High Levels Research Articles

APEX1 Polymorphisms Affect Acute Myeloid Leukemia Risk, and Its Expression Is Involved in Cell Proliferation and Differentiation.

The link between DNA repair gene polymorphisms and cancer susceptibility has gained significant attention. Thus, we investigated the impact of base excision repair (BER) gene polymorphisms on acute myeloid leukemia (AML) risk and pathogenesis. In total, 106 patients with AML and 191 healthy controls were included in the study, wherein polymorphisms in four BER genes (APEX1, MUTYH, OGG1, and XRCC1) were examined. Notably, the APEX1-656 T>G polymorphism exhibited a significant association with AML risk in the recessive (TT vs. TG + GG) (p = 0.046) and co-dominant models (TT vs. GG) (p = 0.02). Assessing APEX1 expression levels, APEX1 expression was elevated in the bone marrow of patients with AML compared with that in controls (p = 0.02). Subsequently, we compared the percentages of CD34+ cells between the APEX1 high or low expression groups, revealing a significant difference (high vs. low = 29.9% vs. 11.5%, p = 0.01). Additionally, we observed reduced APEX1 expression in HL60 cells differentiated with all-trans retinoic acid (p < 0.001). We hypothesized that APEX1 expression could correlate with stemness and analyzed its expression in stem and differentiated cells. In the GSE48558 dataset, AML cells and normal CD34+ cells expressed APEX1 at higher levels than did granulocytes (p < 0.01). Functional experiments revealed that APEX1 knockdown led to a reduction in AML cell proliferation. These findings indicated that APEX1 polymorphisms were a potential risk factor for AML and highlighted the important role of APEX1 in regulating AML cell differentiation and proliferation.

Determination of selected oxysterol levels, oxidative stress, and macrophage activation indicators in children and adolescents with familial hypercholesterolemia.

Elevated levels of cholesterol in the bloodstream, also referred to as hypercholesterolemia, pose a significant risk for the onset of cardiovascular and cerebrovascular diseases. Oxysterols, cholesterol-derived oxidized compounds that form enzymatically or non-enzymatically, contribute to the development of atherosclerosis and coronary artery disease. This study aimed to examine the critical oxysterol levels in children and adolescents with hypercholesterolemia and explore the correlation between these levels, oxidative stress, and atherosclerosis progression. The study included 20 patients with familial hypercholesterolemia (FH) and 20 healthy individuals aged between 6 and 18 years. Participants were categorized into children (6-9 years) and adolescents (10-18 years). Pediatric and adolescent patients were selected from among subjects with LDL-C ≥ 130mg/dL and diagnosed with heterozygous familial hypercholesterolemia (HeFH) based on the presence of mutations in the LDL receptor (LDL-R) gene. Patients with HeFH who were receiving regular atorvastatin therapy were included in the study. There were no notable differences in catalase and paraoxonase (PON1) activities among the groups. However, the patient group displayed substantially higher levels of malondialdehyde (MDA) (P = 0.0108) and superoxide dismutase (SOD) activity (P = 0.0103). Compared to the healthy control group, serum chitotriosidase (CHITO) activity (P = 0.037) and chitinase 3-like protein 1 (YKL-40) levels (P = 0.0027) were significantly elevated in the patient group. Furthermore, the carotid intima-media thickness (CIMT) measurements of the patient group were significantly greater than those of the healthy group (**P < 0.0001****). The patient group exhibited significantly elevated levels of 5,6-α-epoxycholesterol, Cholestane-3β,5α,6β-triol (C-triol), and 7-ketocholesterol (7-KC), whereas 27-hydroxycholesterol (27-OHC) was significantly more abundant in the healthy group. On the other hand, while 27-OHC/Total cholesterol (Total-C) levels were significantly higher in healthy individuals, the C-Triol/Total-C ratio was significantly higher in patients. No significant differences were found between the groups in terms of 7-KC/Total-C and 5,6-α-epoxycholesterol/Total-C levels. This study highlights the key roles of oxysterols, oxidative stress, and macrophage activation in the development of atherosclerosis in pediatric and adolescent patients with FH. Elevated C-Triol levels in FH patients, alongside increased CIMT, point to early vascular changes despite atorvastatin therapy. In contrast, higher 27-OHC levels in healthy controls suggest differential oxysterol regulation due to cholesterol-lowering treatments in FH patients. C-Triol and 27-OHC/Total-C ratios showed potential as biomarkers to distinguish patients with FH. These findings emphasize the need for therapies targeting oxidative stress and macrophage activation in addition to cholesterol-lowering interventions.

Early pregnancy metal levels in maternal blood and pregnancy outcomes.

