nils-herrmann/clean_scirepeval huggingface dataset:
Retention of paclitaxel in cancer cells for 1 week in vivo and in vitro

Clinically, the administration of paclitaxel for ovarian cancer on a dose-dense weekly schedule, rather than the conventional every-3-week schedule, might demonstrate greater tumor-cell death. Here, we investigate the pharmacokinetics and the pharmacodynamics of weekly paclitaxel in cancer cells in vivo and in vitro.  Paclitaxel concentrations were measured by HPLC, and apoptotic cells were detected by TUNEL assay in paclitaxel-pretreated cervical cancer cells treated with paclitaxel (10 ng/ml) and in the tissues of cervical cancer patients treated with weekly paclitaxel (60 mg/m2/week). Polymerized tubulin was detected with a tubulin polymerization assay, and the BrdU cell proliferation assay was used to assess the effect of paclitaxel.  Paclitaxel remained in the cancer tissues of six patients for 6 days after the last medication. In vitro, paclitaxel was retained in all cell lines for 24 h after its removal from the medium, and paclitaxel was still detectable in CaSki cells on day 7. Simultaneous treatment with depolymerizing drugs inhibited the retention of paclitaxel in cells and paclitaxel-induced polymerization of tubulin. After paclitaxel treatment, apoptotic cells were detected in cancer tissues and CaSki cells for 1 week. Under high magnification, apoptotic cells on day 7 after paclitaxel treatment showed multinucleation.  Paclitaxel is unusual in that it accumulates especially in cancer cells and induces apoptosis for 1 week in vivo and in vitro. On the other hand, paclitaxel could not be detected in cancer tissues after 2 weeks. The administration of paclitaxel on a weekly schedule, rather than the standard every-3-week schedule, might produce greater tumor-cell death.
Low prealbumin is strongly associated with adverse outcome in heart failure.

Prealbumin is one of the best indicators of nutritional status. We previously showed that prealbumin predicted in-hospital mortality in heart failure (HF) patients. We evaluated if a low discharge prealbumin after admission with acute HF would predict morbidity and mortality.



We conducted a prospective observational study. Patients admitted with a primary diagnosis of HF were studied. Follow-up was up to 6 months. Endpoints analysed were: all-cause and HF-death; all-cause and worsening HF hospitalisation. Patients with discharge prealbumin ≤15.0 mg/dL and those with prealbumin >15 mg/dL were compared. A Cox-regression analysis was used to evaluate the prognostic impact of low prealbumin.



We studied 514 patients. Mean age was 78 years and 45.7% were male. During follow-up, 101 patients died (78 for HF) and 209 patients were hospital readmitted (140 for worsening HF). Median prealbumin was 20.1 (15.3-25.3) mg/dL. Patients with lower prealbumin were more often women, older aged and with non-ischaemic HF; they had lower albumin, haemoglobin and total cholesterol; and higher glomerular filtration rate, C-reactive protein, B-type natriuretic peptide and length of hospital stay. Lower prealbumin associated with less β-blocker and statin use. Patients with discharge prealbumin ≤15 mg/dL had a multivariate adjusted HR of 6-month all-cause and HF death of 1.67 (1.00 to 2.80) and 2.12 (1.19 to 3.79) respectively and of all-cause and HF readmission of 1.47 (1.01 to 2.14) and 1.58 (1.01 to 2.47).



Patients with discharge prealbumin ≤15 mg/dL have an higher risk of 6 months morbidity and mortality. The unbalance between protein-energy demands and its availability predicts ominous HF outcome.
Clinical features and outcomes of IgA nephropathy with nephrotic syndrome.

Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored.



A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration.



Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P<0.001). The risk of reaching the primary endpoint was significantly higher in the PR (P=0.04) and NR groups (P<0.001) than in the CR group. Among patients with NS, 24 (24%) underwent spontaneous remission (SR). SR occurred more frequently in female patients and in patients with serum creatinine levels ≤1.2 mg/dl and a >50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up.



