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Confirmation of extracellular amyloid deposition across various animal species and tissue types has been a long-standing challenge in veterinary diagnostic pathology. Transmission electron microscopy (TEM) has historically been used to advance the understanding of amyloid fibril morphology and confirm amyloid fibril deposition when histologic methods provide unclear results. We assessed the feasibility of utilizing TEM for routine confirmation of amyloidosis as an addition to histology. We analyzed ex situ amyloid fibrils with direct, negative-contrast TEM and in situ amyloid fibrils with aldehyde-fixed, plastic-embedding TEM to confirm amyloidosis in a variety of cases in which amorphous extracellular amyloid deposits had been identified by H&E and Congo red staining. We compared the 2 TEM methods and documented amyloid fibril morphology and morphometry in 7 species (goat, guinea pig, kudu, fox, sheep, flamingo, and duck). Ex situ fibrils had helical morphology and widths of 15-18 nm across all species. Fibril crossover distances had more interspecies variation of 60-130 nm, and species could be grouped based on pitch (twist size). Twisting patterns of in situ fibrils could not be visualized, but in situ widths of 10 nm were measured across all species. In 4 different chicken cases, fibrils differing morphologically from amyloid were consistently detected via both TEM methods, suggesting the possibility of a non-amyloid deposit that is commonly diagnosed as amyloidosis based on its histologic appearance. When available, we recommend routine confirmation of amyloid fibril deposition by TEM.

BACKGROUND: A substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European (EUR) and Asian ancestries, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L-specific variants among self-reported H/L women. METHODS: PRS performance was evaluated using multivariable logistic regression and the area under the ROC curve. RESULTS: Both EUR and Asian PRSs performed worse in H/L samples compared with original reports. The best EUR PRS performed better than the best Asian PRS in pooled H/L samples. EUR PRSs had decreased performance with increasing Indigenous American (IA) ancestry, while Asian PRSs had increased performance with increasing IA ancestry. The addition of two H/L SNPs increased performance for all PRSs, most notably in the samples with high IA ancestry, and did not impact the performance of PRSs in individuals with lower IA ancestry. CONCLUSIONS: A single PRS that incorporates risk variants relevant to the multiple ancestral components of individuals from Latin America, instead of a set of ancestry-specific panels, could be used in clinical practice. IMPACT: The results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry-specific variants into PRSs for clinical application.

Inclusive education presents a significant challenge for contemporary society. All children should have the opportunity to develop according to their educational needs within an inclusive environment. The effectiveness of the school support team plays a crucial role in achieving this goal. This research aimed to explore the perspectives of teaching staff in kindergartens, including headmasters, teachers, and teaching assistants, regarding inclusive education, with a specific focus on their views and attitudes towards the roles of school special educators and teaching assistants in preschool education. A mixed-methods research strategy was employed to achieve this aim. Data were collected using a self-constructed questionnaire containing both closed and open items, completed by 394 respondents from 142 kindergartens. The findings indicated that teaching staff perceived the existence of a school support team as having a positive impact on addressing various children's issues and enhancing teachers' work. These results contribute to a broader understanding of the roles and responsibilities of the members of a school support team in kindergartens.

In this article, the Education Studies Department (ESD) at Berea College shares lessons learned while becoming an inclusive, justice-focused, and democratic Education Preparation Program (EPP) together with its "Community of Teachers" (CoT). ESD values diversity, equity, inclusion, and belonging (DEI+B) and democratic relationships. These values influence how we do our work. We begin by sharing how the theoretical framework of Community of Practice (CoP) frames our case study. After explaining how a CoP applies to ESD's approach to educator preparation, we give an overview of Berea College. We share some of its history and its eight Great Commitments. We detail how ESD is a unique EPP compared with other more traditional EPPs. Next, we chronicle the story of how ESD "walks its talk" and invests in the teacher profession. We detail the participants of the case study, outline our methodology of the case study, and share the data we analyzed for this article. Data were analyzed and three emergent themes were discovered about the praxis of ESD: (a) community-engaged and justice-focused teacher preparation, (b) community building within teacher preparation programs, and (c) diversity, equity, inclusion, and belonging. The article concludes by sharing implications for EPPs and a conclusion.

