nils-herrmann/clean_scirepeval huggingface dataset:
Memory Function — Effects of Different Antihypertensive Drugs

Improvement in the efficacy of newer antihypertensive agents has resulted in consideration of the side effects of drug therapy. Impairment of memory function resulting from antihypertensive therapy has been clinically suspected. This observation has been supported by a study in which the effects of methyldopa and propranolol on memory function were reported. Recently, memory function has been assessed in a group of patients treated with either a β-blocker (atenolol) or an angiotensin-converting enzyme inhibitor (enalapril) in a randomised, observer-blind study in moderate essential hypertension. The patients were assessed, on placebo and after 16 weeks of treatment on active therapy, by use of a series of 4 memory function tests related to everyday life. In the hypertension study group, 13 received atenolol and 12 received enalapril. Similar reduction of diastolic pressure occurred in both groups, but systolic pressure was significantly reduced in the enalapril group (p < 0.05). In the atenolol group memory performance scores were consistently lower than in the placebo phase in 9 of 28 estimates of memory function. In the enalapril group there were no significant changes. The study indicated that atenolol might produce mild memory impairment, whereas enalapril was devoid of any measurable effect on memory function.
Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin.

An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes.



Enrolled patients (n = 192) had HbA(1c) >7% and < or =12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide < or =2.5 mg, metformin < or =500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n = 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n = 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16.



Final HbA(1c) values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA(1c) (-1.28 vs. -0.67%; P < 0.001) and of fasting plasma glucose (FPG) (-39 vs. -21 mg/dl; P = 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 A.M. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens.



The addition of repaglinide to metformin therapy resulted in reductions of HbA(1c) and FPG values that were significantly greater than the reductions observed for addition of nateglinide.
Pharmacokinetic modeling and dosage adaptation of biapenem in Japanese patients during continuous venovenous hemodiafiltration.

The present study examined the pharmacokinetics of biapenem during continuous venovenous hemodiafiltration (CVVHDF) and assessed the pharmacodynamic exposure, based on a pharmacokinetic model, to consider biapenem dosage adaptation in CVVHDF. Biapenem (300 mg) was administered by 2-h infusion to seven critically ill patients receiving CVVHDF. The flow rates were 60 ml/min for blood, 800 ml/h for filtrate, and 600 ml/h for dialysate. The drug concentrations in plasma and filtrate-dialysate were determined by high-performance liquid chromatography and analyzed pharmacokinetically. The sieving coefficient was 0.92 +/- 0.06 (mean +/- SD). The simulation curves, using a multicompartment model, were well fitted to the measurements in plasma and filtrate-dialysate. The clearance by CVVHDF and the clearance by non-CVVHDF routes were 1.29 +/- 0.08 and 6.14 +/- 1.89 l/h, respectively. The multicompartment model was used to assess the pharmacodynamic exposure (time above the minimum inhibitory concentration of 4 microg/ml) in plasma. When the total daily dose was 600 mg, the duration of time was greater at 300 mg every 12 h than at 600 mg every 24 h. The minimum dosages needed to achieve more than 30% of the dosing interval at filtrate-dialysate flow rates of 1.4, 2.8, and 5.6 l/h were 300 mg every 12 h, 600 mg every 12 h, and 600 mg every 12 h, respectively. These results suggested that low doses or increased dosing intervals should be avoided in patients receiving this renal replacement technique. Information on pharmacodynamic exposure obtained from this model may help us to determine the appropriate biapenem dosage for CVVHDF. Moreover, our pharmacokinetic model may be useful for further pharmacokinetic studies of biapenem.
Effects of donepezil on cortical metabolic response to activation during 18FDG-PET in Alzheimer’s disease: a double-blind cross-over trial

