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Best Practice & Research. Clinical... Sep 2023Neuroendocrine neoplasms are rare and heterogenous group of tumors with varying degrees of clinical presentations and involvement of multiple organ systems in the body.... (Review)
Review
Neuroendocrine neoplasms are rare and heterogenous group of tumors with varying degrees of clinical presentations and involvement of multiple organ systems in the body. In the modern clinical practice somatostatin receptor molecular imaging and targeted radioligand therapy plays a vital role in the diagnosis and management of the disease. Several new and promising radiotracers for NET imaging and theranostics, belonging to various groups and classes are being studied and investigated. This exponential growth of radiotracers poses concerns about the indication, clinical benefit, and safety profile of the agents. We discuss the basis behind these radiotracers clinical use, receptor targeting and intra and inter tumor heterogeneity. Furthermore, role of dual tracer imaging, combination therapy and potential applications of dosimetry in predicting treatment outcome and safety profile is reviewed. Individualized precision medicine with better tumor characterization, maximum therapeutic benefit and minimum toxicity is the way forward for future medicine.
Topics: Humans; Neuroendocrine Tumors; Radiopharmaceuticals; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography; Receptors, Somatostatin
PubMed: 37468403
DOI: 10.1016/j.beem.2023.101797 -
Investigative Ophthalmology & Visual... Jul 2023To investigate the endothelial heterogeneity across distinct vascular beds in the inner and outer blood-retinal barriers.
PURPOSE
To investigate the endothelial heterogeneity across distinct vascular beds in the inner and outer blood-retinal barriers.
METHODS
We evaluated the molecular, cellular, and functional differences between primary human retinal endothelial cells (HRECs) and human choroidal endothelial cells (HCECs) in terms of angiogenic and vasculogenic properties, permeability, and transcytosis. Tube formation assay, cell migration assay, in vitro permeability assay, microfluidic sprouting assay, and transcriptome analysis were performed.
RESULTS
HRECs showed higher proliferation and migration activity than did HCECs, whereas the tube formation ability was similar between HRECs and HCECs. Under angiogenic stimuli, HCECs displayed earlier sprouting angiogenesis, but the overall speed was faster and more stable in HRECs. HRECs expressed higher levels of adherens junctional proteins, whereas the tight junctional genes and transcytosis-related genes were more highly expressed in HCECs. Angiopoietin-2 was predominantly expressed in HRECs, but vascular endothelial growth factor (VEGF) receptors were more strongly expressed in HCECs. Platelet-derived growth factor subunit B (PDGFB) was more highly expressed in HRECs, which correlates to the lower degree of pericyte coverage in choroidal blood vessels.
CONCLUSIONS
Retinal and choroidal ECs showed significant cellular and molecular heterogeneities that correlated with their functional characteristics. Retinal ECs are vasculogenic with high migratory characteristics and faster angiogenic sprouting, and they are more responsive to VEGF-induced permeability. In contrast, choroidal ECs express high levels of transcytosis genes, and they are vasculogenic, rather proliferative, adept in generating tip cells, and less responsive to VEGF-induced permeability.
Topics: Humans; Endothelial Cells; Vascular Endothelial Growth Factor A; Cell Proliferation; Cell Movement; Retina; Cells, Cultured
PubMed: 37504962
DOI: 10.1167/iovs.64.10.35 -
Heliyon Jan 2024In this paper we empirically investigate dividends and repurchases of the UK, and the overarching pattern reveals that their determinants are more driven by payout size...
In this paper we empirically investigate dividends and repurchases of the UK, and the overarching pattern reveals that their determinants are more driven by payout size than they are by payout type. The overall corporate payout policy is influenced by the operating performance and tax framework. Aggregately, the determinants of dividends and repurchases are heterogenous, and for each payout's individual testing the determinants have shown varying influences when controlled for payout size; small, medium and large. Comparatively, the determinants of dividends and repurchases of small size show homogeneity, while those of medium and large sizes exhibit heterogeneity. From a variable-specific perspective, aggregately dividends are positively influenced by asset holdings and ROA, and negatively influenced by independent directions and EPS. While aggregately repurchases are positively influenced by debt exposure and negatively influenced by M/B Ratio.
