nils-herrmann/clean_scirepeval huggingface dataset:
Development of a novel GLUT4 translocation assay for identifying potential novel therapeutic targets for insulin sensitization.

GLUT4 (glucose transporter 4) plays important roles in glucose homoeostasis in vivo. GLUT4 expression and function are diminished in diabetic human and animal subjects. The goal of the present study is to develop a cell-based assay for identifying negative regulators of GLUT4 translocation as potential targets for the treatment of Type 2 diabetes. Traditional GLUT4 translocation assays performed in differentiated myocytes or adipocytes are difficult to perform, particularly in HTS (high-throughput screening) mode. In the present study, we stably co-expressed c-Myc and eGFP [enhanced GFP (green fluorescent protein)] dual-tagged recombinant GLUT4 with recombinant IRS1 (insulin receptor substrate 1) in HEK-293 cells (human embryonic kidney cells) (HEK-293.IRS1.GLUT4 cells). Insulin treatment stimulated both glucose uptake and GLUT4 translocation in these cells. GLUT4 translocation is quantified by a TRF (time-resolved fluorescence) assay in a 96-well HTS format. TRF assays confirmed insulin-stimulated GLUT4 translocation, which can be inhibited by PI3K (phosphoinositide 3-kinase) or Akt [also called PKB (protein kinase B)] inhibitors. Treatment with palmitate increased IRS1 serine phosphorylation and reduced insulin-stimulated Akt phosphorylation and GLUT4 translocation, indicating insulin resistance. Knockdown of PTEN (phosphatase and tensin homologue deleted on chromosome 10) and PTP1B (protein tyrosine phosphatase 1B) gene expression by siRNA (small interfering RNA) treatment significantly increased GLUT4 translocation only in cells treated with palmitate but not in untreated cells. Similar results were obtained on treatment with siRNA of JNK1 (c-Jun N-terminal kinase 1), S6K1 (ribosomal protein S6 kinase, 70 kDa, polypeptide 1) and PKC(theta) (protein kinase C theta). In summary, we have established and validated a novel GLUT4 translocation assay that is optimal for identifying negative regulators of GLUT4 translocation. In combination with more physiologically relevant secondary assays in myotubes and adipocytes, this assay system can be used to identify potential novel therapeutic targets for the treatment of Type 2 diabetes.
Intervention targeted at nurses to improve venous thromboprophylaxis.

To assess the effectiveness of an intervention targeting both physicians and nurses vs. physicians only in improving venous thromboprophylaxis for older patients.



Cluster randomized trial.



Fifty hospital-based post-acute care departments in France.



Patients aged 65 years or older.



A multifaceted intervention to implement a clinical practice guideline addressing venous thromboprophylaxis.



The effectiveness outcomes were elastic stocking use, ambulation or mobilization under the supervision of a physical therapist and anticoagulant-based prophylaxis. Patient outcomes included deep vein thrombosis and anticoagulant-related adverse events.



One department allocated to the intervention targeted at physicians only and seven departments allocated to the intervention targeted at both physicians and nurses dropped out of the study. Compared with the intervention targeted at physicians only (n = 497 patients), the intervention targeted at both physicians and nurses (n = 315 patients) was associated with a higher rate of mobilization (62 vs. 37%, P < 0.001) and comparable levels of elastic stocking (32 vs. 39%, P = 0.74) and anticoagulant (55 vs. 48%, P = 0.36) use. The rates of deep vein thrombosis (15 vs. 13%, P = 0.50), bleeding (1 vs. 1%, P = 0.99) and thrombocytopaenia (0 vs. 0.2%, P = 0.99) did not differ between the two groups.



A multifaceted intervention targeting nurses in addition to physicians can increase the frequency of mobilization of older patients to prevent venous thromboembolism but does not alter the use of elastic stockings and anticoagulant. A differential drop-out of departments might have contributed to creating imbalances in baseline characteristics and outcomes in this study.
Treatment comparisons in the third MRC myelomatosis trial. Medical Research Council's Working Party on Leukaemia in Adults.

