Real-World Effectiveness of Nirmatrelvir in Protecting Long COVID for Outpatient Adult Patients - A Large-Scale Observational Cohort Study from the RECOVER Initiative.

Paxlovid has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30-180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 1, 2023, and among which 165,256 were treated with Paxlovid within 5 days since infection and 307,922 were not treated with Paxlovid or other COVID-19 treatments. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). Paxlovid treatment was associated with reduced risk of all-cause death (HR, 0.53, 95% CI 0.46 to 0.60; risk reduction 0.23 events per 100 persons, 95% CI 0.19 to 0.28) and hospitalization (HR, 0.70, 95% CI 0.68 to 0.73; risk reduction 2.37 events per 100 persons, 95% CI 2.19 to 2.56) in the post-acute phase. For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. Overall, high-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.

On the Rapid Synthesis of Reduced Graphene Oxide via Ultrasound-Promoted Eco-Friendly Reduction Approach and Its Effects on Physicochemical Properties.

The common synthesis approach of reduced graphene oxide (rGO) using toxic reducing agents poses a threat to environmental pollution. This study used banana peel extract as a green reducing agent for the synthesis of rGO. Ultrasonication was assimilated to expedite the synthesis process. For comparison, rGO was also produced by reducing GO with hydrazine treatment under conventional stirring. Both morphological (SEM) and physicochemical (FTIR and XRD) studies have revealed that banana peel extract can reduce GO to rGO, although its reducing effect is much weaker compared to hydrazine. Despite this, the rGO produced using banana peel extract with the assimilation of ultrasonication technique has a greater interlayer spacing than that formed under the conventional stirring method. In terms of electrical properties, the electrical conductance of hydrazine-produced rGO (5.69 × 10-6 S) is higher than the banana peel extract-produced rGO (3.55 × 10-6 S - 4.56 × 10-6 S). Interestingly, it was found that most of the rGO produced by banana peel extract under ultrasound assistance has higher or comparable electrical conductance compared to the rGO produced by banana peel extract under stirring method. This implies the feasibility of using short-period ultrasound to replace conventional stirring in rGO synthesis.

Comparative analysis of the analgesic effects of intercostal nerve block, ultrasound-guided paravertebral nerve block, and epidural block following single-port thoracoscopic lung surgery.

OBJECTIVE: In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery. METHOD: A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects. RESULTS: In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05). CONCLUSION: The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.

Biochar alleviates inhibition effects of humic acid on anaerobic digestion: Insights to performances and mechanisms.

To recover methane from waste activated sludge through anaerobic digestion (AD) is one promising alternative to achieve carbon neutrality for wastewater treatment plants. However, humic acids (HAs) are one of the major compositions in waste activated sludge, and their accumulation performs inhibition effects on AD. This study investigated the potentials of biochar (BC) in alleviating inhibition effects of HAs on AD. Results showed that although the accumulated HAs reduced methane yield by 9.37% compared to control, the highest methane yield, 132.6 mL CH4/g VSS, was obtained after adding BC, which was 45.9% higher than that in HA group. Mechanism analysis showed that BC promoted the activities of hydrolase such as protease and α-glucosidase, which were 69.7% and 29.7% higher than those in HA group, respectively. The conversion of short-chain fatty acids was accelerated. In addition, the evolution of electroactive microorganisms like Clostridium_sensu_stricto_13 and Methanosaeta were consistent with the activitiy of electron transfer and the content of cytochrome c. Furthermore, parts of HAs rather than all of them were adsorbed by BC, and the remaining free HAs and BC formed synergistic effects on methanogenesis, then both CO2 reduction and acetoclastic methanogenesis pathways were improved. The findings may provide some solutions to alleviate inhibition effects of HAs on AD.

Observation of 2†µm multiple annular structured vortex pulsed beams by cavity-mode tailoring.

In the past few years, annular structured beams have been extensively studied due to their unique "doughnut" structure and characteristics such as phase and polarization vortices. Especially in the 2 µm wavelength range, they have shown promising applications in fields such as novel laser communication, optical processing, and quantum information processing. In this Letter, we observed basis vector patterns with orthogonality and completeness by finely cavity-mode tailoring with end-mirror space position in a Tm:CaYAlO4 laser. Multiple annular structured beams including azimuthally, linearly, and radially polarized beams (APB, LPB, and RPB) operated at a Q-switched mode-locking (QML) state with a typical output power of ∼18 mW around 1962 nm. Further numerical simulation proved that the multiple annular structured beams are the coherent superposition of different Hermitian Gaussian modes. Using a self-made M-Z interferometer, we have demonstrated that the obtained multiple annular beams have a vortex phase with orbital angular momentum (OAM) of l = ±1. To the best of our knowledge, this is the first observation of vector and scalar annular vortex beams in the 2 µm solid-state laser.

