nils-herrmann/clean_scirepeval huggingface dataset:
Adrenal hyperplasia and adenomas are associated with inhibition of phosphodiesterase 11A in carriers of PDE11A sequence variants that are frequent in the population.

Several types of adrenocortical tumors that lead to Cushing syndrome may be caused by aberrant cyclic AMP (cAMP) signaling. We recently identified patients with micronodular adrenocortical hyperplasia who were carriers of inactivating mutations in the 2q-located phosphodiesterase 11A (PDE11A) gene. We now studied the frequency of two missense substitutions, R804H and R867G, in conserved regions of the enzyme in several sets of normal controls, including 745 individuals enrolled in a longitudinal cohort study, the New York Cancer Project. In the latter, we also screened for the presence of the previously identified PDE11A nonsense mutations. R804H and R867G were frequent among patients with adrenocortical tumors; although statistical significance was not reached, these variants affected significantly enzymatic function in vitro with variable increases in cAMP and/or cyclic guanosine 3',5'-monophosphate levels in HeLa and HEK293 cells. Adrenocortical tissues carrying the R804H mutation showed 2q allelic losses and higher cyclic nucleotide levels and cAMP-responsive element binding protein phosphorylation. We conclude that missense mutations of the PDE11A gene that affect enzymatic activity in vitro are present in the general population; protein-truncating PDE11A mutations may also contribute to a predisposition to other tumors, in addition to their association with adrenocortical hyperplasia. We speculate that PDE11A genetic defects may be associated with adrenal pathology in a wider than previously suspected clinical spectrum that includes asymptomatic individuals.
Interpersonelle Psychotherapie und Pharmakotherapie bei Post-Stroke-Depression

Die Effektivität von Psychotherapie bei Post-Stroke-Depression (PSD) wurde bislang nur wenig untersucht. Ziel dieser Machbarkeitsstudie war eine Evaluation der Wirksamkeit der interpersonellen Psychotherapie hinsichtlich Depression und Reha-Outcome im Vergleich zur Pharmakotherapie und einer Kombination beider Verfahren. Bei 35% von 485 untersuchten Schlaganfallpatienten lag eine PSD vor. Vierundsiebzig PSD-Patienten wurden randomisiert einer der 3 Behandlungsgruppen interpersonelle Psychotherapie, Medikation und Kombinationsbehandlung zugeführt. Die Untersuchung erfolgte mittels Hamilton-Depressionsskala, Hospital Anxiety and Depression Scale (HADS) und bezüglich des Reha-Outcomes mit dem Barthel-Index (BI) und Indikatoren des Rehastatus (IRES). Zwischen den Behandlungsgruppen wurden keine signifikanten Unterschiede festgestellt. Alle Patienten profitierten von einer gezielten antidepressiven Behandlung auch hinsichtlich Lebensqualität und sozialer Einbindung. Zusätzlich konnte ein Zusammenhang zwischen Rehabilitationsergebnis und Depressivität festgestellt werden. Eine psychotherapeutische antidepressive Behandlung von Patienten mit PSD ist in den Stationsalltag integrierbar und wird von den Patienten akzeptiert. In dieser Studie war die Kombinationsbehandlung aus interpersoneller Psychotherapie und Medikation genauso effektiv wie die jeweiligen Monotherapien. Offenbar sind zwischen den Behandlungsformen nur kleine Unterschiede zu erwarten, was größere Studienproben nötig macht. Only few studies investigated the effectiveness of psychotherapy in post-stroke depression (PSD). The aim of this feasibility study was to compare interpersonal psychotherapy, pharmacotherapy, and their combination regarding depression and rehabilitation outcome. Post-stroke depression was found in 35% of 485 stroke patients examined. Seventy-four PSD patients were randomised to one of three treatment conditions. Severity of depression was measured by the Hamilton Depression Rating Scale and the Hospital Anxiety and Depression Scale. The Barthel Index and a questionnaire for health-related quality of life were used as measurements of rehabilitation outcome. There were no significant differences between the three groups in patient mood or rehabilitation outcome. Concerning the severity of depression, quality of life, and social support, all patients showed benefits from antidepressive treatment. In addition a correlation was found between rehabilitation outcome and depression. In this feasibility study all antidepressive treatments were successfully implemented in the rehabilitation of post-stroke depressed patients. Combination therapy (interpersonal psychotherapy plus medication) was as effective as one of those elements alone. Because of the small sample size however, further randomized trials are required.
In-vivo validation of a new clinical tool to quantify three-dimensional myocardial strain using ultrasound

