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Background: Non-communicable diseases such as type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are causing a significant burden on the human health care system. The present study aims to implement a machine learning (ML) based predictive model for T2DM, CAD and their co-occurrence, followed by identifying key variables for the occurrence of disease. Methods: The study is a data driven approach that applied various supervised ML models to predict the disease occurrence based on biochemical, demographic and physical data collected from 123 subjects. In addition, performance metrics like accuracy and AUC were used to evaluate the classification accuracy of ML models. Results: The data (n = 123 subjects) consist of male (83) and female (40) populace with ages from 35 to 70 years. Among all ML models, the Random Forest was outperformed with an accuracy of 76% (AUC:0.95). Similarly, in T2DM (AUC:0.92) and T2DM + CAD (AUC:0.94) classification, Random Forest achieved the highest accuracy followed by logistic regression for CAD data (AUC:0.98). The major risk factors recognized for T2DM, CAD and T2DM + CAD are HbA1c, FBS, CK-MB, APO.AII, APO.E, IP.10, and total cholesterol. Conclusion: The results suggest that the ML algorithms predict the prevalence of T2DM, CAD and concomitance in the populace through the integration of biochemical, physical and demographic factors. Based on the identified risk contributors for disease occurrence, preventive measures can be drafted to reduce the disease burden.

Background: Globus is a feeling of a sensation of a lump in the throat. A variety of explanations (physical and psychological) have been proposed in its etiology, but it is nonspecific nature and high incidence makes a causative association hard to establish or refute. Objective: To associate the role of Anxiety in the etiology of globus pharyngeus. Materials and Methods: A prospective study was conducted in a rural private hospital in South India. One hundred and ninety-three patients with a sensation of lump in the throat were assessed after obtaining consent. A strict inclusion and exclusion criteria meant only 54 made it to the final study. A pan endoscopy was conducted to rule out local lesions. In each patient with absence of a local lesion, Hamilton-A Anxiety (HAM-A) Scale was issued for the levels of anxiety (values between 0 and 56) and the visual analog scale (VAS) for uneasiness experienced (values between 1 and 10) before and after 12-weeks treatment. Management included oral escitalopram and clonazepam. Results: At the end of the study, the average score for HAM-A Scale was 13.96 compared to 26.17 before treatment, an improvement of 46.65%. The average values before and after treatment in the VAS before and after treatment were 7.43 and 3.33, an improvement of 55.18%. Conclusion: In the absence of a local cause, the diagnosis of globus should be looked at from psychological viewpoints. Undiagnosed or untreated anxiety can cause globus and it is more commonly seen in women in the age group of 36–45 years. The P value was significant in this study where we treated anxiety leading to globus (

Oral health professionals promote universal oral health for diseases that are primarily preventable and/or treated in their early stages. The delivery of oral health care, whether through therapeutic interventions, preventive care, or long-term maintenance, causes pollutants and has a significant carbon footprint. Oral health practitioners share a moral obligation to society to offer optimal oral health services, ensure patient safety, and decrease their environmental impact. To ensure the long-term viability of oral healthcare services, all organisations should recognise the critical need to work together to develop knowledge, identify remedial possibilities, and exchange best practices that are environmentally friendly.

Abstract Angiogenic signaling pathway is a major contributing factor in cancer recurrence and progression, which can cause significantly reduced treatment outcomes, especially in the oxygen‐dependent photo‐ and sonodynamic therapies. VEGF and its receptor (VEGFR) play a crucial role in angiogenesis progression; precisely, upregulated VEGF signaling is mainly associated with angiogenesis progression in many types of cancers. Herein, we report a sunitinib‐conjugated sonosensitizer (TK‐RB: tyrosine kinase‐rose bengal) to enhance the anticancer efficacy through VEGF inhibition‐mediated antiangiogenesis in conjunction with cellular/tumor damage by ROS generated under ultrasound irradiation. TK‐RB reveals good selectivity and cytotoxicity toward VEGFR‐positive cells (U87MG) over VEGFR‐negative cells (MCF‐7). The fluorescent imaging analysis in vivo/ex vivo and the tumor growth investigation in nude mice with U87MG glioblastoma tumor xenografts demonstrate that rose bengal having tyrosine kinase inhibitor (TK‐RB) provides an enhanced antitumor effect. The current strategy will make a great contribution to optimizing anticancer performance by utilizing sonodynamic therapy together with antiangiogenics in several different malignancies.

