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In this work, a microwave-enhanced air-assisted liquid-liquid microextraction method combined with gas chromatography-mass spectrometry has been developed for morphine and oxymorphone assessment in EBC samples. For this purpose, choline chloride-menthol-phenylacetic acid deep eutectic solvent (as an extraction solvent), butyl chloroformate (as a derivatization agent), and picoline (as a catalyst) are used. After performing predetermined extraction cycles in the microextraction method, the obtained cloudy solution is exposed to microwave irradiations to enhance extraction and derivatization efficiencies. The method provided low limits of detection (morphine 2.1 and oxymorphone 1.5 ng mL-1) and quantification (morphine 7.2 and oxymorphone 5.2 ng mL-1) in the EBC samples. The method had proper repeatability, accuracy, and stability expressed as relative standard deviations less than 5.1, 9, and 9%, respectively. The developed method was successfully used to determine morphine and oxymorphone concentrations in the EBC samples of addict patients.This study concerns procedural aspects of planar biaxial experiments on aortic tissues that have not been exhaustively addressed in the literature. The following questions are explored. First, is there a difference in the apparent mechanical properties if the experiments are conducted in a force-controlled regime or a displacement-controlled regime. Second, does it matter whether the deformations of the surface are tracked from one side of the tissue or the other (luminal vs. abluminal surface). The study provides answers to these questions with the help of a series of experiments on porcine aortic tissue, constitutive modelling and statistical analysis. It was found that the loading protocol does not substantially affect the constitutive response, while the surface orientation does.Chronic Obstructive Pulmonary Disease (COPD) is a highly heterogeneous condition projected to become the third leading cause of death worldwide by 2030. To better characterize this condition, clinicians have classified patients sharing certain symptomatic characteristics, such as symptom intensity and history of exacerbations, into distinct phenotypes. In recent years, the growing use of machine learning algorithms, and cluster analysis in particular, has promised to advance this classification through the integration of additional patient characteristics, including comorbidities, biomarkers, and genomic information. This combination would allow researchers to more reliably identify new COPD phenotypes, as well as better characterize existing ones, with the aim of improving diagnosis and developing novel treatments. Here, we systematically review the last decade of research progress, which uses cluster analysis to identify COPD phenotypes. Collectively, we provide a systematized account of the extant evidence, describe the strengths and weaknesses of the main methods used, identify gaps in the literature, and suggest recommendations for future research.Despite the high prevalence of Kirsten rat sarcoma (KRAS) mutations in non-small cell lung cancer (NSCLC), for a long time it has been defined as an 'undruggable target', with precision medicine not considered as an adequate approach to treat this subgroup of patients. After several years of efforts, preliminary data from early clinical trials have recently demonstrated that direct pharmacological inhibition of KRAS p.G12C mutation is possible, emerging as an effective targeted treatment for about 10-12% of patients with advanced NSCLC, with potential relevant impact on their long-term survival and quality of life. This review reports the current status of KRAS mutations detection in the Italian real-word scenario, summarises the biological basis of KRAS inhibition in NSCLC and provides an updated overview of therapeutic strategies, discussing the potential reasons for past failures and analysing the upcoming challenges related to the advent of new targeted agents in clinical practice.
There is a lack of large-scale randomised data evaluating the impact of sex and age in patients undergoing chemotherapy followed by potentially curative surgery for oesophagogastric cancer.
Individual patient data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival analysis, hazard ratios (HRs) were calculated for patients aged <70 and≥70 years, as well as between males and females. Mandard tumour regression grade (TRG) and, ≥grade III toxicities were compared using logistic regression models to calculate odds ratios. All analyses were adjusted for the type of chemotherapy received.
