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1.
COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign.
Mead, MN, Seneff, S, Wolfinger, R, Rose, J, Denhaerynck, K, Kirsch, S, McCullough, PA
Cureus. 2024;(1):e52876
Abstract
Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.
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2.
A Multi-Thresholding-Based Discriminative Neural Classifier for Detection of Retinoblastoma Using CNN Models.
Kumar, P, Suganthi, D, Valarmathi, K, Swain, MP, Vashistha, P, Buddhi, D, Sey, E
BioMed research international. 2023;:5803661
Abstract
Cancer is one of the vital diseases which lead to the uncontrollable growth of the cell, and it affects the body tissue. A type of cancer that affects the children below five years and adults in a rare case is called retinoblastoma. It affects the retina in the eye and the surrounding region of eye like the eyelid, and sometimes, it leads to vision loss if it is not diagnosed at the early stage. MRI and CT are widely used scanning procedures to identify the cancerous region in the eye. Current screening methods for cancer region identification needs the clinicians' support to spot the affected regions. Modern healthcare systems develop an easy way to diagnose the disease. Discriminative architectures in deep learning can be viewed as supervised deep learning algorithms which use classification/regression techniques to predict the output. A convolutional neural network (CNN) is a part of the discriminative architecture which helps to process both image and text data. This work suggests the CNN-based classifier which classifies the tumor and nontumor regions in retinoblastoma. The tumor-like region (TLR) in retinoblastoma is identified using the automated thresholding method. After that, ResNet and AlexNet algorithms are used to classify the cancerous region along with classifiers. In addition, the comparison of discriminative algorithm along with its variants is experimented to produce the better image analysis method without the intervention of clinicians. The experimental study reveals that ResNet50 and AlexNet yield better results compared to other learning modules.
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3.
Theoretical simulation and experimental design of selenium and gold incorporated polymer-based microcarriers for ROS-mediated combined photothermal therapy.
Mitusova, KA, Rogova, A, Gerasimova, EN, Ageev, EI, Yaroshenko, VV, Shipilovskikh, SA, Feng, L, Yang, P, Petrov, AA, Muslimov, AR, et al
Journal of colloid and interface science. 2023;:232-246
Abstract
Recently, multi-modal combined photothermal therapy (PTT) with the use of photo-active materials has attracted significant attention for cancer treatment. However, drug carriers enabling efficient heating at the tumor site are yet to be designed: this is a fundamental requirement for broad implementation of PTT in clinics. In this work, we design and develop hybrid carriers based on multilayer capsules integrated with selenium nanoparticles (Se NPs) and gold nanorods (Au NRs) to realize reactive oxygen species (ROS)-mediated combined PTT. We show theoretically and experimentally that cooperative interaction of Se NPs with Au NRs improves the heat release efficiency of the developed capsules. In addition, after uptake by tumor cells, intracellular ROS level amplified by Se NPs inhibits the tumor growth. As a consequence, the synergy between Se NPs and Au NRs exhibits the advantages of hybrid carriers such as (i) improved photothermal conversion efficiency and (ii) dual-therapeutic effect. The results of in vitro and in vivo experiments demonstrate that the combination of ROS-mediated therapy and PTT has a higher tumor inhibition efficiency compared to the single-agent treatment (using only Se-loaded or Au-loaded capsules). Furthermore, the developed hybrid carriers show negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys and spleen. This study not only provides a potential strategy for the design of multifunctional "all-in-one" carriers, but also contributes to the development of combined PTT in clinical practice.
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4.
Study on the Effect of Bushen Zhuanggu Tablet Combined with Conventional Regimen on Bone Mineral Density Improvement, Functional Recovery and Fracture Risk Prevention in Patients with Postmenopausal Osteoporosis.
