nils-herrmann/clean_scirepeval huggingface dataset:
Lack of effect of a moderate hypocaloric diet on visfatin levels in morbid obese patients: relationship with insulin resistance.

The insulin-mimetic adipocytokine visfatin has been related to obesity. The aim of this study was to examine whether weight loss could change visfatin concentrations in morbidly obese patients and its relationship with insulin resistance.



This was an interventional study analyzing a population of 41 morbidly obese patients. A biochemical analysis was realized before and after 2 months on a hypocaloric diet.



After weight loss (average 4.41%), BMI, weight, fat mass, fat free mass, waist circumference, systolic blood pressure, serum glucose, total cholesterol, insulin and HOMA decreased. The serum concentrations of visfatin did not decrease (43.5 + 30.8 vs. 47.1 + 38.1 ng/ml). In the multivariate analysis visfatin concentrations as a dependent variable, only C reactive protein remained as an independent predictor in the model before diet, with an increase of 1.82 ng/ml (CI 95%: 0.02 - 3.61) basal visfatin concentrations with each increase of 1 mg/dl of CRP. Only HOMA remained as an independent predictor in the model after diet, with an increase of 11.4 ng/ml (CI 95%: 1.76 - 21.11) posttreatment visfatin concentrations with each increase of 1 unit HOMA.



Weight reduction after a 2 months on a hypocaloric diet is not associated with a significant change in circulating visfatin in morbidly obese patients.
Clinical course of patients with insufficient viral suppression during entecavir therapy in genotype C chronic hepatitis B.

The clinical course of patients with insufficient virologic suppression diagnosed with chronic hepatitis B undergoing entecavir therapy is unclear.



We retrospectively investigated the long-term clinical outcomes of entecavir treatment for more than 12 months in 355 nucleos(t)ide-naïve chronic hepatitis B patients, particularly those with primary non-response or partial virologic response.



The median duration of entecavir therapy was 40 months (range, 12-64 months). Virologic response was achieved in 315 patients (88.7%). One hundred forty-four (96.6%) of 149 HBeAg-negative patients achieved virologic response. Among 206 HBeAg-positive patients, 52 (25.2%) achieved HBeAg seroconversion. Virologic breakthrough was observed in 7 patients (2.0%). Of these 7 patients, 5 (1.4%) had genotypic resistance to entecavir. Primary non-response and partial virologic response were evident in 6 (1.7%) and 63 (17.7%) patients, respectively. During continuous prolonged entecavir therapy, virologic response of patients with primary non-response and partial virologic response was achieved in 6 (100%) and 28 (44.4%) patients, respectively.



The vast majority of chronic hepatitis B patients in this study achieved virologic response through prolonged entecavir therapy, with only 1.4% chance of viral resistance. Furthermore, all patients with primary non-response were able to achieve virologic response without adjustment of antiviral therapy.
Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1-34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3-4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds.
Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma.

