nils-herrmann/clean_scirepeval huggingface dataset:
Trajectories of estradiol and follicle-stimulating hormone over the menopause transition and early markers of atherosclerosis after menopause.

The purpose of this study was to assess associations between distinct patterns of circulating estradiol (E2) and follicle-stimulating hormone (FSH) over the menopause transition (MT) and subclinical measures of atherosclerosis after menopause.



Four temporal patterns of E2 decline (Low: low before and after final menstrual period (FMP); Medium: medium before and high after FMP; High-early decline: high prior to FMP and early decline thereafter; High-late decline: high prior to FMP and late decline thereafter) and three of FSH rise (Low, Medium, High) over 9.6 years across FMP were identified and linked to carotid intima-media-thickness (IMT), adventitial diameter (AD), and presence of carotid plaque (cPlaque) measured after menopause at the 12th annual visit (visit 12). Participants were 856 women (age at visit 12 = 59.5 ± 2.7 years) from the Study of Women's Health Across the Nation (SWAN), who never reported a stroke or a heart attack. In models adjusted for visit 12 or baseline cardiovascular disease (CVD) risk factors, odds of having any cPlaque were ∼43% lower among women with the High-early decline E2 trajectory compared to women with the Low E2 trajectory. In contrast, women with the Medium E2 trajectory had significantly higher IMT than those with the Low E2 trajectory adjusting for visit 12 CVD risk factors. Interestingly, adjusting for baseline CVD risk factors attenuated this association. The Low FSH group had lower IMT than the Medium and High FSH groups (p ≤ 0.05) in all models.



During MT, women are subjected to hormonal alterations that could potentially increase their risk of developing CVD after menopause.
Fibromyalgia patients show an abnormal dopamine response to pain.

Fibromyalgia is characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances. Accumulating evidence indicates that fibromyalgia may involve a dysfunction of modulatory systems in the brain. While brain dopamine is best known for its role in pleasure, motivation and motor control, recent evidence suggests that it is also involved in pain modulation. Because dopamine is implicated in both pain modulation and affective processing, we hypothesized that fibromyalgia may involve a disturbance of dopaminergic neurotransmission. Fibromyalgia patients and matched healthy control subjects were subjected to deep muscle pain produced by injection of hypertonic saline into the anterior tibialis muscle. In order to determine the endogenous release of dopamine in response to painful stimulation, we used positron emission tomography to examine binding of [(11)C]-raclopride (D2/D3 ligand) in the brain during injection of painful hypertonic saline and nonpainful normal saline. Fibromyalgia patients experienced the hypertonic saline as more painful than healthy control subjects. Control subjects released dopamine in the basal ganglia during the painful stimulation, whereas fibromyalgia patients did not. In control subjects, the amount of dopamine release correlated with the amount of perceived pain but in fibromyalgia patients no such correlation was observed. These findings provide the first direct evidence that fibromyalgia patients have an abnormal dopamine response to pain. The disrupted dopaminergic reactivity in fibromyalgia patients could be a critical factor underlying the widespread pain and discomfort in fibromyalgia and suggests that the therapeutic effects of dopaminergic treatments for this intractable disorder should be explored.
Incidence of difficult bag-mask ventilation in children: a prospective observational study.

Difficult airway (DA), including difficult bag-mask ventilation (DBMV), and difficult intubation (DI) is an important challenge for the pediatric anesthesiologist. While expected DBMV can be successfully managed with appropriate equipment and personnel, unexpected DBMV relies on the resources available and the experience of the anesthesiologist at the time of the emergency. The incidence and risk factors of unexpected DA in otherwise healthy children, including DBMV among pediatric patients are not known. The aim of this study was to expand the scientific knowledge of unexpected DBMV among pediatric patients.



Patients between the ages of 0 and 8 years, undergoing elective surgery requiring bag-mask ventilation BMV and intubation at the Montreal Children's Hospital were recruited in this prospective observational study. Data on the incidence of DBMV and risk factors were collected over a 3-year period.



