nils-herrmann/clean_scirepeval huggingface dataset:
Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system.

CKS257 (Salmonella typhimurium SL1344 DeltaphoP/phoQDelta aroA Deltaasd DeltastrA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag.



HIV Gag was expressed as a fusion protein of a Salmonella Type III secretion system protein SopE, from a balanced lethal asd-based plasmid. Eighteen healthy adults were given single escalating oral doses of 5 x 10(6) to 1 x 10(10)CFU of CKS257 and were monitored for clinical events, shedding and immune responses.



Adverse events were mild except at the highest dose. Volunteers shed the organism an average of 5.1 days (range 0-13 days). Eighty-three percent (15/18) of subjects had a mucosal immune response to Salmonella LPS and flagella by IgA ELISPOT assay. Seventy-two percent (13/18) of subjects seroconverted to Salmonella antigens. No volunteer had a response to recombinant Gag as measured by serology, IgA ELISPOT, or immediate ex vivo gamma-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving >or=5 x 10(8)CFU had a response to HIV peptides in a cultured gamma-interferon ELISPOT assay.



Although immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development.
Use of electronic pill boxes to assess risk of poor treatment compliance: results of a large-scale trial.

The objective of the present study was to determine the predictive factors of treatment compliance in hypertensive patients. This was an open large-scale multicenter study where mild to moderate essential hypertensive patients received trandolapril (2 mg) once daily for 30 to 60 days in addition to their usual treatment. Trandolapril was packed in electronic pill boxes that registered date and time of each opening. The main compliance parameters were the percentage of missed doses, the percentage of delayed doses, and the percentage of correct dosing periods. Predictive factors of poor compliance (correct dosing periods < 80%) were determined using a multivariate stepwise logistic regression analysis. Two thousand one hundred seventy-three patients aged 60 +/- 12 years were analyzed. Of the total patients 37% were poor compliers; 29% of patients forgot more than 10% of doses and 36% of patients delayed more than 10% of doses. Ranked predictive factors of poor compliance were: age < 60 years (odds ratio [OR], 1.80 [1.49 to 2.17], P = .0001), the Paris area (OR, 1.70 [1.32 to 2.19], P = .0001), smokers (OR, 1.65 [1.29 to 2.11], P = .0001), monotherapy (OR, 1.40 [1.14 to 1.72], P = .0012), and baseline diastolic blood pressure > or = 100 mm Hg (OR, 1.21 [1.01 to 1.46], P = .044). Therefore, we conclude that young hypertensives, large city dwellers, and smokers are more likely to be poor compliers. The presence of some of these characteristics might incite the physician either to encourage patient compliance or to prescribe antihypertensive drugs that have an effect that persists even beyond 24 h.
Screening for lung cancer by imaging: the Nelson study.

The NELSON trial is the first randomised lung cancer screening trial in which pulmonary nodule management is based on volumetry. This led to considerably less false-positive referrals compared to other lung cancer screening trials, with very high negative predictive values found in the first and second screening rounds. Mortality results are still pending, but the knowledge already gained in the NELSON trial and its side-studies provide valuable information in the field of screening for lung cancer.
Reduction of plasma levels of soluble tumor necrosis factor and interleukin-2 receptors by means of a novel immunoadsorption column.

