CD4/CD8 double-negative mycosis fungoides: a review

Mycosis Fungoides (MF) stands as the predominant form of primary cutaneous T-cell lymphoma (CTCL). It manifests a diverse array of clinical, histological, and immunophenotypic variations, each bearing distinct prognostic implications. The typical immunophenotypic profile of mycosis fungoides involves CD3+/CD4+/CD45RO+ memory T cells. Notably, the CD4-/CD8- double-negative variant of MF is a rare occurrence, observed in approximately 12% of early-stage cases and more prevalent in tumor-stage instances, often correlated with atypical clinical presentations. Despite its rarity, scant information is available about double-negative Mycosis Fungoides, with only a limited number of cases documented in the existing literature. This review aims to provide enhanced clarity, comprehension, and a detailed exploration of the spectrum encompassing double-negative mycosis fungoides

Proteomic analysis of morphologically changed tissues after prolonged dexamethasone treatment

Prolonged dexamethasone (Dex) administration leads to serious adverse and decrease brain and heart size, muscular atrophy, hemorrhagic liver, and presence of kidney cysts. Herein, we used an untargeted proteomic approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous identification of changes in proteomes of the major organs in Sprague-Dawley (SD rats post Dex treatment. The comparative and quantitative proteomic analysis of the brain, heart, muscle, liver, and kidney tissues revealed differential expression of proteins (n = 190, 193, 39, 230, and 53, respectively) between Dex-treated and control rats. Functional network analysis using ingenuity pathway analysis (IPA revealed significant differences in regulation of metabolic pathways within the morphologically changed organs that related to: (i) brain-cell morphology, nervous system development, and function and neurological disease; (ii) heart-cellular development, cellular function and maintenance, connective tissue development and function; (iii) skeletal muscle-nucleic acid metabolism, and small molecule biochemical pathways; (iv) liver-lipid metabolism, small molecular biochemistry, and nucleic acid metabolism; and (v) kidney-drug metabolism, organism injury and abnormalities, and renal damage. Our study provides a comprehensive description of the organ-specific proteomic profilesand differentially altered biochemical pathways, after prolonged Dex treatement to understand the molecular basis for development of side effects

PKCβ Facilitates Leukemogenesis in Chronic Lymphocytic Leukaemia by Promoting Constitutive BCR-Mediated Signalling

B cell antigen receptor (BCR) signalling competence is critical for the pathogenesis of chronic lymphocytic leukaemia (CLL). Defining key proteins that facilitate these networks aid in the identification of targets for therapeutic exploitation. We previously demonstrated that reduced PKCα function in mouse hematopoietic stem/progenitor cells (HPSCs) resulted in PKCβII upregulation and generation of a poor-prognostic CLL-like disease. Here, prkcb knockdown in HSPCs leads to reduced survival of PKCα-KR-expressing CLL-like cells, concurrent with reduced expression of the leukemic markers CD5 and CD23. SP1 promotes elevated expression of prkcb in PKCα-KR expressing cells enabling leukemogenesis. Global gene analysis revealed an upregulation of genes associated with B cell activation in PKCα-KR expressing cells, coincident with upregulation of PKCβII: supported by activation of key signalling hubs proximal to the BCR and elevated proliferation. Ibrutinib (BTK inhibitor) or enzastaurin (PKCβII inhibitor) treatment of PKCα-KR expressing cells and primary CLL cells showed similar patterns of Akt/mTOR pathway inhibition, supporting the role for PKCβII in maintaining proliferative signals in our CLL mouse model. Ibrutinib or enzastaurin treatment also reduced PKCα-KR-CLL cell migration towards CXCL12. Overall, we demonstrate that PKCβ expression facilitates leukemogenesis and identify that BCR-mediated signalling is a key driver of CLL development in the PKCα-KR model.</jats:p

The Application of Two-Dimensional Continuous Wavelet Transform Based on Active Infrared Thermography for Subsurface Defect Detection in Concrete Structures

The early condition-based assessment of civil infrastructures plays an essential role in extending their service life, preventing undesirable sudden failures, and reducing maintenance and rehabilitation costs. One of the most commonly used and fastest nondestructive testing (NDT) techniques is infrared thermography (IRT), which has emerged as a powerful method for assessing general concrete quality and detecting subsurface damage in structural members. Nevertheless, the accurate detection and classification of localized defects is still a challenging task to achieve. The contribution made by enhancing defect detection using two-dimensional (2D) wavelet transformation (WT) as a post-processing method, however, has received little attention within the field of active IR thermography. In this study, we explored the use of continuous wavelet transform (CWT) to visualize how the wavelet function at different frequencies could enhance the damage features of thermal images. A concrete slab under an applied heat flux was tested experimentally by an IR camera with well-controlled excitation sources. The qualitative visualization of thermograms was translated into quantitative results by extracting, processing, and post-processing the values assigned to the pixels in the thermal images. With the assumption of there being no oriented damage features, an isotropic (non-directional) Mexican hat wavelet was utilized as the mother wavelet. The experimental results showed that the 2D-CWT method achieved strong detection performance in extracting discriminatory features (defective areas) from the acquired thermal images. Compared with raw thermograms, the resultant CWT-transformed images were less affected by the non-uniform heating effect, and the boundaries of the defects contrasted more strongly. The 2D-CWT method demonstrates good sensitivity when an appropriate wavelet type and scale factor are chosen. Due to the desire to detect localized defects, adjusting the scale factor of the wavelet is important to improve the efficiency of detection as lower scale factors provide the finer details of thermal images, whereas higher scale factors provide the general outline of internal defects. The findings of this study represent a further step toward improving thermographic data for more precise defect-detection imaging, and principally for large concrete structures, that can be verified easily using other NDT surveys

