nils-herrmann/clean_scirepeval huggingface dataset:
Contribution of renal and non-renal clearance on increased total clearance of adalimumab in glomerular disease.

The contribution of renal and non-renal clearance toward targeted concentrations and/or effects of therapeutic proteins in nephrotic patients are unknown. This study dissected the contribution of clearance pathways to adalimumab elimination in patients with focal segmental glomerulosclerosis (FSGS). Urine was collected from seven patients treated with adalimumab. Renal clearance (ClR ) was measured and non-renal clearance (ClNR ) was calculated as the difference between total clearance and ClR . Differences in cumulative amount in urine, ClR, and ClNR between study weeks 1 and 16 and relationships between proteinuria (protein:creatinine ratio (Up/c)), and ClR and ClNR were evaluated. Up to 13% of the adalimumab dose was lost in urine. ClNR contributed more than ClR to enhanced total clearance. There was a nonlinear relationship between Up/c and ClR (R(2) 0.7059); an increase in ClR beginning at Up/c of 12 mg/mg [slope 1.755, (C.I. -7.825 to 11.34)]. There was a linear relationship between Up/c and ClNR (R(2) 0.5039); for every one unit increase in Up/c, ClNR would increase by 3.5 mL/hr (P = 0.01). Both ClR and ClNR contribute to enhanced total clearance of adalimumab in glomerular disease secondary to FSGS. Additional research is needed to identify mechanisms for the increased ClNR pathways.
Toward A Human-Centered Hyperlipidemia Management System: The Interaction between Internal and External Information on Relational Data Search

In a distributed information search task, data representation and cognitive distribution jointly affect user search performance in terms of response time and accuracy. Guided by UFuRT (User, Function, Representation, Task), a human-centered framework, we proposed a search model and task taxonomy. The model defines its application in the context of healthcare setting. The taxonomy clarifies the legitimate operations for each type of search task of relational data. We then developed experimental prototypes of hyperlipidemia data displays. Based on the displays, we tested the search tasks performance through two experiments. The experiments are of a within-subject design with a random sample of 24 participants. The results support our hypotheses and validate the prediction of the model and task taxonomy. In this study, representation dimensions, data scales, and search task types are the main factors in determining search efficiency and effectiveness. Specifically, the more external representations provided on the interface the better search task performance of users. The results also suggest the ideal search performance occurs when the question type and its corresponding data scale representation match. The implications of the study lie in contributing to the effective design of search interface for relational data, especially laboratory results, which could be more effectively designed in electronic medical records.
Immune activation mediated change in alpha-1-acid glycoprotein: impact on total and free lopinavir plasma exposure.

Immune mediated changes in circulating α-1-acid glycoprotein (AAG), a type 1 acute phase protein, which binds protease inhibitors (PI), may alter protein binding and contribute to PI's pharmacokinetic (PK) variability.



In a prospective, 2-phase intensive PK study on antiretroviral naive human immunodeficiency virus (HIV)-infected subjects treated with a lopinavir-/ritonavir-based regimen, steady state PK sampling and AAG assays were performed at weeks 2 and 16 of treatment.



Median entry age was 43 years (n = 16). Median plasma log(10) HIV-1 RNA, CD4 T-cell counts, and AAG were 5.16 copies/mL, 28 cells/µL, and 143 mg/dL, respectively.The total lopinavir area under the concentration time curve (AUC(12_total)) and maximum concentration (C(max_total)) changed linearly with AAG at mean rates of 16±7 mg*hr/L (slope ± SE); P = .04, and 1.6 ± 0.6 mg/L, P = .02, per 100 mg/dL increase in AAG levels, respectively (n = 15).A 29% drop in AAG levels between week 2 and week 16 was associated with 14% (geometric mean ratio [GMR] = 0.86; 90% confidence interval [CI] = 0.74-0.98) and 13% (GMR = 0.87; 90% CI = 0.79-0.95) reduction in AUC(12_total) and C(max_total), respectively. Neither free lopinavir PK parameters nor antiviral activity (HIV-1 RNA average AUC minus baseline) was affected by change in plasma AAG.



Changes in plasma AAG levels alter total lopinavir concentrations, but not the free lopinavir exposure or antiviral activity. This observation may have implications in therapeutic drug monitoring.
The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes.