Cholinergic enhancement is among the best established treatments of Alzheimer’s disease (AD). The cognitive effects of treatment are thought to be mediated by improvement of neuronal transmission. Positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) by measuring cortical metabolic response to activation assesses integrity of neuronal transmission in vivo. To determine the effects of treatment with donepezil, a centrally selective acetylcholinesterase inhibitor, on cortical metabolism in AD using (18)FDG-PET. We enrolled 23 patients, 18 of which completed the study, with mild to moderate probable AD (mini-mental status exam scores of 15–28, inclusive) in a double-blind cross over trial of 8 weeks donepezil compared to 8 weeks placebo with repeated double (18)FDG-PET examinations during passive audio-visual stimulation. Effects of treatment on cortical metabolic response to stimulation were determined with a linear model on a voxel level using Statistical Parametric Mapping (SPM 99, Wellcome Department of Imaging Neuroscience, London). Effects of treatment on cognitive measures were not different between donepezil and placebo. During passive audio-visual stimulation, patients showed activation in posterior visual and auditory areas and decreased activation in frontal cortex and basal ganglia. Resting state metabolism was increased with donepezil in left prefrontal cortex and decreased in right hippocampus. Cortical response to activation was increased in right hippocampus with donepezil compared to placebo. Donepezil treatment shows a spatially limited functional effect on right hippocampus and left prefrontal cortical metabolism, independently of clinical response to treatment.
Multicenter analysis of treatment outcomes in adult patients with lymphoblastic lymphoma who received hyper-CVAD induction followed by hematopoietic stem cell transplantation

The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen has been widely used for lymphoblastic lymphoma (LBL) as a primary treatment. However, there is few data about its treatment outcome in Asian patients. Thus, we conducted this study to evaluate the efficacy of hyper-CVAD induction and stem cell transplantation (SCT) consolidation in LBL patients. The treatment responses of 49 patients treated with the hyper-CVAD regimen were retrospectively analyzed in 13 institutions. Given 24 patients who responded to hyper-CVAD underwent consolidation treatment with SCT, overall survival (OS) and progression-free survival (PFS) of patients who received SCT were compared with patients who did not. The overall response rate was 79 %: 73 % (36/49) complete responses, 6 % (3/49) partial responses, and 4 % (2/49) induction deaths. The major limitation for the delivery of the planned hyper-CVAD cycles was hematological toxicity. Among 39 responders, 24 patients underwent autologous (n = 16) and allogeneic SCT (n = 8) consolidation. Their 3-year OS and PFS rates were 76 and 78 %, respectively, and there was no difference in survival outcomes between autologous and allogeneic SCT. However, 15 patients without SCT consolidation showed poorer PFS even though they all achieved complete response. Thus, only seven patients maintained their response at the time of analysis. In conclusion, the hyper-CVAD regimen is effective for remission induction in LBL, and SCT consolidation after hyper-CVAD induction produced better clinical outcomes than did continuation of hyper-CVAD.
A Model of Shared DASD and Multipathing

This paper presents a model of an I/O subsystem in which devices can be accessed from multiple CPUs and/or via alternative channel and control unit paths. The model estimates access response times, given access rates for all CPU-device combinations. Central to the model's algorithm is the estimation of the rotational position sensing (RPS) miss probabilities by means of the maximum entropy principle.
 Performance differences strongly favored the English-based editor.
Granisetron, tropisetron, and ondansetron in the prevention of acute emesis induced by a combination of cisplatin–Adriamycin and by high-dose ifosfamide delivered in multiple-day continuous infusions

The antiemetic efficacy of granisetron, ondansetron and tropisetron was evaluated in patients treated with cisplatin–Adriamycin (CDP/ADM) and ifosfamide (IFO) by continuous infusion (CI). In all, 90 patients with osteosarcoma were randomly assigned to receive granisetron (2 mg/m2), or ondansetron (5.3 mg/m2), or tropisetron (3.3 mg/m2) plus dexamethasone 8 mg/m2. Chemotherapy consisted of CDP (120 mg/m2, 48-h CI) followed by ADM (75 mg/m2, 24-h CI) and then, in the second cycle, delivered 3 weeks later, IFO 15 g/m2 (120-h CI). Complete protection (CP) from emesis was obtained on 59% of the 717 days of treatment, without significant differences among the three study drugs. A significantly higher rate of CP was obtained during chemotherapy with IFO than with CDP/ADM (69% vs 44%; P<0.0001). The rate of CP declined from the first to the last day of treatment for both CDP/ADM (61% to 27%, P<0.0001) and IFO (95% to 43%) cycles (P<0.0001). When CDP/ADM and IFO are delivered on multiple days by CI, granisetron, ondansetron and tropisetron have the same antiemetic efficacy, which declines from the first day onward through successive days.
The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients.

