Effective Drug For Treatment Research Articles

DrugRepPT: a deep pre-training and fine-tuning framework for drug repositioning based on drug's expression perturbation and treatment effectiveness.

Drug repositioning, identifying novel indications for approved drugs, is a cost-effective strategy in drug discovery. Despite numerous proposed drug repositioning models, integrating network-based features, differential gene expression, and chemical structures for high-performance drug repositioning remains challenging. We propose a comprehensive deep pre-training and fine-tuning framework for drug repositioning, termed DrugRepPT. Initially, we design a graph pre-training module employing model-augmented contrastive learning on a vast drug-disease heterogeneous graph to capture nuanced interactions and expression perturbations after intervention. Subsequently, we introduce a fine-tuning module leveraging a graph residual-like convolution network to elucidate intricate interactions between diseases and drugs. Moreover, a Bayesian multi-loss approach is introduced to balance the existence and effectiveness of drug treatment effectively. Extensive experiments showcase the efficacy of our framework, with DrugRepPT exhibiting remarkable performance improvements compared to SOTA baseline methods (Improvement 106.13% on Hit@1 and 54.45% on mean reciprocal rank). The reliability of predicted results is further validated through two case studies, ie, gastritis and fatty liver, via literature validation, network medicine analysis, and docking screening. The code and results are available at https://github.com/2020MEAI/DrugRepPT. Supplementary data are available at Bioinformatics online.

The treatment of lung cancer by gene editing technology and its comparison with traditional therapies

Abstract. In the past, drug resistance in the anti-cancer process has been a major factor affecting the treatment of non-small cell lung cancer, which has greatly reduced the quality of life of patients, accompanied by greater suffering and lower survival rates. This article mainly discusses the possibility and practical feasibility of gene editing technology for curing some types of cancer under the current state of technology, and through analysis it finds that gene editing technology can greatly improve the negative effects of traditional drug treatment and chemotherapy, but the relatively immature technology and high cost often discourage many people. There are already experimented ways to cure cancer. For example, CRISPR-Cas9 gene editing technology is currently the easiest, most efficient, and most diverse way to edit genomes, and it is also one of the most attractive applications. It is hoped that it will be promoted and applied in the future while reducing costs.

Taraxerone inhibits M1 polarization and alleviates sepsis-induced acute lung injury by activating SIRT1

BackgroundAcute lung injury (ALI) is the most lethal disease associated with sepsis, and there is a lack of effective drug treatment. As the major cells of sepsis-induced ALI, macrophages polarize toward the proinflammatory M1 phenotype and secrete multiple inflammatory cytokines to accelerate the disease process through nuclear factor kappa-B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways. Taraxerone, the main component of the Chinese medicinal Sedum, possesses numerous biological activities. However, uncertainty remains regarding the potential of taraxerone to protect against sepsis-induced ALI. This study aimed to investigate the effects and mechanisms of taraxerone against ALI.MethodsAn animal model for ALI was established by cecal ligation and puncture and treated with taraxerone via intraperitoneal administration. The protective effect of taraxerone on the lungs was analyzed using H&E staining, dihydroethidium staining, ELISA kits, cell counting, myeloperoxidase kit, malondialdehyde kit, glutathione kit, superoxide dismutase kit and flow cytometry. Western blotting, RT-PCR, flow cytometry, co-immunoprecipitation, and immunofluorescence were used to investigate the regulatory of taraxerone on SIRT1.ResultsOur study demonstrates for the first time that taraxerone can activate SIRT1 in macrophages, promoting SIRT1 activity. This activation inhibited the NF-κB signaling pathway primarily through the dephosphorylation and deacetylation of p65. Simultaneously, taraxerone disrupted the NLRP3 inflammasome signaling pathway, thereby alleviating M1 polarization of macrophages and mitigating sepsis-induced pulmonary inflammation and oxidative stress. In vivo, EX527 was used to validate the anti-inflammatory and anti-oxidative stress effects of taraxerone mediated by SIRT1.ConclusionSIRT1-mediated anti-inflammatory and anti-oxidative stress effects may be important targets for taraxerone in treating ALI.