Glucagon-like peptide (GLP)-1 is a gut hormone that exerts incretin effects and suppresses food intake in humans, but its therapeutic use is limited due to its short half-life. This was a randomized, double-blind, parallel-group, placebo-controlled trial investigating the effect of the long-acting GLP-1 derivative liraglutide (NN2211) on glycemic control, body weight, body composition, and 24-h energy expenditure in obese subjects with type 2 diabetes.



Thirty-three patients (mean +/- SD) aged 60.0 +/- 9.5 years, with HbA(1c) 7.5 +/- 1.2% and BMI 36.6 +/- 4.1 kg/m(2), were randomized to treatment with a single daily subcutaneous dose of 0.6 mg liraglutide (n = 21) or placebo (n = 12) for 8 weeks. In addition to weight and glycemic parameters, body composition was assessed by dual-energy X-ray absorptiometry (DEXA) scanning and 24-h energy expenditure in a respiratory chamber.



After 8 weeks, liraglutide reduced fasting serum glucose (liraglutide, -1.90 mmol/l, and placebo, 0.27 mmol/l; P = 0.002) and HbA(1c) (liraglutide, -0.33%, and placebo, 0.47%; P = 0.028) compared with placebo. No change in body weight was detected (liraglutide, -0.7 kg, and placebo, -0.9 kg; P = 0.756). There was a nonsignificant trend toward a decrease in total fat mass (liraglutide, -0.98%, and placebo, -0.12%; P = 0.088) and toward an increase in lean body mass (liraglutide, 1.02%, and placebo, 0.23%; P = 0.118) in the liraglutide group compared with the placebo group. Twenty-four-hour energy expenditure was unaffected by the treatment (liraglutide, -12.6 kJ/h, and placebo, -13.7 kJ/h; P = 0.799).



Eight weeks of 0.6-mg liraglutide treatment significantly improved glycemic control without increasing weight in subjects with type 2 diabetes compared with those on placebo. No influence on 24-h energy expenditure was detected.
Modifying Threat-related Interpretive Bias in Adolescents

Socially anxious feelings sharply increase during adolescence and such feelings have been associated with interpretive biases. Studies in adults have shown that interpretive biases can be modified using Cognitive Bias Modification procedures (CBM-I) and subsequent effects on anxiety have been observed. The current study was designed to examine whether the CBM-I procedure has similar effects in adolescents. Unselected adolescents were randomly allocated to either a positive interpretation training (n = 88) or a placebo-control condition (n = 82). Results revealed that the training was successful in modifying interpretations and effects generalized to a new task. The interpretive bias effects were most pronounced in individuals with a threat-related interpretive bias at pre-test. No effects on state anxiety were observed. The current findings are promising with regard to applying bias modification procedures to adolescents, while further research is warranted regarding emotional effects.
Internal and external validation of a model to predict adverse outcomes in patients with left-sided infective endocarditis.

Early identification of prognostic factors is essential to improve the grim prognosis associated with left-sided infective endocarditis. This group identified three independent risk factors obtained within 72 h of admission, (Staphylococcus aureus, heart failure and periannular complications) for inhospital mortality or urgent surgery in a series of 317 patients diagnosed at five tertiary centres (derivation sample). A stratification score was constructed for the test cohort by a simple arithmetic sum of the number of variables present. The goal was to validate this model internally and externally in a prospective manner with two different cohorts of patients.



The appropriateness of the model was tested prospectively on predicting events in two cohorts of patients with left-sided endocarditis: internally with the 263 consecutive patients diagnosed at the same centres where the model was derived (internal validation sample), and externally with 264 patients admitted at another hospital (external validation sample).



The discriminatory power of the model, expressed as the area under the receiver operating characteristic curve was similar between derivation and both validation samples (internal 0.67 vs 0.68, p=0.79; external 0.67 vs p=0.74, p=0.09). There was a progressive, significant pattern of increasing event rates as the risk stratification score increased in both validation cohorts (p<0.001 by χ² for trend).



The early risk stratification model derived, based on variables obtained within 72 h of admission, is applicable to different populations with left-sided endocarditis. A simple bedside assessment tool is provided to clinicians that identifies patients at high risk of having an adverse event.
Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection.



A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI.



Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians.
Association between PTPN22/CTLA-4 Gene Polymorphism and Allergic Rhinitis with Asthma in Children.

