nils-herrmann/clean_scirepeval huggingface dataset:
Carmustine and streptozocin in refractory melanoma: an attempt at modulation of O-alkylguanine-DNA-alkyltransferase.

The activity of the enzyme O6-alkylguanine-DNA-alkytransferase (AGAT) protects cells from the cytotoxic effects of alkylating agents. This Phase II trial was designed to assess the efficacy of a strategy designed to modulate the resistance to carmustine (BCNU) mediated by AGAT using streptozocin (STZ) in patients with advanced refractory melanoma. Seventeen patients who had failed prior chemotherapy were treated with STZ at 500 mg/m2 daily for 4 days with BCNU at 150 mg/m2 on day 3. Peripheral blood lymphocytes for assay of AGAT activity levels were collected prior to therapy and following the third dose of STZ. There were two partial responses in the 15 patients evaluable for response (13%). Most patients received only a single cycle of therapy due to rapidly progressive disease. Two patients developed fatal pulmonary toxicity, and one developed myelodysplasia. Other toxicities included transient rises in liver function tests. AGAT levels decreased by a mean of 53% in 9 patients but actually increased over baseline in 3 patients while on therapy. Based on these data, BCNU and STZ are not an effective combination for the therapy of advanced refractory melanoma, and pulmonary toxicity due to this combination appears to be increased compared with BCNU alone. STZ is not an effective modulator of AGAT activity when given on this schedule. New strategies designed to deplete AGAT activity using O6-benzylguanine or temozolomide should be explored with careful attention to the possibility that this approach may potentiate both the toxicity and efficacy of BCNU.
Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer

5-Fluorouracil (5-FU) is chemotherapeutic agent widely used for the treatment of colorectal cancer. Unfortunately, advanced colorectal cancer is often resistance to such chemotherapy and poor outcome. An adaptor protein paxillin (PXN) is phosphorylated at Y31/Y118 (pPXN-Y31/Y118) by Src contributes to cell mobility and Ser (S)272 of PXN in LD4 domain is important to the interaction between PXN and Bcl-2. We thus hypothesized that pPXN-Y31/Y118 may be required for Bcl-2 protein stability via PXN interacting with Bcl-2 to confer 5-FU resistance in colorectal cancer. Mechanistically, pPXN-S272 is phosphorylated through pPXN-Y31/Y118-mediated p21 protein-activated kinase 1 (PAK1) activation and pPXN-S272 is required for PXN to interact with Bcl-2. The interaction between PXN and Bcl-2 is essential for Bcl-2 protein stability through phosphorylation of Bcl-2 at S87 (pBcl-2-S87) by pPXN-Y31/Y118-mediated ERK activation. An increase in Bcl-2 expression by PXN is responsible for resistance to 5-FU. The resistance to 5-FU can be abolished by inhibitor of Src and PAK1 or Bcl-2 antagonist in cell and animal models. Among patients, Bcl-2 expression is positively correlated with expression of PXN and pPXN-S272, respectively. Patients with high PXN/high Bcl-2 or high pPXN-S272/high Bcl-2 tumors are commonly to have an unfavorable response to 5-FU-based chemotherapy, compared with patients who have high PXN, high pPXN-S272 or high Bcl-2 tumors alone. Therefore, we suggest that Src, PAK1 or Bcl-2 inhibitor may potentially overcome the resistance of 5-FU-based chemotherapy and consequently to improve outcomes in patients with PXN/Bcl-2 and pPXN-S272/Bcl-2-positive tumors.
Representing and Learning Quality-improving Search Control Knowledge

Generating good, production-quality plans is an essential element in transforming planners from research tools into real-world applications , but one that has been frequently overlooked in research on machine learning for planning. This paper describes quality , an architecture that automatically acquires operational quality-improving control knowledge given a domain theory, a domain-speciic metric of plan quality, and problems which provide planning experience. The framework includes two distinct domain-independent learning mechanisms which differ in the language used to represent the learned knowledge, namely control rules and control knowledge trees, and in the kinds of quality metrics for which they are best suited. quality is fully implemented on top of the prodigy4.0 nonlinear planner and its empirical evaluation has shown that the learned knowledge is able to substantially improve plan quality. Although the learning mechanisms have been developed for prodigy4.0, the framework is general and addresses a problem confronted by any planner that treats planning as a constructive decision-making process.
Cued recall and other cognitive tasks to facilitate dementia recognition in primary care.