Comparing the long-term follow-up anal function between robot-assisted and laparoscopic surgery for low rectal cancer: A meta-analysis and systematic review.

BACKGROUND: Robotic-assisted surgery (RAS) is increasingly used for treating low rectal cancer. Its comparative effectiveness against laparoscopic surgery (LAS) in enhancing long-term anal function remains uncertain. METHODS: A meta-analysis was conducted to compare long-term anal function outcomes between patients undergoing RAS and LAS. Meta-regression and sensitivity analyses were performed to assess available evidence. Studies published up to September 2023 in English or Chinese were included. RESULTS: Seven studies were identified. RAS patients exhibited lower low anterior resection syndrome (LARS) scores (standardised mean difference [SMD] = -1.39; 95% confidence interval [CI]: -2.64 to -0.15) and Wexner scores (SMD = -0.74; 95% CI: -1.20 to -0.27) compared with LAS patients. However, RAS did not significantly reduce major LARS risk (odds ratio = 0.85; 95% CI: 0.68-1.04). CONCLUSIONS: RAS slightly improved postoperative anal function compared with LAS. Further studies with large samples are warranted to confirm or update our findings.

Develop and validate a computable phenotype for the identification of Alzheimer's disease patients using electronic health record data.

INTRODUCTION: Alzheimer's disease (AD) is often misclassified in electronic health records (EHRs) when relying solely on diagnosis codes. This study aimed to develop a more accurate, computable phenotype (CP) for identifying AD patients using structured and unstructured EHR data. METHODS: We used EHRs from the University of Florida Health (UFHealth) system and created rule-based CPs iteratively through manual chart reviews. The CPs were then validated using data from the University of Texas Health Science Center at Houston (UTHealth) and the University of Minnesota (UMN). RESULTS: Our best-performing CP was "patient has at least 2 AD diagnoses and AD-related keywords in AD encounters," with an F1-score of 0.817 at UF, 0.961 at UTHealth, and 0.623 at UMN, respectively. DISCUSSION: We developed and validated rule-based CPs for AD identification with good performance, which will be crucial for studies that aim to use real-world data like EHRs. Highlights: Developed a computable phenotype (CP) to identify Alzheimer's disease (AD) patients using EHR data.Utilized both structured and unstructured EHR data to enhance CP accuracy.Achieved a high F1-score of 0.817 at UFHealth, and 0.961 and 0.623 at UTHealth and UMN.Validated the CP across different demographics, ensuring robustness and fairness.

A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis.

Drug resistance and tumor recurrence remain clinical challenges in the treatment of urothelial carcinoma (UC). However, the underlying mechanism is not fully understood. Here, we performed single-cell RNA sequencing and identified a subset of urothelial cells with epithelial-mesenchymal transition (EMT) features (EMT-UC), which is significantly correlated with chemotherapy resistance and cancer recurrence. To validate the clinical significance of EMT-UC, we constructed EMT-UC like cells by introducing overexpression of two markers, Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Desmin (DES), and examined their histological distribution characteristics and malignant phenotypes. EMT-UC like cells were mainly enriched in UC tissues from patients with adverse prognosis and exhibited significantly elevated EMT, migration and gemcitabine tolerance in vitro. However, EMT-UC was not specifically identified from tumorous tissues, certain proportion of them were also identified in adjacent normal tissues. Tumorous EMT-UC highly expressed genes involved in malignant behaviors and exhibited adverse prognosis. Additionally, tumorous EMT-UC was associated with remodeled tumor microenvironment (TME), which exhibited high angiogenic and immunosuppressive potentials compared with the normal counterparts. Furthermore, a specific interaction of COL4A1 and ITGB1 was identified to be highly enriched in tumorous EMT-UC, and in the endothelial component. Targeting the interaction of COL4A1 and ITGB1 with specific antibodies significantly suppressed tumorous angiogenesis and alleviated gemcitabine resistance of UC. Overall, our findings demonstrated that the driven force of chemotherapy resistance and recurrence of UC was EMT-UC mediated COL4A1-ITGB1 interaction, providing a potential target for future UC treatment.

A new index for cervical curvature evaluation - relative cervical curvature area.

