Clinical Presentation, Management, and Diagnostic Performance of 2021 Criteria for Paraneoplastic Neurologic Syndromes in Childhood.

BACKGROUND AND OBJECTIVES: Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children. METHODS: Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification. RESULTS: Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy). DISCUSSION: OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

Vitamin D3 exacerbates steatosis while calcipotriol inhibits inflammation in non-alcoholic fatty liver disease in Sod1 knockout mice: a comparative study of two forms of vitamin D.

The role of vitamin D (VD) in non-alcoholic fatty liver disease (NAFLD) remains controversial, possibly due to the differential effects of various forms of VD. In our study, Sod1 gene knockout (SKO) mice were utilized as lean NAFLD models, which were administered 15 000 IU VD3 per kg diet, or intraperitoneally injected with the active VD analog calcipotriol for 12 weeks. We found that VD3 exacerbated hepatic steatosis in SKO mice, with an increase in the levels of Cd36, Fatp2, Dgat2, and CEBPA. However, calcipotriol exerted no significant effect on hepatic steatosis. Calcipotriol inhibited the expression of Il-1a, Il-1b, Il-6, Adgre1, and TNF, with a reduction of NFκB phosphorylation in SKO mice. No effect was observed by either VD3 or calcipotriol on hepatocyte injury and hepatic fibrosis. Co-immunofluorescence stains of CD68, a liver macrophage marker, and VDR showed that calcipotriol reduced CD68 positive cells, and increased the colocalization of VDR with CD68. However, VD3 elevated hepatocyte VDR expression, with no substantial effect on the colocalization of VDR with CD68. Finally, we found that VD3 increased the levels of serum 25(OH)D3 and 24,25(OH)2D3, whereas calcipotriol decreased both. Both VD3 and calcipotriol did not disturb serum calcium and phosphate levels. In summary, our study found that VD3 accentuated hepatic steatosis, while calcipotriol diminished inflammation levels in SKO mice, and the difference might stem from their distinct cellular selectivity in activating VDR. This study provides a reference for the application of VD in the treatment of lean NAFLD.

Insomnia-related rodent models in drug discovery.

Despite the widespread prevalence and important medical impact of insomnia, effective agents with few side effects are lacking in clinics. This is most likely due to relatively poor understanding of the etiology and pathophysiology of insomnia, and the lack of appropriate animal models for screening new compounds. As the main homeostatic, circadian, and neurochemical modulations of sleep remain essentially similar between humans and rodents, rodent models are often used to elucidate the mechanisms of insomnia and to develop novel therapeutic targets. In this article, we focus on several rodent models of insomnia induced by stress, diseases, drugs, disruption of the circadian clock, and other means such as genetic manipulation of specific neuronal activity, respectively, which could be used to screen for novel hypnotics. Moreover, important advantages and constraints of some animal models are discussed. Finally, this review highlights that the rodent models of insomnia may play a crucial role in novel drug development to optimize the management of insomnia.

Effect of schooling on flow generated sounds from carangiform swimmers.

Computational models are used to examine the effect of schooling on flow generated noise from fish swimming using their caudal fins. We simulate the flow as well as the far-field hydrodynamic sound generated by the time-varying pressure loading on these carangiform swimmers. The effect of the number of swimmers in the school, the relative phase of fin flapping of the swimmers, and their spatial arrangement is examined. The simulations indicate that the phase of the fin flapping is a dominant factor in the total sound radiated into the far-field by a group of swimmers. For small schools, a suitable choice of relative phase between the swimmers can significantly reduce the overall intensity of the sound radiated to the far-field. The relative positioning of the swimmers is also shown to have an impact on the total radiated noise. For a larger school, even highly uncorrelated phases of fin movement between the swimmers in the school are very effective in significantly reducing the overall intensity of sound radiated into the far-field. The implications of these findings for fish ethology as well as the design and operation of bioinspired vehicles are discussed.

[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

Ultrafast polarization characterization with Mueller matrix based on optical time-stretch and spectral encoding.

