Morphological Heterogeneity Research Articles

Effects of therapeutic factors on brown adipose tissue in order to correct obesity

Adipose tissue has morphological heterogeneity. Currently, five types of fat cells are known: white, beige, brown, yellow and pink adipocytes. In the future, we will consider white, beige and brown adipocytes. The main pathological role in the development of obesity and a number of other metabolic diseases is played by white adipose tissue. The function of energy storage in white adipocytes is well known. However, in pathological conditions, the mass of white fat can increase significantly, amounting to more than 70% of the total body weight. In addition, white adipocytes are prone to inflammation and pathological production of biologically active substances - adipokines. Many adipokines negatively affect musculoskeletal and bone tissues, exacerbate systemic chronic inflammation and the severity of polymorbid pathology. At the same time, brown adipose tissue, due to its pronounced ability to heat production (thermogenesis), has protective properties. Activation of brown adipose tissue and stimulation of the transformation of white adipocytes into brown ones (the so-called “browning”) with the help of physical activity, medications and dietary supplements seems promising. These methods can be successfully used to combat overweight and obesity. In addition, modern advances in genetics and transplantology allow us to hope for the future use of brown adipocyte transplantation in patients who suffer from severe obesity. Research on the interrelationships of adipose tissue, muscles, cardiovascular, nervous, endocrine and other body systems continue. Undoubtedly, there are many interesting scientific discoveries to be made in medical science.

Low-Energy Electron Beam Modification of Metallic Biomaterial Surfaces: Oxygen and Silicon-Rich Amorphous Carbon as a Wear-Resistant Coating.

Metallic biomaterials, such as cobalt chrome molybdenum (CoCrMo), Ti-6Al-4V, and 316L stainless steel are commonly used in orthopedic implant devices. Damage modes such as corrosion and wear are associated with the use of these alloys. One solution to limit wear and corrosion damage is to apply a surface coating to the medical device. In this study, using the low-energy electron beam (LEEB) of scanning electron microscopy (SEM), we induced a highly scratch-resistant oxygen and silicon-rich amorphous carbon film to grow on each of the above metallic biomaterials. LEEB interaction with adventitious surface carbon, silicone, and oxygen deposited on the above three alloys resulted in the layered-deposition formation (LEEB-LD) of a surface coating. Coating chemistry, morphology, and nano-scratch wear properties on each of the three alloys were characterized using atomic force microscopy (AFM) scratch testing and SEM/Energy dispersive spectroscopy (EDS) analysis. We hypothesized that LEEB-LD coatings could be deposited on these three metallic biomaterials with improved tribological properties than the underlying metal substrate. First, we generated coatings on all three biomaterials and documented the coating morphology (thickness and heterogeneity) and chemistry as a function of alloy, exposure time, and scan rate with coating thicknesses generated between 5 and 50 nm after 60 min of treatment, with each factor affecting the thickness. EDS maps showed high amounts of carbon, oxygen, and silicon in the modified surface which depended on the alloy (e.g., CoCrMo and SS had similar compositions while Ti had higher oxygen in the coatings). Coated and uncoated surfaces were then subjected to diamond scratch testing in an AFM at increasing force until the coating delaminated from the surface. Scratch-depth versus load and nominal Hertzian stress were plotted for both the uncoated and coated surfaces. We found that scratch depths were 40%, 75%, and 38% smaller on CoCrMo, Ti, and SS coatings, respectively, at the peak contact stresses tested (⍺ < 0.05), indicating higher hardness and wear resistance for the coatings. These results support the hypothesis that controlled thickness LEEB-LD oxygen and silicon-rich amorphous carbon coatings can be systematically generated using low-power electron beams and that these coatings have increased tribological (scratch-resistance) properties compared to the substrate metal.

Epstein-Barr virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review.

This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with the EBV-negative area showing more complex DNA aberrations, reminiscent of chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and -negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlights the impact of EBV loss on tumour behaviour.

Nanoplastic in aqueous environments: The role of chemo-electric properties for nanoplastic-mineral interaction.

