nils-herrmann/clean_scirepeval huggingface dataset:
Wild-type and modified gp100 peptide-pulsed dendritic cell vaccination of advanced melanoma patients can lead to long-term clinical responses independent of the peptide used

Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients. Several strategies have been employed to load DC with antigen, including peptide loading. To increase immunogenicity of peptides, major histocompatibility complex (MHC) class I binding affinity and stability of peptide–MHC complexes at the cell surface may be improved by modification of the amino acid sequence. In this study, we compared the capacity of DC loaded with wild-type versus modified gp100 peptides with higher binding affinities to induce an immune and clinical response in advanced melanoma patients. Metastatic HLA-A2.1+ melanoma patients were vaccinated intravenously (on average 25 × 106 DC) and intradermally (on average 11 × 106 DC) with mature DC loaded with keyhole limpet hemocyanin (KLH) together with tyrosinase peptide and either wild-type (15 patients) or modified (12 patients) gp100 peptides. All vaccinated patients showed a pronounced proliferative T cell or humoral response against KLH. Gp100-specific T cell responses were monitored in post-treatment delayed type hypersensitivity (DTH) skin biopsies by tetramer and functional analysis. Antigen-specific T cells were found in 2 of 15 patients vaccinated with wild-type gp100-loaded DC, versus 1 of 12 patients vaccinated with modified peptide-loaded DC. These three patients also had the best clinical response, with long-term (>8 years) complete responses in two patients, one in each group. We conclude that vaccination with peptide-loaded DC can result in long-term clinical responses in a minority of metastatic melanoma patients, and that the use of modified as compared to wild-type gp100 peptides for DC loading does not result in a relevant enhanced immune responses.
Spironolactone and hydrochlorothiazide decrease vascular stiffness and blood pressure in geriatric hypertension.

To determine the efficacy of spironolactone (SPIRO) and hydrochlorothiazide (HCTZ) as monotherapy in older patients with hypertension in blood pressure (BP) control and measures of vascular stiffness.



Randomized double-blind trial.



University teaching hospital.



Forty-five subjects with hypertension (24 men, 21 women, mean age 69).



Six months of HCTZ (n=21) or SPIRO (n=24) therapy titrated to a target systolic BP (SBP) less than 140 mmHg.



Baseline (after 4 weeks of antihypertensive drug washout) and 6-month 24-hour ambulatory BP data were obtained. Pulse pressure (PP) was calculated as the difference between 24-hour average SBP and DBP. Pulse wave velocity (PWV) was determined according to noninvasive recordings of carotid and femoral artery pulse waves.



Six months of HCTZ and SPIRO treatment was associated with significant decreases in 24-hour and nocturnal SBP and diastolic BP (DBP) (analysis of variance (ANOVA) P<.001). At 6 months, average 24-hour and nocturnal SBP were lower in the SPIRO than the HCTZ group (P<.001). PP and PWV also decreased significantly with HCTZ and SPIRO treatments (ANOVA P<.001).



Six months of therapy with HCTZ or SPIRO resulted in comparable reductions in 24-hour average and nocturnal SBP and DBP, PP, and PWV in older subjects with hypertension.
Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans.

