nils-herrmann/clean_scirepeval huggingface dataset:
Rifaximin for preventing acute graft-versus-host disease: impact on plasma markers of inflammation and T-cell activation.

In murine allogeneic hematopoietic cell transplantation models, inhibiting bacterial translocation stemming from conditioning-induced damage to the gut mucosa abrogates inflammatory stimulation of donor T cells, preventing acute graft-versus-host disease (AGVHD). We conducted a phase I trial to begin testing the hypothesis that rifaximin, a broadly acting oral antibiotic, would reduce systemic inflammation and T-cell activation. We administered rifaximin to 20 adolescents and younger adults (day -10 through day +30) receiving intensive conditioning. We measured the plasma level of interleukin-6, as a marker of conditioning-induced inflammation, and the levels of soluble tumor necrosis factor receptor-1 and soluble interleukin-2 receptor, as surrogate markers of AGVHD. We formed a historical control group (n=24), from a previous study of biomarkers in AGVHD. The increase in the treatment group's mean interleukin-6 level from baseline to day 0 was 73% less than that in the control group (P=0.006). The increase from baseline to day 15 in the treatment group's mean soluble tumor necrosis factor-1 and soluble interleukin-2 receptor levels was similar to the control group. Incidences of grade 2 to 4 AGVHD also did not differ. This suggests that rifaximin may abrogate bacterial translocation and resultant inflammation, but in alternative donor transplants this does not prevent downstream activation of donor T cells.
The evaluation of psychiatric drug therapy on oral lichen planus patients with psychiatric disorders.

Current treatments of oral lichen planus are palliative, not curative. Because psychiatric disorders significantly influence the development and severity of oral lichen planus, the use of psychiatric drug therapy may be an adjunct in treatment. The purpose of this study was to determine the efficacy of drug therapy of psychiatric disorders in oral lichen planus.



Our controlled clinical study consisted of forty-six patients with oral lichen planus and psychiatric disorders who were randomly divided into two groups. Both groups were given topical corticosteroids and the study group received additional psychiatric drug therapy. Patients were monitored for a period of 6 months. Response to treatment was evaluated in each group and was compared with the other group using Mann-Whitney tests. We evaluated the correlation between psychiatric disorders and the recovery of oral lesions using Spearman's correlation coefficient analysis.



Decrease in the size of the lesions was significantly greater in the study group after six months, but this difference was not significant in relationship to the pain experienced and the kind of lesion. Spearman's correlation coefficient analysis demonstrated that, in the sixth month, there was a significant and direct relationship between recovery from the psychiatric disorders and response to treatment of OLP lesions, particularly as it pertained to the kind of lesion.



The present study indicates that the combination of psychiatric drug therapy and routine treatment methods were effective in reducing the size of the lesions, but did not have any significant effect on the symptoms.
Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics.

Eosinophils play an important role in the pathogenesis of asthma. Several pro-inflammatory responses of eosinophils are primed in vivo in this disease. The aim of the present study was to investigate whether regular antiasthma treatment could modulate priming-sensitive cytotoxic mechanisms of human eosinophils. In a randomized, two-centre, double-blind parallel group study, the effect of 8 weeks of treatment with salmeterol xinafoate 50 microg b.i.d., beclomethasone dipropionate 400 microg b.i.d. or both on pulmonary function and the activation of priming-sensitive cytotoxic mechanisms of eosinophils, i.e. degranulation of eosinophil cationic protein (ECP) in serum, and activation of isolated eosinophils in the context of induction of the respiratory burst and release of platelet-activating factor (PAF) were tested. These effects were evaluated in 40 allergic asthmatics before and 24 h after allergen inhalation challenge. Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and beclomethasone significantly inhibited the allergen-induced increase in serum ECP, and (primed/unprimed) PAF-release, suggesting inhibition of eosinophil priming after allergen challenge. In contrast to the combination therapy, monotherapy with beclomethasone had no influence on allergen-induced PAF-release, suggesting an additional anti-inflammatory effect of salmeterol during combination therapy. Monotherapy with beclomethasone inhibited the prechallenge serum-treated zymosan (STZ) (0.1 mg mL(-1))-induced respiratory burst and the allergen-induced increase in serum ECP levels, reflecting pre- and postchallenge anti-inflammatory effects. During monotherapy with salmeterol, an allergen-induced increase in serum ECP concentration and STZ (0.1 mg x mL(-1))-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytotoxic mechanisms. In conclusion, this study shows that standard asthma therapy leads to inhibition of eosinophil priming of cytotoxic mechanisms in vivo.
A comparison of nasal trauma in preterm infants extubated to either heated humidified high-flow nasal cannulae or nasal continuous positive airway pressure

