Regulating Surface Dipole Moments of TiO2 for the pH-Universal Cathodic Fenton-Like Process.

Although electro-Fenton (EF) processes can avoid the safety risks raised by concentrated hydrogen peroxide (H2O2), the Fe(III) reduction has always been either unstable or inefficient at high pH, resulting in catalyst deactivation and low selectivity of H2O2 activation for producing hydroxyl radicals (•OH). Herein, we provided a strategy to regulate the surface dipole moment of TiO2 by Fe anchoring (TiO2-Fe), which, in turn, substantially increased the H2O2 activation for •OH production. The TiO2-Fe catalyst could work at pH 4-10 and maintained considerable degradation efficiency for 10 cycles. Spectroscopic analysis and a theoretical study showed that the less polar Fe-O bond on TiO2-Fe could finely tune the polarity of H2O2 to alter its empty orbital distribution, contributing to better ciprofloxacin degradation activity within a broad pH range. We further verified the critical role of the weakened polarity of H2O2 on its homolysis into •OH by theoretically and experimentally investigating Cu-, Co-, Ni-, Mn-, and Mo-anchored TiO2. This concept offers an avenue for elaborate design of green, robust, and pH-universal cathodic Fenton-like catalysts and beyond.

Dual-mode fluorescence and colorimetric smartphone-based sensing platform with oxidation-induced self-assembled nanoflowers for sarcosine detection.

BACKGROUND: Early prostatic cancer (PCa) diagnosis significantly improves the chances of successful treatment and enhances patient survival rates. Traditional enzyme cascade-based early cancer detection methods offer efficiency and signal amplification but are limited by cost, complexity, and enzyme dependency, affecting stability and practicality. Meanwhile, sarcosine (Sar) is commonly considered a biomarker for PCa development. It is essential to develop a Sar detection method based on cascade reactions, which should be efficient, low skill requirement, and suitable for on-site testing. RESULTS: To address this, our study introduces the synthesis of organic-inorganic self-assembled nanoflowers to optimize existing detection methods. The Sar oxidase (SOX)-inorganic hybrid nanoflowers (Cu3(PO4)2:Ce@SOX) possess inherent fluorescent properties and excellent peroxidase activity, coupled with efficient enzyme loading. Based on this, we have developed a dual-mode multi-enzyme cascade nanoplatform combining fluorescence and colorimetric methods for the detection of Sar. The encapsulation yield of Cu3(PO4)2:Ce@SOX reaches 84.5 %, exhibiting a remarkable enhancement in catalytic activity by 1.26-1.29 fold compared to free SOX. The present study employing a dual-signal mechanism encompasses 'turn-off' fluorescence signals ranging from 0.5 µM to 60 µM, with a detection limit of 0.226 µM, and 'turn-on' colorimetric signals ranging from 0.18 µM to 60 µM, with a detection limit of 0.120 µM. SIGNIFICANCE: Furthermore, our study developed an intelligent smartphone sensor system utilizing cotton swabs for real-time analysis of Sar without additional instruments. The nano-platform exhibits exceptional repeatability and stability, rendering it well-suited for detecting Sar in authentic human urine samples. This innovation allows for immediate analysis, offering valuable insights for portable and efficient biosensors applicable to Sar and other analytes.

Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) patients with various nucleophosmin 1 (NPM1) mutations are controversial in the prognosis. This study aimed to investigate the prognosis of patients according to types of NPM1 mutations (NPM1mut). METHODS: Bone marrow samples of 528 patients newly diagnosed with AML, were collected for morphology, immunology, cytogenetics, and molecular biology examinations. Gene mutations were detected by next-generation sequencing (NGS) technology. RESULTS: About 25.2% of cases exhibited NPM1mut. 83.5% of cases were type A, while type B and D were respectively account for 2.3% and 3.0%. Furthermore, 15 cases of rare types were identified, of which 2 cases have not been reported. Clinical characteristics were similar between patients with A-type NPM1 mutations (NPM1A - type mut) and non-A-type NPM1 mutations (NPM1non - A-type mut). Event-free survival (EFS) was significantly different between patients with low NPM1non - A-type mut variant allele frequency (VAF) and low NPM1A - type mut VAF (median EFS = 3.9 vs. 8.5 months, P = 0.020). The median overall survival (OS) of the NPM1non - A-type mutFLT3-ITDmut group, the NPM1A - type mutFLT3-ITDmut group, the NPM1non - A-type mutFLT3-ITDwt group, and the NPM1A - type mutFLT3-ITDwt group were 3.9, 10.7, 17.3 and 18.8 months, while the median EFS of the corresponding groups was 1.4, 5.0, 7.6 and 9.2 months (P < 0.0001 and P = 0.004, respectively). CONCLUSIONS: No significant difference was observed in OS and EFS between patients with NPM1A - type mut and NPM1non - A-type mut. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Maternal selenium deficiency during pregnancy in association with autism and ADHD traits in children: the Odense Child Cohort.