PubMed: 38163197
DOI: 10.1016/j.heliyon.2023.e23270 -
Cureus Oct 2023The role of vitamin D in maintaining gum well-being is crucial. However, scientific research reported that the connotations of cholecalciferol and periodontal health... (Review)
Review
The role of vitamin D in maintaining gum well-being is crucial. However, scientific research reported that the connotations of cholecalciferol and periodontal health have been divested in the present literature. However, there is enormous heterogeneity in the data available. The current review aims to systematically review and appraise the available literature investigating the role of vitamin D in maintaining periodontal health. Studies included randomized controlled trials and clinical trials following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and cohort studies reporting associations between vitamin D and oral health in systemically healthy patients. Databases such as PubMed, Google Scholar, Scopus, Embase, and other sources, including hand search, were searched until May 2023 using together-equipped search sequences. Altogether, scientific articles that conform to the inclusion principles underwent a thorough eminence evaluation. All papers meeting inclusion criteria were subject to quality assessment, and the method used to assess the risk of bias was the Cochrane risk of bias tool. The search identified 1883 papers, among which 1435 were excluded after title evaluation. After abstract and title screening, 455 were excluded, and six full texts were assessed. After full-text evaluation, two articles were excluded, and only four were included. The data shows vitamin D's association with oral health maintenance. Along with its action on bone metabolism, it has extended function, which provides for its action as an anti-inflammatory agent and production of anti-microbial peptides, which help maintain oral health. Although the literature available is immense, there is enormous heterogenicity in the papers conducted to appraise the association between vitamin D and oral health. This systematic review has filtered all the data to review a few essential aspects of the role of vitamin D in maintaining oral physiology. Vitamin D has a linear relationship with periodontal health; however, the evidence is insufficient, and further studies must be done.
PubMed: 37899906
DOI: 10.7759/cureus.47773 -
Frontiers in Cell and Developmental... 2023Cancer cell heterogeneity is a key contributor to therapeutic failure and post-treatment recurrence. Targeting cell subpopulations responsible for chemoresistance and... (Review)
Review
Cancer cell heterogeneity is a key contributor to therapeutic failure and post-treatment recurrence. Targeting cell subpopulations responsible for chemoresistance and recurrence seems to be an attractive approach to improve treatment outcome in cancer patients. However, this remains challenging due to the complexity and incomplete characterization of tumor cell subpopulations. The heterogeneity of cells exhibiting stemness-related features, such as self-renewal and chemoresistance, fuels this complexity. Notch signaling is a known regulator of cancer stem cell (CSC) features in colorectal cancer (CRC), though the effects of its heterogenous signaling on CRC cell stemness are only just emerging. In this review, we discuss how Notch ligand-receptor specificity contributes to regulating stemness, self-renewal, chemoresistance and cancer stem cells heterogeneity in CRC.
PubMed: 37860822
DOI: 10.3389/fcell.2023.1231416 -
Trends in Ecology & Evolution Mar 2024Dispersal has a key role in shaping spatial patterns of biodiversity, yet its spatial heterogeneity is often overlooked in biodiversity analyses and management... (Review)
Review
Dispersal has a key role in shaping spatial patterns of biodiversity, yet its spatial heterogeneity is often overlooked in biodiversity analyses and management strategies. Properly parameterised heterogeneous dispersal networks capture the complex interplay between landscape structure and species-specific dispersal capacities. However, this heterogeneity is recurrently neglected when studying the processes underlying biodiversity variation. To address this gap, we introduce a conceptual framework detailing the fundamental processes driving dispersal heterogeneity and its effects on biodiversity dynamics. We propose methods to parameterise heterogeneous dispersal networks, facilitating their integration into commonly used quantitative frameworks for biodiversity analyses. By considering the architecture of heterogeneous dispersal networks, we demonstrate their critical role in guiding biodiversity management strategies.
Topics: Ecosystem; Biodiversity
PubMed: 37891075
DOI: 10.1016/j.tree.2023.10.002 -
Virchows Archiv : An International... Dec 2023Mismatch repair (MMR) immunohistochemical (IHC) evaluation has entered pathology routine practice as the first-line screening method to identify patients with MMR...