A prospective comparative trial of allogeneic versus autologous bone marrow transplant (BMT) was conducted. Sixty-six consecutive patients (median age, 41; range, 15 to 60; female:male ratio = 21:45) entered this clinical trial. Priority for allogeneic BMT was given to patients who were 55 or younger and had a major histocompatibility complex-matched or 1-antigen-disparate sibling donor. Autologous BMT was offered to all other patients whose age was 60 or younger. Patients who had no sibling donor and who had BM involvement at the time of evaluation were not eligible. Thirty-one patients received an allograft, and 35 patients received an autograft. Thirteen patients received a BM graft purged with 4-hydroperoxycyclophosphamide because of previous BM involvement. Patients who had previous radiation to the thoracic and/or abdominal areas of more than 20 Gy received a preparative regimen consisting of cyclophosphamide (1,800 mg/m2/d for 4 days), VP-16 (200 mg/m2 every 12 hours for 8 doses), and 1,3-bis(2-chloroethyl)-1-nitrosourea (600 mg/m2 as 1 dose). Other patients received cyclophosphamide 1,800 mg/m2/d for 4 days followed by total body irradiation of 12 Gy administered as a single daily fraction over 4 days. With a median follow-up of 14 months, the progression-free survival (PFS) for autograft and allograft recipients was 24% +/- 8% (+/- SE) and 47% +/- 9%, respectively, (P = .21). However, the probability of disease progression was significantly higher in the autologous group (69% +/- 9%) than in the allogeneic group (20% +/- 10%; P = .001). When other confounding prognostic factors were adjusted in the multivariate analysis, chemosensitive disease and allograft were found to have a significant favorable influence on probability of disease progression (P = .03 and .003), but only chemosensitive disease had a significant influence on the PFS (P < .002). Our results suggest the existence of graft-versus-lymphoma effect and also support the rationale of using immunotherapy after autologous BMT. Allogeneic BMT should be preferable to autologous BMT in younger patients with lymphoma.
TALL: A list processor for the Philco 2000 computer

Several of the computer languages that are oriented toward problems in symbol manipulation use a list type of memory organization.1 The advantages of such a memory organization have been discussed elsewhere and will not be repeated here. The purpose of this note is to describe the method used in realizing a list language on the Philco 2000.
Information Processing Language V (IPL-V) was chosen as the source language for the list processor for the 2000 because this language has been well documented and has been implemented on several computers.2 Heretofore, IPL-V has been implemented as an interpretive system. The interpretive system has three major components: (1) a loader which translates card images into internal machine words; (2) an interpreter which decodes instructions; and (3) a set of primitive processes, the “J's,” which make up the bulk of the instruction vocabulary. The implementation of such an interpretive system has been a rather lengthy procedure usually estimated as taking six man-months.
, Carlos Step-Down of Enalapril Treatment for Arterial Hypertension

Enalapril treatment (20 mg every 12 hours) of 24 patients with essential hypertension and left ventricular (LV) hypertrophy established normal blood pressures after 8 weeks, and after 5 years, it had reduced LV mass index by 39% (from 148634 to 90616 g/m) and had normalized LV structure and function and QT dispersion. Stepwise reduction of the enalapril dosage from 40 to 30, 20, 10, and 5 mg/d during the eighth year caused no significant change in blood pressure, LV structure, LV systolic function, or QT dispersion, which all likewise remained unaltered during an additional 2-year period of the 5-mg/d regimen. We conclude that for hypertensive patients in whom prolonged treatment with high doses of enalapril has normalized blood pressure, LV structure, LV function, and QT dispersion, the dose may be reduced as much as 8-fold without detriment to cardiovascular control. The use of smaller doses is evidently advantageous from the point of view of health costs.
Safety, Efficacy and Development of Resistance under the New Protease Inhibitor Lopinavir/Ritonavir: 48-Week Results

Within this open-label, uncontrolled prospective trial we evaluated safety, efficacy and development of genotypic resistance under the new protease inhibitor lopinavir/ritonavir (LPV/r) in antiretroviral (ARV) HIV patients. 58 patients with virological failure under their current ARV therapy were started on a LPV/r containing regimen. Median baseline HIV RNA and CD4 count were 4.6 log10 cps/ml (range 2.1–6.4) and 128 × 106/l (0–767), respectively. CD4 count, HIV RNA and metabolic parameters were assessed at weeks 0, 4, 8, 12, 16, 24, 32, 40, 48. Genotypic resistance testing was performed at baseline and again at weeks 12, 24 and 48 in the event of virological failure. Until week 48, viral load (VL) decreased by a median of 1.9 log10 cps/ml (-0.8–3.8). A VL below 80 cps/ml was found in 20/58 patients (34.5%) at week 48. In parallel, CD4 cells increased to a median of 332 × 106/l (8–905). Nine patients discontinued study treatment. At 48 weeks, median triglyceride and cholesterol levels increased significantly. While the median number of overall protease mutations at baseline was four in all patients, it was six in patients virologically failing on LPV/r. The average number of mutations increased significantly to eight at week 48. Several mutations were detected considerably more often in the event of failure than in response to treatment, e. g. at amino acid positions 10, 24, 54, 71, 82, 84. LPV/r is effective in heavily pretreated patients. Discontinuation due to adverse events is infrequent. No individual mutation can be associated with failure on LPV/r. However, a greater number of protease mutations at baseline is associated with poorer treatment outcome and several mutations seem to be related to treatment failure.
Survey of Usual Practice: Dysphagia Therapy in Head and Neck Cancer Patients

