Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging.

Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

Early diagnosis of esophageal cancer: How to put "early detection" into effect?

This editorial comments on the article by Qu et al in a recent edition of World Journal of Gastrointestinal Oncology, focusing on the importance of early diagnosis in managing esophageal cancer and strategies for achieving "early detection". The five-year age-standardized net survival for esophageal cancer patients falls short of expectations. Early detection and accurate diagnosis are critical strategies for improving the treatment outcomes of esophageal cancer. While advancements in endoscopic technology have been significant, there seems to be an excessive emphasis on the latest high-end endoscopic devices and various endoscopic resection techniques. Therefore, it is imperative to redirect focus towards proactive early detection strategies for esophageal cancer, investigate the most cost-effective screening methods suitable for different regions, and persistently explore practical solutions to improve the five-year survival rate of patients with esophageal cancer.

Adnexal Clear Cell Carcinoma Exhibiting Comedonecrosis of the Ear: A Rare Case Treated With Mohs Micrographic Surgery.

Adnexal clear cell carcinoma exhibiting comedonecrosis (ACCCC) is a rare, cutaneous, malignant neoplasm with limited reported cases since its discovery. ACCCC is characterized by unique clinical and histological features, demanding a precise diagnosis due to its potential for aggressive behavior and early metastases, distinct from other cutaneous tumors with clear cytoplasmic cells. We present the case of an 81-year-old male with a history of multiple non-melanoma skin cancers, who presented with a 5 mm erythematous papule on his left tragus. Initial tangential shave biopsy results were invasive clear cell squamous cell carcinoma that was moderately differentiated. Subsequent Mohs micrographic surgery (MMS) necessitating a full-thickness skin graft reconstruction was performed. Histopathological examination afterward confirmed ACCCC with pleomorphic epithelial cells, clear cytoplasm, and central comedonecrosis. Immunohistochemistry supported adnexal differentiation and squamous features. To our knowledge, this is the fifteenth reported case of ACCCC as well as the first documented case of ACCCC treated with MMS, offering a novel approach to managing this rare malignancy.

Effects of eczema calming lotion on the stratum corneum in atopic dermatitis: Corneodesmosin and intercellular lipid lamellae.

OBJECTIVE: Atopic dermatitis (AD) is characterized by compositional and structural changes to the skin at lesional sites. Alteration to the levels and organization of both protein and lipid components are associated with disease status and lead to impaired barrier and hydration. Corneodesmosin (CDSN) and the arrangement and length of the intercellular lipid lamellae (ICLL) are altered in disrupted skin states. The aim of this research was to profile the distribution of CDSN and the ICLL in the stratum corneum (SC) at lesional and non-lesional sites in AD-prone skin and to investigate the impact of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. METHODS: An IRB-approved study was conducted with participants with active AD. From a small subset of participants, tape strips were collected from lesional and non-lesional sites on the arm, prior to and after twice daily application, over 4 weeks of an eczema calming lotion containing petroleum jelly, fatty acids, and colloidal oatmeal. Fluorescent antibody staining was used to investigate the distribution of CDSN. Transmission electron microscopy (TEM) was used to characterize the ICLL. RESULTS: The distribution/coverage of CDSN was similar between lesional and non-lesional sites at baseline; application of the lotion resulted in a more defined honeycomb/peripheral distribution. Normalized ICLL (nICLL) was lower in baseline samples from lesional sites relative to non-lesional sites. Application of the lotion increased this parameter by the end of the study at all sites. CONCLUSION: The eczema calming lotion containing petroleum jelly, fatty acids and colloidal oatmeal provided changes in corneodesmosomal proteins distribution and ICLL, consistent with improvements in corneocyte maturation and improved barrier function in the skin of individuals with atopic dermatitis.

