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1.
Pathologie (Heidelb) ; 2024 Apr 10.
Artigo em Alemão | MEDLINE | ID: mdl-38598097

RESUMO

BACKGROUND: Artificial intelligence (AI) systems have showed promising results in digital pathology, including digital nephropathology and specifically also kidney transplant pathology. AIM: Summarize the current state of research and limitations in the field of AI in kidney transplant pathology diagnostics and provide a future outlook. MATERIALS AND METHODS: Literature search in PubMed and Web of Science using the search terms "deep learning", "transplant", and "kidney". Based on these results and studies cited in the identified literature, a selection was made of studies that have a histopathological focus and use AI to improve kidney transplant diagnostics. RESULTS AND CONCLUSION: Many studies have already made important contributions, particularly to the automation of the quantification of some histopathological lesions in nephropathology. This likely can be extended to automatically quantify all relevant lesions for a kidney transplant, such as Banff lesions. Important limitations and challenges exist in the collection of representative data sets and the updates of Banff classification, making large-scale studies challenging. The already positive study results make future AI support in kidney transplant pathology appear likely.

2.
Int J Mol Sci ; 25(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612532

RESUMO

Cherry stems, prized in traditional medicine for their potent antioxidant and anti-inflammatory properties, derive their efficacy from abundant polyphenols and anthocyanins. This makes them an ideal option for addressing skin aging and diseases. This study aimed to assess the antioxidant and anti-inflammatory effects of cherry stem extract for potential skincare use. To this end, the extract was first comprehensively characterized by HPLC-ESI-qTOF-MS. The extract's total phenolic content (TPC), antioxidant capacity, radical scavenging efficiency, and its ability to inhibit enzymes related to skin aging were determined. A total of 146 compounds were annotated in the cherry stem extract. The extract effectively fought against NO· and HOCl radicals with IC50 values of 2.32 and 5.4 mg/L. Additionally, it inhibited HYALase, collagenase, and XOD enzymes with IC50 values of 7.39, 111.92, and 10 mg/L, respectively. Based on the promising results that were obtained, the extract was subsequently gently integrated into a cosmetic gel at different concentrations and subjected to further stability evaluations. The accelerated stability was assessed through temperature ramping, heating-cooling cycles, and centrifugation, while the long-term stability was evaluated by storing the formulations under light and dark conditions for three months. The gel formulation enriched with cherry stem extract exhibited good stability and compatibility for topical application. Cherry stem extract may be a valuable ingredient for creating beneficial skincare cosmeceuticals.


Assuntos
Antocianinas , Cosméticos , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia
3.
Angew Chem Int Ed Engl ; 63(23): e202401195, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38529534

RESUMO

The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur-containing amino lipids (SALs) involved in biofilm formation and marine surface colonization processes. Despite their physiological relevance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved, hindering progress in biochemical and functional investigations. Herein, we report the structural revision of a new group of SALs, which we named cysteinolides, using a combination of analytical techniques, isolation and degradation experiments and total synthetic efforts. Contrary to the previously proposed homotaurine-based structures, cysteinolides are composed of an N,O-acylated cysteinolic acid-containing head group carrying various different (α-hydroxy)carboxylic acids. We also performed the first validated targeted-network based analysis, which allowed us to map the distribution and structural diversity of cysteinolides across bacterial lineages. Beyond offering structural insight, our research provides SAL standards and validated analytical data. This information holds significance for forthcoming investigations into bacterial sulfonolipid metabolism and biogeochemical nutrient cycling within marine environments.


Assuntos
Lipídeos , Lipídeos/química , Roseobacter/metabolismo , Roseobacter/química , Estrutura Molecular , Organismos Aquáticos/química
4.
Pathologie (Heidelb) ; 45(3): 203-210, 2024 May.
Artigo em Alemão | MEDLINE | ID: mdl-38427066

