Del Nido cardioplegia versus cold blood cardioplegia in adult cardiac surgery: a meta-analysis of randomized clinical trials.

OBJECTIVE: Systematic evaluation of the safety of del Nido cardioplegia compared to cold blood cardioplegia in adult cardiac surgery. METHODS: We systematically searched PubMed, EMbase, The Cochrane Library and ClinicalTrials.gov for randomized clinical trials (published by 14 January 2024) comparing del Nido cardioplegia to cold blood cardioplegia in adult. Our main endpoints were myocardial injury markers and clinical outcomes. We assessed pooled data by use of a random-effects model or a fixed-effects model. RESULTS: A total of 10 studies were identified, incorporating 889 patients who received del Nido cardioplegia and 907 patients who received cold blood cardioplegia. The meta-analysis results showed that compared with the cold blood cardioplegia, the del Nido cardioplegia had less volume of cardioplegia, higher rate of spontaneous rhythm recovery after cross clamp release, lower levels of postoperative cardiac troponin T and creatinine kinase-myocardial band, all of which were statistically significant. However, there was no statistically significant difference in postoperative troponin I and postoperative left ventricular ejection fraction. The clinical outcomes including mechanical ventilation time, intensive care unit stay time, hospital stay time, postoperative stroke, postoperative new-onset atrial fibrillation, postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and in-hospital mortality of both are comparable. CONCLUSION: Existing evidence suggests that del Nido cardioplegia reduced volume of cardioplegia administration and attempts of defibrillation. The superior postoperative results in CTnT and CK-MB may provide a direction for further research on improvement of the composition of cardioplegia.

Inhibiting the self-discharging process of quantum batteries in non-Markovian noises.

One of the main challenges in developing high-performance quantum batteries is the self-discharging process, where energy is dissipated from a quantum battery into the environment. In this work, we investigate the influence of non-Markovian noises on the performance of a quantum battery. Our results demonstrate that adding auxiliary qubits to a quantum battery system can effectively suppress the self-discharging process, leading to an improvement in both the steady-state energy and extractable work. We reveal that the physical mechanism inhibiting the self-discharging process is the formation of system-environment bound states, rather than an increase in non-Markovianity. Our results could be of both theoretical and experimental interest in exploring the ability of quantum batteries to maintain long stored energy in the environment.

Single-Frame Supervision for Spatio-Temporal Video Grounding.

Spatio-Temporal Video Grounding (STVG) aims at localizing the spatio-temporal tube of a specific object in an untrimmed video given a free-form natural language query. As the annotation of tubes is labor intensive, researchers are motivated to explore weakly supervised approaches in recent works, which usually results in significant performance degradation. To achieve a less expensive STVG method with acceptable accuracy, this work investigates the "single-frame supervision" paradigm that requires a single frame labeled with a bounding box within the temporal boundary of the fully supervised counterpart as the supervisory signal. Based on the characteristics of the STVG problem, we propose a Two-Stage Multiple Instance Learning (T-SMILE) method, which creates pseudo labels by expanding the annotated frame to its contextual frames, thereby establishing a fully-supervised problem to facilitate further model training. The innovations of the proposed method are three-folded, including 1) utilizing multiple instance learning to dynamically select instances in positive bags for the recognition of starting and ending timestamps, 2) learning highly discriminative query features by incorporating spatial prior constraints in cross-attention, and 3) designing a curriculum learning-based strategy that iterative assigns dynamic weights to spatial and temporal branches, thereby gradually adapting to the learning branch with larger difficulty. To facilitate future research on this task, we also contribute a large-scale benchmark containing 12,469 videos on complex scenes with single-frame annotation. The extensive experiments on two benchmarks demonstrate that T-SMILE significantly outperforms all weakly-supervised methods. Remarkably, it also performs better than some fully-supervised methods associated with much more annotation labor costs. The dataset and codes are available at https://github.com/qumengxue/T-SMILE.