Three-dimensional (3D) strain analysis based on real-time 3-D echocardiography (RT3DE) has emerged as a novel technique to quantify regional myocardial function. The goal of this study was to evaluate accuracy of a novel model-based 3D tracking tool (eSie Volume Mechanics, Siemens Ultrasound, Mountain View, CA, USA) using sonomicrometry as an independent measure of cardiac deformation. Thirteen sheep were instrumented with microcrystals sutured to the epi- and endocardium of the inferolateral left ventricular wall to trace myocardial deformation along its three directional axes of motion. Paired acquisitions of RT3DE and sonomicrometry were made at baseline, during inotropic modulation and during myocardial ischemia. Accuracy of 3D strain measurements was quantified and expressed as level of agreement with sonomicrometry using linear regression and Bland–Altman analysis. Correlations between 3D strain analysis and sonomicrometry were good for longitudinal and circumferential strain components (r = 0.78 and r = 0.71) but poor for radial strain (r = 0.30). Accordingly, agreement (bias ± 2SD) was −5 ± 6 % for longitudinal, −5 ± 7 % for circumferential, and 15 ± 19 % for radial strain. Intra-observer variability was low for all components (intra-class correlation coefficients (ICC) of respectively 0.89, 0.88 and 0.95) while inter-observer variability was higher, in particular for radial strain (ICC = 0.41). The present study shows that 3D strain analysis provided good estimates of circumferential and longitudinal strain, while estimates of radial strain were less accurate between observers.
Differential diffusions of indinavir and lopinavir in genital secretions of human immunodeficiency virus-infected women.

Plasma and cervicovaginal secretion (CVS) samples were collected from 19 human immunodeficiency virus type 1-infected women on lopinavir- or indinavir-containing regimens. Lopinavir and indinavir were detectable in 29 and 93% of CVS samples, respectively, a finding that may be ascribed to these drugs' differences in protein binding and pK(a). The relationship between lopinavir and indinavir pharmacodynamics and viral evolution in the female genital tract should be assessed over time.
Resolution of exercise oscillatory ventilation with adaptive servoventilation in patients with chronic heart failure and Cheyne-Stokes respiration: preliminary study.

Exercise oscillatory ventilation (EOV) is a common pattern of breathing in heart failure (HF) patients, and indicates a poor prognosis.



To investigate the effects of adaptive servoventilation (ASV) on ventilatory response during exercise.



We studied 39 HF patients with left ventricular ejection fraction (LVEF) £ 45. Cardiorespiratory polygraphy, cardiopulmonary exercise testing (CPET), echocardiography, and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration were performed. Twenty patients with Cheyne-Stokes respiration and apnoea-hypopnoea index (AHI) ≥ 15/h were identified. Of these, 11 patients were successfully titrated on ASV and continued therapy. In the third month of ASV treatment, polygraphy, CPET, echocardiography, and measurement of NT-proBNP concentration were performed again.



The EOV was detected at baseline in 12 (31%) HF patients, including eight (67%) who underwent ASV. The EOV was associated with significantly lower LVEF, peak oxygen uptake (VO(2)), and ventilatory anaerobic threshold (VAT), and a significantly higher left ventricular diastolic diameter (LVDD), slope of ventilatory equivalent for carbon dioxide (VE/VCO(2)), AHI, central AHI and NT-proBNP concentration. In seven patients with EOV, reversal of EOV in the third month of ASV therapy was observed; only in one patient did EOV persist (p = 0.0156).



The EOV can be reversed with ASV therapy. The EOV in association with central sleep apnoea and Cheyne- -Stokes respiration (CSA/CSR) is prevalent in HF patients and correlates with severity of the disease.
The importance of protein kinase A in prostate cancer: relationship to patient outcome in Radiation Therapy Oncology Group trial 92-02.

