The status of digital pathology and associated infrastructure within Alzheimer\u27s Disease Centers

Digital pathology (DP) has transformative potential, especially for Alzheimer disease and related disorders. However, infrastructure barriers may limit adoption. To provide benchmarks and insights into implementation barriers, a survey was conducted in 2019 within National Institutes of Health\u27s Alzheimer\u27s Disease Centers (ADCs). Questions covered infrastructure, funding sources, and data management related to digital pathology. Of the 35 ADCs to which the survey was sent, 33 responded. Most respondents (81%) stated that their ADC had digital slide scanner access, with the most frequent brand being Aperio/Leica (62.9%). Approximately a third of respondents stated there were fees to utilize the scanner. For DP and machine learning (ML) resources, 41% of respondents stated none was supported by their ADC. For scanner purchasing and operations, 50% of respondents stated they received institutional support. Some were unsure of the file size of scanned digital images (37%) and total amount of storage space files occupied (50%). Most (76%) were aware of other departments at their institution working with ML; a similar (76%) percentage were unaware of multiuniversity or industry partnerships. These results demonstrate many ADCs have access to a digital slide scanner; additional investigations are needed to further understand hurdles to implement DP and ML workflows

Machine learning quantification of Amyloid-β deposits in the temporal lobe of 131 brain bank cases.

Accurate and scalable quantification of amyloid-β (Aβ) pathology is crucial for deeper disease phenotyping and furthering research in Alzheimer Disease (AD). This multidisciplinary study addresses the current limitations on neuropathology by leveraging a machine learning (ML) pipeline to perform a granular quantification of Aβ deposits and assess their distribution in the temporal lobe. Utilizing 131 whole-slide-images from consecutive autopsied cases at the University of California Davis Alzheimer Disease Research Center, our objectives were threefold: (1) Validate an automatic workflow for Aβ deposit quantification in white matter (WM) and gray matter (GM); (2) define the distributions of different Aβ deposit types in GM and WM, and (3) investigate correlates of Aβ deposits with dementia status and the presence of mixed pathology. Our methodology highlights the robustness and efficacy of the ML pipeline, demonstrating proficiency akin to experts' evaluations. We provide comprehensive insights into the quantification and distribution of Aβ deposits in the temporal GM and WM revealing a progressive increase in tandem with the severity of established diagnostic criteria (NIA-AA). We also present correlations of Aβ load with clinical diagnosis as well as presence/absence of mixed pathology. This study introduces a reproducible workflow, showcasing the practical use of ML approaches in the field of neuropathology, and use of the output data for correlative analyses. Acknowledging limitations, such as potential biases in the ML model and current ML classifications, we propose avenues for future research to refine and expand the methodology. We hope to contribute to the broader landscape of neuropathology advancements, ML applications, and precision medicine, paving the way for deep phenotyping of AD brain cases and establishing a foundation for further advancements in neuropathological research

Occurrence of Gasterophilus spp. in Weanling Foals in Southern Brazil

Background: The occurrence of gastrointestinal myiasis caused by Gasterophilus spp. larvae (Diptera: Oestridae) in adult horses has been widely characterized, however data on natural infestation in young foals have been lacking. This observation may be related to the absence of conclusive diagnosis in these individuals, most likely due to logistical or financial constraints. Gastric ulceration is a problem and a significant cause of morbidity in foals, particularly during the weaning stage; therefore, gasterophilosis should be included in the differential diagnosis. The primary purpose of this study was to determine the prevalence of gasterophilosis in 4- to 6-month-old weanling foals.Material, Methods & Results: Seventy-one healthy weanling foals were enrolled in the study. Physical assessment blood sampling and was completed in all foals before the commencement of the experiment. Gastroscopy examinations were performed under sedation (Detomidine 0.01 - 0.02 mg/kg) with a flexible endoscope inserted through nasogastric via. The lumen of the stomach was examined in order to search for botflies’ larvae. Following gastroscopy, foals were classified into 2 groups based on the presence of Gasterophilus spp. larvae in their stomachs: 1) Infected and 2) Not Infected. Infected foals received a single dose of commercial trichlorfon and albendazole equine oral gel and were stalled for 24 h. The passed feces were thoroughly examined, searching for elimination of larvae. A Total of 64% of the foals (n=45/71) harbored Gasterophilus spp. larvae in the stomach. Mild hyperemia in the gastric mucosa was observed in the attachment sites of the parasites. Physical assessment and hematological parameters’ data were analyzed with Shapiro-Wilk normality test. Comparison between groups for clinical signs, hematological parameters and Gasterophilus spp. infection rates were evaluated using the Kruskal-Wallis test or Student's t-test. Statistical significance was set at P < 0.05. There were no statistically significant variations in physical and hematological parameters between foals that were affected and those that were not infected. The larvae found in the feces were subjected to morphological examination, which confirmed the diagnosis of Gasterophilus intestinalis.Discussion: No systemic clinical indications compatible with Gasterophilus infestation were seen, as described in previous studies of horses infected with the parasite. No botfly eggs were observed in the hair of evaluated foals. During gastroscopy, mild hyperemic lesions in the gastric mucosa were observed in the larvae fixation sites. Although no changes in clinical or hematological parameters were noted, the confirmation of parasite presence is a cause for concern due to horses' tolerance for low infestation levels and poor diagnosis. Additionally, the presence of this myiasis in foals may be a significant stressor during the weaning period and should be included in the differential diagnosis of recurring abdominal pain. Furthermore, infected foals might be a reservoir for the parasite and, contribute to the elimination and spread of the larvae in the environment. Thus, inclusion of young horses in deworming protocols targeted to botfly larvae is needed. This is the first report of Gasterophilus intestinalis myiasis in foals in Brazil. Further research is necessary to fully understand the epidemiology and prevalence of this condition in young horses in Brazil, based on the findings of this study. Keywords: Gasterophilus intestinalis, cavity myiasis, gastroscopy, Oestridae

