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Abebayehu N Yilma,1,2,* Rajnish Sahu,1,* Praseetha Subbarayan,1,* Francois Villinger,3 Mamie T Coats,4 Shree R Singh,1 Vida A Dennis1 1Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA; 2Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA; 3Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, USA; 4Department of Clinical and Diagnostics Sciences, School of Health Professionals, The University at Alabama at Birmingham (UAB), Birmingham, AL, USA*These authors contributed equally to this workCorrespondence: Vida A Dennis, Center for NanoBiotechnology Research (CNBR), Alabama State University, 1627 Harris Way, Montgomery, AL, USA, Tel +1 334-604-9205, Email vdennis@alasu.eduIntroduction: Interleukin-10 (IL-10) is a key anti-inflammatory mediator in protecting host from over-exuberant responses to pathogens and play important roles in wound healing, autoimmunity, cancer, and homeostasis. However, its application as a therapeutic agent for biomedical applications has been limited due to its short biological half-life. Therefore, it is important to prolong the half-life of IL-10 to replace the current therapeutic application, which relies on administering large and repeated dosages. Therefore, not a cost-effective approach. Thus, studies that aim to address this type of challenges are always in need.Methods: Recombinant IL-10 was encapsulated in biodegradable nanoparticles (Poly-(Lactic-co-Glycolic Acid) and Chitosan)) by the double emulsion method and then characterized for size, surface charge, thermal stability, cytotoxicity, in vitro release, UV–visible spectroscopy, and Fourier Transform-Infrared Spectroscopy as well as evaluated for its anti-inflammatory effects. Bioactivity of encapsulated IL-10 was evaluated in vitro using J774A.1 macrophage cell-line and in vivo using BALB/c mice. Inflammatory cytokines (IL-6 and TNF-α) were quantified from culture supernatants using specific enzyme-linked immunosorbent assay (ELISA), and significance was analyzed using ANOVA.Results: We obtained a high 96% encapsulation efficiency with smooth encapsulated IL-10 nanoparticles of ~100– 150 nm size and release from nanoparticles as measurable to 22 days. Our result demonstrated that encapsulated IL-10 was biocompatible and functional by reducing the inflammatory responses induced by LPS in macrophages. Of significance, we also proved the functionality of encapsulated IL-10 by its capacity to reduce inflammation in BALB/c mice as provoked by Chlamydia trachomatis, an inflammatory sexually transmitted infectious bacterium.Discussion: Collectively, our results show the successful IL-10 encapsulation, slow release to prolong its biological half-life and reduce inflammatory cytokines IL-6 and TNF production in vitro and in mice. Our results serve as proof of concept to further explore the therapeutic prospective of encapsulated IL-10 for biomedical applications, including inflammatory diseases.Keywords: Chlamydia, delivery system, chitosan, nanoparticles, IL-10, inflammation

The Self-Ironing Machine is an innovative solution designed to revolutionize fabric ironing on a small scale, catering to the increasing demand for portable and user-friendly ironing devices. It integrates intelligent features to enhance versatility, including a compact design housing essential elements such as a heating plate, a heating roller, and a temperature identification sensor, alongside specialized buttons for different fabric types. The project's objective was to develop a portable self-ironing machine that simplifies the ironing process while maintaining effectiveness.The machine utilizes a heating plate for precise heating and a weighted roller for consistent pressure application, ensuring optimal results. A standout feature is the integration of a temperature identification sensor, enabling customized ironing treatments tailored to specific fabric requirements. This streamlines the process and reduces the risk of damage to delicate fabrics. User interaction is intuitive with dedicated buttons catering to various fabric needs.Rigorous testing has demonstrated the machine's outstanding performance across different fabric types, highlighting its accuracy and adaptability. In conclusion, the Portable Self-Ironing Machine represents a significant advancement in fabric ironing technology. Its compact and efficient design, coupled with intelligent features, offers an enhanced user experience. With its ability to deliver precise and tailored ironing treatments, this machine stands as a game-changer in the realm of portable fabric care, addressing the needs of modern lifestyles and paving the way for future innovations in the field.

Modern advancement in science and technology has altered the way we detect, treat and prevent different diseases in all aspects of human life. Rheumatoid Arthritis (RA) is chronic progressive autoimmune disease in which body’s immune system has role to protect the health by attacking foreign bacteria but the virus mistakenly attacking the joints as a result thickened synovium, pannus formation, & destruction of bone, cartilage occurs. Researchers are still researching but are unable to know the exact reason for the disease. Although, it is believed that genes and environmental factors play an important role in the development of RA. In this review the pathophysiology, predictors and factors involved in pathogenesis of RA have been investigated. The conventional drug therapeutic agents and emerging novel drug delivery system (NDDS) like nanoparticles, dendrimers, micelles, microspheres, liposomes and so on are discussed, as these are the tools which show promising effect in overcoming the limitations associated with conventional drug delivery systems. Although several NDDS have been used for various purposes, liposomes have been focused and found to have its potential applications in RA diagnosis and therapy. In addition, the therapeutic effectiveness, and challenges for RA by using these novel drug delivery systems have been reviewed along with its future perspectives.