BACKGROUND: The emergence of COVID-19 resulted in a substantial loss of education because of global school closures. Face masks are a potential measure to restrain the COVID-19 spread; therefore, this paper evaluated the effectiveness of face masks in reducing COVID-19 incidence in school settings. METHODS: A systematic review was conducted by searching the literature in the Cochrane COVID-19 Study Register and the World Health Organization COVID-19 global literature. Data were summarized in tabular forms, and the findings were presented as narrative synthesis. RESULTS: A total of 15,709 records were retrieved. The screening and selection led to the inclusion of 12 observational and 2 quasi-experimental studies. Nine studies were conducted in different states, counties, or districts of the United States, and the remaining 5 were reported from Germany, Finland, Spain, and the United Kingdom. The results of 10 out of 14 studies favored mask use in reducing school COVID-19 incidence. Three studies found no link between mask use and COVID-19 incidences, whereas 1 quasi-experimental study noted a higher COVID-19 incidence with mask use in students aged 6-11 years than no use of mask among preschool children aged 3-5 years. CONCLUSION: Mask mandates may lessen the incidence of respiratory infectious diseases in school settings during a pandemic; more well-designed studies are warranted to clarify further the evidence regarding mask use in school settings.

To accelerate medical breakthroughs, the All of Us Research Program aims to collect data from over one million participants. This report outlines processes used to construct the All of Us Social Determinants of Health (SDOH) survey and presents the psychometric characteristics of SDOH survey measures in All of Us. A consensus process was used to select SDOH measures, prioritizing concepts validated in diverse populations and other national cohort surveys. Survey item non-response was calculated, and Cronbachs alpha was used to analyze psychometric properties of scales. Multivariable logistic regression models were used to examine associations between demographic categories and item non-response. Twenty-nine percent (N = 117,783) of eligible All of Us participants submitted SDOH survey data for these analyses. Most scales had less than 5% incalculable scores due to item non-response. Patterns of item non-response were seen by racial identity, educational attainment, income level, survey language, and age. Internal consistency reliability was greater than 0.80 for almost all scales and most demographic groups. The SDOH survey demonstrated good to excellent reliability across several measures and within multiple populations underrepresented in biomedical research. Bias due to survey non-response and item non-response will be monitored and addressed as the survey is fielded more completely.

Abstract High-grade B-cell lymphomas (HGBCLs) are aggressive blood cancers with a severe disease course, especially when the central nervous system (CNS) is involved. Standard histological examination depends on tissue availability and is currently supplemented with molecular tests, as the status of MYC, BCL2, or BCL6 gene rearrangements is required for proper lymphoma classification. This case report demonstrates the relevance of cerebrospinal fluid (CSF) cell-free DNA testing by integrative next-generation sequencing (NGS) panel. The benefit of this approach resided in tumor genotyping alongside the proof of CNS progression despite MRI negativity, revealing a clonal relationship with the primary tumor lesion. In addition, our strategy allowed us to classify the tumor as DLBCL/HGBL-MYC/BCL2 entity. In clinical practice, such a minimally invasive approach provides a more sensitive tool than standard imaging and cell analyzing techniques, enabling more accurate disease monitoring and relapse prediction in particular cases.

Abstract In previous research, we revealed that murine leukemia cells L1210 with induced expression of P-glycoprotein (P-gp, a membrane drug transporter, product of the Abcb1 gene) are better able to withstand endoplasmic reticulum (ER) stress (ERS) than their P-gp negative counterparts. This was associated with increased GRP78/BiP expression and modulation of the expression of several other proteins active in the cellular response to ERS (like CHOP, spliced XBP1, 50-kDa ATF6 protein fragment and others) in P-gp positive cells. Wolframin is an ER transmembrane protein, product of the WFS1 gene whose mutations are associated with Wolfram syndrome. However, this protein is frequently overexpressed in cells undergoing ERS and its expression may accompany changes in the above ERS markers. Therefore, our aim in this work was to investigate wolframin expression in P-gp-negative and P-gp-positive murine leukemia L1210 cells in relation to ERS related proteins in normal or ERS condition. We induced ERS in cells either by blocking N-glycosylation in the ER with tunicamycin or by blocking ER Ca2+-ATPase activity with thapsigargin, as known ER stressors. The results of this paper demonstrated increased wolframin expression in P-gp positive cells compared to P-gp negative cells. Immunoprecipitation experiments revealed the formation of complexes between wolframin and ERS related proteins (PERK, ATF6 and GRP78/BiP), the amount of which varied depending on the presence of the above ER stressors. Graphical Abstract