Due to increasing plastic production, the continuous release of primary and secondary nanoplastic particles (NPs, <1μm) has become an emerging contaminant in terrestrial environments. The fate and transport of NPs in subsurface environments remain poorly understood, largely due to the complex interplay of mineralogical, chemical, biological, and morphological heterogeneity. This study examines interactions between abundant subsurface minerals and NPs under controlled water chemistry (1mM KCl, pH5.5). These conditions minimize potential chemical effects from ions in solution, isolating the impact of mineral complexity. Surface-modified polystyrene nanoparticles (-COOH and -NH2 functional groups) are proxies for degradation products and organic associations found in environmental plastics. Experimental results are compared with theoretical predictions using DLVO (Derjaguin-Landau-Verwey-Overbeek) double-layer force models. Despite all studied minerals maintaining negative surface charges across varying pH, electrostatic double-layer (EDL) interactions played a minor role in NP attachment. Instead, mechanisms such as specific ion-binding interactions (mediated by trace metal ions), bridging via divalent ions, and hydrogen bonding were more significant. Evidence suggests that kinetic effects for most mineral-NP combinations persist beyond 24h. This study highlights the critical role of biogeochemical and mineralogical composition in controlling NP attachment and release in subsurface environments, with implications for their transport and fate in aquifers.

Morphometric Characterization of Economically Important Populations of Black Tiger Shrimp (&lt;em&gt;Penaeus monodon&lt;/em&gt;) Natural Broodstocks in Sri Lanka

Purpose: Presence of morphological heterogeneity and economically superior traits in naturally available brood stock greatly supports yield improvement programs characterizing sub-populations with such traits will provide leverage in doing so. The present study was an attempt to characterise giant tiger shrimp, Penaeus monodon brood stock from Sri Lankan waters to identify whether or not commercially important sub-populations exist based on morphological traits, which can be used for the yield improving P. monodon farming industry in Sri Lanka.Research Method: A total of 495 P. monodon samples were randomly collected from nine areas around the country. Ten selected morphometric traits and the Body Weight (BW) were measured from each. Morphometric measurements were standardized and subjected to multivariate analysis with equation LTs (i)=log10LT(i)[log10 TL(m)/log10 TL(i)]b.Findings: Selected morphological traits were highly correlated with BW showing the highest correlation from hepatic spine width and the lowest correlation by width at the midpoint of the abdominal segment six. In PCA, both PC1 and PC2 accounted for 68.1% of total variation. The scatter plot of PC1 and PC2 indicated that all samples in the nine zones belonged to one population. However, significant variations in BW, standard body length, and abdominal length were observed in different areas and the highest significant BW was recorded in Chilaw, Beruwala, Negombo, and Mullaitivu.Originality/Value: Economically important morphological traits in Penaeus monodon are prominent in a few populations around the country, prompting to selection of individuals from these areas for brood stock improvement programs.

Histology Assessment of Chitosan-Polyvinyl Alcohol Scaffolds Incorporated with CaO Nanoparticles.

Scaffolds for regenerative therapy can be made from natural or synthetic polymers, each offering distinct benefits. Natural biopolymers like chitosan (CS) are biocompatible and biodegradable, supporting cell interactions, but lack mechanical strength. Synthetic polymers like polyvinyl alcohol (PVA) provide superior mechanical strength and cost efficiency but are not biodegradable or supportive of cell adhesion. Combining these polymers optimizes their advantages while adding metal oxide nanoparticles like calcium oxide (CaO NPs) enhances antimicrobial properties by damaging bacterial membranes. In this study, we obtained the formation of CaO NPs by calcinating eggshells, which were mixed in a polymeric network of CS and PVA to obtain four different membrane formulations for subdermal tissue regeneration. The spherical nanoparticles measured 13.43 ± 0.46 nm in size. Their incorporation into the membranes broadened the hydroxyl bands in the Fourier transform infrared (FTIR) analysis at 3331 cm⁻1. X-ray diffraction (XRD) analysis showed changes in the crystalline structure, with new diffraction peaks at 2θ values of 7.2° for formulations F2, F3, and F4, likely due to the increased amorphous nature and concentration of CaO NPs. Additionally, higher CaO NPs concentrations led to a reduction in thermal properties and crystallinity. Scanning electron microscopy (SEM) revealed a heterogeneous morphology with needle-like structures on the surface, resulting from the uniform dispersion of CaO NPs among the polymer chains and the solvent evaporation process. A histological examination of the implanted membranes after 60 days indicated their biocompatibility and biodegradability, facilitated by incorporating CaO NPs. During the degradation process, the material fragmented and was absorbed by inflammatory cells, which promoted the proliferation of collagen fibers and blood vessels. These findings highlight the potential of incorporating CaO NPs in soft tissue regeneration scaffolds.