OBJECTIF: La dermatite atopique (DA) est caractérisée par des modifications de la composition et de la structure de la peau au niveau des sites lésionnels. L'altération des taux et de l'organisation des composants protéiques et lipidiques est associée au statut de la maladie, et entraîne une altération de la barrière et de l'hydratation. La cornéodesmosine (CDSN), et la disposition et la longueur des lamelles lipidiques intercellulaires (LLIC) sont altérées dans les états cutanés perturbés. L'objectif de cette étude était d'établir le profil de la distribution de la CDSN et des LLIC dans la couche cornée (CC) au niveau des sites lésionnels et non lésionnels dans la peau sujette à la DA, et d'étudier l'impact d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. MÉTHODES: Une étude approuvée par un CPP a été menée auprès de participants atteints de DA active. Dans un petit sous­ensemble de participants, des bandes adhésives ont été prélevées sur des sites lésionnels et non lésionnels du bras, avant et après l'application deux fois par jour pendant 4 semaines d'une lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale. Une coloration par anticorps fluorescents a été utilisée pour étudier la distribution de la CDSN. La microscopie électronique en transmission (MET) a été utilisée pour caractériser les LLIC. RÉSULTATS: La distribution/couverture de la CDSN était similaire entre les sites lésionnels et non lésionnels à l'entrée dans l'étude; l'application de la lotion a entraîné une distribution en nid d'abeille/périphérique plus définie. Le taux normalisé de LLIC (LLICn) était plus faible dans les échantillons prélevés à l'entrée dans l'étude au niveau des sites lésionnels par rapport aux sites non lésionnels. L'application de la lotion a augmenté ce paramètre à la fin de l'étude pour tous les sites. CONCLUSIONS: La lotion apaisante contre l'eczéma contenant de la vaseline, des acides gras et de l'avoine colloïdale a entraîné des changements dans la distribution des protéines cornéodesmosomales et des LLIC, ce qui correspond à des améliorations de la maturation des cornéocytes et de la fonction de barrière de la peau des personnes atteintes de dermatite atopique.

A histology and immunochemistry study comparing open versus close and open-method endoscopic saphenous vein harvesting.

Background: The introduction of endoscopic saphenous vein harvesting (ESVH) has been reported to reduce wound pain and infection, compared with open saphenous vein harvesting (OSVH) techniques. There are still controversies regarding this technique. The aim of our study is to investigate the endothelial preservation of saphenous vein (SV) grafts harvested by different techniques. Further observations were made for harvesting and closure time, incision length and effect of pressure distension of the veins to the vein endothelium. Methods: Prospective observational study of sixty human saphenous vein grafts was performed to evaluate endothelial preservation by haematoxylin-eosin and Cluster of Differentiation 31 (CD 31) staining. Saphenous vein was harvested endoscopically either by closed CO2 (carbon dioxide) ESVH, open CO2 ESVH or OSVH harvesting technique. Demographic data and intra-operative data were collected. Two saphenous vein samples were collected from each patient to compare differences before and after distension of the veins. Both haematoxylin-eosin and immunohistochemistry slides were imaged by a high-resolution slide scanning system. Results: Open CO2 ESVH group showed the highest number of endothelial detachments. Mean scoring of the immunohistochemistry method using the CD31 antibody was much lower in the open CO2 ESVH group (33.25% ± 28.71, P < 0.0003). This represents a more poorly preserved endothelial cells in the Open CO2 ESVH than the closed CO2 ESVH. Closure time and incision lengths were significantly shorter in both ESVH groups compared to the OSVH group. Significant low scores of immunohistochemistry for samples were seen in distended veins (39.0% ± 30.08, p = 0.004). The OSVH in random sample B, which represents the conduit that will be used, had a far better endothelium preservation and less endothelial detachment when compared to ESVH. Conclusion: We observed more endothelial detachment in the open CO2 ESVH group, due to lack of subcutaneous tissue separation, poor visualization and traction stress across the wall of the saphenous vein. The closed CO2 ESVH group had more endothelial cells preserved, but the OSVH group fared the best with the least number of endothelial cell detachment and a higher score of CD31 antibody. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-024-01752-3.

Virtual multiplexed immunofluorescence staining from non-antibody-stained fluorescence imaging for gastric cancer prognosis.

BACKGROUND: Multiplexed immunofluorescence (mIF) staining, such as CODEX and MIBI, holds significant clinical value for various fields, such as disease diagnosis, biological research, and drug development. However, these techniques are often hindered by high time and cost requirements. METHODS: Here we present a Multimodal-Attention-based virtual mIF Staining (MAS) system that utilises a deep learning model to extract potential antibody-related features from dual-modal non-antibody-stained fluorescence imaging, specifically autofluorescence (AF) and DAPI imaging. The MAS system simultaneously generates predictions of mIF with multiple survival-associated biomarkers in gastric cancer using self- and multi-attention learning mechanisms. FINDINGS: Experimental results with 180 pathological slides from 94 patients with gastric cancer demonstrate the efficiency and consistent performance of the MAS system in both cancer and noncancer gastric tissues. Furthermore, we showcase the prognostic accuracy of the virtual mIF images of seven gastric cancer related biomarkers, including CD3, CD20, FOXP3, PD1, CD8, CD163, and PD-L1, which is comparable to those obtained from the standard mIF staining. INTERPRETATION: The MAS system rapidly generates reliable multiplexed staining, greatly reducing the cost of mIF and improving clinical workflow. FUNDING: Stanford 2022 HAI Seed Grant; National Institutes of Health 1R01CA256890.

