nils-herrmann/clean_scirepeval huggingface dataset:
Dealing with the complex dynamics of teaching hospitals

Innovation and change in postgraduate medical education programs affects teaching hospital organizations, since medical education and clinical service are interrelated.Recent trends towards flexible, time-independent and individualized educational programs put pressure on this relationship. This pressure may lead to organizational uncertainty, unbalance and friction making it an important issue to analyze.The last decade was marked by a transition towards outcome-based postgraduate medical education. During this transition competency-based programs made their appearance. Although competency-based medical education has the potential to make medical education more efficient, the effects are still under debate. And while this debate continues, the field of medical education is already introducing next level innovations: flexible and individualized training programs. Major organizational change, like the transition to flexible education programs, can easily lead to friction and conflict in teaching hospital organizations.This article analyses the organizational impact of postgraduate medical education innovations, with a particular focus on flexible training and competency based medical education. The characteristics of teaching hospital organizations are compared with elements of innovation and complexity theory.With this comparison the article argues that teaching hospital organizations have complex characteristics and behave in a non-linear way. This perspective forms the basis for further discussion and analysis of this unexplored aspect of flexible and competency based education.
Diffusion magnetic resonance imaging study of schizophrenia in the context of abnormal neurodevelopment using multiple site data in a Chinese Han population

Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention.
Effect of a tomato-rich diet on markers of cardiovascular disease risk in moderately overweight, disease-free, middle-aged adults: a randomized controlled trial.

Cardiovascular disease (CVD) is a major cause of mortality in the United Kingdom. Epidemiologic studies suggest that consumption of tomato-based foods may lower CVD risk. Such potential benefits have been ascribed in part to high concentrations of lycopene in the tomatoes. However, these findings have not yet been validated by comprehensive intervention trials.



The aim of this study was to conduct a single-blind, randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods affects recognized biomarkers of CVD risk.



After a 4-wk run-in period with a low-tomato diet, 225 volunteers (94 men and 131 women) aged 40-65 y were randomly assigned into 1 of 3 dietary intervention groups and asked to consume a control diet (low in tomato-based foods), a high-tomato-based diet, or a control diet supplemented with lycopene capsules (10 mg/d) for 12 wk. Blood samples were collected at baseline, at 6 wk, and after the intervention and were analyzed for carotenoid and lipid profiles and inflammatory markers. Blood pressure, weight, and arterial stiffness were also measured. Dietary intake was also determined during the intervention.



None of the systemic markers (inflammatory markers, markers of insulin resistance and sensitivity) changed significantly after the dietary intervention. Moreover, lipid concentrations and arterial stiffness were also unaffected by the interventions.



These data indicate that a relatively high daily consumption of tomato-based products (equivalent to 32-50 mg lycopene/d) or lycopene supplements (10 mg/d) is ineffective at reducing conventional CVD risk markers in moderately overweight, healthy, middle-aged individuals.
Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study

Micafungin, a clinically important echinocandin antifungal drug, needs to be investigated as empirical therapy in febrile neutropenia in comparison with azole compounds. A prospective randomized study was conducted to compare clinical outcomes between micafungin and intravenous itraconazole as an empirical therapy for febrile neutropenia in hematological malignancies. The antifungal drug (micafungin 100 mg or itraconazole 200 mg IV once daily) was given for high fever that was sustained despite the administration of appropriate antibiotics. Treatment success was determined by composite end points based on breakthrough invasive fungal infection (IFI), survival, premature discontinuation, defervescence, and treatment of baseline fungal infection. Duration of fever, hospital stay, and overall survival (OS) were studied. A total of 153 patients were randomized to receive micafungin or itraconazole. The overall success rate was 7.1 % point higher in the micafungin group (64.4 vs. 57.3 %, p = 0.404), satisfying the statistical criteria for the non-inferiority of micafungin. The duration of fever and hospital stay were significantly shorter in the micafungin group (6 vs. 7 days, p = 0.014; 22 vs. 27 days, p = 0.033, respectively). Grade 3 adverse events including hyperbilirubinemia (2 vs. 7), elevation of transaminase levels (2 vs. 4), electrolyte imbalance (1 vs. 2), atrial fibrillation (1 vs. 0), and anaphylaxis (1 vs. 0) occurred in 7 and 13 patients in the micafungin (10.4 %) and itraconazole (18.8 %) groups, respectively. Micafungin, when compared with itraconazole, had favorably comparable success rate and toxicity profiles on febrile neutropenia in patients with hematological malignancies. In addition, it showed superior effect on shortening the hospital stay.
Intraoperative guidance in parathyroid surgery using near-infrared fluorescence imaging and low-dose Methylene Blue.

