The correct interpretation of breast density is important in the assessment of breast cancer risk. AI has been shown capable of accurately predicting breast density, however, due to the differences in imaging characteristics across mammography systems, models built using data from one system do not generalize well to other systems. Though federated learning (FL) has emerged as a way to improve the generalizability of AI without the need to share data, the best way to preserve features from all training data during FL is an active area of research. To explore FL methodology, the breast density classification FL challenge was hosted in partnership with the American College of Radiology, Harvard Medical Schools' Mass General Brigham, University of Colorado, NVIDIA, and the National Institutes of Health National Cancer Institute. Challenge participants were able to submit docker containers capable of implementing FL on three simulated medical facilities, each containing a unique large mammography dataset. The breast density FL challenge ran from June 15 to September 5, 2022, attracting seven finalists from around the world. The winning FL submission reached a linear kappa score of 0.653 on the challenge test data and 0.413 on an external testing dataset, scoring comparably to a model trained on the same data in a central location.
Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.
OBJECTIVES: Ultrasonic scaling is extensively applied as part of the initial therapy for periodontal diseases, which has been restricted since the outbreak of the COVID-19 pandemic due to droplets and aerosols generated by ultrasonic devices. An extraoral scavenging device (EOS) was designed for diminishing droplets and aerosols in dental clinics. The objective of this study is to evaluate the effect of EOS on eliminating droplets and aerosols during ultrasonic supragingival scaling. METHODS: This single-blinded, randomised controlled clinical trial enrolled 45 patients with generalised periodontitis (stage I or II, grade A or B) or plaque-induced gingivitis. The patients were randomly allocated and received ultrasonic supragingival scaling under three different intervention measures: only saliva ejector (SE), SE plus EOS and SE plus high-volume evacuation (HVE). The natural sedimentation method was applied to sample droplets and aerosols before or during supragingival scaling. After aerobic culturing, colony-forming units (CFUs) were counted and analysed. RESULTS: Compared with the level before treatment, more CFUs of samples throughout treatment could be obtained at the operator's chest and the patient's chest and the table surface when using SE alone (p < 0.05). Compared with the SE group, the SE + EOS group and the SE + HVE group obtained decreasing CFUs at the operator's chest and the patient's chest (p < 0.05), while no significant difference was determined between these two groups. CONCLUSIONS: The EOS effectively eliminated splatter contamination from ultrasonic supragingival scaling, which was an alternative precaution for nosocomial contamination in dental clinics.
Background: Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics. Methods: A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student t-test. Results: Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8+ T cells in PBMCs (P=0.0005), and altered frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8+ stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients. Conclusions: The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.
Soil nematodes are the most abundant animals on Earth and play critical roles in regulating numerous ecosystem processes, from enhancing primary productivity to mineralizing multiple nutrients. In dryland soils, a rich community of microphyte organisms (biocrusts) provide critical habitats for soil nematodes, but their presence is being threatened by increasing aridity induced by global climate change. Despite its importance, how types of biocrusts and aridity index influence soil nematode community in dryland mountain ecosystems remains largely unknown. To fill these knowledge gaps, we conducted a field survey with contrasting aridity indexes (0.2, 0.4, and 0.6) and three types of biocrusts (cyanobacterial, cyanobacterial-moss mixed, and moss crusts) in the topsoil (0-5 cm) from the northern Chinese Loess Plateau. We found that the abundance (number of individuals per gram of soil), richness (number of Operational Taxonomic Units; OTUs), and diversity (number of different species) of soil nematodes were remarkably higher under biocrusts than in bare soils, regardless of aridity index and types of biocrusts. Our results also showed that the same variables had the highest values in moss crusts compared to cyanobacterial and cyanobacterial-moss mixed crusts. Structural equation modelling further revealed that biocrust types and traits (i.e., biocrust thickness, chlorophyll content, shear force, and penetration resistance) are the most important factors associated with both nematode abundance and richness. Together, our findings indicate that biocrusts, especially moss cover, and less stressful aridity conditions favor soil nematodes community in dryland mountain regions. Such knowledge is critical for anticipating the distribution of these animals under climate change scenarios and, ultimately, the numerous ecosystem services supported by soil nematodes.