Prenatal exposure to heavy metals such as Lead (Pb), arsenic (As), cadmium (Cd), and selenium (Se) is associated with various adverse pregnancy outcomes. This study examines the association between early pregnancy maternal blood levels of these metals and adverse pregnancy outcomes, while also addressing the differences between low-risk and high-risk groups based on having a history of preterm birth (PTB). This prospective cohort study recruited parous women during first trimester, categorized into low-risk and high-risk groups. Participants completed a questionnaire, and heavy metal levels were measured in blood samples. Pregnancy outcomes including PTB, low birth weight (LBW), gestational age at delivery, birth weight and head circumference were recorded following delivery. Multivariable analyses were conducted to evaluate the independent associations between heavy metal levels and pregnancy outcomes, while adjusting for maternal age, BMI, employment, smoking, fertility treatments and education. Among 404 participants, the mean (± SD) levels were Pb: 3.12 ± 1.82µg/L, As: 0.41 ± 0.4µg/L, Cd: 0.26 ± 0.34µg/L, and Se: 119.84 ± 21.05µg/L. Significant differences in Pb, Se, Cd and As levels were observed between the low-risk and high-risk groups, with higher levels in the low-risk group. However, no significant associations were found between heavy metal levels and any of the study outcomes in either univariable comparison or multivariable models. These findings highlight the need for further research to understand the potential impact of these metals on pregnancy, considering population-specific factors and exposure timing.

Application of functional magnetic resonance imaging to evaluate renal structure and function in type 2 cardiorenal syndrome.

There is a lack of diagnostic non-invasive imaging technology for assessing the early structural and functional changes of the kidney in type 2 cardiorenal (CRS) patients. This study aims to explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for clinical application in type 2 CRS patients, to provide imaging markers for the assessment of kidney damage. This is a retrospective observational clinical study conducted in Nanjing, China. The clinical characteristics, including age, gender, medical history, laboratory results, and ultrasound and magnetic resonance imaging results were collected from the electronic medical record. Thirty-one patients with type 2 CRS, 20 patients with chronic heart failure (HF) and 20 healthy controls were enrolled and divided into type 2 CRS, HF and control groups. All the participants underwent magnetic resonance imaging (MRI) scanning. The apparent diffusion coefficient (ADC) value and IVIM-DWI parameters including true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were obtained. The correlation between estimated glomerular filtration rate (eGFR), renal size and imaging parameters was evaluated by Spearman correlation analysis. ADC and D of the renal cortex in patients with type 2 CRS were lower than those in the healthy control group. ADC and f in the HF group were lower than those in the control group. D was positively correlated with the length (r = 0.3752, P = 0.0013) and transverse diameter (r = 0.3258, P = 0.0056) of the kidney. ADC (r = 0.2964, P = 0.0121) and D (r = 0.3051, P = 0.0097) were positively correlated with eGFR. Renal cortical ADC and D values could distinguish type 2 CRS patients from the healthy controls with area under the curve (AUC) of 0.723 and 0.706, respectively. The ADC and D values were not only correlated with renal function, but also had lower levels in type 2 CRS. The IVIM-DWI parameter D was also related to kidney size, but further research is needed to determine whether it can be used as a novel imaging marker for type 2 CRS.

The Roles of Vitamin D Levels, Gla-Rich Protein (GRP) and Matrix Gla Protein (MGP), and Inflammatory Markers in Predicting Mortality in Intensive Care Patients: A New Biomarker Link?

