nils-herrmann/clean_scirepeval huggingface dataset:
Low-dose estrogen supplementation improves vascular function in hypogonadal men.

It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean+/-SEM age, 68.7+/-2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treatment, mean estradiol levels increased from <30 to 308+/-65 pmol/L, and both systolic and diastolic blood pressures were reduced. HDL cholesterol levels increased significantly, and vasoconstrictor responses to the NO synthase inhibitor N(G)-monomethyl-L-arginine (1, 2, 4 micromol/min) were enhanced. Vasoconstrictor responses to angiotensin II (8, 16, 32 ng/min) were markedly attenuated by estrogen treatment, as were vasoconstrictor responses to norepinephrine (25, 50, 100 ng/min). Estrogen did not alter the vasodilator responses to acetylcholine (9.25, 18.5, 37 microgram/min) or to the endothelium-independent agent sodium nitroprusside (1.6 microgram/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of vasoconstrictor responses to angiotensin II and norepinephrine. These findings suggest the need to consider a possible clinical role for estrogenic compounds in cardiovascular risk reduction in some groups of men.
Correlation between respiration-induced thoracic expansion and a shift of central structures

The fusion of computed tomography (CT) and positron emission tomography (PET) may improve diagnostic accuracy, but is limited by different breathing protocols. This study aimed at quantifying respiration-induced alignment errors. PET-CT was acquired in 24 patients. Contrast-enhanced whole-body CT was obtained in a single breath hold in the expiratory state of a normal breathing cycle. An inspiratory low-dose CT of the thorax was acquired in the same session, and comparison of the two CT scans was used to assess the potential mismatch of PET and CT fusion. The largest craniocaudal expansion was found in the area of the diaphragm. A considerable sagittal expansion was found in the anterior parts of the lungs. Central tracheo-bronchial structures were displaced during inspiration mainly in the anterior and caudal directions. The craniocaudal shift of central structures showed a linear correlation with the diaphragmatic expansion, whereas the sagittal shift correlated with the sagittal pleural expansion. There was, however, no correlation between craniocaudal and sagittal respiratory motion. Alignment errors are most severe in the base of the lung, but central structures are affected, too. Understanding of the main vectors of respiratory motion may help in image interpretation when PET and CT are acquired separately.
Imatinib for refractory chronic graft-versus-host disease with fibrotic features.

We previously reported that patients with fibrotic, chronic graft-versus-host disease (cGVHD) have antibodies activating the platelet-derived growth factor receptor pathway. Because this pathway can be inhibited by imatinib, we performed a pilot study including 19 patients with refractory cGVHD, given imatinib at a starting dose of 100 mg per day. All patients had active cGVHD with measurable involvement of skin or other districts and had previously failed at least 2 treatment lines. Patient median age was 29 years (range, 10-62 years), and median duration of cGvHD was 37 months (range, 4-107 months). The organs involved were skin (n = 17), lung (n = 11), and bowel (n = 5); 15 patients had sicca syndrome. Imatinib-related, grade 3 to 4 toxicity included fluid retention, infections, and anemia. Imatinib was discontinued in 8 patients: in 3 because of toxicity and in 5 because of lack of response (n = 3) or relapse of malignancy (n = 2). Overall response rate at 6 months was 79%, with 7 complete remissions (CRs) and 8 partial remissions (PRs). With a median follow-up of 17 months, 16 patients are alive, 14 still in CR or PR. The 18-month probability of overall survival is 84%. This study suggests that imatinib is a promising treatment for patients with refractory fibrotic cGVHD.
Wall thickness of the pulmonary vein-left atrial junction rather than electrical information as the major determinant of dormant conduction after contact force-guided pulmonary vein isolation

The usefulness of electrogram (EGM)-based information has been reported for assessing lesion transmurality during atrial fibrillation (AF) ablation, but the wall thickness of the pulmonary vein-left atrial (PV-LA) junction has not been considered. We conducted a study to evaluate the relation between PV-LA junction wall thickness and the presence of adenosine triphosphate (ATP)-provoked dormant PV conduction. Eighteen AF patients underwent extensive encircling pulmonary vein isolation (EEPVI) with a target CF of >10 g. RF energy was delivered point-by-point at a power setting of 25–30 W for 30 s, and EGM-based information (change in filtered unipolar EGM morphology and bipolar EGM amplitude), decrease in impedance, CF, and CT-based measurement of the PV-LA junction wall thickness were characterized at sites of ATP-provoked dormant conduction. After EEPVI, ATP-induced dormant conduction was observed at 12 of the 288 PV sites (8 segments per ipsilateral PVs × 2 × 18 patients). Of the 974 ablation points, 72 were located at dormant conduction sites and were strongly associated with thickened PV-LA junction walls (1.02± 0.23 vs. 0.86 ± 0.26 mm, p < 0.0001) and decreased impedance (13.3 ± 6.4 vs. 14.9 ± 7.1 Ω, p = 0.0498) but not with EGM-based information or CF. Multivariate analysis identified the thickened PV-LA junction wall as the strongest predictor of dormant conduction. A thickened PV-LA junction wall is a robust predictor of ATP-provoked dormant conduction; EGM-based information appears to be insufficient for ensuring adequate lesions during CF-guided EEPVI.
Strategic subcortical hyperintensities in cholinergic pathways and executive function decline in treated Alzheimer patients.