High-speed optical polarization characterization is highly desirable for a wide range of applications, including remote sensing, telecommunication, and medical diagnosis. The utilization of the Mueller matrix provides a superior systematic and comprehensive approach to represent polarization attributes when matter interacts with optical beams. However, the current measurement speed of Mueller matrix is limited to only seconds or milliseconds. In this study, we present an ultrafast Mueller matrix polarimetry (MMP) technique based on optical time-stretch and spectral encoding that enables us to achieve an impressive temporal resolution of 4.83 nanoseconds for accurate Mueller matrix measurements. The unique feature of optical time-stretch technology enables continuous, ultrafast single-shot spectroscopy, resulting in a remarkable speed of up to 207 MHz for spectral encoding Mueller matrix measurement. We have employed an effective Mueller linear reconstruction algorithm based on the measured modulation matrix, accounting for all potential non-ideal effects of polarization components like retardance error and azimuth error. To ensure high precision, prior to the actual measurement, high-order dispersion induced by time-stretch requires adjustment through proper modulation matrix design. Upon such correction, both the results of static and rapid dynamic samples measurements exhibit exceptional accuracy with root-mean-square error (RMSE) approximately equal to 0.04 and 0.07 respectively. This presented ultrafast MMP provides a significant advance over preceding endeavors, enabling superior accuracy and increased speed concurrently.

Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 􀁐g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 􀁐g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Sugar-sweetened beverage intake and long-term mortality in individuals with metabolic dysfunction-associated steatotic liver disease: a longitudinal analysis of the National Health and Nutrition Examination Survey database.

BACKGROUND: Consuming sugar-sweetened beverages (SSBs) has been linked to the development of various adverse health conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated associations between SSB intake and long-term mortality among individuals with MASLD using a nationally representative database. METHODS: This population-based, longitudinal study extracted data of adults aged 20-79 years with MASLD from the USA (US) National Health and Nutrition Examination Survey database 2003-2014. Associations between the amount of SSB intake and all-cause, cancer and cardiovascular disease mortality until the end of 2019 were determined using Cox proportional hazards regression analyses. RESULTS: A total of 12 965 individuals aged 20-79 years who had MASLD were identified in the database. After exclusion, 5630 participants remained for the analyses. This cohort can be extrapolated to 43 420 321 individuals in the entire US after proper weighting. The mean age of the study cohort was 44.1 years. After adjusting for confounders, no significant association was observed between SSB intake (tertile 3 vs. tertile 1) and all-cause [adjusted hazard ratio (aHR): 1.03, 95% confidence interval (CI), 0.60-1.76) or cancer mortality (aHR, 0.41; 95% CI, 0.15-1.16). However, higher SSB intake (tertile 3 vs. tertile 1) was significantly associated with elevated cardiovascular disease mortality risk (aHR = 2.83; 95% CI, 1.01-7.91). CONCLUSION: In US adults with MASLD, high SSB intake is associated with nearly three-fold increased cardiovascular disease mortality risk. The findings underscore the critical need for concerted action on the part of healthcare providers and policymakers.

B7-H3 is associated with the armored-cold phenotype and predicts poor immune checkpoint blockade response in melanoma.

Melanoma is the most suitable tumor type for immunotherapy, but not all melanoma patients could respond to immunotherapy. B7 homolog 3 (B7-H3) belongs to the B7 family and is overexpressed in a number of malignant tumors, but the expression pattern of B7-H3 in melanoma has not been well summarized. The expression of B7-H3 was investigated in melanoma and its correlations with features of the tumor microenvironment (TME) by using various public databases, including the Cancer Genome Atlas (TCGA), the GEPIA, and the Human Protein Atlas databases. In addition, the in-house melanoma tissue microarray was applied to validate the results from public databases. Based on the public and in-house cohorts, we found that B7-H3 was overexpressed in melanoma tumor tissues and high B7-H3 expression was related to poor clinical outcome. Moreover, B7-H3 was negatively correlated with levels of tumor-infiltrating lymphocytes (TILs) and positively correlated with collagen infiltration. With clinical translational value, the predictive value of B7-H3 for conventional immunotherapy was detected using the Kaplan-Meier plotter tool, and the results showed that melanoma patients with high B7-H3 expression were insensitive to anti-PD-1 and anti-CTLA-4 immunotherapy. In conclusion, we first investigate the expression of B7-H3 in melanoma and its correlations with the TME features, and indicate B7-H3 as a promising therapeutic target in melanoma patients that are insensitive to conventional immunotherapy.

