A novel multitrophic biofloc technology for duckweed and Megalobrama amblycephala integrated culture: Improving nutrient utilization and animal welfare.

Biofloc technology (BFT) is an eco-friendly aquaculture model that utilizes zero-exchange water. In this study, we investigated the integration of duckweed into BFT in an effort to enhance nitrogen, phosphorus, and carbon utilization and to improve animal welfare for cultivating Megalobrama amblycephala. The experiment spanned 75 days, comparing a group of M. amblycephala supplemented with duckweed (DM) to a control group (CG) with no supplementation, where duckweed consumption relied solely on the feeding behavior of the fish. The concentrations of nitrate, total nitrogen, and phosphorus accumulation were lower in the DM than in the CG from day 45 onwards, with differences of 16.19, 26.90, and 1.45 mg/L, respectively, at the end of the experiment. The DM showed simultaneous increases of 5.77, 11.20, and 5.07 % in the absolute utilization of nitrogen, phosphorus, and carbon, respectively. The abundance of TM7a (10.27 %), linked to nitrate absorption, became the dominant genus in the water of the DM. Additionally, the abundance of Cetobacterium, associated with carbohydrate digestion, was significantly higher in gut of the DM (23.83 %) than in the gut of CG (1.24 %, P < 0.05). Supplementing the diet of M. amblycephala with duckweed improved digestion and antioxidant enzyme activity. Transcriptome data showed that duckweed supplementation resulted in an increase in the expression of genes related to protein digestion and absorption and carbohydrate metabolism in M. amblycephala, and analysis of the significantly enriched pathways further supported improved antioxidant capacity. Based on the above results, we concluded that as M. amblycephala consumes more duckweed, the differences in nitrogen and phosphorus levels between the DM and CG would continue to increase, along with a simultaneous increase in fixed carbon. Thus, this study achieved the goal of recycling BFT resources and improving animal welfare by integrating duckweed.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study.

BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Investigation of synthetic MRI with quantitative parameters for discriminating axillary lymph nodes status in invasive breast cancer.

OBJECTIVE: To investigate the potential value of quantitative parameters derived from synthetic magnetic resonance imaging (syMRI) for discriminating axillary lymph nodes metastasis (ALNM) in breast cancer patients. MATERIALS AND METHODS: A total of 56 females with histopathologically proven invasive breast cancer who underwent both conventional breast MRI and additional syMRI examinations were enrolled in this study, including 30 patients with ALNM and 26 with non-ALNM. SyMRI has enabled quantification of T1 relaxation time (T1), T2 relaxation time (T2) and proton density (PD). The syMRI quantitative parameters of breast primary tumors before (T1tumor, T2tumor, PDtumor) and after (T1+tumor, T2+tumor, PD+tumor) contrast agent injection were obtained. Similarly, measurements were taken for axillary lymph nodes before (T1LN, T2LN, PDLN) and after (T1+LN, T2+LN, PD+LN) the injection, then theΔT1 (T1-T1+), ΔT2 (T2-T2+), ΔPD (PD-PD+), T1/T2 and T1+/T2+ were calculated. All parameters were compared between ANLM and non-ALNM group. Intraclass correlation coefficient for assessing interobserver agreement. The independent Student's t test or Mann-Whitney U test to determine the relationship between the mean quantitative values and the ALNM. Multivariate logistic regression analyses followed by receiver operating characteristics (ROC) analysis for discriminating ALN status. A P value < 0.05 was considered statistically significant. RESULTS: The short-diameter of lymph nodes (DLN) in ALNM group was significantly longer than that in the non-ALNM group (10.22 ± 3.58 mm vs. 5.28 ± 1.39 mm, P < 0.001). The optimal cutoff value was determined to be 5.78 mm, with an AUC of 0.894 (95 % CI: 0.838-0.939), a sensitivity of 86.7 %, and a specificity of 90.2 %. In syMRI quantitative parameters of breast tumors, T2tumor, ΔT2tumor and ΔPDtumor values showed statistically significant differences between the two groups (P < 0.05). T2tumor value had the best performance in discriminating ALN status (AUC = 0.712), and the optimal cutoff was 90.12 ms, the sensitivity and specificity were 65.0 % and 83.6 % respectively. In terms of syMRI quantitative parameters of lymph nodes, T1LN, T2LN, T1LN/T2LN, T2+LN and ΔT1LN values were significantly different between the two groups (P < 0.05), and their AUCs were 0.785, 0.840, 0.886, 0.702 and 0.754, respectively. Multivariate analyses indicated that the T1LN value was the only independent predictor of ALNM (OR=1.426, 95 % CI: 1.130-1.798, P = 0.039). The diagnostic sensitivity and specificity of T1LN was 86.7 % and 69.4 % respectively at the best cutoff point of 1371.00 ms. The combination of T1LN, T2LN, T1LN/T2LN, ΔT1LN and DLN had better performance for differentiating ALNM and non-ALNM, with AUCs of 0.905, 0.957, 0.964 and 0.897, respectively. CONCLUSION: The quantitative parameters derived from syMRI have certain value for discriminating ALN status in invasive breast cancer, with T2tumor showing the highest diagnostic efficiency among breast lesions parameters. Moreover, T1LN acted as an independent predictor of ALNM.