To compare the accuracy of commonly used tasks with that of the Visual Association Test (VAT), a conceptually different test involving cued recall of pictorial stimuli, in the recognition of dementia within primary care.



A cross-sectional diagnostic study of concurrent validity.



Twenty-nine German primary care practices.



Four hundred twenty-three individuals in primary care participating in a longitudinal cohort study.



Participants underwent a comprehensive neuropsychological interview. The validated clinical dementia diagnosis was used as reference standard. Index tests comprised the VAT, Mini-Cog, clock drawing, verbal fluency, episodic memory, and subjective complaints. Validity parameters were calculated; possible confounders of test performance (age, sex, education, comorbidity, depression, language) were evaluated.



Twenty-one participants (5%) had dementia according to the reference standard. The VAT distinguished dementia from nondementia with a sensitivity of 95.2% (95% confidence interval (CI) = 86.1-100.0), a specificity of 96.0% (95% CI = 94.1-97.9), a positive predictive value (PPV) of 55.6% (95% CI = 39.3-71.8), and a negative predictive value (NPV) of 99.7% (95% CI = 99.2-100.0). The next-most-accurate tasks were the Mini-Cog and immediate and delayed recall. Their sensitivity and NPV are similar to those of the VAT, but their PPV and specificity were significantly lower than those of the VAT. Age and depression affected all test scores.



The VAT (cued recall of pictorial material) is superior to other tasks for the recognition of dementia in terms of higher specificity and PPV. Age-specific cutoff scores may improve the validity of all tests.
The use of fine needle core biopsy under ultrasound guidance in the diagnosis of a parotid mass.

e aimed to evaluate data about the performance of ltrasound-guided core biopsy (USCB) in the diagnosis of arotid swellings and to supplement previous studies in this rea.1–3 Sixtyfive patients were enrolled in this prospective tudy in addition to our previously published series of 135 atients1 with follow-up periods ranging from a few months o nine years. The technique of initial diagnostic ultrasound nd characterisation of the lesion followed by guided core iopsy is identical to that previously described,1–3 using a pring-loaded automated and variable throw biopsy device nd a combination of 18 or 20G needles (mean of two asses/patient). In the previous series all core biopsies were considered ufficient for histological analysis and there were no false postive or false negative results. Of 200 patients in the updated eries,116 were operated on subsequently (Table 1) and 84 atients were not (Table 2). Two core biopsy specimens in he additional study group of 65 patients had nondiagnostic ore biopsy samples and there was also a single false negative esult. In the two patients in whom USCB was not diagnostic, oth lesions had prominent cystic/ necrotic internal compoents as shown on the initial diagnostic ultrasound scans. espite sampling of the solid elements, core biopsy samples ere inadequate for diagnosis. Ultrasound scans had sugested possible diagnoses of Warthin tumour in one case and alignancy in the other. The final histological examination
The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled "amount" and "difficulty". After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.Daily and clinical visit "PROactive physical activity in COPD" instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.
Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus

Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.
Garlic and papaya lack control over gastrointestinal nematodes in goats and lambs.

Gastrointestinal nematodes (GIN) continue to hinder small ruminant production because of anthelmintic resistance and lack of effective products for GIN control in organic production. The objective of this study was to examine the effectiveness of a commercially available certified organic garlic product, fresh garlic juice, or garlic bulbs as an anthelmintic to control GIN in goats and papaya seeds for GIN control in lambs. In the first experiment, weaned meat goat kids were administered water or a commercial garlic juice product (n=7/treatment). In the second experiment, kids were administered water, fresh garlic juice, or fed garlic bulbs (n=9 or 10/treatment). In a third experiment, lambs were administered nothing or papaya seed in water (n=12/treatment). Naturally infected goats were supplemented with bermudagrass hay and corn/soybean supplement in the first experiment or maintained on bermudagrass pasture in the second experiment or lambs grazed mixed grasses in the third. Blood and fecal samples were collected on Days 0, 7, and 14 after administration of treatment to examine changes in blood packed cell volume (PCV) and fecal egg counts (FEC). PCV and FEC were similar by Day 14 between kids treated with a commercial garlic juice and water in the first experiment. Similarly, PCV was not different among treatment groups in the second experiment. FEC of the garlic juice group was lower than the other two groups on Day 0, but was similar among groups by Day 14. Deworming was required in one goat within each treatment group by Day 7 and in three kids in the garlic juice group and two in the garlic bulb group by Day 14. No changes in PCV or FEC were apparent in response to papaya seed compared with untreated lambs. Based on the alternative plant products used in this study, garlic or papaya seed is not recommended as an aid to control GIN in goats or lambs.
Prognostic relavance of cerbB2 expression following neoadjuvant chemotherapy in patients in a randomised trial of neoadjuvant versus adjuvant chemoendocrine therapy