The color stability of artificial white spot lesions treated with resin infiltration after exposure to staining beverages.

BACKGROUND: To evaluate the effect of staining beverages on the color-changing of resin-infiltrated artificial white spot lesions (WSLs). METHODS: Thirty-five artificial WSLs were created by pH cycling on flat bovine teeth specimens. The WSLs were treated with resin infiltration and were divided into five groups based on staining beverages: artificial saliva, coffee, wine, green tea, and Coca-Cola. These specimens were subjected to a 28-day exposure to the respective beverages. Color stability was assessed using a spectrophotometer at different time points: baseline, after 7, 14, 21, and 28 days of exposure, and repolishing. The color difference (∆E) between each time point and the baseline was calculated. Statistical analysis was performed using two-way measures ANOVA with a significance level of p = 0.05. RESULTS: All resin-infiltrated specimens exposed to staining beverages for 7 days exhibited more significant color changes than those exposed to artificial saliva. The color change patterns varied based on the type of beverage. The color alterations intensified with extended immersion in the wine and Coca-Cola groups, while there were no significant differences in the color of specimens after 28 days of immersion in the coffee and green tea groups. However, after cleaning with pumice powder, all specimens showed significantly reduced color changes compared to those observed after 28 days of immersion, except those immersed in coffee. CONCLUSIONS: Exposure of resin-infiltrated bovine tooth specimens to staining beverages resulted in a significant color alteration as the immersion time increased. However, the staining effect could be minimized by cleaning with pumice powder, except for the coffee group. CLINICAL RELEVANCE: After resin infiltration treatment, patients should be advised to minimize the consumption of colored beverages to prevent staining that could impact esthetic appearance.

Di(2-ethylexyl) phthalate and chromosomal damage: Insight on aneugenicity from the cytochalasin-block micronucleus assay.

Bis(2-ethylhexyl) phthalate is the most abundant phthalate used as plasticizer to soften plastics and polymers included in medical devices. Human and environmental exposure may occur because DEHP is not chemically bound to plastics and can easily leach out of the materials. This phthalate is classified as reproductive toxicant and possible carcinogen to humans. The genotoxic potential has still to be clarified, but there are indications suggesting that DEHP may have aneugenic effects. To further investigate DEHP genotoxicity, the cytochalasin-block micronucleus assay was applied and combined with the CREST staining to characterise micronucleus content and gain insights on its genotoxic mode of action. Chromosomal damage was also analysed in metaphase and ana-telophase cells and the morphology of the mitotic spindle was investigated to evaluate the possible involvement of this cellular apparatus as a target of DEHP. Our findings indicated that DEHP induced a statistically significant increase in the frequency of micronuclei as well as in the frequency of CREST-positive micronuclei. Consistently, disturbance of chromosome segregation and induction of numerical chromosome changes were observed together with changes in spindle morphology, formation of multipolar spindles and alteration of the microtubule network. Experiments performed without metabolic activation demonstrated a direct action of DEHP on chromosome segregation not mediated by its metabolites. In conclusion, there is consistent evidence for an aneugenic activity of DEHP. A thresholded genotoxic activity was identified for DEHP, disclosing possible implications for risk assessment.

Methods and Protocol for Single-Cell Motility Assays under Topological Constraints.

The extracellular environment plays a crucial role in many physiological and pathological processes involving cell motility, such as metastatic invasion in cancer development, by heavily impacting the migration strategies adopted by the cells. The study of how mechanical constraints affect the dynamics of cell migration may be relevant to gain more insight into such processes, and it may prove to be a powerful tool in the hands of biologists. In this chapter, we describe the methods used to investigate the ability of neoplastic cells to migrate through narrowing, rigid microstructures upon chemoattractant stimulation.

