Erythrocytes Research Articles

Revolutionizing breast cancer monitoring: emerging hematocrit-based metrics- a narrative review

Breast cancer remains a leading global health concern, with significant strides made in early detection and treatment. However, effective long-term surveillance, particularly for recurrence and metastasis, remains a clinical challenge. Traditional methods like imaging and biopsy are often invasive, costly, and have limited sensitivity in detecting subtle changes during disease progression. Emerging evidence suggests that hematocrit-based metrics—measurements of the proportion of red blood cells (RBCs) in blood—could serve as valuable, minimally invasive biomarkers for monitoring breast cancer. This review highlights recent advancements in hematocrit-focused research and its potential role in revolutionizing breast cancer surveillance. Hematocrit dynamics reflect complex physiological processes influenced by cancer biology, including inflammation, angiogenesis, and treatment-induced bone marrow suppression. Alterations in hematocrit levels have been associated with prognostic outcomes, treatment responses, and early indications of recurrence in breast cancer patients. Coupled with other hematological and molecular markers, hematocrit offers a cost-effective and readily accessible tool to track disease status in real time. Recent technological innovations, such as point-of-care testing, artificial intelligence-driven data analysis, and microfluidic devices, are further advancing the applicability of hematocrit-based metrics in both clinical and remote monitoring settings.

Hollow cerium nanoparticles synthesized by one-step method for multienzyme activity to reduce colitis in mice

BACKGROUND Inflammatory bowel disease (IBD) is a common chronic intestinal inflammatory disease. High oxidative stress is a treatment target for IBD. Cerium oxide (CeO2) nanomaterials as nanozymes with antioxidant activity are potential drugs for the treatment of colitis. AIM To synthesize hollow cerium (H-CeO2) nanoparticles by one-step method and to validate the therapeutic efficacy of H-CeO2 in IBD. METHODS H-CeO2 was synthesized by one-step method and examined its characterization and nanoenzymatic activity. Subsequently, we constructed dextran sulfate sodium (DSS)-induced colitis in mice to observe the effects of H-CeO2 on colonic inflammation. The effects of H-CeO2 on colon inflammation and reactive oxygen species (ROS) levels in IBD mice were detected by hematoxylin and eosin staining and dichlorofluorescein diacetate staining, respectively. Finally, the biological safety of H-CeO2 on mice was evaluated by hematoxylin and eosin staining, blood routine, and blood biochemistry. RESULTS H-CeO2 nanoparticles prepared by the one-step method were uniform, monodisperse and hollow. H-CeO2 had a good ability to scavenge ROS, ∙OH and ∙OOH. H-CeO2 reduced DSS-induced decreases in body weight and colon length, colonic epithelial damage, inflammatory infiltration, and ROS accumulation. H-CeO2 administration reduced the disease activity index of DSS-induced animals from about 8 to 5. H-CeO2 had no significant effect on body weight, total platelet count, hemoglobin, white blood cell, and red blood cell counts in healthy mice. No significant damage to major organs was observed in healthy mice following H-CeO2 administration. CONCLUSION The one-step synthesis of H-CeO2 nanomaterials had good antioxidant activity, biosafety, and inhibited development of DSS-induced IBD in mice by scavenging ROS.

ВЛИЯНИЕ СКАРМЛИВАНИЯ КОМПЛЕКСНОЙ МИНЕРАЛЬНОЙ КОРМОВОЙ ДОБАВКИ НА ГЕМАТОЛОГИЧЕСКИЕ ПОКАЗАТЕЛИ КРОВИ ЯРОК РОМАНОВСКОЙ ПОРОДЫ