Lung Endothelial Cell Heterogeneity in Health and Pulmonary Vascular Disease.

Lung endothelial cells (ECs) are essential for maintaining organ function and homeostasis. Despite sharing some common features with ECs from organ systems, lung ECs exhibit significant heterogeneity in morphology, function, and gene expression. This heterogeneity is increasingly recognized as a key contributor to the development of pulmonary diseases like pulmonary hypertension (PH). In this mini-review, we explore the evolving understanding of lung EC heterogeneity, particularly through the lens of single-cell RNA sequencing (scRNA-seq) technologies. These advances have provided unprecedented insights into the diverse EC subpopulations, their specific roles, and the disturbances in their homeostatic functions that contribute to PH pathogenesis. In particular, these studies identified novel and functionally distinct cell types such as aerocytes and general capillary ECs that are critical for maintaining lung function in health and disease. In addition, multiple novel pathways and mechanisms have been identified that contribute to aberrant pulmonary vascular remodeling in PH. Emerging techniques like single-nucleus RNA sequencing and spatial transcriptomics have further pushed the field forward by discovering novel disease mediators. As research continues to leverage these advanced techniques, the field is poised to uncover novel EC subtypes and disease mechanisms, paving the way for new therapeutic targets in PH and other lung diseases.

Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer's disease progression.

For over a century after their discovery astrocytes were regarded merely as cells located among other brain cells to hold and give support to neurons. Astrocytes activation, "astrocytosis" or A1 functional state, was considered a detrimental mechanism against neuronal survival. Recently, the scientific view on astrocytes has changed. Accumulating evidence indicate that astrocytes are not homogeneous, but rather encompass heterogeneous subpopulations of cells that differ from each other in terms of transcriptomics, molecular signature, function and response in physiological and pathological conditions. In this review, we report and discuss the recent literature on the phenomic differences of astrocytes in health and their modifications in disease conditions, focusing mainly on the hippocampus, a region involved in learning and memory encoding, in the age-related memory impairments, and in Alzheimer's disease (AD) dementia. The morphological and functional heterogeneity of astrocytes in different brain regions may be related to their different housekeeping functions. Astrocytes that express diverse transcriptomics and phenomics are present in strictly correlated brain regions and they are likely responsible for interactions essential for the formation of the specialized neural circuits that drive complex behaviors. In the contiguous and interconnected hippocampal areas CA1 and CA3, astrocytes show different, finely regulated, and region-specific heterogeneity. Heterogeneous astrocytes have specific activities in the healthy brain, and respond differently to physiological or pathological stimuli, such as inflammaging present in normal brain aging or beta-amyloid-dependent neuroinflammation typical of AD. To become reactive, astrocytes undergo transcriptional, functional, and morphological changes that transform them into cells with different properties and functions. Alterations of astrocytes affect the neurovascular unit, the blood-brain barrier and reverberate to other brain cell populations, favoring or dysregulating their activities. It will be of great interest to understand whether the differential phenomics of astrocytes in health and disease can explain the diverse vulnerability of the hippocampal areas to aging or to different damaging insults, in order to find new astrocyte-targeted therapies that might prevent or treat neurodegenerative disorders.

An integrated microfluidic device for sorting of tumor organoids using image recognition.

Tumor organoids present a challenge in drug screening due to their considerable heterogeneity in morphology and size. To address this issue, we proposed a portable microfluidic device that employs image processing algorithms for specific target organoid recognition and microvalve-controlled deflection for sorting and collection. This morphology-activated organoid sorting system offers numerous advantages, such as automated classification, portability, low cost, label-free sample preparation, and gentle handling of organoids. We conducted classification experiments using polystyrene beads, F9 tumoroids and patient-derived tumor organoids, achieving organoid separation efficiency exceeding 88%, purity surpassing 91%, viability exceeding 97% and classification throughput of 800 per hour, thereby meeting the demands of clinical organoid medicine.