Hyperkalaemia is common in patients with advanced renal disease. In this double-blind, randomized, three-sequence, crossover study, we compared the effect of three dialysate bicarbonate concentrations ([HCO3-]) on the kinetics of serum potassium (K+) reduction during a conventional haemodialysis (HD) session in chronic HD patients.



We studied eight stable HD patients. The choice of dialysate [HCO3-] followed a previously assigned treatment protocol and the [HCO3-] used were low bicarbonate (LB; 27 mmol/l), standard bicarbonate (SB; 35 mmol/l) and high bicarbonate (HB; 39 mmol/l). Polysulphone dialysers and automated machines provided blood flow rates of 300 ml/min and dialysis flow rates of 500 ml/min for each HD session. Blood samples were drawn at 0 (baseline), 15, 30, 60 and 240 min from the arterial extracorporeal line to assess blood gases and serum electrolytes. In three of the eight patients, we measured serum K+ 1 h post-dialysis as well as K+ removal by the dialysis. The same procedures were followed until the completion of the three arms of the study, with a 1 week interval between each experimental arm.



Serum K+ decreased from 5.4+/-0.26 (baseline) to 4.96+/-0.20, 4.90+/-0.19, 4.68+/-0.13 and 4.24+/-0.15 mmol/l at 15, 30, 60 and 240 min, respectively, with LB; from 5.38+/-0.21 to 5.01+/-0.23, 4.70+/-0.25, 4.3+/-0.15 and 3.8+/-0.19 mmol/l, respectively, with SB; and from 5.45+/-0.25 to 4.79+/-0.17, 4.48+/-0.17, 3.86+/-0.16 and 3.34+/-0.11 mmol/l, respectively, with HB (P<0.05 for high vs standard and low [HCO3-] at 60 and 240 min). The decrease in serum K+ correlated with the rise in serum [HCO3-] in all but LB (P<0.05). Potassium rebound was 3.9+/-10.2%, 5.2+/-6.6% and 8.9+/-4.9% for LB, SB and HB dialysates, respectively (P=NS), while total K+ removal (mmol/dialysis) was 116.4+/-21.6 for LB, 73.2+/-12.8 for SB and 80.9+/-15.4 for HB (P=NS).



High dialysate [HCO3-] was associated with a faster decrease in serum K+. Our results strongly suggest that this reduction was due to the enhanced shifting of K+ from the extracellular to the intracellular fluid compartment rather than its removal by dialysis. This finding could have an impact for those patients with life-threatening pre-HD hyperkalaemia.
Changing trends in prognostic factors for patients with multiple myeloma after autologous stem cell transplantation during the immunomodulator drug/proteasome inhibitor era

We evaluated the clinical significance of prognostic factors including the International Staging System (ISS) and modified European Group for Blood and Marrow Transplantation response criteria in 1650 Japanese patients with multiple myeloma (MM) who underwent upfront single autologous stem cell transplantation (ASCT). We categorized patients into two treatment cohorts: pre-novel agent era (1995-2006) and novel agent era (2008-2011). The combined percentage of pre-ASCT complete response and very good partial response cases (463 of 988, 47%) significantly increased during the novel agent era compared with the pre-novel agent era (164 of 527, 31%; P < 0.0001). The 2-year overall survival (OS) rate of 87% during the novel agent era was a significant improvement relative to that of 82% during the pre-novel agent era (P = 0.019). Although significant differences in OS were found among ISS stages during the pre-novel agent era, no significant difference was observed between ISS I and II (P = 0.107) during the novel agent era. The factors independently associated with a superior OS were female gender (P = 0.002), a good performance status (P = 0.024), lower ISS (P < 0.001), pre-ASCT response at least partial response (P < 0.001) and ASCT during the novel agent era (P = 0.017). These results indicate that the response rate and OS were significantly improved, and the ISS could not clearly stratify the prognoses of Japanese patients with MM who underwent upfront single ASCT during the novel agent era.
Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer mortality. Carbohydrate antigen 19.9 (CA19.9), the only tumor marker available to detect and monitor PDAC, is not sufficiently sensitive and specific to consistently differentiate early cancer from benign disease. In this study, we aimed to validate recently discovered serum protein biomarkers for the early detection of PDAC and ultimately develop a biomarker panel that could discriminate PDAC from other benign disease better than the existing marker CA19.9.