Multi-objective and multi-solution source mask optimization using NSGA-II for more direct process window enhancement.

Source and mask optimization (SMO) technology is increasingly relied upon for resolution enhancement of photolithography as critical dimension (CD) shrinks. In advanced CD technology nodes, little process variation can impose a huge impact on the fidelity of lithography. However, traditional source and mask optimization (SMO) methods only evaluate the imaging quality in the focal plane, neglecting the process window (PW) that reflects the robustness of the lithography process. PW includes depth of focus (DOF) and exposure latitude (EL), which are computationally intensive and unfriendly to gradient-based SMO algorithms. In this study, we propose what we believe to be a novel process window enhancement SMO method based on the Nondominated Sorting Genetic Algorithm II (NSGA-II), which is a multi-objective optimization algorithm that can provide multiple solutions. By employing the variational lithography model (VLIM), a fast focus-variation aerial image model, our method, NSGA-SMO, can directly optimize the PW performance and improve the robustness of SMO results while maintaining the in-focus image quality. Referring to the simulations of two typical patterns, NSGA-SMO showcases an improvement of more than 20% in terms of DOF and EL compared to conventional multi-objective SMO, and even four times superior to single-objective SMO for complicated patterns.

Enhancing vegetation formation classification: Integrating coarse-scale traditional mapping knowledge and advanced machine learning.

Mapping vegetation formation types in large areas is crucial for ecological and environmental studies. However, this is still challenging to distinguish similar vegetation formation types using existing predictive vegetation mapping methods, based on commonly used environmental variables and remote sensing spectral data, especially when there are not enough training samples. To solve this issue, we proposed a predictive vegetation mapping method by integrating an advanced machine learning algorithm and knowledge in an early coarse-scale vegetation map (VMK). First, we implemented classification using the random forest algorithm by integrating the early vegetation map as an auxiliary feature (VMF). Then, we determined the rationality of classified vegetation types and distinguished the confusing types, respectively, based on the knowledge of the spatial distributions and hierarchies of vegetation. Finally, we replaced each recognized unreasonable vegetation type with its corresponding reasonable vegetation type. We implemented the new method in upstream of the Yellow River based on GaoFen-1 satellite images and other environmental variables (i.e., topographical and climate variables). Results showed that the overall accuracy using the VMK method ranged from 67.7 % to 76.8 %, which was 10.9 % to 13.4 % and 3.2 % to 6.6 %, respectively, higher than that of the method without the early vegetation map (NVM) and the VMF method, based on cross-validation with 20 % to 60 % random training samples. The spatial details of the vegetation map using the VMK method were also more reasonable compared to the NVM and VMF methods. These results indicated that the VMK method can distinctly improve the mapping accuracy at the vegetation formation level by integrating knowledge of existing vegetation maps. The proposed method can largely reduce the requirements on the number of field samples, which is especially important for alpine mountains and arctic region, where collecting training samples is more difficult due to the harsh natural environment.

Impact of age on the host response to sepsis in a murine model of fecal-induced peritonitis.