There is no standardized dysphagia therapy for head and neck cancer patients and scant evidence to support any particular protocol, leaving institutions and individual speech-language pathologists (SLPs) to determine their own protocols based on “typical” practices or anecdotal evidence. To gain an understanding of current usual practices, a national internet-based survey was developed and disseminated to SLPs who treat head and neck cancer (HNC) patients. From a random sample of 4,000 ASHA SID13 members, 1,931 fit the inclusion criteria, and 759 complete responses were recorded for a 39.3 % response rate. Results were analyzed by institution type as well as by individual clinical experience. While some interesting trends emerged from the data, a lack of uniformity and consensus regarding best practices was apparent. This is undoubtedly due to a paucity of research adequately addressing the efficacy of any one therapy for dysphagia in the HNC population.
Steroids for preventing recurrence of acute severe migraine headaches: a meta-analysis.

Recurrence of migraine headaches after treatment is common. The evidence regarding steroids for preventing migraine headache recurrence is controversial. This meta-analysis examined the effectiveness of steroids for prevention of recurrent headaches.



Databases (PubMed, Embase and the Cochrane Library) and conference proceedings were searched for randomized controlled trials comparing steroids and placebo in the treatment of migraine headaches. Two independent reviewers assessed studies and extracted data. Relative risks (RRs) of headache recurrence and adverse events were calculated and reported with 95% confidence intervals (95% CIs).



Eight studies with 905 patients were included. Pooled analysis showed that when steroids were added to standard abortive therapy they reduced the rate of moderate or severe headache recurrence after 24-72 h of follow-up evaluation (RR = 0.71; 95% CI = 0.59-0.86). There was no significant benefit of steroids compared with placebo in the proportion of totally resolved migraines (RR = 1.11; 95% CI = 0.94-1.32). The side effects of steroids are mild and not significant except for dizziness. Subgroup meta-analysis showed that parenteral dexamethasone tends to be more effective in reducing moderate or severe recurrent headaches (RR = 0.68; 95% CI = 0.55-0.84). However, no significant differences were found between oral administration and parenteral administration of steroids (P = 0.37).



When steroids are added to standard abortive therapy for migraine headaches, they are effective and safe for preventing moderate or severe headache recurrence.
Feasibility of whole-body vibration training in nursing home residents with low physical function: a pilot study.

Whole-body vibration (WBV) training may offer an efficient option to improve physical performance of nursing home residents, but the feasibility of WBV training among frail elderly who require continuous institutional care is still open.



Fifteen nursing home residents (mean age 84 years) with low physical performance (mean SPPB score 3.7) participated in this blinded, randomized controlled pilot trial. The intervention was either a 10 week, twice-a-week progressive vibration training with slight exercises done on a side-alternating device or similar sham training without vibration. Physical performance was assessed with Short Physical Performance Battery (SPPB), Timed Up and Go, walk speed and grip strength tests.



Low 12 Hz frequency was well tolerated with mean 95 % compliance in contrast to higher 18 Hz (or 26 Hz) frequency, which was poorly (<30 %) tolerated. While treatment effects were not significant, the mean change in SPPB score was 0.4 (range from -2 to +4) in the WBV group in contrast to -0.1 (from -3 to +3) in the sham group.