The objectives of this study were (1) to devise a nasal trauma score for preterm infants receiving non-invasive respiratory support, (2) to compare the incidence of nasal trauma in preterm infants <32 weeks gestation randomised to either nasal continuous positive airway pressure (NCPAP) or heated humidified high-Flow nasal cannulae (HHHFNC), in the first 7 days post-extubation and (3) to assess the effect of two different nasal dressings in those assigned to NCPAP. We randomly assigned preterm ventilated infants to receive Vapotherm® HHHFNC or NCPAP post-extubation. Infants receiving HHHFNC were treated with Sticky Whiskers® and infants receiving NCPAP received either Sticky Whiskers® or Cannualaide® nasal dressings. Bedside nursing staff scored six sites on each infant’s nose for erythema, bleeding or ulceration. Scores were recorded three times daily for the first 7 days post-extubation. The sum of these 21 scores was used as the summary measure of nasal trauma. The mean nasal trauma score for infants assigned HHHFNC was 2.8 (SD 5.7) compared to 11.7 for NCPAP (SD 10.4), p < 0.001. There was no difference in mean trauma score between infants on NCPAP assigned Sticky Whiskers® 14.4 (SD 12.5) or Cannualaide® 9.5 (SD 7.3), p = 0.06.  HHHFNC resulted in significantly less nasal trauma in the first 7 days post-extubation than NCPAP and was most significant in infants <28 weeks of gestation. The use of protective dressings was not associated with decreased nasal trauma for infants on NCPAP.
Changes in environmental tobacco smoke exposure and asthma morbidity among urban school children.

Environmental tobacco smoke (ETS) exposure is associated with poor asthma outcomes in children. However, little is known about natural changes in ETS exposure over time in children with asthma and how these changes may affect health-care utilization. This article documents the relationship between changes in ETS exposure and childhood asthma morbidity among children enrolled in a clinical trial of supervised asthma therapy.



Data for this analysis come from a large randomized clinical trial of supervised asthma therapy in which 290 children with persistent asthma were randomized to receive either usual care or supervised asthma therapy. No smoking cessation counseling or ETS exposure education was provided to caregivers; however, children were given 20 min of asthma education, which incorporated discussion of the avoidance of asthma triggers, including ETS. Asthma morbidity and ETS exposure data were collected from caregivers via telephone interviews at baseline and at the 1-year follow-up.



At baseline, 28% of caregivers reported ETS exposure in the home and 19% reported exposure outside of the primary household only. Among children whose ETS exposure decreased from baseline, fewer hospitalizations (p = 0.034) and emergency department (ED) visits (p < or = 0.001) were reported in the 12 months prior to the second interview compared to the 12 months prior to the first interview. Additionally, these children were 48% less likely (p = 0.042) to experience an episode of poor asthma control (EPAC).



This is the first study to demonstrate an association between ETS exposure reduction and fewer EPACs, respiratory-related ED visits, and hospitalizations. These findings emphasize the importance of ETS exposure reduction as a mechanism to improve asthma control and morbidity. Potential policy implications include supporting ETS reductions and smoking cessation interventions for parents and caregivers of children with asthma. Research to identify the most cost-effective strategy is warranted.
Blood pressure control in ultra-early basal ganglia intracerebral hemorrhage.

We performed this study to investigate the effect of blood pressure control in ultra-early basal ganglia intracerebral hemorrhage.



120 patients with ultra-early basal ganglia intracerebral hemorrhage were randomly divided into experimental group (strengthened antihypertensive) and control (normal antihypertensive). Each group consists of 60 patients, whose contractive pressure were controlled by intravenous antihypertensive drugs among 130-140 mmHg and 160-180 mmHg respectively for 24 h, after 1 h of beginning treatment. They were all evaluated by NIH Stroke Scale (NIHSS) before and after the treatment. Cranial CT, hematoma volume, hematoma enlargement, edema volume, serum matrix metalloproteinase-9 level were performed and compared between groups.