Elevated low-density lipoproteins (LDLs) are associated with vascular dysfunction evident in the cutaneous microvasculature. We hypothesized that uncoupled endothelial nitric oxide synthase (NOS3) through upregulated arginase contributes to cutaneous microvascular dysfunction in hyperocholesterolaemic (HC) humans and that a statin intervention would decrease arginase activity. Five microdialysis fibres were placed in the skin of nine normocholesterolaemic (NC: LDL level 95±4 mg dl⁻¹) and nine hypercholesterolaemic (HC: LDL: 177±6 mg dl⁻¹) men and women before and after 3 months of systemic atrovastatin. Sites served as control, NOS inhibited, arginase inhibited, L-arginine supplemented and arginase inhibited plus L-arginine supplemented. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilatation. L-NAME was infused after the established plateau in all sites to quantify NO-dependent vasodilatation. Data were normalized to maximum cutaneous vascular conductance (CVC(max)). Skin samples were obtained to measure total arginase activity and arginase I and arginase II protein. Vasodilatation was reduced in hyperocholesterolaemic subjects (HC: 76±2 vs. NC: 94±3%CVC(max), P < 0.001) as was NO-dependent vasodilatation (HC: 43±5 vs. NC: 62±4%CVC(max), P < 0.001). The plateau and NO-dependent vasodilatation were augmented in HC with arginase inhibition (92±2, 67±2%CVC(max), P < 0.001), L-arginine (93±2, 71±5%CVC(max), P < 0.001) and combined treatments (94±4, 65±5%CVC(max), P < 0.001) but not in NC. After statin intervention (LDL: 98±5 mg dl⁻¹) there was no longer a difference between control sites (88±4, 61±5%CVC(max)) and localized microdialysis treatment sites (all P > 0.05). Arginase activity and protein were increased in HC skin (P < 0.05 vs. NC) and activity decreased with atrovastatin treatment (P < 0.05). Reduced NOS3 substrate availability through upregulated arginase contributes to cutaneous microvascular dysfunction in hyperocholesterolaemic humans, which is corrected with atorvastatin therapy.
Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications.



A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status.



For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%).



Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.
Detection of embolic particles with the Doppler guide wire during coronary intervention in patients with acute myocardial infarction: efficacy of distal protection device.

We investigated whether embolic particles could be detected as high-intensity transient signals (HITS) with a Doppler guide wire during percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) We also assessed whether these signals could be reduced using a distal protection (DP) device.



Embolization of thrombi and plaque components to the microcirculation is a major complication of PCI in patients with AMI. Embolic particles running in the cerebral artery are detected as HITS by transcranial Doppler ultrasound.



We prospectively studied 16 consecutive patients with AMI who underwent direct PCI within 24 h after the onset of symptoms. A PercuSurge GuardWire (MedtronicAVE, Santa Rosa, California) was used as the DP device. Eight patients were randomly assigned to the non-DP group, and the remaining eight were assigned to the DP group. Coronary flow velocity was recorded continuously from before the first balloon inflation to after balloon deflation.



All patients in the non-DP group had HITS detected (12 +/- 9 counts) within five consecutive beats (4 +/- 1 beat) after balloon deflation, but none were detected in any of the patients in the DP group.



The Doppler guide wire can be used to visually detect and count emboli as HITS, and the DP device is effective for prevention of distal embolization.
Gender and Communal Trait Differences in the Relations Among Social Behaviour, Affect Arousal, and Cardiac Autonomic Control

To examine the relation between social behaviour and vagal activity, the communal behaviour of healthy college men (N = 33) and women (N = 33) was manipulated while monitoring heart rate (HR) and respiratory sinus arrhythmia (RSA). The subjects were classified as low or high on communal trait. Communal behaviour was manipulated by having the subjects behave in an agreeable or quarrelsome manner in scripted role-plays. HR, RSA and self-report arousal were obtained during or immediately following baseline, experimental and relaxation periods. 2 (Gender) × 2 (Communal Trait; low/high) × 2 (Condition; agreeable/quarrelsome) ANCOVAs were performed. Men had lower RSA values when behaving in a quarrelsome fashion than agreeable and lower RSA values than women in the quarrelsome condition. In the latter condition, low communal men reported more arousal than other groups. Strong but opposite associations between RSA and affect arousal were observed in low communal men and woman. Men, especially more quarrelsome (less communal) men exhibited weaker vagal control during arousing social situations.
Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients

To compare candesartan cilexetil and lisinopril in fixed combination with hydrochlorothiazide with respect to antihypertensive efficacy and tolerability.This was a double-blind (double-dummy), randomised, parallel group comparison in patients with a mean sitting diastolic blood pressure 95–115 mm Hg on prior antihypertensive monotherapy. Treatments were candesartan cilexetil/hydrochlorothiazide 8/12.5 mg once daily (n = 237) and lisinopril/hydrochlorothiazide 10/12.5 mg once daily (n = 116) for 26 weeks. The primary efficacy variable was change in trough sitting diastolic blood pressure. Changes in mean sitting diastolic blood pressure did not differ significantly between the groups (mean difference 0.5 mm Hg; 95% confidence interval −1.6, 2.7, P = 0.20). No significant differences between the groups was found for other haemodynamic variables (sitting systolic blood pressure, standing blood pressure, sitting/erect heart rate, and proportion of responders and controlled patients). Both drugs were well tolerated but the proportion of patients with at least one adverse event was significantly greater in the lisinopril group (80% vs 69%, P = 0.020). The proportion of patients spontaneously reporting cough (23.1% vs 4.6%) and discontinuing therapy due to adverse events (12.0% vs 5.9%) was also higher in the lisinopril group compared with the candesartan cilexetil group. The fixed combinations of candesartan cilexetil and hydrochlorothiazide 8/12.5 mg and lisinopril and hydrochlorothiazide 10/12.5 mg once daily are equally effective as antihypertensive agents. The fixed combination containing candesartan cilexetil is better tolerated than that containing lisinopril.
Zopiclone effects on breathing at sleep in stable chronic obstructive pulmonary disease

More than half of patients with chronic obstructive pulmonary disease (COPD) experiences sleep-related problems and about one fourth uses hypnotics regularly. We explored what the effect zopiclone, a commonly used hypnotic, had on nocturnal gas exchange and the apnea/hypopnea frequency in stable COPD. Randomized crossover study of 31 (ten males) inpatients at a pulmonary rehabilitation hospital, median age 64 years, of which 20 had a forced expiratory volume first second <50 % of predicted. Subjects investigated in randomized order of either baseline sleep or intervention with 5 mg zopiclone by polysomnography including transcutaneous measurement of carbon dioxide pressure increased (ΔPtcCO2). Zopiclone increased the mean ΔPtcCO2 from baseline both in rapid eye movement (REM) sleep, non-REM sleep, and even in stage N0 (awake after sleep onset) with a mean (SD) of 0.25 (0.40) kPa, 0.22 (0.32) kPa, and 0.14 (0.27) kPa, respectively. Subjects with sleep hypoventilation as defined by the American Academy of Sleep Medicine increased from 6 subjects (19 %) to 13 subjects (42 %) (P = 0.020). REM sleep minimum oxygen saturation (minSpO2) did not change significantly from baseline median (interquartile range [IQR]) minSpO2 81.8 (12.1) % to zopiclone sleep median (IQR) minSpO2 80.0 (12.0) % (P = 0.766). Interestingly, zopiclone reduced the number of apneas/hypopneas per hour (AHI) in subjects with overlap (AHI ≥ 15) with a median difference (IQR) of −8.5 (7.8) (N = 11, P = 0.016). In stable COPD, zopiclone moderately increases the mean ΔPtcCO2 without changing minSpO2 at night and reduces AHI in overlap (COPD and obstructive sleep apnea) subjects.
C-reactive protein, an indicator for maintained response or remission to infliximab in patients with Crohn's disease: a post-hoc analysis from ACCENT I.

Secondary loss of response to anti-TNF-α therapy is observed in Crohn's disease patients.



Serum C-reactive protein (CRP) levels at baseline and after infliximab induction therapy at week 14 were assessed as predictors for maintained response or remission through 54 weeks of treatment in patients with Crohn's disease who responded to induction therapy.



ACCENT I was a multicenter, randomised, placebo-controlled study. Patients who received infliximab induction (weeks 0, 2 and 6) and maintenance (5 or 10 mg/kg every 8 weeks beginning at week 14) therapy were considered. Patients in clinical response or remission to induction therapy at week 14 (n = 212 or n = 138 respectively) were analysed. Associations between CRP levels (cut-off points 0.5-3.0 mg/dL), baseline disease variables and maintained clinical response or remission during maintenance therapy were assessed.