The purpose of research is to study the effect of feeding a complex mineral-vitamin supplement on hematological blood parameters and the productivity of the Romanov breed young ewe. Objectives: to determine the deficiency of minerals in basic feed; taking into account the deficiency, complex mineral and vitamin feed supplement, (hereinafter referred to as CMVFS); establish feeding standards and techniques. To conduct scientific and economic experiments at the State Property Committee Yakupov D.N. of Birsk District of the Republic of Bashkortostan, 4 groups of young ewes of Romanov breeds were selected using the method of pair-analogues (by age, live weight) of 10 heads in each (1 control and three experimental). The duration of the experiment was 120 days. Three recipes for the production of CMVFS were developed with the introduction into their composition of local natural zeolite from the Kaltuban deposit of the Republic of Bashkortostan and sapropel, monocalcium phosphate and premix P81-1-89 and feed sulfur. The control group was fed the main diet; the daily norm of CMVFS was fed to the experimental groups as part of a grain mixture once a day. At the end of the experiment, compared with the indicators of the control group, the number of red blood cells in the experimental groups increased by 1.83 %, 6.39 and 10.16 %; leukocytes – by 4.00 %, 12.79 and 15.61 % and hemoglobin – by 3.00 %, 4.25 and 5.21 %. To assess the state of metabolism in the body of experimental animals using the CMVFS, biochemical blood parameters were studied before the experiment and during removal from the experiment. The additional introduction of CMVFS, which contains natural zeolite and sapropel in various proportions, into the diet of the animals, had a positive effect to varying degrees on the biochemical and hematological parameters of the blood, contributed to the improvement of the clinical condition of the animals, and also had a stimulating effect on protein and carbohydrate metabolism, hematopoietic functions organs and heart. All this creates the prerequisites for increasing animal productivity.

Enhancing geriatric trauma mortality prediction: Modifying and assessing the Geriatric Trauma Outcome Score with net benefit and decision curve analysis.

Calibration and discrimination indicators alone are insufficient for evaluating the clinical usefulness of prediction models, as they do not account for the cost of misclassification errors. This study aimed to modify the Geriatric Trauma Outcome Score (GTOS) and assess the clinical utility of the modified model using net benefit (NB) and decision curve analysis (DCA) for predicting in-hospital mortality. The Trauma Quality Improvement Program (TQIP) 2017 was used to identify geriatric trauma patients (≥ 65 years) treated at Level I trauma centers. The outcome of interest was in-hospital mortality. The GTOS was modified to include additional patient, injury, and treatment characteristics identified through machine learning methods, focusing on early risk stratification. Calibration and discrimination indicators, along with NB and DCA, were utilized for evaluation. Of the 67,222 admitted geriatric trauma patients, 5.6% died in the hospital. The modified GTOS score included the following variables with associated weights: initial airway intervention (5), Glasgow Coma Scale ≤13 (5), packed red blood cell transfusion within 24 h (3), penetrating injury (2), age ≥ 75 years (2), preexisting comorbidity (1), and torso injury (1), with a total range from 0 to 19. The modified GTOS demonstrated a significantly higher area under the curve (0.92 vs. 0.84, p < 0.0001), lower misclassification error (4.9% vs. 5.2%), and lower Brier score (0.036 vs. 0.042) compared to the original GTOS. DCA showed that using the modified GTOS for predicting in-hospital mortality resulted in higher NB than treating all, treating none, and treating based on the original GTOS across a wide range of clinician preferences. The modified GTOS model exhibited superior predictive ability and clinical utility compared to the original GTOS. NB and DCA offer valuable complementary methods to calibration and discrimination indicators, comprehensively evaluating the clinical usefulness of prediction models and decision strategies.

