Search Results (2,530)

In this work, we describe a dataset suitable for analyzing the extent to which hematoxylin–eosin (HE)-stained tissue contains information about the expression of Ki67 in immunohistochemistry staining. The dataset provides images of corresponding pairs of HE and Ki67 stainings and is complemented by algorithms for computing the Ki67 index. We introduce a dataset of high-resolution histological images of testicular seminoma tissue. The dataset comprises digitized histology slides from 77 conventional testicular seminoma patients, obtained via surgical resection. For each patient, two physically adjacent tissue sections are stained: one with hematoxylin and eosin, and one with Ki67 immunohistochemistry staining. This results in a total of 154 high-resolution images. The images are provided in PNG format, facilitating ease of use for image analysis compared to the original scanner output formats. Each image contains enough tissue to generate thousands of non-overlapping 224 × 224 pixel patches. This shows the potential to generate more than 50,000 pairs of patches, one with HE staining and a corresponding Ki67 patch that depicts a very similar part of the tissue. Finally, we present the results of applying a ResNet neural network for the classification of HE patches into categories according to their Ki67 label. Full article

Applying a saturated potassium iodide (KI) solution immediately after silver diamine fluoride (SDF) application may affect the inhibitory effects of SDF on biofilm formation. This study compared the efficacy of 38% SDF with and without KI on preventing mixed-species biofilm formation on human root dentin surfaces and assessed ion incorporation into root dentin. The biofilms, composed of Streptococcus mutans, Lactobacillus rhamnosus, and Actinomyces naeslundii, were grown on specimen surfaces treated with either SDF or SDF + KI. After 24 h, the biofilms were evaluated using scanning electron microscopy, live/dead staining, adenosine triphosphate (ATP) assays, colony-forming unit (CFU) counts, and quantitative polymerase chain reaction. A Mann–Whitney U test was used to compare the results between the groups. Ion incorporation was assessed using an electron probe microanalyzer. The relative ATP content in the SDF + KI group was significantly higher than that in the SDF group (p < 0.05). However, biofilm morphology and the logarithmic reduction in CFUs and bacterial DNA were comparable across the groups. The SDF + KI treatment resulted in less silver and fluoride ion incorporation than that yielded by SDF alone. The inhibitory effects of SDF and SDF + KI on mixed-species biofilm formation were almost equivalent, although KI application affected the ion incorporation. Full article

Background: Tyrosine kinase inhibitors (TKIs) inhibit receptor-mediated signals in cells. Axitinib is a TKI with high specificity for vascular endothelial growth factor receptors (VEGFRs). Aim: We determined whether axitinib could induce senescence in human cancer cells and be lysed by the senolytic drug ABT-263. Methods: Human lung and breast adenocarcinoma cell lines were used. These cells were cultured with axitinib or a multi-target TKI lenvatinib. The expression of β-galactosidase, VEGFRs, Ki-67, reactive oxygen species (ROS) of cancer cells, and their BrdU uptake were evaluated by flow cytometry. The mRNA expression of p21 and IL-8 was examined by quantitative PCR. The effects of TKIs on phosphorylation of Akt and Erk1/2, as downstream molecules of VEGFR signaling, were examined by immunoblot. The in vivo anti-cancer effect was examined using a xenograft mice model. Results: Axitinib, but not lenvatinib, induced cellular senescence (increased cell size and enhanced expression of β-galactosidase) in all adenocarcinoma cell lines. Axitinib-induced senescence was unrelated to the expression of VEGFRs on cancer cells. ROS were involved in axitinib-induced senescence. Axitinib-induced senescent lung adenocarcinoma A549 cells were drastically lysed by ABT-263. In A549-xenografted mice, combination therapy with axitinib and ABT-263 significantly suppressed tumor growth with the induction of apoptotic cancer cells. Full article