Results after an average follow-up of 3 years are presented on 485 patients in the 3rd MRC therapeutic trial in myelomatosis. The 353 non-azotaemic patients (199 now dead) were randomized between i.v. cyclophosphamide (CY) and oral melphalan with prednisone (M &P). THose treated with M &P fared slightly, but non-significantly, better. The 132 azotaemic patients (111 now dead) were randomized between i.v. CY and a 4-drug regimen, and both groups fared equally badly. Finally, after one year of the allocated treatment, 297 survivors (126 now dead) were randomized either to stop all treatment until evidence of relapse was obtained, or to continue treatment with azathioprine and vincristine, interrupted every 3 months for a course of the first-allocated treatment. The overall results suggested that maintenance therapy was beneficial, though the results were not statistically significant. Most of the difference was found among the few patients with unfavourable prognostic features who survived one year and were eligible for this randomization. In this, as in the two previous MRC trials, no striking differences have emerged between the therapeutic effects of different schedules of melphalan and/or CY. Consequently, a regimen of intermittent oral melphalan (with or without prednisone) seems satisfactory, because it is among the least toxic and most convenient. The 4th myeloma trial, now beginning, seeks to discover whether the addition of vincristine to the regimen can improve these results.
Hospital volume and quality of laparoscopic gastrectomy in Japan.

Laparoscopic gastrectomy (LG) has become the prevailing surgery of choice for gastric cancer, but the impact of hospital volume or operating room (OR) time has not been evaluated. An observational study was conducted to assess the quality of LG based on hospital volume and OR time.



3,054 LG patients were enrolled in 420 hospitals throughout Japan. Analyzed variables included patient demographics, complications, use of stapling devices or chemotherapy, hospital volume, and teaching status. Hospitals were categorized into high- (>or=4 LG per month), intermediate- (1-3) and low- (<1) volume hospitals. Multivariate analysis was used to measure hospital volume and OR time impact.



259 laparoscopic total gastrectomies (LTGs) were performed. Complications were observed in 269 cases (8.8%). High-volume hospitals treated less severe cases. OR time, but not hospital volume, was associated with complications. Hospital volume, teaching status and stapling devices explained variations in OR time.



OR time was a more significant predictor of complications than hospital volume. OR time was consumed more in the employment of stapling devices and LTG. To promote LG efficiency, training curricula highlighting the applicability of these techniques should be considered by clinical experts.
A novel metronomic chemotherapy regimen of weekly platinum and daily oral etoposide in high-risk non-small cell lung cancer patients.

The aim of this pilot phase II trial was to investigate the toxicity and anti-tumour activity of a novel metronomic regimen of weekly cisplatin (CDDP) and oral etoposide (VP16) in high-risk patients with advanced NSCLC. The study enrolled 31 high-risk patients (27 men and 4 women aged 16-82 years; mean, 64.3) with NSCLC (18 stage IIIB and 13 stage IV) and an ECOG performance status of < or = 3, all of whom received weekly CDDP 30 mg/m2 iv on days 1, 8, 14 and 28 of each cycle and oral daily etoposide 50 mg/m2 on 21 of the 28 days. The most frequent adverse events were grade III leukopenia and anemia; nevertheless, three patients died of pulmonary embolism after 2, 3 and 6 weeks of treatment. The objective response (OR) rate was 45.2% (2 complete and 12 partial), and the disease control rate was 58.1% (14 ORs and 4 disease stabilisations). The mean time to progression and survival were respectively nine months (95% CI, 6.3-15.8 months) and thirteen months (95% CI, 9.1-20.5 months). Pharmacological analysis showed that this metronomic regimen allows a much greater median monthly area under the curve of CDDP and VP16 than conventional treatment schedules. Our findings also suggest that this treatment schedule may affect tumour growth and neoangiogenesis by changing peripheral blood vascular-endothelial growth factor levels. These preliminary results indicate that our metronomic regimen is well tolerated and active, even in patients with a very poor prognosis.
Lifestyle and health determinants of cardiovascular disease among Greek older adults living in Eastern Aegean Islands: An adventure within the MEDIS study.

