nils-herrmann/clean_scirepeval huggingface dataset:
Effect of device-guided breathing exercises on blood pressure in patients with hypertension: a randomized controlled trial.

Hypertension is a chronic disorder with a high prevalence worldwide. Despite considerable efforts, it is sometimes hard to reach treatment goals for blood pressure (BP) with classical treatment options. Reducing breathing frequency has been advocated as a method to reduce BP.



A randomized, single-blind, controlled trial was conducted in 30 non-diabetic patients with hypertension over a period of 9 weeks to evaluate the effect of a device that helps to slow breathing (Resperate) on BP and quality of life (QoL). The control group listened to music and used no other therapeutic device.



There was no significant difference in change in BP between intervention and control; BP -4.2 mmHg (95% CI -12.4 to 3.9)/-2.6 mmHg (95% CI -8.4 to 3.3). This result did not alter in post hoc analyses, when patients not achieving target breathing frequency (<10 breaths/min) or non-compliant patients were excluded. QoL did not change over time.



We found no effect of the Resperate on BP or QoL compared with the control group. We conclude that, at this moment, this device has no added value in the treatment of hypertension.
New Opportunities for PODC?: Massive, Volatile, but Highly Predictable Resources

Classical models for distributed systems focus on fine-grained resources and failures (e.g. single processes and fail-stop or byzantine). Cheap hardware, the rise of the worldwide web, and now the rise of cloud computing has transformed distributed systems practice. Instead of single resources, application sites have ten-thousands of virtual machines, and in addition to independent failures, there are a raft of correlated failure modes.
 Motivated by the reality the computing is the fastest growing consumer of electric power (and associated carbon emissions), we are creating new model for cloud computing systems, Zero-carbon Cloud, that taps a growing phenomenon of "stranded power" -- energy that is generated, but has no economic value. Stranded power is significant today (7.7 terawatt-hours in the Midwest power grid in 2014, perhaps 50 TWH worldwide), and growing rapidly as concerns about climate change drive a conversion of the grid to intermittent renewable energy generation such as wind and solar.
 Zero-carbon cloud resources have several novel properties. First, they have correlated availability at massive scale -- 10K-1M cores in an entire data center will go on or offline at once. Second, these periods may be highly predictable -- external factors such as weather, predicted load, and power markets shape the availability of stranded power. Third, these properties can be engineered -- for example, a small amount of energy storage can be used to "delay" unavailability. We will propose Zero-carbon cloud, or massive volatile resources based on stranded power as an interesting new model for a variety of classical distributed systems challenges (consistency, etc.) and new challenges for optimization.
 More information is available at http://zccloud.cs.uchicago.edu/
A phase I study of quisinostat (JNJ-26481585), an oral hydroxamate histone deacetylase inhibitor with evidence of target modulation and antitumor activity, in patients with advanced solid tumors.

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetic and pharmacodynamic profile of quisinostat, a novel hydroxamate, pan-histone deacetylase inhibitor (HDACi).



In this first-in-human phase I study, quisinostat was administered orally, once daily in three weekly cycles to patients with advanced malignancies, using a two-stage accelerated titration design. Three intermittent schedules were subsequently explored: four days on/three days off; every Monday, Wednesday, Friday (MWF); and every Monday and Thursday (M-Th). Toxicity, pharmacokinetics, pharmacodynamics, and clinical efficacy were evaluated at each schedule.



Ninety-two patients were treated in continuous daily (2-12 mg) and three intermittent dosing schedules (6-19 mg). Treatment-emergent adverse events included: fatigue, nausea, decreased appetite, lethargy, and vomiting. DLTs observed were predominantly cardiovascular, including nonsustained ventricular tachycardia, ST/T-wave abnormalities, and other tachyarhythmias. Noncardiac DLTs were fatigue and abnormal liver function tests. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of quisinostat increased proportionally with dose. Pharmacodynamic evaluation showed increased acetylated histone 3 in hair follicles, skin and tumor biopsies, and in peripheral blood mononuclear cells as well as decreased Ki67 in skin and tumor biopsies. A partial response lasting five months was seen in one patient with melanoma. Stable disease was seen in eight patients (duration 4-10.5 months).