Purpose: Investigation of pigment epithelial detachment (PED) characteristics in central serous chorioretinopathy (CSCR) is underrepresented in the literature. We present a novel computational approach to quantify PED composition indices (PEDCI) in CSCR and track changes over time., Methods: 34 eyes with active CSCR were analyzed quarterly over a 1-year period. Cases were categorized into acute and chronic CSCR depending on a symptom duration of less than 3 months or more than 3 months respectively. PED, retinal and choroidal dimensions were manually measured, and interval changes were compared using repeated measures of variance ANOVA. PED composition analysis involved manual segmentation followed by automated sub segmentation of PED areas to identify serous, neovascular and fibrous tissues. PEDCI for each component was compared among cases of acute and chronic CSCR., Results: CMT and NSD-h decreased by 65.2 µm ( p  = 0.01), and 86.5 µm ( p  < 0.01) respectively at 12 months. At baseline, 7/17 acute CSCR eyes and 8/15 chronic CSCR eyes had a concomitant PED; acute cases had both serous and neovascular components (PEDCI-S: 16.95%, PEDCI-N: 40.3%), whereas chronic cases only had a neovascular component (PEDCI-S: 0%, PEDCI-N: 30.5%). At 12-month follow-up, 6/7 of acute CSCR group and 6/8 chronic CSCR group had a concomitant PED; PEDCI-S was largest for acute CSCR (53.4%) and PEDCI-N was largest for chronic CSCR (46.7%)., Conclusion: We identify a novel biomarker PEDCI to differentiate acute and chronic CSCR with higher PEDCI-S in acute CSCR, and higher PEDCI-N in chronic CSCR.

Purpose: To study the morphological and histological characteristics of the fibrous capsule formed around a novel biodegradable glaucoma drainage device (GDD) implant made of oxidized regenerated cellulose (ORC) after 1 and 3 months of its implantation., Methods: It was a prospective, interventional, preclinical experimental study using New Zealand white rabbits. All animals underwent GDD implantation with a novel biodegradable device. The device's body was made of ORC and attached to a silicone tube, connecting the body to the anterior chamber. Histopathology (hematoxylin and eosin/Masson's trichrome staining) and immunohistochemistry (Alpha-Smooth Muscle Actin expression) characteristics of the bleb formed around the novel device were noted at 1 and 3 months., Results: One month post implantation, the biodegradable material produced a significant foreign body type of reaction evidenced by the exuberant infiltration by macrophages, lymphocytes, and multinucleated giant cells. The granulomatous response subsided by 3 months with disorganized collagen deposition on Masson's trichrome staining. The silicone tube was an internal control, and histopathology demonstrated well-organized collagen deposition around it at 3 months. Immunohistochemistry for α-smooth muscle actin also demonstrated more myofibroblast transformation at the site of the tube than the biodegradable implant., Conclusions: Our results indicate that the tissue response around a biodegradable GDD was different from the response to conventional devices. A diffuse, loose vascularized mesh was observed to develop, which may be more compatible with sustained IOP control over a longer period, in contrast to the usual thick and dense capsule formed around the non-biodegradable devices., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Multisector collaboration is critical for improving population health. Improving alignment between nonprofit hospitals and local health departments is one promising approach to achieving health improvement, and a number of states are exploring policies to facilitate such collaboration. Using public documents, we evaluated the alignment between Ohio nonprofit hospitals and local health departments in the community health needs they identify and those they prioritize. The top three needs identified by hospitals and health departments were mental health, substance use, and obesity. Alignment across organizations was high among the top needs, but it varied more among less commonly identified needs. Alignment related to social determinants of health was low, with health departments being more responsive to social determinants than hospitals. Given the different strengths and capacities of hospitals and health departments, this divergence may be in the best interests of the communities they serve. Community benefit policies should consider how to promote collaboration between hospitals and health departments while also encouraging organizations to use their own expertise to meet community needs.

