nils-herrmann/clean_scirepeval huggingface dataset:
No growth-stimulation of heterotransplanted human testicular cancer cell-lines by recombinant human granulocyte-macrophage colony-stimulating factor (gm-csf).

Hematopoietic growth factors such as granulocyte (G)- and granulocyte-macrophage (GM) colony-stimulating factor (CSF) are currently used as adjunct treatment for cancer chemotherapy in order to ameliorate neutropenia. The current investigation presented here focused on the in vivo effects of GM-CSF on two heterotransplanted human testicular cancer cell lines in a nude mouse model. GM-CSF was applied to tumor bearing mice in a dose range of 3 x 10(5) to 3 x 10(7) U/kg per day i.v. for 14 consecutive days. For all concentrations of GM-CSF a reduction of the tumor volume compared to untreated tumor bearing control mice was noted. The largest retardation of tumor growth was seen at the end of the experiments at day 30 with 3 x 10(7) U/kg of GM-CSF with a relative tumor volume of 72% +/- 8% for cell line H 12.1 and 73.5 +/- 9% for cell line H23.1 in comparison to untreated tumor bearing control mice. No side effects of GM-CSF application such as weight loss or fever were observed. Serum tumor necrosis factor (TNF) levels in mice treated with GM-CSF were considerably lower compared to untreated tumor carrying control animals. No growth stimulation of heterotransplanted human testicular germ cell tumors by GM-CSF has been observed in this nude mice tumor model. Further studies will have to demonstrate, whether GM-CSF is even possibly able to exhibit an antitumor effect. With respect to tumor cell kinetics the clinical use of GM-CSF in the treatment of patients with testicular cancer can be regarded as safe.
Cost-effectiveness of child-focused and parent-focused interventions in a child anxiety prevention program.

In this study, the cost-effectiveness of three indicated anxiety prevention strategies was examined from a societal perspective. Children (aged 8-12) were recruited via primary schools, selecting children scoring as high-anxious on an anxiety screening questionnaire. Participating children and their parents were randomized to a child--a parent-focused, or non-intervention group. All groups completed a diagnostic interview and standardized cost-diaries at pretest, and 1- and 2-year follow-up. Incremental cost-effectiveness ratios per 'ADIS improved' child (based on diagnostic information) were calculated and cost-effectiveness acceptability curves and frontiers were plotted. The base-case and most secondary analyses showed it would be cost-effective to offer high-anxious children an intervention, and the parent-focused intervention to be the optimal strategy at lower monetary threshold values than the child-focused intervention and when parents were anxious. The child-focused intervention was dominant when analyses were performed from a healthcare perspective, for boys, and for children of grades 7-8 of primary school.
Factors influencing adherence in CML and ways to improvement: Results of a patient-driven survey of 2546 patients in 63 countries

Optimal adherence to CML therapy is of key importance to maximize treatment effectiveness. Two clinical studies (ADAGIO and Hammersmith) have proven a clear correlation between adherence and achieving optimal treatment response and have revealed that non-adherence is common in CML patients (Marin et al.  2010, Noens et al. in Haematologica 99(33):437–447, 2014). The aim of this study is to assess the extent of suboptimal adherence and to investigate motivations and behavioural patterns of adherence in a worldwide patient sample. Questionnaires were provided by the CML Advocates Network and were filled in by patients online and offline. Patient characteristics, treatment and motivations were collected. Adherence was assessed by the 8-item Morisky Medication Adherence scale. Logistic regression models were fitted to investigate the influence of different factors on adherence. Overall, 2 546 questionnaires from 63 countries and 79 CML patient organisations were evaluable. 32.7% of participants were highly adherent, 46.5% were in the medium and 20.7% in the low adherence group. Factors increasing the probability of being in the high adherence group are older age, male sex, management of side effects, only one tablet per day and feeling well informed about CML by the doctor. More than 2 years since diagnosis were significantly lowering the chance as was the use of reminding tools. Living arrangements, multiple medication and personal payment obligations increased the probability to be at least in the medium adherent group. This is the most comprehensive study conducted to date to gain knowledge about factors causing non-adherence in CML. Better information on the disease, medication and management of side effects, supported by haematologists, is key to improve adherence.
Comparison of vilanterol, a novel long-acting beta2 agonist, with placebo and a salmeterol reference arm in asthma uncontrolled by inhaled corticosteroids