This study investigated the effect of natural compounds from Nile tilapia (Oreochromis niloticus) skin on wound healing in IL-10 knockout mice. The healing fraction, Fraction T19, was obtained through hydrolysis with trypsin. In vitro, T19 was not cytotoxic to RAW 264.7 macrophage cells, promoting increased cell proliferation and migration. In vivo, mice (n = 30) were divided into three groups with 12 mm wounds in the dorsal region: control (distilled water), T1 (T19 at 125 μg/mL), and T2 (T19 at 250 μg/mL). Daily applications were performed, with tissue removal after nine days. The results showed that T19 increased the production of nitric oxide (NO) and hydrogen peroxide (H₂O₂), preventing wound contamination. There was an increase in pro-inflammatory (IL-2 and IFNγ) and anti-inflammatory (IL-4) cytokines, as well as cell proliferation markers (PCNA and KI67). Antibodies CD31, CD163, and COX-2 indicated an increase in the formation of new vessels and a reduction in inflammation. Both groups treated with T19 showed better healing results, with better effects observed at higher doses. It was concluded that T19 can effectively modulate the skin repair process and represent an alternative therapeutic for improving the quality of wound skin, especially in the clinical context. Formulations using tilapia skin are safe and effective for accelerating wound healing. Full article

Cell spheroids are an important three-dimensional (3D) model for in vitro testing and are gaining interest for their use in clinical applications. More natural 3D cell culture environments that support cell–cell interactions have been created for cancer drug discovery and therapy applications, such as the scaffold-free 3D Petri Dish^® technology. This technology uses reusable and autoclavable silicone micro-molds with different topographies, and it conventionally uses gelled agarose for hydrogel formation to preserve the topography of the selected micro-mold. The present study investigated the feasibility of using a patterned Poly(vinyl alcohol) hydrogel using the circular topography 12–81 (9 × 9 wells) micro-mold to form HeLa cancer cell spheroids and compare them with the formed spheroids using agarose hydrogels. PVA hydrogels showed a slightly softer, springier, and stickier texture than agarose hydrogels. After preparation, Fourier transform infrared (FTIR) spectra showed chemical interactions through hydrogen bonding in the PVA and agarose hydrogels. Both types of hydrogels favor the formation of large HeLa spheroids with an average diameter of around 700–800 µm after 72 h. However, the PVA spheroids are more compact than those from agarose, suggesting a potential influence of micro-mold surface chemistry on cell behavior and spheroid formation. This was additionally confirmed by evaluating the spheroid size, morphology, integrity, as well as E-cadherin and Ki67 expression. The results suggest that PVA promotes stronger cell-to-cell interactions in the spheroids. Even the integrity of PVA spheroids was maintained after exposure to the drug cisplatin. In conclusion, the patterned PVA hydrogels were successfully prepared using the 3D Petri Dish^® micro-molds, and they could be used as suitable platforms for studying cell–cell interactions in cancer drug therapy. Full article

The Hodgkin variant Richter syndrome (HvRS) is an infrequent complication occurring in 1% of lymphocytic lymphoma/chronic lymphocytic leukemia patients. We report a case of HvRS diagnosed in Sub-Saharan Africa. A 63-year-old patient was consulted for the investigation of an abdominal mass that had been evolving for 5 years prior to admission. His history revealed night sweats, 13% weight loss in 3 months and persistent pruritis. Examination revealed bilateral cervical axillary and inguinal macroadenopathies, painless abdominal distension, pruritic lesions and WHO 2 PS. The blood count showed anemia at 9.5 g/dL. Histology revealed a lymphomatous proliferation of diffuse architecture, nodular in places, with Hodgkin and Sternberg cells associated with small lymphocytes, histiocytes and eosinophilic polymorphs. Immunohistochemistry showed CD20, PAX5, BCL2, CD5, CD23 and MYC positivity; Ki67 at 10% and cyclin D1, BCL6 and CD10 negativity; CD30 positivity on Hodgkin and Sternberg cells that remained CD20 negative; difficulty interpreting CD15; EBV positivity (EBERs); and CD3 and CD5 positivity on reactive T cells. CD138 and kappa and lambda light chains were non-contributory. The extension work-up classified the patient as Ann Arbor stage III B with a Hasenclever score of 3/7. This case illustrates the difficulties in diagnosing HvRS in our countries, where the number of haematopathologists is insufficient and the technical facilities are limited. Full article