BACKGROUND: Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. METHODS: 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9 +/- 0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. RESULTS: 155 of 719 (21.6%) children had ASD traits and 59 of 719 (8.2%) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 µg/L increment in selenium was 0.76 (95% CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 µg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. CONCLUSIONS: The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.

Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM: To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS: A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS: Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION: This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.

Impact of tocilizumab on anti-CD19 chimeric antigen receptor T-cell therapy in B-cell acute lymphoblastic leukemia.

BACKGROUND: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T-cell therapy-associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy. METHODS: In total, 93 patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving humanized anti-CD19 CAR T cells were recruited from May 2016 to November 2022. Forty-five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab. RESULTS: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event-free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell-associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells. CONCLUSIONS: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS.

A Fully Metaoptical Zoom Lens with a Wide Range.

Metalenses are typically designed for a fixed focal length, restricting their functionality to static scenarios. Various methods have been introduced to achieve the zoom function in metalenses. These methods, however, have a very limited zoom range, or they require additional lenses to achieve direct imaging. Here, we demonstrate a zoom metalens based on axial movement that performs both the imaging and the zoom function. The key innovation is the use of a polynomial phase profile that mimics an aspheric lens, which allows an extended depth of focus, enabling a large zoom range. Experimental results show that this focal length variation, combined with the extended depth of focus, translates into an impressive zoom range of 11.9× while maintaining good imaging quality. We see applications for such a zoom metalens in surveillance cameras of drones or microrobots to reduce their weight and volume, thus enabling more flexible application scenarios.

Individualized nutritional intervention improves the nutritional status of liver cancer patients after transcatheter arterial chemoembolization.

INTRODUCTION: to explore the effect of individualized nutritional intervention on the nutritional status of patients with liver cancer after transcatheter arterial chemoembolization (TACE). METHODS: 56 patients who underwent TACE in our hospital from March 2022 to March 2023 were selected as the study subjects. The patients were randomly divided into a control group (28 cases) and an intervention group (28 cases). The control group received routine dietary intervention, while the intervention group received individualized nutritional intervention. We analyzed the body mass index (BMI), nutritional risk screening 2002 (NRS 2002), nutritional status, liver function status, and incidence of complications in two groups of patients before TACE, 3 days after TACE, and 1 month after TACE. RESULTS: on the third day after TACE, the nutritional related indicators of both groups of patients showed a significantly decrease compared to those before TACE (p < 0.05), while the majority of liver function indicators significantly increased (p < 0.05). Compared with those at 3 days after TACE, the nutritional status of the intervention group patients significantly improved (p < 0.05) and liver function indicators significantly decreased (p < 0.05) 1 month after TACE. 1 month after TACE, all nutritional indicators in the intervention group were significantly higher than those in the control group (p < 0.05), and AST was significantly lower than that in the control group (p < 0.05). The incidence of gastrointestinal complications and electrolyte disorders in the intervention group were significantly lower than that in the control group (p < 0.05). Conclusion Individualized nutritional intervention can effectively improve nutritional status, improve liver function, and reduce the incidence of postoperative complications in liver cancer patients after TACE. It was worth promoting.

Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice.

Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and that patients with chronically poor sleep undergo an accelerated cognitive decline. Indeed, a single-night of sleep deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how chronic sleep disturbances in isolation from an underlying neurological disease may affect the glymphatic system. Clearance of brain interstitial waste by the glymphatic system occurs primarily during sleep, driven by multiple oscillators including arterial pulsatility, and vasomotion. Herein, we induced sleep fragmentation in young wildtype mice and assessed the effects on glymphatic activity and cognitive functions. Chronic sleep fragmentation reduced glymphatic function and impaired cognitive functions in healthy mice. A mechanistic analysis showed that the chronic sleep fragmentation suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results of this study document that chronic sleep fragmentation suppresses brain metabolite clearance and impairs cognition, even in the absence of disease.

Recent progress on charge transfer engineering in reticular framework for efficient electrochemiluminescence.