Miniaturization and characterization of patient derived hepatocellular carcinoma tumor organoid cultures for cancer drug discovery applications.

Patient derived tumor organoid (PDTO) models retain the structural, morphological, genetic, and clonal heterogeneity of the original tumors. The ability to efficiently generate, expand, and biobank PDTOs has the potential to make the clinical diversity of cancer accessible for personalized medicine assay guided therapeutic drug selection and drug discovery. We describe the miniaturization and growth in 96- and 384-well formats of a single non-tumor liver and two Hepatocellular carcinoma (HCC) organoids derived from cryopreserved PDTO cells and the application of high content imaging (HCI) to characterize the models and enhance drug sensitivity testing. Non-invasive sequentially acquired transmitted light images showed that seeding cryopreserved cells from non-tumoral and HCC PDTOs into 96- or 384-well plates in reduced growth factor Matrigel (rgf-MG) that were fed with growth medium every 3 days supported organoid growth up to 15 days. The number and sizes of organoids increased with longer times in culture. HCC PDTO's had more heterogeneous morphologies than non-tumor organoids with respect to size, shape, and optical density. Organoids cultured in rgf-MG could be stained in situ with HCI reagents without mechanical, chemical or enzymatic disruption of the hydrogel matrices and quantitative data extracted by image analysis. Hoechst and live/dead reagents provided organoid numbers and viability comparisons. HCC PDTO's stained with phalloidin or immuno-stained with α-tubulin antibodies revealed F-actin and microtubule cytoskeleton organization. HCC PDTO's stained with antibodies to signaling pathway proteins and their phosphorylation status allowed comparisons of relative expression levels and inference of pathway activation. Images of HCC PDTO's exposed to ellipticine showed that drugs penetrate Matrigel hydrogels and accumulate in organoid cells. 9-day 384-well HCC organoid cultures exhibited robust and reproducible growth signals suitable for cancer drug testing. Complimenting cell viability readouts with multiple HCI parameters including morphological features and dead cell staining improved the analysis of drug impact and enhanced the value that could be extracted from these more physiologically relevant three-dimensional HCC organoid cultures.

Exploring the Influence of Morphologic Heterogeneity and Discharge on Transient Storage in Stream Systems: 1. Insights From the Field

AbstractHere, we explore how differences in morphologic heterogeneity due to logjams and secondary channels drive transient storage across discharge in two stream reaches within the Front Range of Colorado, USA. During three tracer tests conducted from baseflow to near‐peak snowmelt, we collected instream fluid conductivity measurements and conducted electrical resistivity surveys to characterize tracer movement in the surface and subsurface of the stream system. The reach with two logjams and an intermittent secondary channel exhibited greater heterogeneity in surface transient storage, driving heterogeneity in hyporheic exchange flows, compared to the reach with a single logjam and a perennial secondary channel. As discharge increased, (a) backwater pools created by logjams increased in size in both systems, (b) channel complexity increased as logjams forced flow into secondary channels, and (c) subsurface flowpath distribution increased. Various transient storage indices provide some insight on solute retention but compressing data from this system into simple values was unintuitive given the noise in breakthrough‐curve tails and secondary peaks in concentration. While subsurface exchange increases with discharge in both reaches, retention may not. Flushing of subsurface tracers is highest at medium discharge as interpreted from the electrical resistivity inversions in both reaches, perhaps because of a tradeoff between the increasing extent of subsurface flowpaths with discharge and larger pressure gradients for driving flow. This work is one of the first to explore controls on exchange and retention in stream systems with multiple logjams and evolving channel planform using geophysical data to constrain the subsurface movement of solutes.

Investigation of physicochemical, morphological and biomedical properties of network hydrogels derived from arabinogalactan of acacia-tragacanth gum.