Objectives: Identifying reliable biomarkers to predict mortality in critically ill patients is crucial for optimizing management in intensive care units (ICUs). Inflammatory and metabolic markers are increasingly recognized for their prognostic value. This study aims to evaluate the association of various inflammatory and metabolic markers with ICU mortality. Methods: This prospective observational study was conducted from January 2023 to January 2024 in the City Hospital’s ICU. A total of 160 critically ill patients were enrolled. Laboratory parameters, including white blood cell (WBC) count, red cell distribution width (RDW), platelet count, neutrophil count, mean platelet volume (MPV), monocyte count, lymphocyte count, procalcitonin (PCT), C-reactive protein (CRP), calcium (Ca++), and vitamin D levels, were analyzed. Additionally, ratios such as the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory index (SII), and pan-immune-inflammation value (PIV) were calculated. Plasma levels of Gla-rich protein (GRP) and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) were measured using ELISA. Results: The mean age of the patients included in the study was 60.5 ± 15.8 years. Cardiovascular disease was present in 72 patients (45%), respiratory system disease in 58 (36%), and chronic kidney disease (CKD) in 38 (24%). Additionally, 61 patients (38%) had diabetes, and 68 (42%) had hypertension. Inflammatory markers, including PLR, NLR, and PIV, were all significantly higher in non-survivors, while calcium and vitamin D levels were lower (p &lt; 0.05). Higher WBC, RDW, neutrophil count, PLR, NLR, PIV, CRP, procalcitonin, GRP, and dp-ucMGP levels were positively correlated with longer hospital stays and increased mortality. In contrast, platelet and lymphocyte counts were negatively correlated with both outcomes (p &lt; 0.05). Vitamin D levels showed an inverse relationship with both hospital stay and mortality, indicating that lower levels were associated with worse outcomes (p &lt; 0.05). In multiple logistic regression analysis, elevated WBC count (OR = 1.20, p = 0.02), RDW (OR = 1.35, p = 0.01), neutrophil count (OR = 1.25, p = 0.01), MPV (OR = 1.20, p = 0.02), PLR (OR = 1.30, p = 0.01), NLR (OR = 1.40, p = 0.001), PIV (OR = 1.50, p = 0.001), CRP (OR = 1.32, p = 0.01), procalcitonin (OR = 1.45, p = 0.001), GRP (OR = 1.40, p = 0.001), and dp-ucMGP (OR = 1.30, p = 0.001) levels were significantly associated with increased mortality. Conclusions: Inflammatory and metabolic markers, particularly NLR, PLR, PIV, GRP, and dp-ucMGP, are strong predictors of mortality in ICU patients. These markers provide valuable insights for risk stratification and early identification of high-risk patients, potentially guiding more targeted interventions to improve outcomes.

Abstract B066: Analytical validation of a multiplexed CTC-mRNA assay for androgen receptor pathway inhibitors

Abstract Introduction: Androgen receptor pathway inhibitors (ARPIs) have been shown to improve survival for men with metastatic prostate cancer, however, the use of 2nd line ARPIs has limited efficacy. There is a critical need to develop biomarker-driven treatment strategies for this clinical need. We have previously reported on a novel circulating tumor cell (CTC) multiplexed mRNA biomarker that has prognostic and predictive capability in clinical utility trials to detect AR- driven resistance and Neuroendocrine Prostate Cancer (NEPC). However, before these biomarkers can be tested in prospective clinical validation trials and clinical care, they must undergo thorough analytical validation. We report a novel approach to the analytical validation of rare cell assays for gene expression analysis and the testing of this CTC mRNA assay. Methods: Analytical validation for assays with single-cell level detection is particularly challenging in that results may be categorical as well as quantitative: sometimes measured at higher or lower levels, and other times resulting in no detectable signal, precluding the use of standard measures of precision. The inter-metastatic cellular heterogeneity composition of a liquid biopsy further complicates efforts to demonstrate clinical-grade precision at the single-cell level. To address this, we applied logistic regression to replicates of patient samples, cell lines and unique DNA and mRNA oligonucleotides to define the minimum amount of analyte to achieve high precision for the underlying PCR and exclusion-based sample preparation (ESP) mRNA extraction technologies. Results: We demonstrated clinical-grade precision at the single-cell level, comparable to the sensitivity previously demonstrated for qPCR, and analyte quantities of 15 total transcripts. Equivalent analyte yield was obtained from the extraction of single-cell quantities of cell line cells with or without a maximum of 10,000 background cells, demonstrating robustness to a range of sample purities. Extractions from 10 healthy donors demonstrate analytical specificity of the assay, with a synthetic mRNA spike-in control used to confirm successful extractions. Replicates of cell line extractions at different concentrations were compared to 44 replicate patient samples to delineate technical precision from biological heterogeneity. Discussion: The automated CTC-mRNA extraction technology demonstrates high precision equivalent to PCR with single-cell sensitivity. We can further reproducibly detect as low as 15 transcripts. We have achieved a semi-qualitative assay read-out that maximizes the analytical sensitivity of the assay, allowing the clinical reporting of multiplexed results for clinical utility in prostate cancer. This validation approach also serves as a model for clinical implementation of other single-cell liquid biopsy assays. Currently, this assay is being prospectively evaluated in the ARCTIC trial for patients with prostate cancer treated with an ARPI (NCT06141993). Citation Format: Jennifer L Schehr, Rory M Bade, Anupama Singh, Jacob C Caceres, Nasya A Ramli, Matthew C Mannino, Diego Eyzaguirre, Alyssa M Hintz, Manushi N Vatani, Serena K Wolfe, Kayo Miyazaki, Elizabeth Haas, Joshua Faulkes, Dana E Rathkopf, Susan Halabi, Andrew J Armstrong, Shuang G Zhao, Joshua M Lang. Analytical validation of a multiplexed CTC-mRNA assay for androgen receptor pathway inhibitors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B066.