A significant association was observed between baseline CRP levels and maintained remission. Forty-five percent of patients with baseline CRP ≥ 0.7 mg/dL vs. 22.0% with CRP < 0.7 mg/dL maintained remission (P = 0.012). CRP normalisation during infliximab treatment (decrease from 0.5 mg/dL at baseline to < 0.5 mg/dL at week 14) resulted in higher probability of maintained response (P < 0.001) or remission (P = 0.052). At week 14 low CRP levels were associated with maintained response (56.6% of patients with CRP < 0.5 mg/dL vs. 37.2% with higher CRP, P = 0.005). No optimal predictive CRP cut-off point was observed.



High baseline CRP levels increased the likelihood of maintained remission. Normalised CRP levels at week 14 increased the likelihood of maintained response or remission during 1 year of infliximab maintenance therapy (
Protective effects of inhaled ipratropium bromide on bronchoconstriction induced by adenosine and methacholine in asthma.

Although adenosine-induced bronchoconstriction is mainly due to mast cell mediator release, vagal reflexes have also been implicated in this response. We have investigated the effect of a specific muscarinic-receptor antagonist, ipratropium bromide, on methacholine- and adenosine-induced bronchoconstriction in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Airway response was evaluated as forced expiratory volume in one second (FEV1). Inhaled ipratropium bromide (40 micrograms), administered 20 min prior to bronchoprovocation, increased the provocation dose of inhaled methacholine and adenosine required to reduce FEV1 by 20% from baseline (PD20) from 0.11 to 0.79 mg (p less than 0.01) and from 0.57 to 1.27 mg (p less than 0.01), respectively. The mean baseline FEV1 values after administration of ipratropium bromide were significantly higher than after placebo administration (p less than 0.05). However, there was no correlation between the degree of bronchodilatation and dose-ratios for methacholine and adenosine. The findings of the present study implicate vagal reflexes in the bronchospastic response induced by inhaled adenosine in asthma.
Fecal immunochemical test for colorectal cancer from a prospective cohort with 513,283 individuals

The fecal immunochemical test (FIT) is underutilized, in part, because its benefits have not been fully understood. We assessed the relationship of FIT values with cancer incidence and mortality, and explored how repeated administrations of FIT could aid clinicians. A cohort with 513,283 adults in Taiwan participated in a screening program between 1994 and the end of 2007. Colorectal cancer was identified from National Cancer Registry and not from colonoscopy. Positive FIT was FIT ≥ 100 ng/mL. Number needed to scope (NNS) to identify 1 cancer by different FIT values was calculated for the study time. Only 4% of subjects had FIT ≥ 100 ng/mL but contributed 40% of cancer cases, leading to a NNS of 25 for finding 1 in this group. However, within the same FIT ≥ 100 ng/mL, NNS was different by age: 10 for age 60 to 69 years, 42 for age 40 to 49 years, and 156 for age 20 to 39 years. Furthermore, within the same age, NNS was different by FIT values, for instance, 66 for FIT 100 to 199 ng/mL and 12 for FIT 600 to 799 ng/mL, a difference of 5-fold for age 50 to 59 years. The dose-response relationship of FIT can facilitate consultation regarding the need for colonoscopy by providing a quantitative NNS for cancer risk, an index easily understood by patients. Our conclusion made use of (a) age-dependent and (b) quantitative interpretation of FIT values. This single cutpoint practice obliterates a large amount of valuable cancer risk information available to patients.
THREE-YEAR OUTCOMES OF DIETARY FATTY ACID MODIFICATION AND HOUSE DUST MITE REDUCTION IN THE CHILDHOOD ASTHMA PREVENTION STUDY

