nils-herrmann/clean_scirepeval huggingface dataset:
Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression

Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressant were assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P.M. and CRH stimulation at 3 P.M. on the next day). Twenty-four patients were re-assessed after response was determined or, in cases of non-response, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version). Response was defined as a ΔHDRS of ⩾50% and an endpoint score of < 10. Patients had a significantly higher ACTH and cortisol response to CRH stimulation during lithium augmentation compared with the values at baseline. There was no difference in ACTH and cortisol reaction between responders and non-responders to lithium augmentation. This increase is in contrast to the known normalization of HPA-axis overdrive after treatment with a tricyclic antidepressant like amitriptyline. Because the effect was independent of response status we suggest that this increase reflects an effect of lithium that is independent from the psychopathological state or its change. This effect might be explained by the serotonergic effects of lithium.
Pituitary tumors in children: clinical analysis of 21 cases

The aim of this study is to review the results of surgery for pituitary adenomas in children less than 18 years old. A retrospective review was done of pituitary adenoma patients with the age of less than 18 years who were treated in the period 1979–2003 at Dr. Shariati Hospital. Twenty-one patients (12 girls and 9 boys) were identified. The age range (mean) in girls and boys was 9–18 (15.8) and 9–17 (14.8) years, respectively. The duration of follow-up was 1–23 (13.4) years. Eight patients (38.1%) had adrenocorticotropic hormone-secreting tumors, 33.3% had prolactin-secreting tumors, 19% had growth hormone-secreting tumors, and 9.53% had nonfunctioning adenomas. Multidisciplinary management included surgery and, if necessary, reoperation with/without radiotherapy and pharmacotherapy. Eleven patients, mostly with prolactinomas, acromegaly, and nonfunctioning adenomas, needed reoperation and radiotherapy. There were two deaths, one of which was because of apoplexy. The biological behavior of pediatric pituitary adenomas seems more aggressive than adults’ adenomas. The chance of pituitary apoplexy in pediatric invasive pituitary adenoma is high.
Efficient Simulation of Nested Hollow Sphere Intersections: for Dynamically Nested Compartmental Models in Cell Biology

In the particle-based simulation of cell-biological systems in continuous space, a key performance bottleneck is the computation of all possible intersections between particles. These typically rely for collision detection on solid sphere approaches. The behavior of cell biological systems is influenced by dynamic hierarchical nesting, such as the forming of, the transport within, and the merging of vesicles. Existing collision detection algorithms are found not to be designed for these types of spatial cell-biological models, because nearly all existing high performance parallel algorithms are focusing on solid sphere interactions. The known algorithms for solid sphere intersections return more intersections than actually occur with nested hollow spheres. Here we define a new problem of computing the intersections among arbitrarily nested hollow spheres of possibly different sizes, thicknesses, positions, and nesting levels. We describe a new algorithm designed to solve this nested hollow sphere intersection problem and implement it for parallel execution on graphical processing units (GPUs). We present first results about the runtime performance and scaling to hundreds of thousands of spheres, and compare the performance with that from a leading solid object intersection package also running on GPUs.
Impact of a Glycolic Acid-Containing pH 4 Water-in-Oil Emulsion on Skin pH.

The skin pH is crucial for physiological skin functions. A decline in stratum corneum acidity, as observed in aged or diseased skin, may negatively affect physiological skin functions. Therefore, glycolic acid-containing water-in-oil (W/O) emulsions adjusted to pH 4 were investigated regarding their effect on normal or increased skin pH. A pH 4 W/O emulsion was applied on three areas with pathologically increased skin surface pH in diabetics (n = 10). Further, a 28-day half-side trial (n = 30) was performed to test the long-term efficacy and safety of a pH 4 W/O emulsion (n = 30). In summary, the application of a pH 4 W/O emulsion reduced the skin pH in healthy, elderly and diabetic subjects, which may improve epidermal barrier functions.
Combined exercise training in asymptomatic elderly with controlled hypertension: Effects on functional capacity and cardiac diastolic function

Aging is associated with changes in cardiac structure and function that are associated with left ventricular diastolic dysfunction. Whether diastolic functional alterations during senescence are manifestations of the intrinsic aging process or related to cardiac adaptations to a more sedentary lifestyle is still unsettled. This was a prospective study evaluating the effects of a 6-month combined exercise training period on functional capacity and diastolic function in sedentary elderly patients with controlled arterial hypertension.



Functional capacity was assessed by exercise stress test and muscle strength was evaluated by the one-repetition maximum test. Cardiac structures and function were analyzed by transthoracic echocardiography.