Recently, significant progress has been made in the development of natural polysaccharide-derived functional copolymers for advanced biomedical uses. Herein, the main objective of the present research work was to explore the potential of gum acacia (GA) and tragacanth gum (TG) for developing network hydrogels to use in drug delivery (DD) applications. The copolymers were prepared by grafting of 3-sulfopropylacrlate (SPA) onto gum (GA-TG). FE-SEM, AFM, XRD, XPS, FTIR, 13C NMR and DSC techniques were applied for their characterizations and structural analysis. The physicochemical, morphological and biomedical properties of hydrogels were investigated. The optimized polymer network exhibited a mesh size (ξ) of 13.95mm and a cross-linking density (ρ) of 6.44×10-5mol/cm3. FE-SEM and AFM revealed heterogeneous morphology and rough topology of copolymer hydrogels. The XRD revealed the amorphous state of the copolymer. FTIR and 13C NMR confirmed the incorporation of poly(SPA) chains onto gums. Diffusion of meropenem drug occurred in a sustained manner with a non-Fickian diffusion mechanism. The release profile of the drug was best described by the First-order kinetic model. The results of polymer-blood interactions revealed their non-haemolytic & non-thrombogenic features. Copolymers exhibited antioxidant nature and illustrated 40.72±2.08% scavenging ability during DPPH assay. The hydrogel demonstrated a mucoadhesive nature and required 100±10 mN forces to separate from mucous membrane. The meropenem impregnated hydrogel exhibited antibacterial activity against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) bacteria, respectively. The results of various properties demonstrated the suitability of network hydrogels for DD uses.

Identification of senescence markers on cultured human corneal endothelial cells

Aims/Purpose: Corneal transplantation is currently the most frequent type of transplantation globally. However, a chronic shortage of donor corneas makes traditional methods unsustainable. Alternatives such as bio‐engineered grafts or direct injection of corneal endothelial cells (CECs) into the patient's eye require the primary culture of CECs. Current CEC culture techniques face a significant challenge: cell senescence. Cells often become senescent during in vitro culture, rendering them unsuitable for clinical use and limiting the yield. Identifying specific markers of senescent CECs is crucial for studying this process. This study aims at identify robust markers of senescence in CEC cultures.Methods: Primary CEC cultures were obtained from human corneas following published methods. Various senescence markers for general cells and/or CECs were selected from the literature and applied using immunofluorescence (IF) in CEC cultures exhibiting heterogeneous morphology (presence of both very small and large, senescence‐associated cells) at different cell passages. The selected senescence markers were validated using induced senescent CECs by either removing anti‐senescent agents from the culture medium or adding TGF‐β1 or carteolol. β‐Galactosidase activity staining (SPiDER‐β Gal) was also tested.Results: Two candidate markers appeared suitable for detecting CEC senescence, each with specific attributes. Transgelin marked TGF‐β‐induced senescence, indicating a senescence‐associated secretory phenotype (SASP)‐related senescence, while SPiDER‐β Gal seemed linked to replicative senescence.Conclusions: Transgelin and SPiDER‐β Galactosidase are promising markers for detecting CEC senescence in vitro. Using both markers may help identify the causes of senescence.

Radiofrequency Induced Time-Dependent Alterations in Gene Expression and Apoptosis in Glioblastoma Cell Line.

The widespread use of wireless communication technologies has increased human exposure to radiofrequency electromagnetic fields (RF-EMFs). Considering the brain's close proximity to mobile phones and its entirely electrical transmission network, it emerges as the organ most profoundly impacted by the RF field. This study aims to investigate the potential effects of RF radiation on cell viability, apoptosis, and gene expressions in glioblastoma cells (U118-MG) at different exposure times (1, 24, and 48 h). To achieve this, we designed and implemented an in vitro RF exposure system operating at a frequency of 2.1 GHz, specifically for cell culture studies, with an average specific absorption rate (SAR) of 1.12 ± 0.18 W/kg determined through numerical dosimetry calculations. Results reveal a significant influence of a 48 h exposure to a 2.1 GHz RF field on U118-MG cell viability, gene expression, and the induction of caspase (CASP) dependent apoptosis. Notably, increased CASP3, CASP8, and CASP9 mRNA levels were observed after 24 and 48 h of RF treatment. However, only the 48 h RF exposure resulted in apoptotic cell death and a significant elevation in the BAX/BCL-2 ratio. This observed effect may be influenced by extended exposure durations surpassing the cell's doubling time. The increased BAX/BCL-2 ratio, which acts as a key switch for apoptosis, and the heterogeneous morphology of the astrocyte-derived U118-MG cell line may also play a role in this effect.