INTRODUCTION: Despite older adults being more vulnerable to sepsis, most preclinical research on sepsis has been conducted using young animals. This results in decreased scientific validity since age is an independent predictor of poor outcome. In this study, we explored the impact of aging on the host response to sepsis using the fecal-induced peritonitis (FIP) model developed by the National Preclinical Sepsis Platform (NPSP). METHODS: C57BL/6 mice (3 or 12 months old) were injected intraperitoneally with rat fecal slurry (0.75 mg/g) or a control vehicle. To investigate the early stage of sepsis, mice were culled at 4 h, 8 h, or 12 h to investigate disease severity, immunothrombosis biomarkers, and organ injury. Mice received buprenorphine at 4 h post-FIP. A separate cohort of FIP mice were studied for 72 h (with buprenorphine given at 4 h, 12 h, and then every 12 h post-FIP and antibiotics/fluids starting at 12 h post-FIP). Organs were harvested, plasma levels of Interleukin (IL)-6, IL-10, monocyte chemoattract protein (MCP-1)/CCL2, thrombin-antithrombin (TAT) complexes, cell-free DNA (CFDNA), and ADAMTS13 activity were quantified, and bacterial loads were measured. RESULTS: In the 12 h time course study, aged FIP mice demonstrated increased inflammation and injury to the lungs compared to young FIP mice. In the 72 h study, aged FIP mice exhibited a higher mortality rate (89%) compared to young FIP mice (42%) (p < 0.001). Aged FIP non-survivors also exhibited a trend towards elevated IL-6, TAT, CFDNA, CCL2, and decreased IL-10, and impaired bacterial clearance compared to young FIP non-survivors. CONCLUSION: To our knowledge, this is the first study to investigate the impact of age on survival using the FIP model of sepsis. Our model includes clinically-relevant supportive therapies and inclusion of both sexes. The higher mortality rate in aged mice may reflect increased inflammation and worsened organ injury in the early stage of sepsis. We also observed trends in impaired bacterial clearance, increase in IL-6, TAT, CFDNA, CCL2, and decreased IL-10 and ADAMTS13 activity in aged septic non-survivors compared to young septic non-survivors. Our aging model may help to increase the scientific validity of preclinical research and may be useful for identifying mechanisms of age-related susceptibility to sepsis as well as age-specific treatment strategies.

CD14-CD10-CD45+HLA-DR-SSC+ neutrophils may be granulocytic myeloid-derived suppressor cell-like cells and relate to disease progression in non-Hodgkin's lymphoma patients.

We explored the frequency of CD14-CD10-CD45+HLA-DR-SSC++ neutrophils (CD10- neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10- neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10- and CD10+ neutrophils were sorted, and their cytology was analyzed. CD3+ T cells were also isolated and cultured with the autologous CD10- or CD10+ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10+ or CD10- neutrophils were examined. Few CD10- neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10- neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10- neutrophils were shorter than those with low CD10- neutrophils. CD10- neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10- neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis.

Diagnostic strategy of metagenomic next-generation sequencing for gram negative bacteria in respiratory infections.

OBJECTIVE: This study aims to identify the most effective diagnostic method for distinguishing pathogenic and non-pathogenic Gram-negative bacteria (GNB) in suspected pneumonia cases using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples. METHODS: The effectiveness of mNGS was assessed on BALF samples collected from 583 patients, and the results were compared with those from microbiological culture and final clinical diagnosis. Three interpretational approaches were evaluated for diagnostic accuracy. RESULTS: mNGS outperformed culture significantly. Among the interpretational approaches, Clinical Interpretation (CI) demonstrated the best diagnostic performance with a sensitivity of 87.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98.3%. CI's specificity was significantly higher than Simple Interpretation (SI) at 37.9%. Additionally, CI excluded some microorganisms identified as putative pathogens by SI, including Haemophilus parainfluenzae, Haemophilus parahaemolyticus, and Klebsiella aerogenes. CONCLUSION: Proper interpretation of mNGS data is crucial for accurately diagnosing respiratory infections caused by GNB. CI is recommended for this purpose.

Mask-Moving-Lithography-Based High-Precision Surface Fabrication Method for Microlens Arrays.

Microlens arrays, as typical micro-optical elements, effectively enhance the integration and performance of optical systems. The surface shape errors and surface roughness of microlens arrays are the main indicators of their optical characteristics and determine their optical performance. In this study, a mask-moving-projection-lithography-based high-precision surface fabrication method for microlens arrays is proposed, which effectively reduces the surface shape errors and surface roughness of microlens arrays. The pre-exposure technology is used to reduce the development threshold of the photoresist, thus eliminating the impact of the exposure threshold on the surface shape of the microlens. After development, the inverted air bath reflux method is used to bring the microlens array surface to a molten state, effectively eliminating surface protrusions. Experimental results show that the microlens arrays fabricated using this method had a root mean square error of less than 2.8%, and their surface roughness could reach the nanometer level, which effectively improves the fabrication precision for microlens arrays.