Contrasting copepod community composition in two Greenland fjords with different glacier types

Abstract Greenland's fjord ecosystems are strongly influenced by meltwater discharge from glaciers. Marine-terminating glaciers can significantly enhance primary production during the melt season (compared to land-terminating glaciers), but their impact on secondary producers is not well understood. Here, we study seasonal changes in the zooplankton community (&amp;gt;50 μm) and grazing rates along two fjord transects in southwest Greenland influenced by different glacier types. Zooplankton biomass was comparable between the fjords, but community composition differed during summer. Nuup Kangerlua, a predominantly marine-terminating system, was characterized by large, herbivorous copepods and a longer summer grazing period in connection with the summer bloom. Ameralik, influenced by a land-terminating glacier, was characterized by small, omnivorous copepods, particularly Microsetella norvegica and Oncaea spp., and indicated a faster post-bloom transition towards regenerated production. Local hydrographic conditions also impact copepod biomass. A station with high biomass was found in Ameralik, potentially linked to a frontal zone where fjord water masses meet, providing favorable grazing conditions. We hypothesize that a future transformation from marine- to land-terminating glaciers could result in an increased abundance of smaller copepods, as observed in Ameralik. Such a community would constitute a less lipid-rich food source for higher trophic levels.

Lipoprotein-associated phospholipase A2 and its possible association with COPD development: a case-control study.

The association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with various cardiovascular events has been well-established. However, the exploration of its potential involvement in Chronic obstructive pulmonary disease (COPD) is currently limited. Therefore, our study aims to examine the relationship between Lp-PLA2 and pulmonary conditions, including emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, to provide further evidence of a possible association with COPD development. Using data from the Southwest Hospital Health Management Center, spanning January 2013 to July 2024, we analyze relationship of serum Lp-PLA2 levels with diffuse pulmonary emphysema and pulmonary functions. In univariate analysis, group differences were assessed with t-tests for numerical variables and Chi-square tests for categorical data. Variables found to be statistically significant (two-sided P < 0.05) in univariate analysis were subsequently included as covariates in multivariate analysis, performed using a binary logistic regression model. Odds ratios and 95% confidence intervals were calculated to assess the differences. We established 2 case-control populations: the Imaging population (1056 subjects, mean age 57.666 ± 8.700 years old, 89.9% male) selected from 24,670 initial records, and the Pulmonary Function population (279 subjects, mean age 52.082 ± 11.473 years old, 71.4% male) selected from 1868 initial records. Univariate analysis revealed that serum Lp-PLA2 levels were significantly higher in patients with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction compared to those without (454.682 ± 141.382U/L vs. 423.330 ± 140.658U/L, P < 0.001; 475.059 ± 157.181U/L vs. 420.824 ± 142.119U/L, P = 0.006; 475.31 ± 148.980U/L vs. 439.036 ± 157.977U/L, P = 0.049, respectively). Multivariate analysis further showed higher Lp-PLA2 levels were associated with increased risks of diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction. Using Lp-PLA2 ≤ 300 U/L as reference, odds ratios for the aforementioned conditions showed a gradually increasing trend with every 100U/L increase in Lp-PLA2 levels. Our preliminary study suggests that Lp-PLA2 is independently associated with diffuse pulmonary emphysema, obstructive ventilatory dysfunction as well as small airway dysfunction, which are commonly seen in COPD development. These findings indicated a possible association between Lp-PLA2 and COPD, though further validation is needed in a large cohort of COPD patients.

Effects of Medication Period and Gastrin Levels on Endoscopic Gastric Mucosal Changes in Long-Term Proton Pump Inhibitor Users

Background/Objectives: Proton pump inhibitor (PPI) use has increased worldwide, including in continuous and longer-term users. Recent reports highlight PPI-related endoscopic gastric mucosal changes, including fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cracked and cobblestone-like mucosa (CCLM), and black spots. PPI use elevates gastrin levels because of acid inhibition, and hypergastrinemia might be relevant to these findings. In this cross-sectional study, we retrospectively examined gastric mucosal changes in long-term PPI users, focusing on medication period and gastrin levels. Methods: We enrolled 57 patients who received a PPI (&gt;1 year) at two clinics between January 2021 and March 2022. Participants were classified according to medication period: 1 &lt; 5, 5–10, and ≥10 years. Gastrin levels were categorized as low, middle, and high (&lt;250, 250–500, and ≥500 pg/mL, respectively). Odds ratios (OR) were estimated to assess the risk of endoscopic findings. Results: Of the 57 patients, 6 (10.5%), 25 (43.9%), and 26 (45.6%) were PPI users of 1 &lt; 5, 5–10, and ≥10 years, respectively. There were no significant differences in the incidence of endoscopic findings among the medication periods. Low, middle, and high gastrin groups included 21 (36.8%), 21 (36.8%), and 15 (26.3%) patients, respectively. CCLM incidence was significantly elevated in higher gastrin level groups: middle (OR, 6.60; 95% confidence interval [CI], 1.46–29.75; p = 0.014) and high (OR, 9.00; 95% CI, 1.79–45.23; p = 0.0008) (p-trend = 0.0171). No significant differences were observed for other findings. Conclusions: No elevated risk of PPI-related gastric epithelial changes in long-term PPI users was observed time-dependently. Notably, higher gastrin levels were positively associated with CCLM development, irrespective of the medication period.