The labile fractions of organic carbon (OC), which are a reflection of the properties of soil and its use, appear to be suitable parameters for their use as indicators. The aim of this study was to determine the reliable and relatively simple indicators for detecting the chemical and physical stabilizations of OC, which would respond sensitively to land use. The study includes forest ecosystem (FE) and agroecosystem (AE) with different tillage intensities (reduced tillage, RT and conventional tillage, CT) on real farms. Parameters of the labile C and N were tested. For a depth of < 0.1 m in the FE, the hot water extractable organic carbon (HWEOC) for chemical stabilization and labile nitrogen (NL) for physical stabilization appear as the most suitable indicators. Higher values of HWEOC indicate the OC stabilization by decreasing decomposition, pH or by increasing carbonates, recalcitrant fractions, and higher values of NL by OC incorporation into the silt fraction and larger macro-aggregates. In the AE with RT, these are the HWEOC for chemical stabilization and carbon pool index (CPI) or index of carbon lability (LIC) for physical stabilization. Higher values of CPI and LIC indicate the stabilization by the formation of size-optimal dry-sieved (DSA; 1-3 mm) and wet-sieved (WSA; 1-2 mm) soil aggregates. In the AE with CT, it was the NL. Its higher values point to the stabilization through the carbonates, alkaline cations, size-fraction of > 0.01 mm and the formation of DSA (1-3 mm). For a depth of < 0.3 m in the AE, these are the CL (for RT), higher value of which points to the stabilization by clay and alkaline cations, and HWEOC (for CT), higher value of which indicates the stabilization in the conditions of the soil acidification.

The CompSafeNano project, a Research and Innovation Staff Exchange (RISE) project funded under the European Union's Horizon 2020 program, aims to advance the safety and innovation potential of nanomaterials (NMs) by integrating cutting-edge nanoinformatics, computational modelling, and predictive toxicology to enable design of safer NMs at the earliest stage of materials development. The project leverages Safe-by-Design (SbD) principles to ensure the development of inherently safer NMs, enhancing both regulatory compliance and international collaboration. By building on established nanoinformatics frameworks, such as those developed in the H2020-funded projects NanoSolveIT and NanoCommons, CompSafeNano addresses critical challenges in nanosafety through development and integration of innovative methodologies, including advanced in vitro models, in silico approaches including machine learning (ML) and artificial intelligence (AI)-driven predictive models and 1st-principles computational modelling of NMs properties, interactions and effects on living systems. Significant progress has been made in generating atomistic and quantum-mechanical descriptors for various NMs, evaluating their interactions with biological systems (from small molecules or metabolites, to proteins, cells, organisms, animals, humans and ecosystems), and in developing predictive models for NMs risk assessment. The CompSafeNano project has also focused on implementing and further standardising data reporting templates and enhancing data management practices, ensuring adherence to the FAIR (Findable, Accessible, Interoperable, Reusable) data principles. Despite challenges, such as limited regulatory acceptance of New Approach Methodologies (NAMs) currently, which has implications for predictive nanosafety assessment, CompSafeNano has successfully developed tools and models that are integral to the safety evaluation of NMs, and that enable the extensive datasets on NMs safety to be utilised for the re-design of NMs that are inherently safer, including through prediction of the acquired biomolecule coronas which provide the biological or environmental identities to NMs, promoting their sustainable use in diverse applications. Future efforts will concentrate on further refining these models, expanding the NanoPharos Database, and working with regulatory stakeholders thereby fostering the widespread adoption of SbD practices across the nanotechnology sector. CompSafeNano's integrative approach, multidisciplinary collaboration and extensive stakeholder engagement, position the project as a critical driver of innovation in NMs SbD methodologies and in the development and implementation of computational nanosafety.