Inherent irreversibility in the flow of a reactive third grade fluid though a channel with convective heating is examined. It is well known that heat dissipated from the exothermic chemical reaction passes through fluid in an irreversible manner and as a result entropy is generated continuously within the channel. Analytical solutions of the resulting dimensionless nonlinear boundary-value-problems arising from the governing equations were obtained by using perturbation method. These solutions are utilized to obtain the entropy generation rate and Bejan number for the system. The influence of various important parameters on the entropy generation rate and Bejan number are shown graphically and discussed accordingly.

Malignant melanoma is most deadly of all primary skin cancers. Over 90% of melanomas occur on the skin. Half of such melanomas occur in the oral cavity, followed by nasal cavity (44%) and sinuses (8%). In the oral cavity, the most frequent sites of occurrence are hard palate and maxillary gingiva. Mucosal melanomas represent a diagnostic challenge than the more common cutaneous melanomas because oral melanomas demonstrate significant heterogeneity in morphological features, developmental process, and biological behaviour. This case report highlights an exophytic, lobulated oral malignant melanoma involving maxillary gingiva and is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be examined with suspicion; proper investigation should be carried out to rule out any untoward experiences later.

The present study investigates the entropy generation in magnetized-micropolar fluid flow in between two vertical concentric rotating cylinders of infinite length. The surface of the inner cylinder is heated while the surface of the outer cylinder is cooled. Internal heat generation is incorporated. The Eringen thermo-micropolar fluid model is used to simulate the micro-structural rheological flow characteristics in the annulus region. The flow is subjected to a constant, static, axial magnetic field. The surface of the inner cylinder is prescribed to be isothermal whereas the surface of the outer cylinder was exposed to convection cooling. The conservation equations are normalized and closed-form solutions are obtained for the velocity, microrotation, temperature, entropy generation number, Bejan number and total entropy generation rate. The effects of the relevant parameters are displayed graphically. It is observed that the external magnetic force enhances the entropy production rate and it is maximum in the proximity of the inner cylinder. This causes more wear and tear at the surface of the inner cylinder. Greater Hartmann number also elevates microrotation values in the entire annulus region. The study is relevant to optimization of chemical engineering processes, nuclear engineering cooling systems and propulsion systems utilizing non-Newtonian fluids and magnetohydrodynamics.

The paper deals with the flow of two immiscible couple stress fluids between two homogeneous permeable beds. The flow is considered in two zones: zone I and II contain free flow of two immiscible couple stress fluids between two permeable porous beds at the bottom and top. The flow in the free channel bounded by two permeable beds is assumed to be governed by Stokes’s couple stress fluid flow equations and that in the permeable beds by Darcy’s law. The continuity of velocity, vorticity, shear stress and couple stress are imposed at the fluid-fluid interface and Beavers-Joseph (BJ) slip boundary conditions are employed at the fluid-porous interface. The equations are solved analytically and the expressions for velocity, skin friction and volumetric flow rate are obtained. The effects of the physical governing parameters on velocity are investigated.

Inherent irreversibility in the flow of a reactive third grade fluid though a channel with convective heating is examined. It is well known that heat dissipated from the exothermic chemical reaction passes through fluid in an irreversible manner and as a result entropy is generated continuously within the channel. Analytical solutions of the resulting dimensionless nonlinear boundary-value-problems arising from the governing equations were obtained by using perturbation method. These solutions are utilized to obtain the entropy generation rate and Bejan number for the system. The influence of various important parameters on the entropy generation rate and Bejan number are shown graphically and discussed accordingly. [ABSTRACT FROM AUTHOR]

The present study investigates the entropy generation in magnetized-micropolar fluid flow in between two vertical concentric rotating cylinders of infinite length. The surface of the inner cylinder is heated while the surface of the outer cylinder is cooled. Internal heat generation is incorporated. The Eringen thermo-micropolar fluid model is used to simulate the micro-structural rheological flow characteristics in the annulus region. The flow is subjected to a constant, static, axial magnetic field. The surface of the inner cylinder is prescribed to be isothermal whereas the surface of the outer cylinder was exposed to convection cooling. The conservation equations are normalized and closed-form solutions are obtained for the velocity, microrotation, temperature, entropy generation number, Bejan number and total entropy generation rate. The effects of the relevant parameters are displayed graphically. It is observed that the external magnetic force enhances the entropy production rate and it is maximum in the proximity of the inner cylinder. This causes more wear and tear at the surface of the inner cylinder. Greater Hartmann number also elevates microrotation values in the entire annulus region. The study is relevant to optimization of chemical engineering processes, nuclear engineering cooling systems and propulsion systems utilizing non-Newtonian fluids and magnetohydrodynamics. [ABSTRACT FROM AUTHOR]

