Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy.

BACKGROUND: Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. METHODS: Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. RESULTS: Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102- 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102- 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. CONCLUSION: HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr.

Sorafenib plus TACE with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma.

OBJECTIVES: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 78 patients with intermediate or advanced HCC who were treated at our centers between January 2018 and December 2021. 26 of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. RESULTS: The mOS (22 vs. 10 months, P < 0.001) and mPFS (11 vs. 6 months, P = 0.008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumor progression. For grade I and II adverse events (AEs), the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the two groups (P > 0.05). CONCLUSION: Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. ADVANCES IN KNOWLEDGE: 1.Subgroup analysis demonstrated TACE+ Sorafenib+ Camrelizumab could benefit HCC patients regardless of whether they had PVTT, BCLC B or C, or CHILD A or B；2.We reported the immunotherapy related adverse events (irAEs) occurred with a significant higher incidence in triple treatment, but all the adverse events are tolerable.

Vertically Oriented Perovskites with Minimized Intrinsic Boundaries for Efficient Photovoltaics.

Intrinsic boundaries formed by grain stacks of randomly oriented perovskite crystallites seriously restrict charge transport in the resultant photovoltaic devices, whereas direct passivation of these defects remains unexplored, and it is desirable to modulate perovskite growth with uniform orientation. Herein, we report a simple but effective method to regulate perovskite crystallization by employing a volatile and polymerizable monomer of hydroxyethyl methacrylate (HEMA), which can simultaneously interact with both FA+ and Pb2+ via hydrogen and coordination bonding, respectively, to seed perovskite crystallization with accelerated nucleation and retarded crystal growth. Upon thermal annealing, the gradual volatilization and partial self-condensation of the HEMA drive the perovskite growth perpendicularly to the substrate, leading to largely suppressed defect states, improved crystallinity, and a reduced Young's modulus of the perovskite film. As a result, champion efficiencies exceeding 24 and 22% with improved operational and mechanical stability of the optimized perovskite solar cells based on rigid and flexible substrates were finally achieved.

State of open science in cancer research.

PURPOSE: This study has been focused on assessing the Open Science scenario of cancer research during the period 2011-2021, in terms of the derived scientific publications and raw data dissemination. METHODS: A cancer search equation was executed in the Science Citation Index-Expanded, collecting the papers signed by at least one Spanish institution. The same search strategy was performed in the Data Citation Index to describe dataset diffusion. RESULTS: 50,822 papers were recovered, 71% of which belong to first and second quartile journals. 59% of the articles were published in Open Access (OA) journals. The Open Access model and international collaboration positively conditioned the number of citations received. Among the most productive journals stood out Plos One, Cancers, and Clinical and Translational Oncology. 2693 genomics, proteomics and metabolomics datasets were retrieved, being Gene Expression Omnibus the favoured repository. CONCLUSIONS: There has been an increase in oncology publications in Open Access. Most were published in first quartile journals and received higher citations than non-Open Access articles, as well as when oncological investigation was performed between international research teams, being relevant in the context of Open Science. Genetic repositories have been the preferred for sharing oncology datasets. Further investigation of research and data sharing in oncology is needed, supported by stronger Open Science policies, to achieve better data sharing practices among three scientific main pillars: researchers, publishers, and scientific organizations.

An on-line SPE-LC-MS/MS method for quantification of nucleobases and nucleosides present in biological fluids.