In a sample of 484 children, the incidence of unexpected difficult BMV was 6.6% (95% CI [4.6, 9.2]). The incidence of expected DA among the screened patients (N = 4865) was 0.5% (95% CI [0.3, 0.7]). In a logistic regression analysis, age (OR 0.98; 95%CI [0.97, 0.99]), undergoing otolaryngology (ENT) surgery (OR 2.92; 95% CI [1.08, 7.95]) and use of neuromuscular blocking agents (OR 3.49; 95%CI [1.50-8.11]) were independently associated with DBMV. The incidence of DI was 1.2%. No association between DBMV and DI was found (Fisher's exact test, P = 1.0).



This is the first published report of the incidence of unexpected DBMV among healthy pediatric patients.
Medical resource use, costs, and quality of life in patients with acute decompensated heart failure: findings from ASCEND-HF.

The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) randomly assigned 7,141 participants to nesiritide or placebo. Dyspnea improvement was more often reported in the nesiritide group, but there were no differences in 30-day all-cause mortality or heart failure readmission rates. We compared medical resource use, costs, and health utilities between the treatment groups.



There were no significant differences in inpatient days, procedures, and emergency department visits reported for the first 30 days or for readmissions to day 180. EQ-5D health utilities and visual analog scale ratings were similar at 24 hours, discharge, and 30 days. Billing data and regression models were used to generate inpatient costs. Mean length of stay from randomization to discharge was 8.5 days in the nesiritide group and 8.6 days in the placebo group (P = .33). Cumulative mean costs at 30 days were $16,922 (SD $16,191) for nesiritide and $16,063 (SD $15,572) for placebo (P = .03). At 180 days, cumulative costs were $25,590 (SD $30,344) for nesiritide and $25,339 (SD $29,613) for placebo (P = .58).



The addition of nesiritide contributed to higher short-term costs and did not significantly influence medical resource use or health utilities compared with standard care alone.
Could clopidogrel's platelet inhibition be enhanced by an increased loading dose and eptifibatide?

This prospective, randomized study included patients aged over 18 years who had undergone elective coronary stenting. Exclusion criteria included history of bleeding diathesis, elevated cardiac markers, an acute myocardial infarction within 48 h, a cerebrovascular event 3 months before treatment, chronic vessel occlusion or angiographically visible thrombus, hematocrit under 30%, platelet count under 100 × 109/l and prothrombin time over 1.5 times reference.
Noninvasive sphenopalatine ganglion block for acute headache in the emergency department: a randomized placebo-controlled trial.

We seek to test the efficacy of noninvasive sphenopalatine ganglion block for the treatment of acute anterior headache in the emergency department (ED) using a novel noninvasive delivery device.



We conducted a randomized, double-blind, placebo-controlled trial evaluating bupivacaine anesthesia of the sphenopalatine ganglion for acute anterior or global-based headache. This study was completed in 2 large academic EDs. Bupivacaine or normal saline solution was delivered intranasally (0.3 mL per side) with the Tx360 device. Pain and nausea were measured at 0, 5, and 15 minutes by a 100-mm visual analog scale. The primary endpoint was a 50% reduction in pain at 15 minutes. Telephone follow-up assessed 24-hour pain and nausea through a 0- to 10-point verbal scale and adverse effects.



The median reported baseline pain in the bupivacaine group was 80 mm (IQR 66 mm - 93 mm) and 78.5 mm (IQR 64 mm to 91.75 mm) in the normal saline solution group. A 50% reduction in pain was achieved in 48.8% of the bupivacaine group (20/41 patients) versus 41.3% in the normal saline solution group (19/46 patients), for an absolute risk difference of 7.5% (95% confidence interval [CI] -13% to 27.1%). As a secondary outcome, at 24 hours, more patients in the bupivacaine group were headache free (24.7% difference; 95% CI 2.6% to 43.6%) and more were nausea free (16.9% difference; 95% CI 0.8% to 32.5%).



