Evaluation Of Efficacy Research Articles

Bioactive fiber-reinforced hydrogel to tailor cell microenvironment for structural and functional regeneration of myotendinous junction.

Myotendinous junction (MTJ) injuries are prevalent in clinical practice, yet the treatment approaches are limited to surgical suturing and conservative therapy, exhibiting a high recurrence rate. Current research on MTJ tissue engineering is scarce and lacks in vivo evaluation of repair efficacy. Here, we developed a three-dimensional-printed bioactive fiber-reinforced hydrogel containing mesenchymal stem cells (MSCs) and Klotho for structural and functional MTJ regeneration. In a rat MTJ defect model, the bioactive fiber-reinforced hydrogel promoted the structural restoration of muscle, tendon, and muscle-tendon interface and enhanced the functional recovery of injured MTJ. In vivo proteomics and in vitro cell cultures elucidated the regenerative mechanisms of the bioactive fiber-reinforced hydrogel by modulating oxidative stress and inflammation, thus engineering an optimized microenvironment to support the survival and differentiation of transplanted MSCs and maintain the functional phenotype of resident cells within MTJ tissues, including tendon/muscle cells and macrophages. This strategy provides a promising treatment for MTJ injuries.

Evaluation of the diagnostic efficacy of computed tomography imaging in trauma patients

Aims: The objective of this study was to assess the efficacy of computed tomography imaging tests ordered for trauma patients in the emergency medicine service and to identify pathologies in the imaging. Methods: A retrospective evaluation was conducted on trauma patients who applied to our hospital's Emergency Medicine Department between 01 January 2023 and 01 October 2023 and underwent diagnostic computed tomography imaging (CT). Results: A total of 4193 CT scans were analysed in 3641 patients. Falls were the most common etiological cause (n=3451, 82.3%). Pathology was detected in 25.87% of CT orders. The most frequently used CT type was cranial CT (n=1687, 40.22%). The highest rate of pathology was found in scapula CT (75%), while the lowest rate was observed in cervical spine CT (13%). The most common pathology was detected in cranial CT (n=457). The highest rate of pathology was found in scapula CT (75%), while the lowest rate was observed in cervical spine CT (13%). Conclusion: The accessibility of relevant specialists to emergency physicians reduces the number of unnecessary CT imaging orders. In the emergency department, physicians should adhere to internationally accepted guidelines when ordering advanced imaging studies.

A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy.

The majority of mainstream antidepressants lack the promise of complete amelioration of symptoms. Other pitfalls include the latency period and side effects. These issues prompted investigations concerning thevarious roles of serotonin (5-HT) neurotransmissions in the etiology of depression. In this study, each study participant received vilazodone, vortioxetine, and escitalopram monotherapy for major depressive disorder (MDD)for 16 weeks. After that, the subject's scores on the Hamilton Depression Rating Scale (HDRS)-17 item version and the Montgomery Åsberg Depression Rating Scale (MADRS) were evaluated. In the study population, we kept track of the incidence of adverse events. Ninety-six patients with MDD participated in this open-label, randomized, three-arm study. Participants were allotted into three groups according to a 1:1:1 ratio and given vilazodone (20-40 mg/day), vortioxetine (5-20 mg/day), or escitalopram (10-20 mg/day) for 16 weeks. Vortioxetine and vilazodone are test medications, with escitalopram serving as the control. After the baseline visit, follow-up appointments were scheduled every four weeks. Per-protocol (PP) and intent-to-treat (ITT) populations served as means for efficacy and safety evaluations, respectively. We prospectively registered this research in the Clinical Trial Registry, India (CTRI) (2022/07/043808). Out of the 134 patients we screened, 109 (81.34%) were eligible. Ninety-six (88.07%) of them completed the 16-week trial. In the PP population (n = 96), we analyzed efficacy. They had a mean age of 46.3 ± 6.2 years. At baseline, each group's median HDRS score was 30.0 (p = 0.964). Following 16 weeks of antidepressant therapy, these scores dropped to 15.0, 14.0, and 13.0 (p = 0.002). Baseline MADRS scores for all groups were 36.0 (p = 0.741). They had corresponding values of 20.0, 18.0, and 17.0 at 16 weeks (p < 0.001). Regarding both efficacy endpoints, the post-hoc analysis with the Bonferroni correction demonstrated statistically significant differences (p < 0.001). We performed the safety assessments within our ITT population (n = 109). Ninety-six adverse events were recorded. Nonetheless, none of them seemed serious. Still, five participants opted out because of their side effects. Vomiting and nausea were the most frequent side effects. Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further.