Solid phase extraction (SPE) and liquid chromatographic (LC) separation of nucleobases and nucleosides are challenging due to the high hydrophilicity of these compounds. Herein we report a novel on-line SPE-LC-MS/MS method for their quantification after pre-column derivatization with chloroacetaldehyde (CAA). The method proposed is selective and sensitive with limits of detection at the nano-molar level. Analysis of urine and saliva samples by using this method is demonstrated. Adenine, guanine, cytosine, adenosine, guanosine, and cytidine were found in the range from 0.19 (guanosine) to 1.83 µM (cytidine) in urine and from 0.015 (guanosine) to 0.79 µM (adenine) in saliva. Interestingly, methylation of cytidine was found to be significantly different in urine from that in saliva. While 5-hydroxymethylcytidine was detected at a very low level (<0.05 µM) in saliva, it was found to be the most prominent methylated cytidine in urine at a high level of 3.33 µM. Since on-line SPE is deployed, the proposed LC-MS/MS quantitative assay is convenient to carry out and offers good assay accuracy and repeatability.

Aberrant dynamic functional network connectivity in progressive supranuclear palsy.

BACKGROUND: The clinical symptoms of progressive supranuclear palsy (PSP) may be mediated by aberrant dynamic functional network connectivity (dFNC). While earlier research has found altered functional network connections in PSP patients, the majority of those studies have concentrated on static functional connectivity. Nevertheless, in this study, we sought to evaluate the modifications in dynamic characteristics and establish the correlation between these disease-related changes and clinical variables. METHODS: In our study, we conducted a study on 53 PSP patients and 65 normal controls. Initially, we employed a group independent component analysis (ICA) to derive resting-state networks (RSNs), while employing a sliding window correlation approach to produce dFNC matrices. The K-means algorithm was used to cluster these matrices into distinct dynamic states, and then state analysis was subsequently employed to analyze the dFNC and temporal metrics between the two groups. Finally, we made a correlation analysis. RESULTS: PSP patients showed increased connectivity strength between medulla oblongata (MO) and visual network (VN) /cerebellum network (CBN) and decreased connections were found between default mode network (DMN) and VN/CBN, subcortical cortex network (SCN) and CBN. In addition, PSP patients spend less fraction time and shorter dwell time in a diffused state, especially the MO and SCN. Finally, the fraction time and mean dwell time in the distributed connectivity state (state 2) is negatively correlated with duration, bulbar and oculomotor symptoms. DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.

DIRECTION: Deep cascaded reconstruction residual-based feature modulation network for fast MRI reconstruction.

Deep cascaded networks have been extensively studied and applied to accelerate Magnetic Resonance Imaging (MRI) and have shown promising results. Most existing works employ a large cascading number for the sake of superior performances. However, due to the lack of proper guidance, the reconstruction performance can easily reach a plateau and even face degradation if simply increasing the cascading number. In this paper, we aim to boost the reconstruction performance from a novel perspective by proposing a parallel architecture called DIRECTION that fully exploits the guiding value of the reconstruction residual of each subnetwork. Specifically, we introduce a novel Reconstruction Residual-Based Feature Modulation Mechanism (RRFMM) which utilizes the reconstruction residual of the previous subnetwork to guide the next subnetwork at the feature level. To achieve this, a Residual Attention Modulation Block (RAMB) is proposed to generate attention maps using multi-scale residual features to modulate the image features of the corresponding scales. Equipped with this strategy, each subnetwork within the cascaded network possesses its unique optimization objective and emphasis rather than blindly updating its parameters. To further boost the performance, we introduce the Cross-Stage Feature Reuse Connection (CSFRC) and the Reconstruction Dense Connection (RDC), which can reduce information loss and enhance representative ability. We conduct sufficient experiments and evaluate our method on the fastMRI knee dataset using multiple subsampling masks. Comprehensive experimental results show that our method can markedly boost the performance of cascaded networks and significantly outperforms other compared state-of-the-art methods quantitatively and qualitatively.

Effects of Water Isotope Composition on Stable Isotope Distribution and Fractionation of Rice and Plant Tissues.

