Potential Side Effects Research Articles

Abstract 3168: Amphiphilic dendrimer-mediated siRNA delivery for precision regulation of cAMP pathway in cancer cells

Abstract Exchange proteins directly activated by cAMP (EPACs) are involved in multiple cellular processes. The two EPAC isoforms (EPAC1 and EPAC2) have fundamental differences in structure, expression pattern, and signaling specificity, indicating that they may function independently. Therefore, the highly specific regulation of EPAC1 and EPAC2 could be beneficial in targeting cAMP pathway-related therapies. Small RNA molecules could theoretically target genetic components based on Watson-Crick base pairing, offering a unique and promising approach to achieve precision medicine. In this study, we successfully design small interfere (si)RNAs that specifically target EPAC1 and 2, without cross-reactivity with other isoforms. The use of the amphiphilic dendrimer (AD) efficiently delivers siRNAs, resulting in significant down-regulations of EPAC1 and 2 mRNA and protein expressions in multiple cancer cells, including ovarian, breast, colon, and pancreatic cancers. Functional analysis demonstrate that EPAC1 and EPAC2 regulate cancer progression depending on different mechanisms. siEPAC2-AD is more potent compared to siEPAC1-AD in suppressing cell proliferation by altering energy metabolism. Hence, this siEPACs-AD system not only enhances the drug specificity and reduces potential side effects, but also provides a new strategy for precision pharmaceutical control of the cAMP/PKA/EPAC signaling pathway for cancer treatment. Keywords: EPAC1; EPAC2; siRNA; amphiphilic dendrimer; cAMP signaling; cancer Citation Format: Wanjun Yuan, Zhengyin Gao, Ling Peng, Leo Tsz On Lee. Amphiphilic dendrimer-mediated siRNA delivery for precision regulation of cAMP pathway in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3168.

Poly(malic acid)-budesonide nanoconjugates embedded in microparticles for lung administration.

To improve the therapeutic activity of inhaled glucocorticoids and reduce potential side effects, we designed a formulation combining the advantages of nanoparticles, which have an enhanced uptake by alveolar cells, allow targeted delivery and sustained drug release, as well as limited drug systemic passage, with those of microparticles, which display good alveolar deposition. Herein, a polymer-drug conjugate, poly(malic acid)-budesonide (PMAB), was first synthesized with either 11, 20, 33, or 43mol% budesonide (drug:polymer from 1:8 to 3:4), the drug creating hydrophobic domains. The obtained conjugates self-assemble into nanoconjugates in water, yielding excellent drug loading of up to 73 wt%, with 80-100nm diameters. In vitro assays showed that budesonide could be steadily released from the nanoconjugates, and the anti-inflammatory activity was preserved, as evidenced by reduced cytokine production in LPS-activated RAW 264.7 macrophages. Nanoconjugates were then embedded into microparticles through spray-drying with L-leucine, forming nano-embedded microparticles (NEMs). NEMs were produced with an aerodynamic diameter close to 1µm and a density below 0.1 g.cm-3, indicative of a high alveolar deposition. NEMs spray-dried with the less hydrophobic nanoconjugates, PMAB 1:4, were readily dissolved in simulated lung fluid and were chosen for in vivo experiments to study pharmacokinetics in healthy rats. As it was released in vivo from NEMs, sustained distribution of budesonide was obtained for 48 h in lung tissue, cells, and lining fluid. With high loading rates, modulable release kinetics, and low cytotoxicity, these nanoconjugates delivered by NEMs are promising for the more efficient treatment of pulmonary inflammatory diseases.

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

COVID-19 vaccination rates and factors affecting vaccination in children with rheumatic disease