Multimodal spatiotemporal drug assessment platform based on a microelectrode neural network chip in Alzheimer’s disease

The pathogenesis of Alzheimer’s disease (AD) remains elusive. The development of new drugs is protracted, costly, and fraught with failure, largely due to the lack of convenient methods for dynamically studying the pathogenesis of AD and evaluating drug efficacy in vitro. There is a dearth of in vitro multi-site assay platforms capable of observing the therapeutic effects of AD drugs at the level of cellular and network. Consequently, an in vitro multimodal spatiotemporal drug assessment platform has been developed based on a neuronal network chip. It has a symmetric distribution of electrode points with two different sizes (10 μm and 30 μm), which are more suitable for the detection of neuronal connections. The multifaceted neurophysiological properties, including single neuron firing pattern, intercellular connection, transmission speed, and neural network communication, were detected in real time. The results demonstrated that the differences between experimental groups in electrophysiological properties, could significantly distinguish the effects of AD representative drug treatment after different levels of neurological injury. The administration of the drug at the initial stage of β-amyloid oligomers (AβOs) toxicity was found to effectively retard the deterioration of neurons and network (early stage: firing rate increased by 8 %; middle stage: cross-correlation coefficient decreased by 27 %; late stage: similarity index remained positive and relative transmission speed decreased by 11 %). The neurophysiological mechanism of drug interaction was further elucidated, which may provide the guidance for the optimal timing of drug administration. Following the further extension of biosensor longevity and the expansion of synchronous multidimensional parameter detection, including impedance and electrochemistry, it is anticipated that this will become a novel platform for the preclinical evaluation and screening of AD drugs.

Structural characterization and anti-hyperuricemic effect of a mannogalactan from Armillariella tabescens mycelium

Hyperuricemia and its complications caused by purine metabolism disorder continue to occur, which require effective drug treatment with fewer side effects. This study explored the positive effects of a natural homogeneous polysaccharide (AT-W) from the mycelium of Armillariella tabescens in a mouse hyperuricemia model. Structural characterization showed that the average molecular weight of AT-W is 25.6 kDa, and it is composed of mannose, galactose, arabinose, and fucose, with molar percentages of 11.46:70.9:4.96:12.67. The main backbone of AT-W is composed of partially 3-O-methylated →6)-α-Galp-(1→, and the branches are mainly composed of α-Manp-(1→, →3)-α-Fucp-(1→. In vivo bioactivity evaluation showed AT-W could not only reduce serum uric acid levels by inhibiting the activity of xanthine oxidase, upregulating the expression of ABCG2 and OAT1, and downregulating the expression of URAT1 but also have a significant protective effect on renal damage caused by hyperuricemia. These findings indicate that AT-W has therapeutic potential for hyperuricemia diseases.

Non-Invasive Brain Stimulation Progression in Post-Stroke Depression Treatment: A Systematic Review.

Post-stroke depression (PSD) is the most common psychological disorder in patients with stroke. It not only seriously affects the patient's functional recovery, quality of life, and ability to return to society but also increases stroke recurrence rate and mortality. However, the effectiveness of drug treatment is unpredictable and associated with certain side effects and low compliance. Pharmacological therapy is limited. The field of noninvasive brain stimulation (NIBS) has recently made great progress in developing specific stimulation protocols to alleviate the symptoms of patients with PSD and might offer valid, alternative strategies. We systematically searched PubMed, Embase, and the Cochrane Library for investigating the use of NIBS in the treatment of PSD. The methodological quality of selected studies was assessed according to the Risk of Bias 2 (ROB2). We identified 814 references in 3 databases. After excluding irrelevant and duplicate studies, 14 studies were included. According to the PRISMA checklist, 4 studies were overall comprehensive, 6 had some problems, and 4 had considerable problems with the presented information. The evidence was evaluated using ROB2, with 5 "low-risk" studies, 5 "some concerns" studies, and 4 "high-risk" studies included. This review provides a comprehensive overview of the clinical trials reported in PSD. Noninvasive brain stimulation is a potentially promising treatment strategy. However, an optimal stimulation protocol needs to be formulated, and much work is required before NIBS can be widely applied in the clinic.

