nils-herrmann/clean_scirepeval huggingface dataset:
The use of a protein and energy dense eicosapentaenoic acid containing supplement for malignancy-related weight loss in children.

The aim of nutritional therapy in cancer patients is to prevent weight loss and to improve functional capacity and quality of life. Clinical studies however, have continued to demonstrate that a reduction in body weight loss is difficult to achieve in cancer cachexia. Several studies have shown that supplementation with eicosapentaenoic acid (EPA), an omega-3 fatty acid, has anti-cachectic effects in adult cancer patients. This study evaluated the clinical effects of a protein and energy dense EPA containing nutritional supplement in a group of pediatric cancer patients receiving active chemotherapy treatment.



The study was a prospective, randomized, single center, open-label design. Fifty-two patients diagnosed with pediatric malignant disease and receiving intensive chemotherapy were included. Thirty-three patients received a nutritional supplement containing EPA in addition to their regular food intake. Nineteen control patients did not receive supplementation. Patients were examined and their data (body weight, body mass index, and weight percentile) were recorded regularly once a month for 3 months. A subgroup of patients was evaluated for 6 months.



At 3 months, there were significantly fewer patients in the treatment group as compared to controls that showed losses in body weight (P = 0.001), BMI (P = 0.002), and a negative deviation in weight percentile (P = 0.021). In addition, remission rate was significantly (P = 0.036) higher in the treatment group as compared to controls.



This study demonstrates a decrease in cancer-induced weight loss in pediatric patients fed a protein and energy dense nutrition supplement containing EPA.
Psychiatric morbidity after screening for breast cancer.

One hundred and thirty two women with normal breast screening results were interviewed six months after their attendance at the Edinburgh Breast Screening Clinic. Eight percent of women said screening had made them more anxious about developing breast cancer. Thirty eight percent said they were more aware of the disease since screening but they regarded this as advantageous. Seventy percent of the women were still practising breast self-examination. There was no difference in the psychiatric morbidity of the screened sample when compared with a matched random sample community control group. Neither was there any difference in the General Health Questionnaire case rates before and after screening. Screening does not appear to increase the prevalence of psychiatric morbidity. Twenty nine percent of the interview sample were examining their breasts more than once a month--21% once a week or more. However, these frequent self-examiners did not have a greater prevalence of psychiatric morbidity than their matched controls.
Susceptibility Of Ph-Positive All To Tki Therapy Associated With Bcr-Abl Rearrangement Patterns: A Retrospective Analysis

Tyrosine kinase inhibitors (TKIs) have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL) in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]). The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL.



In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30) years. Overall survival (OS) and event-free survival (EFS) were analyzed.



A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years) were enrolled, including those with BCR/ABL transcripts 190 (n = 52), 210 (n = 25), and 230 (n = 2); BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT), and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008), the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012), and also higher than those with TKI salvage administration (P = 0.004). BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each).



The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.
Circulating IL-2 and IL-10 in Chronic Active Hepatitis C with Respect to the Response to IFN Treatment

The importance of circulating immunoregulatory cytokines in response to IFN treatment and the change of in vivo production of these cytokines during interferion (IFN) treatment are not well known. We aimed to determine whether pretreatment serum levels of IL-2 and IL-10 are predictive of the response to IFN treatment and to investigate if treatment response or nonresponse has any effect on the circulating levels of these cytokines.  37 patients (18 responders and 19 non-responders) with chronic hepatitis C virus (HCV) infection who received IFN-α2b for 6 months were studied. Responders were defined by complete alanine aminotransferase (ALT) normalization and loss of HCV RNA as detected by bDNA assay while patients who had elevated ALT levels and positive HCV RNA after 6 months were considered as nonresponders.  Genotype distribution, ALT and HCG RNA levels were similar in responders and nonresponders. A significant number of patients with chronic hepatitis C (20/37 = 54%) had elevated IL-2 levels while IL-10 levels were not different from controls. No difference in baseline cytokine levels was observed between responders and non-responders. In the posttreatment serum samples some patients lost their detectable IL-2 or IL-10; some patients developed detectable cytokine levels after treatment irrespective of the treatment response.  These results suggest that active liver injury in chronic hepatitis C is associated with increased circulating Th1 cytokine IL-2 but not with Th2 cytokine IL-10 and that circulating levels of these cytokines do not predict the response to IFN treatment. There is no constant and regular change in circulating levels of these cytokines under IFN treatment with respect to treatment response.
Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndromes.

THIS SUBJECT
• Population pharmacokinetics and pharmacodynamics of rivaroxaban have been characterized in healthy subjects and in patients with total venous thromboembolism, deep vein thrombosis or atrial fibrillation.


