Nonparametric Spearman Correlation Research Articles

Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection.

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

Potentially Harmful Elements Accumulation and Health Risk Assessment of Edible Fish Tissues Caught from the Phander Valley, Northern Pakistan.

This study investigated the concentrations of potentially harmful elements (PHE) in edible tissues of trout fish (Salmo trutta) in the Phander Valley, Northern Pakistan. For this purpose, fish were sampled from the Phander Valley (Gilgit River and Phander Lake). PHE concentrations in edible fish tissues (muscle, fins, and skin) were determined using atomic absorption spectrometry (AAS, AAnalyst 700, Perkin Elmer, USA). Among PHE, zinc (Zn) showed the highest concentration of 1097 μg/kg in the skin, followed by manganese (Mn) of 241 μg/kg in the muscle, and the lowest of 3.78 μg/kg for cadmium (Cd) in fins. The concentration of PHE in fish tissues of the study area was observed within the threshold limits set by the food and agriculture organization (FAO). PHE concentration of fish tissues was used for the calculation of chronic risk assessment using the chronic daily intake (CDI) and hazard quotient (HQ) indices. The highest CDI values were observed for Zn through fish tissue consumption in juveniles, followed by Mn, and the lowest for Cd in adults. The HQ values were observed less than 1 for adults throughPHE consumption in fish tissue; however, that of juvenile surpassed the threshold limit through Cd consumption in all studied tissues and that of Pb in the muscle and skins only. Higher HQ values than the threshold limit could pose a potential chronic risk to the exposed community. Spearman's non-parametric correlation showed a varying degree of correlation among PHE in fish tissues and canonical discriminant analyses were used to differentiate the tissues based on PHE accumulation tendencies.

Rank Non-Parametric Correlation Analysis of Indicators of Heavy Metal Transition from Blood to Cow's Milk to Assess its Environmental Safety

Correlation analysis constitutes an essential method of statistical processing of the obtained scientific research results. Its proper application using special computer software and reliable results allow practically facilitating the work of the veterinary and livestock service in the production of environmentally safe high-quality cow's milk. The purpose of this study is to analyse the correlation between the content of toxic metals Cd and Pb in the blood and milk of cows using the STATISTICA computer software version 10.0. Scientific and economic experiments were conducted on dairy cows with different types of feeding. All animals selected according to the analogue method in terms of live weight and productivity were divided into three groups: the first control group and the second and third experimental groups. The diet included feeds with an excess of heavy metals, especially cadmium and lead. The high biological activity of pollutants affected their migration from the feed of the diet through the gastrointestinal tract to milk. To reduce intoxication of the animal body, premix “MP-A” was introduced into the main diet of cows of the second and third experimental groups, and in the third experimental group – premix “MP-” and injection of the biological product “BP-9”. First, using the Shapiro-Wilk's W test, the study verified the obtained data from laboratory tests of blood and milk for the concentration of toxic metals, the law of “normal” (Gaussian) distribution, and then the necessary Spearman's non-parametric rank correlation coefficient was selected for calculation. The analysis revealed a high correlation between the variables, which was within r=0.82-0.91 (Cd) and r=0.78-0.96 (Pb) with probability (p&lt;0.05) in animals with different types of feeding. The discovered high correlation allows veterinary medicine specialists to quickly apply measures to reduce the toxic load of the body with elements only by analysing blood for cadmium and lead, and timely prevent the production of low-quality dairy raw materials, including using premix and phytobiopreparation tested in the experiment. Further research is aimed at analysing the correlation between other indicators of the quality and environmental safety of milk and feed, constructing regression equations that will practically contribute to the activities of specialists whose task is to ensure the production of high-quality environmentally safe cow's milk

Population Pharmacokinetics of Intravenous Amoxicillin Combined With Clavulanic Acid in Healthy and Critically Ill Dogs.

Background: Data regarding antimicrobial pharmacokinetics (PK) in critically ill dogs are lacking and likely differ from those of healthy dogs. The aim of this work is to describe a population PK model for intravenous (IV) amoxicillin–clavulanic acid (AMC) in both healthy and sick dogs and to simulate a range of clinical dosing scenarios to compute PK/PD cutoffs for both populations.Methods: This study used a prospective clinical trial in normal and critically ill dogs. Twelve client-owned dogs hospitalized in the intensive care unit (ICU) received IV AMC 20 mg/kg every 8 h (0.5-h infusion) during at least 48 h. Eight blood samples were collected at predetermined times, including four trough samples before the next administration. Clinical covariates and outcome were recorded, including survival to discharge and bacteriologic clinical failure. Satellite PK data were obtained de novo from a group of 12 healthy research dogs that were dosed with a single AMC 20 mg/kg IV. Non-linear mixed-effects model was used to estimate the PK parameters (and the effect of health upon them) together with variability within and between subjects. Monte Carlo simulations were performed with seven dosage regimens (standard and increased doses). The correlation between model-derived drug exposure and clinical covariates was tested with Spearman's non-parametric correlation analysis. Outcome was recorded including survival to discharge and bacteriologic clinical failure.Results: A total of 218 amoxicillin concentrations in plasma were available for healthy and sick dogs. A tricompartmental model best described the data. Amoxicillin clearance was reduced by 56% in sick dogs (0.147 L/kg/h) compared with healthy dogs (0.336 L/kg/h); intercompartmental clearance was also decreased (p <0.01). None of the clinical data covariates were significantly correlated with individual exposure. Monte Carlo simulations showed that higher PK/PD cutoff values of 8 mg/L could be reached in sick dogs by extending the infusion to 3 h or doubling the dose.Conclusions: The PK of AMC is profoundly different in critically ill dogs compared with normal dogs, with much higher interindividual variability and a lower systemic clearance. Our study allows to generate hypotheses with regard to higher AMC exposure in clinical dogs and provides supporting data to revise current AMC clinical breakpoint for IV administration.