Revealing Drug Treatment Effect from the SERS Profiles of Cell Membrane Biomolecules by a Silver Nanoparticle-Based Magnetic Plasmonic Probe

Revealing Drug Treatment Effect from the SERS Profiles of Cell Membrane Biomolecules by a Silver Nanoparticle-Based Magnetic Plasmonic Probe

Subverting Attachment to Prevent Attacking: Alteration of Effector Immune Cell Migration and Adhesion as a Key Mechanism of Tumor Immune Evasion.

Cell adhesion regulates specific migratory patterns, location, communication with other cells, physical interactions with the extracellular matrix, and the establishment of effector programs. Proper immune control of cancer strongly depends on all these events occurring in a highly accurate spatiotemporal sequence. In response to cancer-associated inflammatory signals, effector immune cells navigating the bloodstream shift from their patrolling exploratory migration mode to establish adhesive interactions with vascular endothelial cells. This interaction enables them to extravasate through the blood vessel walls and access the cancer site. Further adhesive interactions within the tumor microenvironment (TME) are crucial for coordinating their distribution in situ and for mounting an effective anti-tumor immune response. In this review, we examine how alterations of adhesion cues in the tumor context favor tumor escape by affecting effector immune cell infiltration and trafficking within the TME. We discuss the mechanisms by which tumors directly modulate immune cell adhesion and migration patterns to affect anti-tumor immunity and favor tumor evasion. We also explore indirect immune escape mechanisms that involve modifications of TME characteristics, such as vascularization, immunogenicity, and structural topography. Finally, we highlight the significance of these aspects in designing more effective drug treatments and cellular immunotherapies.

Immunoglobin attenuates fulminant myocarditis by inhibiting overactivated innate immune response.

Fulminant myocarditis (FM) is a myocardial inflammatory disease that can result from either viral diseases or autoimmune diseases. In this study, we have determined the treatment effects of immunomodulatory drugs on FM. FM was induced in A/JGpt mice by intraperitoneal administration of coxsackievirus B3, after which immunoglobins were administered daily by intraperitoneal injection. On the seventh day, the cardiac structure and function were determined using echocardiography and cardiac catheterisation. Single-cell RNA sequencing (scRNA-seq) was performed to evaluate CD45+ cells in the heart. Immunoglobin, a typical immunomodulatory drug, dramatically reduced mortality and significantly improved cardiac function in mice with FM. ScRNA-seq revealed that immunoglobin treatment effectively modulated cardiac immune homeostasis, particularly by attenuating overactivated innate immune responses. At the cellular level, immunoglobin predominantly targeted Plac8+ monocytes and S100a8+ neutrophils, suppressing their proinflammatory activities, and enhancing antigen processing and presentation capabilities, thereby amplifying the efficiency and potency of the immune response against the virus. Immunoglobin benefits are mediated by the modulation of multiple signalling pathways, including relevant receptors on immune cells, direction of inflammatory cell chemotaxis, antigen presentation and anti-viral effects. Subsequently, Bst2-ILT7 ligand-receptor-mediated cellular interactions manipulated by immunoglobin were further confirmed in vivo. Immunoglobin treatment significantly attenuated FM-induced cardiac inflammation and improved cardiac function by inhibiting overactivated innate immune responses.

Artificial immunofluorescence in a flash: Rapid synthetic imaging from brightfield through residual diffusion

Immunofluorescent (IF) imaging is crucial for visualising biomarker expressions, cell morphology and assessing the effects of drug treatments on sub-cellular components. IF imaging needs extra staining process and often requiring cell fixation, therefore it may also introduce artefacts and alter endogenous cell morphology. Some IF stains are expensive or not readily available hence hindering experiments. Recent diffusion models, which synthesise high-fidelity IF images from easy-to-acquire brightfield (BF) images, offer a promising solution but are hindered by training instability and slow inference times due to the noise diffusion process. This paper presents a novel method for the conditional synthesis of IF images directly from BF images along with cell segmentation masks. Our approach employs a Residual Diffusion process that enhances stability and significantly reduces inference time. We performed a critical evaluation against other image-to-image synthesis models, including UNets, GANs, and advanced diffusion models. Our model demonstrates significant improvements in image quality (p<0.05 in MSE, PSNR, and SSIM), inference speed (26 times faster than competing diffusion models), and accurate segmentation results for both nuclei and cell bodies (0.77 and 0.63 mean IOU for nuclei and cell true positives, respectively). This paper is a substantial advancement in the field, providing robust and efficient tools for cell image analysis.