Ultrasound-based radiomics for early predicting response to neoadjuvant chemotherapy in patients with breast cancer: a systematic review with meta-analysis.

OBJECTIVE: This study aims to evaluate the diagnostic accuracy of ultrasound imaging (US)-based radiomics for the early prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We comprehensively searched PubMed, Cochrane Library, Embase, and Web of Science databases up to 1 January 2023 for eligible studies. We assessed the methodological quality of the enrolled studies with Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 tools. We performed meta-analyses to summarize the diagnostic efficacy of US-based radiomics in response to NAC in breast cancer patients. RESULTS: Eight studies proved eligible. Eligible studies exhibited an average RQS score of 12.88 (35.8% of the total score), with the RQS score ranging from 8 to 19. In the meta-analyses, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.87 (95% CI 0.81-0.92), 0.78 (95% CI 0.72-0.83), 4.02 (95% CI 3.18-5.08), 0.16 (95% CI 0.10-0.25), and 25.17 (95% CI 15.10-41.95), respectively. Results from subgroup analyses indicated that prospective studies apparently exhibited more optimal sensitivity than retrospective studies. Sensitivity analyses exhibited similar results to the primary analyses. CONCLUSION: US-based radiomics may be a potentially crucial adjuvant method for evaluating the response of breast cancer to NAC. Due to limited data available and low quality of eligible studies, more multicenter prospective studies with rigorous methods are required to confirm our findings.

Monoclonal antibodies for dyslipidemia in adults: a focus on vulnerable patients groups.

INTRODUCTION: Dyslipidemia significantly contributes to atherosclerotic cardiovascular disease (ASCVD). Patients with lipid-rich vulnerable plaques are particularly susceptible to cardiovascular complications. Despite available lipid-lowering therapies (LLTs), challenges in effective lipid management remain. AREAS COVERED: This article reviews monoclonal antibody (mAb) therapy in dyslipidemia, particularly focusing on vulnerable plaques and patients. We have reviewed the definitions of vulnerable plaques and patients, outlined the efficacy of traditional LLTs, and discussed in-depth the mAbs targeting PCSK9. We extensively discuss the potential mechanisms, intracoronary imaging, and clinical evidence of PCSK9mAbs in vulnerable plaques and patients. A brief overview of promising mAbs targeting other targets such as ANGPTL3 is also provided. EXPERT OPINION: Research consistently supports the potential of mAb therapies in treating adult dyslipidemia, particularly in vulnerable patients. PCSK9mAbs are effective in regulating lipid parameters, such as LDL-C and Lp(a), and exhibit anti-inflammatory and anti-thrombotic properties. These antibodies also maintain endothelial and smooth muscle health, contributing to the stabilization of vulnerable plaques and reduction in adverse cardiovascular events. Future research aims to further understand PCSK9 and other targets like ANGPTL3, focusing on vulnerable groups. Overall, mAbs are emerging as a promising and superior approach in dyslipidemia management and cardiovascular disease prevention.

