nils-herrmann/clean_scirepeval huggingface dataset:
Promoter insertion/deletion in the IRF5 gene is highly associated with susceptibility to systemic lupus erythematosus in distinct populations, but exerts a modest effect on gene expression in peripheral blood mononuclear cells.

We examined the genetic association of the promoter insertion/deletion (indel) in IRF5 gene with systemic lupus erythematosus (SLE) in distinct populations and assessed its role in gene expression.



Four IRF5 polymorphisms were genotyped in 1488 SLE patients and 1466 controls. Gene expression was analyzed by quantitative real-time PCR using RNA from peripheral blood mononuclear cells (PBMC).



The promoter indel and rs2070197 had independent genetic effects, which accounted for the association of rs2004640 and rs10954213. Gene expression analysis revealed that rs10954213 exerted the greatest influence on IRF5 transcript levels.



We corroborated the association of the promoter indel with SLE in 5 different populations and revealed that rs10954213 is the main single-nucleotide polymorphism responsible for altered IRF5 expression in PBMC.
Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial

We present results of a randomized, placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density (BMD), bone metabolism and body composition in 225 healthy adults aged 55 to 85 years. Dehydroepiandrosterone (DHEA) levels decline dramatically with age, concurrent with the onset of osteoporosis, suggesting a role for DHEA supplementation in preventing age-related bone loss. We conducted a randomized, placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density (BMD), bone metabolism and body composition in 225 healthy adults aged 55 to 85 years. DHEA treatment increased serum DHEA and DHEA sulfate levels to concentrations seen in young adults. Testosterone, estradiol and insulin-like growth factor (IGF-1) levels increased in women (all p < 0.001), but not men, receiving DHEA. Serum C-terminal telopeptide of type-1 collagen levels decreased in women (p = 0.03), but not men, whereas bone-specific alkaline phosphatase levels were not significantly altered in either sex. After 12 months, there was a positive effect of DHEA on lumbar spine BMD in women (p = 0.03), but no effect was observed for hip, femoral neck or total body BMD, and no significant changes were observed at any site among men. Body composition was not affected by DHEA treatment in either sex. Among older healthy adults, daily administration of 50 mg of DHEA has a modest and selective beneficial effect on BMD and bone resorption in women, but provides no bone benefit for men.
The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: an observational study.

The diagnostic criteria for basal cell carcinoma (BCC) using optical coherence tomography (OCT) have been described previously, but the clinical value of these findings remains unknown.



To investigate the diagnostic value of OCT for BCC in a typical clinical setting. The primary efficacy end point was a diagnosis of BCC for each lesion. Secondary end points were the diagnosis of other possible conditions.



This was an observational, prospective, multicentre study in which consecutive patients with nonpigmented pink lesions suspicious for BCC underwent clinical assessment, dermoscopy and OCT, with the diagnosis recorded at each stage. Once all diagnoses had been recorded, the histological results were disclosed. In total 164 patients with 256 lesions were recruited. Histology was missing for 21 lesions, leaving 235 lesions in 155 patients for analysis.



Sixty per cent of lesions (141 of 235) were identified as BCC by histology. A slight increase of sensitivity was noted following OCT, which did not reach statistical significance. The specificity increased significantly from 28·6% by clinical assessment to 54·3% using dermoscopy and to 75·3% with the addition of OCT (P < 0·001). The positive predictive value for the diagnosis of BCC using OCT was 85·2% [95% confidence interval (CI) 78·6-90·4], and the negative predictive value was 92·1% (95% CI 83·6-97·0). The accuracy of diagnosis for all lesions increased from 65·8% with clinical evaluation to 76·2% following additional dermoscopy and to 87·4% with the addition of OCT.



OCT significantly improved the diagnostic specificity for BCC compared with clinical assessment and dermoscopy alone.
CD 44 v 6 is not a prognostic factor in primary breast cancer

CD44 is an adhesion molecule and represents a highly variable family of isoforms. The isoform CD44v6 has been associated with metastasis formation and poor prognosis in animal models and human colon cancer. Results of studies in primary breast cancer are relatively small and contradictory.  The immunohistochemical expression of CD44v6 was studied in a series of 338 patients with primary breast tumours, uniformly staged and treated in a single center with a long median follow-up of 128 months. The prognostic significance of CD44v6 as well as the correlation with several clinicopathological features were analysed.  Two hundred nineteen of 338 (64.8%) of the breast cancers were CD44v6-positive (>5% of tumour cells with positive staining). CD44v6 expression had no value for prognosticating disease-free or overall survival at this or any other cut-off point.  CD44v6 expression is not a prognostic factor in primary breast cancer.
Participation in life situations of 8-12 year old children with cerebral palsy: cross sectional European study

To evaluate how involvement in life situations (participation) in children with cerebral palsy varies with type and severity of impairment and to investigate geographical variation in participation.