Lymphocyte-derived and lipoprotein-derived inflammatory ratios as biomarkers in bipolar disorder type I: Characteristics, predictive values, and influence of current psychopharmacological treatments

Purpose of this researchThe purpose of this research was to investigate peripheral inflammation by analyzing lymphocyte and lipoprotein-derived inflammatory ratios in patients with bipolar disorder type I (BD-I) and healthy controls (HCs), considering mood stabilizer drug treatments, sex and clinical trajectories. MethodsThis was a cross-sectional case-control study of BD-I patients (n=252) and healthy controls (n=62). We investigated peripheral inflammation biomarkers through blood count values (CBCs), lipoproteins and a complex panel of inflammatory ratios, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-HDL ratio (NHR), monocyte-to-HDL ratio (MHR), platelet-to-HDL ratio (PHR) and lymphocyte-to-HDL ratio (LHR). Furthermore, we examined the effects of sex, drug treatment and clinical outcome on the inflammatory profile. ResultsWe found that the monocyte-to-lymphocyte ratio (MLR) and lipoprotein-derived inflammatory ratio (NHR, MHR, PHR, and LHR) were significantly greater in BD-I patients than in control individuals. The monocyte-to-HDL ratio (MHR) showed acceptable accuracy as a disease predictor. Logistic regression analysis adjusted for sex, age and BMI indicated that the risk of having a BD-I diagnosis was greater for participants with MHR levels in quartiles 3 (OR= 5.2, p=0.001) and 4 (OR=13, p<0.001). There was a strong association between lithium treatment and increased inflammation represented by elevated lymphocyte-derived inflammatory ratios (NLR, MLR, PLR, SII, and SIRI) in lithium-treated BD-I patients compared to those in lithium-free or lithium treatment-naïve BD-I patients. The main limitations are the cross-sectional nature of the study and limited sample size of HCs. Major conclusionsSeveral CBCs, lipoproteins, and a complex panel of inflammatory ratios, including lymphocyte-derived inflammatory ratios (NLR, MLR, PLR, SII, and SIRI) and lipoprotein-derived inflammatory ratios (NHR, MHR, PHR, and LHR), are altered in individuals diagnosed with BD-I. The monocyte-to-HDL ratio (MHR) emerged as a disease predictor in our BD-I sample. A remarkable finding is the association of lithium and valproate treatment with the inflammatory state. Considering the study limitations, our results underscore the importance of pharmacological treatments when researching inflammation markers in mood disorders. Lymphocyte-derived and lipoprotein-derived inflammatory ratios are easy-to-implement and relevant biomarkers in BD-I patients.

130 - The effect of the platinum-based anti-cancer drug treatment with oxaliplatin on detrusor muscle contractility in female rats.

130 - The effect of the platinum-based anti-cancer drug treatment with oxaliplatin on detrusor muscle contractility in female rats.

Molecular Docking and Pharmacokinetic Profiling of Nab-paclitaxel as Advanced Chemotherapeutic Agent Against HER-2 Positive Breast Cancer Patients.

The main objective of the study is to explore the potential molecular benefits of Nab-paclitaxel as an effective advanced chemotherapeutic agent for HER2-positive breast cancer patients. Specifically, the study aims to assess Nab-paclitaxel as a potential drug candidate for breast cancer treatment. This study used bioinformatics and cheminformatics to analyze the HER2 signaling pathway and its possible interactions with Nab-Paclitaxel. This involves using pharmacokinetic profiling software to evaluate its physicochemical properties, analyzing its potential impact on gene expression modulation, and assessing its binding affinity to the HER2 receptor through molecular docking. The results indicate that the most favorable docking pose occurs between chain B of the HER-2 receptor and Paclitaxel, with a binding energy of -9.4 kcal/mol. Notably, a hydrogen bond is observed in ARG849, with 3.0 Angstrom (Å). Previous research highlights Paclitaxel's impact on breast cancer patients' genes, particularly the ABCB1 gene responsible for P-glycoprotein production, contributing to drug resistance in chemotherapy. Nab-paclitaxel exhibits potential ease of metabolism, as it minimally inhibits drug-metabolizing cytochrome P450 enzymes. Additionally, despite initial concerns related to drug-likeness parameters and molecular weight discrepancies, the pharmacokinetic profile of Nab-Paclitaxel suggests improvements in delivery facilitated by an albumin-supported nanoparticle delivery mechanism. The binding energy confirms the secure docking of ligands to receptors, suggesting the stability of the interaction between them. Nevertheless, prolonged administration of Paclitaxel poses the risk of inducing drug resistance, a significant factor contributing to treatment failure. This emphasizes the need to explore new candidate drug combinations or identify alternative drug-binding interaction sites. Such endeavors hold the potential to enhance the effectiveness of drug treatments and address challenges associated with prolonged Paclitaxel use.