Synergistic Effects of a Novel Combination of Natural Compounds Prevent H2O2-Induced Oxidative Stress in Red Blood Cells

Novel strategies to prevent the “storage lesions” of red blood cells (RBCs) are needed to prevent the risk of adverse effects after blood transfusion. One option could be the supplementation of stored blood bags with natural compounds that may increase the basal load of antioxidant protection and the shelf life of RBCs. In this pilot study, we investigated for the first time potential synergistic effects of a triple combination of well-known anti-oxidant compounds curcumin (curc), vitamin E (vit E), and vitamin C (vit C). Briefly, we established an ex vivo model of H2O2-induced oxidative stress and measured the hemolysis ratio (HR) (%) and thiobarbituric acid reactive substances (TBARS) levels in RBCs with or without pre-exposure for 30 min with increasing concentrations of curc, vit E, and vit C and then exposed to 10 mM H2O2. for 60 min. Exposure of RBCs to a triple combination of curc, vit E, and vit C at the highest concentration (100 µM) completely prevented H2O2-induced hemolysis. Surprisingly, we found that pre-treatment of RBCs with curc 100 µM alone completely prevented hemolysis as compared to vit E and vit C alone or in combination at the same concentration. On the other hand, pre-treatment with the triple combination of curc, vit E, and vit C 100 µM was required to totally prevent lipid peroxidation, as compared to curc 100 µM alone, supporting their synergistic effects in preventing RBCs membrane peroxidation. Further experiments are ongoing to investigate the anti-aging effects of the triple combination of curc, vit E, and vit C on cold-stored bags.

A Comparative Study of Common Anesthetics Propofol, Sevoflurane, Isoflurane and Ketamine on Lipid Membrane Fluidity

The membrane fluidity increases induced by popular anesthetic agents (propofol, isoflurane, sevoflurane, and ketamine/xylazine) were measured at the clinical and supra-clinical concentrations in red blood cell (RBC) membrane as well as four model membranes. Membrane fluidity changes were monitored using the excimer/monomer (E/M) ratio of dipyrene-PC and fluorescence anisotropies of DPH-PC and TMA-DPH. Propofol, sevoflurane and isoflurane increased membrane fluidity instantaneously. The largest increase occurs in membranes made of saturated lipids. RBCs were labeled with TMA-DPH, and the increase in membrane fluidity at clinical concentrations of isoflurane and sevoflurane was more than that induced by ten times the legal limit of alcohol in human blood. However, membrane fluidity was essentially unchanged by ketamine/xylazine up to 210 µM. These results strongly correlate with our recent in vivo experiments and reveal a clear connection between increasing membrane fluidity in model membranes, increasing the blood–brain barrier (BBB) permeability in mice, and inducing effective anesthesia in animals. Interestingly, at the most commonly used clinical concentrations, the membrane fluidity increases induced by propofol, sevoflurane, and isoflurane were very similar, despite the fact that different categories of anesthetics were used and their chemical concentrations were different by 100 times. This indicates that at clinical concentrations of these anesthetics, a similar level of membrane disruption at the BBB is achieved. Thus, our results strongly support the lipid hypothesis of the mechanism of general anesthetics.

Use of an anti-D-alloimmunization kinetics model to correct the interval censored D-alloimmunization rate following red blood cell transfusions.

The rate of D-alloimmunization amongst RhD-negative recipients of RhD-positive red blood cell (RBC) transfusions is not certain. Recipients with a short duration between the index RhD-positive transfusion and the last antibody detection test that did not show anti-D might become D-alloimmunized in the future. A regression model was developed to predict how often such patients might develop D-alloimmunization in the future to help account for the immunohematological uncertainty that accompanies having short serological follow up periods. Using the published literature on recipients who were intentionally transfused with RhD-positive RBCs and serially followed with antibody screens, as well as unpublished datasets, a regression model was constructed to demonstrate the timing of D-alloimmunization for recipients who became D-alloimmunized within 6 months following the index transfusion. The model was then applied to a series of RhD-negative hospitalized recipients of at least one unit of RhD-positive RBCs who did not become D-alloimmunized but who had fewer than 6 months of serological follow up to weight their contribution to the D-alloimmunization rate. Overall, the rate of D-alloimmunization was 21/105 (20.0%). There were 39 patients whose last documented antibody screen was performed between 14 days and 6 months after the index RhD-positive transfusion, and these patients were entered into the weighted model. After applying the model, the D-alloimmunization rate rose to 26.3%. Using a weighted model can help reduce the immunohematological uncertainty that accompanies the inclusion of patients with relatively short serological follow up in studies of RBC alloimmunization.