Miniaturization of hiPSC-derived 3D neural cultures in stirred-tank bioreactors for parallelized preclinical assessment of rAAV.

Introduction: Engineered 3D models employing human induced pluripotent stem cell (hiPSC) derivatives have the potential to recapitulate the cell diversity and structure found in the human central nervous system (CNS). Therefore, these complex cellular systems offer promising human models to address the safety and potency of advanced therapy medicinal products (ATMPs), such as gene therapies. Specifically, recombinant adeno-associated viruses (rAAVs) are currently considered highly attractive for CNS gene therapy due to their broad tropism, low toxicity, and moderate immunogenicity. To accelerate the clinical translation of rAAVs, in-depth preclinical evaluation of efficacy and safety in a human setting is primordial. The integration of hiPSC-derived CNS models in rAAV development will require, amongst other factors, robust, small-scale, high-throughput culture platforms that can feed the preclinical trials. Methods: Herein, we pioneer the miniaturization and parallelization of a 200mL stirred-tank bioreactor-based 3D brain cell culture derived from hiPSCs. We demonstrate the applicability of the automated miniaturized Ambr® 15 Cell Culture system for the maintenance of hiPSC-derived neurospheroids (iNSpheroids), composed of neuronal and glial cells. Critical process parameters were optimized, namely, cell density and agitation mode. Results: Under optimized conditions, stable iNSpheroid cultures were attained in the microbioreactors for at least 15days, with high cell viability and astrocytic and neuronal phenotype maintenance. This culture setup allowed the parallelization of different rAAVs, in different multiplicity of infections (MOIs), to address rAAV-host interactions at a preclinical scale. The iNSpheroids were exposed to rAAV2- and rAAV9-eGFP in the microbioreactors. Transgene expression was detected 14days post-transduction, revealing different astrocyte/neuron tropism of the two serotypes. Discussion: We advocate that the iNSpheroid cultures in miniaturized bioreactors are reliable and reproducible screening tools for addressing rAAV transduction and tropism, compatible with preclinical demands.

Modelling and simulation of anisotropic growth in brain tumours through poroelasticity: A study of ventricular compression and therapeutic protocols

AbstractMalignant brain tumours represent a significant medical challenge due to their aggressive nature and unpredictable locations. The growth of a brain tumour can result in a mass effect, causing compression and displacement of the surrounding healthy brain tissue and possibly leading to severe neurological complications. In this paper, we propose a multiphase mechanical model for brain tumour growth that quantifies deformations and solid stresses caused by the expanding tumour mass and incorporates anisotropic growth influenced by brain fibres. We employ a sharp interface model to simulate localised, non-invasive solid brain tumours, which are those responsible for substantial mechanical impact on the surrounding healthy tissue. By using patient-specific imaging data, we create realistic three-dimensional brain geometries and accurately represent ventricular shapes, to evaluate how the growing mass may compress and deform the cerebral ventricles. Another relevant feature of our model is the ability to simulate therapeutic protocols, facilitating the evaluation of treatment efficacy and guiding the development of personalized therapies for individual patients. Overall, our model allows to make a step towards a deeper analysis of the complex interactions between brain tumours and their environment, with a particular focus on the impact of a growing cancer on healthy tissue, ventricular compression, and therapeutic treatment.

Evaluation of Electrochemical and Antimicrobial Efficacy of Green Synthesized Silver Functionalized Reduced Graphene Oxide Nanocomposites

Evaluation of Electrochemical and Antimicrobial Efficacy of Green Synthesized Silver Functionalized Reduced Graphene Oxide Nanocomposites

Automated 3D Perioral Landmark Detection Using High-Resolution Network: Artificial Intelligence-Based Anthropometric Analysis.