Bifidobacterium animalis subsp. lactis LPL-RH improves postoperative gastrointestinal symptoms and nutrition indexes by regulating the gut microbiota in patients with valvular heart disease: a randomized controlled trial.

Gastrointestinal symptoms constitute a frequent complication in postoperative patients with valvular heart disease (VHD), impacting their postoperative recovery. Probiotics contribute to regulating human gut microbiota balance and alleviating postoperative gastrointestinal symptoms. Our objective involved assessing the potential of Bifidobacterium animalis subsp. lactis LPL-RH to alleviate postoperative gastrointestinal symptoms and expedite patient recovery. Adult patients diagnosed with VHD scheduled for valve surgery were enrolled. 110 patients were randomly divided into two groups and received LPL-RH or a placebo for 14 days. Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptoms Questionnaire. An analysis of the time to recovery of bowel function and various postoperative variables was conducted in both study groups. Variations in the intestinal microbiota were detected via 16S rRNA sequencing. The study was completed by 105 participants, with 53 in the probiotic group and 52 in the placebo group. Compared to the placebo group, LPL-RH significantly reduced the total gastrointestinal symptom score after surgery (p = 0.004). Additionally, LPL-RH was found to significantly reduce abdominal pain (p = 0.001), bloating (p = 0.018), and constipation (p = 0.022) symptom scores. Furthermore, LPL-RH dramatically shortened the time to recovery of bowel function (p = 0.017). Moreover, LPL-RH administration significantly enhanced patients' postoperative nutrition indexes (red blood cell counts, hemoglobin level, p < 0.05). Microbiome analysis showed that the composition and diversity of the postoperative intestinal microbiota differed between the probiotic and placebo groups. No adverse incidents associated with probiotics were documented, emphasizing their safety. This study initially discovered that oral B. animalis subsp. lactis LPL-RH can assist in regulating intestinal microbiota balance, alleviating gastrointestinal symptoms, promoting intestinal function recovery, and enhancing nutrition indexes in patients with VHD after surgery. Regulating the intestinal microbiota may represent a potential mechanism for LPL-RH to exert clinical benefits.

Clinical efficacy of high-voltage pulsed radiofrequency combined with stellate ganglion block in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm.

OBJECTIVES: A single therapeutic approach is not always successful in the treatment of herpes zoster neuralgia, and the appropriate combination of different treatments deserves further exploration. In this study, we investigated the clinical efficacy of high-voltage long-duration pulsed radiofrequency (PRF) combined with stellate ganglion block (SGB) in the acute phase of thoracic and dorsal herpes zoster neuralgia under dual guidance of ultrasound and C-arm. METHODS: 79 cases of acute zoster neuralgia were grouped premised upon differing therapeutic approaches: standard voltage PRF (group S, the temperature, duration, pulse width, frequency and voltage were set to 42 °C, 300 s, 20 ms, 2 Hz, and 45 V), high-voltage long-duration PRF (group H, parameters of PRF were set to 42 °C, 900 s, 20 ms, 2 Hz, and 90 V, respectively), and high-voltage long-duration PRF combined with SGB (group C, parameter settings for PRF are the same as those for group H). The therapeutic outcomes were assessed utilizing the numeric rating scale (NRS), Pittsburgh sleep quality index (PSQI), and Hamilton anxiety rating scale (HAMA). The incidence of clinically significant postherpetic neuralgia post-treatment had been documented. RESULTS: Compared to baseline, scores of NRS, PSQI, and HAMA at each time point post-treatment decreased across all groups, and the decrease was more significant in the C group than in the S group. At the later stage of treatment, the consumption of pregabalin and tramadol and the plasma levels of interleukin-6 and galectin-3 in the C group were significantly lower than those in the S group. The incidence of PHN in the C group was significantly lower than in the S group. CONCLUSIONS: The combination of high-voltage long-duration PRF combined with SGB under dual guidance of ultrasound and C-arm represents a safe, effective, environmentally friendly, and cost-efficient method for treating AZN, significantly improving sleep quality, alleviating anxiety, and reducing the risk of PHN occurrence.

Efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil monotherapy for refractory metastatic colorectal cancer: a retrospective cohort study.

Background: Several studies demonstrated trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) had better efficacy than the monotherapy of TAS-102 in refractory metastatic colorectal cancer (mCRC). However, it remains unclear whether Chinese population can benefit from this combination or not. Hence, we conducted this retrospective cohort study to compare the efficacy and safety between TAS-102 plus BEV with TAS-102 monotherapy in refractory mCRC. Methods: This retrospective cohort study enrolled patients (any age) with refractory mCRC from Hunan Cancer Hospital. The main inclusion criteria were histopathologically and/or radiographically confirmed refractory mCRC, World Health Organization (WHO) performance status of 0 to 2, adequate organ function, and initial treatment of TAS-102 with or without BEV between November 2020 and October 2022. Previous therapy with fruquintinib or regorafenib was allowed but not mandatory. Baseline demographic and clinical characteristics were collected appropriately. Every 2 or 3 treatment cycles, the patients were assessed by computed tomography (CT) scans and clinical assessments until disease progression or loss to follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE 5.0) were presented as n (%). The primary endpoint was investigator-evaluated overall survival (OS). As this is a retrospective cohort study, sample size calculation was not performed. Eligible patients would be enrolled as many as possible. Results: A total of 90 patients were enrolled, including 58 patients who received TAS-102 plus BEV and another 32 patients who received TAS-102 monotherapy. The known baseline characteristics were comparable (P<0.05). With a median follow-up of 4.60 months (range, 0.20-22.80), the median OS (mOS) time in the TAS-102 plus BEV group was longer than that in the TAS-102 monotherapy group (10.83 vs. 7.43 months), but the difference was not significant (P=0.79). The median progression-free survival (mPFS) time was comparable between the two groups (4.67 vs. 4.30 months, P=0.96). Multivariate Cox regression analysis demonstrated that undergoing therapy after TAS-102 either with or without BEV was an independent risk factor for OS [hazard ratio (HR) =0.25; 95% confidence interval (CI): 0.09-0.71, P<0.01], and previous treatment with cetuximab was an independent protective factor for PFS (HR =0.17; 95% CI: 0.03-0.91, P=0.04). Of the 70 patients who were evaluated, those receiving TAS-102 plus BEV showed trend of a higher objective response rate (ORR) and disease control rate (DCR) than those who received TAS-102 monotherapy (P=0.16 and P=0.29, respectively). Adverse events (AEs) were similar between the two groups, except that the incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group. Conclusions: There was a trend in favor of the combination of BEV plus TAS-102 regarding OS and DCR, without reaching statistical significance, and it means that there was no clear advantage of one over the other in terms of efficacy. Further prospective studies are still necessary to draw a definite conclusion.

Innovative methods for microplastic characterization and detection: Deep learning supported by photoacoustic imaging and automated pre-processing data.

Plastic products' widespread applications and their non-biodegradable nature have resulted in the continuous accumulation of microplastic waste, emerging as a significant component of ecological environmental issues. In the field of microplastic detection, the intricate morphology poses challenges in achieving rapid visual characterization of microplastics. In this study, photoacoustic imaging technology is initially employed to capture high-resolution images of diverse microplastic samples. To address the limited dataset issue, an automated data processing pipeline is designed to obtain sample masks while effectively expanding the dataset size. Additionally, we propose Vqdp2, a generative deep learning model with multiple proxy tasks, for predicting six forms of microplastics data. By simultaneously constraining model parameters through two training modes, outstanding morphological category representations are achieved. The results demonstrate Vqdp2's excellent performance in classification accuracy and feature extraction by leveraging the advantages of multi-task training. This research is expected to be attractive for the detection classification and visual characterization of microplastics.