3265 patients were included for survival analysis (2668 [82%] male, 597 [18%] female; 2627 (80%) <70 years, 638 (20%) ≥70 years). A significant improvement in overall survival (OS) (HR 0.78; p<0.001) and disease-specific survival (DSS) (HR 0.78; p<0.001) was observed in females compared with males. No significant differences in OS (HR 1.11; p=0.045) or DSS paradigm.In recent years, miRNAs had emerged as promising biomarkers for diagnosis and prognosis of the health-threatening diseases (e.g., cancers), which associated with a broad range of pathological and biological processes, including drug resistance, apoptosis, metastasis, and proliferation. Therefore, accurate detection of the levels of miRNA shown excellent prospects for early diagnosis of the health-threatening diseases. Considering that only trace miRNA existed in biological fluids, many newly developed biosensors for miRNA detection mainly focused on introducing various of signal amplification strategies for improving the detection sensitivity. Duplex-specific nuclease (DSN), a nuclease purified from hepatopancreas of Kamchatka crab, was capable of specifically cleaving double-stranded DNA or DNA in DNA-RNA heteroduplexes and was inactive toward single-stranded oligonucleotides or double-stranded RNA, endowing a possibility for construction of newly miRNA biosensors. Recently, many newly developed DSN-based biosensors architectures for miRNA analysis were reported. In this review, we explained the great potential of miRNAs as promising biomarkers by overviewing DSN-based signal amplification strategies for miRNA detection in the last decades.
Cardiac structure and function in dogs are commonly assessed using echocardiography. A variety of linear, area, and flow-based measurements can be used to calculate left ventricular (LV) total stroke volume (TSV) and forward stroke volume (FSV), but the reproducibility of many of these measurements has not been fully studied. We hypothesized that survey of echocardiographic variables would identify those with high reproducibility and inform future investigation of different methods to measure LV TSV and FSV.
The reproducibility of 25 geometric and flow-based echocardiographic measurements was prospectively evaluated in 23 healthy dogs by two experienced observers. Reproducibility (i.e., interobserver agreement) was described using intraclass correlation coefficients. The reproducibility of various methods to calculate LV TSV and FSV was explored.
Reproducibility was generally good to excellent. Variables of LV width, length, and area and aortic and sinotubular junction diameter and velocity time integraogs.Few studies have described chimeric antigen receptor-modified T cell (CAR-T) therapy for central nervous system (CNS) B-cell acute lymphocytic leukemia (B-ALL) patients due to life-threatening CAR-T-related encephalopathy (CRES) safety issues. In this study, CAR-Ts targeting CD19 with short hairpin RNA (shRNA)-IL-6 gene silencing technology (ssCART-19s) were prepared. We conducted a phase 1 clinical trial (ClinicalTrials.gov number, NCT03064269). Three patients with relapsed CNS B-ALL were enrolled, conditioned with the fludarabine and cyclophosphamide for lymphocyte depletion and infused with ssCART-19s for three consecutive days. click here Clinical symptoms and laboratory examinations were monitored. After ssCART-19 treatment, three patients' symptoms resolved almost entirely. Brain leukemic infiltration reduced significantly based on magnetic resonance imaging (MRI), and there were no leukemic blasts in cerebrospinal fluid (CSF), which was confirmed by cytological and molecular examinations. Additionally, increases in the levels of cytokines and immune cells were observed in the CSF of all patients. Only grade 1 cytokine release syndrome (CRS) manifesting as fever was noted in patients. In conclusion, CAR-Ts with shRNA-IL-6 gene knockdown migrated into the CNS, eradicated leukemic cells and elevated cytokines in CSF with mild, acceptable side effects.
In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES.
We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databaseurvey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.
Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.
Resting-state (rs) network dysfunction is a contributing factor to treatment resistance in epilepsy. In treatment-resistant epilepsy (TRE), pharmacological and nonpharmacological therapies have been shown to improve such dysfunction. In this study, our goal was to prospectively evaluate the effect of highly purified plant-derived cannabidiol (CBD; Epidiolex®) on rs functional magnetic resonance imaging (fMRI) functional connectivity (rs-FC). We hypothesized that CBD would change and potentially normalize the rs-FC in TRE.
Twenty-two of 27 participants with TRE completed all study procedures including longitudinal pre-/on-CBD rs-fMRI (8M/14F, mean age = 36.2 ± 15.9 years, TRE duration = 18.3 ± 12.6 years); there were no differences in age (p = 0.99) or sex (p = 0.15) between groups. Assessments collected included seizure frequency (SF), Chalfont Seizure Severity Scale (CSSS), Columbia Suicide Severity Rating Scale (C-SSRS), Adverse Events Profile (AEP), and Profile of Mood States (POMS). Twenty-three healthy controls (HCs) received rs-fMRI and POMS once.
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