestis infections in canines. Indeed, we detect Y. pestis in an LN dog. Collectively, our data suggest that Y. pestis frequently entered human settlements at the time without causing significant outbreaks.

Abstract The recent return of samples from asteroid 162173 Ryugu provides a first insight into early Solar System prebiotic evolution from known planetary bodies. Ryugu’s samples are CI chondrite-like, rich in water and organic material, and primarily composed of phyllosilicate. This phyllosilicate surrounds micron to submicron macromolecular organic particles known as insoluble organic matter. Using advanced microscopy techniques on Hayabusa-2 samples, we find that aqueous alteration on Ryugu produced organic particles richer in aromatics compared to less altered carbonaceous chondrites. This challenges the view that aromatic-rich organic matter formed pre-accretion. Additionally, widespread diffuse organic material occurs in phyllosilicate more aliphatic-, carboxylic-rich, and aromatic-poor than the discrete organic particles, likely preserving the soluble organic material. Some organic particles evolved to encapsulate phyllosilicate, indicating that aqueous alteration on Ryugu led to the containment of soluble organic matter within these particles. Earth therefore has been, and continues to be, delivered micron-sized polymeric organic objects containing biologically relevant molecules.

Forests cover one-third of the global land and are important components of carbon and nitrogen cycling. Anthropogenic disturbances, such as forest road systems or skid trails for timber harvesting, can dramatically change the nutrient cycling in these ecosystems. Skid trails increase soil erosion and thus the displacement of soil organic carbon (SOC) and total nitrogen (Nt). Additionally, runoff transports high amounts of dissolved organic carbon (DOC), which can have a negative impact on aquatic ecosystems. One of the most important countermeasures against soil erosion is the quick recolonization of vegetation. To date, the extent to which natural vegetation succession influences the relocation of SOC and Nt, and in particular the role of mosses in this context, has not been well investigated. This study investigates the influence of natural vegetation succession and in particular of mosses on the displacement process of SOC and Nt as well as DOC caused by soil erosion. To this end, we combine the results of a field study using in-situ rainfall simulations with small-scale runoff plots in skid trails of the Schönbuch Nature Park in southwestern Germany with the results of ex-situ rainfall simulation experiments with infiltration boxes containing the substrate from the respective skid trails. The eroded sediments of skid trails were on average enriched in SOC by 16% and in Nt by 35% compared to the original soil, which lead to a decrease of the C/N ratio in sediments. As vegetation succession progressed, the displacement of SOC and Nt was reduced, confirmed by a negative correlation between the enrichment ratios of SOC (ERSOC), Nt and total vegetation cover. However, mosses tended to reduce ERSOC more than vascular plants. Additionally, mosses significantly decreased DOC concentration in surface runoff compared to bare soils, while no difference in DOC concentration in percolated water could be observed. Future research should explore the role of mosses in the storage of SOC and Nt in the soil and their impact on soil stability. Thus, utilizing mosses could potentially minimize environmental impacts from soil disturbances in forests.

Objetivo: Identificar la presencia de desigualdades sociales en la mortalidad por lesiones de tránsito en las jurisdicciones argentinas, según su nivel de desarrollo socioeconómico. Metodología: Se realizó un estudio ecológico con nivel de agregación jurisdiccional para los años 2005, 2011 y 2016. La desigualdad entre jurisdicciones se estimó mediante el índice y la curva de concentración. Se utilizó como variable socioeconómica de ordenamiento el índice de desarrollo humano por jurisdicción y sus componentes por separado. Resultados: El índice de concentración arrojó un valor negativo en los tres años (−0,032 en 2005, −0,094 en 2011 y −0,065 en 2016), indicando que existe una mayor concentración de la mortalidad por lesiones de tránsito en las jurisdicciones con menor índice de desarrollo humano, aunque los valores muestran una tendencia a la disminución de estas desigualdades sociales entre los años 2011 y 2016. El componente que explica en mayor medida esta concentración es el indicador de ingresos. Conclusión: Existen desigualdades sociales en la mortalidad por lesiones de tránsito en las jurisdicciones argentinas según su nivel de desarrollo socioeconómico, principalmente explicadas por el nivel de ingreso. Las políticas de prevención de lesiones de tránsito deben tener en cuenta las cuestiones socioeconómicas de la población.

Abstract One of the most challenging aspects of developing advanced cell therapy products (CTPs) is defining the mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented that is consistent with the existing regulatory guidelines, but also accommodates what has been learned from the 27 US FDA-approved CTPs. Available information regarding MOA, potency and efficacy for the 27 FDA-approved CTPs is reviewed to provide background and perspective. Potency process and efficacy process charts are introduced to clarify and illustrate the relationships between six key concepts: MOA, potency, potency test, efficacy, efficacy endpoint and efficacy endpoint test. Careful consideration of the meaning of these terms makes it easier to discuss the challenges of correlating potency test results with clinical outcomes and to understand how the relationships between the concepts can be misunderstood during development and clinical trials. Examples of how a product can be “potent but not efficacious” or “not potent but efficacious” are presented. Two example applications of the framework compare how MOA is assessed in cell cultures, animal models and human clinical trials and reveals the challenge of establishing MOA in humans. Lastly, important considerations for the development of potency tests for a CTP are discussed. These perspectives can help product developers set appropriate expectations for understanding a product’s MOA and potency, avoid unrealistic assumptions and improve communication among team members during the development of CTPs.