Cross sectional study. Trained interviewers visited parents of children with cerebral palsy; multilevel multivariable regression related participation to impairments, pain, and sociodemographic characteristics.



Eight European regions with population registers of children with cerebral palsy; one further region recruited children from multiple sources.



1174 children aged 8-12 with cerebral palsy randomly selected from the population registers, 743 (63%) joined in the study; the further region recruited 75 children.



Children's participation assessed by the Life-H questionnaire covering 10 main areas of daily life. Scoring ignored adaptations or assistance required for participation.



Children with pain and those with more severely impaired walking, fine motor skills, communication, and intellectual abilities had lower participation across most domains. Type of cerebral palsy and problems with feeding and vision were associated with lower participation for specific domains, but the sociodemographic factors examined were not. Impairment and pain accounted for up to a sixth of the variation in participation. Participation on all domains varied substantially between regions: children in east Denmark had consistently higher participation than children in other regions. For most participation domains, about a third of the unexplained variation could be ascribed to variation between regions and about two thirds to variation between individuals.



Participation in children with cerebral palsy should be assessed in clinical practice to guide intervention and assess its effect. Pain should be carefully assessed. Some European countries facilitate participation better than others, implying some countries could make better provision. Legislation and regulation should be directed to ensuring this happens.
Heart valve surgery in hemodialysis-dependent patients: nutrition status impact on surgical outcome

Valve surgery in hemodialysis-dependent patients is associated with postoperative complications and a high mortality rate, and such patients frequently suffer cachexia. This study aimed to determine pre- and intraoperative risk factors associated with in-hospital mortality and long-term survival in hemodialysis-dependent patients undergoing heart valve surgery from the viewpoint of nutrition status. Eighty-seven hemodialysis-dependent patients who underwent valve surgery between January 1998 and October 2015 were retrospectively reviewed. Thirty-seven potential perioperative risk factors were evaluated. The in-hospital mortality rate was 12.6 % (11 patients). Univariate analysis identified New York Heart Association Functional Classification III or IV, emaciation (body mass index <17.6 kg/m2), total cholesterol <120 mg/dl, serum albumin <3.0 mg/dl, emergent/urgent surgery, and intraoperative blood transfusion >3000 ml as predictors of in-hospital death. Multivariate logistic regression analysis confirmed low serum albumin <3.0 mg/dl (hazard ratio 7.22; p = 0.032) and emergent/urgent operation (hazard ratio 43.57; p = 0.035) as independent predictors of in-hospital death. The 1- and 3-year actuarial survival rates were 64.9 ± 5.4 and 51.8 ± 5.8 %, respectively. Long-term survival estimated by log-rank test was negatively impacted by anemia (hemoglobin <10 mg/dl), low serum albumin, emergent/urgent operation, and infective endocarditis. Multivariate analysis using Cox proportional hazards modeling indicated low serum albumin (hazard ratio 2.12; p = 0.047) and emergent/urgent operation (hazard ratio 8.97; p = 0.0002) as independent predictors of remote death. Hypoalbuminemia and emergent/urgent operation are strong predictors of in-hospital and remote death. Malnutrition before surgery should be considered for operative risk estimation, and adequate preoperative nutrition management may improve surgical outcomes for hemodialysis-dependent patients.
Stearate-enriched plant sterol esters lower serum LDL cholesterol concentration in normo- and hypercholesterolemic adults.

Studies in our laboratory have previously demonstrated in hamsters a superior cholesterol-lowering ability of plant sterol (PS) esters enriched in stearate compared with linoleate. We therefore conducted a randomized, double-blind, 2-group parallel, placebo-controlled study to test the cholesterol-lowering properties of stearate-enriched PS esters in normo- and hypercholesterolemic adults. Thirty-two adults, 16 per group with equal number of males and females in each group, participated in the 4-wk study. Participants consumed 3 g/d (1 g three times per day with meals) of either PS esters or placebo delivered in capsules. Serum LDL cholesterol concentration significantly decreased 0.42 mmol/L (11%) and the LDL:HDL cholesterol ratio decreased 10% with PS ester supplementation, whereas LDL particle size and lipoprotein subclass particle concentrations (as measured by NMR) were not affected. The percent change in LDL cholesterol was positively correlated with baseline lathosterol concentration (r = 0.729; P = 0.0014), indicating an association between the magnitude of LDL change and the rate of whole-body cholesterol synthesis. Serum campesterol (but not sitosterol) concentration significantly increased in the PS ester group. Serum tocopherol, retinol, and beta-carotene concentrations were not affected by PS ester supplementation. Thus, our findings demonstrate the usefulness of a novel stearate-enriched PS ester compound in decreasing LDL cholesterol in both normo- and hypercholesterolemic adults. The extent to which PS ester fatty acid composition affects intestinal micelle formation and cholesterol absorption in humans requires further study.
A phase II trial of arsenic trioxide for relapsed and refractory acute lymphoblastic leukemia.