Validation of the Modified Shuttle Test to Predict Peak Oxygen Uptake in Youth Asthma Patients Under Regular Treatment

Background: Oxygen uptake (VO2) evaluations by cardiopulmonary exercise test is expensive and time-consuming. Estimating VO2 based on a field test would be an alternative.Objective: To develop and validate an equation to predict VO2peak based on the modified shuttle test (MST).Methods: Cross sectional study, with 97 children and adolescents with asthma. Participants were divided in two groups: the equation group (EG), to construct the equation model of VO2peak, and the cross-validation group (VG). Each subject performed the MST twice using a portable gas analyzer. The peak VO2peak during MST was used in the equation model. The patients’ height, weight, gender, and distance walked (DW) during MST were tested as independent variables.Results: The final model [-0.457 + (gender × 0.139) + (weight × 0.025) + (DW × 0.002)] explained 87% of VO2peak variation. The VO2peak predicted was similar to VO2peak measured by gas analyzer (1.9 ± 0.5 L/min and 2.0 ± 0.5 L/min, respectively) (p = 0.67), and presented significant ICC 0.91 (IC95% 0.77 to 0.96); p < 0.001. The Bland–Altman analysis showed low bias (-0.15 L/min) and limits of agreement (-0.65 to 0.35 L/min). There was no difference in DW between EG (760 ± 209 m) and VG (731 ± 180 m), p = 0.51.Conclusion: The developed equation adequately predicts VO2peak in pediatric patients with asthma

Razão Amplitude de Distribuição dos Glóbulos Vermelhos (RDW) – Plaquetas (RPR): Novas possibilidades diagnósticas para doenças perinatais em potros neonatos