The adverse event profile of quisinostat was comparable with that of other HDACi. Intermittent schedules were better tolerated than continuous schedules. On the basis of tolerability, pharmacokinetic predictions, and pharmacodynamic effects, the recommended dose for phase II studies is 12 mg on the MWF schedule.
Dexmedetomidine as a novel countermeasure for cocaine-induced central sympathoexcitation in cocaine-addicted humans.

Cocaine-induced acute hypertension is mediated largely by increased central sympathetic nerve activity. We hypothesized that dexmedetomidine, a central sympatholytic, reverses cocaine-induced increases in sympathetic nerve activity, mean arterial pressure (MAP), and heart rate (HR) in cocaine-addicted subjects. First, we conducted a dose-finding study in 15 nontreatment-seeking cocaine-addicted subjects and 12 cocaine-naive healthy controls to find doses of intravenous dexmedetomidine that lower MAP and HR in the absence of acute-cocaine challenge. We then conducted a placebo-controlled treatment trial in 26 cocaine-addicted subjects to determine whether dexmedetomidine reverses MAP and HR increases after intranasal cocaine (3 mg/kg). Skin sympathetic nerve activity (measured in the second protocol) and skin vascular resistance (measured in both protocols) served as indices of cocaine-sensitive central sympathoexcitation. In doses up to 0.6 µg/kg IV, dexmedetomidine alone caused comparable dose-dependent decreases in blood pressure in cases and controls but a 1.0 µg/kg dose was required to lower HR. In cocaine-addicted subjects, low-dose dexmedetomidine (0.4 µg/kg; n=14) abolished cocaine-induced increases in skin sympathetic nerve activity (156 ± 26 versus -15 ± 22%, cocaine/placebo versus cocaine/dexmedetomidine; P<0.05), skin vascular resistance (+10 ± 2 versus -2 ± 3 U; P<0.05), and MAP (+6 ± 1 versus -5 ± 2 mm Hg; P<0.01) without affecting HR (+13 ± 2 versus +9 ± 2 bpm; P=ns). When dexmedetomidine was increased to 1 µg/kg (high dose; n=12) to reverse cocaine-induced increases in HR, MAP did not fall further and increased paradoxically in 4 of 12 subjects. Thus, in a low nonsedating dose, dexmedetomidine constitutes a putative new treatment for cocaine-induced acute hypertension but higher sedating doses can increase blood pressure unpredictably during acute-cocaine challenge and should be avoided.
Bioabsorbable stent implantation vs. common femoral artery endarterectomy: early results of a randomized trial.

To compare clinical and hemodynamic outcome in patients undergoing treatment of common femoral artery (CFA) atherosclerotic lesions by bioabsorbable stent implantation (BASI group) or by common femoral artery endarterectomy (CFE group).



A randomized, controlled, single-center, open-label trial was initiated to compare outcomes of BASI or CFE in patients with chronic atherosclerotic occlusive lesions in the CFA. From May 2011 to April 2013, 116 consecutive patients were recruited; after excluding 36 patients, 80 patients (52 men; mean age 72.2±9.6 years) were enrolled 1:1 and are the subject of this intention-to-treat interim analysis (40 patients in each group). The primary endpoint was surgical site infections; secondary outcome measures were technical success, hemodynamic improvement, clinical improvement, patency, limb salvage, and survival.



There was no statistically significant difference between both groups regarding demographic data, cardiovascular risk factors, or CFA occlusions. The CFE patients presented with 7 surgical site infections (all minor) vs. none in the BASI group (p=0.002) and a longer mean postoperative hospital stay of 7 vs. 2 days for BASI patients (p<0.001). Technical success rates were 97.5% and 100% for the BASI and CFE groups, respectively. Postoperative ankle-brachial index means were comparable (p=0.38). The 30-day primary patency rates were 92.5% and 100% for the BASI and CFE groups, respectively (p=0.038). There were 6 reconstruction failures in CFE patients vs. none in the BASI group (p=0.02); 5 failures involved initial CFA occlusions. At 1 year, the primary and secondary patency rates were 80% vs. 100% (p=0.007) and 84% vs. 100% (p=0.01) for BASI and CFE patients, respectively. Limb salvage was equivalent, and survival rates were 88% and 90% for BASI vs. CFE patients (p=0.51) at 1 year.