This non-randomized open clinical study investigated the safety and efficacy of extracorporeal fractionated plasma adsorption using the Oncosorb immune adsorption column. The column selectively bound soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2) and soluble interleukin-2 receptors (sIL2-R) by lowering plasma levels in patients with metastatic cancer. Nine patients (three men and six women; mean age 48 years, aged 41-68 years) with metastatic cancer received at least 12 immune adsorption procedures. Thrice-weekly immune adsorption separated a low molecular weight (150 000 D) plasma fraction from the patients' blood, passing the plasma fraction through the column in an extracorporeal plasma perfusion circuit. Respective plasma receptor mean concentrations before and after 167 procedures were: sTNF-R1: 1936 +/- 788 pg/mL before treatment vs. 1312 +/- 989 pg/mL after treatment; sTNF-R2: 3140 +/- 1173 pg/mL before treatment vs. 1816 +/- 1 +/- 1677 pg/mL after treatment (P < 0.01 for each inhibitor). Mean reductions in sTNF-R1 (48%), sTNF-R2 (55%), and sIL2-R levels (72%) were observed for treatments 3-12 (P < 0.001). Clinical findings indicated tumor inflammation and necrosis in most patients. Side-effects were low-grade fever, flu-like symptoms; tumor pain and redness, warmth, tenderness, and edema. The column demonstrated safety and efficacy in lowering plasma sTNF-R1, sTNF-R2, and sIL2-R levels. Minor clinical adverse effects common to the use of extracorporeal devices were seen.
Single-course specific immunotherapy with mixed pollen allergoids: results of a multi-centre study.

A short-term immunotherapy vaccine for the treatment of pollen allergy has been developed utilising L-tyrosine adsorbed allergoids. The reduced number of injections could provide advantages over long-term therapy schedules. This would improve compliance and support application of specific immunotherapy (SIT) to a greater extent. We report a multicenter study to evaluate the efficacy and safety of this treatment in a clinical practice setting.



Patients (n = 1808) with a diagnosis of sensitivities to various pollens and symptoms of allergic asthma and/or allergic rhinitis and/or allergic conjunctivitis were selected. The vaccine formulation was made up according to individual sensitivities and contained L-tyrosine adsorbed allergoids. The patients were treated with a 3-injection initial course followed by a 3-injection maintenance course. Efficacy was measured by consumption of symptomatic anti-allergic medication compared with that in the previous season and by physician assessment using a 5-point scale. All adverse events were recorded.



Efficacy was demonstrated by a considerable decrease in regular and frequent use of medication compared with that in the previous season (p < 0.001). In addition, in 80 % of the patients, the physician's assessment was either "good" or "very good". These outcomes were unaffected by the closeness of the treatment course to the onset of the pollen season. Tolerability was good and most local and systemic reactions were mild.



The treatment of pollen-allergic patients with a short-term SIT using a 6-injection pollen allergoid/L-tyrosine vaccine in a clinical practice setting provided a high level of efficacy with a low incidence of mainly mild adverse events.
A randomized trial to promote physical activity among breast cancer patients.

Physical activity (PA) has been shown to provide health benefits for breast cancer patients. The effects of augmenting oncology health care provider (HCP) advice for PA with 3 months of telephone counseling versus contact control were evaluated in a randomized trial.



After receiving brief HCP advice to become physically active, 192 women (age in years: M = 60.0, SD = 9.9) who had completed treatment for Stage 0-IV breast cancer were randomized to telephone counseling to support PA (n = 106) or contact control (n = 86). Their PA, motivational readiness, fatigue, and physical functioning were assessed at baseline (before receiving HCP advice), 3, 6, and 12 months.



Telephone counseling produced significant effects on the primary outcome of moderate-intensity PA of about 30 min/week at both 3 months (95% CI = 0.44, 57.32) and 6 months (95% CI = 3.06, 61.26). Intervention participants were also more than twice as likely as control participants to report improvements in achieving PA guidelines of at least 150 min/week at 3 (OR = 2.43, 95% CI = 1.18, 4.98) and 6 months (OR = 2.11, 95% CI = 1.00-4.48). Telephone counseling was significantly more effective than contact control in increasing motivational readiness for PA at all follow-ups (ORs = 3.93-6.28, all ps <.003). No between-groups differences were found for fatigue, while differential improvements in physical functioning did not remain significant past 3 months (p = .01).