RESUMO

BACKGROUND: Autopsies have long been considered the gold standard for quality assurance in medicine, yet their significance in basic research has been relatively overlooked. The COVID-19 pandemic underscored the potential of autopsies in understanding pathophysiology, therapy, and disease management. In response, the German Registry for COVID-19 Autopsies (DeRegCOVID) was established in April 2020, followed by the DEFEAT PANDEMIcs consortium (2020-2021), which evolved into the National Autopsy Network (NATON). DEREGCOVID: DeRegCOVID collected and analyzed autopsy data from COVID-19 deceased in Germany over three years, serving as the largest national multicenter autopsy study. Results identified crucial factors in severe/fatal cases, such as pulmonary vascular thromboemboli and the intricate virus-immune interplay. DeRegCOVID served as a central hub for data analysis, research inquiries, and public communication, playing a vital role in informing policy changes and responding to health authorities. NATON: Initiated by the Network University Medicine (NUM), NATON emerged as a sustainable infrastructure for autopsy-based research. NATON aims to provide a data and method platform, fostering collaboration across pathology, neuropathology, and legal medicine. Its structure supports a swift feedback loop between research, patient care, and pandemic management. CONCLUSION: DeRegCOVID has significantly contributed to understanding COVID-19 pathophysiology, leading to the establishment of NATON. The National Autopsy Registry (NAREG), as its successor, embodies a modular and adaptable approach, aiming to enhance autopsy-based research collaboration nationally and, potentially, internationally.


Assuntos
Autopsia , COVID-19 , Sistema de Registros , Humanos , COVID-19/epidemiologia , COVID-19/patologia , Alemanha/epidemiologia , Pandemias , SARS-CoV-2
5.
Antioxidants (Basel) ; 13(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38397815

RESUMO

Plant extracts rich in phenolic compounds have been reported to exert different bioactive properties. Despite the fact that there are plant extracts with completely different phenolic compositions, many of them have been reported to have similar beneficial properties. Thus, the structure-bioactivity relationship mechanisms are not yet known in detail for specific classes of phenolic compounds. In this context, this work aims to demonstrate the relationship of extracts with different phenolic compositions versus different bioactive targets. For this purpose, five plant matrices (Theobroma cacao, Hibiscus sabdariffa, Silybum marianum, Lippia citriodora, and Olea europaea) were selected to cover different phenolic compositions, which were confirmed by the phytochemical characterization analysis performed by HPLC-ESI-qTOF-MS. The bioactive targets evaluated were the antioxidant potential, the free radical scavenging potential, and the inhibitory capacity of different enzymes involved in inflammatory processes, skin aging, and neuroprotection. The results showed that despite the different phenolic compositions of the five matrices, they all showed a bioactive positive effect in most of the evaluated assays. In particular, matrices with very different phenolic contents, such as T. cacao and S. marianum, exerted a similar inhibitory power in enzymes involved in inflammatory processes and skin aging. It should also be noted that H. sabdariffa and T. cacao extracts had a low phenolic content but nevertheless stood out for their bioactive antioxidant and anti-radical capacity. Hence, this research highlights the shared bioactive properties among phenolic compounds found in diverse matrices. The abundance of different phenolic compound families highlights their elevated bioactivity against diverse biological targets.

6.
Chem Res Toxicol ; 37(2): 439-449, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38295294

RESUMO

Exposure to environmental pollutants is linked to numerous toxic outcomes, warranting concern about the effect of pollutants on human health. To assess the threat of pollutant exposure, it is essential to understand their biological activity. Unfortunately, gaps remain for many pollutants' specific biological activity and molecular targets. A superfamily of signaling proteins, G-protein-coupled receptors (GPCRs), has been shown as potential targets for pollutant activity. However, research investigating the pollutant activity at the GPCRome is scarce. This work explores pollutant activity across a library of human GPCRs by leveraging modern high-throughput screening techniques devised for drug discovery and pharmacology. We designed and implemented a pilot screen of eight pollutants at 314 human GPCRs and discovered specific polychlorinated biphenyl (PCB) activity at sphingosine-1-phosphate and melatonin receptors. The method utilizes open-source resources available to academic and governmental institutions to enable future campaigns that screen large numbers of pollutants. Thus, we present a novel high-throughput approach to assess the biological activity and specific targets of pollutants.