To investigate changes in cognition, function, and behavior after 1 year in patients with Alzheimer disease being treated with cholinesterase inhibitors, in relation to the presence or absence of subcortical hyperintensities involving the cholinergic pathways.



One-year prospective cohort study.



Memory Clinic, Sunnybrook Health Sciences Centre, University of Toronto.  Ninety patients with possible/probable Alzheimer disease who were being treated with cholinesterase inhibitors at baseline.



Yearly standardized neuropsychological testing and brain magnetic resonance imaging (MRI). The Cholinergic Pathways Hyperintensities Scale (CHIPS) was applied to baseline MRIs to rate the severity of subcortical hyperintensities in cholinergic pathways. The consensus-derived Age-Related White Matter Changes (ARWMC) Rating Scale was used as a general measure of white matter disease burden.



Tests of global cognition, function, and behavior and specific cognitive and functional domains.



Patients in the low CHIPS group were equivalent to those in the high CHIPS group with regard to baseline demographic characteristics, cognitive severity, and vascular risk factors. After covarying age and education, no differences were found after 1 year in overall cognition, function, and behavior or on memory, language, and visuospatial tasks. Patients in the high CHIPS group showed improvement on executive function and working memory tasks compared with those in the low CHIPS group. For the ARWMC scale, groups with and without white matter abnormalities were equivalent on baseline demographics and in cognitive, functional, and behavioral outcomes.



Cerebrovascular compromise of the cholinergic pathways may be a factor that contributes more selectively than does total white matter lesion burden to response to cholinergic therapy in Alzheimer disease, particularly on frontal/executive tasks.
Effect of carbohydrate restriction in patients with hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass.

Hyperinsulinemic hypoglycemia is a rare complication of Roux-en-Y gastric bypass (RYGB) surgery. Meals with a high carbohydrate (carb) content and high glycemic index (GI) may provoke these hypoglycemic attacks. The aim of this study is to assess the effects of reducing meal carb content and GI on glycemic responses in patients with post-RYGB hypoglycemia.



Fourteen patients with post-RYGB hypoglycemia underwent two meal tests: a mixed meal test (MMT) with a carb content of 30 g and a meal test with the low GI supplement, Glucerna SR 1.5® (Glucerna meal test (GMT)). Plasma glucose and serum insulin levels were measured for a period of 6 h.



Peak glucose levels were reached at T 30 during GMT and at T 60 during MMT, and they were 1.5 ± 0.3 mmol/L lower during GMT than during MMT (7.5 ± 0.4 vs 9.0 ± 0.4 mmol/L, P < 0.005). GMT induced the most rapid rise in plasma insulin: at T 30 plasma, insulin was 30.7 ± 8.5 mU/L higher during GMT than during MMT (P < 0.005). None of the carb-restricted meals induced post-prandial hypoglycemia.



A 30-g carb-restricted meal may help to prevent post-prandial hypoglycemia in patients with post-RYGB hypoglycemia. The use of a liquid, low GI, supplement offers no additional advantage.
Validation of histological diagnostic methods for detecting endothelin B receptor expression.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Recently, it was reported that the endothelin B receptor (ETBR) of tumor endothelial cells prevents antitumor immunity. However, the immuno-histochemistry (IHC) conditions required to detect ETBR expression remain unclear. The aim of the present study was to confirm the appropriate conditions for IHC for ETBR using ETBR cDNA and transfectant cells and to assess ETBR expression in PDAC patients. An ETBR-expressing cell was established as an objective positive control and the detectability of ETBR expression was evaluated using several types of anti-ETBR antibodies. ETBR mRNA expression was then studied. Finally, ETBR expression was examined in human PDAC tissue using IHC. As a result, four different anti-ETBR antibodies recognized the cell surface ETBR appropriately. A non-specific reaction was shown in the detection of ETBR in normal human tissues. ETBR mRNA expression was weakly detected only in the adrenal gland. No biologically significant correlation was observed in the ETBR-IHC of human PDAC sections. In conclusion, it is necessary to perform IHC using an appropriate control to assess the tissue expression of ETBR.
Drug attitude as predictor for effectiveness in first-episode schizophrenia: Results of an open randomized trial (EUFEST)