For patients with acute anterior headache, sphenopalatine ganglion block with the Tx360 device with bupivacaine did not result in a significant increase in the proportion of patients achieving a greater than or equal to 50% reduction in headache severity at 15 minutes compared with saline solution applied in the same manner.
The translation and validation of the Japanese version of the patient assessment of constipation quality of life scale

The aim of the present study was to conduct a psychometric evaluation of the patient assessment of constipation quality of life scale (PAC-QOL) in the Japanese language. The PAC-QOL was translated into Japanese. After being linguistically validated, the Japanese version of the PAC-QOL was administered to a sample of 121 patients. Validation studies were conducted to evaluate the internal consistency reliability (Cronbach’s alpha), reproducibility [intraclass correlation coefficients (ICCs)], the convergent validity (correlated with the Short-Forum 36 Health Survey), the discriminant validity [correlated with the constipation scoring system (CSS)], the cross-sectional validity (analysis of variance models), and responsiveness (effect size) of the PAC-QOL scales. The internal consistency was good for all of the scales (Cronbach’s alpha coefficient >0.7) and reproducible (ICCs >0.7). The four scales of the PAC-QOL were significantly correlated with the Short-Forum 36 Health Survey (P < 0.01 except for the satisfaction subscale) and the CSS scores (P < 0.01 except for the satisfaction subscale). The PAC-QOL scale scores were significantly associated with constipation severity (P < 0.05). The effect size in patients reporting improvements in constipation over the treatment period was moderate to large, with a subscale effect size ranging from 0.69 to 1.18 and an overall scale effect size of 1.12. Similar findings were observed in the original validation study. The linguistic and psychometric evaluation demonstrated the validity of the Japanese version of the PAC-QOL.
A randomized phase II presurgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor-positive breast cancer

We previously demonstrated that 1 or 5 mg per day of tamoxifen (T) given for four weeks before surgery reduces Ki-67 in breast cancer (BC) patients to the same extent as the standard 20 mg/d. Given the long half-life of T, a weekly dose (10 mg per week (w)) may be worth testing. Also, raloxifene (R) has shown Ki-67 reduction in postmenopausal patients in a preoperative setting, but data in premenopausal women are limited. We conducted a randomized trial testing T 10 mg/w vs. R 60 mg/d vs. placebo in a presurgical model. Out of 204 screened subjects, 57 were not eligible, 22 refused to participate and 125 were included in the study. The participants were all premenopausal women with estrogen receptor-positive BC. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki-67. Secondary endpoints were modulation of estrogen and progesterone receptors and several other circulating biomarkers. Ki-67 was not significantly modulated by either treatment. In contrast, both selective estrogen receptor modulators (SERMs) significantly modulated circulating IGF-I/IGFBP-3 ratio, cholesterol, fibrinogen and antithrombin III. Estradiol was increased with both SERMs. Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Moreover, a reduction of Ki-67 and a marked increase of sex hormone-binding globulin (SHBG) were observed in the active phenotype. A weekly dose of tamoxifen and a standard dose of raloxifene did not inhibit tumor cell proliferation, measured as Ki-67 expression, in premenopausal BC patients. However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation.
Dopamine and cognitive functioning in de novo subjects with Parkinson's disease: Effects of pramipexole and pergolide on working memory