The aim of the present study was to evaluate lifestyle and health determinants of cardiovascular disease (CVD) risk among Greek elderly residents living in Eastern Aegean islands, in both Greece and Turkey.



Under the context of the MEDIS study, 724 older adults (aged 65 to 100 years) from 8 Eastern Aegean Sea Greek islands (n=100 living in Samothrace, 142 in Lesvos, 150 in Limnos, 76 in Ikaria, 52 in Kassos, 149 in Rhodes and Karpathos) and from Turkey (n=55older adults of Greek origin living on Gökçeada Island) were voluntarily recruited. Overall cardiometabolic risk was measured as the sum (range 0-4) of four common CVD risk factors (hypertension, diabetes, dyslipidemia and obesity).



Greek islanders had higher CVD scores compared to Greeks of Gökçeada (1.9±1.1 vs 1.4±1.0 risk factors / participant, p<0.001). Further analysis revealed that the diet of Greek islanders was similar to the traditional Mediterranean diet; however, these individuals demonstrated 2-times higher odds (95% CI, 1.04-3.87) for having hypertension, 1.53-times higher odds (95% CI, 0.66-3.54) for having diabetes, 3.29-times higher odds (95% CI, 1.58-6.81) for having hypercholesterolemia; whereas they had 0.78-times lower odds (95% CI, 0.40-1.52) for being obese, compared to elderly Greek adults living on Gökçeada.



Overall, CVD risk seems to be low among Eastern Aegean Islanders; certain differences in CVD risk factors exist between Greek islanders and their counterparts living in Gökçeada, and those differences may be attributed to various environmental, cultural and lifestyle factors.
Recovery of motor function after stroke: A polymyography-based analysis

We present a method for assessing muscle activation patterns during goal-directed movement. We present a cohort study from a randomized clinical trial that followed the recovery of motor function during and after intensive gait training, assisted by sensor-driven, four-channel electrical stimulation. The instrument that we developed allows for the simultaneous recordings of up to 16 channels that are wirelessly sent to a host computer, which then provides feedback to the subject. The inputs to the portable instrument support electromyography (EMG) amplifiers, inertial sensors and goniometers. We show that this method is sensitive enough to show changes in muscle activation patterns in stroke patients before and after gait training (four weeks, five days a week, 30 min daily). We also show that the recovery decreases the differences between patterns of muscle activities (e.g., levels of muscle activations and median frequencies) assessed in hemiplegic and healthy subjects. This method allows for the analysis of muscle contributions and activation patterns; therefore, it might be possible to better understand the physiology behind the recovery of function. This EMG analysis provides a quantification of recovery that is a valuable addition to other measures, such as the Fugl-Meyer score, the Berg-Balance score, gait speed, and the symmetry index.
A twin study of the genetics of fear conditioning.

Fear conditioning is a traditional model for the acquisition of fears and phobias. Studies of the genetic architecture of fear conditioning may inform gene-finding strategies for anxiety disorders. The objective of this study was to determine the genetic and environmental sources of individual differences in fear conditioning by means of a twin sample.



Classic fear conditioning data were experimentally obtained from 173 same-sex twin pairs (90 monozygotic and 83 dizygotic). Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure was the electrodermal skin conductance response. We applied structural equation modeling methods to the 3 conditioning phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors underlie individual variation in associative and nonassociative learning.



All components of the fear conditioning process in humans demonstrated moderate heritability, in the range of 35% to 45%. Best-fitting multivariate models suggest that 2 sets of genes may underlie the trait of fear conditioning: one that most strongly affects nonassociative processes of habituation that also is shared with acquisition and extinction, and a second that appears related to associative fear conditioning processes. In addition, these data provide tentative evidence of differences in heritability based on the fear relevance of the stimuli.