Fifteen patients, 68±8 years old, completed the training program. Exercise training significantly improved physical capacity (distance walked: 551±92 vs. 630±153 m, P<0.05; work load: 7.2±1.7 vs. 8.5±3.0 METs, P<0.05) and upper and lower extremity muscle strength (P<0.001). Arterial blood pressure significantly decreased after training (systolic blood pressure: 134±9 vs. 128±8 mmHg; diastolic blood pressure: 82±7 vs. 77±6 mmHg; P<0.05). Cardiac structures and left and right systolic and diastolic function did not change after combined training (P>0.05).



Combined and supervised training for a 6-month period increases physical capacity and muscle strength in elderly patients with controlled arterial hypertension without changing resting left ventricular diastolic function.
Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation.

The response to levodopa changes over time in Parkinson's disease, probably due to alterations in the dopaminergic system, progression of the disease and pulsatile oral intake of the drug. Bilateral high-frequency stimulation of the subthalamic nucleus (STN) allows a large reduction or the complete cessation of levodopa intake in patients with advanced Parkinson's disease. We studied variation in the motor short-duration response (SDR) during a levodopa challenge in bilaterally STN-stimulated patients. Twenty-eight consecutive patients with a mean duration of Parkinson's disease of 16.6 +/- 6.0 years at the time of surgery were enrolled. Fourteen patients were evaluated both before STN stimulation and 3 months after surgery (group 1) whereas the other 14 patients were assessed before implantation and after a mean of 3 years of STN stimulation (group 2). After drug withdrawal for one night, the hand-tapping test (TT) was carried out every 15 min, together with evaluation of dyskinesias using a modified Goetz scale. The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was assessed every 30 min. In operated patients, STN stimulation was stopped 15 min before starting the clinical evaluations. A suprathreshold oral levodopa dose was given after one motor evaluation and two TTs. The clinical evaluation was carried out until the TT score returned to the baseline. In group 1, six patients continued without levodopa after surgery and the other eight received a daily mean dose of 337 mg; in group 2, seven patients continued without levodopa and the other seven received a daily mean dose of 386 mg. The main change in the levodopa SDR was a significant reduction in levodopa-induced dyskinesias in both groups. In those patients of group 1 who did not receive levodopa after surgery, the motor UPDRS magnitude decreased and the 'on' UPDRS motor score worsened. In group 2, the results were similar, but in the patients who continued to receive levodopa after surgery the TT magnitude increased. On the whole, chronic bilateral STN stimulation tended to decrease the magnitude of the levodopa SDR without changing the duration and latency of the response. These results suggest that continuous STN stimulation induces long-term plastic changes of the dopaminergic system, with slow and partial desensitization. In addition, the persistence of levodopa intake after surgery might hinder this beneficial process.
Antithrombotic therapy after bioprosthetic aortic valve implantation: Warfarin versus aspirin, a randomized controlled trial.

The optimal medical strategy for prevention of thromboembolic events after surgical bioprosthetic aortic valve replacement (BAVR) is still debated. The objective of this study was to compare warfarin therapy (target INR of 2.0 to 3.0) with aspirin 150mg daily as antithrombotic therapy for the first three months after BAVR with or without concomitant coronary artery bypass grafting (CABG). The aim was to evaluate thromboembolic complications, major bleeding complications and death.



Prospective, single-centre, open-label, randomized controlled trial. 370 patients were enrolled, 328 were available for data analysis.



At baseline the warfarin and aspirin groups were comparable. Thromboembolic events were comparable between groups 11 (6.6%) vs. 12 (7.5%), p=0.83. Major bleeding events occurred numerically more often in warfarin patients 9 (5.4%) vs. 3 (1.9%), p=0.14. Warfarin was in multivariate analysis significantly associated with major bleeding OR 5.18 (CI 1.06-25.43), p=0.043. 90-day mortality was comparable between groups 8 (4.7%) vs. 6 (3.7%), p=0.79.



Our results suggest that aspirin might be equally effective as warfarin in preventing thromboembolic events after BAVR, but with less major bleedings. Although this is numerically the largest trial testing this hypothesis in a prospective randomized trial, further adequately powered studies are warranted.
Sequential occurrence of thyroid autoantibodies and Graves' disease after immune restoration in severely immunocompromised human immunodeficiency virus-1-infected patients.