The optimal blood glucose is significantly associated with lower mortality in critically ill patients with cardiogenic shock: an analysis revealed with time series blood glucose records.

BACKGROUND: The optimal blood glucose (BG) level for patients with cardiogenic shock in the intensive care unit (ICU) remains unclear. Studies have found that both excessively high and low BG levels contribute to adverse cardiovascular events. Our study aims to investigate the optimal BG level for critically ill patients with cardiogenic shock and evaluate the effects of optimal BG on the prognosis of patients. METHODS: A total of 2013 patients with cardiogenic shock obtained from the Medical Information Mart for Intensive Care (MIMIC) IV database were included in the final cohort for our retrospective observational study for data analysis. The exposure was time-weighted average BG (TWA-BG), which was calculated by the time-series BG records and corresponding time stamps of patients with cardiogenic shock during their stay in the ICU. The cut-off value of TWA-BG was identified by the restricted cubic spline curve and included patients were categorized into three groups: low TWA-BG group (TWA-BG ≤ 104 mg/dl), optimal TWA-BG group (104 < TWA-BG ≤ 138 mg/dl), and high TWA-BG group (TWA-BG > 138 mg/dl). The primary outcome was 28-day mortality, and the secondary outcomes were ICU and in-hospital mortality. We performed the log-rank test to detect whether there is a difference in mortality among different groups in the original cohort. Multiple distinct models were employed to validate the robustness of the results. RESULTS: Our study revealed that the optimal BG level for critically ill patients with cardiogenic shock is 104-138 mg/dl. Compared to the optimal TWA-BG group, the low TWA-BG group (hazard ratio (HR): 1.67, 95% confidence interval (CI): 1.19-2.33, p = 0.002) and high TWA-BG group (HR: 1.72, 95% CI: 1.46-2.03, p < 0.001) exhibited higher 28-day mortality. Similarly, the low TWA-BG group and high TWA-BG group demonstrated higher risks in terms of ICU mortality (low TWA-BG group: HR: 2.30, 95% CI: 1.40-3.79, p < 0.001; high TWA-BG group: HR: 1.77, 95% CI: 1.45-2.17, p < 0.001) and in-hospital mortality (low TWA-BG group: HR: 1.73, 95% CI: 1.19-2.51, p = 0.001; high TWA-BG group: HR: 1.64, 95% CI: 1.38-1.95, p < 0.001). Sensitivity analysis conducted through propensity score matching and the subgroup analysis further substantiated the robustness of the results. CONCLUSION: The optimal BG level for patients with cardiogenic shock is 104-138 mg/dl. BG levels below 104 mg/dl and above 138 mg/dl were associated with a less favorable prognosis.

Decision tree models for the estimation of geo-polymer concrete compressive strength.