Comparison of whole blood versus red blood cells and plasma to correct trauma-induced coagulopathy ex vivo.

Early resuscitation is based on platelet-poor components such as red blood cells and plasma (RBC + P), contributing to platelet dilution and worsening of trauma-induced coagulopathy (TIC). We aimed to compare the ability of cold-stored whole blood (WB) versus RBC + P as a single component to correct TIC. Blood samples were collected on admission from trauma patients who required activation of the major hemorrhage protocol at a single UK major trauma center in 2021/2022. Samples were spiked ex vivo with volumes equivalent to two, four, or eight units of WB or RBC + P stored for a maximum of 2 weeks. Thromboelastometry, platelet counting, and multiple electrode aggregometry (MEA) were performed. Samples from 20 adult trauma patients were analyzed. Median age was 32 years (27-42), 89% were male, 70% had platelet dysfunction (tissue factor-activated ROTEM [EXTEM]-tissue factor-activated ROTEM with cytochalasin D [FIBTEM] clot amplitude at 5 min [A5] ≤ 30 mm), 65% were coagulopathic (EXTEM A5 ≤ 40 mm), and 42% died. EXTEM-FIBTEM A5 was higher following spiking with WB than RBC + P (33 mm, 26-33, vs. 27 mm, 24-30, p < .001). WB-spiking corrected platelet dysfunction in 2 patient samples out of 20, whereas RBC + P increased the frequency of platelet dysfunction (1/20 sample) and TIC (4/20 samples). RBC + P was associated with a dose-dependent deterioration in rotational thromboelastometry (ROTEM) clot strength and dynamics, platelet count, and aggregation in response to multiple agonists compared with WB-spiking, which maintained or partially corrected these abnormalities. Compared with RBC + P, WB better preserves ex vivo platelet-related ROTEM parameters, platelet count, and aggregation, but does not fully correct these common derangements of TIC.

Estimation of Hematocrit Volume Using Blood Glucose Concentration through Extreme Gradient Boosting Regressor Machine Learning Model.

Lifestyle diseases such as cardiovascular disorders, diabetes, etc. affect the physiological metabolism and become chronic upon negligence. Diabetes is one of the key factors that is interlinked with a plethora of diseases. Health management can be achieved through balanced diet, physical exercise, and periodic examination of blood glucose level and hematocrit volume. Our study developed a model to estimate the hematocrit volume (red blood cells) from the correlation of the glucose concentration obtained from a glucometer by employing machine learning techniques. This Article explores the prediction of hematocrit volume in whole blood by applying various machine learning (ML) models such as linear regression (LR), support vector regressor (SVR), decision tree (DT), random forest regressor (RFR), artificial neural network (ANN), and extreme gradient boosting regressor model (XGBoost). We used amperometric signals generated from an electrochemical glucose sensor or glucose strip, which produces current values on glucose concentration. We estimated the hematocrit volume via processing of the amperometric signals to enhance diagnostic capabilities with the least error in the field of biomedical signal processing. The ML models were trained on the data set comprising 80% training set and 20% testing set in the Python programming language. The models were evaluated based on the metrics such as R-squared (R2), mean squared error (MSE), and root mean squared error (RMSE) values, and their reliability was assessed through the three validation mechanisms, namely, the relative error, K-fold cross-validation, and analysis of confidence interval. We observed that the XGBoost regression results were comparatively better than the LR and ANN results as corroborated through reliability analysis. It was concluded that XGBoost demonstrated 15% relative error between actual and predicted data and 68% accuracy with 6% standard deviation in the prediction obtained via a 5-fold cross-validation technique. The XGBoost model demonstrates comparatively better performance in terms of flexibility in tuning and interpretability options, which make it suitable for the regression task in the predictive biomedical analytics.