Flagella and Cell Body Staining of Bacteria with Fluorescent Dyes.

Bacteria can propel themselves by rotating a flagellum or a flagellar bundle. To image this thin structure in motile bacteria, the flagella can be vitally stained with fluorophores. This chapter describes a flagellar staining protocol with the additional possibility of visualizing the cell body. It offers the opportunity to track conformational changes of flagella and simultaneously track the positions of the cell bodies. The additional use of a filter increases the number of motile cells and improves the signal-to-noise ratio of images. The flagellar staining requires a prior introduction of a surface-exposed cysteine, which is not covered in this chapter.

Embedded-deep-learning-based sample-to-answer device for on-site malaria diagnosis.

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis.

In vitro cultivation of adherent cells on microscope slides for downstream applications.

In vitro studies with cultured cells are often conducted as an important part of basic research. Adherent cells are typically cultivated in flasks or trays, for which cell staining and subsequent visualization become impractical. We here present a simple step-by-step method for growing adherent cells directly on glass microscope slides, using low-cost equipment readily available in most laboratories. Most parameters such as type of microscope slide (e.g. surface coating), cell seeding concentrations and incubation times can be adjusted according to cell line characteristics and experimental aims, reflecting the methods' flexibility. Through our experiments, microscope slides proved to provide an acceptable surface for cell adhesion and growth of the tested cell lines, as well as being robust and functional with respect to downstream procedures. The method can potentially be combined with different techniques for visualization of experimental effects, such as histological staining methods, fluorescent staining, and immunochemistry. In our method development we have successfully cultivated three different cell lines directly on microscope slides - Atlantic salmon kidney cells (ASK), rainbow trout gill cells (RTgill-W1), and human cancerous lung cells (A549) - and subjected them to various experimental treatments. Finally, as proof-of-concept we provide examples of successful histological staining of the fixed cells. Experimental design in short:•Cultivate cells and calculate cell concentration•Seed a small volume of growth medium with an appropriate number of cells on microscope slide in an area confined by hydrophobic marker•Let cells adhere over night before adding more growth medium or directly conducting experiments and fixing cells for downstream applications.

Transformation from hematoxylin-and-eosin staining to Ki-67 immunohistochemistry digital staining images using deep learning: experimental validation on the labeling index.

Purpose: Endometrial cancer (EC) is one of the most common types of cancer affecting women. While the hematoxylin-and-eosin (H&E) staining remains the standard for histological analysis, the immunohistochemistry (IHC) method provides molecular-level visualizations. Our study proposes a digital staining method to generate the hematoxylin-3,3'-diaminobenzidine (H-DAB) IHC stain of Ki-67 for the whole slide image of the EC tumor from its H&E stain counterpart. Approach: We employed a color unmixing technique to yield stain density maps from the optical density (OD) of the stains and utilized the U-Net for end-to-end inference. The effectiveness of the proposed method was evaluated using the Pearson correlation between the digital and physical stain's labeling index (LI), a key metric indicating tumor proliferation. Two different cross-validation schemes were designed in our study: intraslide validation and cross-case validation (CCV). In the widely used intraslide scheme, the training and validation sets might include different regions from the same slide. The rigorous CCV validation scheme strictly prohibited any validation slide from contributing to training. Results: The proposed method yielded a high-resolution digital stain with preserved histological features, indicating a reliable correlation with the physical stain in terms of the Ki-67 LI. In the intraslide scheme, using intraslide patches resulted in a biased accuracy (e.g., R = 0.98 ) significantly higher than that of CCV. The CCV scheme retained a fair correlation (e.g., R = 0.66 ) between the LIs calculated from the digital stain and its physical IHC counterpart. Inferring the OD of the IHC stain from that of the H&E stain enhanced the correlation metric, outperforming that of the baseline model using the RGB space. Conclusions: Our study revealed that molecule-level insights could be obtained from H&E images using deep learning. Furthermore, the improvement brought via OD inference indicated a possible method for creating more generalizable models for digital staining via per-stain analysis.

Papillary adenoma of the lung: A case report and literature review.