The transmembrane protein β-amyloid precursor protein (APP) is central to the pathophysiology of Alzheimer’s disease (AD). The β-amyloid hypothesis posits that aberrant processing of APP forms neurotoxic β-amyloid aggregates, which lead to the cognitive impairments observed in AD. Although numerous additional factors contribute to AD, there is a need to better understand the synaptic function of APP. We have found that Drosophila APP-like (APPL) has both shared and non-shared roles at the synapse with Kismet (Kis), a chromatin helicase binding domain (CHD) protein. Kis is the homolog of CHD7 and CHD8, both of which are implicated in neurodevelopmental disorders including CHARGE Syndrome and autism spectrum disorders, respectively. Loss of function mutations in kis and animals expressing human APP and BACE in their central nervous system show reductions in the glutamate receptor subunit, GluRIIC, the GTPase Rab11, and the bone morphogenetic protein (BMP), pMad, at the Drosophila larval neuromuscular junction (NMJ). Similarly, processes like endocytosis, larval locomotion, and neurotransmission are deficient in these animals. Our pharmacological and epistasis experiments indicate that there is a functional relationship between Kis and APPL, but Kis does not regulate appl expression at the larval NMJ. Instead, Kis likely influences the synaptic localization of APPL, possibly by promoting rab11 transcription. These data identify a potential mechanistic connection between chromatin remodeling proteins and aberrant synaptic function in AD. Full article

Background and Objectives: This study explores the complex pathogenesis of pituitary adenomas (PAs), prevalent intracranial tumors in the pituitary gland. Despite their generally benign nature, PAs exhibit a diverse clinical spectrum involving hormone hypersecretion and varying invasiveness, hinting at multifaceted molecular mechanisms and abnormalities in tumorigenesis and gene regulation. Materials and Methods: The investigation focuses on the Ki-67 labeling index, SSTR2 rs2236750, SSTR5 rs34037914, and AIP rs267606574 polymorphisms, alongside serum levels of SSTR2, SSTR5, and AIP, to discern their association with PAs. The Ki-67 labeling index was assessed using immunohistochemical analysis with the monoclonal antibody clone SP6, representing the percentage of tumor cells showing positive staining. Genotyping was performed via real-time polymerase chain reaction, and serum levels were analyzed using ELISA. The study included 128 PA patients and 272 reference group subjects. Results: The results derived from binary logistic regression analysis revealed an intriguing correlation between the SSTR2 rs2236750 AG genotype and approximately a 1.6-fold increased likelihood of PA occurrence. When analyzing SSTR5 rs34037914, statistically significant differences were found between Micro-PA and the reference group (p = 0.022). Additionally, the SSTR5 rs34037914 TT genotype, compared with CC + CT, under the most robust genetic model (selected based on the lowest AIC value), was associated with a 12-fold increased odds of Micro-PA occurrence. However, it is noteworthy that after applying Bonferroni correction, these findings did not retain statistical significance. Conclusions: Consequently, while this study hinted at a potential link between SSTR2 rs2236750 and pituitary adenoma development, as well as a potential link between SSTR5 rs34037914 and Micro-PA development, it underscored the need for further analysis involving a larger cohort to robustly validate these findings. Full article