Mismatch repair (MMR) immunohistochemical (IHC) evaluation has entered pathology routine practice as the first-line screening method to identify patients with MMR deficient (MMRd)/microsatellite instability (MSI) colorectal cancer (CRC), and its misdiagnosis may significantly impact the personalization of CRC patient care. To determine the prevalence of MMR protein intratumor heterogeneity in real-world practice, we collected a series of 8282 CRCs tested for MMR proteins in the setting of Lynch syndrome universal screening. Four heterogenous cases were also investigated for tumor infiltrating lymphocytes count, MSI status, and consensus molecular subtypes by Nanostring nCounter® Platform. Overall, 1056 (12.8%) CRCs showed a MMR altered status, with 46 cases showing a heterogeneous MMR profile (0.56% of the total, and 4.36% of all MMRd cases). To conclude, the authors make some critical remarks regarding the approach to MMR heterogeneity in clinical practice and routine diagnostics.
PubMed: 38141133
DOI: 10.1007/s00428-023-03726-z -
Advanced Materials (Deerfield Beach,... Jul 2023Quantum materials are usually heterogeneous, with structural defects, impurities, surfaces, edges, interfaces, and disorder. These heterogeneities are sometimes viewed... (Review)
Review
Quantum materials are usually heterogeneous, with structural defects, impurities, surfaces, edges, interfaces, and disorder. These heterogeneities are sometimes viewed as liabilities within conventional systems; however, their electronic and magnetic structures often define and affect the quantum phenomena such as coherence, interaction, entanglement, and topological effects in the host system. Therefore, a critical need is to understand the roles of heterogeneities in order to endow materials with new quantum functions for energy and quantum information science applications. In this article, several representative examples are reviewed on the recent progress in connecting the heterogeneities to the quantum behaviors of real materials. Specifically, three intertwined topic areas are assessed: i) Reveal the structural, electronic, magnetic, vibrational, and optical degrees of freedom of heterogeneities. ii) Understand the effect of heterogeneities on the behaviors of quantum states in host material systems. iii) Control heterogeneities for new quantum functions. This progress is achieved by establishing the atomistic-level structure-property relationships associated with heterogeneities in quantum materials. The understanding of the interactions between electronic, magnetic, photonic, and vibrational states of heterogeneities enables the design of new quantum materials, including topological matter and quantum light emitters based on heterogenous 2D materials.
PubMed: 35170112
DOI: 10.1002/adma.202106909 -
Nature Communications Jul 2023Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of...
Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to be clarified. To study the multimodal response of single human cells to herpes simplex virus type 1 (HSV-1) infection, we mapped high-dimensional viral and cellular state spaces throughout the infection using multiplexed imaging and quantitative single-cell measurements of viral and cellular mRNAs and proteins. Here we show that the high-dimensional cellular state scape can predict heterogenous infections, and cells move through the cellular state landscape according to infection progression. Spatial information reveals that infection changes the cellular state of both infected cells and of their neighbors. The multiplexed imaging of HSV-1-induced cellular modifications links infection progression to changes in signaling responses, transcriptional activity, and processing bodies. Our data show that multiplexed quantification of responses at the single-cell level, across thousands of cells helps predict infections and identify new targets for antivirals.
Topics: Humans; Herpesvirus 1, Human; Herpes Simplex; Antiviral Agents; RNA, Messenger; Virus Replication
PubMed: 37500668
DOI: 10.1038/s41467-023-40148-6 -
Heliyon Sep 2023Lung fibroblasts are the major components in the connective tissue of the pulmonary interstitium and play essential roles in the developing of postnatal lung,... (Review)
Review
Lung fibroblasts are the major components in the connective tissue of the pulmonary interstitium and play essential roles in the developing of postnatal lung, synthesizing the extracellular matrix and maintaining the integrity of the lung architecture. Fibroblasts are activated in various disease conditions and exhibit functional heterogeneities according to their origin, spatial location, activated state and microenvironment. In recent years, advances in technology have enabled researchers to identify fibroblast subpopulations in both mouse and human. Here, we discuss pulmonary fibroblast heterogeneity, focusing on the developing, healthy and pathological lung conditions. We firstly review the expression profiles of fibroblasts during lung development, and then consider fibroblast diversity according to different anatomical sites of lung architecture. Subsequently, we discuss fibroblast heterogeneity in genetic lineage. Finally, we focus on how fibroblast heterogeneity may shed light on different pathological lung conditions such as fibrotic diseases, infectious diseases including COVID-19, and lung cancers. We emphasize the importance of comparative studies to illuminate the overlapping characteristics, expression profiles and signaling pathways of the fibroblast subpopulations across disease conditions, a better characterization of the functional complexity rather than the expression of a particular gene may have important therapeutic applications.
PubMed: 37674845
DOI: 10.1016/j.heliyon.2023.e19428