3D facial stereophotogrammetry, as a convenient, non-invasive and highly reliable evaluation tool, has shown great potential in pre-operative planning and treatment efficacy evaluation of plastic surgery in recent years. However, it requires manual identification of facial landmarks by trained evaluators to obtain anthropometric data, which consumes large amount of time and effort. Automatic 3D facial landmark localization may facilitate fast data acquisition and eliminate evaluator error. In this paper, we propose a novel deep-learning method based on dimension-transformation and key-point detection for automated 3D perioral landmark annotation. The 3D facial model is transformed into 2D images on which High-Resolution Network is implemented for key point detection. The 2D coordinates of key points are then mapped back to the 3D model using mathematical methods to obtain the 3D landmark coordinates. This program was trained with 120 facial models and validated in 50 facial models. Our approach achieved satisfactory accuracy of 1.30 ± 0.68 mm error in landmark detection with an average processing time of 5.2 ± 0.21 seconds per model. And subsequent analysis based on these landmarks showed an error of 0.87 ± 1.02 mm for linear measurements and 5.62 ± 6.61° for angular measurements. This automated 3D perioral landmarking method could serve as an effective tool that enables fast and accurate anthropometric analysis of lip morphology for plastic surgery and aesthetic procedures.

Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study.

The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated.

An Integrated mHealth App for Smoking Cessation in Black Smokers With HIV: Protocol for a Randomized Controlled Trial.

Black adults who smoke and have HIV experience immense stressors (eg, racial discrimination and HIV stigma) that impede smoking cessation success and perpetuate smoking-related health disparities. These stressors also place Black adults who smoke and have HIV at an increased risk of elevated interoceptive stress (eg, anxiety and uncomfortable bodily sensations) and smoking to manage symptoms. In turn, this population is more likely to smoke to manage interoceptive stress, which contributes to worse HIV-related outcomes in this group. However, no specialized treatment exists to address smoking cessation, interoceptive stress, and HIV management for Black smokers with HIV. This study aims to test a culturally adapted and novel mobile intervention that targets combustible cigarette smoking, HIV treatment engagement and adherence, and anxiety sensitivity (a proxy for difficulty and responsivity to interoceptive stress) among Black smokers with HIV (ie, Mobile Anxiety Sensitivity Program for Smoking and HIV [MASP+]). Various culturally tailored components of the app are being evaluated for their ability to help users quit smoking, manage physiological stress, and improve health care management. This study is a pilot randomized controlled trial in which Black combustible cigarette smokers with HIV (N=72) are being recruited and randomly assigned to use either (1) the National Cancer Institute's QuitGuide app or (2) MASP+. Study procedures include a web-based prescreener; active intervention period for 6 weeks; smartphone-based assessments, including daily app-based ecological momentary assessments for 6 weeks (4 ecological momentary assessments each day); a video-based qualitative interview using Zoom Video Communications software at week 6 for participants in all study conditions; and smartphone-based follow-up assessments at 0, 1, 2 (quit date), 3, 4, 5, 6, and 28 weeks postbaseline (26 weeks postquitting date). Primary outcomes include biochemically verified 7-day point prevalence of abstinence, HIV-related quality of life, use of antiretroviral therapy, and HIV care appointment adherence at 26 weeks postquitting date. Qualitative data are also being collected and assessed to obtain feedback that will guide further tailoring of app content and evaluation of efficacy. The results of this study will determine whether the MASP+ app serves as a successful aid for combustible cigarette smoking cessation, HIV treatment engagement, and physiological stress outcomes among Black people with HIV infection. If successful, this study will provide evidence for the efficacy of a new means of addressing major mental and physical health difficulties for this high-risk population. If the results are promising, the data from this study will be used to update and tailor the MASP+ app for testing in a fully powered randomized controlled trial that will evaluate its efficacy in real-world behavioral health and social service settings. ClinicalTrials.gov NCT05709002; https://clinicaltrials.gov/study/NCT05709002. PRR1-10.2196/52090.

Emerging roles of hydrogel in promoting periodontal tissue regeneration and repairing bone defect.

Periodontal disease is the most common type of oral disease. Periodontal bone defect is the clinical outcome of advanced periodontal disease, which seriously affects the quality of life of patients. Promoting periodontal tissue regeneration and repairing periodontal bone defects is the ultimate treatment goal for periodontal disease, but the means and methods are very limited. Hydrogels are a class of highly hydrophilic polymer networks, and their good biocompatibility has made them a popular research material in the field of oral medicine in recent years. This paper reviews the current mainstream types and characteristics of hydrogels, and summarizes the relevant basic research on hydrogels in promoting periodontal tissue regeneration and bone defect repair in recent years. The possible mechanisms of action and efficacy evaluation are discussed in depth, and the application prospects are also discussed.