Current maintenance therapies for asthma require twice-daily dosing. Vilanterol (VI) is a novel long-acting beta2 agonist, under development in combination with fluticasone furoate, a new inhaled corticosteroid (ICS). Findings from a previous 4-week study suggested that VI has inherent 24-hour activity and is therefore suitable for once-daily dosing. The study described here was a double-blind, double-dummy, randomised, placebo-controlled trial, the aim of which was to assess the efficacy of once-daily VI compared with placebo in patients with persistent asthma. The primary endpoint was change from baseline in 24-hour weighted mean forced expiratory volume in 1 second after 12 weeks of treatment vs. placebo. An active control arm received salmeterol (SAL) twice daily. All patients were maintained on a stable background dose of ICS. Patients (n = 347) received VI, placebo or SAL (1:1:1). For the primary endpoint, substantial improvements in lung function were seen with VI (359 ml), SAL (283 ml) and placebo (289 ml). There were no statistically significant treatment differences between either the VI (70 ml, P = 0.244) or SAL (-6 ml, P = 0.926) groups and placebo. Both active treatments were well tolerated, with similarly low rates of treatment-related adverse events compared with placebo. No treatment-related serious adverse events occurred. This study failed to show a treatment difference between VI and placebo for the primary endpoint, in the presence of a placebo response of unforeseen magnitude. Because the placebo response was so large, it is not possible to draw meaningful conclusions from the data. The reason for this magnitude of effect is unclear but it may reflect increased compliance with the anti-inflammatory therapy regimen during the treatment period. NCT01181895 at ClinicalTrials.gov.
Therapeutic effects of acupuncture in patients with rheumatoid arthritis: a prospective study using (18)F-FDG-PET.

The purpose of this study was to investigate whether improvement of regional inflammatory findings in knee joints of rheumatoid arthritis (RA) could be detected by positron-emission tomography (PET) using (18)F-Fluorodeoxyglucose (FDG) after acupuncture treatments, as well as improvement of systemic inflammatory markers.



Six RA patients (all female, 61 +/- 12 years old) received 10 acupuncture treatments in 2 months, to 11 traditional acupuncture points around a knee joint considered effective on RA. A visual analogue scale (VAS) for intensity of pain, knee joint range of motion (ROM), face scale for patient mood, and modified health assessment questionnaire (MHAQ) for disability of daily activities were assessed just before and after acupuncture. Maximum standardized uptake value (SUV(max)) and the volume with SUV more than 1.0 [Volume(SUV > 1)] on FDG-PET images as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also measured before and after the treatments.



VAS, ROM, face scale and MHAQ improved in all patients and significantly after acupuncture, but no significant change was detected in ESR, CRP, SUV(max), or Volume(SUV > 1).



Acupuncture relieves symptom, remedies physical function, and improves quality of life in RA patients, but may have no or very limited anti-inflammatory effect systemically. The regional effects of acupuncture are unlikely to be induced through reduction of regional inflammation. We believe this clinical study is the first step for elucidating therapeutic mechanisms of acupuncture, which must be important for the rational use and further development of acupuncture.
Glucocorticoids reduce phobic fear in humans.

Phobias are characterized by excessive fear, cued by the presence or anticipation of a fearful situation. Whereas it is well established that glucocorticoids are released in fearful situations, it is not known whether these hormones, in turn, modulate perceived fear. As extensive evidence indicates that elevated glucocorticoid levels impair the retrieval of emotionally arousing information, they might also inhibit retrieval of fear memory associated with phobia and, thereby, reduce phobic fear. Here, we investigated whether acutely administrated glucocorticoids reduced phobic fear in two double-blind, placebo-controlled studies in 40 subjects with social phobia and 20 subjects with spider phobia. In the social phobia study, cortisone (25 mg) administered orally 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation, exposure, and recovery phase of the stressor. Moreover, the stress-induced release of cortisol in placebo-treated subjects correlated negatively with fear ratings, suggesting that endogenously released cortisol in the context of a phobic situation buffers fear symptoms. In the spider phobia study, repeated oral administration of cortisol (10 mg), but not placebo, 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again 2 days after the last cortisol administration, suggesting that cortisol may also have facilitated the extinction of phobic fear. Cortisol treatment did not reduce general, phobia-unrelated anxiety. In conclusion, the present findings in two distinct types of phobias indicate that glucocorticoid administration reduces phobic fear.
Mutational Analysis of β‐Catenin Gene in Japanese Ovarian Carcinomas: Frequent Mutations in Endometrioid Carcinomas