This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.
Determinants of outcome in anticoagulation-associated cerebral hematoma requiring emergency evacuation.

To analyze the likelihood of recovery and prognostic factors in patients with massive anticoagulation-associated intracerebral hemorrhage treated with surgical evacuation after reversal of anticoagulation.



Retrospective case series.



Neurological-Neurosurgical Intensive Care Unit at Mayo Clinic.  Seventeen consecutive patients with large anticoagulation-associated intracerebral hemorrhage.  Surgical evacuation of intracerebral hemorrhage.  Functional outcome was assessed using the modified Rankin scale.



Before surgery, all patients had pronounced (>1-cm) shift of the septum pellucidum and one third had clinical signs of uncal herniation. Still, favorable outcome (modified Rankin scale score < or =3) was achieved by 11 patients (65%). All patients with good recovery awoke within 36 hours of surgery. Older age (P = .05) and serious systemic complications after surgery (P<.01) were significantly associated with lack of neurological recovery and fatal outcome.



Emergency surgery for select deteriorating patients with large anticoagulation-associated intracerebral hemorrhage is compatible with favorable outcome despite the presence of clinical and radiological signs of herniation before the evacuation.
Baseline neuropsychiatric symptoms are effect modifiers in <ce:italic>Ginkgo biloba</ce:italic> extract (EGb 761®) treatment of dementia with neuropsychiatric features. Retrospective data analyses of a randomized controlled trial

Previous studies suggested that EGb 761® may be more effective when dementia is associated with neuropsychiatric features. To find out whether treatment effects correlate with neuropsychiatric symptom burden at baseline, retrospective analyses of data from a 24-week randomized, placebo-controlled, double-blind clinical trial of EGb 761® (240 mg once daily) were performed. 410 outpatients with mild to moderate AD, VaD or AD with cerebrovascular disease, each associated with neuropsychiatric features, were enrolled. Patients scored 5 or above on the NPI, with at least one item score being ≥3, and between 9 and 23 on the SKT cognitive test battery. Correlations between the NPI composite score at baseline and other efficacy variables were calculated. Regression analyses with the NPI composite score as regressor and efficacy variables as dependent variables were performed. Correlations between changes from baseline and NPI baseline scores were weak to modest, but conspicuously different between active drug and placebo groups. The slopes of the regression lines for the EGb 761® and the placebo groups showed qualitative and statistically significant differences: With increasing NPI baseline scores there was faster deterioration in the placebo group and thus more net benefit from treatment for the EGb 761® group.
A cognitive-ecological approach to preventing aggression in urban settings: initial outcomes for high-risk children.

A multiyear, multicontext aggression prevention intervention was provided during the early or late elementary school years in an inner-city and an urban poor community. Sixteen schools were randomly assigned to 1 of 4 conditions: (a) no-treatment control, (b) general enhancement classroom program, (c) general enhancement plus small-group peer-skills training, or (d) general enhancement plus small-group peer-skills training plus family intervention. This article reports on results for the high-risk subsample of 1,500 children. Results from hierarchical linear modeling indicate that comprehensive interventions, if provided in early grades, can be effective for children in schools in settings with resources adequate to support learning and development, but some unintended effects can occur in schools in the most distressed communities when delivered too late in development.
Salmeterol xinafoate in asthmatic patients under consideration for maintenance oral corticosteroid therapy. UK Study Group.