Decoding self-automated and motivated finger movements using novel single-frequency filtering method – An EEG study

Electroencephalography (EEG) provides the temporal resolution required to map the neural activations for studying motor movements and control. This study aims to compare the power amplitude of electrodes covering the central and frontal regions of a 32-channel scalp EEG. The activations from a standard index finger-tapping and a game paradigm are analyzed. Twenty-five right-handed and five left-handed healthy subjects (range = 18–30 years; mean = 24.25 years; SD = 3.96 years) participated in this study. A novel single-frequency filter (SFF) bank was applied to identify the peak amplitude from the power spectral density plots. The results show that the gaming paradigm yields lower or comparable power amplitudes than the standard finger tapping. We observed that the right-hand finger tapping by the left-handed subjects shows lower between-subject dispersion in amplitude. Nonparametric Spearman correlation showed no association between game scores and power amplitude for the right-handed participants. However, for left-handers, both positive and negative associations were observed. This study demonstrates the efficacy of SFF for extracting power amplitudes with a better signal-to-noise ratio, which has implications in BCI and motor rehabilitation applications. The findings support the role of game paradigms for motor movement research and in understanding bilateral hemispheric activations in cognitive tasks.

Fibrinolytic Dysregulation Contributes to the Hypercoagulable State in Pulmonary Embolism Patients

Introduction: The multifactorial and complex pathophysiology of pulmonary embolism (PE) involves dysregulation of hemostatic system including fibrinolytic imbalance, endothelial compromise and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement. It is estimated that 6000 cases of pulmonary embolism and DVT are reported yearly of which 1000 result in death. PE evolves from a pre-existing venous thrombus, obstructing pulmonary artery leading to pulmonary failure. The progression of clot formation results in increase in right ventricular pressure, systemic hypoperfusion, hypoxemia ischemia and eventually multi organ failure. Fibrinolytic dysregulation and generation of procoagulant mediators result in increased clot burden and lead to adverse outcomes. Profiling of the component of the fibrinolytic system for such mediators as the activators and inhibitors of fibrinolysis, vWF and cellular microparticles may provide additional insights into the pathogenesis of PE. The purpose of this study is to profile plasma samples from PE patients for various mediators of hemostatic dysregulation which contribute to the fibrinolytic dysregulation in PE patients.Material & Method: Seventy-eight patients of 18 years or older age, were included in this study through enrolment conducted in conjunction with an ongoing IRB approved project by the pulmonary embolism response team (PERT) registry. Diagnosis of PE was confirmed by computed tomography (CT), angiography or ventilation perfusion imaging. Blood samples were drawn with in 24 hours of confirmed diagnosis of acute PE in 3.2% sodium citrate tubes at the time of diagnosis, processed for platelet poor plasma and frozen. Control plasma samples were obtained from 50 healthy individuals. Both the patient and control plasma samples were analyzed for D-Dimer, PAI-1 antigen, tPA, TAFI-a, protein C, alpha-2 antiplasmin, microparticles and vWF using ELISA methods (Hypen Biomedical, Franklin, Ohio). A functional PAI-1 chromogenic substrate method and an ELISA based uPA antigen method was used (Biomedica, Halifax, Nova Scotia, Canada). Circulating levels of each of the individual biomarkers were compared to normal plasma, descriptive statistics including non-parametric Mann-Whitney t-test and spearman correlation coefficient analysis was carried out by using GraphPad Prism software. Percent Increase from the normal mean was calculated for each individual parameter. p value <0.05 was considered statistically significant.Result: In comparison to normal group, the PE patients exhibited varying levels of increase in the D-Dimer, tPA, uPA, PAI-1 antigen, PAI-1 functional, TAFI antigen, microparticles and vWF, whereas decreased levels were noted for protein C and alpha-2 antiplasmin as shown on Figure 1. D-Dimer showed the most pronounced increase (368.2-fold) followed by tPA (165.9-fold), PAI-1 antigen (3.91-fold), microparticles (2.14-fold), vWF (1.83-fold), uPA (0.5-fold), TAFI antigen (0.40-fold) and PAI-1 functional (0.34-fold). In correlation analysis, D-Dimer negatively correlated with TAFI antigen (r= -0.3106) and alpha-2 antiplasmin (r= -0.3056), functional PAI-1 levels positively correlated with tPA (r= 0.3117) and protein C (r= 0.4059), tPA negatively correlated with TAFI antigen (r= -0.4601), alpha-2 antiplasmin (r= -0.2460) and positively correlated with microparticles (r= 0.2456) , TAFI antigen positively correlated with protein C (r= 0.3612), alpha-2 antiplasmin (r= 0.3899) and negatively correlated with microparticles (r= -0.2470) whereas protein C showed a negative correlation with vWF (r= -0.2838).Conclusion: The markedly increased D-Dimer levels suggest increase clot burden in PE patients. tPA antigen is also markedly increased, whereas the uPA showed modest increase which may suggest compensatory upregulation, PAI-1 antigen levels were much higher in comparison to PAI-1 functional activity, suggesting consumption of this inhibitor. Decreased alpha-2 antiplasmin and protein C levels also suggest consumption. Increased TAFI antigen contribute to the clot resistant to fibrinolysis. Cellular consumption and endothelial dysfunction results in increased in vWF and microparticles promoting thrombogenesis. Measurement of these biomarkers may be useful in the understanding of the pathogenesis, risk stratification and clinical management of PE patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Therapeutic Modalities of Sickle Cell Disease Reprogram the Platelet Functional-Bioenergetic Profile