Bryophyta , Cyanobacteria , Ecosystem , Nematoda , Soil , Animals , China , Climate Change , Desert Climate , Environmental Monitoring
OBJECTIVE: Recently, large language models (LLMs) have showcased remarkable capabilities in natural language understanding. While demonstrating proficiency in everyday conversations and question-answering (QA) situations, these models frequently struggle in domains that require precision, such as medical applications, due to their lack of domain-specific knowledge. In this article, we describe the procedure for building a powerful, open-source language model specifically designed for medicine applications, termed as PMC-LLaMA. MATERIALS AND METHODS: We adapt a general-purpose LLM toward the medical domain, involving data-centric knowledge injection through the integration of 4.8M biomedical academic papers and 30K medical textbooks, as well as comprehensive domain-specific instruction fine-tuning, encompassing medical QA, rationale for reasoning, and conversational dialogues with 202M tokens. RESULTS: While evaluating various public medical QA benchmarks and manual rating, our lightweight PMC-LLaMA, which consists of only 13B parameters, exhibits superior performance, even surpassing ChatGPT. All models, codes, and datasets for instruction tuning will be released to the research community. DISCUSSION: Our contributions are 3-fold: (1) we build up an open-source LLM toward the medical domain. We believe the proposed PMC-LLaMA model can promote further development of foundation models in medicine, serving as a medical trainable basic generative language backbone; (2) we conduct thorough ablation studies to demonstrate the effectiveness of each proposed component, demonstrating how different training data and model scales affect medical LLMs; (3) we contribute a large-scale, comprehensive dataset for instruction tuning. CONCLUSION: In this article, we systematically investigate the process of building up an open-source medical-specific LLM, PMC-LLaMA.
Cross-modal retrieval for rice leaf diseases is crucial for prevention, providing agricultural experts with data-driven decision support to address disease threats and safeguard rice production. To overcome the limitations of current crop leaf disease retrieval frameworks, we focused on four common rice leaf diseases and established the first cross-modal rice leaf disease retrieval dataset (CRLDRD). We introduced cross-modal retrieval to the domain of rice leaf disease retrieval and introduced FHTW-Net, a framework for rice leaf disease image-text retrieval. To address the challenge of matching diverse image categories with complex text descriptions during the retrieval process, we initially employed ViT and BERT to extract fine-grained image and text feature sequences enriched with contextual information. Subsequently, two-way mixed self-attention (TMS) was introduced to enhance both image and text feature sequences, with the aim of uncovering important semantic information in both modalities. Then, we developed false-negative elimination-hard negative mining (FNE-HNM) strategy to facilitate in-depth exploration of semantic connections between different modalities. This strategy aids in selecting challenging negative samples for elimination to constrain the model within the triplet loss function. Finally, we introduced warm-up bat algorithm (WBA) for learning rate optimization, which improves the model's convergence speed and accuracy. Experimental results demonstrated that FHTW-Net outperforms state-of-the-art models. In image-to-text retrieval, it achieved R@1, R@5, and R@10 accuracies of 83.5%, 92%, and 94%, respectively, while in text-to-image retrieval, it achieved accuracies of 82.5%, 98%, and 98.5%, respectively. FHTW-Net offers advanced technical support and algorithmic guidance for cross-modal retrieval of rice leaf diseases.
Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.
Vision-Language Pre-training (VLP) that utilizes the multi-modal information to promote the training efficiency and effectiveness, has achieved great success in vision recognition of natural domains and shown promise in medical imaging diagnosis for the Chest X-Rays (CXRs). However, current works mainly pay attention to the exploration on single dataset of CXRs, which locks the potential of this powerful paradigm on larger hybrid of multi-source CXRs datasets. We identify that although blending samples from the diverse sources offers the advantages to improve the model generalization, it is still challenging to maintain the consistent superiority for the task of each source due to the existing heterogeneity among sources. To handle this dilemma, we design a Conquer-and-Divide pre-training framework, termed as UniChest, aiming to make full use of the collaboration benefit of multiple sources of CXRs while reducing the negative influence of the source heterogeneity. Specially, the "Conquer" stage in UniChest encourages the model to sufficiently capture multi-source common patterns, and the "Divide" stage helps squeeze personalized patterns into different small experts (query networks). We conduct thorough experiments on many benchmarks, e.g., ChestX-ray14, CheXpert, Vindr-CXR, Shenzhen, Open-I and SIIM-ACR Pneumothorax, verifying the effectiveness of UniChest over a range of baselines, and release our codes and pre-training models at https://github.com/Elfenreigen/UniChest.