The 5-Fluorouracil RNA Expression Viewer (5-FUR) Facilitates Interpreting the Effects of Drug Treatment and RRP6 Deletion on the Transcriptional Landscape in Yeast.

Saccharomyces cerevisiae is an excellent model to study the effect of external cues on cell division and stress response. 5-Fluorocuracil (5-FU) has been used to treat solid tumors since several decades. The drug was initially designed to interfere with DNA replication but was later found to exert its antiproliferative effect also via RNA-dependent processes. Since 5-FU inhibits the activity of the 3'-5'-exoribonuclease Rrp6 in yeast and mammals, earlier work has compared the effect of 5-FU treatment and RRP6 deletion at the transcriptome level in diploid synchronized yeast cells. To facilitate interpreting the expression data we have developed an improved 5-Fluorouracil RNA (5-FUR) expression viewer. Users can access information via genome coordinates and systematic or standard names for mRNAs and Xrn1-dependent-, stable-, cryptic-, and meiotic unannotated transcripts (XUTs, SUTs, CUTs, and MUTs). Normalized log2-transformed or linear data can be displayed as filled diagrams, line graphs or color-coded heatmaps. The expression data are useful for researchers interested in processes such as cell cycle regulation, mitotic repression of meiotic genes, the effect of 5-FU treatment and Rrp6 deficiency on the transcriptome and expression profiles of sense/antisense loci that encode overlapping transcripts. The viewer is accessible at http://5fur.genouest.org.

Discussion on the evaluation of the therapeutic efficacy of uterine artery blood flow parameters and serum PLGF and sFlt-1 in patients with recurrent spontaneous abortion

ObjectiveTo investigate the effects of different drug treatments on uterine artery blood flow parameters, serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and sFlt-1/PLGF in patients with recurrent spontaneous abortion and to explore the predictive value of uterine artery blood flow parameters, serum PLGF, sFlt-1, and sFlt-1/PLGF for pregnancy outcomes.MethodsThis retrospective cohort study included 173 patients who experienced recurrent spontaneous abortion and 100 control patients. Patients with recurrent spontaneous abortion were divided into an aspirin group (75 patients), aspirin combined with low molecular weight heparin (LMWH) group (68 patients), and non-drug group (30 patients) based on different drug treatments. Uterine artery blood flow parameters at gestational weeks 30-31+6 were monitored for the four groups, and serum samples were collected at gestational weeks 30-31+6 to measure the levels of serum PLGF and sFlt-1 and calculate the sFlt-1/PLGF ratio.Results1. Uterine artery blood flow parameters at gestational weeks 30-31+6 were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 2. Serum PLGF levels and the sFlt-1/PLGF ratio at gestational weeks 30-31+6 were significantly lower in the non-drug group than in the aspirin group, combined drug group, and control group, while serum sFlt-1 levels were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 3. Serum PLGF, sFlt-1, and sFlt-1/PLGF had lower diagnostic efficiency for predicting hypertensive disorders during pregnancy than the combined diagnostic efficiency of serum PLGF, sFlt-1, and sFlt-1/PLGF with uterine artery blood flow parameters at gestational weeks 30-31+6.ConclusionAspirin and aspirin combined with LMWH can upregulate serum PLGF and decrease serum sFlt-1 levels in patients with recurrent spontaneous abortion, reduce the miscarriage rate, and significantly improve pregnancy outcomes. The combination of serum PLGF, sFlt-1, sFlt-1/PLGF, and uterine artery blood flow parameters can effectively predict hypertensive disorders during pregnancy.