Clinical evaluation of therapeutic efficacy of a Siddha herbo mineral formulation “Kumaara Veeriya Kaantha Chenduram’’ with “Nellikkai Legiyam” (internal) in the treatment of Iron Deficiency Anemia

Abstract: Background: Kumaara veeriya kaantha chenduram (KVKC) is a siddha herbomineral formulation indicated for paandunoi in Siddha literature (1).Paandu noi is a disease characterized by changes in the body's natural color andpallor found in the skin, nails and conjunctiva. Objectives: To determine the efficacy of the KVKC, the open labed clinical study was conducted in National Institute of Siddha OPD. Materials and Methods: The 30 patients with Iron deficiency anaemiawere selected and treated with KVKC orally with the dose of 260 milli gram twice in a day with Nellikailegiyam6 gram continuously for 45 days. Laboratory investigations for hemoglobin was done on 1st day and every 15 days once of the study. Results: Clinical assessment was done, based on the before and after treatment scores which was compared statistically and recorded.Regarding Hemoglobin level, 24(80%) patients showed increase of 1 to 3 grams from base level, 6(20%) patients showed increase of 0.1 to 0.9 grams from base level.Regarding Serum Ferritin, out of 30 patients, 9 (30%) patients showed 0.1-3.5 ng/ml increase from its base level, 21 (70%) patients showed 3.6-7.0 ng/ml increase from its base level.From the Statistical studies, the Mean ± Standard deviation for Haemoglobin before treatment was 9.7 ± 0.93 and after treatment was 11.18 ± 1.08 which was statistically highly significant (p&lt;0.0001).And Serum ferritin before treatment was 9.27 ± 3.31, after treatment was 13.5 ± 3.49 which was statistically significant (p&lt;0.0001).

Research progress on ultrasound medicine in diagnosis and evaluation of chemotherapy effect of breast cancer

Breast cancer has the highest incidence rate among cancers in the world and is the main cause of death among female cancer patients around the world. The progress of ultrasound technology has continuously improved the ability to identify the shape and microvessels of breast masses. It plays an important role in the differentiation of benign and malignant breast masses and is the main auxiliary diagnostic method for breast cancer. The widespread implementation of neoadjuvant chemotherapy for breast cancer has improved the survival rate of patients. Evaluating the efficacy after chemotherapy and adjusting chemotherapy strategies as needed can help improve the prognosis of patients. Ultrasound can conduct multi-parameter measurements of breast tumor hardness, blood flow velocity and vascular distribution, which can be applied to evaluate the efficacy of neoadjuvant chemotherapy for breast cancer. This article reviewed the application and research progress of multi-modal ultrasound in the diagnosis and evaluation of chemotherapy efficacy of breast cancer.

In situ detection of dopamine in single living cells by molecularly imprinted polymer-functionalized nanoelectrodes

In situ detection of dopamine (DA) at single-cell level is critical for exploring neurotransmitter-related biological processes and diseases. However, the low content of DA and a variety of distractors with similar oxidation potentials as DA in cells brought great challenges. Here, a sensitive and specific electrochemical nanosensor was proposed for in situ detection of DA in single living cells based on nanodiamond (ND) and molecularly imprinted polymer (MIP)-functionalized carbon fiber nanoelectrode (ND/MIP/CFNE). Due to its excellent electrocatalytic property, ND was modified to the surface of CFNE based on amide bonding. Compared with bare CFNE, ND-modified CFNE can enhance oxidation currents of DA by about 4-fold, improving signal-to-noise ratio and detection sensitivity. MIP was further electropolymerized on the surface of nanoelectrodes to achieve specific capture and recognition of DA, which could avoid the interference of complex matrix and analogs in cells. Taking advantage of the precise positioning capability of a single-cell analyzer and micromanipulator, ND/MIP/CFNE could be precisely inserted into different locations of single cells and monitor oxidation signal of DA. The concentration of DA in the cytoplasm of single pheochromocytoma (PC12) cell was measured to be about 0.4 μM, providing a sensitive and powerful method for single-cell detection. Furthermore, the nanoelectrodes can monitor the fluctuation of intracellular DA under drug stimulation, providing new ideas and methods for new drug development and efficacy evaluation.