Assuntos
Poluentes Ambientais , Melatonina , Bifenilos Policlorados , Humanos , Poluentes Ambientais/toxicidade , Bifenilos Policlorados/toxicidade , Receptores de Esfingosina-1-Fosfato , Receptores Acoplados a Proteínas G/metabolismo
7.
Vet Sci ; 10(12)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38133246

RESUMO

This study assessed the impact of a mixture of garlic (Allium sativum) and oregano (Origanum vulgare) essential oils (EOGOs) on in vitro dry matter digestibility (IVDMD) and in vivo apparent nutrient digestibility. Different EOGO inclusion levels were evaluated to assess the dose response and potential effects of the mixture. Three EOGO inclusion levels (0.5, 0.75, and 1 mL/kg of incubated dry matter) were evaluated in vitro, while four treatments (0.5, 0.75, and 1 mL/day of EOGO and a control group) were tested in vivo on 12 West African sheep. A randomized controlled trial was conducted using a 4 × 4 design. Blood parameters (glucose, blood urea nitrogen, and ß-hydroxybutyrate) were measured to observe the effect of EOGO on the metabolism. The results showed that the inclusion of EOGO significantly enhanced IVDMD at low levels (p < 0.052) compared with the highest levels in treatments containing 0.5 and 0.75 mL/kg of EOGO dry matter. A higher intake of dry matter (DM), crude protein (CP), and neutral detergent fiber (NDF) (p < 0.05) was observed in the in vivo diets with the inclusion of EOGO. In terms of in vivo apparent digestibility, significant differences were found among treatments in the digestibility coefficients of DM, CP, and NDF. EOGO inclusion increased the digestibility of DM. CP digestibility displayed a cubic effect (p < 0.038), with the lowest values of digestibility observed at 1 mL EOGO inclusion. Additionally, NDF digestibility showed a cubic effect (p < 0.012), with the highest value obtained at 0.75 mL of EOGO inclusion. The inclusion levels above 0.75 mL EOGO showed a cubic effect, which indicates that higher concentrations of EOGO may not be beneficial for the digestibility of CP and NDF. Although no significant difference was observed in total digestible nutrients, a linear trend was observed (p < 0.059). EOGO improved the intake of DM, CP, and NDF. EOGO supplementation improved the digestibility of DM and NDF, with optimal levels observed at 0.5 mL/day. No significant effects were observed in the blood parameters. These results suggest that EOGO has the potential as an additive in ruminal nutrition to improve food digestibility and serve as an alternative to antibiotic additives. The use of EOGO potentially improves fiber digestion and may reduce the use of antibiotics in livestock production. Garlic (A. sativum) and oregano (O. vulgare) essential oils effectively modulated fiber digestibility at 0.75 mL/day. Garlic (A. sativum) and oregano (O. vulgare) essential oils have the potential to improve digestibility at low inclusion levels and serve as an alternative to antibiotic additives. The effectiveness of essential oils is greater in a mixture and at lower doses.

8.
Br J Pharmacol ; 180 Suppl 2: S1-S22, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123153

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacologia , Humanos , Bases de Dados Factuais , Canais Iônicos , Ligantes , Receptores Citoplasmáticos e Nucleares
9.
Antioxidants (Basel) ; 12(10)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37891971

RESUMO

The constant growth of the cosmetic industry, together with the scientific evidence of the beneficial properties of phytochemicals, has generated great interest in the incorporation of bioactive extracts in cosmetic formulations. This study aims to evaluate the bioactive potential of a mango peel extract for its incorporation into cosmetic formulations. For this purpose, several assays were conducted: phytochemical characterization; total phenolic content (TPC) and antioxidant potential; free-radical scavenging capacity; and skin aging-related enzyme inhibition. In addition, the extract was incorporated into a gel formulation, and a preliminary stability study was conducted where the accelerated (temperature ramp, centrifugation, and heating/cooling cycles) and long-term (storage in light and dark for three months) stability of the mango peel formulations were evaluated. The characterization results showed the annotation of 71 compounds, gallotannins being the most representative group. In addition, the mango peel extract was shown to be effective against the •NO radical with an IC50 of 7.5 mg/L and against the hyaluronidase and xanthine oxidase enzymes with IC50 of 27 mg/L and 2 mg/L, respectively. The formulations incorporating the extract were stable during the stability study. The results demonstrate that mango peel extract can be a by-product to be revalorized as a promising cosmetic ingredient.