Identification of Susceptibility Genes Underlying Bovine Respiratory Disease in Xinjiang Brown Cattle Based on DNA Methylation.

DNA methylation is a form of epigenetic regulation, having pivotal parts in controlling cellular expansion and expression levels within genes. Although blood DNA methylation has been studied in humans and other species, its prominence in cattle is largely unknown. This study aimed to methodically probe the genomic methylation map of Xinjiang brown (XJB) cattle suffering from bovine respiratory disease (BRD), consequently widening cattle blood methylome ranges. Genome-wide DNA methylation profiling of the XJB blood was investigated through whole-genome bisulfite sequencing (WGBS). Many differentially methylated regions (DMRs) obtained by comparing the cases and controls groups were found within the CG, CHG, and CHH (where H is A, T, or C) sequences (16,765, 7502, and 2656, respectively), encompassing 4334 differentially methylated genes (DMGs). Furthermore, GO/KEGG analyses showed that some DMGs were involved within immune response pathways. Combining WGBS-Seq data and existing RNA-Seq data, we identified 71 significantly differentially methylated (DMGs) and expressed (DEGs) genes (p < 0.05). Next, complementary analyses identified nine DMGs (LTA, STAT3, IKBKG, IRAK1, NOD2, TLR2, TNFRSF1A, and IKBKB) that might be involved in the immune response of XJB cattle infected with respiratory diseases. Although further investigations are needed to confirm their exact implication in the involved immune processes, these genes could potentially be used for a marker-assisted selection of animals resistant to BRD. This study also provides new knowledge regarding epigenetic control for the bovine respiratory immune process.

Molecular Epidemiology and Clinical Characteristics of an Outbreak on Respiratory Virus Coinfection in Gansu, China.

This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.

Origin of Interfacial Orbital Reconstruction in Perovskite Superlattices.

The competition between on-site electronic correlation and local crystal field stands out as a captivating topic in research. However, its physical ramifications often get overshadowed by influences of strong periodic potential and orbital hybridization. The present study reveals this competition may become more pronounced or even dominant in two-dimensional systems, driven by the combined effects of dimensional confinement and orbital anisotropy. This leads to electronic orbital reconstruction in certain perovskite superlattices or thin films. To explore the emerging physics, we investigate the interfacial orbital disorder-order transition with an effective Hamiltonian and how to modulate this transition through strains.

Advancing microplastic surveillance through photoacoustic imaging and deep learning techniques.

Microplastic contamination presents a significant global environmental threat, yet scientific understanding of its morphological distribution within ecosystems remains limited. This study introduces a pioneering method for comprehensive microplastic assessment and environmental monitoring, integrating photoacoustic imaging and advanced deep learning techniques. Rigorous curation of diverse microplastic datasets enhances model training, yielding a high-resolution imaging dataset focused on shape-based discrimination. The introduction of the Vector-Quantized Variational Auto Encoder (VQVAE2) deep learning model signifies a substantial advancement, demonstrating exceptional proficiency in image dimensionality reduction and clustering. Furthermore, the utilization of Vector Quantization Microplastic Photoacoustic imaging (VQMPA) with a proxy task before decoding enhances feature extraction, enabling simultaneous microplastic analysis and discrimination. Despite inherent limitations, this study lays a robust foundation for future research, suggesting avenues for enhancing microplastic identification precision through expanded sample sizes and complementary methodologies like spectroscopy. In conclusion, this innovative approach not only advances microplastic monitoring but also provides valuable insights for future environmental investigations, highlighting the potential of photoacoustic imaging and deep learning in bolstering sustainable environmental monitoring efforts.

The role of foam cells in spinal cord injury: challenges and opportunities for intervention.

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.

Dapagliflozin prevents kidney podocytes pyroptosis via miR-155-5p/HO-1/NLRP3 axis modulation.