OBJECTIVE: To put forward a new index of cervical curvature evaluation - relative cervical curvature area,and a new classification of cervical spine was proposed according to the relative cervical curvature area. METHODS: A total of 167 subjects with cervical spondylosis were included in the study. Firstly, 119 subjects were selected to measure C2-C7 lordosis angle by Cobb angle method, Harrison posterior tangent method and Jackson physiological stress line method, and then their relative cervical curvature area, C1-C7 Cobb angle, C7 slope and T1 slope were measured.The correlation between relative cervical curvature area and three measurement methods and common sagittal parameters was analyzed.According to the angle classification method, we calculated the diagnostic boundary value of the relative cervical curvature area classification, and selected 48 subjects to evaluate its diagnostic efficacy.Finally, 119 subjects were re-evaluated according to the diagnostic threshold and the number of intersections to verify the feasibility of the new classification. RESULTS: The results showed that the relative cervical curvature area index had good intra-observer and inter-observer repeatability. Relative cervical curvature area was correlated with Harrison posterior tangent method ( r = 0.930 ), Cobb angle method ( r = 0.886 ) and Jackson physiological stress line method ( r = 0.920 ), and correlated with C1-C7 Cobb angle, C7 slope and T1 slope.The relative cervical curvature area has a good diagnostic performance for distinguishing patients with lordosis, straightening and kyphosis.According to the new classification of cervical spine, 119 subjects were divided into 57 simple lordosis, 11 simple straightening, 4 simple kyphosis, 26 S-type and 21 RS-type. CONCLUSION: The relative cervical curvature area uses the area parameter instead of the original angle parameter and distance parameter to incorporate the change of segmental curvature, which makes up for the shortcomings of the Cobb angle method that only evaluates the curvature of two vertebrae, and better reflects the cervical curvature.Studies have shown that relative cervical curvature area has good repeatability and diagnostic value, and found that it has a good correlation with common cervical sagittal parameters.The new classification of cervical spine makes up for the disadvantage that the angle classification method cannot distinguish between S-type and RS-type, and initially proposes to use the number of intersections and the relative absolute value area to reflect the severity of S-type.

Improved YOLO-FastestV2 wheat spike detection model based on a multi-stage attention mechanism with a LightFPN detection head.

The number of wheat spikes has an important influence on wheat yield, and the rapid and accurate detection of wheat spike numbers is of great significance for wheat yield estimation and food security. Computer vision and machine learning have been widely studied as potential alternatives to human detection. However, models with high accuracy are computationally intensive and time consuming, and lightweight models tend to have lower precision. To address these concerns, YOLO-FastestV2 was selected as the base model for the comprehensive study and analysis of wheat sheaf detection. In this study, we constructed a wheat target detection dataset comprising 11,451 images and 496,974 bounding boxes. The dataset for this study was constructed based on the Global Wheat Detection Dataset and the Wheat Sheaf Detection Dataset, which was published by PP Flying Paddle. We selected three attention mechanisms, Large Separable Kernel Attention (LSKA), Efficient Channel Attention (ECA), and Efficient Multi-Scale Attention (EMA), to enhance the feature extraction capability of the backbone network and improve the accuracy of the underlying model. First, the attention mechanism was added after the base and output phases of the backbone network. Second, the attention mechanism that further improved the model accuracy after the base and output phases was selected to construct the model with a two-phase added attention mechanism. On the other hand, we constructed SimLightFPN to improve the model accuracy by introducing SimConv to improve the LightFPN module. The results of the study showed that the YOLO-FastestV2-SimLightFPN-ECA-EMA hybrid model, which incorporates the ECA attention mechanism in the base stage and introduces the EMA attention mechanism and the combination of SimLightFPN modules in the output stage, has the best overall performance. The accuracy of the model was P=83.91%, R=78.35%, AP= 81.52%, and F1 = 81.03%, and it ranked first in the GPI (0.84) in the overall evaluation. The research examines the deployment of wheat ear detection and counting models on devices with constrained resources, delivering novel solutions for the evolution of agricultural automation and precision agriculture.

A Dual-Modal, Label-Free Raman Imaging Method for Rapid Virtual Staining of Large-Area Breast Cancer Tissue Sections.

As one of the most common cancers, accurate, rapid, and simple histopathological diagnosis is very important for breast cancer. Raman imaging is a powerful technique for label-free analysis of tissue composition and histopathology, but it suffers from slow speed when applied to large-area tissue sections. In this study, we propose a dual-modal Raman imaging method that combines Raman mapping data with microscopy bright-field images to achieve virtual staining of breast cancer tissue sections. We validate our method on various breast tissue sections with different morphologies and biomarker expressions and compare it with the golden standard of histopathological methods. The results demonstrate that our method can effectively distinguish various types and components of tissues, and provide staining images comparable to stained tissue sections. Moreover, our method can improve imaging speed by up to 65 times compared to general spontaneous Raman imaging methods. It is simple, fast, and suitable for clinical applications.