Recent advances in the detection and treatment of breast cancer have led to an intensive search for new markers of both prognosis and chemoresponsiveness. The oncogene cerbB2 has proved to be one of the most promising markers currently under study, both as a predictor of chemoresponsiveness and as a marker of poor prognosis. In addition the increasing use of neoadjuvant chemotherapy has led to the loss of standard prognostic criteria. In order to study the potential role of cerbB2 expression as an indicator of chemoendocrine resistance and poor prognosis, both before and after chemotherapy, we obtained tumour sections from 283 women enrolled onto a neoadjuvant trial. In this trial patients were randomised to receive either primary surgery followed by adjuvant chemoendocrine treatment or neoadjuvant chemoendocrine therapy followed by surgery. CerbB2 status was determined immunohistochemically on all of these patients. Thirty-eight percent of the tumours were cerbB2 positive. There was no significant difference in expression between the adjuvant (41%) and neoadjuvant arms (35%). CerbB2 positive patients were much more likely to have shown non-response to chemoendocrine therapy (p<0.001) and had a worse DES (p<0.05). The best prognosis was seen in cerbB2 negative patients receiving neoadjuvant chemoendocrine therapy who showed a significantly better DFS (p<0.05), than the cerbB2 negative patients receiving adjuvant therapy.
Pattern analysis of sleep-deprived human EEG.

Progress during the past decade in non-linear dynamics and instability theory has provided useful tools for understanding spatio-temporal pattern formation. Procedures which apply principle component analysis (using the Karhunen-Loeve decomposition technique) to the multichannel electroencephalograph (EEG) time series have been developed. This technique shows localized changes of cortical functioning; it identifies increases and decreases of the activity of localized cortical regions over time while the subject performs a simple task or test. It can be used to demonstrate the change in cortical dynamics in response to a continuous challenge. Using 16 EEG electrodes, the technique provides spatio-temporal information not obtained with power spectrum analysis, and includes the weighted information given with omega complexity. As an application, we performed a pattern analysis of sleep-deprived human EEG data in 20 healthy young men. Electroencephalograph recordings were performed on subjects for <2 min, with eyes closed after normal sleep and after 24 h of experimentally-induced sleep deprivation. The significant changes in the eigenvector components indicated the relative changes of local activity in the brain with progressive sleep deprivation. A sleep deprivation effect was observed, which was hemispherically correlated but with opposite directional dynamics. These changes were seen in the temporo-parietal regions bilaterally. The application of the technique showed that the simple test task was performed with a limited unilateral hemispheric involvement at baseline, but needed a much larger cortical participation with decreased frontal activity and increased coherence and bilateral hemispheric involvement. The calculations performed demonstrated that the same weighted changes as those obtained with omega complexity were shown, but the technique had the added advantage of showing the localized directional changes of the principle eigenvector at each studied electrode, pointing out the cortical localized region affected by the sleep deprivation and toward which direction the environmental challenge induced the spatial change. This methodology may allow the evaluation of changes in local dynamics in brain activity in normal and pathological conditions.
Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia : long-term clinical and MRD results of the German CLL Study Group CLL 3 X trial

Peter Dreger,1 Hartmut Döhner,2 Matthias Ritgen,3 Sebastian Böttcher,3 Raymonde Busch,4 Sascha Dietrich,1 Donald Bunjes,2 Sandra Cohen,5 Jörg Schubert,6 Ute Hegenbart,1 Dietrich Beelen,7 Matthias Zeis,8 Michael Stadler,9 Justin Hasenkamp,10 Lutz Uharek,11 Christof Scheid,12 Andreas Humpe,3 Thorsten Zenz,2 Dirk Winkler,2 Michael Hallek,12 Michael Kneba,3 Norbert Schmitz,8 and Stephan Stilgenbauer,2 for the German CLL Study Group
ptimal Timing for the Initiation of reTreatment With 300 mg Clopidogrel efore Percutaneous Coronary Intervention