Genes represent a significant source of individual variation in the habituation, acquisition, and extinction of fears, and genetic effects specific to fear conditioning are involved.
Prospective study of the frequency and outcomes of patients with suspected pulmonary embolism administered heparin prior to confirmatory imaging.

The administration of empiric systemic anticoagulation (ESA) before confirmatory radiographic testing in patients with suspected pulmonary embolism (PE) may improve outcomes, but no data have been published regarding current practice. We describe the use of ESA in a large prospective cohort of emergency department (ED) patients and report the outcomes of those treated with ESA compared with patients not receiving ESA.



12-center, noninterventional study of ED patients who presented with symptoms concerning for PE. Clinical data including pretest probability and decision to start ESA were recorded at point of care by attending physicians. Patients were followed for adverse in-hospital outcomes and recurrence of venous thromboembolism.



ESA was initiated 342/7932 (4.3%) of enrolled patients, including 142/618 (23%) patients with high pretest probability. Patients receiving ESA had more abnormal vital signs and were more likely to have a history of venous thromboembolism than those who did not receive ESA. Overall, 481/7,932 (6.1%) had PE diagnosed, 72/481 (15.0%) with PE had ESA, and 72/342 (21%) of ESA patients had PE. Three patients (0.9%, 95%CI: 0.2-2.5%) who received ESA suffered hemorrhagic complications compared with 38 patients (0.5%, 95%CI: 0.4-0.7%) who did not receive ESA.



In this multicenter sample, ED physicians administered ESA to a small, generally more acutely ill subset of patients with high pretest probability of PE, and very few had hemorrhagic complications. ESA was not associated with any clear difference in outcomes. More study is needed to clarify the risk versus benefit of ESA.
Human-Robot Trust: Just a Button Press Away

Many of the benefits promised by human-robot interaction require successful continued interaction between a human and a robot; trust is a key component of such interaction. We investigate whether having a person "n the loop" with a robot---i.e., the mere involvement of a person with a robot---affects human-robot trust. We posited that people who press a button on a robot to permit its plan execution would exhibit greater trust than people who merely observe a robot's autonomous execution of the same plan. We assessed trust both toward the robot that participants interacted with and toward robots in potential future use contexts. We found (a) a marginally significant and medium-sized effect of the button press on people's trust in the observed robot (p = .12, d = .52), and (b) a significant and large-sized effect on people's trust in potential future robots, but only in social use contexts (p = .04, d = .68).
Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration.

To examine (1) the prevalence of depressive disorders in community-dwelling adults with advanced age-related macular degeneration (AMD) and (2) the relationship in this population between depression, visual acuity, the number of comorbid medical conditions, disability caused by vision loss as measured by the National Eye Institute-Vision Function Questionnaire (NEI-VFQ) and the vision-specific Sickness Impact Profile (SIPV), and disability caused by overall health status as measured by the Sickness Impact Profile-68 (SIP).



Analysis of cross-sectional baseline data from a randomized clinical trial.



Participants were 151 adults aged 60 and older (mean age, 80 years) with advanced macular degeneration whose vision was 20/60 or worse in their better eye.



Subjects were interviewed using measures of depression, disability, and chronic medical conditions. Visual acuity was obtained. Nonparametric correlation analyses and linear regression analyses were performed.



Structured Clinical Interview for DSM-IV (SCID-IV), Geriatric Depression Scale (GDS), NEI-VFQ, SIPV, and SIP.



Of the participants, 32.5% (n = 49) met SCID-IV criteria for depressive disorder, twice the rate observed in previous studies of community-dwelling elderly. Over and above depression (GDS), visual acuity aided in prediction of the level of vision-specific disability (NEI-VFQ and SIPV).