Identification of diseased and normal parathyroid glands during parathyroid surgery can be challenging. The aim of this study was to assess whether near-infrared (NIR) fluorescence imaging using administration of a low-dose Methylene Blue (MB) at the start of the operation could provide optical guidance during parathyroid surgery and assist in the detection of parathyroid adenomas.



Patients diagnosed with primary hyperparathyroidism planned for parathyroidectomy were included. Patients received 0.5 mg/kg MB intravenously directly after start of anesthesia. During the operation, NIR fluorescence imaging was performed to identify parathyroid adenomas. Imaging results were compared with a previous published feasibility study in which 12 patients received MB after intraoperative identification of the adenoma.



A total of 13 patients were included in the current study. In 10 of 12 patients with a histologically proven adenoma, the adenoma was fluorescent. Mean signal to background ratio was 3.1 ± 2.8. Mean diameter of the resected lesions was 17 ± 9 mm (range 5-28 mm). Adenomas could be identified up to 145 minutes after administration, which was the longest timespan until resection. Interestingly, in 3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with a signal to background ratio of 1.8 ± 0.4 were identified using NIR fluorescence imaging.



Early administration of low-dose MB provided guidance during parathyroidectomy by identifying both parathyroid adenomas and normal parathyroid glands. In patients in whom difficult identification of the parathyroid adenoma is expected or when normal glands have to be identified, the administration of MB may improve surgical outcome.
Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1.

Human CD34(+) progenitor-derived Langerhans-type dendritic cells (LCs) are more potent stimulators of T-cell immunity against tumor and viral antigens in vitro than are monocyte-derived DCs (moDCs). The exact mechanisms have remained elusive until now, however. LCs synthesize the highest amounts of IL-15R-α mRNA and protein, which binds IL-15 for presentation to responder lymphocytes, thereby signaling the phosphorylation of signal transducer and activator of transcription 5 (pSTAT5). LCs electroporated with Wilms tumor 1 (WT1) mRNA achieve sufficiently sustained presentation of antigenic peptides, which together with IL-15R-α/IL-15, break tolerance against WT1 by stimulating robust autologous, WT1-specific cytolytic T-lymphocytes (CTLs). These CTLs develop from healthy persons after only 7 days' stimulation without exogenous cytokines and lyse MHC-restricted tumor targets, which include primary WT1(+) leukemic blasts. In contrast, moDCs require exogenous rhuIL-15 to phosphorylate STAT5 and attain stimulatory capacity comparable to LCs. LCs therefore provide a more potent costimulatory cytokine milieu for T-cell activation than do moDCs, thus accounting for their superior stimulation of MHC-restricted Ag-specific CTLs without need for exogenous cytokines. These data support the use of mRNA-electroporated LCs, or moDCs supplemented with exogenous rhuIL-15, as vaccines for cancer immunotherapy to break tolerance against self-differentiation antigens shared by tumors.
The effectiveness of a convergence dialogue meeting with the employer in promoting return to work as part of the cognitive-behavioural treatment of common mental disorders: A randomized controlled trial.

Dialogue between supervisor and employee is of great importance for occupational rehabilitation.



To evaluate the effectiveness of a convergence dialogue meeting (CDM) of employee, therapist and supervisor aimed at facilitating return to work (RTW) as part of cognitive-behavioural treatment.



Randomized controlled trial including 60 employees sick-listed with common mental disorders and referred for specialized mental healthcare. Employees were randomly allocated either to an intervention group (n = 31) receiving work-focused cognitive-behavioural therapy plus CDM or a control group (n = 29) receiving work-focused cognitive-behavioural therapy without CDM.



The time to first RTW was 12 days shorter (p = 0.334) in the intervention group, although full (i.e., at equal earnings as before reporting sick) RTW took 41 days longer (p = 0.122) than the control group. The odds of full RTW at the end of treatment were only 7% higher (p = 0.910) in the intervention group as compared to the control group.