I am, therefore I preserve: Exploring middle-class imagery, biased status perceptions, and pro-environmental behaviour

Extensive research on pro-environmental behaviour (PEB) reveals a significant knowledge gap in understanding the influence of social class, perceived status and the middling tendency on pro-environmental behaviour. Using the International Social Survey Programme Environment dataset, and conducting multilevel mixed-effects linear regressions, we find that the middling tendency and biased status perceptions significantly influences pro-environmental behaviour. Those who deflate their social position have higher pro-environmental behavior and this reinforces the idea that pro-environmental behaviour is driven by a post-materialist effect rather than a status enhancement effect. Moreover, the objective middle class is still a stronger contributor to higher PEB levels compared to subjective middle class. We also find the relation between class, status and PEB vary by country. These findings provide vital insights into the intricate and heterogenous dynamics between class, status and pro-environmental behaviour among different countries and shed light on class and status as driving forces behind pro-environmental behaviour.

Application of platelet transcriptomics for assessing treatment effectiveness and predicting long-term platelet counts recovery in aplastic anemia.

Aplastic anemia (AA) is a bone marrow failure disease for which the means of assessing and predicting the therapeutic effectiveness are still relatively limited. Thrombocytopenia is often the earliest and most severe symptom in patients newly diagnosed with AA (Dx-AA). While clinical consideration is usually given to the quantitative changes in platelets during treatment, there is little focus on the resolution of the molecular characteristics of platelets in AA. To investigate the changes in platelet molecular characteristics throughout the treatment process of AA, and to explore the use of transcriptomics for monitoring and predicting treatment outcomes. We comprehensively analyzed platelet transcriptomic changes in AA patients at initial diagnosis and different stages of treatment effectiveness using bulk transcriptome sequencing. Genes associated with cell proliferation, erythroid function, and amino acid transport were elevated in Dx-AA. Conversely, genes linked to histones, thrombosis, mitochondrial energy metabolism, and signaling pathways were significantly downregulated. 60.6% of the differentially expressed genes were substantially restored following complete remission. Furthermore, through the examination of longitudinal samples, we identified recovery ascending genes (RAG) that could serve as viable biomarkers for assessing treatment effectiveness in AA. Besides, we observed that higher expression levels of RAG may predict superior long-term platelet counts recovery six months in advance in patients with partial response. The platelet transcriptome undergoes profound changes and can serve as a potential indicator for assessing treatment effectiveness and predicting long-term platelet counts recovery in AA.

Assessing light spectrum impact on growth and antioxidant properties of basil family microgreens.

Understanding the influence of light spectra on plant growth and antioxidant activities is crucial for optimizing cultivation practices and enhancing crop quality. In this study, we investigated the effects of different light treatments on growth parameters and antioxidant activities in five plant species: peppermint, Thai basil, cumin, lemon basil, and green holy basil. Our results revealed distinct responses to varying light spectra, with green light consistently promoting taller plant heights across all species. Additionally, blue light induced notable increases in plant width for certain species. Analysis of antioxidant activities demonstrated dynamic fluctuations in Total Phenolic Content (TPC) and Flavonoid Content (TFC) among different light treatments and plant species. While white and red light generally promoted higher TPC levels, blue light unexpectedly exhibited the highest TPC levels at specific time points. Moreover, investigation into DPPH Radical Scavenging activity revealed diverse temporal responses to light spectra, with blue light demonstrating exceptional activity at early stages and white and red light showing heightened activity at later time points. These findings underscore the importance of tailored light regimes in optimizing growth parameters and enhancing antioxidant activities in cultivated plants, thereby offering promising avenues for sustainable agriculture and food production practices.