Diagnostic performance of MRI for assessing axillary lymph node status after neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This systematic review examined the diagnostic performance of magnetic resonance imaging (MRI) for assessing axillary lymph node status (ALNS) after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies and used the QUADAS-2 tool to assess methodological quality of eligible studies. We used STATA version 12.0 to perform data pooling, heterogeneity testing, subgroup analysis, and sensitivity analysis. RESULTS: For the 21 enrolled studies, including 2875 patients, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were respectively 0.63 (95% CI: 0.53-0.72), 0.75 (95% CI: 0.68-0.81), 2.52 (95% CI: 1.98-3.19), 0.50 (95% CI: 0.39-0.63), and 5.08 (95% CI: 3.38-7.63). The AUC was 0.76 (95% CI: 0.72-0.79). I2 values of sensitivity (I2 = 94.41%) and specificity (I2 = 88.97%) were both > 50%. For the initial positive ALN patients, the pooled sensitivity and specificity were 0.64 (95% CI: 0.53-0.75) and 0.74 (95% CI: 0.64-0.82), respectively. Sensitivity analyses by focusing on studies with MRI performed post-NAC, studies using DCE-MRI, or studies with low risk of bias showed similar results to the primary analyses. CONCLUSION: MRI may have suboptimal diagnostic value in assessing ALNS after NAC for breast cancer patients. Due to the inconsistency of NAC regimens, the variability of axillary surgery, and the lack of time interval between MRI and surgery, further studies are needed to confirm our findings. CLINICAL RELEVANCE STATEMENT: Our study provided the diagnostic value of MRI in assessing axillary lymph node status after neoadjuvant chemotherapy for breast cancer patients. KEY POINTS: • MRI may have suboptimal diagnostic value in assessing axillary lymph node status after NAC for general breast cancer patients. • The initial axillary lymph node status has little impact on the diagnostic efficacy of MRI. • The substantial heterogeneity among studies highlights the need for further studies to provide more high-quality evidence in this field.

Rationale and design of a randomized controlled trial: The effect of intensive lipid-lowering therapy with PCSK9 inhibitor on endothelial-coverage of stent strut after percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS): Optical coherence tomography (OCT) study (PIECES-OCT study).

Background: For the patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) for at least 1 year is recommended in the guidelines to minimize the risk of stent thrombosis. Persistently uncovered stent strut means delayed neointima formation and extend the window of time in which the stent is prone to thrombosis. Previous studies showed that statins could improve post-stenting strut endothelial coverage for patients undergoing PCI. However, there are lack of evidences on whether early initiation of proprotein convertase subtilisin/Kexin type 9 monoclonal antibody (PCSK9mAb) after PCI in ACS patients can further improve the rate of stent strut coverage on the background of oral lipid-lowering therapy (LLT). Methods: This is a single-center, randomized trial to enroll 36 patients undergoing PCI with a clinical diagnosis of non-ST-segment elevation ACS. The baseline level of low-density lipoprotein cholesterol (LDL-C) of these patients are between 1.4 mmol/L and 3.4 mmol/L. Patients will be assigned to intensive lipid-lowering therapy (LLT) with PCSK9mAb group and conventional LLT without PCSK9mAb group for 12 weeks in a clinical follow-up setting according to 1: 1 randomization. the rate of stent strut endothelial coverage by optical coherence tomography (OCT) examination at 12 weeks after enrollment between the groups will be compared. Conclusion: This will be the first study to investigate changes in the rate of stent strut endothelial coverage under intensive LLT with PCSK9mAb by OCT examination in ACS patients undergoing PCI. The finding of this study will provide clinical evidence for future research about the hypothesis of a novel strategy of "intensive LLT (PCSK9mAb + statin ± ezetimibe) combined with shortened DAPT duration" for ACS patients undergoing PCI.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: ChiCTR2200063395.

The Effects of Sacubitril/Valsartan Compared to Olmesartan on the Blood Pressure and Glucolipid Metabolism in DM Patients with Primary Hypertension.