The green concretes industry benefits from utilizing gel to replace parts of the cement in concretes. However, measuring the compressive strength of geo-polymer concretes (CSGPoC) needs a significant amount of work and expenditure. Therefore, the best idea is predicting CSGPoC with a high level of accuracy. To do this, the base learner and super learner machine learning models were proposed in this study to anticipate CSGPoC. The decision tree (DT) is applied as base learner, and the random forest and extreme gradient boosting (XGBoost) techniques are used as super learner system. In this regard, a database was provided involving 259 CSGPoC data samples, of which four-fifths of is considered for the training model and one-fifth is selected for the testing models. The values of fly ash, ground-granulated blast-furnace slag (GGBS), Na2SiO3, NaOH, fine aggregate, gravel 4/10 mm, gravel 10/20 mm, water/solids ratio, and NaOH molarity were considered as input of the models to estimate CSGPoC. To evaluate the reliability and performance of the decision tree (DT), XGBoost, and random forest (RF) models, 12 performance evaluation metrics were determined. Based on the obtained results, the highest degree of accuracy is achieved by the XGBoost model with mean absolute error (MAE) of 2.073, mean absolute percentage error (MAPE) of 5.547, Nash-Sutcliffe (NS) of 0.981, correlation coefficient (R) of 0.991, R2 of 0.982, root mean square error (RMSE) of 2.458, Willmott's index (WI) of 0.795, weighted mean absolute percentage error (WMAPE) of 0.046, Bias of 2.073, square index (SI) of 0.054, p of 0.027, mean relative error (MRE) of -0.014, and a20 of 0.983 for the training model and MAE of 2.06, MAPE of 6.553, NS of 0.985, R of 0.993, R2 of 0.986, RMSE of 2.307, WI of 0.818, WMAPE of 0.05, Bias of 2.06, SI of 0.056, p of 0.028, MRE of -0.015, and a20 of 0.949 for the testing model. By importing the testing set into trained models, values of 0.8969, 0.9857, and 0.9424 for R2 were obtained for DT, XGBoost, and RF, respectively, which show the superiority of the XGBoost model in CSGPoC estimation. In conclusion, the XGBoost model is capable of more accurately predicting CSGPoC than DT and RF models.

Increased monocytic myeloid-derived suppressor cells in type 2 diabetes correlate with hyperglycemic and was a risk factor of infection and tumor occurrence.

To investigate the frequency of monocytic myeloid-derived suppressor cells (M-MDSCs) in type 2 diabetes mellitus (T2DM) patients and explore the potential associations between M-MDSCs, glycemic control, and the occurrence of infections and tumor. 102 healthy and 77 T2DM individuals were enrolled. We assessed the M-MDSCs frequency, levels of fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), and other relevant indicators. Each patient underwent a follow-up of at least 6 months after M-MDSCs detection. The M-MDSCs frequency was significantly higher in patients with poor glycemic control (PGC) compared to the healthy population (P < 0.001), whereas there was no significant difference between patients with good glycemic control and the healthy (P > 0.05). There was a positive correlation between the M-MDSCs frequency and FPG, HbA1c (R = 0.517 and 0.315, P < 0.001, respectively). T2DM patients with abnormally increased M-MDSCs have a higher incidence of infection and tumor (48.57% and 11.43% respectively). Our results shed new light on the pathogenesis of T2DM, help to understand why T2DM patients are susceptible to infection and tumor and providing novel insights for future prevention and treatment of T2DM.

The roles and mechanisms of TGFB1 in acute myeloid leukemia chemoresistance.

Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) patients usually have very poor prognoses, and drug-resistance is one of the major limiting factors. In this study, we aimed to explore the functions of Transforming Growth Factor-ß1 (TGFB1) in AML drug-resistance. First, TGFB1 levels in serum and bone marrow are higher in R/R patients compared with newly diagnosed patients, this phenomenon could be due to different sources of secreted TGFB1 according to immunohistochemistry of marrow biopsies. Similarly, TGFB1 expression in AML drug-resistant cell lines is higher than that in their parental cell lines, and blocking the TGFB signaling pathway by specific inhibitors decreased resistance to chemotherapeutic agents. On the other hand, exogenous TGFB1 can also promote AML parental cells senescence and chemotherapy resistance. Next, we found SOX4 level is upregulated in drug-resistant cells, and parental cells treated with exogenous TGFB1 induced upregulation of SOX4 levels. Interference of SOX4 expression by siRNA diminished the TGFB1-induced sensitivity to chemotherapeutic agents. Finally, we conduct metabolomic analysis and find Alanine, aspartate and glutamate metabolism pathway, and Glycerophospholipid metabolism pathway are decreased after inhibiting TGFB signaling pathway or interfering SOX4 expression. This study concludes that TGFB1 level in R/R AML patients and drug-resistant strains is significantly increased. Blocking the TGFB signaling pathway can enhance the chemosensitivity of drug-resistant cells by suppressing SOX4 expression and metabolic reprogramming.