Rice origin authenticity is important for food safety and consumer confidence. The stable isotope composition of rice is believed to be closely related to its water source, which affects its origin characteristics. However, the influence of water availability on the distribution of rice stable isotopes (δ2H and δ18O) is not clear. In this study, three irrigation waters with different isotopic values were used to investigate isotopic water use effects of Indica and Japonica rice, using pot experiments. Under three different water isotope treatments, the δ2H values of Indica polished rice showed significant differences (-65.0 ± 2.3, -60.5 ± 0.8 and -55.8 ± 1.7‰, respectively, p < 0.05) compared to δ13C and δ15N, as did Japonica polished rice. The values of δ2H and δ18O of rice became more positive when applying more enriched (in 2H and 18O) water, and the enrichment effect was higher in rice than in the corresponding plant tissue. In addition, the δ2H and δ18O values of Indica rice leaves decreased at the heading stage, increased at the filling stage, and then decreased at the harvest stage. Japonica rice showed a similar trend. δ2H changes from stem to leaf were more negative, but δ18O changes were more positive, and δ2H and δ18O values from leaf to rice were more positive for both brown and polished rice. The results from this study will clarify different water isotopic composition effects on rice and provide useful information to improve rice origin authenticity using stable isotope-based methods.

Case report: A case of high grade serous carcinoma of peritoneal origin.

This case report describes an 80-year-old female patient admitted to the emergency department due to abdominal distension, abdominal pain, and hematemesis persisting for three days. Subsequent postoperative pathological examination confirmed the diagnosis of peritoneal cancer. The occurrence, diagnosis, treatment, and prognosis of primary peritoneal cancer (PPC) are presented in detail. PPC is a type of cancer originating from the primary peritoneal mesothelium organization, causing diffuse malignant tumors in the abdominal and pelvic regions. Due to the lack of specific clinical manifestations for this disease, the importance of early diagnosis and treatment is hereby emphasized. The article also mentions the histological source of this type of cancer and the advantages of preoperative intraperitoneal chemotherapy in improving the efficacy of PPC treatment. Finally, the importance of a comprehensive treatment approach and proficient use of targeted therapy techniques are highlighted to enhance the treatment outcomes of PPC.

A novel technique to remove migrated esophageal stent under fluoroscopy.

PURPOSE: To evaluate the efficacy and safety of a novel technique for removal of migrated esophageal stent (MES) under fluoroscopy. METHODS: From January 2009 to April 2023, 793 patients with a dysphagia score of 3-4 underwent esophageal stenting at our center, and 25 patients (mean age: 70.06 years old; male/female: 15/10) underwent stent removal using "loop method" under fluoroscopy. The primary outcomes were technical success and complications. The secondary outcomes were procedure time, radiation exposure, biochemical indicators [white blood cell (WBC), hemoglobin (Hb), platelet (PLT), albumin (ALB), alanine transaminase (ALT), total bilirubin (TB), urea nitrogen (UN) and C-reactive protein] of pre- and post-treatment at 2 weeks. RESULTS: Technical success was 100% without major complications. The mean procedure time was (39.44 ± 9.28) minutes, which showed no statistical significance between benign (n = 5) and malignant (n = 20) group [(42.40 ± 8.85) vs (38.71 ± 9.46) mins, p > 0.05]. The mean radiation exposure was (332.88 ± 261.47) mGy, which showed no statistical significance between benign and malignant group [(360.74 ± 231.43) vs (325.92 ± 273.54) mGy, p > 0.05]. Pre- and post-procedure Hb [(114.46 ± 11.96) vs. (117.57 ± 13.12) g/L] and ALB [(42.26 ± 3.39) vs. (44.12 ± 3.77) g/L] showed significant difference (p < 0.05), while WBC, PLT, CRP, and ALT showed no significance (p > 0.05). CONCLUSION: Fluoroscopy-guided "Loop method" for MES removal is an effective and safe alternative technique.

Mitochondrial DNA Leakage and cGas/STING Pathway in Microglia: Crosstalk Between Neuroinflammation and Neurodegeneration.