Papillary adenoma of the lung, a rare and benign tumor, is easily confused with other primary benign or malignant lung tumors and especially with lung adenocarcinoma that has a papillary growth pattern. Enhanced understanding and an accurate diagnosis of papillary adenomas of the lung are crucial for clinical treatment and prognostic assessment. A 61-year-old man who presented with an opportunistic finding in relation to a left lower lobe lung nodule during an examination was admitted to The First Hospital of China Medical University (Shenyang, China) for further treatment. Computed tomography (CT) revealed a well-circumscribed left lower lobe nodule (diameter, ~1 cm), comprising branched papillae with a fibrovascular core and no other structural components. The tumor cells appeared relatively uniform in shape and well arranged with round or oval nuclei. No nucleoli or mitotic figures were observed. Immunohistochemically, the papillary structures of the tumor cells were strongly and diffusely positive for cytokeratin (CK), CK7, Napsin-A and thyroid transcription factor 1. The Ki-67 index was ~1%. A pathological diagnosis of primary papillary adenoma of the lung was made based on these findings. A left lower-lobe wedge resection was performed and the patient's postoperative course was uneventful. Surgical resection is the preferred treatment. Papillary adenoma of the lung is very rare, and its clinical manifestations and CT images are non-specific. It is important to avoid misdiagnosing of papillary adenoma of the lung as another type of lung tumor, especially adenocarcinoma. A clear understanding of the morphological and immunohistochemical features of papillary adenomas is important for the diagnosis of this rare lung tumor.

Vernodalin Triggers ROS-Mediated Apoptosis in TPC-1 Human PapillaryThyroid Cancer Cells via Suppression of the MAPKs Signaling Pathway.

BACKGROUND: Thyroid Cancer (TC) is an endocrine organ malignancy that has become more common in recent decades. Vernodalin (VN), a cytotoxic sesquiterpene, has been reported to exhibit anticancer properties against human breast and liver cancer cells. However, no study has explored the efficacy of VN with respect to its antiproliferative and apoptotic action on human Papillary Thyroid Cancer cells (PTC). OBJECTIVE: The study intended to examine the antitumor and antiproliferative effects of VN and the apoptosis mechanisms underlying its action on TPC-1 human PTC cells. METHODS: In this study, we examined the VN cell viability by MTT assay; performed ROS measurement by DCFH staining method, MMP identification by Rh-123 staining method, and apoptotic morphological assay by employing AO/EB and DAPI stain method, and further, p38 MAPK/ERK/JNK cell proliferation markers were determined by western blotting technique. RESULTS: The findings showed that VN could inhibit the growth of PTC cells by increasing intracellular ROS, damaging MMP, and stimulating apoptosis in a concentration-dependent manner. The study demonstrated how VN inhibited TPC-1 cell viability by causing ROS-induced cell death via the MAPK signaling pathway. CONCLUSION: VN may serve as an agonist to impact apoptosis in PTC cells. In human PTC, VN could play an effective role in chemotherapy. More studies pertaining to animal tumor models are needed to prove its anti-cancer effectiveness in vivo.

Conditions for late gadolinium enhancement MRI in myocardial infarction model rats that better reflect microscopic tissue staining.

Late gadolinium enhancement (LGE) is a widely used magnetic resonance imaging method for assessing cardiac disease. However, the relationship between different LGE signal thresholds and microscopic tissue staining images is unclear. In this study, we performed cardiovascular MRI on myocardial infarction (MI) model rats and evaluated the relationship between LGE with different signal thresholding methods and tissue staining images. We prepared 16 rats that underwent MRI 14-18 days following a surgery to create an MI model. We captured cine and LGE images of the cardiac short-axis and longitudinal two- and four-chamber views. The mean ± 2SD, ± 3SD, and ± 5SD of the pixel values in the non-infarcted area were defined as the LGE area. We compared areas of Sirius red staining, determined by the color tone, with their respective LGE areas at end-diastole and end-systole. We observed that the LGE area calculated as the mean ± 2SD of the non-infarcted area at end-diastole demonstrated a significant positive correlation with the area of Sirius red staining (Pearson's correlation coefficient in both: 0.81 [p < 0.01]). Therefore, the LGE area calculated as the mean ± 2SD of the non-infarcted area at end-diastole best reflected the MI area in tissue staining.

Interaction between polydopamine-based IONPs and human serum albumin (HSA): a spectroscopic analysis with cytotoxicity impact.