Pancreatic duct occupation method assisted wire guide through pancreatic duct stenosis in the treatment of chronic pancreatitis.

Chronic pancreatitis is usually accompanied by pancreatic duct stenosis and pancreatic duct stones (1). Pancreatic duct stent implantation can effectively drain pancreatic fluid and relieve symptoms. However, in many cases this is not easy, because of the presence of stones or the pancreatic duct is too narrow, the guide wire may not be able to enter the distal pancreatic duct. We present a case of chronic pancreatitis with pancreatic duct stenosis in which we assisted the passage of guidewires through the pancreatic duct stenosis by means of pancreatic duct occupation.

A cryptic homotypic interaction motif of insect STING is required for its antiviral signaling.

Stimulator of interferon genes (STING) mediates innate immune response upon binding to cyclic GMP-AMP (cGAMP). It recruits tank-binding kinase 1 (TBK1) and transcription factor interferon regulatory factor 3 (IRF3) through its C-terminal tail and facilitates TBK1-dependent phosphorylation of IRF3 via forming STING polymers in mammalian cells. However, the mechanism behind STING-mediated activation of NF-κB transcription factor, Relish, in insect cells is unknown. Our study revealed that insect STING formed oligomers and the cryptic RIP homotypic interaction motif (cRHIM) was required for its oligomerization and its anti-viral functions. Cells expressing cRHIM-deficient mutants exhibited lower levels of anti-viral molecules, higher viral load after viral infection and weak activation of Relish. Moreover, we observed that under cGAMP stimulation, insect STING interacted with IMD, and deletion of the cRHIM motif on either protein prevented this interaction. Finally, we demonstrated that cGAMP enhanced the amyloid-like property of insect STING aggregates by ThT staining. In summary, our research showed that insect STING employed a homotypic motif to form intermolecular interactions that are essential for its antiviral signaling.

Nanozyme-Inhibited SERS Multichannel Paper-Based Sensor Array for the Quantification and Identification of Biothiols and Cancer Cells Based on Three Ag-Based Nanomaterials.

Biothiols play essential roles in maintaining normal physiological functions, resisting oxidative stress, and protecting cell health. Establishing an effective and reliable sensor array for the accurate quantification and discrimination of diverse biothiols is extremely meaningful. In this work, Ag/Mn3O4, Ag3PO4, and Ag3Cit with excellent oxidase-mimetic activity and surface-enhanced Raman scattering (SERS)-enhanced features have been prepared and loaded onto Whatman filter paper (WFP) to build SERS paper chips as three sensing channels, which can induce 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to SERS-active reporters (TMBox) and concurrently generate prominent SERS signals. Nevertheless, the addition of biothiols can suppress conversion from TMB to TMBox, which can cause the reduction of the SERS signal from TMBox. Interestingly, each SERS sensing channel can generate different TMBox signals' variations due to differences in the oxidative inhibition abilities of diverse biothiols and exclusive properties of each paper chip, which can be plotted as specific fingerprint patterns of each biothiol and further translated into intuitive two-dimensional (2D) clustering profiles through linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA) techniques for precise identification of these six biothiols with the minimum concentration of 1 µM. More importantly, this SERS sensor array is exploited for the precise quantification of intracellular glutathione (GSH), and can differentiate between normal and cancer cells based on different intracellular GSH contents and even identify different types of tumor cells, demonstrating its powerful application prospects in disease diagnosis.

A novel cobalt-iron bimetallic hydrochar for the degradation of triclosan in the aqueous solution: performance, reusability, and synergistic degradation mechanism.

Low activation performance is a critical issue limiting the practical application of low-cost biochar in the advanced oxidation. Given the high potential of transition metals in the persulfate activation process and abundant oxygen-containing groups of hydrochar, hydrochar derived from cobalt (Co)-modified iron (Fe)-enriched sludge was synthesized and its performance and activation mechanism for the degradation of triclosan were investigated. Co modification significantly altered the morphology of hydrochar, and the increased Co-Fe mass ratios transformed hydrochar from granular to rose-shaped lamellar and then to helical sheet structures. Specific surface area, defect degree, and oxygen-containing groups of hydrochar increased with increasing cobalt-iron mass ratios. The highest removal of triclosan was up to 98% in the hydrochar/peroxymonosulfate (PMS) system under a wide range of pHs (3-10) and still remained higher than 90% after four cycles. Both Radical (mainly hydroxyl radical) and nonradical pathways (singlet oxygen and electron transfer) were evidenced to play roles in the triclosan removal. Fe3+ promoted the regeneration of Co2+ and realized the efficient circulation of Co3+/Co2+. A ternary system consisting of electron donor (triclosan)-electron mediator (hydrochar)-electron acceptor (PMS) provided channels for electron transfer. No measurable Co and Fe were released during the reaction, and the toxicity of degradation intermediates was lower than that of triclosan. Beside triclosan, rhodamine B, bisphenol A, sulfamethoxazole, and phenol were also almost degraded completely in this oxidation system. This study provides a promising way for the enhancement of catalytic activity of carbonaceous material.