Intravenous Sodium Ferric Gluconate Complex for Hospitalized Pediatric Patients with Iron Deficiency Anemia

Background/Objectives: Iron deficiency anemia is common in the pediatric population. Red blood cell transfusions, a common acute treatment, pose well-recognized risks including lung injury, circulatory overload, and immune dysfunction. Intravenous iron, specifically sodium ferric gluconate complex (SFGC), is a potential alternative, however investigation on its use in hospitalized children is lacking. This study aims to describe the physiologic response via change in hematologic values to cumulative dose of SFGC, investigate the effect of cumulative dosing on the amount of RBC transfusions received, and comment on its safety. Methods: This is a retrospective investigation of pediatric patients with iron deficiency who received SFGC during their admission to the Helen DeVos Children’s Hospital between 2016 and 2018 (N = 85). Results: A total of 258 doses of intravenous SFGC were provided to 85 patients. The average pre-treatment serum hemoglobin was 8.73 ± 1.33, and 7 days post-treatment this increased to 10.41 ± 1.43. Mean corpuscular volume, ferritin, serum ion, total iron binding capacity, reticulocyte percentage, and reticulocyte hemoglobin all increased 7 days post-treatment, as would be suspected, but without any statistically significant difference between hematologic outcomes and cumulative dose of SFGC. Our study did not reveal any correlation between the cumulative dose of SFGC administered and the amount of RBC transfusions received. Only one adverse event was recorded. Conclusion: Our results complement the trend of increased use and emerging evidence of favorable safety profiles of IV iron in the pediatric population. This descriptive investigation revealed that administering higher cumulative doses of SFGC provided no further benefits in terms of hematologic response or RBC transfusion administration.

Laser-Induced Minimization of Circulating Tumor Cells to Suppress Tumor Metastasis.

Circulating tumor cells (CTCs) are key indicators of tumor metastasis. Effective clearance of CTCs can reduce the probability of metastasis. We designed a system for the real-time dynamic monitoring and clearance of CTCs, capable of monitoring and clearing CTCs in the living circulatory system. Experimental results showed that pulsed laser treatment significantly affects the clearance of melanoma CTCs. Through invivo imaging of small animals and survival analysis of mice, we observed that CTC clearance could reduce the size of distant metastatic lesions and prolong the lifespan of the mice. Additionally, we set up a hemolysis experiment to demonstrate that the laser energy used does not cause damage to red blood cells. This study is based on the physical and mechanical destruction of CTCs, meaning there is no issue of drug resistance. This provides a novel approach and technical means for suppressing tumor metastasis and extending the lifespan of patients in clinical settings.

Red blood cell distribution width is an independent predictor of mortality following amputation for diabetic foot

Red blood cell distribution width (RDW) is a prognostic factor in various disorders. This study aimed to assess the prognostic value of RDW in patients undergoing amputation for diabetic foot. We retrospectively analyzed data on 415 patients who underwent diabetic foot amputation between January 2009 and January 2019. After establishing an optimal cutoff value of preoperative RDW for all-cause mortality, univariable and multivariable analyses with Cox proportional hazard model for survivorship and logistic regression analysis for prolonged hospital length of stay (> 30 days) were performed to identify significant prognostic factors. A preoperative RDW of 14.5% was the optimal cutoff value for predicting all-cause mortality. RDW ≥ 14.5% was significantly associated with increased all-cause mortality (hazard ratio, 2.55; 95% confidence interval [CI], 1.55–4.19; P < 0.001) on multivariable Cox proportional model analysis. Preoperative RDW ≥ 14.5% was also associated with a prolonged hospital length of stay after surgery (odds ratio, 2.17; 95% CI, 1.29–3.66; P = 0.004). Higher preoperative RDW was an independent predictive factor for increased all-cause mortality and prolonged hospital length of stay after diabetic foot amputation. These results suggest that RDW may be a useful laboratory parameter for risk stratification in patients undergoing amputation for diabetic foot.