Iron oxide nanoparticles (IONPs) have been extensively explored in biomedicine, bio-sensing, hyperthermia, and drug/gene delivery, attributed to their versatile and tunable properties. However, owing to its numerous applications, the functionalization of IONPs with appropriate materials is in demand. To achieve optimal functionalization of IONPs, polydopamine (PDA) was utilized due to its ability to provide a superior functionalized surface, near-infrared light absorption, and adhesive nature to customize desired functionalized IONPs. This notion of involving PDA led to the successful synthesis of magnetite-PDA nanoparticles, where PDA is surface-coated on magnetite (Fe3O4@PDA). The Fe3O4@PDA nanoparticles were characterized using techniques like TEM, FESEM, PXRD, XPS, VSM, and FTIR, suggesting PDA's successful attachment with magnetite crystal structure retention. Human serum albumin (HSA), the predominant protein in blood plasma, interacts with the delivered nanoparticles. Therefore, we have employed various spectroscopic techniques, along with cytotoxicity, to inspect the effect of Fe3O4@PDA NPs on the stability and structure of HSA. The structural alterations were examined using circular dichroism (CD) and synchronous fluorescence spectroscopy (SFS). It has been observed that there are no structural perturbations in the secondary structure of the HSA protein after interaction with Fe3O4@PDA. Studies using steady-state fluorescence revealed that the inherent fluorescence intensities of HSA were suppressed after interaction with Fe3O4@PDA. In addition, temperature-dependent fluorescence measurements suggested that the type of quenching consists of both static and dynamic quenching simultaneously. A cytotoxicity study in Drosophila melanogaster larvae revealed no cytotoxic effects but did show a minor genotoxic effect only at higher concentrations.

Dissecting Henipavirus W proteins conformational and fibrillation properties: contribution of their N- and C-terminal constituent domains.

The Nipah and Hendra viruses are severe human pathogens. In addition to the P protein, their P gene also encodes the V and W proteins that share with P their N-terminal intrinsically disordered domain (NTD) and possess distinct C-terminal domains (CTDs). The W protein is a key player in the evasion of the host innate immune response. We previously showed that the W proteins are intrinsically disordered and can form amyloid-like fibrils. However, structural information on W CTD (CTDW) and its potential contribution to the fibrillation process is lacking. In this study, we demonstrate that CTDWS are disordered and able to form dimers mediated by disulfide bridges. We also show that the NTD and the CTDW interact with each other and that this interaction triggers both a gain of secondary structure and a chain compaction within the NTD. Finally, despite the lack of intrinsic fibrillogenic properties, we show that the CTDW favors the formation of fibrils by the NTD both in cis and in trans. Altogether, the results herein presented shed light on the molecular mechanisms underlying Henipavirus pathogenesis and may thus contribute to the development of targeted therapies.

Stain SAN: simultaneous augmentation and normalization for histopathology images.

Purpose: We address the need for effective stain domain adaptation methods in histopathology to enhance the performance of downstream computational tasks, particularly classification. Existing methods exhibit varying strengths and weaknesses, prompting the exploration of a different approach. The focus is on improving stain color consistency, expanding the stain domain scope, and minimizing the domain gap between image batches. Approach: We introduce a new domain adaptation method, Stain simultaneous augmentation and normalization (SAN), designed to adjust the distribution of stain colors to align with a target distribution. Stain SAN combines the merits of established methods, such as stain normalization, stain augmentation, and stain mix-up, while mitigating their inherent limitations. Stain SAN adapts stain domains by resampling stain color matrices from a well-structured target distribution. Results: Experimental evaluations of cross-dataset clinical estrogen receptor status classification demonstrate the efficacy of Stain SAN and its superior performance compared with existing stain adaptation methods. In one case, the area under the curve (AUC) increased by 11.4%. Overall, our results clearly show the improvements made over the history of the development of these methods culminating with substantial enhancement provided by Stain SAN. Furthermore, we show that Stain SAN achieves results comparable with the state-of-the-art generative adversarial network-based approach without requiring separate training for stain adaptation or access to the target domain during training. Stain SAN's performance is on par with HistAuGAN, proving its effectiveness and computational efficiency. Conclusions: Stain SAN emerges as a promising solution, addressing the potential shortcomings of contemporary stain adaptation methods. Its effectiveness is underscored by notable improvements in the context of clinical estrogen receptor status classification, where it achieves the best AUC performance. The findings endorse Stain SAN as a robust approach for stain domain adaptation in histopathology images, with implications for advancing computational tasks in the field.