This interim analysis suggests that BASI is not an option for CFA occlusion and is only a limited option for CFA stenosis. Clinical and hemodynamic results are comparable for BASI and CFE. An increased rate of redo procedures in the BASI patients outweighs lower surgical site infection rates compared to CFE. Short-term patency rates are significantly worse in patients undergoing CFA stenting with BASI.
Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for ∼ 5% of Hodgkin lymphoma cases. The disease is characterized by a strong CD20 expression on the malignant cells and a more indolent clinical course compared with classic HL. Anti-CD20 antibody treatment has shown clinical activity in relapsed NLPHL. In this phase 2 trial, we investigated rituximab in newly diagnosed stage IA NLPHL patients. Four weekly applications at 375 mg/m(2) were given. Among the 28 evaluable patients, overall response rate was 100%, 24 patients (85.7%) achieved complete remission, and 4 (14.3%) achieved partial remission. At a median follow-up of 43 months, overall survival was 100%; progression-free survival at 12, 24, and 36 months was 96.4%, 85.3%, and 81.4%, respectively. No grade 3 or 4 toxicity was observed. Although treatment results with rituximab appear inferior compared with radiotherapy and combined-modality approaches in early-stage patients, investigation of anti-CD20 antibody-based combinations in NLPHL is warranted.
Silent reflux: ex juvantibus criteria for diagnosis and treatment of laryngeal disorders.

Some primary laryngeal pathologies with specific clinical presentation may be related to silent laryngeal reflux. An ex adjuvantibus proton pump inhibitor (PPI) treatment may be helpful for showing evidence of such a hidden laryngeal disorder.



To assess the validity of PPI as an ex adjuvantibus criterion for diagnosis and treatment of suspected reflux-associated laryngitis.



Sixty patients with clinical suspicion of laryngo-pharyngeal reflux (LPR) were identified on the grounds of laryngeal symptoms (dysphonia, cough, globus sensation, increased throat clearing, bad taste, and laryngeal spasm), laryngeal features (arytenoid edema/erythema, partial or total vocal fold erythema, and posterior glottic edema) with or without gastro-esophageal reflux disorder (GERD). They were consequently subdivided in three groups: type I, with LPR symptoms and features without GERD; type II with LPR symptoms and features with GERD; and type III with LPR features only. Types I and III were randomly treated with omeprazole (group A) or with immunostimulating vaccine (group B) for 3 months. Pre- and post-treatment laryngeal features and symptoms in all groups were evaluated by laryngo-stroboscopy and analyzed for statistical correlation.



All omeprazole-treated patients showed improvement of laryngeal features and symptoms. With PPI treatment, a more significant improvement was noticed with respect to nonspecific immunostimulant therapy. Also, patients without LPR symptoms showed improvement of laryngeal features.
Increased Skeletal Muscle Capillarization After Aerobic Exercise Training and Weight Loss Improves Insulin Sensitivity in Adults With IGT

Transcapillary transport of insulin is one determinant of glucose uptake by skeletal muscle; thus, a reduction in capillary density (CD) may worsen insulin sensitivity. Skeletal muscle CD is lower in older adults with impaired glucose tolerance (IGT) compared with those with normal glucose tolerance and may be modifiable through aerobic exercise training and weight loss (AEX+WL). We tested the hypothesis that 6-month AEX+WL would increase CD to improve insulin sensitivity and glucose tolerance in older adults with IGT.



Sixteen sedentary, overweight-obese (BMI 27-35 kg/m2), older (63 ± 2 years) men and women with IGT underwent hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, oral glucose tolerance tests, exercise and body composition testing, and vastus lateralis muscle biopsies to determine CD before and after 6-month AEX+WL.



Insulin sensitivity (M) and 120-min postprandial glucose (G120) correlated with CD at baseline (r = 0.58 and r = -0.60, respectively, P < 0.05). AEX+WL increased maximal oxygen consumption (VO2max) 18% (P = 0.02) and reduced weight and fat mass 8% (P < 0.02). CD increased 15% (264 ± 11 vs. 304 ± 14 capillaries/mm(2), P = 0.01), M increased 21% (42.4 ± 4.0 vs. 51.4 ± 4.3 µmol/kg FFM/min, P < 0.05), and G120 decreased 16% (9.35 ± 0.5 vs. 7.85 ± 0.5 mmol/L, P = 0.008) after AEX+WL. Regression analyses showed that the AEX+WL-induced increase in CD independently predicted the increase in M (r = 0.74, P < 0.01) as well as the decrease in G120 (r = -0.55, P < 0.05).