HCP advice plus telephone counseling improved PA among breast cancer patients at 3 and 6 months and also differentially improved patients' motivational readiness at all follow-ups, suggesting the potential for exercise promotion in cancer follow-up care.
Phase I clinical and pharmacokinetic trial of the podophyllotoxin derivative NK611 administered as intravenous short infusion

NK611 is a novel podophyllotoxin derivative. Compared with etoposide, NK611 carries a dimethyl-amino group at the D-glucose moiety. The antitumor activity of NK611 showed to be equal or superior to etoposide in a variety of in vitro and in vivo tumor models. The aim of our present study was to determine the maximum tolerated dose and the dose-limiting toxicities of NK611 administered as intravenous infusion over 30 min every 28 days.  45 patients (7 female, 38 male; median age 54 [range 37–73]) were enrolled. In a first stage, NK611 was administered without hematopoietic growth factor support; in a second stage, G-CSF was used for further dose escalation. Toxicities were assessed using WHO-criteria.  Initially, the dose was escalated from 60 mg/m2 to 120 mg/m2. In a second patient cohort, doses were further escalated with G-CSF support with doses ranging from 140 mg/m2 to 250 mg/m2. Dose-limiting toxicities were granulocytopenia and thrombocytopenia. Non-hematologic toxicities consisted of alopecia, mild nausea, and infection. Four partial responses were observed: two at 200 mg/m2 (pleural mesothelioma, response duration 7 months, and non-small cell lung cancer, response duration 13 months), and two at 250 mg/m2 (hepatocellular carcinoma, response duration 7 months, and non-small cell lung cancer, response duration 2 months). Pharmacokinetic analyses were performed in all patients. Using an open 3-compartment model, the terminal half-life (t1/2γ) was 14.7 ± 3.7 h. The AUC at 250 mg/m2 was determined to be 330 ± 147 μg/mlh, the plasma clearance of NK611 was 16.2 ± 8.2 ml/min · m2 and the Vss was 16.8 ± 3.3 l/m2. Protein binding of NK611 was 98.7%.  the recommended dose for clinical Phase II studies is 120 mg/m2 without G-CSF support and 200 mg/m2 with G-CSF support.
A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection

To determine if there is a biological mechanism that explains the association between HIV disease progression and increased mortality with low circulating vitamin D levels; specifically, to determine if restoring vitamin D levels induced T-cell functional changes important for antiviral immunity.



This was a pilot, open-label, three-arm prospective phase 1 study.



We recruited 28 patients with low plasma vitamin D (<50 nmol/l 25-hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment-naive) and 11 healthy controls, who received a single dose of 200 000 IU oral cholecalciferol. Advanced T-cell flow cytometry methods measured CD4 T-cell function associated with viral control in blood samples at baseline and 1-month after vitamin D supplementation.



One month of vitamin D supplementation restored plasma levels to sufficiency (>75 nmol/l) in 27 of 28 patients, with no safety issues. The most striking change was in HIV+ HAART+ patients, where increased frequencies of antigen-specific T cells expressing macrophage inflammatory protein (MIP)-1β - an important anti-HIV blocking chemokine - were observed, with a concomitant increase in plasma MIP-1β, both of which correlated significantly with vitamin D levels. In addition, plasma cathelicidin - a vitamin D response gene with broad antimicrobial activity - was enhanced.



Vitamin D supplementation modulates disease-relevant T-cell functions in HIV-infected patients, and may represent a useful adjunct to HAART therapy.
Relationship of vitamin D, HIV, HIV treatment, and lipid levels in the Women's Interagency HIV Study of HIV-infected and uninfected women in the United States.

Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±antiretroviral therapy [ART]) were investigated with Women's Interagency HIV Study data (n = 1758 middle-aged women) using multivariable regression. Sixty-three percent of women had vitamin D deficiency. Median 25-hydroxyvitamin D (25-OH vitamin D) was highest in HIV-infected + ART-treated women (17 ng/mL; P < .001) and was the same in HIV-uninfected or HIV-infected women without ART (14 ng/mL). Vitamin D levels were lower if efavirenz (EFV) was included in ART (15 versus 19 ng/mL; P < .001). The most common lipid abnormality was high triglycerides (≥200 mg/dL) in HIV-infected + ART-treated women (13% versus 7% of HIV-infected without ART and 5% of HIV-uninfected; P < .001), with a positive relationship between 25-OH vitamin D and triglycerides (95% confidence interval 0.32-1.69; P < .01). No relationships between 25-OH vitamin D and cholesterol were detected. Vitamin D deficiency is common irrespective of HIV status but influenced by HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART-treated HIV-infected women and unrelated to cholesterol.
A 10-year comparison of anterior cruciate ligament reconstructions with hamstring tendon and patellar tendon autograft: a controlled, prospective trial.