Red Blood Cell Casts on Kidney Biopsy and Progression of IgA Nephropathy.

Renal red blood cell casts (RBCC) are common in IgA nephropathy (IgAN), but their role in kidney disease progression of patients with IgAN remains unclear. 1425 patients in Peking University First Hospital IgAN (PKU-IgAN) cohort and 279 patients in TESTING trial were enrolled to test the association between RBCC and kidney outcome. RBCC was defined as positive (+) when at least one cast was identified within the renal tubules by light microscopy. Kidney endpoint was the composite of the first occurrence of a sustained 30% decrease in estimated glomerular filtration rate or end stage kidney disease or death due to kidney disease. Cox regression analysis was used. In PKU-IgAN, 529 patients (37%) had RBCC; in TESTING trial, 78 patients (28%) had RBCC. Patients with RBCC had more crescentic lesions, and less segmental sclerosis compared with patients without RBCC. In PKU-IgAN, after a median follow-up of 54 months, 119 patients (22%) with RBCC and 260 patients (29%) without RBCC reached the composite kidney endpoint (P=0.009). In multivariable analysis, RBCC was independently associated with composite kidney endpoint (HR 0.79; 95%CI 0.63 - 0.99; P=0.038). RBCC and immunosuppressive therapy (IST) had an interaction (P=0.001). RBCC was independently associated with composite kidney endpoint in patients who received IST (HR 0.56; 95%CI 0.40 - 0.77; P<0.001). In TESTING trial, after a median follow-up of 57 months, 26 patients (33%) with RBCC and 96 patients (48%) without RBCC reached the composite kidney endpoint (P=0.041). In univariate analysis, RBCC was associated with composite kidney endpoint (HR 0.64; 95%CI 0.42 - 0.99; P=0.047). Renal RBCC was frequent in IgAN and was associated with a higher incidence of acute active lesions and better renal prognosis, especially in those who received IST, warranting particular attention.

Developmental Immunotoxicity Study of Tris(chloropropyl) phosphate (TCPP) in Hsd:Sprague Dawley® SD® Rats Exposed Through Dosed Feed.

Tris(Chloropropyl) phosphate (TCPP) is a member of organophosphate flame retardants (OPFRs) used commonly as a replacement for polybrominated diphenyl ethers in consumer and commercial products. Flame retardants have been shown to modulate immune function in vivo and in vitro and there is evidence that at least some related compounds such as organophosphate pesticides can cause developmental immunotoxicity. Developmental immunotoxicology studies were conducted by administering 0, 2500, 5000 or 10000 ppm TCPP in feed to pregnant Hsd: Sprague Dawley® SD® rats from gestation day (GD) 6 through weaning on postnatal day (PND) 28. Feed exposure to TCPP was continued in the F1 offspring until terminal euthanasia at approximately 16-21 weeks of age when assessments for developmental immunotoxicity were conducted. Innate, humoral, and cell mediated immune function were assessed in the F1 adults. The antibody forming cells (AFC) response to sheep red blood cells (SRBC) was reduced in male and female F1 rats in the 10000 ppm treatment group but coincided with reduced bodyweights. The AFC response was also significantly reduced in male rats exposed to 5000 ppm where only moderate effects on bodyweights occurred. TCPP exposure affected baseline T-cell proliferation without stimulation; however, the relevance of this change for immunotoxicity risk is unknown. TCPP exposure did not affect cytotoxic T-lymphocyte activity. Only minor and inconsistent treatment related effects on hematology, innate NK cell function, and immune cell population distributions in the spleen were observed. Taken together, these data indicate that TCPP has the potential to impact humoral immune responses following developmental exposure.