Diabetic nephropathy (DN) is a significant clinical microvascular complication associated with diabetes mellitus (DM), and end-stage diabetes giving rise to kidney failure is developing into the major etiological factor of chronic kidney failure. Dapagliflozin is reported to limit podocyte damage in DM, which has proven to protect against renal failure. Mounting evidence has demonstrated that pyroptosis is associated with DM progression. Nevertheless, whether pyroptosis causes DN and the underlying molecular pathways remain obscure. In this study, we aimed to explore the antipyroptotic attributes of dapagliflozin and elucidate the underlying mechanisms of kidney damage in diabetes. In vivo, experiments were conducted in streptozotocin (STZ)-induced type 2 diabetic mice, which were administered dapagliflozin via gavage for 6 weeks. Subsequently, the specific organizational characteristics and expression of pyroptosis-related genes were evaluated. Intragastric dapagliflozin administration markedly reduced renal tissue injury. Meanwhile, dapagliflozin also attenuated the expression level of pyroptosis associated genes, including ASC, cleaved Caspase-1, GSDMD N-termini, NLRP3, IL-18, and IL-1ß in renal tissue of dapagliflozin-treated animals. Similar antipyroptotic effects were observed in palmitic acid (PA)-treated mouse podocytes. We also found that heme oxygenase 1 (HO-1) enhanced the protection of mouse podocyte clone 5 cells (MPC5). Moreover, miR-155-5p inhibition increased pyroptosis in PA-treated MPC5 cells, suggesting that miR-155-5p acts as an endogenous stimulator that increases HO-1 expression and reduces pyroptosis. Hence, our findings imply that dapagliflozin inhibits podocyte pyroptosis via the miR-155-5p/HO-1/NLRP3 axis in DM. Furthermore, dapagliflozin substitution may be regarded as an effective strategy for preventing pyroptosis in the kidney, including a therapeutic option for treating pyroptosis-related DN.

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes.

BACKGROUND: Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvß3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy. AIM: To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux. METHODS: SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50 µg/kg cerulein plus lipopolysaccharide. mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAP-induced liver injury. Cilengitide, a specific αvß3/5 integrin inhibitor, was used to investigate the possible mechanism of MFG-E8. RESULTS: The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice, enhanced autophagy flux in hepatocyte, and worsened the degree of ferroptosis. Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner. Mechanistically, MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells. Cilengitide abolished MFG-E8's beneficial effects in SAP-induced liver injury. CONCLUSION: MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury. MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrin αVß3/5.

Study on the interaction protein of transcription factor Smad3 based on TurboID proximity labeling technology.

TurboID is a highly efficient biotin-labelling enzyme, which can be used to explore a number of new intercalating proteins due to the very transient binding and catalytic functions of many proteins. TGF-ß/Smad3 signaling pathway is involved in many diseases, especially in diabetic nephropathy and inflammation. In this paper, a stably cell line transfected with Smad3 were constructed by using lentiviral infection. To further investigate the function of TGF-ß/Smad3, the protein labeling experiment was conducted to find the interacting protein with Smad3 gene. Label-free mass spectrometry analysis was performed to obtain 491 interacting proteins, and the interacting protein hnRNPM was selected for IP and immunofluorescence verification, and it was verified that the Smad3 gene had a certain promoting effect on the expression of hnRNPM gene, and then had an inhibitory effect on IL-6. It lays a foundation for further study of the function of Smad3 gene and its involved regulatory network.

Enhancing subcellular protein localization mapping analysis using Sc2promap utilizing attention mechanisms.