Depressive disorder is a significant problem for the elderly afflicted with advanced macular degeneration. Further research on psychopharmacologic and psychotherapeutic interventions for depressed AMD patients is warranted to improve depression and enhance functioning. Over and above depression, visual acuity aided in predicting vision-specific disability. Treatment strategies that teach patients to cope with vision loss should be developed and evaluated.
High-intensity versus low-level laser therapy in the treatment of patients with knee osteoarthritis: a randomized controlled trial

The aim of this randomized controlled study was to compare the effects of low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) on pain relief and functional improvement in patients with knee osteoarthritis (KOA). A total of 53 male patients participated in this study, with a mean (SD) age of 54.6 (8.49) years. Patients were randomly assigned into three groups and treated with HILT and exercise (HILT + EX), LLLT and exercise (LLLT + EX), and placebo laser plus exercise (PL + EX) in groups 1, 2, and 3, respectively. The outcomes measured were pain level measured by visual analog scale (VAS) and knee function measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Statistical analyses were performed to compare the differences between baseline and posttreatment measurements. The level of statistical significance was set as P < 0.05. The result showed that HILT and LLLT combined with exercise were effective treatment modalities in decreasing the VAS and WOMAC scores after 6 weeks of treatment. HILT combined with exercises was more effective than LLLT combined with exercises, and both treatment modalities were better than exercises alone in the treatment of patients with KOA.
A one-year school-based diet/exercise intervention improves non-traditional disease biomarkers in Mexican-American children.

School-based interventions are an effective way to treat childhood obesity. The purpose of the present study was to biologically validate an established school-based intervention designed to reduce standardised body mass index (zBMI) over a period of 12 months. This intervention focused on a subset of Mexican-American children who were participating in a larger clinical weight loss study. Plasma samples were analysed from self-identified Mexican-American children (12-14 years) who were randomised to either a school-based intervention (IN, n = 152) or self-help control (CN, n = 69). Treatment was 4 days week⁻¹ of exercise (45 min day⁻¹) and 1 day week⁻¹ of nutritional counselling for 6 months. Fasting (>8 h) blood samples were collected at baseline, 6 months (end of active intervention) and 12 months (6 months after the end of the active intervention). Plasma resistin, adiponectin and leptin concentration were measured using a multiplex assay. Separate linear mixed models and a P < 0.05 were used to test for significance. Significant group × time interactions were found for resistin (P < 0.0001), adiponectin (P = 0.001) and leptin (P = 0.013). For resistin, IN was 12% lower at 6 months than CN. Adiponectin concentration in IN was greater at 6 months (26%) and 12 months (8%) than CN. Leptin concentration was 22% lower for IN at 12 months than CN. We have previously reported that our school-based intervention reduced zBMI and now reported alterations in biologically relevant disease biomarkers. Some of the observed changes were only present at the end of the active intervention (resistin), while others persisted until 12 months (leptin and adiponectin). These changes underscore the effectiveness of our school-based intervention at not only improving zBMI but also at reducing disease risk.
Cardiovascular and hormonal responses to food ingestion in humans with spinal cord transection

In sympathetic denervation due to primary autonomic failure, ingestion of food causes a fall in blood pressure (BP) and exacerbates postural hypotension. It is not known whether these responses occur in tetraplegics with physiologically complete cervical spinal cord transection, who also have sympathetic dysfunction because of disruption of descending spinal sympathetic pathways. We, therefore, studied the effect of a liquid meal on BP, heart rate (HR) and neurohormonal levels in tetraplegics. Paraplegics with low lesions and without sympathetic dysfunction served as controls. After food ingestion, there was no fall in BP in tetraplegics or in controls. HR did not change in either group. After food, plasma noradrenaline was unchanged in tetraplegics, but rose in controls, while plasma renin activity (PRA) rose in tetraplegics but not in controls. The fall in BP and rise in HR on head-up tilt after the meal in tetraplegics was similar to that before the meal. There was no change in PRA following pre-prandial tilt in either group; postpprandial tilt raised levels in the tetraplegics, unlike in controls. Thus there is considerable variance in the responses to food between tetraplegics and paraplegic controls, and even greater differences when compared with published data in other autonomic disorders with sympathetic dysfunction; this may relate to the site and the nature of the sympathetic lesion and the ability to activate compensatory mechanism.