Evaluation of clinical efficacy of scaling and root planing with copper nanoparticles gel and/or chlorhexidine gel in patients with periodontitis: A randomized control trial

Antibiotic resistance of bacteria to medications can be resolved using nanotechnology. Resistance to antibiotic mechanisms, such as regulation of permeability, multi-drug efflux pumps, antibiotic disintegration, and target area attraction, are dealt with by nanoparticles. These NPs are composed of Ag and Cu as heavy metals. Being both an essential nutrient as well as an especially hazardous matter, copper represents the two poles of the survival range for microorganisms. Because copper fittings and work surfaces are capable of eliminating methicillin-resistant S. aureus (MRSA) to prevent cross-contamination,they act as an additional obstacle. Additional research is needed, as the mode of action of nanoparticles is not fully understood. Existing information concerning NPs encourages further research to explore their use in the control of dental infections.

Comparative evaluation of efficacy of Pippalyadi Agada as an adjuvant drug vs. standard drug therapy in the management of acute food poisoning: A Study Protocol

Antimicrobial resistance, a pressing challenge in modern medicine, arises from excessive antibiotic use in veterinary and human care. Underreporting and complex links between food contamination and illnesses have led to underestimating foodborne disease impacts. The World Bank’s 2019 analysis projected $15B annual treatment costs and $95.2B productivity loss in low- to middle-income countries due to foodborne diseases. “Agada” refers to symptom-relieving medications, like “Vishaghnakalpa.” Pippalyadi Agada, from Vishaghana plants, treats “Dooshivisha Chikitsa,” e.g., Kitibha, rashes, shwas. It has anti-inflammatory, antioxidant properties, aiding acute food poisoning with nausea, vomiting, fever, diarrhea. It is a carminative, curbing prolonged diarrhea, and anti-toxic. Pippalyadi Agada pacifies imbalanced Vata and Kapha, promising better relief than Agni and Pittastana interventions. As an Ayurvedic remedy, it is administered as Vati, 500mg twice daily with Anuapan Honey for 7 days. This study aims to comparatively evaluate the effectiveness of Pippalyadi Agada as an adjunct to standard drug therapy in managing acute food poisoning. Following a comprehensive drug analysis, a total of 60 eligible participants will be selected and assigned to two groups, each comprising 30 individuals. Group A will receive standard drug therapy, while Group B will receive standard drug therapy alongside Pippalyadi Agad, administered twice daily for 7 days. Assessments will occur on days 0, 3, 5, and 8, both before and after the intervention. The study anticipates that the use of Pippalyadi Agada as an adjunct to standard drug therapy will lead to improved symptom relief and faster recovery in individuals with acute food poisoning, as demonstrated by significant reductions in symptoms such as nausea, vomiting, fever, and diarrhea. The observed outcomes will contribute to a more comprehensive understanding of the potential benefits of Ayurvedic interventions in managing foodborne illnesses.

Trophoblast stem cells, trophoblast invasion, and organoids - advancements in gynecology.

The human placenta serves as a vital barrier between the mother and the developing fetus during pregnancy. A defect in the early development of the placenta is associated with severe pregnancy disorders. Despite its complex development, various molecular processes control placental development, and the specialization of trophoblast cells is still not fully understood. One primary obstacle is the lack of suitable cell model systems. Traditional two-dimensional (2D) cell cultures fail to mimic in vivo conditions and do not capture the intricate intercellular interactions vital for studying placental development. However, three-dimensional (3D) organoid models derived from stem cells that replicate natural cell organization and architecture have greatly improved our understanding of trophoblast behavior and its medicinal applications. Organoids with relevant phenotypes provide a valuable platform to model both placental physiology and pathology, including the modeling of placental disorders. They hold great promise for personalized medicine, improved diagnostics, and the evaluation of pharmaceutical drug efficacy and safety. This article provides a concise overview of trophoblast stem cells, trophoblast invasion, and the evolving role of organoids in gynecology.

A taste alteration-related scale assesses megestrol to improve chemotherapy-induced anorexia.

We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration. We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships. The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients. The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.

Efficacy evaluation of hydrogen peroxide disinfectant based zinc oxide nanoparticles against diarrhea causing Escherichia coli in ruminant animals and broiler chickens