Chen, T, Li, G, Xu, Y
Computational and mathematical methods in medicine. 2023;:4846392
Abstract
OBJECTIVE This case-control study was to explore the effect of Bushen Zhuanggu tablet combined with routine regimen on bone mineral density (BMD) improvement, functional recovery, and fracture prevention in postmenopausal osteoporosis (PMOP) patients. METHODS 180 postmenopausal osteoporosis patients were randomly selected from communities A, B, and C cohorts as research subjects from January to May 2021. The study subjects were divided into three groups. The groups were in a 1 : 1 ratio according to the principles of nonrandomised, concurrent controlled trials, and methods. There were 60 participants in each group (group A, group B, and group C). Group A was treated with Bushen Zhuanggu tablet for antiosteoporosis + basic treatment (calcium supplement and vitamin D). Group C was given Bushen Zhuanggu tablet for antiosteoporosis intervention. Group B was given basic treatment (calcium supplement and vitamin D supplementation) as a control group. The follow-up time was 6 months after treatment. Finally, we compare the differences in calcium and phosphorus metabolism indexes, BMD, bone metabolism indexes, upper and lower limb muscle strength, and quality of life scores. RESULTS Group A, B, and C's effective rate was 98.33%, 80.00%, and 93.33%, respectively. The group A's effective rate was significantly higher than that in group B and C, and the difference was statistically significant (P < 0.05). After 6 months intervention, the levels of serum Ca2+, serum phosphorus (P), serum creatinine (Cr), and parathyroid hormone (PTH) in 3 groups decreased. Ca, P, Scr, and PTH levels in group A were the lowest among study groups, and the difference was statistically significant (P < 0.05). The increase in the BMD of lumbar spine, the left femoral neck, and Ward's triangle area of the three groups were observed with the highest data in group A. After 6 months of treatment, the levels of serum N-terminal propeptide of type I procollagen, PINP, and serum osteocalcin (OC) increased, while the levels of β-cross-linked C-terminal telopeptide of type I collagen (β-CTX) and alkaline phosphatase (ALP) decreased in the three groups. The improvement of all bone metabolic indexes in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). The enhanced upper limb muscle strength and the shorter standing-walking timing test (TUGT) time were observed after 6 months of treatment. The improvement effect of upper and lower limb muscle strength in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). There were significant differences in physiological function, life function, general health status, physical pain, mental state, emotional function, vitality, and social function among the three groups after 6 months treatment, and the difference was statistically significant (P < 0.05). The score of quality of life in group A was higher than that in B and C groups, and the difference was statistically significant (P < 0.05). CONCLUSION Bushen Zhuanggu tablet combined with conventional therapy is effective in the postmenopausal osteoporosis treatment, which effectively increase the BMD, regulate calcium and phosphorus metabolism, promote the recovery of limb function, prevent the recurrence of fracture, and improve the patients' quality of life. This treatment scheme is worth popularizing.
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5.
The Effect of Hyperlipidemia on Peri-implant Health: A Clinical and Radiographical Prospective Study.
De Angelis, P, Rella, E, Manicone, PF, Gasparini, G, Giovannini, V, Liguori, MG, Camodeca, F, De Rosa, G, Cavalcanti, C, D'Addona, A
BioMed research international. 2023;:7570587
Abstract
High levels of cholesterol and triglycerides may have a negative effect on the immune system and bone health, leading to lower bone mineral density, an increased risk of osteoporosis, and bone fractures, and could therefore also be related to a significant worsening of peri-implant health. The purpose of the following study was to evaluate whether the altered lipid profile in patients who undergo implant insertion surgery represents a prognostic factor capable of influencing clinical outcomes. This prospective observational study was conducted on 93 subjects; patients were required to have taken blood tests to obtain triglycerides (TG), total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels prior to the surgical procedure to classify them according to current American Heart Association guidelines. The outcomes considered were marginal bone loss (MBL) 3 years after implant placement, full-mouth plaque score (FMPS), and full-mouth bleeding score (FMBS) 3 years after surgery. A statistically significant correlation was found between hypertriglyceridemia and MBL as well as between total cholesterol and MBL. There is no statistically significant correlation between the variables analyzed and the secondary outcomes 3 years after implant placement. Peri-implant marginal bone loss may be influenced by hyperlipidemia. However, further studies are needed, with larger samples and more extensive follow-ups, to confirm these results.