BACKGROUNDSickle cell disease (SCD) is a group of inherited hemoglobinopathies that continues to be highly morbid and lethal. SCD-associated platelet hyperreactivity is a well-recognized contributor to the pathophysiology of the disease via complex interactions with the immune system and endothelium. Aberrant platelet bioenergetics have been implicated as a biological mechanism for SCD-associated platelet hyperreactivity, however, little is known about the impact current medical interventions (e.g., hydroxyurea [HU] and red blood cell [RBC] exchange transfusions) have on the platelet functional-bioenergetic profile. In this study we investigate the effects of hydroxyurea and RBC exchange transfusions on reprograming the platelet functional-bioenergetic profile and provide insight into biological pathways that may be amenable to intervention. METHODSPlatelets from sex-, race-, and aged-matched adult healthy control subjects and adult patients with homozygous SCD (HbSS), actively being treated with hydroxyurea (HU group) or RBC exchange transfusions (RBC exchange transfusion group), were isolated and washed following standard protocols. Platelet activation by flow cytometry was determined at baseline and following activation with thrombin (0.075U/ml) and ADP (1.25uM). Platelet-activated fibrinogen binding site (αIIbβIII), P-selectin, and phosphatidylserine (PS) surface marker expression (as measured by mean fluorescence intensity [MFI]) was determined with PAC-1, P-selectin, and lactadherin antibodies, respectively. The bioenergetic profile of washed platelets was determined by the 24-well format Seahorse extracellular flux analyzer. Statistical analyses were performed using the one-way ANOVA. Correlations were performed by 2-tailed nonparametric Spearman correlations and linear regression analysis with 95% confidence interval (GraphPad Software v9.1.2). Data expressed as mean plus or minus standard error of the mean (SEM). Differences were considered significant at p < 0.05. RESULTSPlatelets from patients in the HU group exhibited increased surface marker expression of αIIbβIII (p = 0.004), P-selectin (p = 0.003), and PS (p = 0.003) at resting conditions when compared to the RBC exchange transfusion group and healthy controls. Additionally, an increase in PS expression was seen in the HU group upon activation with ADP (p = 0.0003). No significant differences were seen in the platelet functional profile after activation with thrombin. The platelet bioenergetic profile in the HU group demonstrated an elevated proton leak (p = 0.03) when compared to the RBC exchange transfusion group. Elevated proton leak in SCD was found to have positive correlation with P-selectin and PS expression (Figure 1). CONCLUSIONWhile therapeutic interventions have improved overall outcomes in patients with SCD, adverse events continue to be a deterrent to many patients prompting the need for safer, more tolerable, and cost-effective alternatives. We have identified that while HU has little impact on the hyperreactive and procoagulant platelet phenotype in SCD, RBC exchange transfusions appear to mitigate the phenotype and reprogram the bioenergetic profile. Amongst treatment groups, a strong correlation was found between platelet activation markers (i.e., P-selectin and PS) and proton leak, suggesting an interplay between alterations in platelet bioenergetics and SCD-associated platelet hyperreactivity. Further studies are needed to elucidate the metabolic pathways that are responsible for the aberrant platelet functional-bioenergetic profile seen in SCD. These observations are important as targeting the platelet bioenergetic profile via less invasive and toxic therapeutic modalities may be equally efficacious as current interventions. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Assessment and Prognostic Value of Immediate Changes in Post-Ablation Intratumor Density Heterogeneity of Pulmonary Tumors via Radiomics-Based Computed Tomography Features.