Background: Children with autism spectrum disorder (ASD) face unique challenges related to oral health, which can negatively impact their day-to-day lives, significantly compromising their overall quality of life. Primary caregivers of children with ASD have a critical role in delivering and seeking oral health care. Hence, it is vital to study their perspective towards their children's oral health and its impact on their quality of life., Aim: To explore the parental perception of oral health-related quality of life in children with autism., Methods: A systematic electronic and manual search was conducted in Medline (via PubMed), Embase, Google Scholar, Scopus, and LILACS of articles published from January 2003 to May 2023 using appropriate MeSH terms, keywords, and other terms. A four-phase study selection process was followed according to PRISMA guidelines, and data extraction and synthesis were performed using an extraction form. The selected studies were critically appraised using the QATSDD and Crombie's assessment tool. The inter-reviewer agreement was assessed using the kappa with a linear weighting coefficient., Results: Out of the 885 results, 15 studies were included in the review after the two selection phases, and the study characteristics were summarized in tabular form. Study quality varied considerably, and out of a total possible QATSDD score of 42, scores for the individual studies ranged from 14 to 40. The risk of bias for the seven criteria was found to be low., Conclusion: The parental perception of the OHRQoL in children with ASD is poor, and the most significant perceived impact is on the child's functional and social well-being aspects. Parental-Caregiver Perception Questionnaire was the most commonly used. The most frequent symptoms include bad breath, food lodgment, mouth breathing and night grinding. The familial impact and influence on the OHRQoL of siblings were also studied., (© 2023 Special Care Dentistry Association and Wiley Periodicals LLC.)

Purpose: To evaluate novel, automated biomarkers, pigment epithelial detachment composition indices (PEDCI) in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy through 24 months., Methods: Retrospective analysis of 37 eyes (34 patients) with PED associated with nAMD receiving as-needed anti-VEGF treatment was performed. Best-corrected visual acuity (BCVA) and optical coherence tomography images were acquired at a treatment-naïve baseline and 3-, 6-, 12-, 18-, and 24-month visits. Previously validated automated imaging biomarkers, PEDCI-S (serous), PEDCI-N (neovascular), and PEDCI-F (fibrous) within PEDs were measured. ANOVA analysis and Spearman correlation were performed., Results: Mean BCVA (in logMAR) was 0.60 ± 0.47, 0.45 ± 0.41, 0.49 ± 0.49, 0.61 ± 0.54, 0.59 ± 0.56, and 0.67 ± 0.57 at baseline, 3, 6, 12, 18, and 24 months respectively. Overall, BCVA showed minimal worsening of 0.07 ± 0.54 logMAR (p = 0.07). 13.38 ± 3.77 anti-VEGF injections were given through 24 months. PEDCI-F showed an increase of 0.116, 0.122, 0.036, and 0.006 at months 3, 6, 12, and 18 respectively and a decrease of 0.004 at month 24 (p = 0.03); PEDCI-S showed a decrease of 0.064, 0.130, 0.091, 0.092, and 0.095 at months 3, 6, 12, 18, and 24 respectively (p = 0.16); PEDCI-N showed a decrease of 0.052 at month 3 and an increase of 0.008, 0.055, 0.086, and 0.099 at months 6, 12, 18, and 24 respectively (p = 0.06). BCVA was negatively correlated with PEDCI-F (r = -0.28, p < 0.01), and positively correlated with PEDCI-N (r = 0.28, p < 0.01) and PEDCI-S (r = 0.15, p = 0.03)., Conclusion: Longitudinal analysis of PEDCI supports their utility as biomarkers that characterize treatment related effects by quantifying the relative composition of PEDs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study assessed the staffing allocations and associated costs incurred by Ohio local health departments (LHDs) in response to the challenges posed by the COVID-19 pandemic. Data were extracted from the annual financial reports of Ohio LHDs for 2020 and 2021, encompassing a sample of 38 LHDs in 2020 and 60 LHDs in 2021. Descriptive analysis showed that Ohio LHDs committed substantial resources to responding to the COVID-19 pandemic. Although there was considerable variability across LHDs, median staffing and compensation collectively constituted 22% of total staffing and compensation. Multivariate regression analysis found minimal associations between the examined agency and community-level variables and the differences in staffing allocations and associated costs incurred by LHDs in response to the COVID-19 pandemic. After decades of underfunding and understaffing, securing sustainable funding will be crucial to equip LHDs across the country with the necessary resources to deliver comprehensive public health services in their communities., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In recent years, carbon quantum dots (CQDs) have garnered considerable attention as a promising material for biomedical applications because of their unique optical and biological properties. In this study, CQDs were derived from the leaves of Hibiscus rosa-sinensis Linn. via microwave-assisted technique and characterized using different techniques such as ultraviolet-visible, Fourier transform infrared, fluorescence spectrometry, X-ray diffraction, dynamic light scattering, transmission electron microscopy and energy-dispersive X-ray spectroscopy. Subsequently, their potential for biomedical applications was investigated through in vitro assays assessing scratch healing, anti-inflammatory, antibacterial, and cytotoxicity properties. It was found that the CQDs were fluorescent, polycrystalline, quasi-spherical, ~ 12 nm in size with presence of -OH and -COOH groups on their negatively charged surfaces, and demonstrated good anti-inflammatory by inhibiting protein denaturation, cyclooxygenase-2 and regulating inflammatory cytokines. The CQDs also exhibited antimicrobial activity against Klebsiella pneumoniae and Bacillus cereus, good biocompatibility, along with excellent promotion of cell proliferation in vitro, indicating their potential as a anti-inflammatory and wound healing material. The properties were more enhanced than their precursor, H. rosa-sinensis leaf extract. Hence, the CQDs synthesized from the leaves of H. rosa-sinensis can serve as a potential biomedical agent., (© 2024. The Author(s).)