Objectives: This study aimed to investigate coronavirus disease 2019 (COVID-19) vaccination rates and factors affecting vaccination in children with rheumatic diseases. Patients and methods: This multicenter cross-sectional survey-based study was conducted between July 2022 and September 2022. Four hundred seventy-four patients (256 females, 218 males; median age: 15 years; interquartile range, 13 to 16 years) were included in the patient group, and 211 healthy children (124 females, 87 males; median age: 15 years; interquartile range, 13 to 16 years) were included in the control group. A questionnaire was administered to the parents face-to-face during routine outpatient visits. Results: Of the patients, 220 were followed up with the diagnosis of autoinflammatory disease, 174 with juvenile idiopathic arthritis, 48 with connective tissue disease, 23 with vasculitis, eight with uveitis, and one with sarcoidosis. In the study group, 256 (54%) patients and 115 (54.5%) healthy children received at least one dose of COVID-19 vaccine. Parents' concern regarding potential side effects of the vaccine was the most common reason for COVID-19 vaccination hesitancy in both groups. The median patient age, follow-up period, colchicine treatment rates, childhood vaccination and influenza vaccination rates, median parental age, parental vaccination rate, and parental education level were higher in vaccinated patients (p<0.05 for all). In addition, vaccination rates were high in patients who shared their concerns about vaccination with the rheumatology team (p<0.001). Conclusion: Parents' concerns about safety and side effects were found to be the most important factors affecting vaccination success. Identification of the underlying causes of parental vaccine hesitancy will facilitate the development of effective vaccination strategies for potential future outbreaks.

Mitoxantrone encapsulated photosensitizer nanomicelle as carrier-free theranostic nanomedicine for near-infrared fluorescence imaging-guided chemo-photodynamic combination therapy on cancer

Combination therapy exhibits higher efficacy than any single therapy, inspiring various nanocarrier-assisted multi-drug co-delivery systems for the combined treatment of cancer. However, most nanocarriers are inert and non-therapeutic and have potential side effects. Herein, an amphiphilic polymer composed of a hydrophobic photosensitizer and hydrophilic poly(ethylene glycol) was employed as the nanocarriers and photosensitizers to encapsulate the chemotherapeutic drug mitoxantrone for chemo-photodynamic combination therapy. The resulting nanodrug consisted solely of pharmacologically active ingredients, thus avoiding potential toxicity induced by inert excipients. This multifunctional nanoplatform demonstrated significantly superior treatment performance compared to monotherapy for colorectal cancer, both in vitro and in vivo, achieving near-infrared fluorescence imaging-mediated chemo-photodynamic combined eradication of malignancy.

Ratiometric detection of lithium ions in serum and living cells using DNAzyme-assisted hybridization chain reaction

Lithium, a first-line mood stabilizer for bipolar disorder (BD), presents challenges due to its narrow therapeutic window (0.6–1.2 mM) and potential side effects in overdose. Hence, it is crucial to accurately and sensitively detect lithium ions (Li+) in serum and living cells for timely monitoring of BD progression and gaining mechanistic insight into lithium-based therapy. In this study, we design a Li+-responsive DNAzyme-HCR amplifier by combining hybridization chain reaction (HCR) and the Li+-specific DNAzyme. The presence of Li+ catalytically cleaves the DNAzyme, releasing the embedded HCR DNA trigger and generating numerous DNAzyme-assisted HCR products, ultimately activating the fluorescence resonance energy transfer response. Our results demonstrate that the DNAzyme-HCR amplifier enables amplified Li+ detection in serum, which are consistent with the results obtained using the inductively coupled plasma optical emission spectroscopy (ICP-OES) method. Furthermore, the DNAzyme-HCR amplifier allows for Li+ imaging in living cells, showing promising potential in monitoring treatment effects against BD.

Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis

IntroductionThe study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA). AimThe aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators. MethodsDescriptive and pharmacovigilance disproportionality analyses was performed. ResultsA total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 ‘serious’ cases related to selected ADRs were registered during 2005–2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide). DiscussionSuicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations. ConclusionsWith the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.

Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis.

Ankylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed drugs and uncovering new therapeutic targets. Our objective is to pinpoint innovative therapeutic protein targets for AS and assess the potential adverse effects of druggable proteins. We conducted a comprehensive proteome-wide MR study to assess the causal relationships between plasma proteins and the risk of AS. The plasma proteins were sourced from the UK Biobank Pharma Proteomics Project (UKB-PPP) database, encompassing GWAS data for 2,940 plasma proteins. Additionally, GWAS data for AS were extracted from the R9 version of the Finnish database, including 2,860 patients and 270,964 controls. The colocalization analysis was executed to identify shared causal variants between plasma proteins and AS. Finally, we examined the potential adverse effects of druggable proteins for AS therapy by conducting a phenome-wide association study (PheWAS) utilizing the extensive Finnish database in version R9, encompassing 2,272 phenotypes categorized into 46 groups. The findings revealed a positive genetic association between the predicted plasma levels of six proteins and an elevated risk of AS, while two proteins exhibited an inverse association with AS risk (P fdr < 0.05). Among these eight plasma proteins, colocalization analysis identified AIF1, TNF, FKBPL, AGER, ALDH5A1, and ACOT13 as shared variation with AS(PPH3+PPH4>0.8), suggesting that they represent potential direct targets for AS intervention. Further phenotype-wide association studies have shown some potential side effects of these six targets (P fdr < 0.05). Our investigation examined the causal connections between six plasma proteins and AS, providing a comprehensive understanding of potential therapeutic targets.