After 24 h, hematoma volume and hematoma enlargement in the experimental group was significantly lower than control (p < 0.05). After 14 days, NIHSS score in the experimental group was significantly lower than control (p < 0.05). Cerebral edema amount and serum MMP-9 level in the experimental group were significantly lower than control after 5 days and 14 days.



Ultra-early basal ganglia intracerebral hemorrhage can remarkably reduce hematoma enlargement, cerebral edema, serum MMP-9 level, and improve the neurological function.
Isothermic vs thermoneutral hemodiafiltration evaluation by indirect calorimetry

HD and HDF as hemodialytic therapies normally alter patient's haemodynamic stability, due to the inflammatory response to extracorporeal blood circuit, producing increment of the core temperature (+1.0 °C). However, such increase in temperature could be controlled by lowering dialysate's temperature using two main modalities techniques (isothermic and thermoneural) with different patient's thermal balance consequences, not yet well studied. In this work, energy expenditure (EE) was measured by indirect calorimetry in a group of 12 patients waiting kidney transplant. In each patient, EE was assessed (as a power generation) during isothermic and thermoneutral modalities as a manner of cross and prospective study (a) at before therapy, (b) during therapy and (c) at the end of the HDF therapy. Wheraeas, power extraction was measured by a BTM (Blood Temperature Monitor from Fresenius Inc) in order to determine power balance in a thermodynamic model of the extracorporeal circuit. The results showed significant differences in the power balance when EE at during therapy was subtracted from the EE at before therapy. Then, EE increments were 32 Kcal/4-hours during isothermic and 3.6 Kcal/4-hours during thermoneutral HDF sessions (p < 0.05). While, BTM totals power extraction was 91 and 16.1 Kcal/4-hours (p<0.05), respectively. Additionally, it was estimated a 12 % of EE/day increment during HDF-isothermic at during therapy stage compared with none significative EE increment during thermoneutral modality. The statistical evidence confirmed the expected hypothesis that both modalities affect in different manner the patient's EE. Also, we conclude there is no satisfactory data interpretation when the thermodynamic model was applied expecting null balance between EE increment and BTM power extraction. Therefore, these findings force to think there is need of different BTM design and measurement setting with ability to follow dynamic patient's EE changes with the purpose to achieve a better power balance.
Investigation of possible endogenous hypoxia markers in colorectal cancer.

We evaluated the potential of some recently proposed hypoxia markers, being monocarboxylic acid transporter 1 (MCT1), MCT4 and prolyl hydroxylase 2 (PHD2); and a more established hypoxia marker, glucose transporter-1 (GLUT-1), by testing the association with the exogenous marker pimonidazole.



Paraffin embedded tumour sections of 20 colorectal cancer patients were stained for blood vessels together with either pimonidazole or carbonic anhydrase-IX (CA-IX) and single stained for MCT1, MCT4, GLUT-1, and PHD2. Expression of all markers was compared with expression of pimonidazole and micro-vessel density (MVD) and with disease-free survival (DFS) and overall survival (OS).



No correlation was found between the different intrinsic hypoxia markers tested and pimonidazole. A trend for high MCT1 expression in biopsies with low CA-IX expression was found (R = -0.45, p = 0.06) and also the expression of MCT1 was higher in tumours with a high MVD (R = 0.49, p = 0.04). The more advanced tumours showed a higher expression of GLUT-1 (p = 0.03). A low CA-IX expression in the tumour correlated with better DFS (p = 0.03) and related to better OS (p = 0.07).