ObjectivesTo retrospectively observe the instantaneous changes in intratumor density heterogeneity after microwave ablation (MWA) of lung tumors and to determine their prognostic value in predicting treatment response and local tumor progression (LTP).MethodsPre- and post-MWA computed tomography (CT) images of 50 patients (37-males; 13-females; mean-age 65.9 ± 9.7y, 39 primary and 11 metastasis) were analyzed to evaluate changes in intratumor density. Global, regional, and local scale radiomics features were extracted to assess intratumor density heterogeneity. In four to six weeks, chest enhanced CT was used as the baseline evaluation of treatment response. The correlations between the parametric variation immediately after ablation and the visual score of ablation response (Rvisu) were analyzed by nonparametric Spearman correlation analysis. The 1-year LTP discrimination power was assessed using the area under the receiver operating characteristic (ROC) curves. A Cox proportional hazards regression model was used to identify the independent prognostic features.ResultsAlthough no significant volume changes were observed after ablation, the radiomics parameters changed in different directions and degrees. The mean intensity value from baseline CT image was 30.3 ± 23.2, and the post-MWA CT image was -60.9 ± 89.8. The ratio of values change was then calculated by a unified formulation. The largest increase (522.3%) was observed for cluster prominence, while the mean CT value showed the largest decline (321.4%). The pulmonary tumors had a mean diameter of 3.4 ± 0.8 cm. Complete ablation was documented in 36 patients. Significant correlations were observed between Rvisu and quantitative features. The highest correlations were observed for changes in local features after MWA, with r ranging from 0.594 to 0.782. LTP developed in 22 patients. The Cox regression model revealed Δcontrast% and response score as independent predictors (Δcontrast%: odds ratio [OR]=5.61, p=0.001; Rvisu: OR=1.73, p=0019). ROC curve analysis showed that Δcontrast% was a better predictor of 1-year LTP. with higher sensitivity (83.5% vs. 71.2%) and specificity (87.1% vs. 76.8%) than those for Rvisu.ConclusionsThe changes in intratumor density heterogeneity after MWA could be characterized by analysis of radiomics features. Real-time density changes could predict treatment response and LTP in patients with pulmonary tumors earlier, especially for tumors with larger diameters.

Urban mobility and COVID-19 in Brazil: Comparison between 2020 and 2021.

The aim of this study was to analyze and compare the indicators of urban mobility and the number of new cases of COVID-19 recorded daily between 2020 and 2021. An observational study was carried out involving new cases of COVID-19 registered daily in the state of Pernambuco, Brazil between March 12, 2020 and March 28, 2021 and six indicators of urban mobility. For analysis, the study was divided into two periods: the first was composed of 295 days and represents the year 2020 and the second was composed of 86 days and represents the year 2021. Spearman's non-parametric correlation was used. In 2021, the greatest reductions in relation to the baseline were observed in parks (-29.0) and in retail and recreation areas (-28.7). However, these reductions were smaller than those observed in the previous year, indicating a greater circulation of people in 2021 when compared with mobility in 2020. In contrast, in residential areas, there was a reduction in the percentage change in relation to the previous year (11.2 in 2019 and 7.6 in 2021). In grocery and pharmacy, there was an increase 1.8 times greater than that observed in 2020 (9.1 in 2020 and 17.0 in 2021). It is also noteworthy that the daily average of new cases almost doubled in value (753.4 in 2020 and 1409.1 in 2021). More vigorous measures must be taken to adequately control the pandemic.

Evaluation of Cardiorespiratory Fitness and Its Correlation with Team Performance, Player Position and Physical Characteristics in the Soccer Premium League of Iran

Background: This study is one of the first to specifically analyze cardiorespiratory fitness and its association with age, weight, height, body fat percentage (BFP), body mass index (BMI), team performance, and player position for a large number of soccer players in an Asian top league. Methods: 213 players (age = 25 ± 5 years, height = 181.2 ± 6.8 cm, weight = 76.1 ± 8.1 kg, BFP = 11.3 ± 3.1) affiliated with 16 soccer clubs from Iran’s Premier League (i.e., the highest level of club football in Iran), were tested for maximal aerobic power (VO2 max), first and second ventilatory thresholds (VT1 and VT2), and ventilatory efficiency at rest (VO2 rest). The nonparametric Spearman's correlation test was performed to check for correlations, and the resulting rank correlation coefficients (rs) and probability value (P) are presented. Results: In terms of mean ± standard deviation, the 213 male players participating in this study have VO2max = 55.3 ± 5.4 mL.kg-1.min-1, VT1 = 57.3 ± 4.2 (% max), VT2 = 92.6 ± 3.4 (% max) and VO2rest = 7.1 ± 1.4 mL.kg-1.min-1. No correlation between VO2max and team performance or BFP was observed. The correlations between VO2max and age (rs= -0.23, P = 10-3), height (rs = -0.34, P ≅ 0), weight (rs = -0.42, P ≅ 0) and BMI (rs = -0.30, P = 10-5) were considered statistically significant. The difference between VO2max of players in different positions was also statistically significant. Goalkeepers possessed the lowest VO2max, with a mean value of 49.8 mL.kg-1.min-1. Defenders had the lowest mean VO2max value players (equal to 54.7 mL.kg-1.min-1) amongst outfield players, and midfielders had the highest mean VO2max (= 56.9 mL.kg-1.min-1). The other indices of cardiorespiratory fitness (VT1, VT2 and VO2rest) had no statistically significant correlation with the physical characteristics of the soccer players, team performance and player position. Conclusions: The study demonstrates that VT1, VT2, and VO2rest are not distinguishing factors amongst different categories of age, weight, height, team performance, and player position, but VO2max varies with age, weight, height, and BMI. The study also shows that there is a high correlation between the physical demands of player positions during a game and the aerobic capacity of players in those positions, and this must be taken into account in soccer training.