BACKGROUND: Aberrant protein localization is a prominent feature in many human diseases and can have detrimental effects on the function of specific tissues and organs. High-throughput technologies, which continue to advance with iterations of automated equipment and the development of bioinformatics, enable the acquisition of large-scale data that are more pattern-rich, allowing for the use of a wider range of methods to extract useful patterns and knowledge from them. METHODS: The proposed sc2promap (Spatial and Channel for SubCellular Protein Localization Mapping) model, designed to proficiently extract meaningful features from a vast repository of single-channel grayscale protein images for the purposes of protein localization analysis and clustering. Sc2promap incorporates a prediction head component enriched with supplementary protein annotations, along with the integration of a spatial-channel attention mechanism within the encoder to enables the generation of high-resolution protein localization maps that encapsulate the fundamental characteristics of cells, including elemental cellular localizations such as nuclear and non-nuclear domains. RESULTS: Qualitative and quantitative comparisons were conducted across internal and external clustering evaluation metrics, as well as various facets of the clustering results. The study also explored different components of the model. The research outcomes conclusively indicate that, in comparison to previous methods, Sc2promap exhibits superior performance. CONCLUSIONS: The amalgamation of the attention mechanism and prediction head components has led the model to excel in protein localization clustering and analysis tasks. GENERAL SIGNIFICANCE: The model effectively enhances the capability to extract features and knowledge from protein fluorescence images.

Robust treatment planning for small animal radio-neuromodulation using focused kV x-ray beams.

BACKGROUND: In preclinical radio-neuromodulation research, small animal experiments are pivotal for unraveling radiobiological mechanism, investigating prescription and planning techniques, and assessing treatment effects and toxicities. However, the target size inside a rat brain is typically in the order of sub-millimeters. The small target inside the visual cortex neural region in rat brain with a diameter of around 1 mm was focused in this work to observe the physiological change of this region. Delivering uniform doses to the small target while sparing health tissues is challenging. Focused kV x-ray technique based on modern x-ray polycapillary focusing lens is a promising modality for small animal radio-neuromodulation. PURPOSE: The current manual planning method could lead to sub-optimal plans, and the positioning uncertainties due to mechanical accuracy limitations, animal immobilization, and robotic arm motion are not considered. This work aims to design a robust inverse planning method to optimize the intensities of focused kV x-ray beams located in beam trajectories to irradiate small mm-sized targets in rat brains for radio-neuromodulation. METHODS: Focused kV x-ray beams were generated through polycapillary x-ray focusing lenses on achieving small (≤0.3 mm) focus perpendicular to the beam. The beam trajectories were manually designed in 3D space in scanning-while-rotating mode. Geant4 Monte Carlo (MC) simulation generated a dose calculation matrix for each focused kV x-ray beam located in beam trajectories. In the proposed robust inverse planning method, an objective function combining a voxel-wise stochastic programming approach and L1 norm regularization was established to overcome the positioning uncertainties and obtain a high-quality plan. The fast iterative shrinkage thresholding algorithm (FISTA) was utilized to solve the objective function and obtain the optimal intensities. Four cases were employed to validate the feasibility and effectiveness of the proposed method. The manual and non-robust inverse planning methods were also implemented for comparison. RESULTS: The proposed robust inverse planning method achieved superior dose homogeneity and higher robustness against positioning uncertainties. On average, the clinical target volume (CTV) homogeneity index (HI) of robust inverse plan improved to 13.3 from 22.9 in non-robust inverse plan and 53.8 in manual plan if positioning uncertainties were also present. The average bandwidth at D90 was reduced by 6.5 Gy in the robust inverse plan, compared to 9.6 Gy in non-robust inverse plan and 12.5 Gy in manual plan. The average bandwidth at D80 was reduced by 3.4 Gy in robust inverse plan, compared to 5.5 Gy in non-robust inverse plan and 8.5 Gy in manual plan. Moreover, the dose delivery time of manual plan was reduced by an average reduction of 54.7% with robust inverse plan and 29.0% with non-robust inverse plan. CONCLUSION: Compared to manual and non-robust inverse planning methods, the robust inverse planning method improved the dose homogeneity and delivery efficiency and was resistant to the uncertainties, which are crucial for radio-neuromodulation utilizing focused kV x-rays.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

SPI1 exacerbates iron accumulation and promotes osteoclast formation through inhibiting the expression of Hepcidin.