Neurodegenerative diseases, characterized by abnormal deposition of misfolded proteins, often present with progressive loss of neurons. Chronic neuroinflammation is a striking hallmark of neurodegeneration. Microglia, as the primary immune cells in the brain, is the main type of cells that participate in the formation of inflammatory microenvironment. Cytoplasmic free mitochondrial DNA (mtDNA), a common component of damage-associated molecular patterns (DAMPs), can activate the cGas/stimulator of interferon genes (STING) signalling, which subsequently produces type I interferon and proinflammatory cytokines. There are various sources of free mtDNA in microglial cytoplasm, but mitochondrial oxidative stress accumulation plays the vital role. The upregulation of cGas/STING pathway in microglia contributes to the abnormal and persistent microglial activation, accompanied by excessive secretion of neurotoxic inflammatory mediators such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which exacerbates the damage of neurons and promotes the development of neurodegeneration. Currently, novel therapeutic approaches need to be found to delay the progression of neurodegenerative disorders, and regulation of the cGas/STING signaling in microglia may be a potential target.

Image Reconstruction for Accelerated MR Scan With Faster Fourier Convolutional Neural Networks.

High quality image reconstruction from undersampled k -space data is key to accelerating MR scanning. Current deep learning methods are limited by the small receptive fields in reconstruction networks, which restrict the exploitation of long-range information, and impede the mitigation of full-image artifacts, particularly in 3D reconstruction tasks. Additionally, the substantial computational demands of 3D reconstruction considerably hinder advancements in related fields. To tackle these challenges, we propose the following: 1) A novel convolution operator named Faster Fourier Convolution (FasterFC), aims at providing an adaptable broad receptive field for spatial domain reconstruction networks with fast computational speed. 2) A split-slice strategy that substantially reduces the computational load of 3D reconstruction, enabling high-resolution, multi-coil, 3D MR image reconstruction while fully utilizing inter-layer and intra-layer information. 3) A single-to-group algorithm that efficiently utilizes scan-specific and data-driven priors to enhance k -space interpolation effects. 4) A multi-stage, multi-coil, 3D fast MRI method, called the faster Fourier convolution based single-to-group network (FAS-Net), comprising a single-to-group k -space interpolation algorithm and a FasterFC-based image domain reconstruction module, significantly minimizes the computational demands of 3D reconstruction through split-slice strategy. Experimental evaluations conducted on the NYU fastMRI and Stanford MRI Data datasets reveal that the FasterFC significantly enhances the quality of both 2D and 3D reconstruction results. Moreover, FAS-Net, characterized as a method that can achieve high-resolution (320, 320, 256), multi-coil, (8 coils), 3D fast MRI, exhibits superior reconstruction performance compared to other state-of-the-art 2D and 3D methods.

Immune-related adverse events in non-small cell lung cancer: Occurrence, mechanisms and therapeutic strategies.

The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non-small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune-related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ-specific irAEs in patients with NSCLC and provide an in-depth analysis of recent advancements in understanding the mechanisms driving ICI-induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

SNORD45A Affects Content of HIF-1α and Promotes Endothelial Angiogenic Function.

To find out the differentially expressed small nucleolar RNAs (snoRNAs) in corneal neovascularization and their effect on angiogenesis. The rat model of corneal neovascularization induced by alkali burn was established, and the differentially expressed snoRNAs were sifted by high-throughput sequencing. Human genome homologs were screened and verified in cytopathological models. Polymerase chain reactions (PCRs) and Western blot assays were applied to detect mRNA and corresponding proteins affected by the differentially expressed snoRNA. In vitro, experiments were promoted to identify whether snoRNA affects endothelial cell migration and angiogenesis. Forty-seven differentially expressed snoRNAs were sifted from transparent cornea and neovascularization. According to sequencing and cytopathological model results, SNORD45A was selected for subsequent experiments. At mRNA and protein levels, SNORD45A affected the expression of HIF-1α. SNORD45A promoted endothelial angiogenesis through endothelial cell migration and tube formation regulation. The research suggested that SNORD45A partakes in the corneal neovascularization formation and can become one of the targets for corneal neovascularization therapy.