Electrochemiluminescence (ECL) is a luminescence production technique triggered by electrochemistry, which has emerged as a powerful analytical technique in bioanalysis and clinical diagnosis. During ECL, charge transfer (CT) is an important process between electrochemical excitation and luminescent emission, and dramatically affects the efficiency of exciton generation, playing a pivotal role in the light-emitting properties of nanomaterials. Reticular framework materials with intramolecular/intermolecular interactions offer a promising platform for regulating CT pathways and enhancing luminescence efficiency. Deciphering the role of intramolecular/intermolecular CT processes in reticular framework materials allows for the targeted design and synthesis of emitters with precisely controlled CT properties. This sheds light on the microscopic mechanisms of electro-optical conversion in ECL, propelling advancements in their efficiency and breakthrough applications. This mini-review focuses on recent advancements in engineering CT within reticular frameworks to boost ECL efficiency. We summarized strategies including intra-reticular charge transfer, CT between the metal and ligands, and CT between guest molecules and frameworks within reticular frameworks, which holds promise for developing next-generation ECL devices with enhanced sensitivity and light emission.

A prefrontal motor circuit initiates persistent movement.

Persistence reinforces continuous action, which benefits animals in many aspects. Diverse information may trigger animals to start a persistent movement. However, it is unclear how the brain decides to persist with current actions by selecting specific information. Using single-unit extracellular recordings and opto-tagging in awake mice, we demonstrated that a group of dorsal mPFC (dmPFC) motor cortex projecting (MP) neurons initiate a persistent movement selectively encoding contextual information rather than natural valence. Inactivation of dmPFC MP neurons impairs the initiation and reduces neuronal activity in the insular and motor cortex. Finally, a computational model suggests that a successive sensory stimulus acts as an input signal for the dmPFC MP neurons to initiate a persistent movement. These results reveal a neural initiation mechanism on the persistent movement.

Linc01588 deletion inhibits the malignant biological characteristics of hydroquinone-induced leukemic cells via miR-9-5p/SIRT1.

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9-5p, miR-9-5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9-5p, miR-9-5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9-5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9-5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9-5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL.

Sparse-view cone-beam computed tomography iterative reconstruction based on new multi-gradient direction total variation.

AIM: The accurate reconstruction of cone-beam computed tomography (CBCT) from sparse projections is one of the most important areas for study. The compressed sensing theory has been widely employed in the sparse reconstruction of CBCT. However, the total variation (TV) approach solely uses information from the i-coordinate, j-coordinate, and k-coordinate gradients to reconstruct the CBCT image. MATERIALS AND METHODS: It is well recognized that the CBCT image can be reconstructed more accurately with more gradient information from different directions. Thus, this study introduces a novel approach, named the new multi-gradient direction total variation minimization method. The method uses gradient information from the ij-coordinate, ik-coordinate, and jk-coordinate directions to reconstruct CBCT images, which incorporates nine different types of gradient information from nine directions. RESULTS: This study assessed the efficacy of the proposed methodology using under-sampled projections from four different experiments, including two digital phantoms, one patient's head dataset, and one physical phantom dataset. The results indicated that the proposed method achieved the lowest RMSE index and the highest SSIM index. Meanwhile, we compared the voxel intensity curves of the reconstructed images to assess the edge structure preservation. Among the various methods compared, the curves generated by the proposed method exhibited the highest level of consistency with the gold standard image curves. CONCLUSION: In summary, the proposed method showed significant potential in enhancing the quality and accuracy of CBCT image reconstruction.

The impact of housing prices and land financing on economic growth: Evidence from Chinese 277 cities at the prefecture level and above.

With the rapid progress of urbanization in China, the real estate industry, characterized by a long industrial chain, has become a pillar industry for economic development. Therefore, we inspect the nexus between land finance, housing prices, and economic growth. For this purpose, we use the panel data of 277 cities at the prefecture level or above in China from 2011 to 2019, and empirically examine it by using the Panel Vector Auto Regression (PVAR) model. The results show that there is a causal relationship between housing prices and economic growth. Housing prices promote economic growth in the short term and inhibit it in the long term. Both economic growth and housing prices have a significant impact on land finance. The economic growth show a significantly positive impact, while housing prices promote land finance in the short term with a long-term trend from positive to negative. This is the first study that tries to probe the relationship between urban housing prices, land finance, and economic growth by considering 277 prefecture-level and above cities in China. To promote the stable development of the regional economy, local governments need to overcome their dependence on the housing market and land finance and promote the healthy development of the housing market.

Predicting the bioavailability of polycyclic aromatic hydrocarbons in rhizosphere soil using a new novel in situ solid-phase microextraction technique.