tween exclusive breastfeeding and physician-diagnosed AD in infants with a family history of AD (odds ratio [OR]: 0.92), in those without a family history of AD (OR: 0.97), or in those with itchy rash (OR: 1.2 and 0.92, respectively). In group I, exclusive breastfeeding was protective for AD, compared with feeding with a conventional cow’s milk formula (OR: 0.64). If stratified by family history of AD, there was no difference in effect of breastfeeding on physician-diagnosed AD and itchy rash in group I. The difference in the NI group was not determined because of the small number of participants.  Exclusive breastfeeding for the first 4 months of infancy was not shown to increase the risk of developing AD in infants with or without a family history of AD. Reviewers’ Comments. A number of studies have shown that breastfeeding could be a risk factor for atopic dermatitis and even suggest a detrimental effect of continuing to breastfeed infants with severe AD and food allergy. The role of breastfeeding in allergic diseases has been controversial, but the weight of the evidence in meta-analyses and in this study support a protective effect in regard to prevention.
Computerized decision support for medication dosing in renal insufficiency: a randomized, controlled trial.

Emergency physicians prescribe several discharge medications that require dosage adjustment for patients with renal disease. The hypothesis for this research was that decision support in a computerized physician order entry system would reduce the rate of excessive medication dosing for patients with renal impairment.



This was a randomized, controlled trial in an academic emergency department (ED), in which computerized physician order entry was used to write all prescriptions for patients being discharged from the ED. The sample included 42 physicians who were randomized to the intervention (21 physicians) or control (21 physicians) group. The intervention was decision support that provided dosing recommendations for targeted medications for patients aged 18 years and older when the patient's estimated creatinine clearance level was below the threshold for dosage adjustment. The primary outcome was the proportion of targeted medications that were excessively dosed.



For 2,783 (46%) of the 6,015 patient visits, the decision support had sufficient information to estimate the patient's creatinine clearance level. The average age of these patients was 46 years, 1,768 (64%) were women, and 1,523 (55%) were black. Decision support was provided 73 times to physicians in the intervention group, who excessively dosed 31 (43%) prescriptions. In comparison, control physicians excessively dosed a significantly larger proportion of medications: 34 of 46, 74% (effect size=31%; 95% confidence interval 14% to 49%; P=.001).



Emergency physicians often prescribed excessive doses of medications that require dosage adjustment for renal impairment. Computerized physician order entry with decision support significantly reduced excessive dosing of targeted medications.
Pulmonary vein isolation by duty-cycled bipolar and unipolar antrum ablation using a novel multielectrode ablation catheter system: first clinical results

The electrical disconnection of the pulmonary veins (PV) plays an important role in the ablation strategy of paroxysmal atrial fibrillation (PAF). Circumferential antral ablation with a conventional ablation technique using a steerable ablation catheter is sometimes difficult to perform and does not always result in isolation of the targeted PV. Patients with symptomatic PAF were treated with a novel circular mapping/ablation catheter (PVAC). Ablation was performed in the antral region of the PV with a power-modulated bipolar/unipolar RF generator using 8–10 W until isolation of the vein was achieved. Seven-day Holter monitor recordings were performed off antiarrhythmic drugs at 3 and 6 months after the initial procedure. A subgroup of patients had received an implantable recorder before ablation, and the device was interrogated at the same time. The primary objective of this study is acute isolation of the targeted PV, and the second objective is clinical efficacy with a short-term follow-up. In 73 patients, 290 PV could be reached with the PVAC. Antral ablation was performed in 244 PV showing PV potentials. Acutely, 243 PV (99%) were isolated with the PVAC after 21 ± 7 energy applications per patient with a mean fluoroscopy time of 20 ± 11 min. Total procedure time was 122 ± 27 min. No complications were observed. Follow-up at 3 and 6 months showed freedom from AF in 61 of 73 (84%) patients and 38 of 45 patients (85%), respectively, off antiarrhythmic drugs. PV isolation by duty-cycled unipolar/bipolar RF ablation can be effectively and safely performed with a circular, decapolar catheter. Clinical results at 3 and 6 months after ablation are encouraging with the need for longer follow-up intervals.