There are no controlled, prospective studies comparing the 10-year outcomes of anterior cruciate ligament (ACL) reconstruction using patellar tendon (PT) and 4-strand hamstring tendon (HT) autografts.



Comparable results are possible with HT and PT autografts.



Cohort study; 
One hundred eighty ACL-deficient knees that met inclusion criteria underwent ACL reconstruction (90 HT autograft, 90 PT autograft) by one surgeon and were treated with an accelerated rehabilitation program. All knees were observed in a prospective fashion with subjective, objective, and radiographic evaluation at 2, 5, 7, and 10-year intervals.



At 10 years, there were no differences in graft rupture rates (7/90 PT vs. 12/90 HT, P = .24). There were 20 contralateral ACL ruptures in the PT group, compared with 9 in the HT group (P = .02). In all patients, graft rupture was associated with instrumented laxity >2 mm at 2 years (P = .001). Normal or near-normal function of the knee was reported in 97% of patients in both groups. In the PT group, harvest-site symptoms (P = .001) and kneeling pain (P = .01) were more common than in the HT group. More patients reported pain with strenuous activities in PT knees than in HT knees (P = .05). Radiographic osteoarthritis was more common in PT knees than the HT-reconstructed knees (P = .04). The difference, however, was composed of patients with mild osteoarthritis. Other predictors of radiographic osteoarthritis were <90% single-legged hop test at 1 year and the need for further knee surgery. An "ideal" outcome, defined as an overall International Knee Documentation Committee grade of A or B and a radiographic grade of A at 10 years after ACL reconstruction, was associated with <3 mm of instrumented laxity at 2 years, the absence of additional surgery in the knee, and HT grafts.



It is possible to obtain excellent results with both HT and PT autografts. We recommend HT reconstructions to our patients because of decreased harvest-site symptoms and radiographic osteoarthritis.
Intravitreal Bevacizumab with or without triamcinolone for refractory diabetic macular oedema.

We evaluate the effect of intravitreal injections of Bevacizumab (IVB) alone or combined with triamcinolone (IVT) in the first injection for treatment of refractory diabetic macular oedema (DME). Sixty eyes of sixty patients with refractory DME were included. Half of them received injections of IVB (1.25 mg/0.05 ml) or combined IVB and IVT (1.25 mg/0.05 ml and 2 mg/0.05 ml respectively). The primary outcome measure was change in central macular thickness (CMT). Secondary outcome measures were change in best-corrected logMAR visual acuity (BCVA) and incidence of potential adverse events. Central macular thickness was reduced significantly in both the IVB and IVB/IVT groups. At week 24, CMT change compared to the baseline was -93.7 microm (95% CI, -172.2 to -19.26) in the IVB group and -93.1 microm (95% CI, -154.4 to -29.7) in the IVB/IVT group. There was not a significant difference between the IVB and the IVB/IVT groups. Improvement of BCVA was initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively. Anterior chamber reaction was noticed in six (20%) and six (20%) eyes respectively in the IVB and IVB/IVT groups the day after injection, and it resolved with no sequel. Elevation of intraocular pressure (IOP) occurred in two eyes (6%) in the IVB/IVT group. Intravitreal injections of Bevacizumab had a beneficial effect on refractory DME in terms of CMT reduction and BCVA improvement. Addition of triamcinolone in the injection seemed to induce earlier visual improvement; however, it did not show any significant additive effect later during follow-up.
Timing of Intubation and Clinical Outcomes in Adults With Acute Respiratory Distress Syndrome.