Accurate seismic ground response analysis is crucial for the design and safety of civil infrastructure and establishing effective mitigation measures against seismic risks and hazards. This is a complex process due to the nonlinear soil properties and complicated underground geometries. As a simplified approach, the one-dimensional wave propagation model, which assumes that seismic waves travel vertically through a horizontally layered medium, is widely adopted for its reasonable performance in many practical applications. This study explores the potential of sequence deep learning models, specifically 1D convolutional neural networks (1D-CNNs), long short-term memory (LSTM) networks, and transformers, as an alternative for seismic ground response modeling. Utilizing ground motion data from the Kiban Kyoshin Network (KiK-net), we train these models to predict ground surface acceleration response spectra based on bedrock motions. The performance of the data-driven models is compared with the conventional equivalent-linear analysis model, SHAKE2000. The results demonstrate that the deep learning models outperform the physics-based model across various sites, with the transformer model exhibiting the smallest average prediction error due to its ability to capture long-range dependencies. The 1D-CNN model also shows a promising performance, albeit with occasional higher errors than the other models. All the data-driven models exhibit efficient computation times of less than 0.4 s for estimation. These findings highlight the potential of sequence deep learning approaches for seismic ground response modeling. Full article

Background: Constipation and outlet obstruction may persist after successful pull-through in Hirschsprung Disease (HD). The radiographic assessment of the faecal load is widely used but exposes the child to radiation. This study aims to evaluate whether the transrectal diameter (TRD) assessed with ultrasound correlates with symptoms of faecal load and whether the TRD normalises when symptoms disappear. Method: Children with HD after pullthrough and functional constipation presenting to our colorectal clinic between 4/23 and 4/24 were assessed for symptoms of constipation, smearing and outlet obstruction, as well as healthy controls. Ultrasound measurement of the TRD was conducted. Bowel management was initiated according to our institutional pathway using Peristeen© irrigation after an orthograde disimpaction regime. Results: A total of 193 children underwent TRD assessment. Of 60 children with HD, 26 (43.3%) presented with obstructive symptoms, and 34 (56.7%) were asymptomatic. In asymptomatic patients with HD, the mean TRD of 2.26 cm (SD 0.61) was significantly (p < 0.001) lower than in HD with symptoms, with a mean TRD of 3.35 cm (SD 1.03). Individuals without colorectal pathology had a mean TRD of 2.04 cm (SD 0.37), and children with functional constipation and symptoms showed a mean TRD of 4.36 cm (SD 1.32). The mean TRD after symptom resolution was 2.37 cm. Conclusions: Children with HD without obstructive symptoms have a TRD < 3 cm, as do controls. The transrectal diameter allows the clinician to sonographically assess the faecal load in children with HD at the bedside without radiation. The TRD is useful for monitoring a bowel management program in children with HD. Full article

Regular detection of land-use and land-cover (LULC) changes with high accuracy is necessary for natural resources management and sustainable urban planning. The produced LULC maps from Google Earth Engine (GEE) also illustrate the transformation of the LULC for the respective landscape over time. The selected study area, Cottbus City and the Spree-Neisse district in northeastern Germany, has undergone significant development over the past decades due to various factors, including urbanization and industrialization; also, the landscape has been converted in some areas for post-mining activities. Detection of LULC changes that have taken place over the last few decades thus plays a vital role in quantifying the impact of these factors while improving the knowledge of these developments and supporting the city planners or urban management officials before implementing further long-term development initiatives for the future. Therefore, the study aims to (i) detect LULC changes for the time slices 2002 and 2022, testing machine learning (ML) algorithms in supervised and unsupervised classification for Landsat satellite imageries, and (ii) validate the newly produced LULC maps with the available regional database (RDB) from the federal and state statistical offices, Germany, and the Dynamic World (DW) near real-time 10 m global LULC data set powered by artificial intelligence (AI). The results of the Random Forest (RF) and the Smilecart classifiers of supervised classification using Landsat 9 OLI-2/TIRS-2 in 2022 demonstrated a validation accuracy of 88% for both, with Kappa Index (KI) of 83% and 84%, respectively. Moreover, the Training Overall Accuracy (TOA) was 100% for both years. The wekaKMeans cluster of the unsupervised classification also illustrated a similar transformation pattern in the LULC maps. Overall, the produced LULC maps offered an improved representation of the selected region’s various land-cover classes (i.e., vegetation, waterbodies, built areas, and bare ground) in the last two decades (20022 to 2022). Full article