As doenças perinatais são a principal causa de morte em potros de até 7 dias de idade. Os sinais clínicos de enfermidades em potros frequentemente são inespecíficos e animais não tratados agravam rapidamente o quadro clínico. Portanto, a detecção precoce do início do processo é essencial. É necessário o desenvolvimento de marcadores rápidos e sensíveis para auxiliar no diagnóstico de doenças perinatais em potros. Os parâmetros RDW e RPR são derivados do hemograma e estão sendo estudados em medicina humana como marcadores de inflamação em diversas enfermidades. Portanto, o objetivo deste trabalho foi reportar os valores de RDW e RPR e investigar a possível aplicação destes índices em potros neonatos classificados como saudáveis ou de risco, baseado em informações obstétricas e clínicas. Realizou-se um estudo caso-controle retrospectivo, em que 309 potros Puro Sangue Inglês ≤ 24h nascidos a termo foram avaliados 15 minutos após o parto e amostras de sangue foram coletadas dentro das primeiras 24 horas de vida. Um escore de risco foi calculado baseado em dados clínicos e obstétricos e os potros foram categorizados em dois grupos: saudáveis e de risco. Os potros que apresentaram reflexos comportamentais, exame físico e hemograma dentro dos parâmetros de referência e tempo de gestação entre 320 e 365 dias foram considerados saudáveis. Potros que nasceram de parto distócico, apresentaram reflexos comportamentais alterados (decúbito esternal > 5 minutos, reflexo de sucção > 20 minutos, permanecer em estação > 1 hora), tempo gestacional > 365 dias, e/ou apresentando características físicas/hematológicas de dismaturidade (pelagem fina, abaulamento de cabeça, flacidez de orelhas, desproporção na razão granulócito:linfócito) foram categorizados no grupo de risco. A normalidade dos dados foi avaliada utilizando o teste Shapiro-Wilk. A influência dos grupos e do sexo dos potros nas variáveis hematológicas (hemácias, hemoglobina, VCM, HCM, HCMC, RDW, plaquetas e contagem total de leucócitos) foi verificada por meio do teste T. A correlação entre tempo gestacional e RDW e RPR foi analisada por meio do teste de coeficiente de Pearson. Variáveis contínuas estão apresentadas como média ± desvio padrão. Variáveis categóricas estão apresentadas como frequências e porcentagens. As análises estatísticas foram conduzidas no pacote estatístico R, e o valor de significância estabelecido em P < 0.05. Com base no escore de risco, 221 (71,6%) dos potros foram classificados como saudáveis e 88 potros (28,4%) foram considerados em risco de desenvolvimento de doenças perinatais (grupo de risco). O tempo de gestação médio de todos os potros foi 346,31 ± 9,69 dias. Os valores de RDW não foram diferentes entre os grupos. O tempo gestacional demonstrou ter correlação negativa com RDW (r = -0,156, P = 0,005) e VCM (r = -0,135, P = 0,01), indicando uma relação destas variáveis com maturidade dos potros. Os valores de RPR foram mais altos para os potros de risco (0,073 ± 0,018) do que nos potros saudáveis (0.068 ± 0,014, P = 0.01). Portanto, o RPR é um índice de baixo custo, acessível, e pode ser um indicador promissor de enfermidades na triagem a campo de potros neonatos, e rapidamente estimar possíveis alterações sistêmicas. Mais estudos longitudinais multicêntricos são necessários para expandir a aplicabilidade do RPR em potros neonatos.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESPerinatal diseases are the leading cause of death among foals up to 7 days of age. Early clinical signs of diseases in neonatal foals are often non-specific, and untreated foals deteriorate rapidly. Therefore, early detection of the disease onset is essential. The development of rapid and accurate markers to aid in diagnosing neonatal foals is needed. The CBC parameters redblood cell distribution width (RDW) and RDW to platelet ratio (RPR) have been used in human medicine as markers of inflammation in many diseases. Therefore, the purpose of this work was to report the values of RDW and RPR in neonatal foals and to investigate their possible correlation with a risk score based on obstetric and clinical data. In this retrospective case-control study, 309 full-term Thoroughbred foals less than 24h old were clinically evaluated within 15 minutes after birth, and blood samples were collected within 24h of life. Foals showing an unremarkable physical examination, normal gestational length (320 to 365 days), adequate righting reflexes, and CBC values within the normal range were considered healthy. Foals that were born through dystocia, displayed delayed adaptative milestones (sternal recumbence > 5 minutes, suckling reflex > 20 minutes, stand >1 hour), gestational length > 365 days, and/or displayed physical/hematological characteristics of dysmaturity (silky hair-coat, domed head, floppy ears, abnormal granulocyte:lymphocyte ratio), were categorized in the group at-risk. Extracted data were assessed for normal distribution using the Shapiro-Wilk test. The Student’s T-test was used to evaluate the influence of groups and foal sex on hematological variables (RBC, hematocrit, hemoglobin, MCV, MCH, MCHC, RDW, platelets, WBC). Pearson's coefficient test was used to analyze the associations between gestational length and RDW, and RPR. Continuous variables are presented as mean ± SD. Categorical variables are presented as frequencies and percentages. All statistical analysis was conducted in the statistical package R Studio, and significance was set at P < 0.05. Based on the risk score, 221 (71.6%) foals were healthy, and 88 (28.4%) were considered at risk of developing perinatal disease (at-risk group). The mean gestational age for all the foals was 346.31 ± 9.69 days. RDW values did not differ between groups. Gestational length demonstrated to have a negative correlation with RDW (r = -0.156, P = 0.005) and MCV (r = -0.135, P = 0.01), indicating a link of these variables to foal maturity. RPR was higher for at-risk (0.073 ± 0.018) than for healthy foals (0.068 ± 0.014, P = 0.01). Therefore, the RPR ratio is a low-cost, readily accessible index and might be a promising early indicator of disease for the field triage of neonatal foals and rapidly estimate possible systemic disorders. For further expanding the applicability of RPR in neonatal foals, multicenter longitudinal studies with a larger number of healthy and critically ill neonates are necessary