Quality comparison of autotransfusion devices in cardiac surgery: a prospective observational cohort study.

We sought to conduct a quality improvement initiative to compare the wash quality and speed of autologous red blood cell (RBC) processing of four autotransfusion devices during cardiac surgery. Using a prospective observational cohort study approach, we prospectively evaluated four commercially available autologous cell savage devices (autoLog IQ™, Medtronic plc, Minneapolis, MN, USA [135mL]; Xtra™, LivaNova, plc, Houston, TX, USA [125mL, 225mL]; Cell Saver® Elite®+, Haemonetics Corp., Boston, MA, USA [125mL, 225mL]; and CATSmart®, Fresenius Kabi AG, Bad Homburg vor der Höhe, Germany) in adult patients undergoing cardiac surgery. Device settings were determined by manufacturer recommendations for optimal wash quality. We collected pre- and postprocessing samples, volumes, and processing times from each device to calculate removal ratios of heparin, potassium, plasma free hemoglobin (PfHb), white blood cells (WBCs), platelets, reinfusion concentrations of heparin and potassium, and red blood cell (RBC) recovery rates. A total of 130 consecutive patients underwent autologous cell salvage, but 15 cases were excluded because of incomplete data. All devices removed > 99% heparin, > 95% potassium, > 94% platelets, and > 85% PfHb from collected shed blood. Comparison of processing sets showed significant differences in median [interquartile range] WBC removal ratios, ranging from 26 [19-33]% to 59 [42-68]%, and median heparin reinfusion concentrations, which ranged from 0.09 [0.08-0.11] to 0.63 [0.55-0.70] U·mL-1 processed red cells. Median RBC recovery rates also showed significant differences between processing sets, ranging from 8 [8-10] mL RBC·min-1 to 24 [22-25] mL RBC·min-1. Wash quality and processing speed differed between autotransfusion devices and processing sets. These findings may have clinical implications when large volumes of shed blood are processed and reinfused.

Prediction of hemolytic peptides and their hemolytic concentration.

Peptide-based drugs often fail in clinical trials due to their toxicity or hemolytic activity against red blood cells (RBCs). Existing methods predict hemolytic peptides but not the concentration (HC50) required to lyse 50% of RBCs. This study develops classification and regression models to identify and quantify hemolytic activity. These models train on 1926 peptides with experimentally determined HC50 against mammalian RBCs. Analysis indicates that hydrophobic and positively charged residues were associated with higher hemolytic activity. Among classification models, including machine learning (ML), quantum ML, and protein language models, a hybrid model combining random forest (RF) and a motif-based approach achieves the highest area under the receiver operating characteristic curve (AUROC) of 0.921. Regression models achieve a Pearson correlation coefficient (R) of 0.739 and a coefficient of determination (R²) of 0.543. These models outperform existing methods and are implemented in HemoPI2, a web-based platform and standalone software for designing peptides with desired HC50 values ( http://webs.iiitd.edu.in/raghava/hemopi2/ ).

Picolinic acid, a tryptophan metabolite, triggers cellular senescence by targeting NOS/p38 MAPK/CK1α/MLKL signaling and metabolic exhaustion in red blood cells

Picolinic acid, a tryptophan metabolite, triggers cellular senescence by targeting NOS/p38 MAPK/CK1α/MLKL signaling and metabolic exhaustion in red blood cells

The effect of GM-CSF and predictors of treatment outcome in pediatric septic shock patients