PURPOSE: Given the beneficial effects of sacubitril/valsartan on blood pressure generally, this study investigates its antihypertension effects in diabetes mellitus (DM) patients with primary hypertension specifically, and the effect of sacubitril/valsartan on glycolipid metabolism. METHODS: We conducted a randomized, open-label, active-controlled study to compare the antihypertension effects of sacubitril/valsartan in DM individuals with primary hypertension. The primary end point was reduction in mean systolic blood pressure (SBP) from baseline with sacubitril/valsartan vs. olmesartan at week 8. The secondary endpoints included the changes in diastolic blood pressure (DBP), daytime SBP/DBP, nighttime SBP/DBP, BP achievement (office sitting BP < 130/80 mmHg), and lipid profile. The trial was registered with chictr.org.cn (ChiCTR2200066428) on Dec 22, 2022. RESULTS: A total of 124 patients were included in the final analysis. SBP decreased to a greater extent in the sacubitril/valsartan group from baseline to 8 weeks [between-treatment difference: 3.51 mm Hg, 95% confidence interval (95% CI) 0.41 to 6.62 mm Hg, P = 0.03]. Furthermore, more patients achieved the blood pressure goal with sacubitril/valasartan (74.60% vs. 54.70%, P = 0.03). Multiple logistical regression analysis showed that sacubitril/valsartan was associated with BP achievement [odds ratio (OR) 0.33, 95% CI 0.14-0.73, P = 0.007], but the difference in SBP, DBP, day time SBP/DBP, and night time SBP/DBP reduction did not approach statistical significance. HbA1C1, total cholesterol, and low-density lipoprotein-cholesterol were lower than baseline in both groups (P < 0.05); however, there was no difference in the effects on glucose and lipid metabolism from sacubitril/valsartan compared to olmesartan. CONCLUSIONS: Sacubitril/valsartan not only provided superior BP reduction compared to olmesartan, it did so without adverse effects on glycemic control and lipid parameters in DM patients with primary hypertension.

MRI radiomics for the preoperative evaluation of lymphovascular invasion in breast cancer: A meta-analysis.

PURPOSE: To evaluate the ability of preoperative MRI-based radiomic features in predicting lymphovascular invasion (LVI) in patients with breast cancer. METHODS: PubMed, Embase, Web of Science, Cochrane Library databases, and four Chinese databases were searched to identify relevant studies published up until June 15, 2023. Two reviewers screened all papers independently for eligibility. We included diagnostic accuracy studies that used radiomics-MRI for LVI in patients with breast cancer, using histopathology as the reference standard. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score. Overall diagnostic odds ratio (DOR), sensitivity, specificity and area under the curve (AUC) were calculated to assess the prediction efficacy of MRI-based radiomic features in patients with breast cancer. Spearman's correlation coefficient was calculated and subgroup analysis performed to investigate causes of heterogeneity. RESULTS: Eight studies comprising 1685 female patients were included. The pooled DOR, sensitivity, specificity, and AUC of radiomics in detecting LVI were 23 [confidence interval (CI) 16,32], 0.89(0.86,0.92), 0.82 (0.78,0.86), and 0.83(0.78,0.87), respectively. The meta-analysis showed significant heterogeneity among the included studies. No threshold effect was detected. Subgroup analysis showed that more than 200 participants, radiomics with clinical factors, semiautomatic segmentation method and peritumoral or intra- and peritumoral model [DOR: 28(18,42), 26(19,37), 34(16,70), 40(10,156), respectively] could improve diagnostic performance compared with less than 200 participants, only radiomics, manual segmentation method, and tumor model [DOR: 16(7,37), 21(6,73), 20(12,32), 21(13,32), respectively], but 3.0 T MR and multiple sequences approach [DOR: 27(15,49),17(8,35)] couldn't improve diagnostic performance compared with 1.5 T and DCE radiomic features [DOR:27(7,99),25(17,37)]. CONCLUSION: Our meta-analysis showed that preoperative MRI-based radiomic features performs well in predicting LVI in patients with breast cancer. This noninvasive and convenient tool may be used to facilitate preoperative identification of LVI in breast cancer.

Thirty years of research on photoacoustic imaging in the field of cancer: A scientometric analysis of hotspots, bursts, and research trends.