In situ measurement of the bioavailability of organic pollutants in soil is crucial for understanding their environmental behavior and assessing health risks. Due to the high heterogeneity of soil, microscale determination is crucial for achieving high accuracy, but few methods are available. In this study, microsized probes coated with polydimethylsiloxane (PDMS) were used to measure the bioavailability of polycyclic aromatic hydrocarbons (PAHs) in soil in situ. The concentrations of PAHs enriched by the PDMS-coated probes correlated well with the results of bioassays using earthworms (R2 = 0.92-0.99) and ryegrass roots (R2 = 0.92-0.99). Compared with other chemical extraction methods, such as n-butanol extraction, the proposed method has advantages such as in situ operation, microvolume analysis, and negligible interference to the soil environment. In the soil rhizosphere zone, PAHs bioavailability decreased in the following order: rhizosphere > near-rhizosphere > far-rhizosphere. The bioavailability of PAHs in soil amended with biochar was also successfully characterized by the proposed method. Thus, this study developed an in situ and microscale method to predict the bioavailability of organic pollutants in contaminated soils and provides new insight into migration and transformation processes in rhizosphere soil.

Salidroside prevents gestational hypertension-induced impairment of offspring learning and memory via Wnt/Skp2 pathway.

BACKGROUND: Salidroside (Sal) has been found to protect against multiple impairments caused by diabetes, and we designed this study to investigate the effect of Sal on gestational hypertension (GHP)-induced impairment of offspring learning and memory. METHODS: We established a GHP rat model by intraperitoneal injection of NG-nitro-L-arginine methyl ester (L-NAME), and treated with Sal by daily gavage. We used Morris Water Maze test to evaluate the learning and memory ability of offspring rats. HE staining was used to measured the pathological changes in hippocampus of offspring. Immunohistochemistry, cellular immunofluorescence and western blot were used to detect the protein expression. RESULTS: The learning and memory abilities of GHP offspring rats were significantly lower than those of normal rat offspring, while Sal treatment could significantly improve the learning and memory abilities of GHP offspring rats. HE staining did not reveal pathological differences in the hippocampus of normal rats, GHP rats and Sal-treated GHP offspring rats. However, Sal treatment can significantly increase the expression of Wnt1 and Skp2 protein, and decrease the expression of P27kiwf and P21waf1 protein in the hippocampus of GHP offspring rats. In vitro, Sal significantly promoted the proliferation and differentiation on neural stem cell, while Wnt1 knockdown could reverse these promotions by Sal. In the hippocampus of GHP offspring rats, Sal treatment significantly increased the expression of Tuj1, SOX2, Ki67 and DCX protein. CONCLUSION: Salidroside significantly improves the learning and memory impairment of offspring caused by GHP, and its mechanism may be related to the fact that Salidroside promotes the proliferation and differentiation of neural stem cells by activating the Wnt1/Skp2 signaling pathway.

Near-Infrared Absorbing BODIPY-Xanthene Hybrids for Multiplexed Photoacoustic Imaging.

We report a series of ethenylene-bridged D-π-A BODIPY-xanthene hybrid dyes with precisely regulated absorption bands ranging from the far-red to the near-infrared region (NIR, 700-1000 nm) through rational molecular design. These dyes have excellent photoacoustic properties, and their biocompatibility can be significantly improved by facilely introducing water-soluble groups. In vivo two-channel multiplexed photoacoustic imaging demonstrated their high-resolution imaging capabilities, making them promising candidates for future NIR bioimaging applications.

Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma.

OBJECTIVE: Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma. METHODS: Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma. RESULTS: CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation. CONCLUSIONS: The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTM-based survival models can enable clinicians to evaluate patients' response to surgery as well as their outcomes.

Understand the FDA-cleared fentanyl testing: A clinical evaluation of the SEFRIA fentanyl immunoassay.

BACKGROUND: Screening for fentanyl has been adopted by many clinical laboratories to detect illicit drug use and monitor medication adherence. However, compared to other urine drug testing, fentanyl screening assays are relatively new and therefore their clinical performances are largely unknown. This study extensively evaluated the clinical performance, positive cutoff, and interference profile of SEFRIA fentanyl immunoassay in real patient settings. METHODS: The FDA-cleared cutoff of 1.0 was verified with 21 urine samples with low or undetectable levels of fentanyl. After assay implementation, all screened-positive samples were confirmed by liquid chromatography-tandem mass spectrometry. A new cutoff was derived from the numeric values of the false positive (FP) screening results. The FP rates before and after implementing the new cutoff were compared. Interferences were identified by an untargeted drug analysis and confirmed by spiking experiments. RESULTS: A total of 3951 screening results were reviewed in the first two months of the assay utilization, 410 were screened-positive, and 157 (38 %) were FP. After a new cutoff of 1.3 was implemented, the FP rate was reduced to 17 % based on 11119 screening results. Trazodone, labetalol, and haloperidol were identified as major interferents, accounting for 56 % of the FP results using the cutoff of 1.3. CONCLUSION: By applying the new cutoff and including an interference comment to positive screening results, the FP rate was reduced from initial 38 % to 7.5 % (17 % times 56 %).