In severe chronic asthma, long-term oral steroids may be necessary to control symptoms. In patients in whom such treatment was under consideration, the efficacy and safety of salmeterol xinafoate 100 micrograms b.i.d. was investigated in a randomized, double-blind, placebo-controlled parallel-group, multicentre study. One hundred and nineteen chronic symptomatic asthmatics were randomized to receive either salmeterol, 100 micrograms b.i.d. (n = 55; baseline % predicted morning peak expiratory flow (PEF) 59%; forced expiratory volume in one second (FEV1) 66%) or placebo (n = 64; baseline % predicted morning PEF 63%; FEV1 66%) both via the Diskhaler. Morning and evening PEF and asthma symptoms were recorded in daily record booklets by the patient over a 12 week period. A significant improvement in morning PEF was achieved after 1 month in the salmeterol treated group; this persisted throughout the treatment period (estimated treatment difference 22 L.min-1). There was a significant increase in the proportion of symptom-free nights experienced by the salmeterol treated group (33 (SD 32) %) compared with placebo (13 (26) %), and a significant decrease in daily use of relief medication (mean decrease 5.1 (4.7) doses per day with salmeterol, 2.5 (4.0) doses with placebo). Both treatments were well-tolerated, with no evidence of any difference in the side-effects associated with beta 2-agonists. In conclusion, the addition of salmeterol (100 micrograms daily) to the existing treatment of chronic asthmatics under consideration for maintenance oral corticosteroid therapy is well-tolerated, improves lung function and provides additional symptom control.
Development of the Japanese version of the Pediatric Quality of Life Inventory™ Brain Tumor Module

The Pediatric Quality of Life Inventory (PedsQL) is a widely-used modular instrument for measuring health-related quality of life in children aged 2 to 18 years. The PedsQL Brain Tumor Module is comprised of six scales: Cognitive Problems, Pain and Hurt, Movement and Balance, Procedural Anxiety, Nausea, and Worry. In the present study, we developed the Japanese version of the PedsQL Brain Tumor Module and investigated its feasibility, reliability, and validity among Japanese children and their parents.



Translation equivalence and content validity were verified using the standard back-translation method and cognitive debriefing tests. Participants were recruited from 6 hospitals in Japan and the Children's Cancer Association of Japan, and questionnaires were completed by 137 children with brain tumors and 166 parents. Feasibility of the questionnaire was determined based on the amount of time required to complete the form and the percentage of missing values. Internal consistency was assessed using Cronbach's coefficient alpha. Test-retest reliability was assessed by retesting 22 children and 27 parents. Factorial validity was verified by exploratory factor analyses. Known-groups validity was described with regard to whole brain irradiation, developmental impairment, infratentorial tumors, paresis, and concurrent chemotherapy. Convergent and discriminant validity were determined using Generic Core Scales and State-Trait Anxiety Inventory for children.



Internal consistency was relatively high for all scales (Cronbach's coefficient alpha > 0.70) except the Pain and Hurt scale for the child-report, and sufficient test-retest reliability was demonstrated for all scales (intraclass correlation coefficient = 0.45-0.95). Factorial validity was supported through exploratory factor analysis (factor-item correlation = 0.33-0.96 for children, 0.55-1.00 for parents). Evaluation of known-groups validity confirmed that the Cognitive Problems scale was sensitive for developmental impairment, the Movement and Balance scale for infratentorial tumors or paresis, and the Nausea scale for a patient currently undergoing chemotherapy. Convergent and discriminant validity with the PedsQL Generic Core Scales and State-Trait Anxiety Inventory for children were acceptable.



The Japanese version of the PedsQL Brain Tumor Module is suitable for assessing health-related quality of life in children with brain tumors in clinical trials and research studies.
Acceptability of Praneem polyherbal vaginal tablet among HIV uninfected women & their male partners in Pune, India--Phase I study.

The number of HIV infected women is steadily increasing worldwide and women controlled methods to prevent HIV are urgently needed. Vaginal microbicides are products for vaginal administration that can be used to prevent HIV infection and other sexually transmitted diseases (STDs). We conducted a Phase I safety and acceptability study of Praneem polyherbal tablet, a candidate microbicide, among HIV uninfected women in Pune, India.



Twenty eligible women were requested to use the product intravaginally once daily for 14 consecutive days between menses. Safety was assessed by clinical examination, laboratory monitoring and colposcopy. Acceptability was assessed after 14 days of product use through structured questionnaires, focus group discussions among participating women, and in-depth interviews with a subset of 5 randomly selected male partners.