As a novel imaging modality based on photoacoustic effects, photoacoustic imaging (PAI) has shown great potential in biomedical applications, especially in the field of cancer. The purpose of our research was to identify collaborations between different institutions, authors, and countries, and to explore the hotspots and prospects of PAI research in the field of cancer. We downloaded publications on PAI research from the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection database. Bibliometric analysis was performed using VOSviewer and CiteSpace software. A total of 2561 papers related to PAI research in the field of cancer were identified. A total of 10,105 authors participated in the PAI study, of which the majority (69.33%) authors participated in only 1 article. China (1638, 63.96%) was the country with the most articles in this field, and the Chinese Academy of Sciences (329, 12.85%) was the most productive institution. ACS Applied Materials & Interfaces (146, 5.70%) was the most productive journal and ACS Nano (7262 co-citations) was the most co-cited journal. Current hot topics of PAI research in the cancer field were the construction and development of multifunctional photoacoustic nanoprobes to achieve the integration of tumor detection and treatment. The application of photoacoustic imaging in the field of cancer is in the vigorous development stage and has a bright prospect. There was a wealth of cooperation between authors, countries, and institutions. Our findings can provide information about the future direction of funding agencies and research groups.

Molnupiravir for treatment of adults with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The effects of molnupiravir in treating patients with non-severe COVID-19 remain uncertain. OBJECTIVES: To evaluate the efficacy and safety of molnupiravir in adult patients with mild or moderate COVID-19. DATA SOURCES: PubMed, Embase, CENTRAL, Web of Science, and WHO COVID-19 database up to 27 December 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials with no language restrictions. PARTICIPANTS: Adults with mild or moderate COVID-19. INTERVENTIONS: Molnupiravir against standard care or placebo. ASSESSMENT OF RISK OF BIAS: We used a revision of RoB-2 criteria. METHODS OF DATA SYNTHESIS: Outcomes were mortality, hospital admission, viral clearance, time to viral clearance, time to symptom resolution or clinical improvement, any adverse events, and serious adverse events. We performed DerSimonian-Laird random-effects meta-analyses to summarize the evidence and evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Nine randomized controlled trials enrolling 30 472 patients proved eligible. Majority of patients were outpatients, with a mean age ranging from 35 to 56.6 years. In adult patients with mild or moderate COVID-19, molnupiravir probably reduces mortality (relative risk [RR], 0.43; 95% CI, 0.20-0.94; risk difference [RD], 0.1% fewer; moderate certainty) and the risk of hospital admission (RR, 0.67; 95% CI, 0.45-0.99; RD, 1.4% fewer; moderate certainty) and may reduce time to viral clearance (mean difference, -1.81 days; 95% CI, -3.31 to -0.31; low certainty) and time to symptom resolution or clinical improvement (mean difference, -2.39 days; 95% CI, -3.71 to -1.07; low certainty). Molnupiravir probably increases the rate of viral clearance (RR, 3.47; 95% CI, 2.43-4.96; RD 16.1% more; moderate certainty) at 7 days (±3 days) and likely does not increase serious adverse events (RR, 0.84; 95% CI, 0.61-1.15; RD 0.1% fewer; moderate certainty). CONCLUSIONS: In adult patients with mild or moderate COVID-19, molnupiravir likely reduces mortality and risk of hospital admission probably without increasing serious adverse events.

Comparative efficacy and acceptability of interventions for insomnia in breast cancer patients: A protocol for systematic review and network meta-analysis.

BACKGROUND: Symptoms of insomnia are highly prevalent in patients with breast cancer. There are a large number of pharmacological and non-pharmacological interventions that can be used for the management of insomnia in breast cancer patients; however, their comparative effectiveness and acceptability remain uncertain. This review aims to evaluate the efficacy and acceptability of different interventions for insomnia in breast cancer patients using a Bayesian network meta-analysis (NMA). METHODS: We will perform a comprehensive literature search in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PsycINFO from inception to November 2022. We will include randomized controlled trials (RCTs) that compared the effects of different interventions on the management of insomnia in breast cancer patients. We will assess the risk of bias assessment using a modified Cochrane instrument. We will conduct a Bayesian random-effects framework NMA to estimate relative effects of interventional procedures. We will use Grading of Recommendations Assessment, Development and Evaluation to rate the certainty of evidence. DISCUSSION: To our knowledge, this will be the first systematic review and network meta-analysis to compare the effectiveness and acceptability of all currently available interventions for insomnia in patients with breast cancer. The results of our review will help provide more evidence for the treatment of insomnia in breast cancer patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021282211.