We previously reported that protein kinase A type I (PKA(RIalpha)) overexpression was predictive of outcome in prostate cancer patients treated with radiotherapy (RT) +/- short-term androgen deprivation (STAD) on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Here, we attempt to verify our prior findings and test the hypothesis that the relationship of the length of AD to patient outcome is affected by PKA(RIalpha) overexpression.



There were 313 cases in the RTOG 92-02 study cohort with available tissue and suitable staining by immunohistochemistry. Median follow-up was 10.1 years. The intensity of PKA(RIalpha) staining intensity was quantified manually and by image analysis. Multivariate analyses were done for overall mortality using Cox proportional hazards models and for local failure, biochemical failure, distant metastasis, and cause-specific mortality using Fine and Gray's regression models.



The expression levels of PKA(RIalpha), determined by manual and image analysis, were strongly correlated (P < 0.0001). In the multivariate analyses, manual-quantified and image analysis-quantified PKA(RIalpha) staining intensities were independent predictors of distant metastasis (P < 0.01), local failure (P < 0.05), and biochemical failure (P <or= 0.01). Furthermore, the benefit of long-term AD over STAD was much less when PKA(RIalpha) expression was high.



PKA(RIalpha) overexpression has been shown in two RTOG trials to be associated with an increased risk of failure after AD + RT. In this series of contemporary high-risk patients, PKA(RIalpha) overexpression was associated with diminished response to LTAD + RT relative to STAD + RT, suggesting that such patients would be ideal for a PKA(RIalpha) knockdown strategy.
Ambulatory oxygen therapy in stable kyphoscoliosis.

Patients with chronic obstructive pulmonary disease (COPD) may benefit from ambulatory oxygen; however, the effect of exercise on arterial oxygen saturation (Sa,O2) in patients with kyphoscoliosis and of correction with ambulatory oxygen have not been previously reported. Twelve patients with stable kyphoscoliosis (mean (SD) Cobb angle 79 (26) degrees) were studied, with mean (SD) arterial oxygen tension (Pa,O2) 8.96 (0.93) kPa, arterial carbon dioxide tension (Pa,CO2) 6.52 (0.66), forced expiratory volume in one second (FEV1) 0.90 (0.15) L, forced vital capacity (FVC) 1.34 (0.46) L. Six-minute walking tests with oximetry and visual analogue scores (VAS) for breathlessness were performed on air (baseline), and with cylinders containing air and oxygen at 2 L-min-1. Cylinder walks were in random order, with patients blinded to cylinder content. Patients showed oxygen desaturation at each stage of the study. At baseline, oxygen desaturation during exercise was correlated with deterioration in VAS breathlessness scores. Ambulatory oxygen produced significant improvements in desaturation, breathlessness scores and recovery time compared to baseline and air cylinder walks. There was no relationship between baseline desaturation and changes in walking distance. Although exercise desaturation, breathlessness and recovery times were significantly improved with ambulatory oxygen at 2 L.min-1, walking distance was unaffected. We conclude that patients with moderate to severe kyphoscoliosis have significant oxygen desaturation on exercise and should thus routinely receive oximetry on exercise and assessment for ambulatory oxygen therapy.
[Validation of geriatric depression scale in a general outpatient clinic].

The Geriatric Depression Scale for screening depressive symptoms in the elderly has not been assessed in elderly outpatients who seek primary health care in Brazil. The objective was to determine the validity of the Short Scale for Major Depressive Episode or Dysthymia (GDS-15) in elderly outpatients.



The scale was applied in 302 subjects with 65 years and older and then examined by an independent geriatrician, blinded to the results. Major depression and dysthymia were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Sensitivity and specificity were calculated at several cutoff values and a Receiver Operating Characteristic curve was plotted.



The best equilibrium was at the cutoff value of 5/6 showing 81% sensitivity and 71% specificity; the area under the Receiver Operating Characteristic curve was 0.85 (95% CI: 0.79-0.91).