Impact of induction agents and maintenance immunosuppression on torque teno virus loads and year-one complications after kidney transplantation

BackgroundTorque teno virus load (TTVL) is gaining importance as a surrogate parameter to assess immunocompetence in kidney transplant recipients. Although the dynamics of TTVL have been investigated before, the impact of different induction agents and variations in immunosuppressive maintenance therapies on TTVL remain unknown.MethodsIn this retrospective study, TTVL was quantified in 537 plasma or serum samples from 134 patients transplanted between 2018 and 2021. TTVL was examined pre-transplantation and 30-, 90-, 180-, and 360-days post-transplant. To assess the influence of induction therapy on TTVL, 67 patients receiving anti-thymocyte globulin (ATG) induction were matched with 67 patients receiving an interleukin-2 receptor antagonist (IL2-RA) induction in terms of age, sex, and donor modality.ResultsFollowing transplantation, there was a steep increase in TTVL post-transplant for all patients with peak viral loads at 90 days post-transplant (median TTVL [IQR] 7.97×106, [4.50×105–1.12×108]) followed by subsequently declining viral loads. Compared to patients receiving IL2-RA as induction therapy, patients receiving ATG had significantly higher peak viral loads 3 months post-transplant (median TTVL [IQR] 2.82×107 [3.93×106–1.30×108] vs. median TTVL [IQR] 2.40×106 [5.73×104–2.60×107]; P&amp;lt;0.001). Throughout all post-transplant time points, patients receiving additional rituximab for induction along with higher tacrolimus target levels exhibited the highest TTVL.Patients whose TTVL 3-months post-transplant exceeded the currently proposed cutoff to predict infections within the first year post-transplant [6.2 log10] showed a trend towards a higher risk of being hospitalized with an infection in the following 9 months, albeit without being statistically significant (HR=1.642, P=0.07).ConclusionsHigher TTVL reflects the greater immunosuppressive burden in immunological high-risk patients receiving intensive immunosuppression. The choice of induction agent and intensified immunosuppressive maintenance therapy notably affects TTVL at 3 months post-transplant and beyond, necessitating careful consideration when interpreting and applying TTVL cutoffs to monitor immunocompetence post-transplant.

Dyslipidemia induced inflammation mediated the association between obesity and Osteoarthritis: a population-based study.

This study aims to evaluate the mediation effect of dyslipidemia induced inflammation on the causal associations between obesity and Osteoarthritis (OA). This cross-sectional study used data from the National Health and Nutrition Examination Survey (1999-2010). The association between general and abdominal obesity (exposure), OA (outcome) and mediators (total cholesterol, high-density lipoprotein, and C-reactive protein) was assessed using multivariate linear and logistic regression models and mediation analysis. A total of 23,308 participants were enrolled in this study, and 2,180 were diagnosed with OA. Participants with obesity were more likely to have OA (general obesity: OR = 2.508, 95%CI: 1.602, 4.197, P < 0.001; abdominal obesity: OR = 3.814, 95%CI: 3.242, 4.509, P < 0.001) than those without the obesity. High quantile of total cholesterol (OR:1.399; 95%CI:1.235, 1.257; P < 0.001), high-density lipoprotein (OR:1.644; 95%CI:1.443, 1.874; P < 0.001) and C-reactive protein (OR:1.952; 95%CI:1.707, 2.237; P < 0.001) increased the risk of OA when compared to lowest quartile. In the linear regression, the betas varied from 0.668 (95%CI: 0.635, 0.741; P < 0.001) to 0.693 (95%CI: 0.674, 0.712; P < 0.001), suggesting that individual with obesity had higher C-reactive protein levels. Additionally, total cholesterol and high-density lipoprotein were associated with C-reactive protein. Mediation analyses showed that the causal association of obesity with OA risk was mediated by high-density lipoprotein and C-reactive protein, with the mediation proportion ranging from 17.216 to 45.058%. Moreover, high-density lipoprotein to C-reactive protein path acting as serial mediators in the associations between obesity and OA (general obesity: β = 0.012; 95%CI: 0.009-0.014; abdominal obesity: β = 0.011; 95%CI: 0.008-0.014). The association between obesity and OA is partially mediated by systemic inflammation caused by dyslipidemia. Our study suggested anti-lipid therapy may be positive for obese individuals with OA.

The assessment of psychosocial distress in hospitalized cancer patients during radio-oncological treatment: a monocentric experience study.

