Tag: pubmed

Clin Pharmacokinet. 2024 Aug 10. doi: 10.1007/s40262-024-01407-x. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Overactivation of the PI3K/AKT pathway can occur in many cancers. Capivasertib is a potent, selective pan-AKT inhibitor. The objectives of this analysis were to develop a population pharmacokinetic model for capivasertib and to quantitatively assess the impact of intrinsic and extrinsic factors on the pharmacokinetics of capivasertib.

METHODS: Pharmacokinetic data from four phase I and II studies were combined. Capivasertib was administered orally at a dose range of 80-800 mg twice daily over 28-day and 21-day cycles as monotherapy or in combination with paclitaxel or fulvestrant, using continuous dosing or one of two intermittent dosing schedules: either 4 days on, 3 days off (4/3) or 2 days on, 5 days off (2/5). Several models and approaches were tested for their ability to describe capivasertib disposition. The covariates assessed included dose, schedule, age, body weight, race, sex, creatinine clearance, hepatic function, renal function, smoking status, food effect, formulation, and concomitant use with paclitaxel, fulvestrant, cytochrome P450, family 3, subfamily A (CYP3A) inducers, CYP3A inhibitors and acid-reducing agents.

RESULTS: A total of 3963 capivasertib plasma concentrations from 441 patients were included. Capivasertib pharmacokinetics was adequately described by a three-compartment model where the apparent clearance (CL/F) presented a moderate time-dependent and dose-dependent clearance. Following oral administration of multiple doses of capivasertib (400 mg twice daily; [4/3]), the initial CL/F was 62.2 L/h (between-subject variability 39.3%), and after approximately 120 hours, CL/F decreased by 18%. The effective half-life was 8.34 h. Steady state was predicted to be reached on every third and fourth dosing day each week from the second week with exposure levels that produced robust inhibition of AKT but not of other related kinases. The area under the plasma concentration-time curve and maximum plasma concentration of capivasertib were proportional between the dose levels of 80-480 mg after multiple doses but more than proportional beyond 480 mg. Schedule, age, race, sex, creatinine clearance, hepatic function, renal function, smoking status and concomitant use with fulvestrant, CYP3A inducers, CYP3A inhibitors or acid-reducing agents were not significant covariates for capivasertib pharmacokinetics. Concomitant use of paclitaxel, food effect and formulation statistically significantly affected capivasertib pharmacokinetics, but the effect was low. Body weight was statistically significantly related to capivasertib CL/F, with a 12% reduction in CL/F at steady state and a 14% increase in the area under the curve for 12 hours at steady state and maximum concentration at steady state at a lower body weight (47 kg vs 67 kg reference).

CONCLUSIONS: Capivasertib pharmacokinetics showed moderate between-subject variability, and most covariates assessed had no significant impact. Body weight, dose, concomitant use of paclitaxel, food effect and formulation showed statistically significant effects. However, these were predicted to impact exposure to capivasertib by <20% and were not expected to be clinically relevant. Based on the population pharmacokinetics, no a priori dose adjustment is needed for intrinsic and extrinsic factors.

PMID:39127854 | DOI:10.1007/s40262-024-01407-x

Sci Rep. 2024 Aug 10;14(1):18599. doi: 10.1038/s41598-024-69462-9.

ABSTRACT

Fault detection and isolation in unmanned aerial vehicle (UAV) propellers are critical for operational safety and efficiency. Most existing fault diagnosis techniques rely basically on traditional statistical-based methods that necessitate better approaches. This study explores the application of untraditional feature extraction methodologies, namely Permutation Entropy (PE), Lempel-Ziv Complexity (LZC), and Teager-Kaiser Energy Operator (TKEO), on the PADRE dataset, which encapsulates various rotor fault configurations. The extracted features were subjected to a Chi-Square (χ²) feature selection process to identify the most significant features for input into a Deep Neural Network. The Taguchi method was utilized to test the performance of the recorded features, correspondingly. Performance metrics, including Accuracy, F1-Score, Precision, and Recall, were employed to evaluate the model’s effectiveness before and after the feature selection. The achieved accuracy has increased by 0.9% when compared with results utilizing traditional statistical methods. Comparative analysis with prior research reveals that the proposed untraditional features surpass traditional methods in diagnosing UAV propeller faults. It resulted in improved performance metrics with Accuracy, F1-Score, Precision, and Recall reaching 99.6%, 99.5%, 99.5%, and 99.5%, respectively. The results suggest promising directions for future research in UAV maintenance and safety protocols.