The GDS-15 can be used for screening depressive symptoms in Brazilian elderly outpatients. The previously suggested cutoff value of 5/6 is adequate.
A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers

The prognosis of advanced biliary tract carcinoma is poor with chemotherapy limited to a palliative role. This randomised study was designed to evaluate the effectiveness of a new liposomal thymidylate synthase inhibitor (TSI), OSI-7904L, in parallel with a modified de Gramont regimen of 5-FU/LV in patients with advanced biliary cancer. Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI-7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5-FU/LV (intravenous l-LV 200 mg/m2, bolus 5-FU 400 mg/m2 and a 46-h infusion of 5-FU 2,400 mg/m2) every 14 days. Twenty-two patients were randomised, 11 to each group. No patients responded in the OSI-7904L arm, while one patient achieved a partial response in the 5-FU/LV arm. The rates of disease stabilisation were 4/11 (OSI-7904L) and 10/11 (5-FU/LV). Both treatment arms were generally well tolerated. These results show that the activity of OSI-7904L is below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilisation. A simplified de Gramont schedule appears to have marginally more activity. Both treatments were well tolerated.
Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome.

Early-generation β-blockers lower blood pressure and reduce cardiovascular morality in coronary artery disease and congestive heart failure but worsen glucose homeostasis and fibrinolytic balance. Nebivolol is a third-generation β-blocker that increases the bioavailability of nitric oxide. We compared the effect of nebivolol (5 mg/d) and the β(1)-selective antagonist metoprolol (100 mg/d) on glucose homeostasis and markers of fibrinolysis in 46 subjects with metabolic syndrome. Subjects underwent a frequently sampled IV glucose tolerance test after 3-week washout and placebo treatment and after randomized treatment with study drug. After 12-week treatment, nebivolol and metoprolol equivalently decreased systolic blood pressure, diastolic blood pressure, and heart rate. Neither drug affected β-cell function, disposition index, or acute insulin response to glucose. Metoprolol significantly decreased the insulin sensitivity index. In contrast, nebivolol did not affect insulin sensitivity, and the decrease in sensitivity was significantly greater after metoprolol than after nebivolol (-1.5±2.5×10(-4)×min(-1) per milliunit per liter versus 0.04±2.19×10(-4)×min(-1) per milliunit per liter after nebivolol; P=0.03). Circulating plasminogen activator inhibitor also increased after treatment with metoprolol (from 9.8±6.8 to 12.3±7.8 ng/mL) but not nebivolol (from 10.8±7.8 to 10.5±6.2 ng/mL; P=0.05 versus metoprolol). Metoprolol, but not nebivolol, increased F(2)-isoprostane concentrations. In summary, treatment with metoprolol decreased insulin sensitivity and increased oxidative stress and the antifibrinolytic plasminogen activator inhibitor 1 in patients with metabolic syndrome, whereas nebivolol lacked detrimental metabolic effects. Large clinical trials are needed to compare effects of nebivolol and the β(1) receptor antagonist metoprolol on clinical outcomes in patients with hypertension and the metabolic syndrome.
Ultrasound Imaging for the rheumatologist XXVII. Sonographic assessment of the knee in patients with rheumatoid arthritis.

The aims of our study were to investigate the prevalence of ultrasound (US) pathologic abnormalities and to compare them with the clinical findings in the knee of rheumatoid arthritis (RA) patients. One hundred RA patients were enrolled in the study. Bilateral US examination of the knee was performed to visualise the presence of effusion, synovial proliferation, bone erosions, femoral cartilage abnormalities, quadricipital and/or patellar enthesopathy. The popliteal fossa and the calf region were also evacuate to detect popliteal cyst. We observed joint effusion in 140 out of 200 (70%) knees. Synovial hypertrophy was present in 115 out of 140 (82%) knees associated with effusion and in 22 out of 115 (19%) knees intra-articular power Doppler (PD) signal was found. Hyperechoic spots within the cartilage layer, suggestive of pyrophosphate crystals deposit, were detected in the knees of 3 patients. US signs of quadricipital and/or patellar enthesopathy were detected in 53 out 200 (26%) knees. Bone erosions were visualised in 16 out 200 (8%) knees. Popliteal cyst was found in 66 out of 200 (33%) joints. US examination of the knee is more sensitive than clinical examination in the detection of joint inflammation and allows for the identification of different patterns of pathologic changes at knee level, including morphostructural changes at both cartilage and tendon level.
The use of intradialytic parenteral nutrition in acutely ill haemodialysed patients.