We analyzed the kinetics of CD4 cells, human immunodeficiency virus (HIV) viral load, and autoantibodies in acquired immune deficiency syndrome patients with Graves' disease (GD) after immune restoration on highly active antiretroviral therapy (HAART; retrospective study). Five patients (median age, 41 yr) were diagnosed with GD after 20 (range, 14-22) months on HAART on the basis of clinical and biological hyperthyroidism, diffuse hyperfixation of thyroid scan, and the presence of anti-TSH receptor (anti-TSHR) antibodies (Ab). GD was diagnosed several months after the plasma HIV ribonucleic acid load became undetectable, when the CD4+ cell count had risen from 14 (range, 0-62) to 340 (range, 163-460) x 10(6) cells/L. Antithyroid peroxidase (anti-TPO) and anti-TSHRAb appeared 14 (range, 9-18) and 14 (range, 11-20) months after starting HAART and 12 (range, 6-15) and 11 (range, 9-17) months after the increase in CD4+ cells. In 3 patients, TPOAb preceded TSHRAb by 3-10 months. No other autoantibodies were detected. Thyroid antibodies were absent in a group of 55 HIV-1-positive patients with comparable response to HAART and no symptoms of hyperthyroidism (cross-sectional study). Thyroid-specific autoimmunity can occur upon immune restoration with HAART. Our observations suggest a relationship between thymus-dependent immune reconstitution after immunosuppression and autoimmunity and may provide insight into the pathophysiology of GD.
The relationship of ST segment elevation shape with preserved myocardium and signal-averaged electrocardiography in acute anterior myocardial infarction

Although a relation between magnitude of ST segment elevation and myocardial damage has been shown in the early period of acute myocardial infarction (AMI), such a relation between the shape of the ST segment elevation, myocardial damage, and the clinical course remains obscure. For this purpose 62 first anterior AMI patients admitted in the first 6 h were enrolled for the study. On the basis of precordial V3 derivation prior to thrombolytic therapy, the shape of the ST elevation was separated into three groups: concave (n = 26), straight (n = 24), or convex types (n = 12). The relation between the shape of the ST elevation recorded on admission, and the results of predischarge low-dose dobutamine stress echocardiography (LDE) performed (n = 53) and signal-averaged ECG values were investigated. The basal wall motion score index (WMSI) and response to LDE in the concave group were better in the infarct zone. Additionally, the average akinetic segment number in the infarct zone was higher, and improvement in these segments was less in the convex and straight groups (concave 3.78 ± 2 vs 2.17 ± 2.1, P < 0.01; straight 5.15 ± 2.7 vs 4.45 ± 2.8, not significant (NS); convex 5.4 ± 2.3 vs 4.8 ± 2.1, NS; basal vs LDE). While only 13% (3/23) of the patients did not respond to LDE (P < 0.05 vs group B and P < 0.01 vs group C), 35% (7/20) of group B and 60% (6/10) of group C patients did not respond to LDE. Although no relation was found between better left ventricular function (WMSI < 2) and shape of the ST elevation in basal evaluation by multiple logistic regression analysis (P = 0.06), an independent relation was found between them following LDE (P = 0.01, odds ratio (OR) 4.5, 95% Confidence Interval (CI) 1.3–14.7). The incidence of ventricular late potential (LP) positivity was 11% (3/26) in the concave group, 16% (4/24) in the straight group, and 58% (7/12) in the convex group (P < 0.001 vs concave and P < 0.05 vs straight groups). We found that shape of the ST elevation could significantly predict the presence of late potentials in multiple logistic regression analysis (P = 0.003, OR 10.7, 95% CI 2.2–51.7). There was no in-hospital death in the concave group, whereas five patients died in either the straight or the convex group. Furthermore, arrhythmia was lower in the concave group during this period (P < 0.05), and exercise capacity was lower. In conclusion, we determined that there was a higher viable myocardium, and lower LP(positivity) and in-hospital mortality in patients with concave ST elevation on admission.
Evaluation of food effect on pharmacokinetics of vismodegib in advanced solid tumor patients.

Vismodegib, an orally bioavailable small-molecule Smoothened inhibitor, is approved for treatment of advanced basal cell carcinoma (BCC). We conducted a pharmacokinetic study of vismodegib in patients with advanced solid tumors to explore the effects of food on drug exposure.



In part I, patients were randomized to fasting overnight (FO), a high fat meal (HF), or a low fat meal (LF) before a single dose of vismodegib 150 mg. Plasma concentrations of vismodegib were determined by a validated liquid chromatography-tandem mass spectrometry assay. Primary endpoints were C(max) and area under the curve (AUC(0-168)). In part II, patients randomized to FO or HF in part I took vismodegib 150 mg daily after fasting; those randomized to LF took it after a meal. Primary endpoints after two weeks were C(max) and AUC(0-24).