Exploring the Impact of the Gamified Metaverse on Knowledge Acquisition and Library Anxiety in Academic Libraries

This paper investigates the potential of the Gamified Metaverse as a platform for promoting library services. The study compares the effectiveness of a traditional library program with a Metaverse-based library program in terms of knowledge acquisition and library anxiety. The research also examines students’ perceptions of implementing gamification within the context of the Gamified Metaverse platform. A mixed-methods approach was adopted, including pre- and post-test analysis, statistical analysis, and qualitative data collection. The results indicate that both the traditional and Metaverse-based library programs effectively increased the participants’ knowledge, with no significant difference between the two approaches. However, the Metaverse-based program was found to be less effective in facilitating interaction with librarians and reducing library anxiety. Additionally, students expressed positive perceptions of implementing gamification in the Gamified Metaverse platform, finding it engaging and motivating. These findings contribute to the understanding of the effect of the Metaverse as a tool for promoting library services and enhancing knowledge acquisition. However, it is not as effective in reducing library anxiety, particularly in terms of interaction with librarians and staff. It should be noted that the platform may have limitations such as high costs and potential side effects of virtual reality, making it more suitable as an additional tool for promoting library services, taking into account its feasibility and potential benefits for specific student populations and larger libraries.

Expert dialogue on topical minocycline gel in acne vulgaris: minologue India

Acne vulgaris is a common skin disorder with a global prevalence of about 9.4%. Oral antibacterials are recommended but they are associated with potential systemic side effects. Topical minocycline 4% has been recently approved by the United States Food and Drug Administration (US-FDA) for the management of moderate to severe acne. Although efficacy and safety are established, little is known of its real word usage. To review and appraise existing literature and make recommendations on the real world usage and positioning of topical minocycline 4% in acne management. The minocycline 4% consensus was developed by nine acne experts and was evidence-based on a review of recent topical minocycline 4% literature. A total of 11 questions were discussed regarding different domains like positioning of topical minocycline in acne management as monotherapy and combination therapy, safety and use in special population. Several recommendations were given regarding topical minocycline use like: no monotherapy use; consider use in combination with other anti-acne treatments like isotretinoin, adapalene and benzoyl peroxide; not recommended to be combined with systemic antibiotics; low chances for hyperpigmentation; use of sun protection measures; consider risk benefit ratio in pregnancy; use in lactation not recommended; and can be used only in children &gt;9 years of age. This consensus has discussed and answered many real world usage questions and place in therapy for topical minocycline in acne management and finds it a useful addition to the existing armamentarium.

Periplcymarin targets glycolysis and mitochondrial oxidative phosphorylation of esophageal squamous cell carcinoma: Implication in anti-cancer therapy

BackgroundEsophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer (EC) in China, and demonstrates varying levels of resistance to multiple chemotherapeutic agents. Our previous studies have proved that periplocin (CPP), derived from the extract of cortex periplocae, exhibiting the capacity to hinder proliferation and induce apoptosis in ESCC cells. Several studies have identified additional anti-cancer constituents in the extract of cortex periplocae, named periplcymarin (PPM), sharing similar compound structure with CPP. Nevertheless, the inhibitory effects of PPM on ESCC and their underlying mechanisms remain to be further elucidated. PurposeThe aim of this study was to investigate function of PPM inhibiting the growth of ESCC in vivo and in vitro and to explore its underlying mechanism, providing the potential anti-tumor drug for ESCC. MethodsInitially, a comparative analysis was conducted on the inhibitory activity of three naturally compounds obtained from the extract of cortex periplocae on ESCC cells. Among these compounds, PPM was chosen for subsequent investigation owing to its comparatively structure and anti-tumor activity simultaneously. Subsequently, a series of biological functional experiments were carried out to assess the impact of PPM on the proliferation, apoptosis and cell cycle arrest of ESCC cells in vitro. In order to elucidate the molecular mechanism of PPM, various methodologies were employed, including bioinformatics analyses and mechanistic experiments such as high-performance liquid chromatography combined with mass spectrometry (HPLC-MS), cell glycolysis pressure and mitochondrial pressure test. Additionally, the anti-tumor effects of PPM on ESCC cells and potential toxic side effects were evaluated in vivo using the nude mice xenograft assay. ResultsOur study revealed that PPM possesses the ability to impede the proliferation of ESCC cells, induce apoptosis, and arrest the cell cycle of ESCC cells in the G2/M phase in vitro. Mechanistically, PPM exerted its effects by modulating glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as confirmed by glycolysis pressure and mitochondrial pressure tests. Moreover, rescue assays demonstrated that PPM inhibits glycolysis and OXPHOS in ESCC cells through the PI3K/AKT and MAPK/ERK signaling pathways. Additionally, we substantiated that PPM effectively suppresses the growth of ESCC cells in vivo, with only modest potential toxic side effects. ConclusionOur study provides novel evidence that PPM has the potential to simultaneously target glycolysis and mitochondrial OXPHOS in ESCC cells. This finding highlights the need for further investigation into PPM as a promising therapeutic agent that targets the tumor glucose metabolism pathway in ESCC.

Proteome-Wide Mendelian Randomization and Colocalization Analysis Identify Therapeutic Targets for Knee and Hip Osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease. Although some biomarkers and drug targets of OA have been discovered and employed, limitations and challenges still exist in the targeted therapy of OA. Mendelian randomization (MR) analysis has been regarded as a reliable analytic method to identify effective therapeutic targets. Thus, we aimed to identify novel therapeutic targets for OA and investigate their potential side effects based on MR analysis. In this study, two-sample MR, colocalization analysis, summary-data-based Mendelian randomization (SMR) and Mendelian randomization phenome-wide association study (MR-PheWAS) were conducted. We firstly analyzed data from 4907 plasma proteins to identify potential therapeutic targets associated with OA. In addition, blood expression quantitative trait loci (eQTLs) data sources were used to perform additional validation. A protein-protein interaction (PPI) network was also constructed to delve into the interactions among identified proteins. Then, MR-PheWASs were utilized to assess the potential side effects of core therapeutic targets. After MR analysis and FDR correction, we identified twelve proteins as potential therapeutic targets for knee OA or hip OA. Colocalization analysis and additional validation supported our findings, and PPI networks revealed the interactions among identified proteins. Finally, we identified MAPK3 (OR = 0.855, 95% CI: 0.791-0.923, p = 6.88 × 10-5) and GZMK (OR = 1.278, 95% CI: 1.131-1.444, p = 8.58 × 10-5) as the core therapeutic targets for knee OA, and ITIH1 (OR = 0.847, 95% CI: 0.784-0.915, p = 2.44 × 10-5) for hip OA. A further MR phenome-wide association study revealed the potential side effects of treatments targeting MAPK3, GZMK, and ITIH1. This comprehensive study indicates twelve plasma proteins with potential roles in knee and hip OA as therapeutic targets. This advancement holds promise for the progression of OA drug development, and paves the way for more efficacious treatments of OA.

Current trends in Nigella sativa L. (Black seed) from traditional to modern medicine with advances in extraction, formulation, quality control, regulatory status, and pharmacology

For the first time ever, this novel review enters the enigmatic world of the L. (black seed), known for centuries as a potent source of healing including their relevance to the food and pharmaceutical industries. Written at professional and reference level, it is directed at normal readers with more professional scientists in pharmacy and food science affiliations to serve as a rich source of data on black seed. We embark on an exploration that encompasses the background, significance, and objectives guiding our exploration. Detailed botanical and chemical profiles unravel the mysteries of the black seed, providing insight into its taxonomy, morphology, and chemical composition. Traditional uses, extraction methods, and formulation approaches paint a comprehensive picture of the versatile ways in which the black seed has been employed throughout history. Quality control and standardization practices ensure the integrity of black seed-derived products, while a global regulatory overview brings into focus the challenges and triumphs of incorporating this botanical powerhouse into mainstream pharmacopeias. As we delve into the pharmacological activities, clinical studies, and efficacy of the black seed, we confront safety considerations and potential side effects. The exploration extends into the future, addressing the challenges in commercialization, identifying research gaps, and concluding with the implications of our findings for both healthcare and industry. It should therefore be of special value to researchers affiliated with food science and technology, pharmacy, and pharmaceutical producers requiring up-to-date information on their raw materials, which will probably already have been processed, at least in part.