Antibody–drug conjugates and immune checkpoint inhibitors in cancer treatment: a systematic review and meta-analysis

Although antibody–drug conjugate (ADC) or immune checkpoint inhibitors (ICIs) alone fosters hope for the treatment of cancer, the effect of single drug treatment is limited and the safety profile of ADC and ICI therapy remains unclear. This meta-analysis aimed to examine the efficacy and safety of the combination of ADC and ICI therapy. This study type is a systematic review and meta-analysis. Literature retrieval was carried out through PubMed, Embase, Cochrane from inception to Jun. 5, 2024. Then, after data extraction, overall response rate (ORR) and adverse effects (AEs) were used to study its efficiency and safety. Publication bias was also calculated through Funnel plot, Begg's Test and Egger's test. Heterogeneity was investigated through subgroup and sensitivity analysis. The research protocol was registered with the PROSPERO (CRD42023375601). A total of 12 eligible clinical studies with 584 patients were included. The pooled ORR was 58% (95%CI 46%, 70%). Subgroup analysis showed an ORR of 77% (95%CI 63%, 91%) in classical Hodgkin lymphoma (cHL) and an ORR of 73% (95%CI 56%, 90%) in non-Hodgkin lymphoma (NHL). The most common AEs was peripheral neuropathy (38.0%). Meanwhile, AEs on skin (13.1–20.0%) and digestive system (9.0–36.0%) was hard be overlooked. ADC + ICI therapy may be recommended in cancer treatment, especially in cHL and NHL. However, strategies to manage toxicities warranted further exploration.

Clinical Decision Support Systems to Identify Drug-Related Problems in Diabetes Mellitus Patients: A Systematic Review

Clinical Decision Support Systems (CDSSs) has been developed for utilization to provide rational therapy to Diabetes Mellitus (DM) patients including preventing Drug-related Problems (DRPs) such as the effect of drug treatment being not optimal, untreated indications and symptoms, unnecessary therapy, and adverse drug reactions. This study aims to summarize the available evidence on the intervention of CDSSs, key outputs, and impact of the user in DM patients. This study was a systematic review using PubMed, Scopus database, and by manually searching the bibliographies of articles that have been found. We included studies reporting on evaluated CDSSs that had been implemented in medication prescription, reducing medication errors, adverse drug events, drug-allergy checking, drug dosing support, and so on. A total of 8 studies were selected among 855 studies. CDSSs are used in hospitals and primary care settings to identify potential drug interactions, correct therapy regimens, monitor therapy, blood glucose documentation, ensure patients receive medication according to the guideline, provide nutritional advice, and schedule physical activity. The usage of CDSSs improves blood glucose levels, detects possible drug interactions, reduces face-to-face consultations, improves documentation, assists in identifying dose, and promotes prescribing in line with the guideline. The use of CDSSs can help to reduce the risk of errors in management therapy.

Drug-Related Problems Among Peritoneal Dialysis Patients: A 12-Year Retrospective Cohort Study.