Very few studies have investigated the relationship between dopaminergic therapy and working memory (WM) functioning in Parkinson's disease (PD) patients. The aim of the present study was to explore the effects of pharmacological treatment with pergolide (a D1+D2 receptor agonist) and pramipexole (a D2+D3 receptor agonist) on performance in visual-spatial, visual-object, and verbal WM tasks in PD patients. Participants included 19 "de novo" PD patients and 13 healthy controls (HC). The experimental task consisted of an n-back paradigm with verbal, visual-object, or visual-spatial stimuli. PD patients performed the task twice: after 18-24 h of therapy wash-out and after administration of pergolide (nine patients) or pramipexole (ten patients). HCs performed the task only once, without drug administration. Depending on how they performed in the "Off" and "On" therapy conditions, the nine PD patients each were classified into groups of low performers (i.e., performance on the n-back paradigm was below the median value of the experimental sample) and high performers (i.e., performance was above the median value). One PD patient was excluded from the analysis because his performance pattern clearly revealed that he was an outlier. In the low performer PD patients, administration of both pergolide and pramipexole improved accuracy on all WM tasks. No effect of the drugs was found in the high performer patients. The results of the present study show that stimulation of dopaminergic receptors improves high-level WM processes in PD patients, possibly by modulating activity in frontal-striatal circuits.
Prospective Single-Arm Protocol of Carvedilol in Children with Ventricular Dysfunction

The objective of this study was to evaluate the safety and efficacy of carvedilol in pediatric patients with stable moderate heart failure. We performed a single-arm prospective drug trial at three academic medical centers and the results were compared to historical controls. Patients were 3 months to 17 years old with an ejection fraction <40% in the systemic ventricle for at least 3 months on maximal medical therapy including ACE inhibitors. Treated patients were started on 0.1 mg/kg/day and uptitrated to 0.8 mg/kg/day or the maximal tolerated dose. Echocardiographic parameters of function were prospectively measured at entry and at 6 months. Two composite endpoints were recorded: severe decline in status and significant clinical change. Adverse events were reviewed by a safety committee. Data were also collected from untreated controls with dilated cardiomyopathy meeting entry criteria, assessed over a similar time frame. Twenty patients [12 dilated cardiomyopathy (DCM) and 8 congenital] with a median age of 8.4 years (range, 8 months to 17.8 years) were treated with carvedilol. Three patients discontinued the drug during the study. At entry, there was no statistical difference in age, weight, or ejection fraction between the treated group and controls. The ejection fraction of the treated DCM group improved significantly from entry to 6 months (median, 31 to 40%, p = 0.04), with no significant change in ejection fraction in the control group [median, 29 to 27%, p = not significant (NS)]. The median increase in ejection fraction was larger for the treated DCM group than for the untreated DCM controls (7 vs 0%, p = 0.05). By Kaplan–Meier analysis, time to death or transplant tended to be longer in treated patients (p = 0.07). The difference in the proportion of patients with severe decline in status or significant clinical change in the treated group was not significant compared to the controls (5 vs 12%, p = NS). We conclude that in this prospective protocol of pediatric patients, the use of adjunct carvedilol in the DCM group improved ejection fraction compared to untreated controls and trended toward delaying time to transplant or death.
A multicenter study of the early detection of synaptic dysfunction in Mild Cognitive Impairment using Magnetoencephalography-derived functional connectivity

Synaptic disruption is an early pathological sign of the neurodegeneration of Dementia of the Alzheimer's type (DAT). The changes in network synchronization are evident in patients with Mild Cognitive Impairment (MCI) at the group level, but there are very few Magnetoencephalography (MEG) studies regarding discrimination at the individual level. In an international multicenter study, we used MEG and functional connectivity metrics to discriminate MCI from normal aging at the individual person level. A labeled sample of features (links) that distinguished MCI patients from controls in a training dataset was used to classify MCI subjects in two testing datasets from four other MEG centers. We identified a pattern of neuronal hypersynchronization in MCI, in which the features that best discriminated MCI were fronto-parietal and interhemispheric links. The hypersynchronization pattern found in the MCI patients was stable across the five different centers, and may be considered an early sign of synaptic disruption and a possible preclinical biomarker for MCI/DAT.
Human immunodeficiency virus-1 (HIV-1) gp120 superantigen-binding serum antibodies. A host factor in homosexual HIV-1 transmission.