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6.
Biosynthesis of Iron Oxide Nanoparticles Using Leaf Extract of Ruellia tuberosa: Mechanical and Dynamic Mechanical Behaviour Kevlar-Based Hybrid Epoxy Composites.
Natrayan, L, Rao, YS, Vaidya, G, Bhattacharya, S, Kaliappan, S, Patil, PP, Paramasivam, P
Bioinorganic chemistry and applications. 2023;:1731931
Abstract
One of the more enticing, ecologically responsible, as well as safe and sustainable methodologies is eco-friendly nanomaterial synthesis. Vegetation materials will be used as reductants instead of toxic substances for synthesising nanoparticles. The current study used Ruellia tuberosa (RT) leaf extract digest to synthesise FeO nanomaterials, which were then characterised using XRD. Following that, microbially produced FeO molecules were mixed with a Kevlar-based polymeric matrix to study the blended consequences. To examine the interbreeding, the current experimental analyses were performed, including both static and dynamic mechanical characteristics. The addition of FeO nanofillers improved the elastic modulus, tensile strength, and storage modulus of the nanocomposite. Impact force uptake has been raised to a certain extent by the addition of nanoparticles. The findings of this research show that incorporating FeO nanofillers into Kevlar fabrics is a promising technique for increasing the mechanical characteristics of hybrid laminated composites. As per DMA evaluation, the sample without nanomaterials had a more volcanic lava response, which is a useful thing for body systems for missile use. Another critical aspect of a nanoparticles-filled nanocomposite that must be addressed is the relatively uniform scattering of padding as well as the development of interfacial adhesion in such a combination. The presence of FeO fillers in polymeric composites is confirmed by XRD analysis.
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7.
Hemp bioactive peptides: Nutrition, functional properties and action mechanisms to maximize their nutraceutical applications and future prospects.
Ashaolu, TJ, Le, TD, Suttikhana, I, Olatunji, OJ, Farag, MA
Food chemistry. 2023;:135691
Abstract
The dietary protein requirement for the world population that just clocked 8 billion should ideally come from the environmentally sustainable lithosphere and should be a plant-based and cost-affordable resource. Hemp proteins and peptides come to mind based upon increasing interest by consumers worldwide. We herein describe the composition and nutrition of hemp protein, including the enzymatic production of hemp peptides (HPs), which reportedly have hypoglycemic, hypocholesterolemic, antioxidative, antihypertensive, and immunomodulatory effects. The action mechanisms involved in each of the reported bioactivities are presented, while not undermining the applications or opportunities associated with HPs. The study's major goal is to compile the status of the art of the various therapeutic HPs and their prospect as drugs for multiple diseases while highlighting needed future developments. We present first the composition, nutrition, and functionality of hemp proteins, prior to reports on their hydrolysis for the production of HPs. It is concluded that HPs present excellent functional ingredients as nutraceuticals targeting hypertension and other degenerative diseases, which have yet to be capitalized upon for commercial uses.
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8.
AZ63/Ti/Zr Nanocomposite for Bone-Related Biomedical Applications.