There is a need for the assessment of respiratory hazard potential and mode of action of carbon nanotubes (CNTs) before their approval for technological or medical applications. In CNT-exposed lungs, both alveolar macrophages (MФs), which phagocytose CNTs, and alveolar epithelial type II cells (AECII cells), which show tissue injury, are impacted but cell–cell interactions between them and the impacted mechanisms are unclear. To investigate this, we first optimized an air–liquid interface (ALI) transwell coculture of human AECII cell line A549 (upper chamber) and human monocyte cell line THP-1 derived macrophages (lower chamber) in a 12-well culture by exposing macrophages to CNTs at varying doses (5–60 ng/well) for 12–48 h and measuring the epithelial response markers for cell differentiation/maturation (proSP-C), proliferation (Ki-67), and inflammation (IL-1β). In optimal ALI epithelial-macrophage coculture (3:1 ratio), expression of Ki-67 in AECII cells showed dose dependence, peaking at 15 ng/well CNT dose; the Ki-67 and IL-1β responses were detectable within 12 h, peaking at 24–36 h in a time-course. Using the optimized ALI transwell coculture set up with and without macrophages, we demonstrated that direct interaction between CNTs and MФs, but not a physical cell–cell contact between MФ and AECII cells, was essential for inducing immunotoxicity (proliferative and inflammatory responses) in the AECII cells. Full article

Background/Objectives. Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). Here, the expression of two proteins controlling the epithelial–mesenchymal transition (EMT)—an underlying NF-PitNET pathogenic mechanism—were analyzed as prognostic markers: E-cadherin (E-Cad) and KLHL14. Methods. The immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NF-PitNET patients, with low and high invasiveness grades (respectively, Ki67⁺ < and ≥3%) was carried out. Results. The analysis of healthy vs. NF-PitNET tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad and KLHL14 shifted from a cytoplasmic (C) form in a low invasive NF-PitNET to a nuclear (N) localization in a high invasive NF-PitNET. A significant correlation was found between E-Cad/KLHL14 co-localization in the cytoplasm (p = 0.01) and nucleus (p = 0.01) and with NF-PitNET invasiveness grade. Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected in high invasive NF-PitNET patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67⁺ ≥ 3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NF-PitNET patients have to be analyzed to definitively recognize a key prognostic role for KLHL14. Full article

Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC. Full article

The aim of this work was to determine the changes in the chemical and physical-mechanical properties of gauze compresses under the influence of various sterilizations. Gauze compresses are made of cotton; therefore, all methods used focused on cotton. The methods used to test possible damage to cotton materials (pH value (pH paper, KI starch paper), yellowing test, Fehling reaction, reaction to the formation of Turnbull blue (Berlin blue), microscopic staining with methylene blue and swelling reaction with Na-zincate) did not show that the sterilizations affected the cotton compresses. The morphological characteristics were examined with a scanning electron microscope (SEM). The SEM images showed that there were no morphological changes in the cotton fibers. FTIR-ATR spectroscopy revealed that the sterilization processes did not alter the characteristic bands of the cotton. The length of the macromolecules was increased (DP), showing that the sterilization processes had affected the cotton. The results of the wet strength test followed. The samples showed values below 100%, with the exception of two samples. It is known from theory that the relative wet strength is less than 100% when the material is damaged. The t-test performed on the strength results showed that the p-value was greater than 0.05 for all samples tested, with the exception of one sample. The degree of swelling capacity was determined, with non-sterilized samples having the highest capacity, followed by samples sterilized with ethylene oxide and then samples sterilized by steam sterilization. The results obtained are a contribution to the innovation of the topic of this work and a scientific confirmation for manufacturers and anyone interested in the influence of the sterilization process on natural fibers (cotton). Full article