Dysregulated zinc and sphingosine-1-phosphate signaling in pulmonary hypertension: Potential effects by targeting of bone morphogenetic protein receptor type 2 in pulmonary microvessels.

Recently identified molecular targets in pulmonary artery hypertension (PAH) include sphingosine-1-phosphate (S1P) and zinc transporter ZIP12 signaling. This study sought to determine linkages between these pathways, and with BMPR2 signaling. Lung tissues from a rat model of monocrotaline-induced PAH and therapeutic treatment with bone marrow-derived endothelial-like progenitor cells transduced to overexpress BMPR2 were studied. Multifluorescence quantitative confocal microscopy (MQCM) was applied for analysis of protein expression and localization of markers of vascular remodeling (αSMA and BMPR2), parameters of zinc homeostasis (zinc transporter SLC39A/ZIP family members 1, 10, 12 and 14; and metallothionein MT3) and S1P extracellular signaling (SPHK1, SPNS2, S1P receptor isoforms 1, 2, 3, 5) in 20-200 µm pulmonary microvessels. ZIP12 expression in whole lung tissue lysates was assessed by western blot. Spearman nonparametric correlations between MQCM readouts and hemodynamic parameters, Fulton index (FI), and right ventricular systolic pressure (RVSP) were measured. In line with PAH status, pulmonary microvessels in monocrotaline-treated animals demonstrated significant (p < .05, n = 6 per group) upregulation of αSMA (twofold) and downregulation of BMPR2 (20%). Upregulated ZIP12 (92%), MT3 (57.7%), S1PR2 (54.8%), and S1PR3 (30.3%) were also observed. Significant positive and negative correlations were demonstrated between parameters of zinc homeostasis (ZIP12, MT3), S1P signaling (S1PRs, SPNS2), and vascular remodeling (αSMA, FI, RVSP). MQCM and western blot analysis showed that monocrotaline-induced ZIP12 upregulation could be partially negated by BMPR2-targeted therapy. Our results indicate that altered zinc transport/storage and S1P signaling in the monocrotaline-induced PAH rat model are linked to each other, and could be alleviated by BMPR2-targeted therapy.

Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase.

Immunotherapy using immune checkpoint inhibitors has demonstrated durable responses and has significantly improved survival in patients with non-small cell lung cancer (NSCLC). Moreover, immunotherapy is increasingly used in combination with cytotoxic treatments such as chemotherapy and radiotherapy. Although the combined treatments are more effective, the underling mechanisms that lead to higher antitumor activity are not fully understood. Therefore, the aim of the current retrospective study was to determine the relationship between expression of immune checkpoints [programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1)] and the enzyme DNA-dependent protein kinase (DNA-PK), which is part of a key pathway involved in the repair of cytotoxic cancer therapy induced damage. Surgically excised NSCLC tissues (n=121) were histologically examined for overall extent of inflammation (score 0-3). Expression levels of PD-1 (number of PD-1 positive cells), PD-L1 [tumor proportion score (TPS); %] and DNA-PK (proportion of DNA-PK positive tumor cells; %) were determined using immunohistochemistry. Expressions of these markers were compared in different clinicopathological subgroups and later used for nonparametric Spearman correlation analysis to determine associations. In patients with NSCLC, PD-1 was significantly expressed in males (P=0.030) and in patients with no or trivial inflammation scores (P=0.030). PD-L1 expression was also significantly higher in current smokers (P=0.025). Correlation analysis was based on the individual values of patients and revealed a significant association between one of the targets of immune checkpoint inhibitors and tumor cell DNA-PK. Tumors with higher numbers of PD-1 positive cells also demonstrated higher tumor cell DNA-PK expressions (P=0.027). The results demonstrated a significant positive correlation between the PD-1/PD-L1 axis and tumor cell DNA-PK expression in patients with NSCLC. Further studies are required to clarify the significance of this correlation and its effect on the efficacy of immunotherapy and cytotoxic cancer therapy combinations.