Perfluoroalkyl substances (PFASs) are persistent and toxic to human health. It is demanding for high-efficient and green technologies to remove PFASs from water. In this study, a novel PFAS treatment technology was developed, utilizing polytetrafluoroethylene (PTFE) particles (1-5â µm) as the catalyst and a low frequency ultrasound (US, 40â kHz, 0.3â W/cm2) for activation. Remarkably, this system can induce near-complete defluorination for different structured PFASs. The underlying mechanism relies on contact electrification between PTFE and water, which induces cumulative electrons on PTFE surface, and creates a high surface voltage (tens of volts). Such high surface voltage can generate abundant reactive oxygen species (ROS, i.e., O2â -, HOâ , etc.) and a strong interfacial electrostatic field (IEF of 109~1010â V/m). Consequently, the strong IEF significantly activates PFAS molecules and reduces the energy barrier of O2â - nucleophilic reaction. Simultaneously, the co-existence of surface electrons (PTFE*(e-)) and HOâ enables synergetic reduction and oxidation of PFAS and its intermediates, leading to enhanced and thorough defluorination. The US/PTFE method shows compelling advantages of low energy consumption, zero chemical input, and few harmful intermediates. It offers a new and promising solution for effectively treating the PFAS-contaminated drinking water.
Extensive applications of chiral lattice structures in the field of acoustic wave manipulation and vibration modulation show the effectiveness of chirality route to the design of phononic crystals. However, how and to what extent the material chirality affects the band gap properties of phononic crystals remains unclear. In this study, one-dimensional phononic crystals made of chiral materials is proposed, and a theoretical model of shear horizontal (SH) wave propagation in the chiral phononic crystals is developed based on the noncentrosymmetric micropolar elasticity theory. Through the transfer matrix method, the dispersion relationship of SH wave propagation is obtained and the effects of material chirality on the band-gap properties are investigated. Our work demonstrates that the change of material chirality can significantly affect the dispersion relationship of phononic crystals, leading to the wide band gap and low frequency. In a unit cell, when the chiral coefficients of the two parts have opposite signs but the same magnitude and the chiral directions are consistent with the vibrational direction, it is the most favorable for the phononic crystals to achieve the lowest frequency and widest band gap. This study suggests that the material chirality can be harnessed to effectively tune the band-gap properties of phononic crystals. The present study provides insight for the chirality route to the design of phononic crystals.
Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood-testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood-testis barrier.
Blood-Testis Barrier , Histone Deacetylases , Sertoli Cells , Animals , Male , Mice , Blood-Testis Barrier/metabolism , Cell Differentiation , Sertoli Cells/metabolism , Spermatocytes/metabolism , Spermatogenesis/genetics , Testis/metabolism , Tight Junctions/metabolism , Histone Deacetylases/genetics , Histone Deacetylases/metabolism
Cr coatings with a thickness of about 19 µm were synthesized on Zr-4 cladding using plasma-enhanced arc ion plating. A Zr-Cr micro-diffusion layer was formed via Cr ion cleaning before deposition to enhance the interface bonding strength. Cr coatings exhibit an obvious columnar crystal structure with an average grain size of 1.26 µm using SEM (scanning electron microscopy) and EBSD (electron backscatter diffraction) with a small amount of nanoscale pores on the surface. A long-term aqueous test at 420 ± 3 °C, 10.3 ± 0.7 MPa and isothermal oxidation tests at 900~1300 °C in air were conducted to evaluate the Cr-coated Zr-4 cladding. All the results showed that the Cr coatings had a significant protective effect to the Zr-4 alloy. However, the corrosion deterioration mechanism is different. A gradual thinning of the Cr coating was observed in a long-term aqueous test, but a cyclic corrosion mechanism of void initiation-propagation-cracking at the oxide film interface is the main corrosion characteristic of the Cr coating in isothermal oxidation. Different corrosion models are constructed to explain the corrosion mechanism.
Puccinia striiformis f. sp. tritici (Pst) secretes effector proteins that enter plant cells to manipulate host immune processes. In this report we present an important Pst effector, Pst03724, whose mRNA expression level increases during Pst infection of wheat (Triticum aestivum). Silencing of Pst03724 reduced the growth and development of Pst. Pst03724 targeted the wheat calmodulin TaCaM3-2B, a positive regulator of wheat immunity. Subsequent investigations revealed that Pst03724 interferes with the TaCaM3-2B-NAD kinase TaNADK2 association and thus inhibits the enzyme activity of TaNADK2 activated by TaCaM3-2B. Knocking down TaNADK2 expression by virus-mediated gene silencing (VIGS) significantly increased fungal growth and development, suggesting a decrease in resistance against Pst infection. In conclusion, our findings indicate that Pst effector Pst03724 inhibits the activity of NAD kinase by interfering with the TaCaM3-2B-TaNADK2 association, thereby facilitating Pst infection.