Although none of the tested intrinsic hypoxia markers correlated with pimonidazole staining, we confirmed the important role of both GLUT-1 and CA-IX for a more advanced pTNM (pathological tumour-node-metastasis) stage and DFS respectively.
Rapid and highly specific screening for NPM1 mutations in acute myeloid leukemia

NPM1 mutations, the most frequent molecular alterations in acute myeloid leukemia (AML), have become important for risk stratification and treatment decisions for patients with normal karyotype AML. Rapid screening for NPM1 mutations should be available shortly after diagnosis. Several methods for detecting NPM1 mutations have been described, most of which are technically challenging and require additional laboratory equipment. We developed and validated an assay that allows specific, rapid, and simple screening for NPM1 mutations. FAST PCR spanning exons 8 to 12 of the NPM1 gene was performed on 284 diagnostic AML samples. PCR products were visualized on a 2 % agarose E-gel and verified by direct sequencing. The FAST PCR screening method showed a specificity and sensitivity of 100 %, i.e., all mutated cases were detected, and none of negative cases carried mutations. The limit of detection was at 5–10 % of mutant alleles. We conclude that the FAST PCR assay is a highly specific, rapid (less than 2 h), and sensitive screening method for the detection of NPM1 mutations. Moreover, this method is inexpensive and can easily be integrated in the routine molecular diagnostic work-up of established risk factors in AML using standard laboratory equipment.
The impact of cryoballoon-based catheter ablation on left atrial structural and potential electrical remodeling in patients with paroxysmal atrial fibrillation

While atrial fibrillation (AF) begets AF via structural, contractile, and electrical remodeling, it was shown that successful radiofrequency ablation of AF has effectively reversed left atrial (LA) remodeling. However, there was little data regarding the efficacy of cryoablation on LA remodeling. Herein, we aimed to assess the impact of cryoablation on LA structural and potential electrical remodeling in paroxysmal AF patients. A total of 41 symptomatic patients with non-valvular paroxysmal AF underwent their first catheter ablation via cryoballoon technique. All patients had transthoracic echocardiography before, 6 and 12 months after cryoablation. LA volume index (LAVI), left intra-, right intra-, and inter-atrial electromechanical conduction delay (AEMD) were calculated in all patients. Postprocedural first 3 months was accepted as blanking period. All 179 pulmonary veins were isolated successfully in 41 patients with no major complication. During median 18 months (12–20 months) follow-up, recurrent atrial arrhythmia was found in nine patients (21.9 %). In multivariate Cox regression analysis, only early recurrence was found as the independent predictor of late recurrence. At 12th month visit compared to baseline, there was no change in LAVI (p = 0.647) but significant increase in left intra- and inter-AEMD (p < 0.05). However, in non-recurrent group, both LAVI (30.63 ± 3.6 to 28.42 ± 3.63, p < 0.001), left intra-AEMD (18.75 ± 8.77 to 12.5 ± 4.65, p < 0.001), and inter-AEMD (25.2 ± 13.2 to 18.84 ± 8.52, p < 0.001) were significantly decreased. Our study findings revealed that successful cryoballoon-based AF ablation yields LA structural and potential electrical reverse remodeling. However, LA remodeling process cannot be halted by cryoablation in patients with AF recurrence during follow-up.
Relationship between clinical effects, serum drug concentration and serotonin uptake inhibition in depressed patients treated with citalopram

Three dose levels (5, 25, and 50 mg once daily) of the selective serotonin uptake inhibitor citalopram were compared in a four-week, double-blind trial in depressed patients. Serum levels of citalopram and desmethylcitalopram, and the inhibitory effect of serum on serotonin uptake by fresh platelets, were assessed once weekly during the trial. The serum concentrations of citalopram were highly correlated with inhibition of serotonin uptake. Less of the metabolite was found, it being detected only in the higher dose groups. Steady state levels of citalopram, attained after 1 week, were linearly related to dose. The relationship between improvement (percentage reduction in total score on the Montgomery-Åsberg Depression Rating Scale) and serum level of citalopram indicated a lower limit of effect in endogenous depression at about 100 nM, corresponding to an average dose of 15 mg. Marked improvement was seen in ten patients with steady state levels in the range 70 to 335 nM. The ten nonendogenously depressed patients had steady state levels from 15 to 620 nM; complete remission was seen in the three with the lowest levels (15–25 nM). No significant correlation was found between serum drug level and the few reported side effects.
A phase I study of decitabine with pegylated interferon α-2b in advanced melanoma: impact on DNA methylation and lymphocyte populations