Protein/caloric malnutrition is a problem in chronically haemodialysed patients, and is an independent risk factor for increased mortality in these patients.



To assess the safety and efficiency of intradialytic parenteral nutritional (IDPN) as nutritional support in acutely ill haemodialysis patients.



Twenty-two haemodialysis patients received IDPN after either major surgical or medical illnesses. Parameters measured included possible complications of IDPN, dialysis adequacy, patients' weight, protein catabolic rate (PCR) and serum levels of albumin, pre-albumin, creatinine, cholesterol, c-reactive protein (c-RP) and haemoglobin. After the end of the study all patients were followed-up for a further 6 months.



Patients received IDPN for 1.5-48 months. Eighteen patients received IDPN <6 months. IDPN was safe for all patients. Throughout this period dialysis remained adequate. Weight loss in all patients ceased after approximately 2 months of IDPN. PRC, serum albumin, pre-albumin, cholesterol and creatinine levels all increased significantly. c-RP dropped from 77+/-86 mg/l to 9+/-10 mg/l.



IDPN can be safely used in haemodialysed patients who are acutely ill and are unable to meet daily nutritional requirements with an oral intake. All studied parameters of nutrition and inflammation improved significantly while patients were treated with IDPN.
Preneoplasia in mouse models

The main focus of this review is the role of mammary stem cells in normal breast development and carcinogenesis. We have developed a new in vitro culture system that permits, for the first time, the propagation of mammary stem and progenitor cells in an undifferentiated state, which should facilitate the elucidation of pathways that regulate normal mammary stem-cell self-renewal and differentiation. Furthermore, we propose a model in which transformation of stem cells, or early progenitor cells, results in carcinogenesis. A key event in this process is the deregulation of normal self-renewal in these cells. Transformed mammary stem or progenitor cells undergo aberrant differentiation processes that result in generation of the phenotypic heterogeneity found in human and rodent breast cancers. This phenotypic diversity is driven by a small subset of mammary tumour stem cells. We will discuss the important implications of this mammary tumour stem-cell model.
Is informed consent related to success in exercise and diet intervention as evaluated at 12 months? DR's EXTRA study

There is a permanent need to evaluate and develop the ethical quality of scientific research and to widen knowledge about the effects of ethical issues. Therefore we evaluated whether informed consent is related to implementation and success in a lifestyle intervention study with older research participants. There is little empirical research into this topic.



The subjects (n = 597) are a subgroup of a random population sample of 1410 men and women aged 57-78 years who are participating in a 4-year randomized controlled intervention trial on the effects of physical exercise and diet on atherosclerosis, endothelial function and cognition. Data were collected in two steps: A questionnaire about informed consent was given to all willing participants (n = 1324) three months after the randomization. Data on implementation and success in the exercise and diet interventions were evaluated at 12 months by intervention-group personnel. The main purpose of the analysis procedure performed in this study was to identify and examine potential correlates for the chosen dependent variables and to generate future hypotheses for testing and confirming the independent determinants for implementation and success. The nature of the analysis protocol is exploratory at this stage.



About half of the participants (54%) had achieved good results in the intervention. Nearly half of the participants (47%) had added to or improved their own activity in some sector of exercise or diet. Significant associations were found between performance in the interventions and participants' knowledge of the purpose of the study (p < 0.001), and between success in interventions and working status (p = 0.02), and the participants' knowledge of the purpose of the study (p = 0.04).



The main finding of this study was that those participants who were most aware or had understood the purpose of the study at an early stage had also attained better results at their 12-month intervention evaluation. Therefore, implementation and success in intervention is related to whether subjects receive a sufficient amount and are able to comprehend the information provided i.e. the core principles of informed consent.