Sathish, T, Saravanan, R, Shreepad, S, Amuthan, T, Raj, JID, Gaur, P, Vijayan, V, Rajkumar, S
BioMed research international. 2023;:6297372
Abstract
Considering the unique properties of magnesium and its alloy, it has a vast demand in biomedical applications, particularly the implant material in tissue engineering due to its biodegradability. But the fixing spares must hold such implants till the end of the biodegradation of implant material. The composite technology will offer the added benefits of altering the material properties to match the requirements of the desired applications. Hence, this experimental investigation is aimed at developing a composite material for manufacturing fixing spares like a screw for implants in biomedical applications. The matrix of AZ63 magnesium alloy is reinforced with nanoparticles of zirconium (Zr) and titanium (Ti) through the stir casting-type synthesis method. The samples were prepared with equal contributions of zirconium (Zr) and titanium (Ti) nanoparticles in the total reinforcement percentage (3%, 6%, 9%, and 12%). The corrosive and tribological studies were done. In the corrosive study, the process parameters like NaCl concentration, pH value, and exposure time were varied at three levels. In the wear study, the applied Load, speed of sliding, and the distance of the slide were considered at four levels. Taguchi analysis was employed in this investigation to optimize the reinforcement and independent factors to minimize the wear and corrosive losses. The minimum wear rate was achieved in the 12% reinforced sample with the input factor levels of 60 N of load on the pin, 1 m/s of disc speed at a sliding distance was 1500 m, and the 12% reinforce samples also recorded a minimum corrosive rate of 0.0076 mm/year at the operating environment of 5% NaCl-concentrated solution with the pH value of 9 for 24 hrs of exposure. The prediction model was developed based on the experimental results.
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9.
The Effective Components, Core Targets, and Key Pathways of Ginseng against Alzheimer's Disease.
Wang, Y, Liu, X
Evidence-based complementary and alternative medicine : eCAM. 2023;:9935942
Abstract
BACKGROUND Panax ginseng C. A. Mey (ginseng) is a traditional Chinese medicinal herb used for the treatment of nervous system disorders, such as Alzheimer's disease (AD). However, the pharmacological mechanisms of ginseng involved in AD have not been systematically investigated. Here, a network pharmacology approach was adopted to explore the effective components, core targets, and key pathways of ginseng against AD. METHODS TCMSP database was used to screen the active ingredients of ginseng. Prediction of the targets of ginseng and AD-related genes was performed using online public databases. "Compound-Target," "Compound-Target-Disease," "Protein-Protein Interaction (PPI)," "Compound-Target-Pathway," and "Compound-Target-GO-Pathway" networks were constructed with Cytoscape 3.7.2 software. Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed by using the DAVID database. RESULTS A total of 22 bioactive compounds were identified from ginseng, and 481 targets of ginseng and 763 AD-related targets were obtained from public databases. The PPI network screened out 19 hub genes of ginseng against AD. According to GO function enrichment, ginseng influenced cell proliferation, death, the nitric oxide biosynthetic process, hypoxia response, and synaptic transmission. Neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling, cAMP signaling, FoxO signaling, Ras signaling, and PI3K-AKT signaling were among the most key regulatory pathways. The compound-target-GO-route network found EGFR, MAPK1, MAPK14, AKT1, CASP3, and PRKACA as key genes, with PI3K-AKT signaling being the most important pathway for ginseng's anti-AD activity. CONCLUSION Ginseng exerts neuroprotective effects in AD patients through multicomponent, multitarget, and multipathway modes, providing novel insight into the pharmacological and experimental research on ginseng against AD.
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10.
Correlation Decomposition between TCM Syndrome Types and Calcium and Phosphorus Metabolism in 50 Maintenance Hemodialysis Sufferers.
Li, Y
Contrast media & molecular imaging. 2022;:3927989
Abstract
Aiming to reveal the relationship between TCM syndrome types and calcium and phosphorus metabolism in maintenance hemodialysis (MHD) sufferers, 50 sufferers diagnosed with MHD who were admitted to Suixi County Hospital in Anhui Province are selected for retrospective decomposition. The data of TCM classification and laboratory indicators of the sufferers are collected. The experimental results indicate that calcium and phosphorus metabolism disorder is common in maintenance hemodialysis patients, especially calcium and phosphorus product and blood phosphorus elevation. The increase of the calcium-phosphorus product is closely related to the mortality and calcification rate of the subcutaneous soft tissue. It can provide a reference for the diagnosis and therapy of abnormal calcium and phosphorus metabolism in sufferers, which is worthy of clinical application.