This study sought to determine the optimal timing of a 300-mg clopidogrel loading dose before percutaneous coronary intervention (PCI) in patients enrolled in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.  A loading dose of clopidogrel before a PCI has become relatively commonplace, although the data supporting this practice are limited and sometimes conflicting.  Patients were randomized to receive either 300 mg clopidogrel or a matching placebo administered a minimum of 3 h and a maximum of 24 h before PCI. The primary 28-day combined end point was death, myocardial infarction, or urgent target vessel revascularization. Linear splines were used to summarize the effect of the time of pre-treatment as a continuous variable.  A total of 1,762 patients were evaluated. For patients randomized to placebo, there was no relationship between the duration of pre-treatment and the occurrence of the primary end point, whereas longer durations of pre-treatment in patients randomized to clopidogrel were associated with improved outcomes. The event rates diverged maximally at 24 h. The difference in outcomes between placebo and clopidogrel pre-treated patients was not significant until 15 h pre-treatment, with a 58.8% (p 0.028) reduction in the primary end point in patients pre-treated with clopidogrel 15 h compared with placebo.  When a 300-mg loading dose of clopidogrel is used, little benefit is obtained compared with just 75 mg at the time of the PCI when the treatment duration is 12 h. In patients pre-treated for longer durations, the optimal duration seems to approach 24 h. (
Study of oxidative, enzymatic mitochondrial respiratory chain function and apoptosis in perinatally HIV-infected pediatric patients.

Mitochondrial toxicity in perinatally human immunodeficiency virus (HIV)-infected pediatric patients has been scarcely investigated. Limited data are available about HIV or antiretroviral (ARV)-mediated mitochondrial damage in this population group, specifically, regarding oxygen consumption and apoptosis approach. We aimed to elucidate whether a given mitochondrial DNA depletion is reflected at downstream levels, to gain insight on the pathology of HIV and highly active antiretroviral therapy (HAART) in perinatally HIV-infected pediatric patients. We studied 10 healthy control participants and 20 perinatally HIV-infected pediatric patients (10 under ARV treatment and 10 off treatment). We determined mitochondrial mass, subunits II and IV of complex IV, global and specific mitochondrial enzymatic and oxidative activities, and apoptosis from peripheral blood mononuclear cells. Global oxygen consumption was significantly compromised in HIV-infected untreated patients, compared to the control group (0.76 ± 0.01 versus 1.59 ± 0.15; P = 0.014). Apoptosis showed a trend to increase in untreated patients as well. The overall complex (C) CI-III-IV activity of the mitochondrial respiratory chain (MRC) was significantly decreased in HIV-infected treated patients with respect to the control group (1.52 ± 0.38 versus 6.38 ± 1.53; P = 0.02). No statistically significant differences were found between untreated and HAART-treated patients. These findings suggest the pathogenic role of both HIV and HAART in mitochondrial dysfunction in vertical infection. The abnormalities in mitochondrial genome may be downstream reflected through a global alteration of the MRC. Mitochondrial impairment associated with HIV and HAART was generalized, rather than localized, in this series of perinatally HIV-infected patients.
Effects of an angiotensin II receptor blocker on the impaired function of endothelial progenitor cells in patients with essential hypertension.

Endothelial progenitor cells (EPCs) induce neovascularization and repair vascular damage. We have demonstrated that EPC function is impaired in hypertensive rats with increases in oxidative stress and that angiotensin II receptor blockers improved the impaired function of EPCs. In this study, we investigated basal EPC functions in normotensive control subjects and patients with essential hypertension and the effect of losartan on EPC function in hypertensive patients.



Eighteen normotensive control subjects and 36 patients with essential hypertension who were undergoing treatment participated in the study. Hypertensive patients were randomly selected to receive 50mg of losartan or 4 mg of trichlormethiazide daily for 4 weeks. Peripheral blood mononuclear cells were isolated and cultured to assay EPC colony formation. Blood pressure, biological examination, and oxidative stress were evaluated in all subjects.



The number of EPC colonies was significantly lower in patients with essential hypertension than in normotensive control subjects. EPC colony number was significantly and inversely correlated with systolic and diastolic blood pressure in all subjects. EPC colony number was significantly increased by treatment with losartan in patients with essential hypertension but not affected by treatment with trichlormethiazide.



EPC function was inversely correlated with blood pressure and was impaired in essential hypertension. Losartan significantly improved the impaired EPC function in hypertensive patients. Impaired EPC function may determine the cardiovascular complications in essential hypertension. The improvement of EPC function with the administration of angiotensin II receptor blockers is considered to be one of the cardiovascular protective effects.