HIV-1 gp120 is an immunoglobulin superantigen which can bind to preimmune serum Ig. We hypothesize that levels of such preimmune antibodies vary in the population and might affect host resistance or susceptibility to viral transmission. This study tests two predictions: (a) levels of preimmune anti-gpl20 Igs are a polymorphic trait; and, (b) these levels are correlated with resistance or susceptibility to HIV-1 transmission. The first prediction was confirmed in a longitudinal study of a low-risk seronegative population. In this group, levels of both endogenous anti-gpl20 IgM and IgG varied widely, but were characteristic and stable for each individual. The second prediction was addressed in a study of participants of the Multicenter AIDS Cohort Study, in which men "susceptible" and "resistant" to HIV infection were identified based on numbers of sexual partners and eventual seroconversion. Specimens consisted of archival sera obtained > 2 yr before seroconversion. Men in the susceptible population (low-risk seroconverters) were distinguished by low levels of anti-gpl20 IgG. We conclude that the level of preimmune anti-gpl20 IgG is a polymorphic population trait, and low levels are a potentially specific and significant factor in homosexual transmission of HIV infection.
Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy.

Oral Silibinin (SIL) is widely used for treatment of hepatitis C, but its efficacy is unclear. Substantially higher doses can be administered intravenously (IV).



Pedigreed nonresponders to full-dose pegylated (Peg)-interferon/ribavirin (PegIFN/RBV) were studied. First, 16 patients received 10 mg/kg/day SIL IV (Legalon Sil; Madaus, Köln, Germany) for 7 days. In a subsequent dose-finding study, 20 patients received 5, 10, 15, or 20 mg/kg/day SIL for 14 days. In both protocols, PegIFN alpha-2a/RBV were started on day 8. Viral load was determined daily.



Unexpectedly, in the first study, HCV-RNA declined on IV SIL by 1.32 +/- 0.55 log (mean +/- SD), P < .001 but increased again in spite of PegIFN/RBV after the infusion period. The viral load decrease was dose dependent (log drop after 7 days SIL: 0.55 +/- 0.5 [5 mg/kg, n = 3], 1.41 +/- 0.59 [10 mg/kg, n = 19], 2.11 +/- 1.34 [15 mg/kg, n = 5], and 3.02 +/- 1.01 [20 mg/kg, n = 9]; P < .001), decreased further after 7 days combined SIL/PegIFN/RBV (1.63 +/- 0.78 [5 mg/kg, n = 3], 4.16 +/- 1.28 [10 mg/kg, n = 3], 3.69 +/- 1.29 [15 mg/kg, n = 5], and 4.85 +/- 0.89 [20 mg/kg, n = 9]; P < .001), and became undetectable in 7 patients on 15 or 20 mg/kg SIL, at week 12. Beside mild gastrointestinal symptoms, IV SIL monotherapy was well tolerated.



IV SIL is well tolerated and shows a substantial antiviral effect against HCV in nonresponders.
Architecture of the medial gastrocnemius in children with spastic diplegia.

Ultrasound images were obtained of the medial gastrocnemius at different ankle joint positions with the knee extended. Fascicle length and deep fascicle angle were measured in five normally developing adults (mean age 33 years, age range 24 to 36 years) and in five normally developing children (mean age 7.8 years, age range 7 to 11 years), and in seven children with spastic diplegia (mean age 10 years, age range 6 to 13 years). These architectural variables were similar in the groups of normally developing adults and children. Importantly, no statistical difference could be found between the normally developing children and those with diplegia for fascicle length. Deep fascicle angles were reduced significantly in the clinical group at a particular ankle joint angle but not at the resting angles. The difference in deep fascicle angles is explained as a function of resting muscle length and is not attributed any clinical importance. Our results do not explain the structural origin of muscle contracture explicitly. However, they do indicate that most of the fixed shortness in the medial gastrocnemii of ambulant children with spastic diplegia is not due to reduced muscle fibre length. We suggest that muscle contracture may be better explained in terms of shortness of the aponeuroses of pennate muscles, such as the medial gastrocnemius, through reduced muscle fibre diameter.