 THIS STUDY ADDS
• This article is the first description of the population pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in patients with acute coronary syndrome (ACS). It is the largest population pharmacokinetic and pharmacodynamic study on rivaroxaban conducted to date (n= 2290). The PK and PK-PD relationship of rivaroxaban in patients with ACS were similar to those in other patient populations. In addition, model-based simulations showed that the influence of renal function and age on the exposure to rivaroxaban in the ACS population were similar to the findings from Phase 1 special population studies. These findings suggest that rivaroxaban has highly predictable PK-PD and may provide a consistent anticoagulant effect across the studied patient populations, which allows an accurate prediction of the dose to control anticoagulation optimally.



The aim of this analysis was to use a population approach to facilitate the understanding of the pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndrome (ACS) and to evaluate the influence of patient covariates on the exposure of rivaroxaban in patients with ACS.  A population pharmacokinetic model was developed using pharmacokinetic samples from 2290 patients in Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 46. The relationship between pharmacokinetics and the primary pharmacodynamic end point, prothrombin time, was evaluated.



The pharmacokinetics of rivaroxaban in patients with ACS was adequately described by an oral one-compartment model. The estimated absorption rate, apparent clearance and volume of distribution were 1.24 h(-1) (interindividual variability, 139%), 6.48 l h(-1) (31%) and 57.9 l (10%), respectively. Simulations indicate that the influences of renal function, age and bodyweight on exposure in ACS patients are consistent with the findings in previous Phase 1 studies. Rivaroxaban plasma concentrations exhibit a close-to-linear relationship with prothrombin time in the ACS population, with little interindividual variability. The estimated pharmacokinetic and pharmacodynamic parameters for the ACS patients were comparable to those for venous thromboembolism prevention, deep vein thrombosis and atrial fibrillation patients.



The similarity in pharmacokinetics/pharmacodynamics of rivaroxaban among different patient populations and the low interindividual variability in the exposure-prothrombin time relationship indicate that the anticoagulant effect of rivaroxaban is highly predictable and consistent across all the patient populations studied.
Identifying Neurobiological Phenotypes Associated with Alcohol Use Disorder Severity

Although numerous studies provide general support for the importance of genetic factors in the risk for alcohol use disorders (AUDs), candidate gene and genome-wide studies have yet to identify a set of genetic variations that explain a significant portion of the variance in AUDs. One reason is that alcohol-related phenotypes used in genetic studies are typically based on highly heterogeneous diagnostic categories. Therefore, identifying neurobiological phenotypes related to neuroadaptations that drive the development of AUDs is critical for the future success of genetic and epigenetic studies. One such neurobiological phenotype is the degree to which exposure to alcohol taste cues recruits the basal ganglia, prefrontal cortex, and motor areas, all of which have been shown to have a critical role in addictive behaviors in animal studies. To that end, this study was designed to examine whether cue-elicited responses of these structures are associated with AUD severity in a large sample (n=326) using voxelwise and functional connectivity measures. Results suggested that alcohol cues significantly activated dorsal striatum, insula/orbitofrontal cortex, anterior cingulate cortex, and ventral tegmental area. AUD severity was moderately correlated with regions involved in incentive salience such as the nucleus accumbens and amygdala, and stronger relationships with precuneus, insula, and dorsal striatum. The findings indicate that AUDs are related to neuroadaptations in these regions and that these measures may represent important neurobiological phenotypes for subsequent genetic studies.
Opportunities for strengthening provider-initiated testing and counselling for HIV in Namibia

This short report identifies enablers and barriers to the uptake of provider-initiated testing and counselling for HIV (PITC) in Namibia and identifies key opportunities for strengthening this vital aspect of the national HIV response. We explored this through facility mapping, register reviews and qualitative methods including focus group discussions and in-depth interviews. Four health facilities (clinics and hospitals) in two regions were included in the study. We identified that PITC in Namibia was largely delivered by lay counsellors operating in designated rapid testing rooms located in health facilities and found a large number of missed opportunities for HIV testing through this model. Nurses did not see it as an integral part of their role, were not aware of HIV testing and counselling policy, felt inadequately trained and supported, and experienced staffing shortages. Institutional issues also acted as barriers to nurses performing or initiating discussions about PITC. Wider dissemination and implementation of policy, increasing privacy of consultation spaces and community sensitisation are simple measures that represent opportunities for strengthening this response and ensuring that symptomatic individuals who are unaware of their HIV status do not fall through the net.
Lung cancer in never-smokers: a case-control study in a radon-prone area (Galicia, Spain).