We designed a phase II trial of arsenic trioxide (AT) for the treatment of relapsed and refractory acute lymphoblastic leukemia (ALL). The dose administered was 0.25 mg/kg/day intravenously for 5-7 days per week for up to 60 days. Of 11 patients eligible, eight had B-cell and three T-cell ALL and two were Philadelphia chromosome-positive. The median duration of therapy was 21 days (range 7-28). One patient died of an infection. There were no responses. Ten patients have died. The median survival was 3.2 months (range 1.2-4.1). We conclude that AT is not active in the treatment of ALL.
Vascular and fibrinolytic effects of intra-arterial tumour necrosis factor-alpha in patients with coronary heart disease.

Elevated plasma t-PA (tissue plasminogen activator) and serum CRP (C-reactive protein) concentrations are associated with an adverse cardiovascular risk. In the present study, we investigated whether acute local inflammation causes vascular dysfunction and influences t-PA release in patients with stable coronary heart disease. Serum CRP, plasma t-PA and PAI-1 (plasminogen activator inhibitor type 1) concentrations were determined in 95 patients with stable coronary heart disease. A representative subpopulation of 12 male patients received an intra-brachial infusion of TNF-alpha (tumour necrosis factor-alpha) and saline placebo using a randomized double-blind cross-over study design. Forearm blood flow and plasma fibrinolytic and inflammatory variables were measured. Serum CRP concentrations correlated with plasma t-PA concentrations (r=0.37, P<0.001) and t-PA/PAI-1 ratio (r=-0.21, P<0.05). Intra-arterial TNF-alpha caused a rise in t-PA concentrations (P<0.001) without affecting blood flow or PAI-1 concentrations. TNF-alpha pretreatment impaired acetylcholine- and sodium nitroprusside-induced vasodilatation (P<0.001 for both) whilst doubling bradykinin-induced t-PA release (P=0.006). In patients with stable coronary heart disease, plasma fibrinolytic factors correlate with a systemic inflammatory marker and local vascular inflammation directly impairs vasomotor function whilst enhancing endothelial t-PA release. We suggest that the adverse prognosis associated with elevated plasma t-PA concentrations relates to the underlying causative association with vascular inflammation and injury.
Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomised controlled trial

Hot flushes and night sweats (HFNS) affect 65-85% of women after breast cancer treatment; they are distressing, causing sleep problems and decreased quality of life. Hormone replacement therapy is often either undesirable or contraindicated. Safe, effective non-hormonal treatments are needed. We investigated whether cognitive behavioural therapy (CBT) can help breast cancer survivors to effectively manage HFNS.



In this randomised controlled trial, we recruited women from breast clinics in London, UK, who had problematic HFNS (minimum ten problematic episodes a week) after breast-cancer treatment. Participants were randomly allocated to receive either usual care or usual care plus group CBT (1:1). Randomisation was done in blocks of 12-20 participants, stratifying by age (younger than 50 years, 50 years or older), and was done with a computer-generated sequence. The trial statistician and researchers collecting outcome measures were masked to group allocation. Group CBT comprised one 90 min session a week for 6 weeks, and included psycho-education, paced breathing, and cognitive and behavioural strategies to manage HFNS. Assessments were done at baseline, 9 weeks, and 26 weeks after randomisation. The primary outcome was the adjusted mean difference in HFNS problem rating (1-10) between CBT and usual care groups at 9 weeks after randomisation. Analysis of the primary endpoint was done by modified intention to treat. The trial is registered, ISRCTN13771934, and was closed March 15, 2011.



Between May 5, 2009, and Aug 27, 2010, 96 women were randomly allocated to group CBT (n=47) or usual care (n=49). Group CBT significantly reduced HFNS problem rating at 9 weeks after randomisation compared with usual care (mean difference -1·67, 95% CI -2·43 to -0·91; p<0·0001) and improvements were maintained at 26 weeks (mean difference -1·76, -2·54 to -0·99; p<0·0001). We recorded no CBT-related adverse events.