PMID:39127843 | DOI:10.1038/s41598-024-69462-9

J Clin Monit Comput. 2024 Aug 10. doi: 10.1007/s10877-024-01204-8. Online ahead of print.

ABSTRACT

During surgery for congenital heart disease (CHD) temperature management is crucial. Vesical (T_ves) and nasopharyngeal (T_NPH) temperature are usually measured. Whereas T_ves slowly responds to temperature changes, T_NPH carries the risk of bleeding. The zero-heat-flux (ZHF) temperature monitoring systems SpotOn™ (T_SpotOn), and Tcore™ (T_core) measure temperature non-invasively. We evaluated accuracy and precision of the non-invasive devices, and of T_ves compared to T_NPH for estimating temperature. In this prospective observational study in pediatric and adult patients accuracy and precision of T_SpotOn, T_core, and T_ves were analyzed using the Bland-Altman method. Proportion of differences (PoD) and Lin´s concordance correlation coefficient (LCC) were calculated. Data of 47 patients resulted in sets of matched measurements: 1073 for T_SpotOn vs. T_NPH, 874 for T_core vs. T_NPH, and 1102 for T_ves vs. T_NPH. Accuracy was – 0.39 °C for T_SpotOn, -0.09 °C for T_core, and 0.07 °C for T_ves. Precisison was between – 1.12 and 0.35 °C for T_SpotOn, -0.88 to 0.71 °C for T_core, and – 1.90 to 2.05 °C for T_ves. PoD ≤ 0.5 °C were 71% for T_SpotOn, 71% for T_core, and 60% for T_ves. LCC was 0.9455 for T_SpotOn, 0.9510 for T_core, and 0.9322 for T_ves. Temperatures below 25.2 °C (T_SpotOn) or 27.1 (T_core) could not be recorded non-invasively, but only with T_ves. Trial registration German Clinical Trials Register, DRKS00010720.

PMID:39127818 | DOI:10.1007/s10877-024-01204-8

Sci Rep. 2024 Aug 10;14(1):18611. doi: 10.1038/s41598-024-69517-x.

ABSTRACT

A new area of applied chemistry called chemical graph theory uses combinatorial techniques to explain the complex interactions between atoms and bonds in chemical systems. This work investigates the use of edge partitions to decipher molecular connection patterns. The main goal is to use topological indices that capture important topological features to create a connection between the thermodynamic properties and structural characteristics of chemical molecules. We specifically examine the complex web of atoms and links that make up the Fe phthalocyanine chemical graph. Moreover, our study demonstrates a relationship between the calculated topological indices and the thermodynamic properties of Fe phthalocyanine (Phthalocyanine Iron (II)). This work offers insight into the thermodynamic consequences of molecule structures. It advances the subject of chemical graph theory, providing a useful perspective for future applications in catalysis and materials science.

PMID:39127814 | DOI:10.1038/s41598-024-69517-x

Ophthalmol Ther. 2024 Aug 10. doi: 10.1007/s40123-024-01015-9. Online ahead of print.

ABSTRACT

INTRODUCTION: This study compared the efficacy of hydroxypropyl guar (HPG)/hyaluronic acid (HA) and carboxymethylcellulose (CMC)/HA lubricant eye drops for post-cataract surgery dry eye disease (DED).

METHODS: This was a prospective, open-label, assessor-masked, parallel, randomized controlled study. Seventy patients with DED who underwent cataract surgery were randomized in a 1:1 ratio to receive 1-2 drops of HPG/HA or CMC/HA lubricant four times daily for 3 weeks. Efficacy assessments included changes from baseline in corneal fluorescein staining (CFS) score, Ocular Surface Disease Index score, Schirmer’s test score (without anesthesia), tear break-up time, and central corneal sensitivity at weeks 1 and 3.