The present study synthesized a series of cobalt (II) metal ion frame hybrid candidates ( 6a-6f ) bearing phyto-flavonol galangin with substituted aryl diazenyl coumarins, and further structural confirmation was validated by various spectral techniques, including NMR, ATR-FTIR, UV-vis, HPLC, XRD, etc. Therapeutic potency was investigated via PASS (prediction of activity spectra for substances), molecular docking, molecular dynamics simulation, prediction of toxicity, pharmacokinetics, and drug-likeness scores, along with the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), with their energy gaps (ΔE H-L ) to locate the most potential therapeutic candidates. The PASS prediction (Pa > Pi score) showed that proposed metal complexes have kinase inhibitors, antioxidative, and antischistosomal activities with potential molecular docking scores (> -7 kcal/mol) against selected targeted enzymes. Further, the MD-simulation (RMSD, RMSF, Rg, and H-bonds) of the most potential docking complex, ' HER2-6d' , showed a minimum deviation similar to the standard drug (lapatinib) at 100 ns, indicating that 6d could be a potential noncovalent anticancer inhibitor. In addition, metal complexes possess a non-toxic and ideal drug-ability profiles, and positive electron space in an excited state increases the binding affinity towards target enzymes. Among all six ligands, 6c and 6d were the two most multipotent therapeutic agents from the above analyses. In summary, this could be a feasible approach towards the utilization of phytochemicals in mainstream therapeutic applications, where bioinformatics tools help to select a lead drug candidate at an early stage and guide for higher experimental success by proceeding with potential candidates.Communicated by Ramaswamy H. Sarma.

Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications.

Purpose was to study 3-dimensional choroidal contour at choroidal inner boundary (CIB) and choroidal outer boundary (COB) in healthy eyes. Healthy eyes imaged on wide field swept-source optical coherence tomography were included. Delineation of CIB and COB was done based on our previously reported methods. Quantitative analysis of the surfaces of CIB and COB was based on analyzing best fit spherical radius (R) (overall and sectoral). One hundred and seven eyes of 74 subjects with a mean age of 46.4 ± 19.3 years were evaluated. Overall, R COB (mean ± SD: 22.5 ± 4.8 mm) < R CIB (32.4 ± 9.4 mm). Central sector had the least R at COB (7.2 ± 5.9 mm) as well as CIB (25.1 ± 14.3 mm) across all age groups. Regression analysis between R (CIB) and age (r = -0.31, r 2  = 0.09) showed negative correlation (P < 0.001) and that between R (COB) and age was positive (r = 0.26, r 2  = 0.07) (P = 0.01). To conclude, central sector is the steepest sector in comparison to all the other sectors. This is indicative of a prolate shape of choroidal contour at CIB and COB. Outer boundary of choroid is steeper than inner boundary across all age groups. However, with ageing, outer boundary becomes flatter and inner boundary becomes steeper., (© 2024. The Author(s).)