10.
Cancers (Basel) ; 15(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37627180

RESUMO

Waldenström Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with bone marrow (BM) involvement and IgM monoclonal gammopathy. To date, no studies have focused specifically on peripheral blood (PB) involvement. In this study, 100 patients diagnosed with WM according to the World Health Organization (WHO) criteria were included based on the demonstration of MYD88mut in BM and the availability of PB multiparametric flow cytometry (MFC) analysis. Leukemic involvement by MFC was detected in 50/100 patients. A low percentage of mature small lymphocytes in PB smears was observed in only 15 cases. MYD88mut by AS-qPCR was detected in PB in 65/100 cases. In cases with leukemic expression by MFC, MYD88mut was detected in all cases, and IGH was rearranged in 44/49 cases. In 21/50 patients without PB involvement by MFC, molecular data were consistent with circulating disease (MYD88mut by AS-qPCR 3/50, IGH rearranged 6/50, both 12/50). Therefore, PB involvement by standard techniques was detected in 71/100 patients. MYD88mut was detected in PB by dPCR in 9/29 triple negative cases. Overall, 80% of the patients presented PB involvement by any technique. Our findings support the role of PB MFC in the evaluation of patients with IgM monoclonal gammopathy and provide reliable information on correlation with molecular features. The development of a feasible MFC assay may stand as an objective tool in the classification of mature B cell neoplasms presenting with IgM monoclonal gammopathy.

11.
J Food Sci ; 88(6): 2439-2462, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37183914

RESUMO

Bioactive compounds in wheat have received a great interest in the last few years due to their nutritional and health benefits. Various analytical procedures were used to identify these compounds in wheat kernels. An ultra-performance liquid chromatography coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) was used for the screening of bioactive compounds in seven Tunisian durum wheat extracts. The aim of this study was to realize a screening of several classes of bioactive compounds in the same analysis and to identify specific metabolite markers for discriminating the durum wheat varieties. The UPLC-ESI-QTOF-MS/MS allows the detection of 81 metabolites, belonging to different chemical families such as sugars, organic acids, amino acids, fatty acids, and phenolic compounds represented by benzoic and cinnamic acid derivatives, phenolic alcohols, flavones, lignans, and condensed tannins. Chemical profiles identified varied greatly between different wheat genotypes. As far as the authors know, this is the first time that different chemical classes were detected at the same time in durum wheat kernels using UPLC-ESI-QTOF-MS/MS. This study gives the most complete map of metabolites in Tunisian durum wheat and proves that UPLC-QTOF-MS/MS coupled with chemometric analysis is a great tool for discrimination between durum wheat cultivars.


Assuntos
Espectrometria de Massas em Tandem , Triticum , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Quimiometria , Espectrometria de Massas por Ionização por Electrospray/métodos , Extratos Vegetais/química
12.
Sensors (Basel) ; 23(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37050500

RESUMO

Chemically pure plastic granulate is used as the starting material in the production of plastic parts. Extrusion machines rely on purity, otherwise resources are lost, and waste is produced. To avoid losses, the machines need to analyze the raw material. Spectroscopy in the visible and near-infrared range and machine learning can be used as analyzers. We present an approach using two spectrometers with a spectral range of 400-1700 nm and a fusion model comprising classification, regression, and validation to detect 25 materials and proportions of their binary mixtures. one dimensional convolutional neural network is used for classification and partial least squares regression for the estimation of proportions. The classification is validated by reconstructing the sample spectrum using the component spectra in linear least squares fitting. To save time and effort, the fusion model is trained on semi-empirical spectral data. The component spectra are acquired empirically and the binary mixture spectra are computed as linear combinations. The fusion model achieves very a high accuracy on visible and near-infrared spectral data. Even in a smaller spectral range from 400-1100 nm, the accuracy is high. The visible and near-infrared spectroscopy and the presented fusion model can be used as a concept for building an analyzer. Inexpensive silicon sensor-based spectrometers can be used.