Praneem polyherbal tablet was found acceptable by the study participants with 90 per cent of the participants showing 80 per cent and more acceptability score. Discharge of the product residue was reported as a concern by 6 (30%) of participants. Nineteen (95%) female participants liked the smell and the same number reported that the product was easy to use and did not affect the usual sexual pleasure. However, men reported lack of sexual satisfaction.



Product characteristics received good acceptability score in women. However, studies of long-term safety and acceptability among at-risk population would provide more detailed information about its long term acceptability.
White Matter Changes Associated with Antipsychotic Treatment in First-Episode Psychosis

Second-generation antipsychotics are utilized extensively in the treatment of psychotic disorders and other psychiatric conditions, but the effects of these medications on human brain white matter are not well understood. We thus investigated the effects of second-generation antipsychotics on white matter integrity using tract-based spatial statistics in patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure, and how potential changes were associated with metabolic side effects. Thirty-five (26 men/9 women) patients experiencing a first episode of psychosis received diffusion tensor imaging (DTI) exams, clinical assessments, and provided fasting blood samples at the onset of antipsychotic treatment, and then again after 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 35 (26 men/9 women) healthy volunteers received DTI exams at a baseline time point and then after 12 weeks. Patients demonstrated significant (p<0.05; family-wise error corrected) fractional anisotropy reductions within the parietal and occipital white matter following antipsychotic treatment. Greater overall fractional anisotropy reduction was significantly correlated with greater increases in low-density lipoprotein. There were no significant fractional anisotropy increases among patients following treatment. Moreover, healthy volunteers did not demonstrate either significant increases or decreases in fractional anisotropy across a comparable 12-week interval. The use of antipsychotics may be associated with a subtle loss of white matter integrity that is related to greater side effects, thus raising potentially important considerations regarding risk/benefit in their usage. Limitations of the current study, however, include a prior history of substance use among patients and our inability to exclude the possibility of disease progression.
Treatment outcomes of recommended first-line antiretroviral regimens in resource-limited clinics.

Although used globally, little data exist on the efficacy of nevirapine (NVP) used in combination with tenofovir (TDF)/emtricitabine or lamivudine (XTC), and no large randomized prospective control trials exists comparing this combination with efavirenz (EFV)/TDF/(XTC).



As part of the AIDSRelief program, a retrospective review of patient medical chart information along with a cross-sectional viral load, and adherence measurement was conducted between 2004 and 2009. An on-treatment analysis excluded patients who died, transferred out of care, or were lost to follow-up. A switch of antiretrovirals for any reason was considered a failure in the intent-to-treat analysis. Patients with only clinically relevant reasons for switching such as toxicity, adverse effects, viral failure or clinical/immunological failure, lost to follow-up, and death were considered failures as part of the modified-intent-to-treat analysis. Step-wise multiple regression analysis was used to identify variables that were associated with viral suppression.



A random sample of 3862 patients met criteria and were included in this analysis. In the on-treatment analysis, older age (P < 0.004) and baseline CD4 <100 cells per cubic millimeter (P < 0.021) were the most significant variables impacting viral load. Patients on TDF/XTC/EFV achieved higher rates of viral suppression compared with patients on TDF/XTC/NVP or azidothymidine (AZT)/lamivudine (3TC)/NVP.



Our data show that patients on TDF/XTC/EFV had better outcomes than patients on TDF/XTC/NVP, AZT/3TC/EFV, or AZT/3TC/NVP. High rates of virologic suppression seen in patients on this regimen are consistent with previous studies and indicate the need to increase use of this regimen in HIV programs to promote sustainable viral suppression over time.
Epidemiological composition, clinical and treatment characteristics of the patient cohort of the german competence network for HIV/AIDS

As its central basis for research, the Competence Network for HIV/AIDS (KompNet) established a nationwide cohort study on HIV-positive patients being in medical care in Germany. In this paper, we describe the epidemiological composition, and clinical as well as treatment characteristics of the KompNet cohort over time.



