Tag: pubmed

BMJ. 2024 May 28;385:e078876. doi: 10.1136/bmj-2023-078876.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy.

DESIGN: Randomised, double blind, placebo controlled, phase 3 study.

SETTING: 146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023.

PARTICIPANTS: 1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease.

INTERVENTIONS: Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator’s choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator’s choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity.

MAIN OUTCOME MEASURES: The primary endpoint was overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment.

RESULTS: Of 1657 patients screened between 13 December 2018 and 9 February 2021, 660 were ineligible due to not meeting the eligibility criteria, withdrawal of consent, adverse events, or other reasons. Overall, 997 were randomly assigned to receive tislelizumab plus chemotherapy (n=501) or placebo plus chemotherapy (n=496). Tislelizumab plus chemotherapy showed statistically significant improvements in overall survival versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5% (median 17.2 months v 12.6 months; hazard ratio 0.74 (95% confidence interval 0.59 to 0.94); P=0.006 (interim analysis)) and in all randomised patients (median 15.0 months v 12.9 months; hazard ratio 0.80 (0.70 to 0.92); P=0.001 (final analysis)). Grade 3 or worse treatment related adverse events were observed in 54% (268/498) of patients in the tislelizumab plus chemotherapy arm versus 50% (246/494) in the placebo plus chemotherapy arm.

CONCLUSIONS: Tislelizumab added to chemotherapy as primary treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5%, and in all randomised patients.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03777657.

PMID:38806195 | DOI:10.1136/bmj-2023-078876

RMD Open. 2024 May 28;10(2):e003616. doi: 10.1136/rmdopen-2023-003616.

ABSTRACT

OBJECTIVES: This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren’s syndrome (pSS) cases.

METHODS: A retrospective analysis was conducted on pregnant individuals with pSS, who received outpatient or inpatient care across multiple hospitals in Anhui Province, China, from January 2015 to December 2022.

RESULTS: This study included 164 pregnant women with pSS and 328 control subjects, with no statistically significant difference in average age between the two groups. Analysis of pregnancy outcomes revealed that, compared with the control group, pregnant women in the pSS group were more likely to experience miscarriages, both spontaneous (12.80% vs 1.52%, p<0.001) and therapeutic (6.10% vs 0.91%, p<0.05). The proportion of placental abnormalities detected during prenatal ultrasound in women from the pSS group was higher (14.63% vs 6.40%, p<0.05). In the analysis of pregnancy outcomes for live-born neonates, a higher incidence of congenital heart abnormalities was observed in the pSS group (27.34% vs 12.03%, p<0.05). While there were no significant differences between the pSS pregnancies in terms of both normal and adverse pregnancy outcomes, a comparison of fetal survival and fetal loss in pSS pregnancies revealed a greater use of prophylactic anticoagulant therapy in the fetal survival group. Notably, the application of low molecular weight heparin (LMWH) emerged as an independent protective factor for fetal survival.

CONCLUSIONS: Compared with non-autoimmune controls, pregnancy in women with pSS presents more challenges. Importantly, we observed that the use of LMWH as anticoagulant therapy is an independent protective measure for fetal survival.

PMID:38806189 | DOI:10.1136/rmdopen-2023-003616

Cutan Ocul Toxicol. 2024 May 28:1-31. doi: 10.1080/15569527.2024.2360735. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the ocular effects seen among eye cosmetic wearers in the Indian Population.

METHODS: This cross sectional study was conducted on female participants who had fulfilled the inclusion and exclusion criteria. A detailed history was obtained and thorough ophthalmic evaluation was done. Mann Whitney U test was used. Statistical analysis was done using IBM SPSS. p < 0.05 was taken as the level of statistical significance.

RESULTS: Among a total of 225 participants in our study, the mean age was 24.23 ± 1.8 which comprised of young student females. Majority of the females used one eye cosmetics with Kajal (n = 156) being the most predominant. Most frequently encountered symptom upon using eye cosmetics was watering from eyes and ocular pain was the least encountered symptom. Anterior segment examination showed- allergic conjunctivitis and meibomian gland dysfunction being the most and least predominant respectively. Our study highlights that Kajal predisposes the eyes to significant ocular morbidity with p = 0.039 for Dry Eye Disease, p = 0.041 for Allergic Conjunctivitis, p = 0.036 for conjunctival pigmentation. Prolonged use of such formulations for more than 4 times a week (p = 0.046) or even daily(p = 0.031)for a duration of either 1-5 years (p = 0.033) or greater than 5 years (p = 0.027) was found to be statistically significant in causing ocular signs. Non removal of eye cosmetics at the end of the day was significant in causing allergic conjunctivitis (p = 0.035) and conjunctival pigmentation (p = 0.021). Plain tap water has been found to be the least effective technique in the removal of such ocular cosmetics with a statistical significance of p = 0.031 in causing ocular signs.

CONCLUSIONS: Eye cosmetics are a significant contributor to the development of ocular surface diseases. Removal of products along with decreased usage seems to be a significant contributor in dampening unwanted adverse effects.

PMID:38806172 | DOI:10.1080/15569527.2024.2360735

Eur J Dent. 2024 May 28. doi: 10.1055/s-0044-1779422. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the linear dimensional change of polymerization of three materials and two techniques of the union of molding transfers for implant-supported prostheses used in the open-tray technique.

MATERIALS AND METHODS: A nylon maxilla-shaped matrix was made, two osseous integrated implants were installed, and, over these two, straight conical mini-pillars were installed. Open-tray impression transfers were attached to the mini-pillars, and a silicone guide was made to standardize the connections between the transfers. The samples were divided into six groups (n = 20): PA (Pattern Resin LS, chemically activated acrylic resin in the single step technique); DU (Durallay, chemically activated acrylic resin in the single step technique); BI (Protemp4, bisacrylic resin in the single step technique); PAC (Pattern Resin LS in sectioning and joining of segments technique); DUC (Durallay, in sectioning and joining of segments technique); and BIC (Protemp4, in sectioning and joining of segments technique). The linear dimensional change values that occurred among these transfers were measured in a profile projector (VB300; Starret) coupled to the Quadra Check device, with a resolution of 0.001 mm, performed by a single calibrated operator.

STATISTICAL ANALYSIS: Data were submitted to a two-way analysis of variance and Tukey’s test (p < 0.01).

RESULTS: Statistically significant mean values were found in all comparisons. The PA showed the lowest mean values (µm) of linear dimensional change, both in the single-step technique and in the sectioning and joining technique, in the following order: BI 255.73 (3.81), DU 173.75 (2.30), PA 95.97 (3.20), BIC 23.82 (1.71), DUC 20.85 (2.53), and PAC 13.27 (2.09). The single-step technique showed the worst results, regardless of the material.

CONCLUSION: The sectioning and joining technique reduced the dimensional change in all materials, and the Pattern Resin LS showed the lowest shrinkage mean values, followed by Durallay and Protemp4.

PMID:38806161 | DOI:10.1055/s-0044-1779422

Rofo. 2024 May 28. doi: 10.1055/a-2301-3349. Online ahead of print.

ABSTRACT

Structured reporting (SR) not only offers advantages regarding report quality but, as an IT-based method, also the opportunity to aggregate and analyze large, highly structured datasets (data mining). In this study, a data mining algorithm was used to calculate epidemiological data and in-hospital prevalence statistics of pulmonary embolism (PE) by analyzing structured CT reports.All structured reports for PE CT scans from the last 5 years (n = 2790) were extracted from the SR database and analyzed. The prevalence of PE was calculated for the entire cohort and stratified by referral type and clinical referrer. Distributions of the manifestation of PEs (central, lobar, segmental, subsegmental, as well as left-sided, right-sided, bilateral) were calculated, and the occurrence of right heart strain was correlated with the manifestation.The prevalence of PE in the entire cohort was 24% (n = 678). The median age of PE patients was 71 years (IQR 58-80), and the sex distribution was 1.2/1 (M/F). Outpatients showed a lower prevalence of 23% compared to patients from regular wards (27%) and intensive care units (30%). Surgically referred patients had a higher prevalence than patients from internal medicine (34% vs. 22%). Patients with central and bilateral PEs had a significantly higher occurrence of right heart strain compared to patients with peripheral and unilateral embolisms.Data mining of structured reports is a simple method for obtaining prevalence statistics, epidemiological data, and the distribution of disease characteristics, as demonstrated by the PE use case. The generated data can be helpful for multiple purposes, such as for internal clinical quality assurance and scientific analyses. To benefit from this, consistent use of SR is required and is therefore recommended. · SR-based data mining allows simple epidemiologic analyses for PE.. · The prevalence of PE differs between outpatients and inpatients.. · Central and bilateral PEs have an increased risk of right heart strain.. · Jorg T, Halfmann MC, Graafen D et al. Structured reporting for efficient epidemiological and in-hospital prevalence analysis of pulmonary embolisms. Fortschr Röntgenstr 2024; DOI 10.1055/a-2301-3349.

PMID:38806150 | DOI:10.1055/a-2301-3349

Sci Total Environ. 2024 May 26:173557. doi: 10.1016/j.scitotenv.2024.173557. Online ahead of print.

ABSTRACT

Despite the success of the growing data-driven landslide susceptibility prediction, the model training heavily relies on the quality of the data (involving topography, geology, hydrology, land cover, climate, and human activity), the structure of the model, and the fine-tuning of the model parameters. Few data-driven methods have considered incorporating ‘landslide priors’, as in this article the prior knowledge or statistics related to landslide occurrence, to enhance the model’s perception in landslide mechanism. The main objective and contribution of this study is the coupling of landslide priors and a deep learning model to improve the model’s transferability and stability. This is accomplished by selecting non-landslide sample grounded on landslide statistics, disentangling input landslide features using a variational autoencoder, and crafting a loss function with physical constraints. This study utilizes the SHAP method to interpret the deep learning model, aiding in the acquisition of feature permutation results to identify underlying landslide causes. The interpretation result indicates that ‘slope’ is the most influential factor. Considering the extreme rainfall impact on landslide occurrences in Hong Kong, we combine this prior into the deep learning model and find feature ranking for ‘rainfall’ improved, in comparison to the ranking result interpreted from a pure MLP. Further, the potency of MT-InSAR is utilized to augment the landslide susceptibility map and promote efficient cross-validation. A comparison of InSAR results with historical images reveals that detectable movement before their occurrence is evident in only a minority of landslides. Most landslides occur spontaneously, exhibiting no precursor motion. Comparing with other data-driven methods, the proposed methods outperform in accuracy (by 2 %-5 %), precision (by 2 %-7 %), recall (by 1 %-3 %), F1-score (by 8 %-10 %), and AuROC (by 2 %-4 %). Especially, the Cohen Kappa performance surpasses nearly 20 %, indicating that the knowledge-aware methodology enhances model generalization and mitigates training bias induced by unbalanced positive and negative samples.

PMID:38806128 | DOI:10.1016/j.scitotenv.2024.173557

Sci Total Environ. 2024 May 26:173559. doi: 10.1016/j.scitotenv.2024.173559. Online ahead of print.

ABSTRACT

Although cycling has numerous health benefits, the increased breathing volume and lack of protection from exposure to the environment while cycling poses health risks that cannot be disregarded. Previous studies evaluating the exposure of cyclists to air pollution have typically focused on assessing exposure to a single pollutant or exposure concentrations on specific urban routes, and have not performed a comprehensive assessment considering the distribution of cyclists. The present study used bicycle-sharing big data to conduct a more comprehensive and refined real-time population weighted exposure risk assessment of pileless bike sharing riders in Beijing. We quantified the spatial distribution of high exposure areas at different times and found that the exposure risk during the evening peak period was significantly higher than that during the morning peak and early morning periods, particularly in the city center and its environs. By establishing stepwise regression models, we identified the significant impact of various urban points of interest (POIs) on exposure risk, with sports venues, public toilets, educational institutions, scenic spots, and financial entities particularly influential at different time periods. Medical institutions and shopping venues have a significant negative impact on the exposure levels of PM_2.5 and NO₂ among cyclists in most cases. These findings emphasize the need for targeted pollution control strategies. The aim of this study is to mitigate the impact of air pollution on cyclists and create a healthier cycling environment. The research results can provide new ideas for urban health planning and support scientific decision-making for sustainable urban development.

PMID:38806121 | DOI:10.1016/j.scitotenv.2024.173559

Sci Total Environ. 2024 May 26:173555. doi: 10.1016/j.scitotenv.2024.173555. Online ahead of print.

ABSTRACT

A sound evaluation of the cadmium (Cd) mass balance in agricultural soils needs accurate data of Cd leaching. Reported Cd concentrations from in situ studies are often one order of magnitude lower than predicted by empirical models, which were calibrated to pore water data from stored soils. It is hypothesized that this discrepancy is related to the preferential flow of water (non-equilibrium) and/or artefacts caused by drying and rewetting soils prior to pore water analysis. These hypotheses were tested on multiple soils (n = 27) with contrasting properties. Pore waters were collected by soil centrifugation from field fresh soil samples and also after incubating the same soils (28 days, 20 °C), following two drying-rewetting cycles, the idea being that chemical equilibrium in the soil is reached after incubation. Incubation increased pore water Cd by a factor 4, on average, and up to a factor 16. That increase was statistically related to the decrease of pore water pH and the increase of nitrate, both mainly related to incubation-induced nitrification. After correcting for both factors, the Cd rise was also highest at higher pore water Ca. This suggests that higher Ca in soil enlarges Cd concentration gradients among pore classes in field fresh soils because high Ca promotes soil aggregation and separation of mobile from immobile water. Several empirical models were used to predict pore water Cd. Predictions exceeded observations up to a factor 30 for the fresh pore waters but matched well with those of incubated soils; again, deviations from the 1:1 line in field fresh soils were largest in high Ca (>0.8 mM) soils, suggesting that local equilibrium conditions in field fresh soils are not found at higher Ca. Our results demonstrate that empirical models need recalibration with field fresh pore water data to make accurate soil Cd mass balances in risk assessments.

PMID:38806120 | DOI:10.1016/j.scitotenv.2024.173555

Toxicol In Vitro. 2024 May 26:105853. doi: 10.1016/j.tiv.2024.105853. Online ahead of print.

ABSTRACT

Pentachlorophenol (PCP) is a persistent organic compound that is widely present in the environment. The estimation of internal exposure levels for a given external exposure using toxicokinetic models is key to the human health risk assessment of PCP. The present study developed a physiologically based multicompartmental pharmacokinetic (PBTK) model to describe and predict the behavior of pentachlorophenol (PCP) in an organism. The model consists of stomach, intestines, adipose tissue, kidneys and fast- and poorly perfused tissues that are interconnected via blood circulation. We constructed a PBTK model of PCP in rats and extrapolated it to human dietary PCP exposure. The toxicokinetic data of PCP in human tissues and excreta were obtained from the published literature. Based on the collected PCP dietary survey and internal exposure data of pregnant women in Shanghai, Bayesian statistical analysis was performed for the model using Markov chain Monte Carlo (MCMC) simulation. The posterior distributions of the sensitive parameters were estimated, and the model was parameter optimized and validated using the pregnant women’s test dataset. The results showed that the root mean square error (RMSE) improved 37.3% compared to the original model, and a systematic literature search revealed that the optimized model achieved acceptable prediction results for other datasets in China. A PCP metabolism model based on the exposure characteristics of pregnant women in China was constructed in the present study. The model provides a theoretical basis for the study of PCP toxicity and risk assessment.

PMID:38806067 | DOI:10.1016/j.tiv.2024.105853

Nanotechnology. 2024 May 28. doi: 10.1088/1361-6528/ad50e4. Online ahead of print.

ABSTRACT

Nanotechnology has gained immense popularity and observed rapid development due to the remarkable physio-chemical properties of nanoparticles (NPs) and related nanomaterials. The green production of nanoparticles has many benefits over traditional techniques because the current procedures are expensive, time-consuming, and involve harmful substances that limit their applicability. This study aimed to use a novel green source, the Salsola imbricata (SI) plant, which is commonly found in Central Asia and known for its medicinal properties as a reducing and stabilizing agent for the synthesis of AgNPs. The current study also utilized efficient statistical design, the Plackett-Burman Design of Experiment (DOE) method to synthesize the nanoparticles. The characterization of nanoparticles was carried out using UV-Vis spectroscopy, Fourier Transform Infrared Spectroscopy, and scanning electron microscopy (SEM). The Plackett-Burman design results showed that only two out of four factors i.e., AgNO3 concentration and incubation time, were significant for the synthesis of AgNPs. While remaining factors, incubation temperature and plant extract: AgNO3 ratio were non-significant. The SEM analysis result showed that SI-AgNPs had a size of 20-50nm. The SI-AgNPs demonstrated strong antimicrobial activity against oral pathogens such as Streptococcus mutans and Lactobacillus acidophilus, with the highest efficacy observed at a concentration of 2 mg/ml. The addition of SI-AgNPs in glass ionomer cement significantly increased the antimicrobial efficacy of GIC at different concentration (p≤0.000 for 0.2% and 0.1%, p≤0.01 for 0.05% and p≤0.05 for 0.025% respectively). Based on the results of the current study, the plant based AgNPs can be further evaluated in detail as alternate antimicrobial agent either alone or in combination with other antimicrobial agents for different dental applications.

PMID:38806018 | DOI:10.1088/1361-6528/ad50e4