Melanoma cell lines treated with decitabine show upregulation of cancer antigens, and interferon-α upregulates MHC Class I antigens in cancer cells, leading to enhanced T-cell recognition and T-cell mediated tumor apoptosis. We evaluated the synergy between the hypomethylating effects of decitabine and the immunomodulatory effects of interferon in a combination regimen administered to advanced melanoma patients in a phase 1 trial.  Patients with one prior systemic therapy were eligible. Using a modified 3 + 3 design, patients received escalating doses of decitabine and pegylated interferon α-2b (PEG-IFN) during every 28-day treatment cycle. Global DNA methylation was measured on days 1 and 5 of cycles 1 and 3. Cytokine profiling and quantification of T-cell subpopulations by FACS were performed at baseline and cycle 3.  Seventeen patients were assigned to one of four dose levels. Decitabine 15 mg/m2/d + PEG-IFN 3 μg/kg was the maximum tolerated dose (MTD). Grade 3/4 cytopenias were seen across all dose levels: anemia (1), neutropenia (7), and thrombocytopenia (2). One patient remained progression-free for 37 weeks. The other 16 patients progressed at or before 12 weeks. Median overall survival was 39 weeks. Hypomethylation was seen at all dose levels. Due to treatment-induced lymphocytopenia, absolute changes in T-cell populations post-treatment were too small to be meaningfully interpreted.  The response to this combination regimen was characterized by significant myelosuppression, particularly neutropenia. Although disappointing efficacy and slow accrual led to early closure of the trial, hypomethylation showed pharmacodynamic evidence of a therapeutic effect of decitabine at all dose levels.
Circadian rhythm of cortisol and neighborhood characteristics in a population-based sample: the Multi-Ethnic Study of Atherosclerosis.

Although stress is often hypothesized to contribute to the effects of neighborhoods on health, very few studies have investigated associations of neighborhood characteristics with stress biomarkers. This study helps address the gap in the literature by examining whether neighborhood characteristics are associated with cortisol profiles. Analyses were based on data from the Multi-Ethnic Study of Atherosclerosis Stress study, which collected multiple measures of salivary cortisol over three days on a population based sample of approximately 800 adults. Multilevel models with splines were used to examine associations of cortisol levels with neighborhood poverty, violence, disorder, and social cohesion. Neighborhood violence was significantly associated with lower cortisol values at wakeup and with a slower decline in cortisol over the earlier part of the day, after sociodemographic controls. Associations were weaker and less consistent for neighborhood poverty, social cohesion, and disorder. Results revealed suggestive, though limited, evidence linking neighborhood contexts to cortisol circadian rhythms.
Gender-Disparities in Adults with Type 1 Diabetes: More Than a Quality of Care Issue. A Cross-Sectional Observational Study from the AMD Annals Initiative

We evaluated gender-differences in quality of type 1 diabetes (T1DM) care. Starting from electronic medical records of 300 centers, 5 process indicators, 3 favorable and 6 unfavorable intermediate outcomes, 6 treatment intensity/appropriateness measures and an overall quality score were measured. The likelihood of women vs. men (reference class) to be monitored, to reach outcomes, or to be treated has been investigated through multilevel logistic regression analyses; results are expressed as Odd Ratios (ORs) and 95% confidence intervals (95%CIs). The inter-center variability in the achievement of the unfavorable outcomes was also investigated. Overall, 28,802 subjects were analyzed (45.5% women). Women and men had similar age (44.5±16.0 vs. 45.0±17.0 years) and diabetes duration (18.3±13.0 vs. 18.8±13.0 years). No between-gender differences were found in process indicators. As for intermediate outcomes, women showed 33% higher likelihood of having HbA1c ≥8.0% (OR = 1.33; 95%CI: 1.25-1.43), 29% lower risk of blood pressure ≥140/90 mmHg (OR = 0.71; 95%CI: 0.65-0.77) and 27% lower risk of micro/macroalbuminuria (OR = 0.73; 95%CI: 0.65-0.81) than men, while BMI, LDL-c and GFR did not significantly differ; treatment intensity/appropriateness was not systematically different between genders; overall quality score was similar in men and women. Consistently across centers a larger proportion of women than men had HbA1c ≥8.0%, while a smaller proportion had BP ≥140/90 mmHg. No gender-disparities were found in process measures and improvements are required in both genders. The systematic worse metabolic control in women and worse blood pressure in men suggest that pathophysiologic differences rather than the care provided might explain these differences.