The aim of the study was to assess the effect of residential radon exposure on the risk of lung cancer in never-smokers and to ascertain if environmental tobacco smoke modifies the effect of residential radon. We designed a multicentre hospital-based case-control study in a radon-prone area (Galicia, Spain). All participants were never-smokers. Cases had an anatomopathologically confirmed primary lung cancer and controls were recruited from individuals undergoing minor, non-oncological surgery. Residential radon was measured using alpha track detectors. We included 521 individuals, 192 cases and 329 controls, 21% were males. We observed an odds ratio of 2.42 (95% CI 1.45-4.06) for individuals exposed to ≥200 Bq·m(-3) compared with those exposed to <100 Bq·m(-3). Environmental tobacco smoke exposure at home increased lung cancer risk in individuals with radon exposure>200 Bq·m(-3). Individuals exposed to environmental tobacco smoke and to radon concentrations>200 Bq·m(-3) had higher lung cancer risk than those exposed to lower radon concentrations and exposed to environmental tobacco smoke. Residential radon increases lung cancer risk in never-smokers. An association between residential radon exposure and environmental tobacco smoke on the risk of lung cancer might exist.
Breast Cancer Detection Based on Incremental Biochemical and Physiological Properties of Breast Cancers : A Six-Year , Two-Site Study 1

To demonstrate that near-infrared spectroscopy would achieve sufficient sensitivity and specificity in human breast cancer to reach ROC/AUC values in the 90s and yet to warn of the potential liabilities of introduction of a novel technology in this field.  116 subjects from two nations (44 were cancer-verified by biopsy and histopathology) were reviewed. NIR spectroscopy of total hemoglobin and its relative oxygenation were monitored in breast cancers and compared to their contralateral breast in a 2D nomogram for diagnostic evaluation. A novel handheld NIR breast cancer detector pad with a 3-wavelength LED and 8 detectors with 4 cm separation between source and detectors was placed on the subject’s breast. The method is convenient, rapid, and safe and has achieved high patient compliance with minimal patient apprehension of compression, confinement, or radioactivity.  The absorbance increments of the cancerous region are referred to the mirror image location on the contralateral breast. The two metrics are increased hemoglobin concentration due to angiogenesis and decreased hemoglobin saturation due to hypermetabolism of the cancer. The 2D nomogram display of these two metrics shows Zone 1 contains verified cancers and Zone 2 contains noncancers. ROC evaluation of the nomogram gives 95% AUC for the two sites, Philadelphia and Leipzig.  A simple, economical breast cancer detector has achieved high patient compliance and a high ROC/AUC score for a population which involved a range of tumors down to and including those of 0.8–1 cm in diameter.
Sub-patterns of language network reorganization in pediatric localization related epilepsy: a multisite study.

To study the neural networks reorganization in pediatric epilepsy, a consortium of imaging centers was established to collect functional imaging data. Common paradigms and similar acquisition parameters were used. We studied 122 children (64 control and 58 LRE patients) across five sites using EPI BOLD fMRI and an auditory description decision task. After normalization to the MNI atlas, activation maps generated by FSL were separated into three sub-groups using a distance method in the principal component analysis (PCA)-based decisional space. Three activation patterns were identified: (1) the typical distributed network expected for task in left inferior frontal gyrus (Broca's) and along left superior temporal gyrus (Wernicke's) (60 controls, 35 patients); (2) a variant left dominant pattern with greater activation in IFG, mesial left frontal lobe, and right cerebellum (three controls, 15 patients); and (3) activation in the right counterparts of the first pattern in Broca's area (one control, eight patients). Patients were over represented in Groups 2 and 3 (P < 0.0004). There were no scanner (P = 0.4) or site effects (P = 0.6). Our data-driven method for fMRI activation pattern separation is independent of a priori notions and bias inherent in region of interest and visual analyses. In addition to the anticipated atypical right dominant activation pattern, a sub-pattern was identified that involved intensity and extent differences of activation within the distributed left hemisphere language processing network. These findings suggest a different, perhaps less efficient, cognitive strategy for LRE group to perform the task.
First Administration of the Fc-Attenuated Anti-β Amyloid Antibody GSK933776 to Patients with Mild Alzheimer’s Disease: A Randomized, Placebo-Controlled Study

To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the Fc-inactivated anti-β amyloid (Aβ) monoclonal antibody (mAb) GSK933776 in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).