Frail nursing home residents form not only a potential but also challenging target group for physical rehabilitation with WBV. Side-alternating WBV training performed at low 12 Hz frequency was found generally feasible, whereas higher frequencies appeared formidable. Nevertheless, it is possible that physical performance of some frail elderly without contraindications to WBV can be improved with this type of rapidly executable physical training.
A randomised controlled trial of the effect of anticipation of a blood test on blood pressure

Blood pressure is affected by situational anxiety, such as the white coat effect. We hypothesised that blood pressure would also be affected by anticipation of a blood test. Volunteer subjects were recruited on the campus of Birmingham University. Subjects were randomly assigned to intervention and control groups. After a period of rest, three seated blood pressure measurements were taken at 1-min intervals using an electronic sphygmomanometer. Between the second and third measurements subjects in the intervention group were told that a blood test would be carried out after the last measurement. No blood test was carried out. Three blood pressure measurements were made in all 213 randomised subjects. Analysis was by intention-to-treat. In the control group mean systolic and diastolic blood pressure fell in successive measurements. Between the second and third measurements mean systolic blood pressure fell by 1.4 mm Hg in the control group and rose by 2.6 mm Hg in the intervention group (difference 4.0 mm Hg, P < 0.0001). A rise in diastolic blood pressure between the second and third measurements did not reach statistical significance. It was concluded that anticipation of a blood test affects measured systolic blood pressure in volunteers. The practice of taking blood tests at the same time as measuring blood pressure may potentially bias estimations of blood pressure.
Indirubin and Indirubin Derivatives for Counteracting Proliferative Diseases

Indirubin is the active component of Danggui Longhui Wan, a traditional Chinese medicine formulation. The encouraging clinical results from the 1980s obtained in chronic myelocytic leukemia patients treated with indirubin stimulated numerous studies on this compound. These investigations explored the use of indirubin in different types of cancer and reported the synthesis of novel derivatives with improved chemical and pharmacokinetic properties. In this paper, we review the impressive progress that has been made in elucidating the mechanistic understanding of how indirubin and its derivatives affect physiological and pathophysiological processes, mainly by inhibition of cell proliferation and induction of cell death. Furthermore, we survey the therapeutic use of these compounds in combating proliferative diseases such as cancer, restenosis, and psoriasis.
A phase II study of erlotinib in gemcitabine refractory advanced pancreatic cancer.

Erlotinib induced skin toxicity has been associated with clinical benefit in several tumour types. This phase II study evaluated the efficacy of erlotinib, dose escalated to rash, in patients with advanced pancreatic cancer previously treated with gemcitabine.



Erlotinib was given at an initial dose of 150 mg/day, and the dose was escalated by 50mg every 2 weeks (to a maximum of 300 mg/day) until >grade 1 rash or other dose limiting toxicities occurred. Erlotinib pharmacokinetics were performed, and baseline tumour tissue was collected for mutational analysis and epidermal growth factor receptor (EGFR) expression. The primary end-point was the disease control rate (objective response and stable disease >8 weeks).



Fifty-one patients were accrued, and 49 received treatment. Dose-escalation to 200-300 mg of erlotinib was possible in 9/49 (18%) patients. The most common ⩾ grade 3 adverse events included fatigue (6%), rash (4%) and diarrhoea (4%). Thirty-seven patients were evaluable for response, and the best response was stable disease in 12 patients (32% (95% confidence interval (CI) 17-47%)). Disease control was observed in nine patients (24% (95% CI: 10-38%)). Median survival was 3.8 months, and 6 month overall survival rate was 32% (95% CI 19-47%). Mutational analysis and EGFR expression were performed on 29 patients, with 93% having KRAS mutations, none having EGFR mutations, and 86% expressing EGFR. Neither KRAS mutational status nor EGFR expression was associated with survival.



