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Heated tobacco products (HTPs) are a recent category of tobacco products, with their relative safety compared to cigarette smoking and potential to help smokers to quit being two reasons why regulators may consider their market approval. Designed to heat tobacco rather than to burn in order to produce aerosol, different heating techniques are applied to commercial HTPs, which may result in differing aerosol formation. Therefore, each product requires separate assessment. This work focuses on a closed-end HTP (coded as HTP-A), which is electrically heated and designed to allow puffing air flow to bypass its tobacco section, resulting in reduced oxygen concentration within the tobacco section during heating and aerosol forming. To provide a preliminary aerosol chemistry and in vitro toxicological screening, this study assessed HTP-A against a commercial electrically heated HTP (IQOSTM, coded as HTP-B) and a 3R4F reference cigarette. Under Health Canada Intense (HCI) smoking regime, the levels of 9 regulatory priority toxicants in the aerosol of HTP-A were either reduced or comparable to those in HTP-B on a per-stick basis. Additionally, both HTPs showed significant reduction (greater than 90%) in comparison to those measured in mainstream smoke of 3R4F cigarette for these toxicants. Using a set of standard in vitro toxicological assays (Ames, Micronucleus and Neutral Red Uptake), the two HTPs showed no observable responses while significant toxicity responses were recorded for 3R4F’s total particulate matter. Based on these preliminary results, the novel closed-end HTP-A design may provide similar toxicological profiles to the comparator HTP-B. Further toxicological and clinical assessments are warranted to evaluate HTP-A’s potential for exposure or disease risk reduction. [Contrib. Tob. Nicotine Res. 32 (2023) 146–156]

BackgroundSevere traumatic brain injuries (TBIs) are an important health issue worldwide, which are associated with harmful side effects. This meta-analysis investigates the cognitive and functional outcomes in severe brain trauma cases. It assesses the impact on memory, verbal and visual abilities, attention, learning, and the presence of depression. The study provides a comprehensive overview of the consequences of severe brain trauma injury on cognitive and functional domains.ObjectiveThe main objective of the current comprehensive meta-analysis study is to assess and analyze the impact of severe TBI on functional and cognitive outcomes, including verbal, visual, attention, learning, memory, and emotional stability.MethodsWe collected data from three online databases, including PubMed, Cochrane Library, and Embase. Case–control trials related to severe TBI association with cognitive and functional outcomes were included. Verbal strength, visual functions, learning abilities, attention, memory, and depression were considered primary outcomes.ResultsWe have included 13 case–control studies with 1,442 subjects in this meta-analysis, which provide adequate data to determine the pooled effect size for targeted outcomes. The effect of severe TBI on the inducement of depression and impairment of memory, verbal, visual, attention, and learning abilities compared to the control group showed statistically significant outcomes (p

Freeze casting is an attractive method for designing lamellar ceramic-aluminum composites with a unique combination of strength and toughness. However, there are few studies on the detailed mechanical properties, especially wear resistance, of lamellar Ti(C,N)/Al–Cu composites. Herein, nacre-inspired Ti(C,N)/Al–Cu composites are fabricated via freeze and squeeze casting, and their mechanical and frictional wear properties are investigated. The results show that compressive strength, bending strength, crack-initiation toughness (KIC), and crack-growth toughness (KJC) of composites are 769.2–996.8 MPa, 547.8 MPa, 13.9 MPa m1/2, and 31.1 MPa m1/2, respectively. The achieved strength and toughness are higher than those of most nacre-inspired ceramic/Al composites. The high damage tolerance is affected by interface binding strength between Ti(C,N) and Al, as well as multiple mechanisms. Moreover, friction and wear properties of composites exhibit obvious anisotropy and the transverse section, i.e., perpendicular to freeze direction, exhibits the best wear resistance with a wear rate of only 0.98 × 10−4 mm3/Nm. This anisotropy can be attributed to the different arrangements of ceramic layers on the different sections, which affects their bearing capacity.

The rail corrugation will lead to noise pollution and abnormal vibration in the railway operation process which greatly influences the safety, comfort, and stability of the train operation. However, although the advantages of abrasive belt rail grinding in repairing rail diseases have been verified, there is still no relative grinding control strategy for rail corrugation repair process due to its characteristics of regionality and no grinding benchmark. Therefore, this paper analyzed the difference between the grinding process of rail corrugation and ideal rail surface, and established material removal model for repairing of rail corrugation. By comparing the average valid value of moving wave amplitude and the improvement degree of rail corrugation, the most suitable grinding control strategies for repairing different types of corrugation diseases were obtained, which can further improve the grinding quality and efficiency of abrasive belt rail grinding in repairing rail corrugation. [ABSTRACT FROM AUTHOR]

Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam‐like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of L‐oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double‐blind, parallel‐group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: L‐oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow‐up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that L‐oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565. [ABSTRACT FROM AUTHOR]