BackgroundPediatric septic shock is a critical condition associated with high mortality rates, largely due to sepsis-induced immunosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been explored as a therapeutic intervention to counteract this immunosuppression. Despite its potential, the efficacy of GM-CSF in pediatric septic shock has not been clearly established. This study aims to investigate the impact of GM-CSF administration on survival rates and to identify key predictors of treatment outcomes in pediatric septic shock patients.MethodsWe conducted a retrospective cohort study at the Pediatric Intensive Care Unit (PICU) of Children’s Hospital of Fudan University, Shanghai, from January 1, 2019, to December 31, 2023. The study included pediatric patients diagnosed with septic shock, analyzing their demographic data, GM-CSF and adjunctive therapies, laboratory results, and clinical outcomes. We employed univariate and multivariate logistic regression models to assess the influence of GM-CSF on 28-day mortality and identify significant predictors of treatment outcomes.ResultsThe study included 200 pediatric patients, with 66 receiving GM-CSF treatment and 134 not treated with GM-CSF. The initial comparison showed a higher 28-day mortality in the GM-CSF group (59.1%) compared to the non-GM-CSF group (35.1%, P = 0.001). Notably, after adjustment for confounding factors, multivariate analysis revealed that the effect of GM-CSF treatment on 28-day mortality among pediatric septic shock patients did not reach statistical significance, with an odds ratio (OR) of 0.472 and a 95% confidence interval (CI) ranging from 0.153 to 1.457 (P = 0.192). However, the analysis indicated a potential trend suggesting that GM-CSF treatment may contribute to a reduction in 28-day mortality. In addition, significant predictors of treatment outcomes included hematopoietic stem cell transplantation (HSCT), lactic acid (LAC) levels, hospital-acquired septic shock (HASS), red blood cell (RBC) count, and platelet (PLT) count.ConclusionsGM-CSF treatment may benefit pediatric septic shock patients, especially those with higher lactic acid, and lower RBC and platelet counts. These factors, which are significant predictors of outcomes, should be monitored during therapy.

Biomimetic Chromatography/QSAR Investigations in Modeling Properties Influencing the Biological Efficacy of Phenoxyacetic Acid-Derived Congeners

A hybrid method—combining liquid biomimetic chromatography techniques (immobilized artificial membrane chromatography and biopartitioning micellar chromatography) and Quantitative Structure–Activity Relationships—was used to derive helpful models for predicting selected biological properties such as penetration through the plant cuticle, the skin and the blood–brain barrier, and binding to human serum albumin of phenoxyacetic acid-derived congeners regarded as potential herbicides. Reliable, high-concept models were developed indicating the lipophilicity, polarizability, and sum of hydrogen bond donors and acceptors as properties that determine the biological efficacy of the title compounds. These models were validated by leave-one-out cross-validation. Modeling the toxicity of phenoxyacetic acid-derived congeners to red blood cells allowed the identification of the most toxic substances as well as those molecular descriptors that determine their hemolytic properties.

Association of Altered Baseline Hematological Parameters with Adverse Tuberculosis Treatment Outcomes

Tuberculosis (TB) treatment monitoring is an essential tool for effective TB treatment management. Identifying parameters that predict adverse TB treatment outcomes could significantly improve clinical management. The association of hematological parameters with poor TB treatment outcomes is not well defined. To study the relationship of hematological parameters with TB treatment outcomes, we examined data from pulmonary tuberculosis (PTB) patients with successful (controls) and unsuccessful (cases) treatment outcomes. We enrolled 68 cases and 133 controls through a nested 1:2 case–control study, matching for age, sex, body mass index, diabetes status, alcohol and smoking. Hematological profiling showed significant difference in the absolute counts of white blood cells, lymphocytes, neutrophils and monocytes between cases and controls. In addition, increased neutrophil to lymphocyte ratio (NL) ratio and monocyte to lymphocyte (ML) ratio were present in cases in comparison to controls. Similarly, decreased hematocrit and red blood cell counts were detected in cases when compared with controls. Univariate and multivariate analysis demonstrated a significant association of absolute counts of WBC, neutrophils, monocytes, NL and ML ratios with poor treatment outcomes. The altered baseline hematological parameters are clearly associated with the poor TB treatment outcomes, showing potential for clinical prediction to enhance management of at-risk cases.