BACKGROUND: Energy metabolism has a complex intersection with pathogenesis and development of breast cancer (BC). This allows for the possibility of identifying energy-metabolism-related genes (EMRGs) as novel prognostic biomarkers for BC. 7-dehydrocholesterol reductase (DHCR7) is a key enzyme of cholesterol biosynthesis involved in many cancers, and in this paper, we investigate the effects of DHCR7 on the proliferation and mitochondrial function of BC. METHODS: EMRGs were identified from the Gene Expression Omnibus (GEO) and MSigDB databases using bioinformatics methods. Key EMRGs of BC were then identified and validated by functional enrichment analysis, interaction analysis, weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, Cox analysis, and immune infiltration. Western blot, qRT-PCR, immunohistochemistry (IHC), MTT assay, colony formation assay and flow cytometry assay were then used to analyze DHCR7 expression and its biological effects on BC cells. RESULTS: We identified 31 EMRGs in BC. These 31 EMRGs and related transcription factors (TFs), miRNAs, and drugs were enriched in glycerophospholipid metabolism, glycoprotein metabolic process, breast cancer, and cell cycle. Crucially, DHCR7 was a key EMRG in BC identified and validated by WGCNA, LASSO regression and receiver operating characteristic (ROC) curve analysis. High DHCR7 expression was significantly associated with tumor immune infiltration level, pathological M, and poor prognosis in BC. In addition, DHCR7 knockdown inhibited cell proliferation, induced apoptosis and affected mitochondrial function in BC cells. CONCLUSIONS: DHCR7 was found to be a key EMRG up-regulated in BC cells. This study is the first to our knowledge to report that DHCR7 acts as an oncogene in BC, which might become a novel therapeutic target for BC patients.
Biomarkers, Tumor , Breast Neoplasms , Cell Proliferation , Gene Expression Regulation, Neoplastic , Mitochondria , Oxidoreductases Acting on CH-CH Group Donors , Humans , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Oxidoreductases Acting on CH-CH Group Donors/genetics , Oxidoreductases Acting on CH-CH Group Donors/metabolism , Female , Cell Proliferation/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Mitochondria/metabolism , Mitochondria/genetics , Cell Line, Tumor , Energy Metabolism/genetics , Prognosis , MCF-7 Cells
Moiré effects arising from mutually twisted metasurfaces have showcased remarkable wave manipulation capabilities, unveiling tantalizing emerging phenomena such as acoustic moiré flat bands and topological phase transitions. However, the pursuit of strong near-field coupling in layers has necessitated acoustic moiré metasurfaces to be tightly stacked at narrow distances in the subwavelength range. Here, moiré effects beyond near-field interlayer coupling in acoustics are reported and the concept of coupling-immune moiré metasurfaces is proposed. Remote acoustic moiré effects decoupled from the interlayer distance are theoretically, numerically, and experimentally demonstrated. Tunable out-of-plane acoustic beam scanning is successfully achieved by dynamically controlling twist angles. The engineered coupling-immune properties are further extended to multilayered acoustic moiré metasurfaces and manipulation of acoustic vortices. Good robustness against external disturbances is also observed for the fabricated coupling-immune acoustic moiré metasurfaces. The presented work unlocks the potential of twisted moiré devices for out-of-plane acoustic beam shaping, enabling practical applications in remote dynamic detection, and multiplexed underwater acoustic communication.
BACKGROUND: Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS: This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS: Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS: Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.