Allergic rhinitis (AR) is an IgE-mediated upper airway disease, and its impact on asthma has been widely recognized. Protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms have been reported to be associated with several immune-related diseases. Here we investigated the reffect of these two genes' polymorphisms on the risk of AR and asthma in Chinese Han children. A total of 106 AR patients, 112 AR with asthma patients, and 109 healthy children were enrolled in the study. The SNPs of PTPN22 (rs2488457, rs1310182, rs3789604) and CTLA-4 (rs3087243, rs11571302, rs11571315, rs231725, rs335219727, and rs4553808) were genotyped using a PCR-restriction fragment length polymorphism assay. For PTPN22, an increased prevalence of the CC genotype and C allele in rs1310182 were identified in AR group. For CTLA-4, AA genotype and A allele in rs3087243 and rs231725 were increased in AR with asthma group while in AR group, AA genotype and A allele in rs231725 were obviously decreased. This study reveals a significant association between SNPs in PTPN22, CTLA-4 gene and AR with asthma in Chinese Han children, which might be susceptibility factors for AR and asthma.
Novel description of the 24-hour circadian rhythms of brachial versus central aortic blood pressure and the impact of blood pressure treatment in a randomized controlled clinical trial: The Ambulatory Central Aortic Pressure (AmCAP) Study.

Elevated brachial blood pressure (BP) is associated with increased cardiovascular risk and predicts morbidity and mortality in humans. Recently, 24-hour ambulatory BP monitoring and assessment of central aortic BP have been introduced to improve BP phenotyping. The Ambulatory Central Aortic Pressure (AmCAP) study combines these approaches and describes, for the first time, the diurnal patterns of simultaneously measured 24-hour ambulatory brachial and central pressures in a prespecified substudy embedded within a clinical trial of BP lowering in patients with hypertension. Twenty-four-hour ambulatory brachial and central pressure measurements were acquired using a tonometer mounted into the articulating strap of a wristwatch-like device (BPro) in 171 participants with hypertension recruited into the ASSERTIVE (AliSkiren Study of profound antihypERtensive efficacy in hyperTensIVE patients) trial. Participants were randomly assigned to BP lowering with either aliskiren 300 mg QD or telmisartan 80 mg QD for 12 weeks. Ambulatory brachial and central BP was measured in all participants both at baseline and at study end. Brachial and central BP both demonstrated typical diurnal patterns with lower pressures at night. However, night time was associated with smaller reductions in central relative to brachial pressure and decreased pulse pressure amplification (P<0.0001 for both). These effects were not modulated after BP lowering and were maintained after adjustment for day and night-time BP and heart rate (P=0.02). This study demonstrates that brachial and central pressure show different diurnal patterns, which are not modulated by BP-lowering therapy, with relatively higher night-time central pressures. These novel data indicate that night-time central BP may provide prognostic importance and warrants further investigation.
Comparative Trial of Pinacidil versus Prazosin in Mild to Moderate Arterial Hypertension

This paper' summarises the results of a randomised, non-blind study, in which pinacidil was compared with prazosin, with respect to antihypertensive efficacy and side effects in patients with mild to moderate arterial hypertension. The major haemodynamic change in patients with arterial hypertension seems to be an increase in total peripheral resistance (Lund-Johansen 1967). Therefore, drugs that reduce total peripheral resistance are a logical therapeutic approach. Since hypertension is primarily diagnosed and treated in general practice, the study was carried out by a group of general practitioners in Denmark.
Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults.

Adult patients suffering from acute asthma presenting to the Emergency Department with an FEV1 of less than 40% of predicted were randomized into four treatment groups. They were treated with nebulized albuterol at a high (7.5 mg) or standard (2.5 mg) dose given either continuously through 1 h, or intermittently every hour, for 2 h. When the FEV1 improvements for the different groups at 2 h were compared, the groups treated with continuous nebulization had the greatest improvement. The improvements (1.07 L for the high-dose group, and 1.02 L for the standard-dose group) were significantly greater than the improvement seen with standard-dose intermittent treatment (0.72 L; p < 0.05). The improvement in FEV1 of the high-dose, hourly treated group was intermediate in magnitude between these (0.09 L). There was no difference in the improvement seen between the two groups treated with continuous nebulization. The potassium fall, present in all groups, was more pronounced in the groups treated with high doses of albuterol. Only one person (high dose, continuous treatment group) developed hypokalemia of less than 3.0 mmol/L. The high-dose hourly treated group had the highest incidence of side effects, and the standard-dose continuously treated group had the lowest. The standard-dose continuous-treatment regimen had the greatest improvement in FEV1 with the least number of side effects.
Prospective longitudinal evaluation of quality of life in patients with permanent colostomy after curative resection for rectal cancer: a preliminary study.