13.
Commun Chem ; 6(1): 79, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095327

RESUMO

Macrotermitinae termites have farmed fungi in the genus Termitomyces as a food source for millions of years. However, the biochemical mechanisms orchestrating this mutualistic relationship are largely unknown. To deduce fungal signals and ecological patterns that relate to the stability of this symbiosis, we explored the volatile organic compound (VOC) repertoire of Termitomyces from Macrotermes natalensis colonies. Results show that mushrooms emit a VOC pattern that differs from mycelium grown in fungal gardens and laboratory cultures. The abundance of sesquiterpenoids from mushrooms allowed targeted isolation of five drimane sesquiterpenes from plate cultivations. The total synthesis of one of these, drimenol, and related drimanes assisted in structural and comparative analysis of volatile organic compounds (VOCs) and antimicrobial activity testing. Enzyme candidates putatively involved in terpene biosynthesis were heterologously expressed and while these were not involved in the biosynthesis of the complete drimane skeleton, they catalyzed the formation of two structurally related monocyclic sesquiterpenes named nectrianolins.

14.
Sensors (Basel) ; 23(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36991862

RESUMO

Spectrometers measure diffuse reflectance and create a "molecular fingerprint" of the material under investigation. Ruggedized, small scale devices for "in-field" use cases exist. Such devices might for example be used by companies in the food supply chain for inward inspection of goods. However, their application for the industrial Internet of Things workflows or scientific research is limited due to their proprietary nature. We propose an open platform for visible and near-infrared technology (OpenVNT), an open platform for capturing, transmitting, and analysing spectral measurements. It is built for use in the field, as it is battery-powered and transmits data wireless. To achieve high accuracy, the OpenVNT instrument contains two spectrometers covering a wavelength range of 400-1700 nm. We conducted a study on white grapes to compare the performance of the OpenVNT instrument against the Felix Instruments F750, an established commercial instrument. Using a refractometer as ground truth, we built and validated models to estimate the Brix value. As a quality measure, we used coefficient of determination of the cross-validation (R2CV) between the instrument estimation and ground truth. With 0.94 for the OpenVNT and 0.97 for the F750, a comparable R2CV was achieved for both instruments. OpenVNT matches the performance of commercially available instruments at one tenth of the price. We provide an open bill of materials, building instructions, firmware, and analysis software to enable research and industrial IOT solutions without the limitations of walled garden platforms.

15.
Nutrients ; 15(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36678322

RESUMO

Neurodegenerative diseases are known for their wide range of harmful conditions related to progressive cell damage, nervous system connections and neuronal death. These pathologies promote the loss of essential motor and cognitive functions, such as mobility, learning and sensation. Neurodegeneration affects millions of people worldwide, and no integral cure has been created yet. Here, bioactive compounds have been proven to exert numerous beneficial effects due to their remarkable bioactivity, so they could be considered as great options for the development of new neuroprotective strategies. Phenolic bioactives have been reported to be found in edible part of plants; however, over the last years, a large amount of research has focused on the phenolic richness that plant by-products possess, which sometimes even exceeds the content in the pulp. Thus, their possible application as an emergent neuroprotective technique could also be considered as an optimal strategy to revalorize these agricultural residues (those originated from plant processing). This review aims to summarize main triggers of neurodegeneration, revise the state of the art in plant extracts and their role in avoiding neurodegeneration and discuss how their main phenolic compounds could exert their neuroprotective effects. For this purpose, a diverse search of studies has been conducted, gathering a large number of papers where by-products were used as strong sources of phenolic compounds for their neuroprotective properties. Finally, although a lack of investigation is quite remarkable and greatly limits the use of these compounds, phenolics remain attractive for research into new multifactorial anti-neurodegenerative nutraceuticals.


Assuntos
Doenças Neurodegenerativas , Fármacos Neuroprotetores , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fenóis/farmacologia , Fenóis/química , Antioxidantes/farmacologia , Antioxidantes/química , Doenças Neurodegenerativas/prevenção & controle , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Plantas/química
16.
Angiogenesis ; 26(2): 233-248, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36371548