Despite the apparent copious fluorescent probes targeting mitochondria, the development of low cytotoxic probes is still needed for improving validation of mitochondrial function assessment. Herein, we report a novel cyanine-based NIR fluorescent probe, T2, which selectively targets mitochondria with significantly low toxicity by modulating the intracellular redox status. Additionally, T2 inhibits oxidative stress-induced cell death in cortical neurons. This study provides new insight into developing low-toxic mitochondrial imaging agents by regulating redox homeostasis.

Cancer remains as one of the most significant health problems, with approximately 19 million people diagnosed worldwide each year. Chemotherapy is a routinely used method to treat cancer patients. However, current treatment options lack the appropriate selectivity for cancer cells, are prone to resistance mechanisms, and are plagued with dose-limiting toxicities. As such, researchers have devoted their attention to developing prodrug-based strategies that have the potential to overcome these limitations. This tutorial review highlights recently developed prodrug strategies for cancer therapy. Prodrug examples that provide an integrated diagnostic (fluorescent, photoacoustic, and magnetic resonance imaging) response, which are referred to as theranostics, are also discussed. Owing to the non-invasive nature of light (and X-rays), we have discussed external excitation prodrug strategies as well as examples of activatable photosensitizers that enhance the precision of photodynamic therapy/photothermal therapy. Activatable photosensitizers/photothermal agents can be seen as analogous to prodrugs, with their phototherapeutic properties at a specific wavelength activated in the presence of disease-related biomarkers. We discuss each design strategy and illustrate the importance of targeting biomarkers specific to the tumour microenvironment and biomarkers that are known to be overexpressed within cancer cells. Moreover, we discuss the advantages of each approach and highlight their inherent limitations. We hope in doing so, the reader will appreciate the current challenges and available opportunities in the field and inspire subsequent generations to pursue this crucial area of cancer research.

A new conjugate formulation, SIWV-PB-SN, based on glioblastoma (GBM)-homing SIWV tetrapeptide and an ROS-responsive prodrug is reported. SIWV-PB-SN selectively penetrates the GBM cells and releases anti-GBM drug (SN-38) via ROS-induced linker cleavage. This study presents a new insight for a more advanced therapeutic approach to overcoming GBM.

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with a GSH-sensitive linker. Further conjugation of the triphenylphosphonium moiety allows M1 to undergo specific activation in the mitochondria, where mitochondria-mediated apoptosis is observed. Moreover, M1 has enormous effects on genomic DNA ascribed to FUDR's primary function of impeding DNA/RNA synthesis combined with diminishing PP2A-activated DNA repair pathways. Importantly, mechanistic studies highlight the PP2A obtrusion in FUDR/5-fluorouracil (5-FU) therapy and underscore the importance of its inhibition to harbor therapeutic potential. HCT116 cell xenograft-bearing mice that have a low response rate to 5-FU show a prominent effect with M1, emphasizing the importance of DNA damage response targeting strategies using tumor-specific microenvironment-activatable systems., (© 2022 Wiley-VCH GmbH.)

Photodynamic therapy (PDT) has been extensively investigated for decades for tumor treatment because of its non-invasiveness, spatiotemporal selectivity, lower side-effects, and immune activation ability. It can be a promising treatment modality in several medical fields, including oncology, immunology, urology, dermatology, ophthalmology, cardiology, pneumology, and dentistry. Nevertheless, the clinical application of PDT is largely restricted by the drawbacks of traditional photosensitizers, limited tissue penetrability of light, inefficient induction of tumor cell death, tumor resistance to the therapy, and the severe pain induced by the therapy. Recently, various photosensitizer formulations and therapy strategies have been developed to overcome these barriers. Significantly, the introduction of nanomaterials in PDT, as carriers or photosensitizers, may overcome the drawbacks of traditional photosensitizers. Based on this, nanocomposites excited by various light sources are applied in the PDT of deep-seated tumors. Modulation of cell death pathways with co-delivered reagents promotes PDT induced tumor cell death. Relief of tumor resistance to PDT with combined therapy strategies further promotes tumor inhibition. Also, the optimization of photosensitizer formulations and therapy procedures reduces pain in PDT. Here, a systematic summary of recent advances in the fabrication of photosensitizers and the design of therapy strategies to overcome barriers in PDT is presented. Several aspects important for the clinical application of PDT in cancer treatment are also discussed.