To investigate the contribution of the beta-catenin gene to the development of ovarian carcinomas, mutational analysis of exon 3 of the beta-catenin gene was conducted. We analyzed 61 primary ovarian carcinomas, consisting of 49 non-endometrioid-type and 12 endometrioid-type tumors, for genetic alteration of the beta-catenin gene. Five carcinomas showed beta-catenin mutations (S37C, T41I, T41A), including 4 (33%) of 12 endometrioid-type tumors and 1 (14%) of 7 mucinous-type tumors. All of these mutations altered at the serine/threonine residues that are potential sites of GSK3-beta phosphorylation. We detected no carcinomas with interstitial deletion involving exon 3 of beta-catenin. Furthermore, we immunohistochemically studied 27 of the 61 ovarian carcinomas. Both nuclear and cytoplasmic beta-catenin expressions were demonstrated in 4 of the 27 ovarian carcinomas for which tissue samples were available for examination. All 4 cases exhibited mutations in exon 3 of beta-catenin, including a mucinous carcinoma. Our results suggested that beta-catenin gene mutation at potential GSK3-beta phosphorylation sites results in accumulation of beta-catenin protein within the cells and its translocation to nuclei. Accumulated beta-catenin protein may be involved in the development of endometrioid-type ovarian carcinomas, and some mucinous-type ovarian carcinomas.
Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Val-HeFT (Valsartan Heart Failure Trial).

This study sought to evaluate the association between changes over time of N-terminal pro-brain natriuretic peptide (NT-proBNP) expressed in different ways and outcome in patients with stable and chronic heart failure (HF).



Although previous studies examined the prognostic value of repeated determinations of BNP in HF, there are only limited data on the clinical utility of serial measurements of the inactive peptide NT-proBNP in a large population of ambulatory patients with chronic HF with sufficient follow-up time.



The NT-proBNP was measured at randomization and after 4 months in 1,742 patients enrolled in the placebo arm of Val-HeFT (Valsartan Heart Failure Trial). Changes in NT-proBNP concentrations over 4 months were expressed as absolute change from baseline, percent relative changes, or categorical changes across a threshold value and related to subsequent mortality.



A single determination of NT-proBNP (area under the curve at 4 months: 0.702, 95% confidence interval [CI]: 0.669 to 0.735) showed a higher prognostic discrimination than continuous changes of concentrations, expressed either as absolute (0.592, 95% CI: 0.549 to 0.634) or relative changes (0.602, 95% CI: 0.566 to 0.639). A Cox proportional hazards model showed that stratification of patients into 4 categories according to NT-proBNP levels at 2 time points 4 months apart with respect to a threshold concentration provided prognostic information in patients with chronic HF beyond that of a single determination.



Serial determinations of NT-proBNP concentration and classification into few categories of changes according to threshold levels may be a superior strategy for risk stratification of patients with chronic and stable HF.
Internet-based self-help versus one-session exposure in the treatment of spider phobia: a randomized controlled trial.

The authors compared guided Internet-delivered self-help with one session of live-exposure treatment in a sample of spider-phobic patients. A total of 30 patients were included following screening on the Internet and a structured clinical interview. The Internet treatment consisted of five weekly text modules, which were presented on a web page, a video in which exposure was modelled, and support provided via Internet. The live-exposure treatment was delivered in a 3-hr session following a brief orientation session. The main outcome measure was the behavioural approach test (BAT), and as secondary measures the authors used questionnaires measuring anxiety symptoms and depression. Results showed that the groups did not differ at posttreatment or follow-up, with the exception of the proportion showing clinically significant change on the BAT. At posttreatment 46.2% of the Internet group and 85.7% in the live-exposure group achieved this change. At follow-up the corresponding figures were 66.7% for the Internet group and 72.7% for the live treatment. Within-group effect sizes for the spider phobia questionnaire were large (d = 1.84 and 2.58 for the Internet and live-exposure groups, respectively, at posttreatment). The authors conclude that guided Internet-delivered exposure treatment is a promising new approach in the treatment of spider phobia.
New onset executive function difficulties at menopause: a possible role for lisdexamfetamine