Group CBT seems to be a safe and effective treatment for women who have problematic HFNS after breast cancer treatment with additional benefits to mood, sleep, and quality of life. The treatment could be incorporated into breast cancer survivorship programmes and delivered by trained breast cancer nurses.
Features of the spike activity of globus pallidus neurons and pallido-thalamic functional interactions during targeted verbally cued movements in humans

This paper reports the results of an analysis of evoked spike activity in neurons of the human globus pallidus during performance of a targeted verbally cued movement, along with a comparison with the results of previous experiments on evoked spike activity of neurons in the reticular and ventrolateral thalamic nuclei in an identical test, recorded during stereotaxic surgery with a microelectrode technique in patients with Parkinson’s disease. The following observations are reported for the first time: 1) The existence in the outer segment of the human pallidus of neurons with convergent properties, selectively responding with activation to significant “stimulatory” verbal command stimuli initiating the launch and performance of a targeted movement; 2) similarity in the dynamics of concordantly occuring responses of convergent neurons in the integrative centers of the striopallidothalamic circuit in functionally important phases of movement act performance. It is suggested that the similar concordantly developing dynamics of neuronal rearrangements during the performance of a targeted movement act within the structures of this circuit reflects functional interstructural and interneuronal interactions occurring in the striopallidothalamocortical system of the human brain, which is involved in organizing verbally cued targeted forms of activity.
A Randomized, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of 0.5 mg and 1 mg Alosetron in Women With Severe Diarrhea-predominant IBS

Alosetron is indicated for women with chronic, severe diarrhea-predominant IBS (d-IBS) who have not responded adequately to conventional therapy. Constipation is the most common adverse event with alosetron treatment. Multiple dosing regimens were assessed in a randomized, double-blind, placebo-controlled study (S3B30040) to determine efficacy, tolerability, and evaluate constipation rate.METHODS:705 women with severe d-IBS were randomized to placebo, alosetron 0.5 mg once daily, 1 mg once daily, or 1 mg twice daily for 12 wk. The primary end point was the proportion of week 12 responders (patients with moderate or substantial improvement in IBS symptoms) on the 7-point Likert Global Improvement Scale (GIS). Secondary end points were average rate of adequate relief of IBS pain and discomfort, and bowel symptom improvements.The proportion of GIS responders at week 12 (primary time point) was significantly greater in all alosetron groups compared with placebo (54/176 [30.7%], 90/177 [50.8%], 84/175 [48%], and 76/177 [42.9%] for placebo, 0.5, 1 mg once daily, and 1 mg twice daily alosetron groups, respectively; P ≤ 0.02). Results were similar for the average adequate relief rate (treatment effects ≥12%, P ≤ 0.038). Bowel symptoms were improved in all alosetron groups. Constipation was the most common adverse event (9%, 16%, and 19% patients in the 0.5 mg, 1 mg once daily, and 1 mg twice daily groups, respectively). One event of intestinal obstruction and one of ischemic colitis occurred in the 0.5 mg group, and one event of fecal impaction occurred in the 1 mg twice-daily group. All were self-limited and resolved without sequelae.Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a decreased constipation rate.
Characteristics and survival to discharge of patients with STEMI between a PPCI-capable hospital and a non-PPCI hospital: a prospective observational study.

Primary percutaneous coronary intervention (PPCI) is a key therapeutic method in the treatment of ST-elevation myocardial infarction (STEMI). We studied the characteristics and survival to discharge in STEMI patients who presented in a PPCI-capable hospital and a non-PPCI hospital.



This prospective observational study included 240 consecutive patients. One basic questionnaire was distributed along with an explanatory letter to the participants, who were followed until discharge from the hospital or death.



Of the 240 patients, 234 (97.5%) survived to hospital discharge. Only 6 (5%) patients who were initially presented to a non-PPCI hospital died after inter-facility transfer. Also, 36 (92.3%) of the 39 patients with an intervening time of over 90 min were admitted initially in a non-PPCI hospital. Although there was a statistically significant correlation between the type of the hospital and the delay from the onset of symptoms to PPCI (P=0.001), such correlation was not found between the delay PPCI and the outcome of the patients (P>0.05).



Patients with STEMI may be transferred to a non-PPCI hospital due to the lack of prehospital triage. However, prompt inter-facility transfer results in good outcome.
Prospects for Anti-Biofilm Pharmaceuticals

This commentary highlights several avenues currently being pursued in research labs to the development of new anti-biofilm pharmaceuticals. There is a real need for alternative therapeutic modalities for treating the persistent infections that sometimes form on implanted medical devices or compromised niches within the body. Strategies being researched include discovering new antimicrobial agents that kill microorganisms in biofilms more effectively than do existing antibiotics, designing drugs that block microbial adhesion or interfere with intercellular communication, developing chemistries to disperse biofilms, and combining agents with different mechanisms of action. Though the need is great, the pathway to commercialization of new drugs is steep. One possible streamlined approach to navigating the regulatory approval process is to repurpose old drugs, a strategy that a few groups have shown can yield agents with anti-biofilm properties.
Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer

Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial.Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured.Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers.This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.