Correlation between neck pressure pain threshold and forward head posture in patients with temporomandibular joint disorders

Objective: To investigate the association between neck muscles pressure pain thresholds (PPT) and forward head posture (FHP) in patients with temporomandibular disorders (TMD). Methods: A total of 145 TMD patients, including 23 males and 122 females with a median age of 28 years, were enrolled in the Department of Rehabilitation Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from December 2019 to April 2020. Informations of FHP and neck muscles PPT were collected for all participants. FHP was characterized by the craniocervical angle (CVA) between C7, the tragus of the ear and the horizontal line. Each of the participants completed a questionaire of the neck disability index (NDI). The patients with CVA≤51 ° were asigned into FHP group, otherwise the patients with CVA>51° were asigned into non-FHP group. PPT were measured at the midpoint of the upper trapezius and 1 cm aside from C5-C6 articular pillars. Nonparametric test and Spearman correlation analysis were conducted for the data analysis. Results: There were 70 patients in the FHP group and 75 patients in the non-FHP group. The trapezius PPT of the FHP group [2.82(0.86) kg] was significantly higher than that of the non-FHP group [2.46(0.80) kg] (P<0.01). No significant differences in PPT and NDI were observed between the two groups (P>0.05). Low correlation was found between trapezius PPT and FHP negatively (r=-0.273, P<0.01) and no correlation was found between C5-C6 PPT and FHP (r=-0.124, P>0.05). PPT in trapezius and C5-C6 was negatively correlated with NDI in moderate (r=-0.301, P<0.01) and low (r=-0.206, P<0.05) levels. Conclusions: The trapezius PPT was correlated with FHP negatively. The more FHP, the more pain tolerant of trapezius muscles. There was no correlation between neck function and FHP directly. The higher threshold was followed by better neck function.

What Is The Best Time Sampling For The Two Direct Oral Anticoagulants, Dabigatran and Rivaroxaban?

Introduction Thanks to their predictable pharmacokinetic profile, frequent monitoring of direct oral anticoagulants (DOACs) effects or levels is not recommended in the majority of patients, but it is anticipated that a non-negligible proportion of patients will achieve either insufficient or supra-therapeutic levels of the drug. Moreover, in pharmacokinetic studies with dabigatran etexilate (DE) and rivaroxaban marked interindividual variation in drug levels has been observed. The question about the most appropriate test to assess the treatment response has already been addressed and it was additionally stated that the interval between the drug intake and the blood sampling is mandatory. However, no information regarding the most appropriate delay for monitoring is currently provided. Therefore, the objective of this work is to evaluate the interindividual response at different time points in order to identify which interval between the drug intake and the blood sampling should be preferred for the assessment of the individual response. Methods Series of patients treated with rivaroxaban (AF n=25; VTE n=8) or DE (AF n=18) were included in the study. For each patient, blood was taken at 3 different intervals: - At Ctrough o 22 to 26 hours after the last intake of rivaroxaban o 11 to 13 hours after the last intake of DE - Two hours and three hours after drug administration For rivaroxaban samples, prothrombin time was performed with Triniclot PT Excel S®, RecombiPlasTin 2G® and Innovin®. Rivaroxaban plasma concentration was estimated with the Biophen Direct Factor Xa Inhibitor®. For DE samples, activated Partial Thromboplastin Time (aPTT) was perfomed with STA®-C.K.Prest and SynthasIL®. Plasma dabigatran concentration was estimated with the Hemoclot Thrombin Inhibitor®. Wilcoxon analyses were performed between the different blood sampling intervals. Test for effective pairing was computed with the Spearman non-parametric correlation coefficient with a one-tailed P value. Results Table 1 shows the minimum, the median and the maximum obtained with each tests at each time sampling. [Figure 1][1] provides the box-plot and whiskers (min to max) of the different assays performed on rivaroxaban samples at the different time sampling. [Figure 2][1] provides the box-plot and whiskers (min to max) of the different assays performed on dabigatran samples at the different time sampling. ![Figure 1][2] Figure 1 ![Figure 2][2] Figure 2 Discussion Our results confirm that there is a non-negligible interindividual variation in drug levels at same time points. When comparing intervals, whatever the test used in our study, we can see that results at Ctrough clearly differ from results obtained 2 or 3 hours after the intake of the drug ([Table 1][3]). Interestingly, for rivaroxaban, the median after 2 or 3 hours are closely the same with similar 25th – 75th percentile values whatever the test. Based on our results, we can affirm that for the majority of patients in our study, the Cmax is reached within 2 to 3 hours after the intake. For dabigatran, the plasma concentration is higher at 3h than at 2 hours ([Table 1][3]). However, the power of the study is not sufficient to show a statistically significant effect. Interestingly, this phenomenon is not encountered with the aPTT. This may be due to the well-known flattening curve effect at these higher concentrations. View this table: Table 1 Conclusion Based on our results, we can assert that it seems preferable to take the blood 3 hours after the last intake of DE to avoid missing the Cmax. For rivaroxaban, whatever the blood is taken 2 or 3 hours after the intake, results are similar. Therefore, we recommend to systematically performing blood sampling 3 hours after the intake of the drug to assess the maximal response at these treatments. Sampling at Ctrough is also required to evaluate the clearance. As a limitation, our results should be confirmed in larger cohort studies. Disclosures: No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes [3]: #T1