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study.

BACKGROUND: Contemporary risk-directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome. METHODS: The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation. RESULTS: The overall 5-year event-free survival was 84.4% (95% confidence interval [CI], 80.6-88.3) and 5-year overall survival 88.9% (95% CI, 85.5-92.4). Independent factors associated with lower 5-year event-free survival were male sex (80.4%, [95% CI, 74.8-86.4] vs. 88.9%, [95% CI, 84.1-93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2-87.4] vs. 87.1%, [95% CI, 83.4-90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5-year event-free survival (33.3% [95% CI, 11.6-96.1] vs. 83.0% [95% CI, 77.5-88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2-14.5], p < .001). CONCLUSIONS: These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL.

Alterations in immune cell heterogeneities in the brain of aged zebrafish using single-cell resolution.

Immunocytes, including the microglia, are crucial in the neurodegenerative process in old people. However, the understanding of regarding microglia heterogeneity and other involved immunocytes remains elusive. We analyzed 26,456 immunocytes from 12-and 26-month-old zebrafish brains at single-cell resolution. Microglia and T lymphocytes were detected in the brain at both time points. Two types of microglia were annotated, namely, ac+ microglia and xr+ microglia, which were clustered into subsets 1, 2, 3, 4, 5, and subsets 6, 7, 8, 9, respectively. Diversified microglia predominated the adult brains and cooperated with T cells to perform the functions of immune response and neuronal nutrition. We validated the specific microglia markers. The novel transgenic lines, Tg(lgals3bpb:eGFP) and Tg(apoc1:eGFP), were created, which faithfully labeled ac+ microglia and served as valuable labeling tools. However, the microglia population reduced while T cells of six subtypes intriguingly increased to serve as the primary immune cells in aged brains. Unlike in 12-month-old brains, T cells, together with microglia, exhibited a coordinated signature of inflammation in the 26-month-old brains. Our findings revealed the immunocytes atlas in aged zebrafish brains. It implied the involvement of microglia and T cells in the progression of neurodegeneration in aging.

Different Imaging Modalities for the Diagnosis of Axillary Lymph Node Metastases in Breast Cancer: A Systematic Review and Network Meta-Analysis of Diagnostic Test Accuracy.

BACKGROUND: Accurate diagnosis of axillary lymph node metastasis (ALNM) of breast cancer patients is important to guide local and systemic treatment. PURPOSE: To evaluate the diagnostic performance of different imaging modalities for ALNM in patients with breast cancer. STUDY TYPE: Systematic review and network meta-analysis (NMA). SUBJECTS: Sixty-one original articles with 8011 participants. FIELD STRENGTH: 1.5 T and 3.0 T. ASSESSMENT: We used the QUADAS-2 and QUADAS-C tools to assess the risk of bias in eligible studies. The identified articles assessed ultrasonography (US), MRI, mammography, ultrasound elastography (UE), PET, CT, PET/CT, scintimammography, and PET/MRI. STATISTICAL ANALYSIS: We used random-effects conventional meta-analyses and Bayesian network meta-analyses for data analyses. We used sensitivity and specificity, relative sensitivity and specificity, superiority index, and summary receiver operating characteristic curve (SROC) analysis to compare the diagnostic value of different imaging modalities. RESULTS: Sixty-one studies evaluated nine imaging modalities. At patient level, sensitivities of the nine imaging modalities ranged from 0.27 to 0.84 and specificities ranged from 0.84 to 0.95. Patient-based NMA showed that UE had the highest superiority index (5.95) with the highest relative sensitivity of 1.13 (95% confidence interval [CI]: 0.93-1.29) among all imaging methods when compared to US. At lymph node level, MRI had the highest superiority index (6.91) with highest relative sensitivity of 1.13 (95% CI: 1.01-1.23) and highest relative specificity of 1.11 (95% CI: 0.95-1.23) among all imaging methods when compared to US. SROCs also showed that UE and MRI had the largest area under the curve (AUC) at patient level and lymph node level of 0.92 and 0.94, respectively. DATA CONCLUSION: UE and MRI may be superior to other imaging modalities in the diagnosis of ALNM in breast cancer patients at the patient level and the lymph node level, respectively. Further studies are needed to provide high-quality evidence to validate our findings. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Carrageenan-Based Pickering Emulsion Gels Stabilized by Xanthan Gum/Lysozyme Nanoparticle: Microstructure, Rheological, and Texture Perspective.