This was a two-part, single blind, placebo-controlled, first-time-in-human (FTIH) study of single (n = 18) and repeat dose (n = 32) intravenous GSK933776 0.001-6 mg/kg (ClinicalTrials.gov: NCT00459550). Additional safety data from an open-label, uncontrolled, single dose study of intravenous GSK933776 1-6 mg/kg (n = 18) are included (
There were no cases of amyloid-related imaging abnormalities-edema (ARIA-E) or -hemorrhage (ARIA-H) after GSK933776 administration in both studies. Three patients across the two studies developed anti-GSK933776 antibodies. Plasma GSK933776 half-life (t1/2) was 10-15 days after repeat dosing. After each of three administrations of GSK933776, plasma levels of total Aβ42 and Aβ increased whereas plasma levels of free Aβ decreased dose dependently; no changes were observed for placebo. For total Aβ42 the peak:trough ratio was ≤2 at doses ≥3 mg/kg; for total Aβ the ratio was ≤2 at 6 mg/kg. CSF concentrations of Aβ showed increases from baseline to week 12 for Aβ X-38 (week 12:baseline ratio: 1.65; 95%CI: 1.38, 1.93) and Aβ X-42 (week 12:baseline ratio: 1.18; 95%CI: 1.06, 1.30) for values pooled across doses.



In this FTIH study the Fc-inactivated anti-Aβ mAb GSK933776 engaged its target in plasma and CSF without causing brain ARIA-E/H in patients with mild AD or MCI.
Overview of preclinical and clinical studies of interferon alfa-2b in combination with cytotoxic drugs

Both in vitro and in vivo studies have demonstrated antiproliferative effects of interferon alfa-2b (Intron A; Schering-Plough) when tested with human tumor cells. A clonogenic assay has been widely used to determine its direct antiproliferative effects on human tumor cells in vitro using colony reduction as a reproducible endpoint. As a single agent, interferon alfa-2b shows maximum tumor cell colony reduction when used in high concentrations with continuous cell exposure. Short-term exposure to interferon alfa-2b does not produce significant tumor cell colony reduction. Clonogenic assays have also been used to test combinations of interferon alfa-2b with cytotoxic drugs. Variations in drug scheduling, sequencing and concentrations have indicated the best combinations which maximize tumor cell colony reduction. Combinations of interferon alfa-2b with doxorubicin, cisplatin, vinblastine, melphalan and cyclophosphamide have been shown to have at least additive and occasionally synergistic antiproliferative effects. In clinical trials, optimal pairs of agents have been identified frequently combining either doxorubicin, cisplatin or vinblastine with interferon alfa-2b. Pretreatment with interferon alfa-2b has been adopted from in vitro studies and applied to most clinical trials. One study has enrolled 135 patients having a variety of advanced or recurrent solid tumor types, using a schema which combines interferon alfa-2b and doxorubicin administration, both given on a weekly basis for three weeks, followed by treatments every two weeks in responding patients. Clinical responses have been seen using this regimen in patients with ovarian, cervical, colorectal and pancreatic carcinomas and in one lymphoma patient. Another study has been designed combining melphalan, prednisone and interferon alfa-2b for the treatment of patients with relapsing multiple myeloma. This is also based upon preclinical data. New methods of administration are being studied giving interferon alfa-2b as a single agent or in combination with cisplatin by the intraperitoneal route to patients with relapsing ovarian carcinomas limited to the peritoneal cavity. This method can maximize both the levels of interferon alfa-2b as well as the tumor cell exposure time.
Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device.

Ventricular assist devices (VADs) are an accepted therapy for patients with end-stage heart failure. The implantable devices that are available produce a pulsatile flow and are very large. In 6 patients, beginning in November 1998, we started to use the continuous-flow implantable DeBakey VAD device, which weighs 93 g. To detect the flow in peripheral vessels, we measured transcranial Doppler signals in patients after implantation.



Transcranial Doppler studies were performed with the MULTI-DOP X4 device with two 2-MHz probes (for the middle cranial arteries) in 4 patients for up to 12 weeks twice weekly after implantation. The blood velocity was measured, and the pulsation index (PI) calculated. The measured pump flow and rotations per minute were registered. The preoperative echocardiographic assessment values were compared with those acquired 6 weeks after implantation. The PI increased continually in all patients after VAD implantation, left ventricular (LV) ejection fraction did not improve, but right ventricular (RV) ejection fraction after implantation improved compared with preoperative values. The LV end-diastolic diameter after implantation decreased between 11% and 46% intraindividually. There was no correlation between PI and blood pressure or, except in 1 patient, between PI and blood flow through the VAD.



The DeBakey VAD unloads the LV, which leads to a decrease in LV end-diastolic LV diameter and to the restoration of RV function. The unloaded LV and partially recovered RV provide a nearly physiological pulsatile flow despite the continuous flow of the VAD. Pulsatility is independent of peripheral vascular resistance. The first clinical experience with the DeBakey VAD was positive and has resulted in its continued use.