Noninvasive Monitoring After Azathioprine Withdrawal in Patients With Inflammatory Bowel Disease in Deep Remission

There is uncertainty regarding the optimal duration of treatment with azathioprine (AZA) in ulcerative colitis (UC) and Crohn's disease (CD). We analyzed the clinical course and predictors of relapse after AZA withdrawal in patients in sustained deep remission. A prospective study was performed on patients who stopped their treatment with AZA while being in steroid-free, extended deep remission (normal clinical, endoscopic, and histologic indexes, C-reactive protein, and fecal calprotectin [FC]). Standard biochemical tests and FC were measured at 3 and 6 months, then every 6 months. Bowel ultrasounds and ileocolonoscopy were performed every 6 and 12 months, respectively. Multivariate analysis for predictors of relapse was performed using a Cox proportional hazards model and hazard ratios were calculated. Spearman nonparametric correlation test was also used. The accuracy of significant predictors was calculated. Fifty-seven patients with inflammatory bowel disease stopped AZA after median 7 years (range, 5-19) and were followed up for median 50 months (range, 25-85). Twenty-six patients (18/31 UC, 8/26 CD; P= .003) relapsed, within a median 15 months (range, 2-37). FC was the only variable significantly correlated with later relapse of both diseases (UC: hazard ratio, 3.3; 95% confidence interval, 1.2-10; CD: hazard ratio, 4.5; 95% confidence interval, 1.4-12.5). The sensitivity, specificity, and positive and negative predictive values of FC were 50%, 100%, 100%, and 59% in UC and 50%, 94%, 80%, and 81% in CD. More than half patients with UC and one-third of patients with CD relapse after AZA withdrawal despite previous deep remission. FC positivity is associated with high risk of relapse, allowing early correction of the therapeutic strategy.

The impact of social media usage intensity on self-esteem: survey on emerging adulthood of instagram user

Social media can be used to increase individual popularity, one of which is Instagram. Instagram can be used to increase individual self-popularity or increase self-esteem. The purpose of this study, namely to determine the relationship between the intensity of using Instagram and self-esteem in emerging adulthood. This research is a quantitative-survey research, with 259 students at “X” University as many as male and female participants aged 18-25 years. The measuring instrument used is the Rosenberg Self Esteem Scale and the Instagram Intensity Scale. The analysis used was the Spearman non-parametric correlation test. The results show that there is a significant correlation between the intensity of using Instagram and self-esteem on emerging adulthood, there is also a correlation between emotional attachment to Instagram and self-esteem on emerging adulthood. Thus the higher the intensity of using Instagram or the higher the emotional attachment to Instagram, the higher the self-esteem of emerging adulthood. The higher the intensity of a person using Instagram, the higher the desire or motivation of the individual to become more prominent.

MO434CHRONIC KIDNEY DISEASE AND ITS RELATIONSHIP WITH THE STATE OF THE INTESTINAL MICROBIOTA AND INDICATORS OF SYSTEMIC INFLAMMATION

Abstract Background and Aims In view of the fact that the human microbiota varies depending on many factors, including comorbid pathology, it seems reasonable to investigate the gut microbiota in patients with chronic kidney disease and its likely relationship with markers of systemic inflammation. To reveal the relationship between some biomarkers of inflammation with changes in the composition of the intestinal microbiota in patients with chronic kidney disease. Method The study included 85 patients with CKD C 2-4. The average age of the patients was 52 ± 4 years (48 men and 37 women). The control group consisted of 30 healthy volunteers aged 50 ± 3 years, 15 men and 15 women, comparable to the main group in terms of sex and age. Blood samples were taken using standard methods. GFR was assessed using the CKD-EPI formula (2011). In addition, biomarkers such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) were evaluated. Bacteriological examination of feces was carried out in the bacteriological laboratory.Markers of systemic inflammation were assessed based on an increase in the level of leukocytes (&amp;gt; 11 × 109 / L), C - reactive protein (&amp;gt; 5.0 mg / L) by immunoturbodimetric method, fibrinogen (&amp;gt; 4.0 g / L), as well as interleukin 6 by enzyme immunoassay. Differences between groups were considered statistically significant at p`0.05; correlation analysis was performed using Spearman's nonparametric rank correlation method. Results Analysis of fecal matter showed a deficiency of Bifidobacterium bacteria (&amp;lt;108 CFU) in the examined patients. In addition, the examined patients showed an increase in the number of Echerichia (&amp;gt; 108 CFU). According to the results of the study, in the group of CKD patients, the level of inflammatory markers was higher (CRP-55%, IL-6-60%, leukocytes 62%) than in the control group (CRP-45%, IL-6-40%, leukocytes 38% ). In men, the IL-6 index was higher than in women. The results of the study demonstrated that in patients with CKD, an imbalance of the intestinal microbiota is combined with an increased level of CRP, IL-6, and leukocytes. Conclusion The study of markers responsible for pro-inflammatory effects in the body showed that indicators such as IL-6, CRP, fibrinogen showed a significant correlation with the composition of the microbiota in patients with CKD.