Reports of cognitive decline, particularly in the domains of executive functions (EFs), are common among menopausal women. This study aims to determine the impact of the psychostimulant lisdexamfetamine (LDX) on subjective and objective cognitive function among menopausal women who report new-onset EF complaints. Thirty-two healthy perimenopausal and early postmenopausal women experiencing mid-life-onset executive function difficulties as measured using the Brown Attention Deficit Disorder Scale (BADDS) were administered LDX 40–60 mg/day for 4 weeks in this double-blind, placebo-controlled, cross-over study. Diagnosis of lifetime ADHD was exclusionary. BADDS total and subscale scores and performance on verbal memory and working memory tasks were outcomes of interest. Analyses revealed a significant effect of LDX treatment over placebo for total BADDS scores (p = 0.0001) and for four out of the five BADDS subscales (all p < 0.004). LDX treatment also resulted in significant improvement in delayed paragraph recall (p = 0.018), but there was no significant effect of treatment on other cognitive measures. Systolic blood pressure (p = 0.017) and heart rate increased significantly (p = 0.006) when women were on LDX but remained, on average, within the normal range. LDX 40–60 mg/day was well tolerated and improved the subjective measures of executive function as well as objective measures of delayed verbal recall in this sample of healthy menopausal women.
Randomized Controlled Trial of a Cognitive-Behavioral Intervention for HIV-Positive Persons: An Investigation of Treatment Effects on Psychosocial Adjustment

Questions remain regarding the clinical utility of psychological interventions for HIV-positive persons because randomized controlled trials have utilized stringent inclusion criteria and focused extensively on gay men. The present randomized controlled trial examined the efficacy of a 15-session, individually delivered cognitive-behavioral intervention (n = 467) compared to a wait-list control (n = 469) in a diverse sample of HIV-positive persons who reported HIV transmission risk behavior. Five intervention sessions that dealt with executing effective coping responses were delivered between baseline and the 5 months post-randomization. Additional assessments were completed through 25 months post-randomization. Despite previously documented reductions in HIV transmission risk, no intervention-related changes in psychosocial adjustment were observed across the 25-month investigation period. In addition, there were no intervention effects on psychosocial adjustment among individuals who presented with mild to moderate depressive symptoms. More intensive mental health interventions may be necessary to improve psychosocial adjustment among HIV-positive individuals.
A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy

This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients.  Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE).  Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, ‘no vomiting’, ‘no significant nausea’ and ‘no nausea’. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 ) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade ≥ 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048).  The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.
Continuous intra-articular infusion anesthesia for pain control after total knee arthroplasty: study protocol for a randomized controlled trial

Postoperative pain control after total knee arthroplasty (TKA) remains a great challenge. The management of pain in the immediate postoperative period is one of the most critical aspects to allow speedier rehabilitation and reduce the risk of postoperative complications. Recently, periarticular infiltration anesthesia has become popular, but the outcome is controversial. Some studies have shown transient effects, "rebound pain", or no effectiveness in pain control. Continuous intra-articular infusion technique has been introduced to improve these transient effects, but more clinical studies are needed. Furthermore, the potential risk of early periprosthetic joint infection is causing concerning. We plan to compare continuous intra-articular infusion anesthesia with epidural infusion anesthesia after TKA to assess the effectiveness of this technique in reducing pain, in improving postoperative function, and to look at the evidence for risk of early infection.



This trial is a randomized, controlled study. Patients (n = 214) will be randomized into two groups: to receive continuous intra-articular infusion anesthesia (group C); and epidural infusion anesthesia (group E). For the first 3 postoperative days, pain at rest, active range of motion (A-ROM), rescue analgesia and side effects will be recorded. At 3-month and 6-month follow-up, A-ROM, C-reactive protein, erythrocyte sedimentation rate, and synovial fluid cell count and culture will be analyzed.



The results from this study will provide clinical evidence on the efficacy of a continuous intra-articular infusion technique in reducing pain, postoperative functional improvement and safety. It will be the first randomized controlled trial to investigate infection risk with local anesthesia after TKA.