Although first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is effective for treating EGFR-mutant non-small cell lung cancer (NSCLC), it is now understood that drug-tolerant persister (DTP) cells escaping from initial treatment eventually drives drug resistance. Here, through integration of metabolomics and transcriptomics, we found that the neurotransmitter acetylcholine (ACh) was specifically accumulated in DTP cells, and demonstrated that treatment with EGFR-TKI heightened the expression of the rate-limiting enzyme choline acetyltransferase (ChAT) in ACh biosynthesis via YAP mediation. Genetic and pharmacological manipulation of ACh biosynthesis or ACh signaling could predictably regulate the extent of DTP formation in vitro and in vivo. Strikingly, pharmacologically targeting ACh/M3R signaling with an FDA-approved drug, darifenacin, retarded tumor relapse in vivo. Mechanistically, upregulated ACh metabolism mediated drug tolerance in part through activating WNT signaling via ACh muscarinic receptor 3 (M3R). Importantly, we showed that aberrant ACh metabolism in patients with NSCLC played a potential role in predicting EGFR-TKI response rate and progression-free survival. Our study therefore defines a therapeutic strategy--targeting the ACh/M3R/WNT axis--for manipulating EGFR TKI drug tolerance in the treatment of NSCLC., Introduction Patients with non-small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) clearly benefit from EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy (1). However, like other [...]

Aim: We aim to identify the specific CD4+ T‐cell subtype influenced by brain‐to‐CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). Method: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T‐cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time‐of‐flight analysis (CyTOF) or fluorescence‐activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) staining. Results: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b‐positive CD4+ T cells, within the affected region. The population of CD4+CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine‐1‐phosphate receptor‐1 (S1PR1) on these cells. Administration of CD4+CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. Conclusion: The infiltration of CD4+CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain‐to‐CLN signaling. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity < 0.40). Additionally, our machine learning-derived prognostic model demonstrates superior performance to traditional models utilizing clinical parameters and effectively stratifies patients into different risk groups to guide precision interventions. Collectively, our findings reveal the metabolic landscape of GC and identify two distinct biomarker panels that enable early detection and prognosis prediction respectively, thus facilitating precision medicine in GC. Gastric cancer detection by endoscopy is intrusive and time-consuming, and early detection is key to improving survival. Here, the authors propose a metabolite-based model to enable early detection. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone. [ABSTRACT FROM AUTHOR]

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Background: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. Methods/design: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. Result: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. Conclusion: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. Trial registration: ChiCTR2200057179 [ABSTRACT FROM AUTHOR]

Nowadays, piezoelectric nanogenerators (PENGs) based on poly-(vinylidene fluoride) (PVDF) have exhibited extensive potential applications in wearable electronics. Improving the piezoelectric performance of PVDF-based PENGs through low-cost and nontoxic fillers is an attractive technology for industrial applications. Herein, we propose a superior piezoelectric performance of PVDF-based PENG with cheap and nontoxic TiO2 nanorods as the regulated fillers. The built-in electric field of the constructed heterostructures in mixed-phase (anatase–rutile) TiO2 nanorods enriches the formation of electroactive β-phase (87.6%) in PVDF. Moreover, the piezoelectric output of the TiO2@PVDF-based PENG (TP-PENG) reaches 42.5 V, which is 15.7 times higher than the pure PVDF-based PENG with the same electrospinning process. The TP-PENG exhibits superior durability within 9000 cycles, being capable of charging the capacitors, powering the diode light-emitting diode (LED) lights, and monitoring real-time human movements. This promotes the great potential of the PENG for a variety of applications, including biomechanical energy harvesting, motion sensing, and powering microelectronic devices. Most importantly, this study demonstrates that the strategy of controlling phase transition and switching between crystal structures is of great relevance to extending the kinds of possible regulating fillers to enhance the performance of PVDF-based PENGs. It provides a promising low-cost and nontoxic approach for the development of high-performance PENGs. [ABSTRACT FROM AUTHOR]

Due to the difficulties in designing sensor arrays with a wide detection range, high sensitivity, and the sensing ability to convert tangential force into normal force on the same substrate, the integration of shape and texture recognitions in one electronic skin (e‐skin) has not been realized so far. Herein, an e‐skin tactile‐sensing system is presented, based on resistive pressure‐sensing units (serving as Meissner corpuscles) unevenly distributed on a bionic hand‐shaped polyimide substrate, which can realize shape and texture recognitions concurrently. A multilayer microporous structure with different pores is designed and introduced into the sensor, which enables each sensing unit ultrahigh sensitivity and a wide detection range. Meanwhile, a customized micro‐pyramid array is developed and assembled to the sensor array, which realizes the transformation from tangential force to normal force. With the help of artificial intelligence technology, the recognition accuracy reaches 100% for 8 different shapes, and 99.7% for 10 different textures, respectively. The proposed design strategy enables compatible fabrication, simple signal processing, and convenient extension of bionic free‐shaped e‐skin, which paves a promising way for the popularization of e‐skin in large‐scale intelligent wearable fields. [ABSTRACT FROM AUTHOR]