PERANAN PENYULUH PERTANIAN DALAM MENINGKATKAN KINERJA KELEMBAGAAN KELOMPOK TANI PADI SAWAH PENERIMA BANTUAN RICE MILLING UNIT (RMU) DI KOTA BANDAR LAMPUNG

This study aims to analyze: 1) the level of the role of agricultural agents; 2) the level of institutional performance of farmer groups; 3) the relationship between the level of the role of agricultural extension agents and the institutional performance of rice farmer groups in the use of RMU in Bandar Lampung City. This research was conducted in the city of Bandar Lampung with 56 farmer respondents. Methods of data collection using a survey method, with descriptive analysis and using a non-parametric rank spearman correlation statistical test to test the hypothesis. The results showed that the role of agricultural extension agents in improving the institutionalization of rice farmer groups receiving RMU assistance was in the medium category, the institutional level of farmer groups in the use of RMU was in the medium category, and the role of agricultural instructors had a significant relationship with the institutional performance of farmer groups.Key words: role, extension agent, institutional, farmers.

Correlations of typical pain patterns with SPECT/CT findings in unhappy patients after total knee arthroplasty

PurposeThe diagnostic process in patients after painful total knee arthroplasty (TKA) is challenging. The more clinical and radiological information about a patient with pain after TKA is included in the assessment, the more reliable and sustainable the advice regarding TKA revision can be. The primary aim was to investigate the position of TKA components and evaluate bone tracer uptake (BTU) using pre-revision SPECT/CT and correlate these findings with previously published pain patterns in painful patients after TKA.MethodsA prospectively collected cohort of 83 painful primary TKA patients was retrospectively evaluated. All patients followed a standardized diagnostic algorithm including 99m-Tc-HDP-SPECT/CT, which led to a diagnosis indicating revision surgery. Pain character, location, dynamics and radiation were systematically assessed as well as TKA component position in 3D-CT. BTU was anatomically localized and quantified using a validated localization scheme. Component positioning and BTU were correlated with pain characteristics using non-parametric Spearman correlations (p < 0.05).ResultsBased on Spearman’s rho, significant correlations were found between pain and patients characteristics and SPECT/CT findings resulting in nine specific patterns. The most outstanding ones include: Pattern 1: More flexion in the femoral component correlated with tender/splitting pain and patella-related pathologies. Pattern 3: More varus in the femoral component correlated with dull/heavy and tingling/stinging pain during descending stairs, unloading and long sitting in patients with high BMI and unresurfaced patella. Pattern 6: More posterior slope in the tibial component correlated with constant pain.ConclusionThe results of this study help to place component positioning in the overall context of the "painful knee arthroplasty" including specific pain patterns. The findings further differentiate the clinical picture of a painful TKA. Knowing these patterns enables a prediction of the cause of the pain to be made as early as possible in the diagnostic process before the state of pain becomes chronic.Level of evidenceLevel III

The relationship between brain abnormalities and autistic psychopathology in pervasive developmental disorders.

The aim of the present research has been to determine whether there is a relationship between brain abnormalities found on magnetic resonance imaging (MRI) and autistic psychopathology. A retrospective analysis covering a period between 1998 and 2015 included 489 children with autism (404 boys, 85 girls; average age 8.0 ± 4.2 years) who underwent an MRI of the brain. For clinical diagnosis of autism, the International Classification of Diseases, 10th revision (ICD-10), was used. Autistic psychopathology was evaluated by means of the Autism Diagnostic Interview - Revised. The Spearman nonparametric correlation analysis and chi-square test were used to examine the possible relationships between variables. The group of autistic children did not manifest a statistically significant correlation between the parameters examined on MRI and autistic psychopathology. A correlation between other cysts and repetitive behavior was significant only at trend level (P = 0.054). Gliosis of the brain was significantly more frequent in autistic children with mental retardation than in children without mental retardation (14.1% vs. 7.4%; P = 0.028). Nonmyelinated areas in the brain were significantly more frequent in autistic children with autistic regression than in children without autistic regression (29.9% vs. 15.7%; P = 0.008). Mental retardation was significantly more frequent in autistic children with autistic regression than in children without regression (73.2% vs. 52.5%; P = 0.002). Our research study did not reveal a statistically significant correlation of brain abnormalities on MRI with autistic psychopathology.