Different strains of Escherichia coli that exhibit genetic characteristics linked to diarrhea pose a major threat to both human and animal health. The purpose of this study was to determine the prevalence of pathogenic Escherichia coli (E. coli), the genetic linkages and routes of transmission between E. coli isolates from different animal species. The efficiency of disinfectants such as hydrogen peroxide (H2O2), Virkon®S, TH4+, nano zinc oxide (ZnO NPs), and H2O2-based zinc oxide nanoparticles (H2O2/ZnO NPs) against isolated strains of E. coli was evaluated. Using 100 fecal samples from different diarrheal species (cow n = 30, sheep n = 40, and broiler chicken n = 30) for E. coli isolation and identification using the entero-bacterial repetitive intergenic consensus (ERIC–PCR) fingerprinting technique. The E. coli properties isolated from several diarrheal species were examined for their pathogenicity in vitro. Scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), Fourier-transform infrared spectrum (FT-IR), X-ray diffraction (XRD), zeta potential, and particle size distribution were used for the synthesis and characterization of ZnO NPs and H2O2/ZnO NPs. The broth macro-dilution method was used to assess the effectiveness of disinfectants and disinfectant-based nanoparticles against E. coli strains. Regarding the results, the hemolytic activity and Congo red binding assays of pathogenic E. coli isolates were 55.3 and 44.7%, respectively. Eleven virulent E. coli isolates were typed into five ERIC-types (A1, A2, B1, B2, and B3) using the ERIC-PCR method. These types clustered into two main clusters (A and B) with 75% similarity. In conclusion, there was 90% similarity between the sheep samples' ERIC types A1 and A2. On the other hand, 89% of the ERIC types B1, B2, and B3 of cows and poultry samples were comparable. The H2O2/ZnO NPs composite exhibits potential antibacterial action against E. coli isolates at 0.04 mg/ml after 120 min of exposure.

De novo drug design as GPT language modeling: large chemistry models with supervised and reinforcement learning

In recent years, generative machine learning algorithms have been successful in designing innovative drug-like molecules. SMILES is a sequence-like language used in most effective drug design models. Due to data’s sequential structure, models such as recurrent neural networks and transformers can design pharmacological compounds with optimized efficacy. Large language models have advanced recently, but their implications on drug design have not yet been explored. Although one study successfully pre-trained a large chemistry model (LCM), its application to specific tasks in drug discovery is unknown. In this study, the drug design task is modeled as a causal language modeling problem. Thus, the procedure of reward modeling, supervised fine-tuning, and proximal policy optimization was used to transfer the LCM to drug design, similar to Open AI’s ChatGPT and InstructGPT procedures. By combining the SMILES sequence with chemical descriptors, the novel efficacy evaluation model exceeded its performance compared to previous studies. After proximal policy optimization, the drug design model generated molecules with 99.2% having efficacy pIC50 > 7 towards the amyloid precursor protein, with 100% of the generated molecules being valid and novel. This demonstrated the applicability of LCMs in drug discovery, with benefits including less data consumption while fine-tuning. The applicability of LCMs to drug discovery opens the door for larger studies involving reinforcement-learning with human feedback, where chemists provide feedback to LCMs and generate higher-quality molecules. LCMs’ ability to design similar molecules from datasets paves the way for more accessible, non-patented alternatives to drug molecules.

Cytisine eye drops for benzalkonium chloride-induced dry eye: safety and efficacy evaluation

This experiment aimed to investigate the feasibility of cytisine (CYT) in treating eye diseases with ocular topical application. An in vitro cytotoxicity test, a hen’s egg test-chorioallantoic membrane (HET-CAM), and a mouse eye tolerance test were used to fully reveal the ocular safety profiles of CYT. For the efficacy evaluations, CYT’s effects on cell wound healing, against H2O2-induced oxidative stress damages on cells, and on benzalkonium chloride (BAC)–induced dry eye disease (DED) in mice were evaluated. Results showed that CYT did not show any cytotoxicities at concentrations no higher than 250 μg/ml, while lipoic acid (α-LA) at 250 μg/ml and BAC at 1.25 μg/ml showed significant cytotoxicities within 48 h incubation. The HET-CAM and mouse eye tolerance test confirmed that 0.5% CYT eye drops demonstrated good safety characteristics. Efficacy evaluations showed that CTY significantly promoted cell migration and wound healing. CYT significantly improved cell survival against H2O2-induced oxidative stress damage by reversing the imbalance between the reactive oxygen species (ROS) and antioxidant defense mechanisms. The animal evaluation of the BAC-induced dry eye model revealed that CYT demonstrated a strong treatment effect, including reversing ocular surface damages, recovering corneal sensitivity, and inhibiting neovascularization; HMGB1/NF-κB signaling was involved in this DED treatment by CTY. In conclusion, CYT had strong experimental treatment efficacy against DED with good ocular safety profiles, and it might be a novel and promising drug for DED.