CDM did not significantly reduce the time to RTW. We recommend that therapists who are trained on CDM focus on barriers and solutions for RTW.
Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy.

Fatigue is a common problem among colon cancer patients and typically increases during chemotherapy. Exercise during chemotherapy might have beneficial effects on fatigue. To investigate the short- and long-term effects of an exercise program in colon cancer patients during adjuvant treatment, the Physical Activity During Cancer Treatment study was conducted.



In this multicenter randomized controlled trial, 33 colon cancer patients undergoing chemotherapy (21 men and 12 women) were randomly assigned to either a group receiving an 18-wk supervised exercise program (n = 17) or to usual care (n = 16). The primary outcome was fatigue as measured by the Multidimensional Fatigue Inventory and the Fatigue Quality List. Secondary outcomes were quality of life, physical fitness, anxiety, depression, body weight, and chemotherapy completion rate. Outcome assessment took place at baseline, postintervention (18 wk) and at 36 wk.



Intention-to-treat mixed linear model analyses showed that patients in the intervention group experienced significantly less physical fatigue at 18 wk and general fatigue at 36 wk (mean between group differences, -3.2; 95% confidence interval [CI], -6.2 to -0.2; effect size [ES], -0.9 and -2.7; 95% CI, -5.2 to -0.1; ES, -0.8, respectively), and reported higher physical functioning (12.3; 95% CI, 3.3-21.4; ES, 1.0) compared with patients in the usual care group.



The Physical Activity During Cancer Treatment trial shows that an 18-wk supervised exercise program in colon cancer patients during chemotherapy is safe and feasible. The intervention significantly reduced physical fatigue at 18 wk and general fatigue at 36 wk. Considering the number of patients included in the present study, replication in a larger study population is required.
The effect of incremental endurance exercise training on left ventricular mechanics: a prospective observational deformation imaging study.

Exercise training has been known to cause structural and functional alterations in the heart called athletes heart. We aimed to investigate the effects of incremental endurance exercise training (IEET) on the left ventricular (LV) mechanics in healthy subjects.



This prospective observational study included 34 healthy young men who participated in competitive sports. The participants were subjected to a six-month IEET program. The LV mechanics measured using two-dimensional speckle tracking echocardiography was recorded while the participants were in an inactive state before and at the end of the six months. To compare continuous variables before and after IEET, Wilcoxon or paired-t test were used.



Baseline and post training echocardiographic measurements showed that there was no significant change in LV ejection fraction (%) (p=0.64) and there were an increase in end-systolic and end-diastolic diameters, posterior and septal wall thickness, relative wall thickness and LV mass index (p<0.05, for all). LV mechanical parameters such as global strain (S) (19.8±1.33% vs. 20.4±1.26%, p=0.001), apical four -chamber S (19.4±1.96% vs. 20.1±1.86%, p=0.01), apical two- chamber S (19.9±1.75% vs. 20.7±1.75%, p=0.003), apical (23.0±3.1% vs. 23.6±3.2%, p=0.03), and basal circumferential S (21.1±2.2 % vs. 21.6±2.5%, p=0.03), and apical rotation (degree) (7.9±0.95 vs. 8.4±0.74, p=0.001) values were significantly increased by IEET.



We demonstrated that IEET has led to exercise related cardiac structural and functional changes such as LV dilatation and LV hypertrophy, accompanied by a significant increase in LV systolic S and LV twist measurements.
Comparative study related to cardiovascular safety between bupivacaine (S75-R25) and ropivacaine in brachial plexus block.

Bupivacaine is a first choice for regional anesthesia considering its effectiveness, long duration and less motor blockade. Bupivacaine (S75-R25) is a mixture of optical isomers containing 75% levobupivacaine (S-) and 25% dextrobupivacaine (R+) created by a Brazilian pharmaceutical company. This investigation compared cardiac safety and efficacy of bupivacaine S75-R25 with vasoconstrictor and ropivacaine for brachial plexus blockade.