We performed a retrospective blinded evaluation of 400 serum samples collected from individuals recruited on a consecutive basis. The sample population consisted of 250 individuals with PDAC at various stages, 130 individuals with benign conditions and 20 healthy individuals. The serum levels of each biomarker were determined by ELISAs or automated immunoassay.



By randomly splitting matched samples into a training (n = 186) and validation (n = 214) set, we were able to develop and validate a biomarker panel consisting of CA19.9, CA125, and LAMC2 that significantly improved the performance of CA19.9 alone. Improved discrimination was observed in the validation set between all PDAC and benign conditions (AUCCA19.9 = 0.80 vs. AUCCA19.9+CA125+LAMC2 = 0.87; P < 0.005) as well as between early-stage PDAC and benign conditions (AUCCA19.9 = 0.69 vs. AUCCA19.9+CA125+LAMC2 = 0.76; P < 0.05) and between early-stage PDAC and chronic pancreatitis (CP; AUCCA19.9 = 0.59 vs. AUCCA19.9+CA125+LAMC2 = 0.74; P < 0.05).



The data demonstrate that a serum protein biomarker panel consisting of CA125, CA19.9, and LAMC2 is able to significantly improve upon the performance of CA19.9 alone in detecting PDAC.
Correlation between tumor size and blood volume in lung tumors: a prospective study on dual-energy gemstone spectral CT imaging

The purpose of this study was to investigate the relationship between tumor size and blood volume for patients with lung tumors, using dual-energy computed tomography (DECT) and a gemstone spectral imaging (GSI) viewer. During the period from March 2011 to March 2013, 50 patients with 57 medically inoperable lung tumors underwent DECT before stereotactic body radiotherapy (SBRT) of 50-60 Gy in 5-6 fractions. DECT was taken for pretreatment evaluation. The region-of-interest for a given spatial placement of the tumors was set, and averages for CT value, water density and iodine density were compared with tumor size. The average values for iodine density in tumors of ≤ 2 cm, 2-3 cm, and >3 cm maximum diameter were 24.7, 19.6 and 16.0 (100 µg/cm(3)), respectively. The average value of the iodine density was significantly lower in larger tumors. No significant correlation was detected between tumor size and average CT value or between tumor size and average water density. Both the average water density and the average CT value were affected by the amount of air in the tumor, but the average iodine density was not affected by air in the tumor. The average water density and the average CT value were significantly correlated, but the average iodine density and the average CT value showed no significant correlation. The blood volume of tumors can be indicated by the average iodine density more accurately than it can by the average CT value. The average iodine density as assessed by DECT might be a non-invasive and quantitative assessment of the radio-resistance ascribable to the hypoxic cell population in a tumor.
Differentiated thyroid cancer: a new perspective with radiolabeled somatostatin analogues for imaging and treatment of patients.

The expression of somatostatin receptors (SSTR) in thyroid cells may offer the possibility to identify metastatic lesions and to select patients for peptide receptor radionuclide therapy (PRRT). We investigated (68)Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) to select patients with progressive differentiated thyroid cancer (DTC) for PRRT as well as treatment response and toxicity in treated patients.



We enrolled 41 patients with progressive radioiodine-negative DTC (24 women and 17 men; mean age=54.3 years, median=59 years, range=19-78 years). In all patients, [(18)F]FDG-PET/CT was performed to determine recurrent disease with enhanced glucose metabolism, and (68)Ga-DOTATOC PET/CT was used to identify SSTR expression. Dosimetric evaluation was performed with (111)In-DOTATOC scintigraphy. Eleven patients were treated with PRRT receiving a fractionated injection of 1.5-3.7 GBq (90)Y-DOTATOC/administration. Serial (68)Ga-DOTATOC PET/CT scans were performed in all treated patients to evaluate treatment response. Parameters provided by (68)Ga-DOTATOC PET/CT were analyzed as potential therapeutic predictors to differentiate responding from nonresponding. In all treated patients, adverse events and toxicity were recorded.