Introduction Studies regarding drug-related problems (DRPs) can be found in other diseases, but data are lacking among peritoneal dialysis (PD) populations. Despite advancements in PD care, there remains a significant gap in understanding and addressing DRPs in the PD population. DRPs can lead to serious consequences, including medication errors, adverse reactions, and nonadherence, affecting patient outcomes and healthcare costs. Aim The aim of this study was to identify the prevalence of DRPs, types, causes, interventions performed, acceptance of interventions, and outcomes of DRPs among patients undergoing PD. In addition to this, the study sought to identify factors associated with DRPs in the PD population. Methods This single-center retrospective study recruited adult PD patients with at least one medication from January 2009 until November 2021. Pharmacy medication therapy adherence clinic (MTAC) clinical activity sheets were reviewed, and DRPs were classified based on the Pharmaceutical Care Network Europe Classification (PCNE) v9.1. The PCNE system consists of five essential domains: Problems (P), Causes (C), Interventions (I), Acceptance of the Intervention (A), and Outcomes (O). As part of the pharmacists' MTAC activities, DRPs were meticulously documented. Three pharmacists initially gathered and examined these recorded DRPs. Each identified DRP was then classified according to the type of problem, the underlying cause, any intervention performed to address the DRP, the level of acceptance, and the resulting outcome. Subsequently, these classifications were reviewed by two independent pharmacists to ensure accuracy and consistency. Results Out of 562 patients, 70.6% (n = 397) were on more than 10 drugs. Most patients (n = 520, 92.5%) had at least one DRP. From the 3,333 DRPs identified, the most common were effects of drug treatment not optimal (n = 1,595, 47.8%), followed by untreated symptoms (n = 843, 25.3%) and adverse drug events (n = 730, 21.9%). The main cause of the suboptimal treatment effect was patients' noncompliance (n = 891, 55.9%). For untreated symptoms, the main cause was no drug prescribed despite existing indications (n = 789, 93.6%). Interventions for DRPs were at either prescriber level (n = 2,064, 61.9%), patient-level (n = 1,244, 37.3%), or at other levels, such as with nurses (n = 25, 0.8%). Prescribers accepted 83% (n = 1713) of interventions suggested by pharmacists. Overall, 73.2% (n = 2,439) of DRPs were resolved. Number of medications (b = 0.223, 0.102-0.345) and number of MTAC visits (b = 0.381, 0.344-0.419) were predictive factors of the number of DRPs (p < 0.001). Conclusion There is a high prevalence of DRPs in PD patients. Pharmacists play an important role in detecting, intervening, and resolving DRPs to improve patients' outcomes.

A scalable, data analytics workflow for image-based morphological profiles

Cell Painting is an established community-based microscopy-assay platform that provides high-throughput, high-content data for biological readouts. In November 2022, the JUMP-Cell Painting Consortium released the largest publicly available Cell Painting dataset with CellProfiler features, comprising more than 2 billion cell images. This dataset is designed for predicting the activity and toxicity of 115k drug compounds, with the aim to make cell images as computable as genomes and transcriptomes. In this context, our paper introduces a scalable and computationally efficient data analytics workflow created to meet the needs of researchers. This data-driven workflow facilitates the comparison of drug treatment effects through significant and biologically relevant insights. The workflow consists of two parts: first, the Equivalence score (Eq. score), a straightforward yet sophisticated metric highlighting relevant deviations from negative controls based on cell image morphology; second, the scalability of the workflow, by utilizing the Eq. scores on a large scale to predict and classify the subtle morphological changes in cell image profiles. By doing so, we show classification improvements compared to using the raw CellProfiler features on the CPJUMP1-pilot dataset on three types of perturbations.We hope that our workflow’s contributions will enhance drug screening efficiency and streamline the drug development process. As this process is resource-intensive, every incremental improvement is valuable. Through our collective efforts in advancing the understanding of high-throughput image-based data, we aim to reduce both the time and cost of developing new, life-saving treatments.

Phytic acid-loaded polyvinyl alcohol hydrogel promotes wound healing of injured corneal epithelium through inhibiting ferroptosis

As the important barrier of intraocular tissue, cornea is easy to suffer various kinds of injuries. Among them, acute alkali burn is a thorny ophthalmic emergency event, which can lead to corneal persistent epithelial defects, ulcers, and even perforation. Ferroptosis, a mode of regulatory cell death, has been found to play a key role in the process of corneal alkali burn, of which lipid peroxidation and intracellular iron levels are considered to be the possible therapeutic targets. To seek new effective treatments, the study herein focused on the occurrence of oxidative stress and ferroptosis in corneal alkali burn, exploring the role of phytic acid (PA), a natural small molecule with both antioxidant and iron chelating capacity, in the repair of corneal epithelial injury. The in vivo therapeutic results showed that PA eyedrops treatment promoted the recovery of corneal morphology and function, and in vitro experiments proved that PA prompted the repair of oxidative stress induced-corneal epithelial injury through ferroptosis inhibition. In addition, better drug treatment effect could be achieved through hydrogel delivery and sustained release, and our in vivo experiments showed the superior therapeutic effects of PA delivered by PVA hydrogels with larger molecular weights on corneal injury. In summary, this study demonstrated the excellent effect of natural small molecule PA with antioxidant and high efficiency chelating ferrous ions on ferroptosis inhibition, and showed the outstanding application prospect of PVA/PA hydrogels in the treatment of corneal epithelial injury.