Erlotinib dose escalated to rash was well tolerated but not associated with significant efficacy in non-selected patients with advanced pancreatic cancer.
Frovatriptan and Rizatriptan Economic EVAluation: the FREEVA study

The present pharmacoeconomic study compared the direct and indirect costs of using frovatriptan versus rizatriptan in the acute treatment of migraine. Data on the cost-efficacy of the two triptans were derived from a recently published Italian, multicenter, randomized, double-blind, cross-over patient preference study, comparing frovatriptan versus rizatriptan. The direct costs were obtained by calculating the drug consumption, both of triptans and rescue medications. Prices of currently marketed drugs were obtained from Italian Drug Agency price list. The indirect costs were those related to absenteeism from the workplace due to migraine. 129 of the 148 patients with a current history of migraine randomized to the two study drugs and completing the study were analyzed. The number of attacks treated with only 1 dose of study drug was higher with frovatriptan (157 vs. 147), whereas the number of attacks treated with ≥2 doses of study medication was higher with rizatriptan (122 vs. 110 and 74 vs. 67, respectively). However, more patients treated with frovatriptan took a rescue medication (71 vs. 59). The total direct cost per attack (including study drug rescue medication) was 9.12 € for frovatriptan and 13.54 € for rizatriptan (p < 0.05 between-treatments). As for indirect costs, in the group of patients treated with frovatriptan the mean number of lost working hours was significantly (p < 0.05) lower (1.5 h) compared to the subjects who used rizatriptan (2.8 h). Based on the earned income per unit of work, indirect costs per attack resulted to be 24.55 € for frovatriptan and 45.84 € for rizatriptan. Overall, the total costs, including direct and indirect costs, were evaluated to be 33.67 € for frovatriptan and 59.38 € for rizatriptan, respectively. Within the limitations of this model analysis, frovatriptan was found to be significantly more cost-effective than rizatriptan. This outcome can be explained by the lower acquisition cost of frovatriptan, the need for fewer doses, and the loss of fewer working hours. This finding could drive selection of the most appropriate oral treatment for acute migraine attacks based on both individual patient’s needs and the cost-effectiveness of the available drugs. 2006-002572-17 (EudraCT).
A phase-I Trial Using a Universal GM-CSF-producing and CD40L-expressing Bystander Cell Line (GM.CD40L) in the Formulation of Autologous Tumor Cell-based Vaccines for Cancer Patients with Stage IV disease

Significant antitumor T-cell responses are generated in vitro when human lymphocytes are stimulated with autologous tumor cells in the presence of bystander cells transfected with CD40L and GM-CSF. Our goal was to test this bystander-based vaccine strategy in vivo in cancer patients with stage IV disease. Patients received three intradermal vaccine injections (irradiated autologous tumor cells plus GM.CD40L bystander cells) at 28-day intervals. Patients with no disease progression received three additional vaccines at 4, 12, and 24 months. Patients were monitored for toxicity, tumor response, and tumor-specific immune responses. Twenty-one patients received at least three vaccine injections, with no toxicity attributable to the vaccine. Immunohistochemistry of vaccine injection site biopsies with CD1a and CD86 antibodies confirmed recruitment and activation of dendritic cells. There was no tumor regression after vaccination, but many patients had stable disease, including six of ten melanoma patients. Four patients developed tumor-specific T-cell responses on ELISPOT testing. One patient, who had stable disease for 24 months, demonstrated an increase in MART-1-specific T-cells by tetramer analysis after re-immunization; biopsy of the tumor that progressed 2 years after the onset of vaccination revealed a massive peritumoral and intratumoral T-cell infiltrate. Vaccination of cancer patients with autologous tumor cells and GM.CD40L bystander cells (engineered to express GM-CSF and CD40L) is safe, can recruit and activate dendritic cells, and can elicit tumor-specific T-cell responses. Phase-II trials are underway to evaluate the impact of bystander-based vaccines on melanoma and mantle cell lymphoma.