The KompNet cohort is an open, retrospective and prospective, multi-center, disease-specific and nationwide cohort study that started gathering data in June 2004. Semiannually, follow up visits of the patients are documented, covering a wide range of clinical and sociodemographic data. At enrollment and three years afterwards, an EDTA-sample is taken; a serum-sample is taken at every follow up.



As of 20.10.2008, a total of 15,541 patients were enrolled by 44 documenting sites. In September 2007, the cohort size was reduced to ten outpatient clinics and fifteen private practitioners, covering a total of 9,410 patients. The documentation of these patients comprised 24,117 years of follow up-time since enrollment (mean: 2.6 years), 62,862 person years inclusive data documented retrospectively on course of HIV-infection and antiretroviral therapy (ART, mean: 6.7 years). Due to the short period of recruitment till now, rates of death (0.3%-0.8%) and losses to follow up (1.1%-5.5%) were low. 84.9% of patients were men. Main risk of transmission was sex between men (MSM: 62.9%). Mean age was 45 years. About two third of patients were classified as CDC-stage B or C. Therapy regimens of currently treated patients complied with recent guidelines. Trends of mean CD4 cell count/microl regarding the initial therapy and concerning the population under treatment reflected the developments and the changing standards of antiretroviral therapy over time.



The KompNet cohort covers about a quarter of all patients estimated as being under treatment in Germany. Its composition can be accounted approximately representative for the situation of clinical care and treatment in the scope of HIV/AIDS in Germany. Therefore, it is an important instrument for measuring the course of HIV/AIDS, the reality of use of antiretroviral therapy and its clinical and psychosocial outcomes in Germany.
Long-Latency Somatosensory Evoked Potentials of the Subthalamic Nucleus in Patients with Parkinson’s Disease

Somatosensory evoked potentials (SSEPs) are a viable way to measure processing of somatosensory information. SSEPs have been described at the scalp and the cortical level by electroencephalographic, magnetoencephalographic and intracranial cortical recordings focusing on short-latency (SL; latency<40 ms) and long-latency (LL; latency>40 ms) SSEPs as well as by deep brain stimulation (DBS) electrode studies targeting SL-SSEPs. Unfortunately, LL-SSEPs have not been addressed at the subcortical level aside from the fact that studies targeting the characteristics and generators of SSEPs have been neglected for the last ten years. To cope with these issues, we investigated LL-SSEPs of the subthalamic nucleus (STN) in twelve patients with Parkinson's disease (PD) that underwent deep brain stimulation (DBS) treatment. In a postoperative setting, LL-SSEPs were elicited by median nerve stimulation (MNS) to the patient's wrists. Ipsilateral or contralateral MNS was applied with a 3 s inter-stimulus interval. Here, we report about four distinctive LL-SSEPs ("LL-complex" consisting of P80, N100, P140 and N200 component), which were recorded by using monopolar/bipolar reference and ipsi/contralateral MNS. Phase reversal and/or maximum amplitude provided support for the generation of such LL-SSEPs within the STN, which also underscores a role of this subcortical structure in sensory processing.
Emergent epileptiform activity in neural networks with weak excitatory synapses

Brain electrical activity recorded during an epileptic seizure is frequently associated with rhythmic discharges in cortical networks. Current opinion in clinical neurophysiology is that strongly coupled networks and cellular bursting are prerequisites for the generation of epileptiform activity. Contrary to expectations, we found that weakly coupled cortical networks can create synchronized cellular activity and seizure-like bursting. Evaluation of a range of synaptic parameters in a detailed computational model revealed that seizure-like activity occurs when the excitatory synapses are weakened. Guided by this observation, we confirmed experimentally that, in mouse neocortical slices, a pharmacological reduction of excitatory synaptic transmission elicited sudden onset of repetitive network bursting. Our finding provides powerful evidence that onset of seizures can be associated with a reduction in synaptic transmission. These results open a new avenue to explore network synchrony and may ultimately lead to a rational approach to treatment of network pathology in epilepsy.