RESULTS: There were 35 patients in each group. The HPG/HA group demonstrated superior improvements in CFS scores (expressed as means and standard deviations) to the CMC/HA group at week 1 ( – 1.0 [1.7] vs. – 0.1 [1.7], p = 0.039) and demonstrated comparable results at week 3 ( – 1.6 [1.8] vs. – 1.3 [1.9], p = 0.552). No statistical differences were observed in other secondary outcomes between groups at weeks 1 and 3 (p > 0.05). Only one adverse event was reported in this study, which occurred in the HPG/HA group. The AE of ocular hypertension was mild, deemed unrelated to the study treatment, and resolved within a week.

CONCLUSIONS: The HPG/HA lubricant eye drops resulted in greater CFS scores at 1 week after treatment compared with CMC/HA drops. The HPG/HA and CMC/HA drops were safe and well tolerated.

GOV IDENTIFIER: NCT06221345.

PMID:39127813 | DOI:10.1007/s40123-024-01015-9

Sci Rep. 2024 Aug 10;14(1):18615. doi: 10.1038/s41598-024-69569-z.

ABSTRACT

This study presents a 3D pick-rock contact calculation method for conical picks, aiming to develop a predictive method with high accuracy and lithological tolerance for peak cutting force (PCF). The method is based on the projection profile method and D. L. Sikarskie stress distribution function. By integrating Griffith’s theory with rock damage constitutive model, the energy relationship between the rock fracturing process and crack propagation process is analyzed. Furthermore, in order to accurately correct the PCF, the energy correction function (C-K_f) is proposed to calculate the damage intensity index (K_e), which accounts for the relationship between rock brittleness and rock damage elastic-plastic energy. To validate the method, it is compared with full-scale cutting tests and three existing models, and statistical analysis confirms its high lithological tolerance and accuracy, the present model has the highest R² of 0.90404, which is at least 12.5% higher relative to the mainstream models. Moreover, incorporating K_e into the method further enhances its predictive capability.

PMID:39127807 | DOI:10.1038/s41598-024-69569-z

Arch Orthop Trauma Surg. 2024 Aug 10. doi: 10.1007/s00402-024-05408-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The purpose of this study was to evaluate the perspectives of aspiring orthopaedic surgeons on artificial intelligence (AI), analysing how gender, AI knowledge, and technical inclination influence views on AI. Additionally, the extent to which recent AI advancements sway career decisions was assessed.

MATERIALS AND METHODS: A digital survey was distributed to student members of orthopaedic societies across Germany, Switzerland, and Austria. Subgroup analyses explored how gender, AI knowledge, and technical inclination shape attitudes towards AI.

RESULTS: Of 174 total respondents, 86.2% (n = 150) intended to pursue a career in orthopaedic surgery and were included in the analysis. The majority (74.5%) reported ‘basic’ or ‘no’ knowledge about AI. Approximately 29.3% believed AI would significantly impact orthopaedics within 5 years, with another 35.3% projecting 5-10 years. AI was predominantly seen as an assistive tool (77.8%), without significant fear of job displacement. The most valued AI applications were identified as preoperative implant planning (85.3%), administrative tasks (84%), and image analysis (81.3%). Concerns arose regarding skill atrophy due to overreliance (69.3%), liability (68%), and diminished patient interaction (56%). The majority maintained a ‘neutral’ view on AI (53%), though 32.9% were ‘enthusiastic’. A stronger focus on AI in medical education was requested by 81.9%. Most participants (72.8%) felt recent AI advancements did not alter their career decisions towards or away from the orthopaedic specialty. Statistical analysis revealed a significant association between AI literacy (p = 0.015) and technical inclination (p = 0.003). AI literacy did not increase significantly during medical education (p = 0.091).

CONCLUSIONS: Future orthopaedic surgeons exhibit a favourable outlook on AI, foreseeing its significant influence in the near future. AI literacy remains relatively low and showed no improvement during medical school. There is notable demand for improved AI-related education. The choice of orthopaedics as a specialty appears to be robust against the sway of recent AI advancements.

LEVEL OF EVIDENCE: Cross-sectional survey study; level IV.

PMID:39127806 | DOI:10.1007/s00402-024-05408-0

Psychometrika. 2024 Aug 10. doi: 10.1007/s11336-024-09998-x. Online ahead of print.