Biofeedback combined with percutaneous electrical pudendal nerve stimulation for the treatment of low anterior rectal resection syndrome: a study protocol for a randomized controlled trial.

BACKGROUND: Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25-80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). METHODS AND ANALYSIS: In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). DISCUSSION: We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. TRIAL REGISTRATION: Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023.

Risk Factors for Unplanned Readmission in Adult Liver Transplant Patients: A Retrospective Study.

INTRODUCTION: Unplanned readmission is an important indicator for evaluating medical care quality. Adult liver transplant patients have high risk for readmission, which seriously affects their recovery. As there is currently a lack of research on risk factors for unplanned readmission of adult liver transplant patients in China, the purpose of this study was to elucidate such risk factors. METHODS: Data for patients undergoing liver transplantation surgery at a tertiary hospital in Zhejiang Province from March 2018 to July 2022 were retrospectively collected. Patients were divided into readmission and nonreadmission groups based on whether unplanned readmission occurred within 90 days. Univariate analysis and logistic regression were used to analyze risk factors for unplanned readmission. RESULTS: In total, 123 adult liver transplant patients were included; 38 had unplanned readmission, for a rate of 30.8%. There was a statistically significant difference between the groups in terms of age, educational level, operation time, intraoperative bleeding volume, number of complications, postoperative hospital stay, and hemoglobin (P < .05). Logistic regression analysis showed that age [OR = 1.085, 95% CI (1.022, 1.152)], operation time [OR = 1.010, 95% CI (1.001, 1.020)], postoperative hospital stay [OR = 1.124, 95% CI (1.023, 1.235)], and number of complications [OR = 4.487, 95% CI (1.234, 16.319)] were independent risk factors for unplanned readmission in adult liver transplant patients (P < .05). CONCLUSIONS: The current situation of unplanned readmission for adult liver transplant patients cannot be ignored, indicating that staff should identify risk factors for unplanned readmission as soon as possible and take targeted personalized measures and health education to reduce readmission risk.

A novel dual-model photoelectrochemical/electrochemical sensor based on Z-scheme TiO2 disks/methylene blue for kanamycin detection.

Herein, a new dual-model photoelectrochemical (PEC)/electrochemical (EC) sensor based on Z-scheme titanium dioxide (TiO2) disk/methylene blue (MB) sensibilization for the detection of kanamycin (Kana) was developed. Metal-organic framework-derived porous TiO2 disks were synthesized and exhibited excellent anodic photocurrent under visible light excitation. Subsequently, amino-labeled double-stranded DNA (dsDNA) was introduced into the modified electrode. Photocurrent was enhanced with MB embedded in dsDNA to form Z-scheme TiO2/MB sensibilization. When the target, Kana, was present, it specifically bound to the aptamer in the dsDNA, leading to the disruption of the dsDNA structure and the release of MB. This release of MB and the increase in target spatial resistance resulted in a significant weakening of PEC signal and a decreased oxidation peak current of MB. The PEC sensor successfully detected Kana in the range of 2-1000 pM with an LOD of 0.17 pM. Meanwhile, the EC sensor for Kana detection showed a linear range of 5-500 pM with an LOD of 1.8 pM. Additionally, the sensor exhibited excellent selectivity, reproducibility, stability, and good recoveries when applied to milk and honey samples. As a result, this method has the potential for application in ensuring food safety through the rapid determination of antibiotics in food.

Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis.

The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (nCase = 3,418, nControl = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections (P BH = 3.28e-5, 0.05/1,525). These proteins were involved in amino acids and organic acid synthesis pathways. Colocalization analysis further identified six proteins associated with TCs (VCAM1, LGMN, NPTX1, PLEKHA7, TNFAIP3, and BMP1). Tissue validation confirmed BMP1, LGMN, and PLEKHA7's differential expression between normal and TC tissues. We found limited evidence for linking circulating proteins and the risk of TCs. Our study highlighted the contribution of proteins, particularly those involved in amino acid metabolism, to TCs.