The Application of Two-Dimensional Continuous Wavelet Transform Based on Active Infrared Thermography for Subsurface Defect Detection in Concrete Structures

The early condition-based assessment of civil infrastructures plays an essential role in extending their service life, preventing undesirable sudden failures, and reducing maintenance and rehabilitation costs. One of the most commonly used and fastest nondestructive testing (NDT) techniques is infrared thermography (IRT), which has emerged as a powerful method for assessing general concrete quality and detecting subsurface damage in structural members. Nevertheless, the accurate detection and classification of localized defects is still a challenging task to achieve. The contribution made by enhancing defect detection using two-dimensional (2D) wavelet transformation (WT) as a post-processing method, however, has received little attention within the field of active IR thermography. In this study, we explored the use of continuous wavelet transform (CWT) to visualize how the wavelet function at different frequencies could enhance the damage features of thermal images. A concrete slab under an applied heat flux was tested experimentally by an IR camera with well-controlled excitation sources. The qualitative visualization of thermograms was translated into quantitative results by extracting, processing, and post-processing the values assigned to the pixels in the thermal images. With the assumption of there being no oriented damage features, an isotropic (non-directional) Mexican hat wavelet was utilized as the mother wavelet. The experimental results showed that the 2D-CWT method achieved strong detection performance in extracting discriminatory features (defective areas) from the acquired thermal images. Compared with raw thermograms, the resultant CWT-transformed images were less affected by the non-uniform heating effect, and the boundaries of the defects contrasted more strongly. The 2D-CWT method demonstrates good sensitivity when an appropriate wavelet type and scale factor are chosen. Due to the desire to detect localized defects, adjusting the scale factor of the wavelet is important to improve the efficiency of detection as lower scale factors provide the finer details of thermal images, whereas higher scale factors provide the general outline of internal defects. The findings of this study represent a further step toward improving thermographic data for more precise defect-detection imaging, and principally for large concrete structures, that can be verified easily using other NDT surveys

Exploring <i>Ocimum basilicum</i>’s Secondary Metabolites: Inhibition and Molecular Docking against <i>Rhynchophorus ferrugineus</i> for Optimal Action

The objective of our work is to create a practical procedure to produce in vitro cell suspensions of O. basilicum and to ascertain the factors that encourage enhanced secondary metabolite production. We investigated the impact of these metabolites on Rhynchophorus ferrugineus’s adult and larval target enzymes. The explants were cultivated on Murashige and Skoog (MS) media with 0.1 to 1 mg/L plant growth regulators (PGRs) to create calluses. 2,4-Dichlorophenoxyacetic acid (2,4-D), kinetin, 1-naphthylacetic acid (NAA), and indole-3-butryic acid (IBA) at 0.5, 0.5, 0.1, and 1 mg/L, respectively, with 3% sucrose led to the highest biomass accumulation. In cell suspensions, the total phenolic content (TPC) and total flavonoid content (TFC) were 39.68 and 5.49 mg/g DW, respectively, with abiotic Verticillium dahliae as an activator. Rosmarinic acid, ursolic acid, nepetoidin A and B, salvigenin, and quercetin-3-O-rutinoside as flavonoids and phenolics were analyzed using UPLC-I TQD MS, with the highest concentrations reached after 40 days. The extract demonstrates insecticidal activity against the fourth-instar larvae of R. ferrugineus, with adults at 1197 µg/mL and 12.5 µg/larvae as LC50 and LD50 values. The extract inhibited acetylcholine esterase (AChE), acid phosphatases (ACPs), alkaline phosphatases (ALPs), and gamma-aminobutyric acid-transaminase (GABA-T) in larval tissue in vitro, with IC50 values of 124.2, 149.3, 157.8, and 204.8 µg/mL, and in vivo, with IC50 values of 157.2, 179.4, 185.3, and 241.6 µg/mL, after 24 h. Pure compounds identified the activity of the extract, showing the inhibition of AChE, ACPs, ALPs, and GABA-T with IC50 values ˂ 200 µg/mL (in vitro). The ABMET examination revealed good oral permeability, and docking tests showed that the compounds bind AChE, ACPs, ALPs, and GABA-T. These findings show that a green bioprocessing method such as an O. basilicum cell suspension is a quick and straightforward technique for producing phenolic compounds, and it may be used to develop sustainable bio-insecticides and new green procedures

COVID-19 Intelligence-Driven Operational Response Platform: Experience of a Large Tertiary Multihospital System in the Middle East

The COVID-19 pandemic has resulted in global disruptions within healthcare systems, leading to quick dynamic fluctuations in hospital operations and supply chain management. During the early months of the pandemic, tertiary multihospital systems were highly viewed as the go-to hospitals for handling these rapid healthcare challenges caused by the rapidly increasing number of COVID-19 cases. Yet, this pandemic has created an urgent need for coordinated mechanisms to alleviate increasing pressures on these large multihospital systems and ensure services remain high-quality, accessible, and sustainable. Digital health solutions have been identified as promising approaches to address these challenges. This case report describes results for developing multidisciplinary visualizations to support digital health operations in one of the largest tertiary multihospital systems in the Middle East. The report concludes with some lessons and insights learned from the rapid development and delivery of this user-centric COVID-19 multihospital operations intelligent platform

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a similar to 20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (similar to 600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD(+)). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions