Tag: pubmed

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(12):3312-3319. doi: 10.19540/j.cnki.cjcmm.20231220.401.

ABSTRACT

Urine metabolomics based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was utilized to investigate the metabolic regulation mechanism of Tingli Dazao Xiefei Decoction(TLDZ) in rats with allergic asthma. SD male rats were divided into a normal group, a model group, a dexamethasone group, and a TLDZ group. The allergic asthma model was established by intraperitoneal injection of ovalbumin(OVA) to induce allergy, combined with atomization excitation. Urine metabolites from all rats were collected by UHPLC-Q-TOF-MS. The metabolic profiles of rats in each group were built by principal component analysis(PCA). Besides, the differential metabolites between the model group and the TLDZ group were selected by orthogonal partial least squares discriminant analysis(OPLS-DA), t-test(P<0.05), and variable importance in the projection(VIP) values of more than 3. The differential metabolites were identified through HMDB, METLIN, and other online databa-ses. Heat maps and clustering analysis for relative quantitative information of biomarkers in each group were drawn by MeV 4.8.0 software. Finally, MetaboAnalyst, MBRole, and KEGG databases were used to enrich related metabolic pathways and construct metabolic networks. The result demonstrated that TLDZ could effectively regulate the disordered urine metabolic profiles of asthmatic rats. Combined with multivariate statistical analysis and online databases, a total of 45 differential metabolites with significant changes(P<0.05) between the model group and the TLDZ group were screened out. Metabolic pathways including histidine metabolism, tryptophan metabolism, and arginine and proline metabolism were enriched. TLDZ could improve asthma by regulating related metabolic pathways and interfering with pathological processes such as immune homeostasis airway inflammation. The study investigates the molecular mechanism of anti-asthma of TLDZ from the perspective of urine metabolomics, and combined with previous pharmacological studies, it provides a scientific basis for the clinical development and application of TLDZ in the treatment of asthma.

PMID:39041094 | DOI:10.19540/j.cnki.cjcmm.20231220.401

Clin Mol Hepatol. 2024 Jul 23. doi: 10.3350/cmh.2024.0333. Online ahead of print.

ABSTRACT

INTRODUCTION: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

METHODS: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab.

RESULTS: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of anti-tumor macrophages and activated T-cells, potentially explaining its better response.

CONCLUSIONS: Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

PMID:39038962 | DOI:10.3350/cmh.2024.0333

AJNR Am J Neuroradiol. 2024 Jul 22:ajnr.A8424. doi: 10.3174/ajnr.A8424. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Accelerated and blood-suppressed post-contrast 3D intracranial vessel wall MRI (IVW) enables high-resolution rapid scanning but is associated with low SNR. We hypothesized that a deep-learning (DL) denoising algorithm applied to accelerated, blood-suppressed post-contrast IVW can yield high-quality images with reduced artifacts and higher SNR in shorter scan times.

MATERIALS AND METHODS: Sixty-four consecutive patients underwent IVW, including conventional post-contrast 3D T1-sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) and delay-alternating with nutation for tailored excitation (DANTE) blood-suppressed and CAIPIRINHIA-accelerated (CAIPI) 3D T1-weighted TSE post-contrast sequences (DANTE-CAIPI-SPACE). DANTE-CAIPI-SPACE acquisitions were then denoised using an unrolled deep convolutional network (DANTECAIPI-SPACE+DL). SPACE, DANTE-CAIPI-SPACE, and DANTE-CAIPI-SPACE+DL images were compared for overall image quality, SNR, severity of artifacts, arterial and venous suppression, and lesion assessment using 4-point or 5-point Likert scales. Quantitative evaluation of SNR and contrast-to-noise ratio (CNR) was performed.

RESULTS: DANTE-CAIPI-SPACE+DL showed significantly reduced arterial (1 [1-1.75] vs. 3 [3-4], p<0.001) and venous flow artifacts (1 [1-2] vs. 3 [3-4], p<0.001) compared to SPACE. There was no significant difference between DANTE-CAIPI-SPACE+DL and SPACE in terms of image quality, SNR, artifact ratings and lesion assessment. For SNR ratings, DANTE-CAIPI-SPACE+DL was significantly better compared to DANTE-CAIPI-SPACE (2 [1-2], vs. 3 [2-3], p<0.001). No statistically significant differences were found between DANTECAIPI-SPACE and DANTE-CAIPI-SPACE+DL for image quality, artifact, arterial blood and venous blood flow artifacts, and lesion assessment. Quantitative vessel wall SNR and CNR median values were significantly higher for DANTE-CAIPI-SPACE+DL (SNR: 9.71, CNR: 4.24) compared to DANTE-CAIPI-SPACE (SNR: 5.50, CNR: 2.64), (p<0.001 for each), but there was no significant difference between SPACE (SNR: 10.82, CNR: 5.21) and DANTE-CAIPI-SPACE+DL.

CONCLUSIONS: Deep-learning denoised post-contrast T1-weighted DANTE-CAIPI-SPACE accelerated and blood-suppressed IVW showed improved flow suppression with a shorter scan time and equivalent qualitative and quantitative SNR measures relative to conventional post-contrast IVW. It also improved SNR metrics relative to post-contrast DANTE-CAIPI-SPACE IVW. Implementing deep-learning denoised DANTE-CAIPI-SPACE IVW has the potential to shorten protocol time while maintaining or improving the image quality of IVW.

ABBREVIATIONS: DL=deep learning; IVW=Intracranial vessel wall MRI; SPACE=sampling perfection with application-optimized contrasts by using different flip angle evolution; DANTE=delay-alternating with nutation for tailored excitation; CAIPI=controlled aliasing in parallel imaging; CNR=contrast-to-noise ratio.

PMID:39038956 | DOI:10.3174/ajnr.A8424

Inj Prev. 2024 Jul 22:ip-2024-045257. doi: 10.1136/ip-2024-045257. Online ahead of print.

ABSTRACT

OBJECTIVES: There has been extensive debate in the USA as to how laws regulating the carrying of concealed firearms affect crime and public safety. This study examines whether US state laws making it easier for civilians to obtain permits to carry concealed handguns in public increase defensive gun uses against violent threats and attacks in public.

METHODS: We used National Crime Victimization Survey data from 39 metropolitan statistical areas (MSAs) in the USA over a 19-year period (1986-2004) to examine whether laws making it easier for civilians to obtain concealed carry permits are linked to higher levels of defensive gun use against violence in public spaces of metropolitan areas. Bivariate χ² tests and multivariate logistic regression models (controlling for actor and situational characteristics) were used with 7196 public incidents to examine whether the likelihood of the victim using a gun against an attacker(s) varied based on the type of concealed carry law in the MSA at the time of the incident.

RESULTS: The prevalence of self-defensive gun use in this sample was not clearly related to the passage of permissive gun carrying laws. Although defensive gun use was more common in MSAs with permissive gun carrying laws, this difference was not consistently related in magnitude or statistical significance to the passage of those laws or the length of time they had been in effect.

CONCLUSIONS: Permissive concealed carry permit laws do not produce evident increases in self-defensive gun uses against crime in public locations.

PMID:39038941 | DOI:10.1136/ip-2024-045257

Inj Prev. 2024 Jul 22:ip-2023-045019. doi: 10.1136/ip-2023-045019. Online ahead of print.

ABSTRACT

OBJECTIVE: Drunk driving is a major cause of road traffic injuries and deaths in Latin America. We evaluated the impact of a drunk driving intervention in Leon, Mexico on road traffic safety.

METHODS: The intervention included increased drunk driving penalties, enhanced sobriety checkpoints and a young adult-focused mass media campaign, beginning 19 December 2018. We created a synthetic control Leon from 12 Mexican municipalities from a pool of 87 based on similarity to Leon using key predictors from 2015 to 2019. We assessed the effect of the intervention on road traffic collisions overall and collisions with injuries, deaths and involving alcohol, using data from police, insurance claims and vital registration.

RESULTS: As compared with the synthetic control, Leon experienced significant postintervention lower police-reported total collision rate (17%) and injury collisions (33%). Alcohol-involved collisions were 38% lower than the synthetic control. Fatal collisions reported by police were 28% lower while vital registration road traffic deaths were 12% lower, though these declines were not statistically significant. We found no impact on insurance collision claims. There was heterogeneity in these changes over the evaluation year, with stronger initial effects and weaker effects by the end of the year.

CONCLUSIONS: Drunk driving policies in Leon led to fewer traffic collisions and injuries during the first year of implementation, with a weakening of this effect over time, similar to interventions in high-income settings and other Latin American countries. Supporting the expansion of similar policies to other cities in the region could improve road safety.

PMID:39038940 | DOI:10.1136/ip-2023-045019

J Immunother Cancer. 2024 Jul 22;12(7):e009278. doi: 10.1136/jitc-2024-009278.

ABSTRACT

BACKGROUND: Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome.

METHODS: In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included ¹⁸F-BMS-986192 (PD-L1) PET and ¹⁸F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology.

RESULTS: Grade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8⁺ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1.

CONCLUSION: Together these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations.

PMID:39038919 | DOI:10.1136/jitc-2024-009278

BMJ Open Respir Res. 2024 Jul 22;11(1):e002401. doi: 10.1136/bmjresp-2024-002401.

ABSTRACT

OBJECTIVES: To investigate the association of early snus use initiation (≤15 years of age) with asthma and asthma symptoms.

DESIGN: Cross-sectional analysis of a population-based cohort.

SETTING: Study centres in Norway, Sweden, Iceland, Denmark and Estonia, from 2016 to 2019.

PARTICIPANTS: 9002 male and female participants above 15 years of age of the Respiratory Health in Northern Europe, Spain and Australia study.

MAIN OUTCOME MEASURES: Current asthma and asthma symptoms.

RESULTS: The median age of study participants was 28 years (range 15-53) and 58% were women. 20% had used snus, 29% men and 14% women. Overall, 26% of males and 14% of females using snus started ≤15 years of age. Early snus use initiation was associated with having three or more asthma symptoms (OR 2.70; 95% CI 1.46 to 5.00) and a higher asthma symptom score (β-coefficient (β) 0.35; 95% CI 0.07 to 0.63) in women. These associations were weak in men (OR 1.23; 95% CI 0.78 to 1.94; β 0.16; 95% CI -0.06 to 0.38, respectively). There was evidence for an association of early snus initiation with current asthma (OR 1.72; 95% CI 0.88 to 3.37 in women; OR 1.31; 95% CI 0.84 to 2.06 in men). A sensitivity analysis among participants without smoking history showed stronger estimates for all three outcomes, in both men and women, statistically significant for three or more asthma symptoms in women (OR 3.28; 95% CI 1.18 to 9.10). Finally, no consistent associations with asthma outcomes were found for starting snus after age 15 years.

CONCLUSIONS: Snus initiation in puberty was associated with higher likelihood of asthma and asthma symptoms, with the highest estimates in females and those without smoking history. These results raise concerns about the health adversities of early snus initiation and emphasise the need for public health initiatives to protect young people from this tobacco product.

PMID:39038916 | DOI:10.1136/bmjresp-2024-002401

BMJ Open Respir Res. 2024 Jul 22;11(1):e002029. doi: 10.1136/bmjresp-2023-002029.

ABSTRACT

INTRODUCTION: Disability, resulting from altered interactions between individuals and their environment, is a worldwide issue causing inequities and suffering. Many diseases associated with breathlessness cause disability but the relationship between disability and the severity of breathlessness itself is unknown.This study evaluated associations between disability using the WHO’s Disability Assessment Schedule (WHODAS) 2.0 and levels of long-term breathlessness limiting exertion.

METHODS: This population-based, cross-sectional online survey (n=10 033) reflected the most recent national census (2016) by age, sex, state/territory of residence and rurality. Assessments included self-reported disability (WHODAS 2.0 12-item (range 12 (no disability) to 60 (most severe disability)) assessed in 6 domains) and long-term breathlessness limiting exertion (modified Medical Research Council (mMRC) breathlessness scale; 0-4 (4-most severe)). Days in the last month affected by breathlessness were reported.

RESULTS: Of respondents (52% women; mean age 45), mean total disability score was 20.9 (SD 9.5). 42% (n=4245) had mMRC >0 (mMRC1 31% (n=3139); mMRC2 8% (n=806); mMRC3,4 3% (n=300)). Every level of long-term breathlessness limiting exertion was associated with greater levels of disability (total p <0.001; each domain p <0.001). The most compromised domains were Mobility and Participation.In the last 30 days, people with severe breathlessness (mMRC 3-4): experienced disability (20 days); reduced activities/work (10 days); and completely forwent activities (another 5 days).

CONCLUSIONS: Disability should be in the definition of persistent breathlessness as it is systematically associated with long-term breathlessness limiting exertion in a grade-dependent, multidimensional manner. Disability should be assessed in people with long-term breathlessness to optimise their social well-being and health.

PMID:39038915 | DOI:10.1136/bmjresp-2023-002029

BMJ Paediatr Open. 2024 Jul 22;8(1):e002365. doi: 10.1136/bmjpo-2023-002365.

ABSTRACT

INTRODUCTION: Treatment in the intensive care unit (ICU) generates complex data where machine learning (ML) modelling could be beneficial. Using routine hospital data, we evaluated the ability of multiple ML models to predict inpatient mortality in a paediatric population in a low/middle-income country.

METHOD: We retrospectively analysed hospital record data from 0-59 months old children admitted to the ICU of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. Five commonly used ML models- logistic regression, least absolute shrinkage and selection operator, elastic net, gradient boosting trees (GBT) and random forest (RF), were evaluated using the area under the receiver operating characteristic curve (AUROC). Top predictors were selected using RF mean decrease Gini scores as the feature importance values.

RESULTS: Data from 5669 children was used and was reduced to 3505 patients (10% death, 90% survived) following missing data removal. The mean patient age was 10.8 months (SD=10.5). The top performing models based on the validation performance measured by mean 10-fold cross-validation AUROC on the training data set were RF and GBT. Hyperparameters were selected using cross-validation and then tested in an unseen test set. The models developed used demographic, anthropometric, clinical, biochemistry and haematological data for mortality prediction. We found RF consistently outperformed GBT and predicted the mortality with AUROC of ≥0.87 in the test set when three or more laboratory measurements were included. However, after the inclusion of a fourth laboratory measurement, very minor predictive gains (AUROC 0.87 vs 0.88) resulted. The best predictors were the biochemistry and haematological measurements, with the top predictors being total CO₂, potassium, creatinine and total calcium.

CONCLUSIONS: Mortality in children admitted to ICU can be predicted with high accuracy using RF ML models in a real-life data set using multiple laboratory measurements with the most important features primarily coming from patient biochemistry and haematology.

PMID:39038911 | DOI:10.1136/bmjpo-2023-002365

Int J Radiat Oncol Biol Phys. 2024 Aug 1;119(5):1344-1346. doi: 10.1016/j.ijrobp.2024.02.051.

NO ABSTRACT

PMID:39038908 | DOI:10.1016/j.ijrobp.2024.02.051