Six-month AEX+WL increases skeletal muscle CD in older adults with IGT. This represents one mechanism by which AEX+WL improves insulin sensitivity in older adults with IGT.
Randomized, double-blind trial of simultaneous right and left atrial epicardial pacing for prevention of post-open heart surgery atrial fibrillation.

The purpose of this study was to assess simultaneous right and left atrial pacing as prophylaxis for postoperative atrial fibrillation.



In a double-blind, randomized fashion, 118 patients who underwent open heart surgery were assigned to right atrial pacing at 45 bpm (RA-AAI; n=39), right atrial triggered pacing at a rate of >/=85 bpm (RA-AAT; n=38), or simultaneous right and left atrial triggered pacing at a rate of >/=85 bpm (Bi-AAT; n=41). Holter monitoring was performed for 4. 8+/-1.4 days after surgery to assess for episodes of atrial fibrillation lasting >5 minutes. The prevalence of postoperative atrial fibrillation was significantly less in the patients randomized to biatrial AAT pacing when compared with the other 2 pacing regimens (P=0.02). An episode of atrial fibrillation occurred in 4 (10%) of 41 patients in the Bi-AAT group compared with 11 (28%) of 39 patients in the RA-AAI group (P=0.03 versus Bi-AAT) and 12 (32%) of 38 patients in the RA-AAT group (P=0.01 versus Bi-AAT). There was no difference in the occurrence of atrial fibrillation between the right atrial AAI and AAT groups (P=0.8). There was no significant difference among the 3 groups with regard to the number of postoperative hospital days (7.3+/-4.2 days), morbidity (5.1%), or mortality rate (2.5%).



Simultaneous right and left atrial triggered pacing is well tolerated and significantly reduces the prevalence of post-open heart surgery atrial fibrillation.
Bone morphogenetic proteins 2 and 4 are selectively expressed by late outgrowth endothelial progenitor cells and promote neoangiogenesis.

Endothelial progenitor cells are currently identified either by their surface antigen expression or by their generation of early colonies in culture (CFU-Hill). Another population, endothelial colony-forming cells (ECFCs), has strong vessel-forming capacity but is less well characterized. Given the potential usefulness of CFU-Hill and ECFCs as cell therapy products, their thorough characterization is of major importance.



CFU-Hill and ECFCs were expanded from human cord and adult blood. Bone morphogenetic proteins 2 and 4 (BMP2/4) were selectively expressed by ECFCs but not by CFU-Hill. The BMP pathway was involved in ECFC commitment and angiogenic potential in vitro. In vivo, BMP inhibition strongly reduced plug vascularization in bFGF-containing Matrigel plugs implanted in C57/Bl6 mice. Moreover, ECFC exposure to BMP increased their therapeutic potential in a nude mouse model of hindlimb ischemia. In amputation specimens from patients with critical leg ischemia who had received a local therapeutic injection of bone marrow mononuclear cells, newly formed vessels were strongly positive for BMP2/4, suggesting that endothelial cells involved in neovascularization have an ECFC-like phenotype.



BMP2/4 are a marker of ECFCs and play a key role in ECFC commitment and outgrowth during neovascularization.
Comparison of enoxaparin and dalteparin with unfractionated heparin in the treatment of non-ST elevated acute coronary syndrome.

The term non-ST elevated Acute Coronary Syndrome (ACS) encompasses unstable Angina (USA) and non-ST segment elevated Myocardial Infarction (NSTEMI), both of which may end up in death or a fatal/non-fatal Myocardial Infarction (MI). Unfractionated heparin (UFH) has been shown to reduce death and MI in patients with USA and NSTEMI. Of late, there has been a great interest in the role of low molecular weight heparins (LMWHs) in the two conditions and they have been found to be at least as effective as or even more effective than UFH.



A total of 90 patients who presented to CCU of Khyber Teaching Hospital. Peshawar with USA or NSTEMI, from June 2008 to June 2009, were enrolled into the study. An equal number of patients were randomly assigned to one of the three arms for 5 days each: Group A received enoxaparin, group B received dalteparin and group C received UFH. The primary end points of the study were all cause mortality, STEMI, refractory USA, recurrent USA or a major bleed. The secondary end point was minor bleeding.



At the end of the study, there were 2 deaths each in the dalteparin and UFH group, whereas no such event was recorded in the enoxaparin group. Two patients had STEMI in the UFH group but none in the other two groups.