Pharmacokinetics and relative bioavailability study of two cefquinome sulfate intramammary infusions in cow milk.

In this study, two intramammary infusions of cefquinome sulfate were investigated for pharmacokinetics and bioavailability. Twelve lactating cows for each group were administered an effective dose of 75 mg/gland for cefquinome, with milk samples collected at various time intervals. The concentrations of cefquinome in milk at different times were determined by the UPLC-MS/MS method. Analyses of noncompartmental pharmacokinetics were conducted on the concentration of cefquinome in milk. Mean pharmacokinetic parameters of group A and group B following intramammary administration were as follows: AUClast 300558.57 ± 25052.78 ng/mL and 266551.3 ± 50654.85 ng/mL, Cmax 51786.35 ± 11948.4 ng/mL and 59763.7 ± 8403.2 ng/mL, T1/2 5.69 ± 0.62 h and 5.25 ± 1.62 h, MRT 7.43 ± 0.79 h and 4.8 ± 0.78 h, respectively. Pharmacokinetic experiments showed that the relative bioavailability of group B was 88.69% that of group A. From our findings, group B (3 g: 75 mg) shows a quicker drug elimination process than group A (8 g: 75 mg), which suggests that the withdrawal period for the new formulation may be shorter.

Influence of boundary layer jets on the vertical distribution of ozone in Guangdong, China.

The planetary boundary layer (PBL) characteristics during ozone (O3) episodes in China have been extensively studied; however, knowledge of the impact of boundary layer jets (BLJs) on O3 vertical distribution is limited. This study conducted a field campaign from 1 to 8 December 2020 to examine the vertical structure of the O3 concentration and wind velocity within the boundary layer at two sites (Foshan: FS, Maoming: MM) in Guangdong. Utilising lidar observations and the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem), distinct spatial distribution patterns of O3 over FS and MM influenced by BLJs were identified. The BLJs at both locations exhibited pronounced diurnal variations with a nocturnal maximum exceeding 11 m/s at a height of approximately 500 m. The nocturnal enhancement of BLJs resulted from inertial oscillations coupled with diurnal thermal forcing over sloping terrain. A stronger BLJ at FS induced an evident uplift of O3 and the prevailing northeasterly wind facilitated the transport of O3 in the nocturnal residual layer from FS to MM. After sunrise, surface heating and the development of the PBL caused the air mass with elevated O3 levels in the residual layer to descend to ground level. At MM, calm surface winds, a weaker BLJ at 500 m height, and strong downdrafts collectively contributed to a significant increase in surface O3 concentration in subsequent days. These findings contribute to our understanding of the interactions between BLJs and variations in surface air pollutant concentrations, thereby providing important insights for future regional emissions control measures.

A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

An implantable device for wireless monitoring of diverse physio-behavioral characteristics in freely behaving small animals and interacting groups.

Comprehensive, continuous quantitative monitoring of intricately orchestrated physiological processes and behavioral states in living organisms can yield essential data for elucidating the function of neural circuits under healthy and diseased conditions, for defining the effects of potential drugs and treatments, and for tracking disease progression and recovery. Here, we report a wireless, battery-free implantable device and a set of associated algorithms that enable continuous, multiparametric physio-behavioral monitoring in freely behaving small animals and interacting groups. Through advanced analytics approaches applied to mechano-acoustic signals of diverse body processes, the device yields heart rate, respiratory rate, physical activity, temperature, and behavioral states. Demonstrations in pharmacological, locomotor, and acute and social stress tests and in optogenetic studies offer unique insights into the coordination of physio-behavioral characteristics associated with healthy and perturbed states. This technology has broad utility in neuroscience, physiology, behavior, and other areas that rely on studies of freely moving, small animal models.