Air Pollutants , Air Pollution , Environmental Pollutants , Ischemic Stroke , Humans , Air Pollutants/adverse effects , Air Pollutants/analysis , Nitrogen Dioxide/adverse effects , Nitrogen Dioxide/analysis , Ischemic Stroke/chemically induced , UK Biobank , Biological Specimen Banks , Particulate Matter/adverse effects , Particulate Matter/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Nitrogen Oxides , Nitric Oxide , Genetic Risk Score , Environmental Exposure/adverse effects
Lepista sordida is a type of high-quality rare edible and medicinal mushroom, and its research boom is just beginning. More than 80 million tons of grain crop residues are produced each year in Heilongjiang Province. To realize the exploration and utilization of wild L. sordida mushrooms and also provide a theoretical support for the high-value utilization of these resources in Heilongjiang Province, we evaluated the cultivation of L. sordida mushrooms using rice straw, corncob, and soybean straw as substrates. L. sordida grew on all three substrates, and the biological efficiency and yield of the mushrooms grown on soybean straw and corncob were 32.33 ± 1.78% and 4.20 ± 0.23 kg m-2, and 30.15 ± 0.93% and 3.92 ± 0.12 kg m-2, respectively, which increased by 9.38% and 2.08% compared with that on the rice straw substrate with 3.84 ± 0.12 kg m-2 and 29.56 ± 0.89%. The time it took for the mycelia to colonize and initiate primordia on the soybean straw substrate was 22.33 ± 0.58 d and 19.67 ± 0.58 d, respectively, which was delayed by 2 d and 3 d compared with that on the rice straw substrate with 20.67 ± 2.08 d and 16.33 ± 0.58 d, respectively. The fruiting bodies grown on corncob and soybean straw substrates were relatively larger than those on the rice straw substrate. The highest amount of crude protein was 57.38 ± 0.08 g 100 g-1, and the lowest amount of crude polysaccharide was 6.03 ± 0.01 g 100 g-1. They were observed on mushrooms collected from the corncob substrate. The contents of the heavy metal mercury, lead, arsenic, and cadmium in the fruiting bodies grown on each substrate were within the national safety range.
BACKGROUND: Nervous system toxicity (NST) is one of the most frequent and dangerous side effects of chimeric antigen receptor T-cell (CAR-T) therapy, which is an effective treatment for related tumors in most relapsed/refractory (r/r) hematologic malignancies. Current clinical trial data do not fully reflect the real-world situation. Therefore, this study evaluated the NST of CAR-T therapy using the FDA Adverse Event Reporting System (FAERS). METHODS: Data were retrieved from FAERS for the period from January 1, 2017 to March 31, 2023. Disproportionality analysis and Bayesian analysis were used for data mining. The reporting odds ratio (ROR) for NST with 95% confidence interval (CI) was calculated for each CAR-T product. The time to onset (TTO) and clinical outcomes due to CAR-T therapy-associated NST were assessed. RESULTS: Overall, 6946 cases of NST associated with CAR-T therapy were identified. The patients had a median age of 61 years (interquartile range [IQR]: 47-69 years). Significant signals were observed for all CAR-T products (ROR: 2.19, 95% CI: 2.13-2.44). Anti-CD19 CAR-T products showed a higher NST signal than anti-B cell maturation antigen (BCMA) CAR-T products (ROR025 2.13 vs. 1.98). Brexucabtagene autoleucel (ROR: 3.17, 95% CI: 2.90-3.47) and axicabtagene ciloleucel (ROR: 2.92, 95% CI: 2.81-3.03) had the two highest NST signals. For the preferred term "brain edema," the highest signals were obtained for CD28 CAR-T products. The median TTO of NST for all CAR-T products was 7 days (IQR: 3-17 days). The proportion of death, life-threatening and hospitalization adverse events associated with NST was 20.06%, 7.21%, and 32.70%, respectively. The proportion of death outcomes was higher in patients treated with tisagenlecleucel (30.36%) than in those treated with other CAR-T products, except ciltacabtagene autoleucel (P < 0.001). The proportion of hospitalizations was significantly higher for lisocabtagene maraleucel-associated NST (53.85%) than for other drugs, except for ciltacabtagene autoleucel (P < 0.001). CONCLUSIONS: NST is more closely associated with anti-CD19 CAR-Ts and CAR-Ts containing CD28. Serious NST (brain oedema) is likely to occur with CAR-Ts that contain CD28. CAR-T-related NST warrants greater attention owing to the high proportion of serious adverse events and delayed NST.
Hematologic Neoplasms , Receptors, Chimeric Antigen , Humans , Middle Aged , Aged , Bayes Theorem , CD28 Antigens , Neoplasm Recurrence, Local , Adaptor Proteins, Signal Transducing , Antibodies , Antigens, CD19/adverse effects , Immunotherapy, Adoptive/adverse effects , Cell- and Tissue-Based Therapy