Patients were randomized to receive brachial plexus anesthesia with either bupivacaine S75-R25 with epinephrine 1:200,000 (bupi) or ropivacaine (ropi), both at 0.50%, in 30 mL solution. We registered a continuous Holter ECG throughout the procedure, as well as the Lovett scale of force in addition to monitoring (heart rate, pulse oximetry and non-invasive blood pressure). The incidence of adverse events was compared with the chi-square or Fisher test.



We allocated forty-four patients into two groups. They did not show any difference related to age, weight or height, gender, as well as for surgical duration. Supraventricular arrhythmias were not different before or after the plexus blockade, independent of the local anesthetic chosen. Loss of sensitivity was faster for the bupivacaine group (23.1 ± 11.7 min) compared to the ropivacaine one (26.8 ± 11.5 min), though not significant (p = 0.205, Student t). There was a reduction in the cardiac rate, observed during the twenty-four-hour Holter monitoring.



This study showed similar efficacy between bupivacaine S75-R25 for brachial plexus blockade and ropivacaine, with similar incidences of supraventricular arrhythmias.
Shared care by paediatric oncologists and family doctors for long-term follow-up of adult childhood cancer survivors: a pilot study.

Since 75% of children with cancer will become long-term survivors, late effects of treatment are an ever increasing issue for patients. Paediatric oncologists generally agree that cancer survivors should be followed up for the remainder of their lives, but they might not be the most suitable health-care providers to follow up survivors into late adulthood. We designed a 3-year study to assess whether shared-care by paediatric oncologists and family doctors in the long-term follow-up of survivors of childhood cancers is feasible, whether a shared-care model is compatible with collection of data needed for registration of late effects, and how a shared-care model is assessed by survivors and family doctors.



In 2004 and 2005, adult survivors of childhood cancers were randomly chosen from eligible patients diagnosed with childhood cancer (excluding CNS tumours) or Langerhans-cell histiocytosis between January, 1968, and December, 1997, and recalled to the long-term follow-up (LTFU) clinic at the University Medical Centre Groningen, Groningen, Netherlands, where they underwent physical and clinical assessments by an on-site family doctor (visit 1). At this visit, assessments were done according to guidelines of the UK Children's Cancer Study Group Late Effects Group, and late effects were graded by use of Common Terminology Criteria for Adverse Events (version 3). Follow-up assessments were done 1 year later in 2005 and 2006 by local family doctors (visit 2), who were asked to return data to the LTFU clinic. At this visit, the local family doctors were asked to complete a three-item questionnaire and patients were asked to complete a seven-item questionnaire about their satisfaction with the shared-care model. At the next consultation, which was planned for the end of the study (visit 3), the on-site family doctor advised patients about future follow-up on the basis of their individual risk of late effects. Main endpoints were numbers of participants, satisfaction ratings, and proportions of local family doctors who returned data that they obtained at visit 2 to the LTFU clinic.



133 individuals were chosen at random from 210 enrolled adult survivors. 123 of 133 (92%) randomly selected survivors and 115 of 117 (98%) of their family doctors agreed to participate in the share-care programme. 103 of 115 (90%) family doctors returned data to the LTFU clinic at visit 2. 89 of 101 (88%) of survivors were satisfied with this shared-care model, as were 94 of 115 (82%) family doctors; 18 of 115 (16%) family doctors had no views either way; and three of 115 (3%) family doctors were dissatisfied.



Shared-care by paediatric oncologists and family doctors is feasible for long-term follow-up of adult survivors of childhood cancers.
Bottoms up: improvisational micro-agents

This paper describes our current approach in implementing computational improvisational micro-agents, agents that perform one specific aspect of our findings from the Digital Improv Project. This approach is intended to foster bottom-up research to better understand how to build more complex agent behaviors in a theatrical improvisational setting. The Digital Improv Project is a multi-year study at the Georgia Institute of Technology focused on studying real life theatrical improvisers with an aim towards better understanding the cognition employed in improvisation at the individual and group level.
Pharmacokinetic interaction between telaprevir and methadone.

Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of R- and S-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound R-methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (C(min)), the maximum plasma concentration (Cmax), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC(0-24)) for R-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC0-24 ratio of S-methadone/R-methadone was not altered. The median unbound percentage of R-methadone increased by 26% in the presence of telaprevir. The R-methadone median (absolute) unbound C(min) values in the absence (10.63 ng/ml) and presence (10.45 ng/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total R-methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound R-methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.).