In this study, Pickering emulsion gels were prepared by the self-gel method based on kappa carrageenan (kC). The effects of particle stabilizers and polysaccharide concentrations on the microstructure, rheological characteristics, and texture of Pickering emulsion gels stabilized by xanthan gum/lysozyme nanoparticles (XG/Ly NPs) with kC were discussed. The viscoelasticity of Pickering emulsion gels increased significantly with the increase of kC and XG/Ly NPs. The results of temperature sweep showed that the gel formation mainly depended on the kC addition. The XG/Ly NPs addition could accelerate the formation of Pickering emulsion gels and increase its melting temperature (Tmelt), which is helpful to improve the thermal stability of emulsion gels. Cryo-scanning electron microscope (Cryo-SEM) images revealed that Pickering emulsion gel has a porous network structure, and the oil droplets were well wrapped in the pores. The hardness increased significantly with the increase of XG/Ly NPs and kC. In particular, the Pickering emulsion gel hardness was up to 2.9 Newton (N) when the concentration of kC and XG/Ly NPs were 2%. The results showed that self-gelling polysaccharides, such as kC, could construct and regulate the structure and characteristics of Pickering emulsion gel. This study provides theoretical support for potential new applications of emulsion gels as functional colloids and delivery systems in the food industry.

Brain milieu induces early microglial maturation through the BAX-Notch axis.

Microglia are derived from primitive myeloid cells and gain their early identity in the embryonic brains. However, the mechanism by which the brain milieu confers microglial maturation signature remains elusive. Here, we demonstrate that the baxcq55 zebrafish and Baxtm1Sjk mouse embryos exhibit similarly defective early microglial maturation. BAX, a typical pro-apoptotic factor, is highly enriched in neuronal cells and regulates microglial maturation through both pro-apoptotic and non-apoptotic mechanisms. BAX regulates dlb via the CaMKII-CREB axis calcium-dependently in living neurons while ensuring the efficient Notch activation in the immigrated pre-microglia by apoptotic neurons. Notch signaling is conserved in supporting embryonic microglia maturation. Compromised microglial development occurred in the Cx3cr1Cre/+Rbpjfl/fl embryonic mice; however, microglia acquire their appropriate signature when incubated with DLL3 in vitro. Thus, our findings elucidate a BAX-CaMKII-CREB-Notch network triggered by the neuronal milieu in microglial development, which may provide innovative insights for targeting microglia in neuronal disorder treatment.

The medial wall and medial compartment of the cavernous sinus: an anatomic study using plastinated histological sections.

The medial wall of the cavernous sinus (CS) has a significant role in evaluation and treatment of pituitary adenomas. This study was conducted to clarify the fine architecture of the medial wall and medial compartment of the CS at both macro- and micro-levels in twenty-one human cadaveric heads by using the epoxy sheet plastination technique. The sellar part medial wall is an intact dural layer that separates the CS from the pituitary gland. This dural wall adhered to the diaphragma sellae and the periosteum of the sella turcica to form fibrous triangles. Eight micro-protrusions of the pituitary gland were found at both sides of that wall. The thickness of the sellar part medial wall at its central portion was significantly thinner than that at the other surrounding portions. From the superior view, tortuous intracavernous carotid arteries can be divided into outward bending type and inward bending type. The inward bending intracavernous carotid was apt to bent towards the central part of the sellar part medial wall, where there were usually wide and short fibrous bands with more densely stained connective tissues between them. The micro-protrusion of the pituitary gland in the medial wall of the CS could provide an anatomical basis for the occult tumor invasion and the recurrence of residual tumor. Different bending facing states of tortuous intracavernous carotid arteries in the lateral direction may be a factor of the determination of the direction of growth of pituitary tumors.