ABSTRACT

In multidimensional tests, the identification of latent traits measured by each item is crucial. In addition to item-trait relationship, differential item functioning (DIF) is routinely evaluated to ensure valid comparison among different groups. The two problems are investigated separately in the literature. This paper uses a unified framework for detecting item-trait relationship and DIF in multidimensional item response theory (MIRT) models. By incorporating DIF effects in MIRT models, these problems can be considered as variable selection for latent/observed variables and their interactions. A Bayesian adaptive Lasso procedure is developed for variable selection, in which item-trait relationship and DIF effects can be obtained simultaneously. Simulation studies show the performance of our method for parameter estimation, the recovery of item-trait relationship and the detection of DIF effects. An application is presented using data from the Eysenck Personality Questionnaire.

PMID:39127801 | DOI:10.1007/s11336-024-09998-x

Eur Arch Otorhinolaryngol. 2024 Aug 10. doi: 10.1007/s00405-024-08761-3. Online ahead of print.

ABSTRACT

PURPOSE: Evaluating the impact of radioiodine therapy (RIT) on olfactory function in thyroid cancer patients through quantitative and qualitative olfactory tests.

METHOD: In this cohort study, patients with thyroid cancer were included. Demographic, clinical, and laboratory data were collected. To subjectively evaluate the olfactory changes aftter RIT, the Visual Analog Scale (VAS), Self-Reported Mini-Olfactory Questionnaire (self-MOQ), and the University of Washington Quality of Life Questionnaire (UW-QOL) were assessed. Out of UW-QOL questions those related to saliva, taste, and overall health condition were analysed. For objective assessment, patients underwent both the Butanol Threshold Test (BTT) and the a version of Smell Identification Test (SIT). Patients were assessed before, one month, and six months after RIT.

RESULTS: Ninety eight patients were included (Male = 17). A statistically significant decrement was observed in olfaction based on the VAS, between the baseline and one (pvalue = 0.015) and six months (pvalue = 0.031) of follow-up. Additionally, saliva (pvalue = 0.001), taste (pvalue = 0.000), and overall health condition (pvalue = 0.010) significantly decreased one-month after RIT. The measures were not different between the baseline and 6-month follow up and the improvement of index of taste was significant from 1-month to 6-months follow ups (pvalue = 0.000). However, none of the objective tests (the BTT and the SIT) indicated a significant decline in olfaction during the follow up.

CONCLUSION: A subjective RIT related decrease in smell function, taste, and saliva production was documented without any objective olfactory dysfunction.

PMID:39127798 | DOI:10.1007/s00405-024-08761-3

Evid Based Dent. 2024 Aug 10. doi: 10.1038/s41432-024-01051-1. Online ahead of print.

ABSTRACT

DESIGN: The study conducted by Olmedo-Gaya et al. aimed to investigate the effects of various surgical techniques on the initial stability of implants placed in the posterior maxilla through a randomized controlled clinical trial. The study compared insertion torque (IT) and implant stability quotients (ISQ) among implants placed using under preparation, expanders, and standard surgical instrumentation.

CASE SELECTION: The study enrolled 108 patients, each receiving one implant in the posterior maxilla region. Patients were distributed into three groups: group 1 (n = 36) with the under preparation technique, group 2 (n = 36) using the expander technique, and group 3 (n = 36) with conventional drilling.

DATA ANALYSIS: IT was measured using a torque indicator, while ISQ was recorded through resonance frequency analysis immediately post-surgery. The ISQ values were analyzed in relation to the patient’s bone quality, categorized into types II, III, and IV.

RESULTS: ISQ values varied significantly with bone quality, being highest in type II (76.65) and type III (73.60), and lowest in type IV (67.34) bone, with a significant difference (p < 0.0001). The conventional drilling technique yielded lower ISQ values (69.31) compared to under preparation (74.29) and expander techniques (73.99), with statistical significance (p = 0.008 and p = 0.005, respectively).

CONCLUSIONS: Surgical technique significantly influences primary stability in low-quality bone. Conventional drilling results in lower ISQ values, suggesting that alternative techniques such as under preparation or expanders should be used in low-quality bone to achieve better primary stability.

CLINICAL RELEVANCE: For implants in low-quality bone, replacing the conventional drilling technique with under preparation or expander techniques can enhance primary stability.

PMID:39127794 | DOI:10.1038/s41432-024-01051-1