HYDROXYAPATITE NANOPARTICLES: A REVIEW OF THEIR EMERGING ROLE IN DRUG DELIVERY APPLICATIONS

This literature review assesses existing research on hydroxyapatite-based drug delivery systems, with a focus on evaluating their effectiveness. Researchers are actively exploring strategies to enhance drug loading capacity, involving surface modifications of nanoparticles and the innovation of novel drug encapsulation techniques. Elevating drug loading has the potential to clearly increase the therapeutic efficacy of these systems. Stability issues also present a challenge in the clinical translation of nanoparticle-based drug delivery systems. Furthermore, scientists are underway to minimize potential side effects by judiciously selecting biocompatible materials for nanoparticle synthesis and conducting comprehensive toxicity studies before advancing to clinical trials.

Where does the EU-path on new genomic techniques lead us?

Recently, the European Commission (EC) published a regulatory proposal on plants generated with new genomic techniques (NGTs) (5 July 2023). According to this proposal, NGT plant applications are categorized into category 1 NGT (NGT1) and category 2 NGT (NGT2) based on their molecular characteristics, which diverges from the current legislation centered around Directive 2001/18/EC. To demonstrate where the path of the proposal leads to in practice, we applied the proposed criteria for categorization to a list of NGT plant applications currently in the commercialization pipeline. Combining literature research and a descriptive statistical approach, we can show that 94% of the plant applications affected by the EC proposal, would be classified as NGT1 and thus would receive market approval without risk assessment, monitoring, and sufficient labeling provisions. The remaining 6% of applications would be classified as NGT2 plants, for which, in deviation from the current regulation, an adapted risk assessment is proposed. Screening of the intended traits in the pipeline highlights that certain NGT1 plants can pose similar environmental risks (e.g., invasiveness) to other genetically modified organisms (GMOs), as defined in Directive 2001/18/EC. For example, NGT1 applications based on RNA interference technology can exhibit insecticidal effects with potential side effects on non-target organisms (i.e., other insects). Our quantitative and case-specific elaboration of how the current EC regulatory proposal would affect the environment, health, and consumer protection will be informative for decision-makers and politicians.

Attitudes on participation in clinical drug trials: A nationally representative survey of older adults with multimorbidity.

Older adults with multimorbidity are under-represented in clinical drug trials. Their inclusion will not increase unless they are willing and able to participate. Data on motivators and barriers to participation in trials of new medications of older adults with multimorbidity are needed. Cross-sectional internet and telephone survey of a nationally representative sample of adults ≥65 years with ≥3 chronic conditions (NORC University of Chicago Amerispeak Panel) conducted from March-April, 2023 to determine motivators and barriers to drug trial participation, described graphically and using statistics. Surveyed 1318 (1142 Internet, 176 phone) with mean age 72.3 ± 6.3 (SD), 52% women; race: 83% White, 10% Black or African American, 5% Hispanic or Latino, 1.1% Asian; 4.4 ± 1.9 chronic conditions (of 16 queried), taking 7.5 ± 3.3 medications. Barriers included fear of side effects (48%), taking too many medications (44%), placebo (44%), mobility (33%), bathroom needs (25%), hearing (19%), eyesight (15%), video visits (33%; higher in women, Black or African-American respondents, and those ≥80 years). Sixty-five percent would join all in-person trials, 49% would join all-video trials. Travel >1 h was difficult for 66%, most difficult for women. Trust was a concern in 25% of Black respondents. Caregiving responsibilities or lack of time were not obstacles. Participants were most likely to consider a drug trial for a problem they have (63%) versus prevention (44%) and if invited by a physician (80%) or University healthcare system (58%). Getting better care was ranked very important (79%) followed by helping others (57%). Major concerns of older patients with multimorbidity about participation in drug trials are potential side effects, taking too many medicines, and video visits. Physicians have the greatest influence on decisions and in-person visits are preferred. Proposed changes in trial design to increase enrollment of under-represented older adults may not align with patient-reported preferences.