RESUMO

A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). We employed conventional histopathology, multiplexed immunohistochemistry (MPX), microvascular corrosion casting, scanning electron microscopy, X-ray phase-contrast tomography using synchrotron radiation, and direct multiplexed measurements of gene expression, to assess morphological and molecular changes holistically. Based on histopathology, none of the COVID-19 samples fulfilled the established diagnostic criteria of viral myocarditis. However, quantification via MPX showed a significant increase in perivascular CD11b/TIE2 + -macrophages in COVID-19 over time, which was not observed in influenza or non-SARS-CoV-2 viral myocarditis patients. Ultrastructurally, a significant increase in intussusceptive angiogenesis as well as multifocal thrombi, inapparent in conventional morphological analysis, could be demonstrated. In line with this, on a molecular level, COVID-19 hearts displayed a distinct expression pattern of genes primarily coding for factors involved in angiogenesis and epithelial-mesenchymal transition (EMT), changes not seen in any of the other patient groups. We conclude that cardiac involvement in COVID-19 is an angiocentric macrophage-driven inflammatory process, distinct from classical anti-viral inflammatory responses, and substantially underappreciated by conventional histopathologic analysis. For the first time, we have observed intussusceptive angiogenesis in cardiac tissue, which we previously identified as the linchpin of vascular remodeling in COVID-19 pneumonia, as a pathognomic sign in affected hearts. Moreover, we identified CD11b + /TIE2 + macrophages as the drivers of intussusceptive angiogenesis and set forward a putative model for the molecular regulation of vascular alterations.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Miocardite , Humanos , Remodelação Vascular , SARS-CoV-2 , Inflamação
17.
Am J Pathol ; 193(1): 73-83, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36309103

RESUMO

Convolutional neural network (CNN)-based image analysis applications in digital pathology (eg, tissue segmentation) require a large amount of annotated data and are mostly trained and applicable on a single stain. Here, a novel concept based on stain augmentation is proposed to develop stain-independent CNNs requiring only one annotated stain. In this benchmark study on stain independence in digital pathology, this approach is comprehensively compared with state-of-the-art techniques including image registration and stain translation, and several modifications thereof. A previously developed CNN for segmentation of periodic acid-Schiff-stained kidney histology was used and applied to various immunohistochemical stainings. Stain augmentation showed very high performance in all evaluated stains and outperformed all other techniques in all structures and stains. Without the need for additional annotations, it enabled segmentation on immunohistochemical stainings with performance nearly comparable to that of the annotated periodic acid-Schiff stain and could further uphold performance on several held-out stains not seen during training. Herein, examples of how this framework can be applied for compartment-specific quantification of immunohistochemical stains for inflammation and fibrosis in animal models and patient biopsy specimens are presented. The results show that stain augmentation is a highly effective approach to enable stain-independent applications of deep-learning segmentation algorithms. This opens new possibilities for broad implementation in digital pathology.


Assuntos
Aprendizado Profundo , Corantes , Ácido Periódico , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Rim/patologia
18.
J Med Primatol ; 52(1): 3-16, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36156802

RESUMO

BACKGROUND: The robust brown capuchin monkey (Sapajus apella) is a South American primate with preferences for arboreal locomotion, which requires specific thoracic limb muscle adaptations. The present investigation studied the gross anatomy of the extrinsic and intrinsic scapular and brachial muscles. METHODS: Gross dissections were performed in both thoracic limbs of four formaldehyde-fixed specimens. RESULTS: Three rhomboideus muscles were present (capitis, cervicis, and thoracis). The trapezius muscle was divided into two parts (cervicis and thoracis). The pectoralis abdominalis and omotransversarius muscles were present. The anconeus muscle was found as an individual muscle or fused to the caput mediale of the triceps brachii muscle. The brachialis muscle had among one and two heads. The anconeus epitrochlearis was absent. CONCLUSION: These muscles of Sapajus apella are adapted for arboreal locomotion and some terrestrial habits, since these have many similarities with other primates with a similar locomotor patterns.


Assuntos
Músculo Esquelético , Sapajus apella , Animais , Músculo Esquelético/anatomia & histologia , Membro Anterior , Locomoção/fisiologia , Primatas
20.
Mod Pathol ; 35(12): 1759-1769, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36088478

RESUMO

Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers, pathologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations on compiling test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help pathologists and regulatory agencies verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future.


Assuntos
Inteligência Artificial , Patologia , Humanos , Previsões , Conjuntos de Dados como Assunto
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