The aim of this study was to evaluate health-related quality of life in patients with a colostomy immediately before and during the first year after surgery.



Patients (aged ≥20 years) who were diagnosed with rectal cancer and scheduled to undergo curative surgery with a permanent colostomy were recruited for this study. Data were collected at 2 university hospitals in Tokyo.



Participants were asked to complete a self-administered questionnaire regarding health-related quality of life before surgery and a mailed or hand delivered questionnaire to evaluate quality of life at 2, 6, and 12 months after surgery using the Short Form-36 version 2. For patients who responded at all 4 time points, the scores at each time point were compared using paired t tests to examine longitudinal changes in quality of life after surgery.



Mean quality-of-life scores in most domains before surgery and during the first year after surgery were lower than the normal control in the norm-based scoring method. Scores at 2 months after surgery were lower than those before surgery. At 12 months after surgery, however, quality-of-life scores improved almost to the level observed before surgery, with the exception of the score in the social functioning domain. Statistical differences in scores between the time points of the survey were observed in the role-physical, bodily pain, and mental health domains.



These results suggest that patients with permanent colostomy after curative resection for rectal cancer need additional medical support and care before surgery and during the first year after surgery.
Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors

B and T cells play a key role in rheumatoid arthritis (RA) pathophysiology. RasGRP1 and RasGRP3 are involved in T and B cell receptors signaling, and belong to gene combination able to predict infliximab responsiveness, leading to the question of RasGRP1 and RasGRP3 involvement in RA.



RasGRP1 and RasGRP3 expression levels were measured by qRT-PCR and/or western-blot in peripheral blood mononuclear cells (PBMCs), in T and B cells from untreated RA patients and in RA patients treated by TNFα inhibitors. T and B cells from healthy controls (HC) were cultured with TNFα, and TNFα receptors neutralizing antibodies to highlight the TNFα effects on RasGRP1 and RasGRP3 pathways. MAPK pathways and apoptosis were respectively analyzed using the Proteome Profiler arrays and flow cytometry.



In PBMCs from RA patients, gene expression levels of RasGRP1 were invariant while RasGRP3 was downregulated under TNFα inhibitors and upregulated under TNFα. In T cells from RA patients, RasGRP1 was decreased and its gene expression level was correlated with disease activity. In T cells from HC, TNFα stimulation increased RasGRP1 gene expression level while it reduced RasGRP1 protein expression level. Bryostatin-1 experiments have confirmed that the TNFα effect observed on T cells proliferation was due to the decrease of RasGRP1 expression. Besides, RasGRP3 expression level increased in PBMCs from RA patients under TNFα and in B cells from HC leading us to conclude that RasGRP3 in B cells was modulated by TNFα.



This study demonstrates RasGRP1 dysregulation in RA patients while RasGRP3 is characterized as a biomarker linked to TNFα inhibitors. After binding to TNFR1, TNFα reduced RasGRP1 protein expression resulting in inhibition of T cell activation.
The effects of endoscopic variceal ligation and propranolol on portal hypertensive gastropathy: a prospective, controlled trial.

Endoscopic treatment of esophageal varices may accentuate portal hypertensive gastropathy. The impact of the combination of band ligation and propranolol on this condition remains unknown.



Patients with history of variceal bleeding were randomized to receive band ligation alone (control group, 40 patients) or a combination of band ligation and propranolol (propranolol group, 37 patients). Serial endoscopic evaluation of gastropathy was performed. Gastropathy was classified into 3 grades and scored as 0, 1, or 2.



Before endoscopic treatment, 17% of the control group and 22% of the propranolol group had gastropathy (p = 0.78). The occurrence of gastropathy after endoscopic treatment was significantly higher in the control group than in the propranolol group (p = 0.002). Serial endoscopic follow-up revealed that the mean gastropathy score was significantly higher in the control group than in the propranolol group (p < 0.05). In patients with gastropathy the gastropathy score reached a peak at 6 months after endoscopic treatment in both the control and propranolol groups (85% vs. 48%, respectively). After variceal obliteration, accentuation of gastropathy was significant in the control group (p < 0.01) but not in the propranolol group. Gastropathy was less likely to develop in patients who developed gastric varices. Esophageal variceal recurrence was not related to the development of gastropathy after variceal obliteration with banding. Only one patient in the control group bled from gastropathy.



Band ligation of esophageal varices may accentuate gastropathy, which in this study was partly relieved by propranolol.