Neurodegenerative diseases are debilitating disorders that feature progressive and selective loss of function or structure of anatomically or physiologically associated neuronal systems. Both chronic and acute neurodegenerative diseases are associated with high morbidity and mortality along with the death of neurons in different areas of the brain; moreover, there are few or no effective curative therapy options for treating these disorders. There is an urgent need to diagnose neurodegenerative disease as early as possible, and to distinguish between different disorders with overlapping symptoms that will help to decide the best clinical treatment. Recently, in neurodegenerative disease research, fluorescent-probe-mediated biomarker visualization techniques have been gaining increasing attention for the early diagnosis of neurodegenerative diseases. A survey of fluorescent probes for sensing and imaging biomarkers of neurodegenerative diseases is provided. These imaging probes are categorized based on the different potential biomarkers of various neurodegenerative diseases, and their advantages and disadvantages are discussed. Guides to develop new sensing strategies, recognition mechanisms, as well as the ideal features to further improve neurodegenerative disease fluorescence imaging are also explored., (© 2020 Wiley-VCH GmbH.)

Cancer stem cells (CSCs), also called tumor-initiating cells (TICs), have been studied intensively due to their rapid proliferation, migration, and role in the recurrence of cancer. In general, CSC marker-positive cells [CD133, CD44, CD166, aldehyde dehydrogenase (ALDH), and epithelial cell adhesion molecule (EpCAM)] exhibit a 100-fold increased capacity to initiate cancer. Within a heterogeneous tumor mass, only approximately 0.05-3% of cells are suspected to be CSCs and able to proliferate under hypoxia. Interestingly, CSCs, cancer cells, and normal stem cells share many cytochemical properties, such as inhibition of the redox system for reactive oxygen species (ROS) production and high expression of drug resistance transporters. However, compared to normal stem cells, CSCs develop unique metabolic flexibility, which involves switching between oxidative phosphorylation (OXPHOS) and glycolysis as their main source of energy. Due to the similarities between CSCs and other cancer cells and normal stem cells, limited chemotherapeutic and bio-imaging reagents specific for CSCs have been developed. In this short review, we address the current knowledge regarding CSCs with a focus on designing chemotherapeutic and bio-imaging reagents that target CSCs.

Lysosomes, an important organelle of eukaryotic cells, are covered with the cell membrane and contain an array of degradative enzymes. The disrupt in lysosomal functions may lead to the development of severe diseases. In nanotechnology, nanomaterials working mechanism and its biomedical output are highly dependent on the lysosomes as it plays a crucial role in intracellular transport. Several nanomaterials specifically designed for lysosome-related actions are highly advantageous in trafficking and delivering the loaded imaging/therapeutic agents. But for other applications, especially gene-based therapeutic delivery into the sub-organelles such as mitochondria and nucleus, lysosomal related degradation could be an obstacle to achieve a maximal therapeutic index. In order to understand the relationship between lysosomes and designed nanomaterials for kind of desired application in biomedical research, complete knowledge of their various designing strategies, size dependent or ligand supportive cellular uptake mechanisms, trafficking, and localizations in eukaryotic cells is highly desired. In this review, we intended to discuss various nanomaterial types that have been applied in biomedical applications based on lysosomal internalization and escape from endo/lysosomes and explored their related advantages/disadvantages. Additionally, we also deliberated nanomaterials direct translocation mechanism, their autophagic accumulation and the underlying mechanism to induced autophagy. Finally, some challenges and critical issues in current research from clinical application perspective has also been addressed. Great understanding of these factors will help in understanding and facilitating the development of safe and effective lysosomal related nanomaterial-based imaging/therapeutic systems for future applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Stereoselective synthesis of a novel regiomer of the natural nonenolide, herbarumin I has been accomplished. The synthesis involves the coupling of the alcohol and acid fragments of the molecule using Yamaguchi protocol followed by intramolecular ring closing metathesis. The cytotoxic and antimicrobial properties of the synthetic regiomer have been studied., (Copyright © 2013 Elsevier Ltd. All rights reserved.)