This study investigated the prevalence and determinants of psychosocial distress among hospitalized patients undergoing radiotherapy to identify opportunities for interventions to enhance patient well-being. Between January 2021 and May 2023, 137 hospitalized patients received radiotherapy treatment at the Department of Radiation Oncology of the Fondazione A. Gemelli IRCCS were recruited. Participants completed a questionnaire comprising the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). The study revealed a significant correlation among anxiety, depression, total HADS scores, and Distress Thermometer scores (p < 0.001). Female patients exhibited higher total HADS scores and anxiety levels compared to males (p < 0.004, p < 0.010, respectively). Sleep disturbances were associated with increased anxiety, depression, and overall distress (p < 0.05). Younger patients (< 65years old) demonstrated elevated anxiety and depression levels, while no significant depressive tendency was observed among older participants (> 65years old). These findings underscore the intricate interplay between demographic variables, psychological distress, and treatment-related symptoms among patients during radiotherapy treatments. The study highlights the critical necessity of promptly identifying and addressing psychosocial distress in this population. It suggests that implementing a psychological therapeutic approach, particularly one focused on support, could effectively deter the onset of depression, especially among younger patients. Future research should focus on longitudinal studies to explore distress trajectories and interventions' effectiveness in mitigating distress, with collaborative efforts to translate research findings into evidence-based clinical practice for improved patient care.

BN SO08 - A Comparison of outcomes following Laparoscopic Cholecystectomies before and after COVID-19

Abstract Background The COVID-19 pandemic led to the suspension of elective surgeries between March 2020 and March 2021 in the NHS and large parts of the world. In Prince Charles Hospital, elective services were phased in from April 2021 and elective laparoscopic cholecystectomies resumed in June 2021. There is an almost universal perception among surgeons that the cholecystectomies after covid disruption, have become more technically demanding, resulting in longer operative times and poorer outcomes. This study aims to quantify the differences in indications, CLOC score, Parkland grades, and outcomes, following elective cholecystectomy, one year before and after COVID Method Laparoscopic Cholecystectomies performed on elective lists between January 2019 and December 2019 by two UGI surgeons were included in the pre-COVID group. Cholecystectomies performed between September 2021 and August 2022 by the same UGI surgeons were included in the post-COVID group. Cholecystectomies on the CEPOD list and procedures which included CBD exploration or choledochoscopies were excluded. Demographics, ASA, indications, waiting times, operative times, CLOC and Parkland scores were collected. Outcome measures were complications, drains, hospital stay and proportion of subtotal colectomy, day case surgeries, and conversions to open. An online calculator for social science statistics was used to analyze data. Results The pre-covid(n=92) and post-covid(n=98) groups were comparable in age(P=.37), gender(P=.06) and ASA(P= .057). Pre Covid, lower Proportion of patients underwent cholecystectomy for previous cholecystitis(precovid 13.04%, post-covid 35.7%)(P&amp;lt;.001). Pre Covid Cholecystectomies were shorter(pre-covid 74 minutes, post-covid 85 minutes, P=.018). The mean CLOC score and Parkland grade in precovid group (CLOC= 4.03, Parkland 1.8) were less than in the postcovid group(mean CLOC=5.41, mean Parkland 2.5)( P&amp;lt;.001, P=.006). Apart from the Subtotal Cholecystectomy rate (5.4% pre-covid vs 12.2 postcovid, P=-04) and drains (P=.02), there were no significant differences in outcome measures. Conclusion This study demonstrares that the COVID disruption resulted in more challenging procedures, indicated by the increase in CLOC score, Parkland grade, and longer operating times. This is a reflection of a much larger proportion of surgeries being performed for previous cholecystitis. There are however no significant differences in outcome, except the higher rates of subtotal cholecystectomy. This suggests that the skills and techniques have compensated for higher difficulty levels. Data does show an approximately 15% difference between the groups in all other outcome measures which however does not reach statistical significance. A larger sample is needed to clarify this.

A mathematical model to study the role of dystrophin protein in tumor micro-environment.

In this research work, the authors have developed a mathematical model to examine the interaction between dystrophin protein and tumor. The authors formulated a system of ordinary differential equations to describe the dynamics of the dystrophin-tumor interaction system. Jacobian matrix and Routh-Hurwitz stability techniques were used to determine equilibrium points, perform stability and bifurcation analysis, and establish the conditions required for the stability of the proposed model. Numerical simulations are performed using Euler's method to investigate the temporal evolution of the proposed model under different parameter values, such as tumor growth rate and feedback strength of dystrophin protein. The numerical results are presented in tables, and corresponding to each table, a graphical analysis is done. The graphical analysis includes creating phase portraits to visually represent stability regions around the equilibrium points, bifurcation diagrams to identify critical points, and time series analysis to highlight the behavior of the proposed model. The authors explore how variations in dystrophin expression impact tumor progression, identifying potential therapeutic implications of maintaining higher dystrophin levels. This comprehensive analysis enhances our understanding of the dystrophin-tumor interaction, providing a basis for further experimental validation and potential therapeutic strategies.