(68)Ga-DOTATOC PET/CT were positive in 24/41 of radioiodine-negative DTC patients. Based on the high expression of SSTR detected by (68)Ga-DOTATOC PET/CT, 13 patients were suitable for PRRT. Two out of 13 patients were not treated due to the lack of fulfillment of other study inclusion criteria. PRRT induced disease control in 7/11 patients (two partial response and five stabilization) with a duration of response of 3.5-11.5 months. Objective response was associated with symptoms relief. Functional volume (FV) over time obtained by PET/CT was the only parameter demonstrating a significant difference between lesions responding and nonresponding to PRRT (p=0.001). Main PRRT adverse events were nausea, asthenia, and transient hematologic toxicity. One patient experienced permanent renal toxicity.



In our series, SSTR imaging provided positive results in more than half of the cases with radioiodine-negative DTC, and about one third of patients were eligible for PRRT. (68)Ga-DOTATOC PET/CT seems a reliable tool both for patient selection and evaluation of treatment response. In our experience, FV determination over time seems to represent a reliable parameter to determine tumor response to PRRT, although further investigations are needed to better define its role.
Now You Can Compete With Anyone: Balancing Players of Different Skill Levels in a First-Person Shooter Game

When player skill levels differ widely in a competitive First-Person Shooter (FPS) game, enjoyment suffers: weaker players become frustrated and stronger players become less engaged. Player balancing techniques attempt to assist the weaker player and make games more competitive, but these techniques have limitations for deployment when skill levels vary substantially. We developed new player balancing schemes to deal with a range of FPS skill difference, and tested these techniques in one-on-one deathmatches using a commercial-quality FPS game developed with the UDK engine. Our results showed that the new balancing schemes are extremely effective at balancing, even for players with large skill differences. Surprisingly, the techniques that were most effective at balancing were also rated as most enjoyable by both players -- even though these schemes were the most noticeable. Our study is the first to show that player balancing can work well in realistic FPS games, providing developers with a way to increase the audience for this popular genre. In addition, our results demonstrate the idea that successful balancing is as much about the way the technique is applied as it is about the specific manipulation.
Treating fibromyalgia with mindfulness-based stress reduction: Results from a 3-armed randomized controlled trial

Mindfulness-based stress reduction (MBSR) is a structured 8-week group program teaching mindfulness meditation and mindful yoga exercises. MBSR aims to help participants develop nonjudgmental awareness of moment-to-moment experience. Fibromyalgia is a clinical syndrome with chronic pain, fatigue, and insomnia as major symptoms. Efficacy of MBSR for enhanced well-being of fibromyalgia patients was investigated in a 3-armed trial, which was a follow-up to an earlier quasi-randomized investigation. A total of 177 female patients were randomized to one of the following: (1) MBSR, (2) an active control procedure controlling for nonspecific effects of MBSR, or (3) a wait list. The major outcome was health-related quality of life (HRQoL) 2 months post-treatment. Secondary outcomes were disorder-specific quality of life, depression, pain, anxiety, somatic complaints, and a proposed index of mindfulness. Of the patients, 82% completed the study. There were no significant differences between groups on primary outcome, but patients overall improved in HRQoL at short-term follow-up (P=0.004). Post hoc analyses showed that only MBSR manifested a significant pre-to-post-intervention improvement in HRQoL (P=0.02). Furthermore, multivariate analysis of secondary measures indicated modest benefits for MBSR patients. MBSR yielded significant pre-to-post-intervention improvements in 6 of 8 secondary outcome variables, the active control in 3, and the wait list in 2. In conclusion, primary outcome analyses did not support the efficacy of MBSR in fibromyalgia, although patients in the MBSR arm appeared to benefit most. Effect sizes were small compared to the earlier, quasi-randomized investigation. Several methodological aspects are discussed, e.g., patient burden, treatment preference and motivation, that may provide explanations for differences. In a 3-armed randomized controlled trial in female patients suffering from fibromyalgia, patients benefited modestly from a mindfulness-based stress reduction intervention.