LMWHs are far more superior to unfractionated heparin.
BMI is superior to symptoms in predicting response to proton pump inhibitor: randomised trial in patients with upper gastrointestinal symptoms and normal endoscopy.

In most patients undergoing endoscopy for upper gastrointestinal (GI) symptoms in the Western world, no macroscopic abnormality or evidence of Helicobacter pylori infection is identified. Following this negative investigation, proton pump inhibitor (PPI) therapy is usually prescribed. The aim of this study was to assess the value of such treatment compared with placebo and to identify predictors of response.



Prospective parallel randomised study.



Dyspepsia Research Clinic.


PARTICIPANT
105 patients (49 men, median age 44 years, IQR 22) with normal endoscopy and H pylori negative with ongoing upper GI symptoms following 2-week run-in period.  Full demographic symptom severity and characteristics were assessed and 24 h oesophageal pH metry and oesophageal manometry were performed prior to randomisation to 2 weeks of treatment with lansoprazole 30 mg/day or placebo (2:1), with reassessment of symptom severity during the second week of treatment.


PRIMARY OUTCOME
50% reduction in Glasgow Dyspepsia Severity Score (GDSS).



According to intention to treat analysis, the response was 35.7% for the active group and 5.7% for the placebo group (p < 0001). The only non-invasive independent predictor of response to PPI in multivariable analysis was the patient's body mass index (BMI) (p = 0.003). The association of BMI with response to PPI was apparent across the full range of quartiles (p values for trend=0.01). BMI had a similar predictive value to either 24 h oesophageal pH metry or manometry. Predominant symptom and symptom subgroups were unhelpful in predicting the response to PPI. Including all pretreatment assessments, only BMI (p < 0.05) and lower oesophageal sphincter pressure (p < 0.05) were independent predictors of response.



The response to PPI therapy is likely to be related to underlying acid reflux. The strong predictive value of BMI is probably due to its association with underlying reflux disease and the fact that it is a more objective and reproducible measure than symptom characteristics. It is recommended that BMI should be measured in patients with upper GI symptoms.
Unexpected drug-drug interactions in human immunodeficiency virus (HIV) therapy: induction of UGT1A1 and bile efflux transporters by Efavirenz.

Efavirenz is an inducer of drug metabolism enzymes. We studied the effect of efavirenz and ritonavir-boosted darunavir on serum unconjugated and conjugated bilirubin, as probes for UGT1A1 and bile transporters.



Healthy volunteers were enrolled in a clinical trial. There were 3 periods: Period 1, 10 days of darunavir 900 mg with ritonavir 100 mg once daily; Period 2, 14 days of efavirenz 600 mg with darunavir/ritonavir once daily; and Period 3, 14 days of efavirenz 600 mg once daily. Serum bilirubin (conjugated and unconjugated) concentrations were obtained at baseline, at the end of each phase and at exit.



We recruited 7 males and 5 females. One subject developed grade 3 hepatitis on efavirenz and was excluded. Mean serum unconjugated bilirubin concentrations were 6.09 μmol/L (95% confidence interval [CI], 4.99 to 7.19) at baseline, 5.82 (95% CI, 4.88 to 6.76) after darunavir/ritonavir, 4.00 (95% CI, 2.92 to 5.08) after darunavir/ritonavir with efavirenz, 3.55 (95% CI, 2.58 to 4.51) after efavirenz alone and 5.27 (95% CI, 3.10 to 7.44) at exit (P <0.01 for the efavirenz phases). Mean serum conjugated bilirubin concentrations were 3.55 μmol/L (95% CI, 2.73 to 4.36) at baseline, 3.73 (95% CI, 2.77 to 4.68) after darunavir/ritonavir, 2.91 (95% CI, 2.04 to 3.78) after darunavir/ritonavir with efavirenz, 2.64 (95% CI, 1.95 to 3.33) after efavirenz alone and 3.55 (95% CI, 2.19 to 4.90) at exit (P <0.05 for the efavirenz phases).



Efavirenz decreased unconjugated bilirubin by 42%, suggesting UGT1A1 induction. Efavirenz also decreased conjugated bilirubin by 26%, suggesting induction of bile efflux transporters. Ritonavir-boosted darunavir had no effect on bilirubin concentrations. These results indicate that efavirenz may reduce concentrations of drugs or endogenous substances metabolized by UGT1A1 or excreted by bile efflux transporters.