BACKGROUND: Osteoporosis (OP) can be caused by an overactive osteoclastic function. Anti-osteoporosis considerable therapeutic effects in tissue repair and regeneration because bone resorption is a unique osteoclast function. In this study, we mainly explored the underlying mechanisms of osteoclasts' effects on osteoporosis. METHODS: RAW264.7 cells were used and induced toward osteoclast and iron accumulation by M-CSF and RANKL administration. We investigated Hepcidin and divalent metal transporter 1 (DMT1) on iron accumulation and osteoclast formation in an ovariectomy (OVX)-induced osteoporosis. Osteoporosis was induced in mice by OVX, and treated with Hepcidin (10, 20, 40, 80 mg/kg, respectively) and overexpression of DMT1 by tail vein injection. Hepcidin, SPI1, and DMT1 were detected by immunohistochemical staining, western blot and RT-PCR. The bioinformatics assays, luciferase assays, and Chromatin Immunoprecipitation (ChIP) verified that Hepcidin was a direct SPI1 transcriptional target. Iron accumulation was detected by laser scanning confocal microscopy, Perl's iron staining and iron content assay. The formation of osteoclasts was assessed using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: We found that RAW264.7 cells differentiated into osteoclasts when exposed to M-CSF and RANKL, which increased the protein levels of osteoclastogenesis-related genes, including c-Fos, MMP9, and Acp5. We also observed higher concentration of iron accumulation when M-CSF and RANKL were administered. However, Hepcidin inhibited the osteoclast differentiation cells and decreased intracellular iron concentration primary osteoclasts derived from RAW264.7. Spi-1 proto-oncogene (SPI1) transcriptionally repressed the expression of Hepcidin, increased DMT1, facilitated the differentiation and iron accumulation of mouse osteoclasts. Overexpression of SPI1 significantly declined luciferase activity of HAMP promoter and increased the enrichment of HAMP promoter. Furthermore, our results showed that Hepcidin inhibited osteoclast differentiation and iron accumulation in mouse osteoclasts and OVX mice. CONCLUSION: Therefore, the study revealed that SPI1 could inhibit Hepcidin expression contribute to iron accumulation and osteoclast formation via DMT1 signaling activation in mouse with OVX.

Fast Real-Time Brain Tumor Detection Based on Stimulated Raman Histology and Self-Supervised Deep Learning Model.

In intraoperative brain cancer procedures, real-time diagnosis is essential for ensuring safe and effective care. The prevailing workflow, which relies on histological staining with hematoxylin and eosin (H&E) for tissue processing, is resource-intensive, time-consuming, and requires considerable labor. Recently, an innovative approach combining stimulated Raman histology (SRH) and deep convolutional neural networks (CNN) has emerged, creating a new avenue for real-time cancer diagnosis during surgery. While this approach exhibits potential, there exists an opportunity for refinement in the domain of feature extraction. In this study, we employ coherent Raman scattering imaging method and a self-supervised deep learning model (VQVAE2) to enhance the speed of SRH image acquisition and feature representation, thereby enhancing the capability of automated real-time bedside diagnosis. Specifically, we propose the VQSRS network, which integrates vector quantization with a proxy task based on patch annotation for analysis of brain tumor subtypes. Training on images collected from the SRS microscopy system, our VQSRS demonstrates a significant speed enhancement over traditional techniques (e.g., 20-30 min). Comparative studies in dimensionality reduction clustering confirm the diagnostic capacity of VQSRS rivals that of CNN. By learning a hierarchical structure of recognizable histological features, VQSRS classifies major tissue pathological categories in brain tumors. Additionally, an external semantic segmentation method is applied for identifying tumor-infiltrated regions in SRH images. Collectively, these findings indicate that this automated real-time prediction technique holds the potential to streamline intraoperative cancer diagnosis, providing assistance to pathologists in simplifying the process.