Sixty (22 FO, 20 HF, 18 LF) and 52 (25 fasting, 27 fed) patients were evaluable for primary endpoints in parts I and II, respectively. Mean C(max) and AUC(0-168) after a single dose were higher in HF than FO patients [ratios of geometric means (90% CI) = 1.75 (1.30, 2.34) and 1.74 (1.25, 2.42), respectively]. There were no significant differences in C(max) or AUC(0-24) between fasting and fed groups after daily dosing. The frequencies of drug-related toxicities were similar in both groups.



A HF meal increases plasma exposure to a single dose of vismodegib, but there are no pharmacokinetic or safety differences between fasting and fed groups at steady-state. Vismodegib may be taken with or without food for daily dosing.
Tolerability of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance.

Currently, no consensus has been reached regarding the management of hyperlipidemia in patients who develop statin-associated myalgia (SAM). Many statin-intolerant patients use alternative lipid-lowering therapies, including red yeast rice. The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia. The study was conducted in a community-based setting in Philadelphia, Pennsylvania. A total of 43 adults with dyslipidemia and a history of statin discontinuation because of myalgia were randomly assigned to red yeast rice 2,400 mg twice daily or pravastatin 20 mg twice daily for 12 weeks. All subjects were concomitantly enrolled in a 12-week therapeutic lifestyle change program. The primary outcomes included the incidence of treatment discontinuation because of myalgia and a daily pain severity score. The secondary outcomes were muscle strength and plasma lipids. The incidence of withdrawal from medication owing to myalgia was 5% (1 of 21) in the red yeast rice group and 9% (2 of 22) in the pravastatin group (p = 0.99). The mean pain severity did not differ significantly between the 2 groups. No difference was found in muscle strength between the 2 groups at week 4 (p = 0.61), week 8 (p = 0.81), or week 12 (p = 0.82). The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.
Nonattendance in the Stockholm mammography screening trial: Relative Mortality and reasons for nonattendance

The first objective of this study was to analyze the survival rate in a group of 69 breast cancers detected among nonattenders in a randomized mammographic screening trial in relation to 142 clinically detected cancers in a nonscreened control population. By analyzing the cancers of the nonattenders we identified two subgroups, one (A) had actively avoided mammography, had cancers in more advanced stages on diagnosis, and had significantly higher mortality from breast cancer than the control group (p = 0.003). The second subgroup (B) had mammography done outside the screening program. This subgroup had a nonsignificant, slightly better survival (p = 0.19) compared to the control group. Concerning stage the cancers in group B were similar to the cancers by the screening program. The second objective was to analyze women's reasons for nonattendance in the screening program. We interviewed 200 randomly selected nonattenders; 33% stated that they never could imagine having mammography (definite nonattenders), 29.5% that they for various reasons had missed the mammography but could imagine having it next time (possible future attenders), and 32% had been examined outside the program. Reasons for nonattendance included disinterest, medical problems, and fear of X-rays. From this interview investigation we believe that the subgroup of definite nonattenders (33%) is difficult to influence. The second subgroup classified as possible future attenders (29.5%) we believe can be influenced by more information and a new opportunity to receive mammography, i.e., a reminder letter. The third subgroup, those examined outside the screening program (32%) were aware of the benefit of mammography, taking action on their own. Concerning these women's health this seems acceptable; screening outside the program seemed equivalent to that inside the program concerning stage and mortality in breast cancer as shown in the first part of the study.
Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population.



The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up.



Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5.



In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.
Relationship between primary headache and nutrition: a questionnaire about dietary habits of patients with headache

The role of food associated with the headache has been the subject of scientific research since 1900, especially for migraine patients. A substantial proportion of patients (ranging from 12 to 60 %) report that their migraine attacks may be precipitated by dietary elements, certain eating habits (fasting) and abuse (caffeine and alcoholic beverages abuse and withdrawal). The biological mechanism by means of triggers in general and food in particular precipitate migraine attacks remains obscure. Based on the data in the literature, we performed an osservational study searching for possible correlations between nutrition and primary headaches. We enrolled 50 consecutive patients from the Headache Center of the Neurology Department of Hospital “Cardinal Massaia” of Asti and submitted them a 14-item questionnaire for the assessment of relationship between primary headache and food. Our preliminary data, although the follow up is still in progress, show that there are strong associations between the onset of the headache and dietary habits. It will be necessary to analyze a larger sample in order to draw more precise conclusions on this topic.