Integrated Electrochemical Aptasensor Array toward Monitoring Anticancer Drugs in Sweat.

In the realm of clinical practice, the concurrent utilization of anticancer medications can enhance their overall therapeutic efficacy. However, it is crucial to acknowledge that the interactions among these anticancer drugs can potentially yield detrimental consequences on their intended outcomes. Consequently, the assessment of both anticancer potency and potential toxic side effects is greatly refined when multiple anticancer drugs are simultaneously detected and evaluated. Here, we designed a wearable electrochemical aptasensor array for monitoring multiple anticancer drugs in sweat. The integrated sensor array consists of three working electrodes modified with three different aptamers (Apt1, Apt2, and Apt3), a Au counter electrode, and a Ag/AgCl reference electrode. Molecular docking simulations were performed to show the binding affinities between three anticancer drugs and their corresponding aptamers. Various eigenvalues were derived from the square-wave voltammetry electrochemical signals, and these data sets were subjected to rigorous analysis through multivariate data analysis techniques. This analytical approach demonstrated exceptional performance by achieving flawless 100% accuracy in the precise identification of nine anticancer drugs consistently at uniform concentrations. Furthermore, the integrated wearable sensor array exhibited impressive capabilities, correctly recognizing all nine anticancer drugs with 100% accuracy and successfully distinguishing between these drugs in artificial sweat samples. The proposed sensor array presents good stability for 15 days. Flexibility tests showed stable device performance after 500 twisting cycles. This innovative wearable sensing array represents a novel approach for achieving real-time monitoring and precise adjustment of drug dosages. It offers invaluable insights for tailoring the treatment of anticancer drugs to individual patients, predicting both drug efficacy and potential adverse reactions within the field of clinical medicine.

Prediction and detection of side effects severity following COVID-19 and influenza vaccinations: utilizing smartwatches and smartphones

Vaccines stand out as one of the most effective tools in our arsenal for reducing morbidity and mortality. Nonetheless, public hesitancy towards vaccination often stems from concerns about potential side effects, which can vary from person to person. As of now, there are no automated systems available to proactively warn against potential side effects or gauge their severity following vaccination. We have developed machine learning (ML) models designed to predict and detect the severity of post-vaccination side effects. Our study involved 2111 participants who had received at least one dose of either a COVID-19 or influenza vaccine. Each participant was equipped with a Garmin Vivosmart 4 smartwatch and was required to complete a daily self-reported questionnaire regarding local and systemic reactions through a dedicated mobile application. Our XGBoost models yielded an area under the receiver operating characteristic curve (AUROC) of 0.69 and 0.74 in predicting and detecting moderate to severe side effects, respectively. These predictions were primarily based on variables such as vaccine type (influenza vs. COVID-19), the individual's history of side effects from previous vaccines, and specific data collected from the smartwatches prior to vaccine administration, including resting heart rate, heart rate, and heart rate variability. In conclusion, our findings suggest that wearable devices can provide an objective and continuous method for predicting and monitoring moderate to severe vaccine side effects. This technology has the potential to improve clinical trials by automating the classification of vaccine severity.

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors.

: The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

A Review of High-Intensity Focused Ultrasound

For 80 years, high-intensity focused ultrasound (HIFU) has been the subject of interest in medical research. It is a non-invasive procedure that causes the death of cells in a very select area through one of two mechanisms, either heat or cavitation. While diagnostic ultrasound is well known in the medical profession and ultrasound is also used in physiotherapy, high-intensity focused ultrasound is less known but is becoming increasingly important as a non-invasive tool that can be used in many ways, including in the treatment of several cancers as well as benign uterine fibroids. Other interesting developments are underway, including its use in the treatment through an intact skull of essential tremors and the tremor associated with Parkinson’s disease, and in a modified form, it is used to target drug delivery to the brain due to its potential opening of the blood–brain barrier. The depth of penetration of HIFU is variable depending on the type of transducer used and the distance from it. Clinical trials of abdominal malignancies and benign uterine fibroids are reviewed in this article along with potential side effects of the procedure. Over the past two decades, the technology has improved considerably, and the clinical indications have broadened. The current limitations of the technology are also discussed, along with the potential advances in the field that may be made over the next decade.