nils-herrmann/clean_scirepeval huggingface dataset:
Inverse Association of Serum Docosahexaenoic Acid With Newly Diagnosed Hypertension: A Community-based Case-control Study.

Observational studies on circulating fatty acid (FA) and primary prevention of hypertension have yielded inconsistent results, and the association among the Chinese population is not fully clear. The aim of the study was to discern important FAs that can discriminate hypertensive patients from normotensive persons, and investigate associations between the important FAs and risk of hypertension.We conducted a case-control study nested within a community-based cohort of 2447 Chinese participants aged 35 to 79 years who completed a baseline assessment between October 2012 and April 2013. In all, 480 patients with newly diagnosed hypertension were identified at baseline and 480 normotensive individuals were randomly selected as matched normotensive controls. Controls were individually matched to cases by age (±2 y), sex, and recruitment center, with a 1:1 case-to-control ratio. Serum FA profile was compared between cases and controls by orthogonal partial least squares-discriminant analyses. Odds ratio (OR) with 95% confidence interval (CI) for newly diagnosed hypertension was estimated by a conditional logistical analysis.After adjustment for body mass index, education, profession, family history of hypertension, salt intake, heart rate, blood lipids, and fasting glucose levels, serum FA profile in hypertensive patients was typically characterized by higher 16:0 and 16:1n-7, and lower 18:2n-6 and 22:6n-3, compared with normotensive controls. Docosahexaenoic acid (22:6n-3) and palmitoleic acid (16:1n-7) were identified as the important FA contributing most to the intergroup separations. When comparing the highest and lowest quartile of FA composition, newly diagnosed hypertension was negatively associated with 22:6n-3 (OR 0.65; 95% CI, 0.45-0.93; P for trend = 0.02), but positively associated with 16:1n-7 (OR 2.14; 95% CI, 1.46-3.12; P for trend < 0.001). The associations remained pronounced after multiple adjustments and in further stratified analyses.In distinguishing hypertensive patients and normotensive persons, 22:6n-3 was considered as an important n-3 FA. Increased serum proportion of 22:6n-3 was associated with decreased odds of newly diagnosed hypertension, which suggests that high levels of 22:6n-3 in serum or perhaps in diet may be beneficial for prevention of hypertension in the Chinese population.
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor PF-734200 added to metformin in Type 2 diabetes.

PF-734200 is a potent and selective oral dipeptidyl peptidase-4 (DPP-4) inhibitor. This study assessed the efficacy and safety of PF-734200 at dose rates of 20 and 30 mg/day in subjects with Type 2 diabetes mellitus inadequately controlled on metformin monotherapy.


This was a placebo-controlled, double-blind, randomized, multicentre, 12 week study. Subjects with Type 2 diabetes mellitus were eligible if screening glycosylated haemoglobin (HbA(1c) ) was 7-11% (53.0-96.7 mmol/mol) and they had been receiving metformin monotherapy for ≥2 months. Subjects receiving metformin and an insulin secretagogue or metformin and thiazolidinedione needed to have a screening HbA(1c) of 6.5-9.5% (47.5-80.3 mmol/mol), measured prior to discontinuing the insulin secretagogue or thiazolidinedione. The primary end-point of the study was a change from baseline to week 12 in HbA(1c) levels.


Baseline characteristics for 289 subjects randomized to PF-734200 or placebo groups were similar (mean age 56.5 years, mean body mass index 32.2 kg/m(2) and mean HbA(1c) 8.2%, 66.1 mmol/mol). In the predefined per protocol data set, least-squares mean HbA(1c) at week 12 was reduced by 0.79 (8.6 mmol/mol 95% confidence interval -1.10 to -0.49, -12.0 to -5.4 mmol/mol) and 0.92% (10.1 mmol/mol; -1.23 to -0.61, -13.4 to -6.7 mmol/mol) in the 20 and 30 mg groups, respectively, compared with placebo. Differences from placebo were statistically significant (P<0.0001), but the differences between the 20 and 30 mg groups were not. The intent-to-treat analysis yielded similar findings.


The HbA(1c) was significantly and meaningfully reduced by both doses of PF-734200, but 20 mg appears to be the more appropriate therapeutic dose for Type 2 diabetes mellitus, contingent upon confirmation by long-term controlled studies.
Dental Prophylaxis and Osteoradionecrosis: A Population-Based Study.