Safety and immunogenicity of freeze-dried human rabies vaccines: A phase 3 clinical trial of Zagreb and Essen regimes

ABSTRACT Recently optimized freeze-dried rabies vaccines (Vero cell) are promising for rabies prevention; however, comparisons of Essen 5-dose and Zagreb 4-dose regimens are needed for clinical applications. This phase III clinical trial aimed to assess the safety and immunogenicity of candidate freeze-dried rabies vaccines developed for human use by Shandong Yeedo Biotechnology (Registration No.: CTR20182016, http://www.chinadrugtrials.org.cn/index.html). In total, 40 participants in stage I and 1797 subjects in stage II with an age range of 10–60 years were recruited. Both 4-dose and 5-dose experimental vaccines were well-tolerated in stage 1, with similar overall adverse event (AE) rates. In stage 2, systemic fever (35.39%) and local pain (48.91%) were common, and the rate of Grade 3 AEs was approximately 2.5%. Rates of local reactions and unsolicited AEs differed among groups (p = .045 and 0.011). Immunogenicity analyses showed higher antibody levels, seroconversion rates, and pre-immune seroconversion rates in the 4-dose experimental group versus the 5-dose group (p < .001) on day 7 post-first dose, with similar GMCs (geometric mean concentrations) by day 14. Pre-immune negative subjects had comparable antibody levels in the 4-dose and 5-dose experimental groups, outperforming the 5-dose control group (p = .039). The rate difference (95% CI) for first-dose seroconversion at 14 days post-vaccination among pre-immune antibody-negative subjects indicated non-inferiority between the 5-dose experimental and control groups. Overall, the Shandong Yeedo rabies vaccine demonstrated satisfactory safety and efficacy, offering a new option for rabies prevention.

Dimethyl Fumarate Augments Anticancer Activity of Ångstrom Silver Particles in Myeloma Cells through NRF2 Activation

AbstractMultiple myeloma (MM) is an incurable hematological malignancy characterized by relapse and drug resistance. This study investigates the potential of angstrom‐scale silver particles (F‐AgÅPs) to selectively target and eliminate MM cells, focusing on their susceptibility and underlying mechanisms. F‐AgÅPs are synthesized using a pure physical high‐efficiency evaporation‐condensation method and coated with fructose, and their cytotoxic effects on MM cell lines are evaluated through cell viability assays and flow cytometry. Reactive oxygen species (ROS) levels are measured to elucidate oxidative stress, while the role of nuclear factor erythroid 2‐related factor 2 (NRF2) is examined via western blotting and quantitative PCR. In vivo, the therapeutic potential of F‐AgÅPs is assessed using a MM xenograft mouse model. F‐AgÅPs exhibited significant cytotoxicity in MM cells at low concentrations, with higher ROS levels leading to oxidative damage and NRF2 accumulation. This effect is mitigated by the ROS scavenger N‐acetyl‐l‐cysteine. Additionally, the NRF2 activator dimethyl fumarate (DMF) enhanced F‐AgÅPs‐induced cytotoxicity in vitro and suppressed myeloma growth in vivo. These findings suggest that combining DMF with F‐AgÅPs is a promising therapeutic strategy for MM, effectively targeting ROS‐induced oxidative damage through NRF2 activation.

Increased mercury concentrations in walleye and yellow perch in lakes invaded by zebra mussels.

Zebra mussels (Dreissena polymorpha) are invasive species that alter ecosystems and food webs with the potential to affect aquatic mercury cycling and bioaccumulation in fishes, although the effect of zebra mussels on fish tissue mercury has not been tested in inland lakes. We assessed differences in fish tissue mercury concentrations and food webs in Minnesota lakes with and without zebra mussels while controlling for other lake and watershed characteristics. Mercury concentrations in adult walleye (Sander vitreus) and yellow perch (Perca flavescens) were 72 % and 157 % higher, respectively, in lakes containing zebra mussels compared to uninvaded lakes. Mercury in young of year (age-0) fish was also elevated, with mercury concentrations 97 % and 82 % higher in age-0 walleye and yellow perch, respectively, in zebra mussel lakes. Walleye mercury concentrations exceeded 0.22 ppm - a threshold triggering more restrictive human consumption advisories for sensitive populations - at a 23 % smaller size, and average-sized walleye (420 mm) exceeded this threshold at a rate of 77 % in invaded lakes, compared to 35 % in uninvaded lakes. Walleye and yellow perch relied more on littoral resources in lakes with zebra mussels but did not feed at meaningfully higher trophic levels. Increased fish tissue mercury in lakes invaded by zebra mussels have consequential implications for fisheries and human health.