Identification of senescence markers on cultured human corneal endothelial cells

Aims/Purpose: Corneal transplantation is currently the most frequent type of transplantation globally. However, a chronic shortage of donor corneas makes traditional methods unsustainable. Alternatives such as bio‐engineered grafts or direct injection of corneal endothelial cells (CECs) into the patient's eye require the primary culture of CECs. Current CEC culture techniques face a significant challenge: cell senescence. Cells often become senescent during in vitro culture, rendering them unsuitable for clinical use and limiting the yield. Identifying specific markers of senescent CECs is crucial for studying this process. This study aims at identify robust markers of senescence in CEC cultures.Methods: Primary CEC cultures were obtained from human corneas following published methods. Various senescence markers for general cells and/or CECs were selected from the literature and applied using immunofluorescence (IF) in CEC cultures exhibiting heterogeneous morphology (presence of both very small and large, senescence‐associated cells) at different cell passages. The selected senescence markers were validated using induced senescent CECs by either removing anti‐senescent agents from the culture medium or adding TGF‐β1 or carteolol. β‐Galactosidase activity staining (SPiDER‐β Gal) was also tested.Results: Two candidate markers appeared suitable for detecting CEC senescence, each with specific attributes. Transgelin marked TGF‐β‐induced senescence, indicating a senescence‐associated secretory phenotype (SASP)‐related senescence, while SPiDER‐β Gal seemed linked to replicative senescence.Conclusions: Transgelin and SPiDER‐β Galactosidase are promising markers for detecting CEC senescence in vitro. Using both markers may help identify the causes of senescence.

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion and drug screening

Brain organoids offer unprecedented insights into brain development and disease modeling and hold promise for drug screening. Significant hindrances, however, are morphological and cellular heterogeneity, inter-organoid size differences, cellular stress, and poor reproducibility. Here, we describe a method that reproducibly generates thousands of organoids across multiple hiPSC lines. These High Quantity brain organoids (Hi-Q brain organoids) exhibit reproducible cytoarchitecture, cell diversity, and functionality, are free from ectopically active cellular stress pathways, and allow cryopreservation and re-culturing. Patient-derived Hi-Q brain organoids recapitulate distinct forms of developmental defects: primary microcephaly due to a mutation in CDK5RAP2 and progeria-associated defects of Cockayne syndrome. Hi-Q brain organoids displayed a reproducible invasion pattern for a given patient-derived glioma cell line. This enabled a medium-throughput drug screen to identify Selumetinib and Fulvestrant, as inhibitors of glioma invasion in vivo. Thus, the Hi-Q approach can easily be adapted to reliably harness brain organoids’ application for personalized neurogenetic disease modeling and drug discovery.

Preoperative CT-based morphological heterogeneity for predicting survival in patients with colorectal cancer liver metastases after surgical resection: a retrospective study

ObjectiveTo explore the value of preoperative CT-based morphological heterogeneity (MH) for predicting local tumor disease-free survival (LTDFS) and progression-free survival (PFS) in patients with colorectal cancer liver metastases (CRLM).MethodsThe latest CT data of 102 CRLM patients were retrospectively analyzed. The morphological score of each liver metastasis was obtained, and the morphological heterogeneity difference (MHD) was calculated. The receiver operating characteristic (ROC) curve was drawn, and the cutoff value was found. The Kaplan-Meier method was used to draw survival curves of patients with or without MH. The Cox regression analysis was used to build the model with MH and clinical characteristics for predicting PFS.ResultsIn 78 patients without MH, median PFS was 9.0 months (95% CI:6.5–11.5), while in 24 patients with MH, median PFS was 6.0 months (95% CI:4.0-8.1), indicating that MH significantly affected PFS (p = 0.001). MH affected PFS in both the chemotherapy group and the chemotherapy combined with targeted therapy group (p = 0.005, p = 0.043). MH, preoperative carcinoembryonic antigen (CEA) and chemotherapy after surgery were independent predictors for postoperative PFS in patients with CRLM.ConclusionPreoperative CT-based MH had good efficacy for predicting LTDFS and PFS of CRLM patients after surgical resection, regardless of preoperative treatment. MH is one of the independent predictors of PFS.