The prevalence, clinical characteristics, and outcomes of critically ill, nonintubated patients with evidence of the acute respiratory distress syndrome remain inadequately characterized.



Secondary analysis of a prospective observational cohort study.



Vanderbilt University Medical Center.



Among adult patients enrolled in a large, multi-ICU prospective cohort study between the years of 2006 and 2011, we studied intubated and nonintubated patients with acute respiratory distress syndrome as defined by acute hypoxemia (PaO2/FIO2 ≤ 300 or SpO2/FIO2 ≤ 315) and bilateral radiographic opacities not explained by cardiac failure. We excluded patients not committed to full respiratory support.



None.



Of 457 patients with acute respiratory distress syndrome, 106 (23%) were not intubated at the time of meeting all other acute respiratory distress syndrome criteria. Nonintubated patients had lower morbidity and severity of illness than intubated patients; however, mortality at 60 days was the same (36%) in both groups (p = 0.91). Of the 106 nonintubated patients, 36 (34%) required intubation within the subsequent 3 days of follow-up; this late-intubation subgroup had significantly higher 60-day mortality (56%) when compared with the both early intubation group (36%, P<0.03) and patients never requiring intubation (26%; p = 0.002). Increased mortality in the late intubation group persisted at 2-year follow-up. Adjustment for baseline clinical and demographic differences did not change the results.



A substantial proportion of critically ill adults with acute respiratory distress syndrome were not intubated in their initial days of intensive care, and many were never intubated. Late intubation was associated with increased mortality. Criteria defining the acute respiratory distress syndrome prior to need for positive pressure ventilation are required so that these patients can be enrolled in clinical studies and to facilitate early recognition and treatment of acute respiratory distress syndrome.
A prospective study of supraventricular activity and incidence of atrial fibrillation.

Atrial fibrillation (AF) episodes are thought to be started by an electrical trigger reaching susceptible atria. Such a trigger could be present long before the occurrence of sustained symptomatic arrhythmia.



We sought to determine whether supraventricular extrasystoles (SVESs) and supraventricular tachycardias (SVTs) measured at 24-hour Holter electrocardiogram were associated with an increased incidence of AF.



In 1998-2000, 389 individuals (44% men; mean age 65 years) were examined using 24-hour Holter electrocardiogram. Six individuals with known prevalent AF were excluded. After a mean follow-up of 10.3 years, there were 45 cases of incident AF. Hazard ratios (HRs) were computed using multivariable Cox regression adjusting for age, sex, systolic blood pressure, height, weight, smoking, and homeostatic model assessment of insulin resistance.



Frequency of SVESs as well as SVT episodes per hour were independent predictors of incident AF (HR per log unit 1.38; 95% confidence interval 1.14-1.68; P = .001 and HR 1.95; 95% confidence interval 1.21-3.13; P = .006, respectively). Further adjustment for education level, alcohol use, use of medication, and physical activity did not substantially alter the results, nor did analysis using competing risks regression accounting for a competing risk of death. The maximum duration of SVT or the heart rate at SVT was not significantly associated with the incidence of AF.



SVESs and SVTs independently predict AF. The prognostic significance was similar for SVESs, SVTs, and a combination of the two. Repeated efforts to detect AF could be of merit in individuals with frequent supraventricular activity.
Correlation of p53 status with outcome of neoadjuvant chemotherapy using paclitaxel and doxorubicin in stage IIIB breast cancer.

The role of p53 in modulating apoptosis has suggested that it may affect efficacy of anticancer agents. We prospectively evaluated p53 alterations in 73 patients with locally advanced breast cancer (IIIB) submitted to neoadjuvant chemotherapy.



Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression using immunohistochemistry and DNA sequencing.



An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of the 25 patients who obtained a complete clinical response, two were classified as positive (P = 0.004, chi-square). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, chi-square).  The combination is highly effective in locally advanced breast cancer. A negative expression of p53 indicates a higher chance of responding to this regimen. The p53 status may be used as a biological marker to identify those patients who would benefit from more aggressive treatments.