The aim of this study was to investigate the association of different dental prophylactic modalities and osteoradionecrosis (ORN) and determine the risk of ORN under different timing periods of scaling, with the use chlorhexidine mouth rinse after surgery and with different strategies of fluoride gel application in head and neck cancer (HNC) participants. A cohort of 18,231 HNC participants, including 941 ORN patients and 17,290 matched control cases, were enrolled from a Longitudinal Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) in Taiwan. Based on different dental prophylactic modalities before radiotherapy, including chlorhexidine mouth rinse, scaling, and fluoride gel, all HNC subjects were stratified into different groups. The Cox proportional hazard regression was used to compare ORN incidences under different dental prophylactic modalities. The results revealed that scaling and chlorhexidine mouth rinse were significantly related to ORN risk ( P = 0.004 and P < 0.0001). Chlorhexidine mouth rinse was highly correlated to ORN occurrence (hazard ratio [HR], 1.83-2.66), as exposure increased the risk by 2.43-fold among oral cancer patients, regardless of whether they had received major oral surgery or not. Oral cancer patients receiving scaling within 2 wk before radiotherapy increased their incidence of ORN by 1.28-fold compared with patients who had not undergone scaling within 6 mo. There is no significance of fluoride application for dental prophylaxis in increasing ORN occurrence. In conclusion, dental prophylaxis before radiotherapy is strongly correlated to ORN in HNC patients. Chlorhexidine exposure and dental scaling within 2 wk before radiotherapy is significantly related to ORN risk, especially in oral cancer patients. The use of 1.1% NaF topical application did not significantly increase the risk of ORN in HNC patients. An optimal dental prophylaxis protocol to reduce ORN should concern cancer location, cautious prescription of chlorhexidine mouth rinse, and proper timing of scaling.
Variability in individual response to various doses of omeprazole

This study was carried out in order to perform a combined prospective assessment of the individual pharmacodynamic response and of duodenal ulcer healing in patients treated with three different doses of omeprazole. Ninety-nine patients with endoscopically proven duodenal ulcers were subdivided into three parallel groups of 33 cases, who were randomly assigned to receive orally at 0800 hr, in single blind fashion, either 10 mg, 20 mg, or 40 mg of omeprazole. All of them underwent continuous intragastric pH monitoring both in basal conditions and on the fifth day of each dose regimen; ulcer healing was then assessed endoscopically after four weeks of treatment. All three doses of omeprazole caused pH values to increase significantly (P<0.001) over the whole 24-hr period. In patients treated with omeprazole 10 mg, the individual responses showed the highest variability: the acid inhibition, expressed in terms of time spent above pH 3.0, lasted for more than 16 hr in 42% of cases, for more than 8 hr in 28%, and for less than 6 hr in 30%. In patients treated with omeprazole 20 mg, the pharmacological response was more marked and uniform and lasted for more than 16 hr in 79% of cases; however, it is worth noting it lasted for less than 6 hr in three patients (10%). In patients treated with omeprazole 40 mg, the individual response was excellent (more than 16 hr) in 94% of cases, and it lasted for less than 6 hr in only one patient (3%). The mean durations of antisecretory effect of 10, 20 and 40 mg of omeprazole were 13.21, 19.10, and 21.45 hr, and the respective four-week healing rates were 68%, 87%, and 98%. Thus, the longer-lasting the acid inhibition, the higher the healing rate (P<0.05). A dose of omeprazole as low as 10 mg produces a consistent acid inhibition in 70% of cases, and this can be associated with frequent, but unpredictable, clinical benefit. The acid suppression obtained with omeprazole 20 mg is remarkable in the majority of patients, but is poor in 10% of cases, and this finding may result in clinical nonresponse. The 40-mg dose of omeprazole produces the most uniform response and is only occasionally unsuccessful in the clinical setting.
Alzheimer's disease - input of vitamin D with mEmantine assay (AD-IDEA trial): study protocol for a randomized controlled trial

Current treatments for Alzheimer's disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine.



The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] < 30 ng/mL), normocalcemia (i.e., serum calcium < 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer's Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up & Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone.



The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD.
Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus.

Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin.



Adult type 2 diabetes mellitus patients (N = 801) with glycated haemoglobin (HbA(1c)) 6.5-10% on stable metformin doses (1500-3000 mg/day) were randomized 1 : 1 to add-on 5 mg saxagliptin or 100 mg sitagliptin once daily for 18 weeks. The primary efficacy analysis was a comparison of the change from baseline HbA(1c) at week 18 in per-protocol patients. Noninferiority was concluded if the upper limit of the two-sided 95% confidence interval of the HbA(1c) difference between treatments was < 0.3%.



The adjusted mean changes in HbA(1c) following the addition of saxagliptin or sitagliptin to stable metformin therapy were - 0.52 and - 0.62%, respectively. The between-group difference was 0.09% (95% confidence interval, - 0.01 to 0.20%), demonstrating noninferiority. Both treatments were generally well tolerated; incidence and types of adverse events were comparable between groups. Hypoglycaemic events, mostly mild, were reported in approximately 3% of patients in each treatment group. Body weight declined by a mean of 0.4 kg in both groups.