Microdissection of Distinct Morphological Regions Within Uveal Melanomas Identifies Novel Drug Targets.

Background/Objectives: Uveal melanomas (UMs) are rare but often deadly malignancies that urgently require viable treatment options. UMs often exhibit tumour heterogeneity, with macroscopic and microscopic differences in morphology between different regions of the same tumour. However, to date, the clinical significance of this and how it may help guide personalised therapy have not been realised. Methods: Using targeted DNA and RNA sequencing of a small case series of large, high-risk primary UMs, we explored whether morphologically distinct regions of the same tumour were associated with distinct molecular profiles. Results: In four of the seven tumours analysed, we detected different sets of genetic variants following the separate analysis of microdissected melanotic and amelanotic regions of the same tumour. These included a MET exon 14 skipping RNA transcript that predicts sensitivity to crizotinib and variants in other genes that are important in active clinical trials for patients with UM and advanced solid tumours. The integration of TCGA data also identified recurrent mutational events in genes that were not previously implicated in UM development (FANCA, SLX4, BRCA2, and ATRX). Conclusions: Our findings show that the molecular analysis of spatially separated and morphologically distinct regions of the same tumour may yield additional, therapeutically relevant genetic variants in uveal melanomas and have implications for the future molecular testing of UMs to identify targeted therapies.

Spatially Resolved Molecular Characterization of Noninvasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features (NIFTPs) Identifies a Distinct Proteomic Signature Associated with RAS-Mutant Lesions.

Follicular-patterned thyroid neoplasms comprise a diverse group of lesions that pose significant challenges in terms of differential diagnosis based solely on morphologic and genetic features. Thus, the identification of easily testable biomarkers complementing microscopic and genetic analyses is a highly anticipated advancement that could improve diagnostic accuracy, particularly for noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs). These tumors exhibit considerable morphological and molecular heterogeneity, which may complicate their distinction from structurally similar neoplasms, especially when genetic analyses reveal shared genomic alterations (e.g., RAS mutations). Here, we integrated next-generation sequencing (NGS) with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to perform a proteogenomic analysis on 85 NIFTPs (n = 30 RAS-mutant [RAS-mut] and n = 55 RAS-wild type [RAS-wt]), with the aim to detect putative biomarkers of RAS-mut lesions. Through this combined approach, we identified four proteins that were significantly underexpressed in RAS-mut as compared to RAS-wt NIFTPs. These proteins could serve as readily accessible markers in morphologically borderline cases showing RAS mutations. Additionally, our findings may provide insights into the distinct pathogenic pathways through which RAS-mut and RAS-wt NIFTPs arise, highlighting the pivotal role of constitutive RAS-mitogen-activated protein kinase (MAPK) pathway activation in the development and progression of RAS-mut tumors.

Association Between Polymorphisms in DNA Repair Genes and Glioma Susceptibility: A Meta-Analysis of Four Single Nucleotide Polymorphisms (rs3212986, rs13181, rs25487, and rs861539).

Cases with central nervous system tumors represent a small amount of all tumors, and the diagnosis of high-grade gliomas (HGGs) is mostly difficult as they frequently show intratumoral morphological heterogeneity. Genetic factors, such as single nucleotide polymorphisms (SNPs), have an important role in modifying glioma susceptibility. We conducted a comprehensive meta-analysis to investigate the ERCC1 (rs3212986), ERCC2 (rs13181), XRCC1 (rs25487), and XRCC3 (rs861539) genes to see if they are any risk factors for glioma susceptibility. We identified 30 eligible studies investigating the PubMed records (up to January 2024) via a mishmash of the subsequent terms: brain tumors, glioma, glioblastoma, gene associations, SNPs, XRCC1, XRCC3, ERCC1, and ERCC2. The total number of patients was 23678 (9731 in cases (poor outcome) and 13947 in controls (good outcome)). This comprehensive meta-analysis declared a significant association between ERCC2 rs13181, XRCC1 rs25487, and the risk of glioma.