Introduction. Acinetobacter baumannii is a nosocomial pathogen with a high potential to cause food-borne infections. It is designated as a critical pathogen by the World Health Organization due to its multi-drug resistance and mortalities reported. Biofilm governs major virulence factors, which promotes drug resistance in A. baumannii . Thus, a compound with minimum selection pressure on the pathogen can be helpful to breach biofilm-related virulence. Hypothesis/Gap Statement. To identify anti-biofilm and anti-virulent metabolites from extracts of wild Mangifera indica (mango) brine pickle bacteria that diminishes pathogenesis and resistance of A. baumannii . Aim. This study reports anti-biofilm and anti-quorum sensing (QS) efficacy of secondary metabolites from bacterial isolates of fermented food origin. Method. Cell-free supernatants (CFS) of 13 bacterial isolates from fermented mango brine pickles were screened for their efficiency in inhibiting biofilm formation and GC-MS was used to identify its metabolites. Anti-biofilm metabolite was tested on early and mature biofilms, pellicle formation, extra polymeric substances (EPS), cellular adherence, motility and resistance of A. baumannii . Gene expression and in silico studies were also carried out to validate the compounds efficacy. Results. CFS of TMP6b identified as Bacillus vallismortis, inhibited biofilm production (83.02 %). Of these, major compound was identified as 2,4-Di- tert -butyl phenol (2,4-DBP). At sub-lethal concentrations, 2,4-DBP disrupted both early and mature biofilm formation. Treatment with 2,4-DBP destructed in situ biofilm formed on glass and plastic. In addition, key virulence traits like pellicle (77.5 %), surfactant (95.3 %), EPS production (3-fold) and cell adherence (65.55 %) reduced significantly. A. baumannii cells treated with 2,4-DBP showed enhanced sensitivity towards antibiotics, oxide radicals and blood cells. Expression of biofilm-concomitant virulence genes like csuA/B , pgaC , pgaA , bap , bfmR , katE and ompA along with QS genes abaI, abaR significantly decreased. The in silico studies further validated the higher binding affinity of 2,4-DBP to the AbaR protein than the cognate ligand molecule. Conclusion. To our knowledge, this is the first report to demonstrate 2,4- DBP has anti-pathogenic potential alone and with antibiotics by in vitro, and in silico studies against A. baumannii . It also indicates its potential use in therapeutics and bio-preservatives.

Purpose: To compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months., Methods: This was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F)., Results: A total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = - 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = - 0.53; p < 0.001 and PCV, r = - 0.09; p = 0.58)., Conclusion: PEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months., (© 2024. The Author(s).)

To begin to optimize the immunization routes for our reported PLGA-rMOMP nanovaccine [PLGA-encapsulated Chlamydia muridarum (Cm) recombinant major outer membrane protein (rMOMP)], we compared two prime-boost immunization strategies [subcutaneous (SC) and intramuscular (IM-p) prime routes followed by two SC-boosts)] to evaluate the nanovaccine-induced protective efficacy and immunogenicity in female BALB/c mice. Our results showed that mice immunized via the SC and IM-p routes were protected against a Cm genital challenge by a reduction in bacterial burden and with fewer bacteria in the SC mice. Protection of mice correlated with rMOMP-specific Th1 (IL-2 and IFN-γ) and not Th2 (IL-4, IL-9, and IL-13) cytokines, and CD4+ memory (CD44highCD62Lhigh) T-cells, especially in the SC mice. We also observed higher levels of IL-1α, IL-6, IL-17, CCL-2, and G-CSF in SC-immunized mice. Notably, an increase of cytokines/chemokines was seen after the challenge in the SC, IM-p, and control mice (rMOMP and PBS), suggesting a Cm stimulation. In parallel, rMOMP-specific Th1 (IgG2a and IgG2b) and Th2 (IgG1) serum, mucosal, serum avidity, and neutralizing antibodies were more elevated in SC than in IM-p mice. Overall, the homologous SC prime-boost immunization of mice induced enhanced cellular and antibody responses with better protection against a genital challenge compared to the heterologous IM-p., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Although Otto Warburg may be right about the role of glycolysis versus OXPHOS in cancer metabolism, it remains unclear whether an altered metabolism is causative or correlative and is the main driver or a mere passenger in the pathogenesis of cancer. Currently, most of our successful treatments are designed to eliminate non-cancer stem cells (non-CSCs) such as differentiated cancer cells. When the treatments also happen to control CSCs or the stem-ness niche, it is often unintended, unexpected, or undetected for lack of a pertinent theory about the origin of cancer that clarifies whether cancer is a metabolic, genetic, or stem cell disease. Perhaps cellular context matters. After all, metabolic activity may be different in different cell types and their respective microenvironments-whether it is in a normal progenitor stem cell vs. progeny differentiated cell and whether it is in a malignant CSC vs. non-CSC. In this perspective, we re-examine different types of cellular metabolism, e.g., glycolytic vs. mitochondrial, of glucose, glutamine, arginine, and fatty acids in CSCs and non-CSCs. We revisit the Warburg effect, an obesity epidemic, the aspartame story, and a ketogenic diet. We propose that a pertinent scientific theory about the origin of cancer and of cancer metabolism influences the direction of cancer research as well as the design of drug versus therapy development in cancer care.