Effectiveness has become more and more important as a comprehensive outcome measure for (long-term) treatment in schizophrenia. Early predictors to identify patients at a high risk for not succeeding the initiated treatment would be very useful. Discontinuation of the initiated treatment was used as criterion for effectiveness and patients' drug attitude was shown to be predictive for non-adherence or discontinuation of long-term treatment in schizophrenia. Accordingly, the predictive validity of the Drug Attitude Inventory (DAI) for effectiveness should be evaluated. Based on a sub-sample of patients from the EUFEST study for whom DAI assessments were available significant predictors for effectiveness as measured by discontinuation of initiated treatment were identified based on a logistic and a Cox-regression analysis. A Receiver-Operating Characteristic- (ROC-) analysis was conducted for the DAI, prognostic / diagnostic parameters (sensitivity, specificity) were calculated and a cut-off value suggested. In a sample of 228 first-episode patients, the DAI score was the most powerful predictor for effectiveness (p<0.001) besides two other significant predictors (PANSS-positive score and sexual side effects). The ROC-analysis revealed an area under the curve of 0.64 (p<0.001). The suggested cut-off point of about 20 yielded a sensitivity of 70-75% and a specificity of 40-45%. Study results indicate that the Drug Attitude Inventory, filled in by patients early in treatment seems to be a valid predictor for effectiveness as measured by discontinuation of the initiated treatment. DAI scores could also serve as an (differential) indicator for the need of enhanced treatment monitoring. These findings have to be validated in other (first-episode) samples.
Clinical predictors for the manifestation of late gadolinium enhancement after acute myocardial infarction

Despite prompt revascularization, some patients with acute myocardial infarction (AMI) develop myocardial scars, which can be visualized by late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). Our goal was to identify angiographic findings that were predictive for scar development in patients after reperfused AMI.We examined 136 patients after first ST-elevated myocardial infarction by CMR after a median of 4 days (range: 2-7). Patients with manifestation of LGE were matched to patients without LGE by means of age and gender. Clinical follow-up with a combined primary endpoint including myocardial reinfarction, congestive heart failure, stroke, death and development of left ventricular thrombus was reported after 24 months.Patients with manifestation of LGE had a significant longer time of symptom-to-intervention, a higher prevalence of anterior AMI, and more proximal culprit lesions. Furthermore, left ventricular ejection fraction was significantly decreased, and peak values of infarct markers were significantly higher in these patients. Preinterventional thrombolysis in myocardial infarction-0-flow was significantly more frequent in patients with LGE manifestation. The presence of 3-vessel disease (odds ratio 53.99, 95% confidence interval 8.22-354.63, P <.001), a proximal culprit lesion, and high creatine kinase myocardial band (CK-MB) values were identified as independent predictors of LGE. Follow-up demonstrated a higher incidence of clinical events in the group with LGE, with the most common cause of heart failure (38.2% vs 7.4%, P <.001).The extent of angiographic findings in AMI plays a major role in the manifestation of LGE. The presence of a multivessel disease, a proximal culprit lesion, and high values of CK-MB are strong independent predictors for LGE manifestation.
Expressive disclosure and benefit finding among breast cancer patients: mechanisms for positive health effects.

A randomized trial (n = 60; A. L. Stanton, S. Danoff-Burg, L. A. Sworowski, et al., 2002) revealed that 4 sessions of written expressive disclosure or benefit finding produced lower physical symptom reports and medical appointments for cancer-related morbidities at 3-month follow-up among breast cancer patients relative to a fact-control condition. The goal of this article is to investigate mechanisms underlying these effects. Within-session heart rate habituation mediated effects of expressive disclosure on physical symptoms, and greater use of negative emotion words in essays predicted a decline in physical symptoms. Postwriting mood and use of positive emotion and cognitive mechanism words in essays were not significant mediators, although greater cognitive mechanism word use was related to greater heart rate habituation and negative emotion word use.
Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study

The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors. A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] p trend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] p trend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (phet = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.
Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults.

In addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability.



To increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5.



A cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007.



Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus.



Level of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test.



Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.
Generator replacement is associated with an increased rate of ICD lead alerts.

Lead malfunction is an important cause of morbidity and mortality in patients with an implantable cardioverter-defibrillator (ICD). We have shown that the failure of recalled high-voltage leads significantly increases after ICD generator replacement. However, generator replacement has not been recognized as a predictor of lead failure in general.



The purpose of this study is to assess the effect of ICD generator exchange on the rate of ICD lead alerts.



A time-dependent Cox proportional hazards model was used to analyze a database of remotely monitored ICDs. The model assessed the impact of generator exchange on the rate of lead alerts after ICD generator replacement.



The analysis included 60,219 patients followed for 37 ± 19 months. The 5-year lead survival was 99.3% (95% confidence interval 99.2%-99.4%). Of 60,219 patients, 7458 patients (12.9%) underwent ICD generator exchange without lead replacement. After generator replacement, the rate of lead alerts was more than 5-fold higher than in controls with leads of the same age without generator replacement (hazard ratio 5.19; 95% confidence interval 3.45-7.84). A large number of lead alerted within 3 months of generator replacement. Lead alerts were more common in patients with single- vs dual-chamber ICDs and in younger patients. Sex was not associated with lead alerts.



Routine generator replacement is associated with a 5-fold higher risk of lead alert compared to age-matched leads without generator replacement. This suggests the need for intense surveillance after generator replacement and the development of techniques to minimize the risk of lead damage during generator replacement.