Abstract Background Non-invasive ventilation (NIV) uses positive pressure to assist people with respiratory muscle weakness or severe respiratory compromise to breathe. Most people use this treatment during sleep when breathing is most susceptible to instability. The benefits of using NIV in motor neurone disease (MND) are well-established. However, uptake and usage are low (~ 19%) and there is no consensus on how to best implement NIV in MND in Australia. Consequently, clinical practice models are highly variable. Our team has recently provided evidence that specific and individualised NIV titration using a sleep study (polysomnography; PSG) leads to better outcomes in people with MND. However, for this clinical practice model to result in sustained benefits, evidence of effectiveness across multiple sites, as well as culture and practice change, must occur. Methods A two-arm, assessor-blinded, individual participant randomised controlled trial in MND care centres across Australia will be undertaken. Two-hundred and forty-four participants will be randomised (1:1) to either the intervention group (PSG-assisted commencement of NIV settings; PSG) or a control group (sham PSG). Participants will be asked to use their NIV device for 7 weeks and will then return for follow-up assessments. Respiratory, sleep and patient-reported outcome measures will be collected at baseline and follow-up. The primary aim is to determine if the proportion of participants using NIV for > 4 h/day during the intervention period is higher in the PSG than the control group. A process evaluation, health economic evaluation and 12-month cohort follow-up will be undertaken and reported separately. Discussion The results of this trial will demonstrate the effects of PSG-assisted titration of NIV on usage of NIV in people with MND. We hypothesise that the PSG intervention will improve synchrony between the user and the machine, which will lead to greater NIV usage compared to the control group. Trial registration ClinicalTrials.gov NCT05136222. Registered on November 25, 2021.

America's diet-related illness crisis intersects with a lack of nutrition literacy, nutrition security, and systemic inequities. The Cooperative Extension Service's (CES) national infrastructure could potentially provide equitable access to quality nutrition education in the US utilizing a Master Food Volunteer (MFV) model. This research brief examined preliminary evidence for the MFV model as a support for CES agents and paraprofessionals, and results show a paucity of evidence. Further research and a pilot program with pre-established measures for health-related knowledge and behaviors could elucidate the model's potential to increase equitable access to evidence-based programming, nutrition, and implementation guidance.

• Antecedentes: Durante los últimos años, la producción láctea ha incrementado de un 2 a 3% por vaca por año y con ello los requerimientos de las necesidades nutricionales. Se han estudiado diferentes alternativas de alimentación de la especie bovina para poder satisfacer dichas demandas. Evaluar el efecto del reemplazo de la pasta de soya por el grano de chocho (Lupinus mutabilis) en un alimento balanceado para vacas lecheras. Materiales y métodos: El trabajo se llevó a cabo en la granja experimental “Irquis” de la Universidad de Cuenca ubicada en provincia del Azuay. Se seleccionaron 6 pares de vacas Holstein no registradas en la asociación de la raza, cada pareja con igual paridad, y se dividieron en dos grupos con una vaca de cada par. Se utilizó un diseño de cambio Switchback para dos tratamientos; balanceado con lupino y balanceado con soya, de tres periodos, con recesos entre ellos, cada uno compuesto de tres días de adaptación iniciales y luego siete de mediciones con pesaje de la leche producida individualmente. Al llegar al último día de cada periodo se tomaron muestras de 400 ml de leche de las doce vacas y se transportó al laboratorio de Lactología de la Universidad de Cuenca para ser analizados en %grasa, %proteína, %lactosa, %sólidos totales, %sólidos grasos y densidad. Resultados: Los resultados de producción láctea, calidad de la leche, el porcentaje de grasa, sólidos totales, densidad y pH no presentaron diferencia significativa (P ˃ 0,05) entre ambos tratamientos. Sin embargo, el tratamiento con soya fue superior, (P < 0, 05) en proteína, lactosa y sólidos no grasos. Conclusiones: El uso del lupino en la alimentación para vacas lecheras pudiera reemplazar efectivamente a la pasta de soya como fuente proteica y de extracto etéreo para la fabricación de alimentos balanceados, ya que debido a su composición nutricional puede influir en la producción láctea a niveles similares que la pasta de soya, pero se requieren más experimentos en este tema. • Palabras clave: bóvidos, lupino, concentrado, producción lechera (Fuente: AGROVOC)