Saxagliptin added to metformin therapy was effective in improving glycaemic control in patients with type 2 diabetes mellitus inadequately controlled by metformin alone; saxagliptin plus metformin was noninferior to sitagliptin plus metformin, and was generally well tolerated.
Stressors Related to Immigration and Migration Background in Turkish Patients with Psychiatric Disorder: Validity of a Short Questionnaire (MIGSTR10)

The validity of a brief 10-item instrument for the assessment of stressors potentially related to migration and migration background (MIGSTR10) was evaluated in a retrospective analysis. To show convergent and discriminant validity, MIGSTR10 scores and general psychosocial stressors derived from DSM-IV axis IV (DSMSTR9) were compared between a randomly selected group of 30 inpatients with Turkish migration background (MIG) and a native German control group (CON), matched for age, gender, and diagnosis. The differential contribution of MIGSTR10 and DSMSTR9 to global functioning (GAF scores) was calculated. Multivariate analysis showed significantly higher distress in MIG compared to CON with regard to MIGSTR10 (λ = 0.33; P < 0.0005) and DSMSTR9 (λ = 0.703; P = 0.030); significant differences of single stressor severities between MIG and CON were found for “communication problems”, “migration history”, “loss of status”, and “homesickness” (adjusted P < 0.01) of the MIGSTR10, but for none of the DSMSTR9 stressors. Multiple regression analyses revealed a significant independent contribution of MIGSTR10, but not of DSMSTR9 sum scores, to GAF scores (R² = 23%, P = 0.011) in the MIG group whereas no significant overlap between stressor severity and GAF scores was found in CON. The results corroborate the validity of the MIGSTR10 to assess migration-related stressors which can affect global functioning and mental health in patients with migration background.
Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects.



Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay.



Serum growth hormone levels failed to correlate with age (r2 = 3.03) in the entire group of normal subjects (i.e. 20 - 80 years). In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092). Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269) in the 20 - 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 - 80 yrs) or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p < 0.001) in systemic lupus erythematosus patients, but only when compared to the entire group of normal subjects. Serum somatostatin levels differed from normal subjects only in older (i.e. >55 yrs) systemic lupus erythematosus patients.



These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal hyperostosis and hypermobility syndrome where significantly higher serum growth hormone levels were found. Somatostatin levels in elderly systemic lupus erythematosus patients may provide a clinical marker of disease activity in these patients.
Practice Pattern of Gastroenterologists for the Management of GERD Under the Minimal Influence of the Insurance Reimbursement Guideline: A Multicenter Prospective Observational Study

The objective of the study was to document practice pattern of gastroenterologists for the management of gastroesophageal reflux disease (GERD) under the minimal influence of the insurance reimbursement guideline. Data on management for 1,197 consecutive patients with typical GERD symptoms were prospectively collected during 16 weeks. In order to minimize the influence of reimbursement guideline on the use of proton pump inhibitors (PPIs), rabeprazole was used for the PPI treatment. A total of 861 patients (72%) underwent endoscopy before the start of treatment. PPIs were most commonly prescribed (87%). At the start of treatment, rabeprazole 20 mg daily was prescribed to 94% of the patients who received PPI treatment and 10 mg daily to the remaining 6%. At the third visits, rabeprazole 20 mg daily was prescribed to 70% of those who were followed and 10 mg daily for the remaining 30%. Continuous PPI treatment during the 16-week period was performed in 63% of the study patients. In conclusion, a full-dose PPI is preferred for the initial and maintenance treatment of GERD under the minimal influence of the insurance reimbursement guideline, which may reflect a high proportion of GERD patients requiring a long-term treatment of a full-dose PPI.
Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial.

Weight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated interferon alpha-2a (Peg-IFN-α2a) ± ribavirin in the Pediatric Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual-energy X-ray absorptiometry scan, as well as dietary and activity assessments during and after treatment. One hundred and fourteen (55% male) children, with a mean age of 11 ± 3 years, were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into three groups according to duration of treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to 0.50 z score were observed for weight, height, and BMI while on therapy among all groups (P ≤ 0.01, compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ) score. Though weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long-treatment duration group (P = 0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores, and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment.



Peg-IFN-α2a was associated with significant changes in body weight, linear growth, BMI, and body composition in children. These effects were generally reversible with cessation of therapy, although HAZ scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.
RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses

F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in multiple cancers through genetic deletion and mutations in a broad range of tumours. Loss of FBXW7 functionality results in the stabilisation of multiple major oncoproteins, culminating in increased cellular proliferation and pro-survival pathways, cell cycle deregulation, chromosomal instability and altered metabolism. Currently, there is no therapy to specifically target FBXW7-deficient tumours.We performed a siRNA kinome screen to identify synthetically lethal hits to FBXW7 deficiency.We identified and validated cyclin G-associated kinase (GAK) as a potential new therapeutic target. Combined loss of FBXW7 and GAK caused cell cycle defects, formation of multipolar mitoses and the induction of apoptosis. The synthetic lethal mechanism appears to be independent of clathrin-mediated receptor endocytosis function of GAK.Conclusions:These data suggest a putative therapeutic strategy for a large number of different types of human cancers with FBXW7 loss, many of which have a paucity of molecular abnormalities and treatment options.