nils-herrmann/clean_scirepeval huggingface dataset:
Enhanced differentiation of human adipose tissue-derived stromal cells into insulin-producing cells with glucagon-like peptide-1.

Type 1 diabetes mellitus (T1DM) is mainly caused by reduction of the endogenous insulin secretion due to autoimmune destruction of pancreatic β cells, and a promising therapeutic approach for T1DM is pancreas and islet cell replacement. The major obstacle is the limited source of insulin-producing cells. Here, we report an efficient approach to induce human adipose-derived stromal cells (hADSCs) to differentiate into insulin-producing cells, with glucagon-like peptide-1 (GLP-1). hADSCs were successfully isolated from the adipose tissue, with adipogenic and osteogenic differentiation potency. Islet-like cell clusters formed in the culture, which was enhanced with the treatment of GLP-1. Reverse transcription polymerase chain reaction analysis showed the expression of the pancreas-related genes in the differentiated cells, such as pdx-1, ngn3, insulin, glucagon, somatostatin, glucokinase n and glut2. Immunocytochemical analysis showed that the induced cells co-expressed insulin, C-peptide and PDX-1. The GLP-1 receptor was present in the differentiated cells. In addition, flow cytometry analysis and ELISA showed that, in the presence of GLP-1, the percentage of insulin-producing cells was increased from 5.9% to 28.0% and the release of insulin increased from 9.53±0.7 pmol/106 cells to 15.86±1.3 pmol/106 cells. Insulin was released in response to glucose stimulation in a manner comparable to that of adult human islets. These results indicated that hADSCs isolated from adipose tissues can be induced to differentiate into insulin-producing cells, which is further enhanced with the treatment of GLP-1. These findings confirm that the differentiation of hADSCs to insulin-producing cells is indeed possible and indicate that the differentiated insulin-producing cells can be used as a potential source for transplantation into patients with T1DM.
Short-term effects of a combined nutraceutical of insulin-sensitivity, lipid level and indexes of liver steatosis: a double-blind, randomized, cross-over clinical trial

Overweight subjects easily develop alterations of the glucose and lipid metabolism and are exposed to an increased cardiometabolic risk. This condition is potentially reversible through the improvement of dietary and behavioural habits. However, a well-assembled nutraceutical would be a useful tool to better improve the metabolic parameters associated to overweight and insulin resistance.



To evaluate the effect of a combined nutraceutical containing berberine, chlorogenic acid and tocotrienols, we performed a double blind, cross-over designed trial versus placebo, in 40 overweight subjects with mixed hyperlipidaemia. After the first 8 weeks of treatment (or placebo), patients were asked to observe a 2-week washout period, and they were then assigned to the alternative treatment for a further period of 8 weeks. Clinical and laboratory data associated to hyperlipidaemia and insulin resistance have been obtained at the baseline, at the end of the first treatment period, after the washout, and again after the second treatment period.



Both groups experienced a significant improvement of anthropometric and biochemical parameters versus baseline. However, total cholesterol, LDL cholesterol, triglycerides, non-HDL cholesterol, fasting insulin, HOMA-IR, GOT and Lipid Accumulation Product decreased more significantly in the nutraceutical group versus placebo.



This combination seems to improve a large number of metabolic and liver parameters on the short-term in overweight subjects. Further studies are needed to confirm these observations on the middle- and long-term.
NCIC CTG IND.181: Phase I study of AT9283 given as a weekly 24 hour infusion in advanced malignancies

AT9283 is a potent inhibitor of the mitotic regulators, Aurora-kinases A and B, and has shown anti-tumor activity in patients with solid and haematological malignancies. This phase I study assessed safety, tolerability, pharmacokinetic and pharmacodynamic properties of AT9283.  Patients with advanced, incurable solid tumors or non-Hodgkin’s lymphoma received AT9283 as a continuous 24-hour infusion on days 1, 8 of a 21-day cycle. A 3 + 3 dose escalation design was used with a starting dose of 1.5 mg/m2/day. Pharmacokinetic samples were collected from all patients on cycle one, and pharmacodynamic samples were collected from 4 patients at the recommended phase II dose (RP2D).  patients were evaluable for toxicity and 32 were evaluable for response. AT9283 was well tolerated, with main toxicities being reversible dose-related fatigue, gastrointestinal disturbance, anemia, lymphocytopenia and neutropenia. The dose limiting toxicities were febrile neutropenia (two patients) and neutropenia with grade 3 infection (1 patient) at 47 mg/m2/day (established as the maximum tolerated dose). The RP2D was 40 mg/m2/day. Pharmacokinetic analyses showed AT9283 appeared to follow linear kinetics, with a mean elimination half-life of 8.2 h. Pharmacodynamic analyses showed no consistent or significant changes, but trends suggested evidence of AT9283 inhibition and anti-proliferative activity. One patient had partial response and four patients experienced RECIST stable disease (median 2.6 months).  In this study, AT9283 was well tolerated. The RP2D is 40 mg/m2/day on days 1, 8 of a 21-day cycle. Ongoing AT9283 trials will assess efficacy and safety in solid and haematological cancers.
Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1.

We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity.



Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS).



From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B.



IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.
Statistical Blockade: A Novel Method for Very Fast Monte Carlo Simulation of Rare Circuit Events, and its Application

Circuit reliability under statistical process variation is an area of growing concern. For highly replicated circuits such as SRAMs and flip flops, a rare statistical event for one circuit may induce a not-so-rare system failure. Existing techniques perform poorly when tasked to generate both efficient sampling and sound statistics for these rare events. Statistical Blockade is a novel Monte Carlo technique that allows us to efficiently filter---to block---unwanted samples insufficiently rare in the tail distributions we seek. The method synthesizes ideas from data mining and Extreme Value Theory, and shows speed-ups of 10X-100X over standard Monte Carlo.
A comparison of phenytoin-loading techniques in the emergency department.

To compare the effectivenesses of three phenytoin-loading techniques.



Patients with subtherapeutic phenytoin concentrations who presented within 48 hours of a seizure were randomized to receive either 20 mg/kg of oral phenytoin (PO), divided in maximum doses of 400 mg every two hours, 18 mg/kg of intravenous phenytoin (IVP) at an initial infusion rate of 50 mg/min, or 18 mg/kg (phenytoin equivalents) of intravenous fosphenytoin (IVF) at an initial infusion rate of 150 mg/min.



A total of 45 patients were enrolled: 16 in the PO group, 14 in the IVP group, and 15 in the IVF group. The times required to reach therapeutic drug concentrations were (mean +/- standard deviation [SD]) 5.62 +/- 0.28 hours, 0.24 +/- 0.3 hours, and 0.21 +/- 0.28 hours, respectively. A total of 17, 27, and 32 adverse drug events were observed in the PO, IVP, and IVF groups, respectively, with significantly fewer events in the PO group (p = 0.02, p = 0.01). No significant difference was found between the numbers of necessary adjustments to the infusions in the two IV groups. The average time to safe emergency department discharge was significantly shorter for the IV groups compared with the PO group (p < 0.001).



Oral loading has fewer adverse drug events than either IV loading method, but its use may be limited when therapeutic concentrations are required quickly. Although IVF loading is faster, from an adverse-drug event perspective, no advantage of IVF over IVP was apparent.
Proximal Gastrectomy Reconstructed by Jejunal Pouch Interposition for Upper Third Gastric Cancer: Prospective Randomized Study

Proximal gastrectomy with jejunal pouch interposition (PGJP) has been advocated as an alternative operation for upper third gastric cancer. However, there has been no prospective randomized trial comparing PGJP with total gastrectomy with Roux-en-Y esophagojejunostomy (TGRY). The aim of this study was to compare the short- and medium-term results of PGJP and TGRY in a randomized clinical trial. Fifty-one patients with upper third gastric cancer were randomized to either PGJP (n = 25) or TGRY (n = 26). Outcome measures were postoperative complications, nutritional status assessed by serum nutritional parameters, and postgastrectomy symptoms. There were no significant differences in operating time, hospital stay, and postoperative complications. Blood loss was significantly less in the PGJP group (P = 0.036). Nineteen patients (73%) in the TGRY group had one or more postgastrectomy symptoms, which was significantly more frequent than in the PGJP group (32%; P = 0.012). There were also significant differences between the two groups with regard to food intake, weight recovery, hemoglobin, and serum vitamin B12 levels in favor of PGJP. In conclusion, proximal gastrectomy with jejunal pouch interposition for upper third gastric cancer is safe, and is associated with a greater reduction in postgastrectomy symptoms and better nutritional status compared with conventional total gastrectomy.
Advantages and pitfalls of 18F-fluoro-2-deoxy-D-glucose positron emission tomography in detecting locally residual or recurrent nasopharyngeal carcinoma: comparison with magnetic resonance imaging

This prospective study was designed to elucidate the advantages and pitfalls of 18F-FDG PET in detecting locally residual/recurrent nasopharyngeal carcinoma (NPC) in comparison with MRI. We recruited NPC patients from two ongoing prospective trials. One is being performed to evaluate suspected local recurrence (group A) and the other to assess local treatment response 3 months after therapy (group B). Both groups received 18F-FDG PET and head and neck MRI. The gold standard was histopathology or clinical/imaging follow-up. An optimal cut-off standardised uptake value (SUV) was retrospectively determined. From January 2002 to August 2004, 146 patients were eligible. Thirty-four were from group A and 112 from group B. In all, 26 had locally recurrent/residual tumours. Differences in detection rate between 18F-FDG PET and MRI were not statistically significant in either group. However, 18F-FDG PET showed significantly higher specificity than MRI in detecting residual tumours among patients with initial T4 disease (p=0.04). In contrast, the specificity of 18F-FDG PET for patients with an initial T1–2 tumour treated with intracavitary brachytherapy (ICBT) was significantly lower than that for patients not treated by ICBT (72.2% vs 98.1%, p=0.003). At an SUV cut-off of 4.2, PET showed an equal and a higher accuracy compared with MRI in groups A and B, respectively. 18F-FDG PET is superior to MRI in identifying locally residual NPC among patients with initial T4 disease but demonstrates limitations in assessing treatment response in patients with initial T1–2 disease after ICBT. A cut-off SUV is a useful index for aiding in the visual detection of locally residual/recurrent NPC.
Cortical excitability and sleep deprivation: a transcranial magnetic stimulation study.

The objective was to assess the changes in cortical excitability after sleep deprivation in normal subjects. Sleep deprivation activates EEG epileptiform activity in an unknown way. Transcranial magnetic stimulation (TMS) can inform on the excitability of the primary motor cortex. Eight healthy subjects (four men and four women) were studied. Transcranial magnetic stimulation (single and paired) was performed by a focal coil over the primary motor cortex, at the "hot spot" for the right first dorsal interosseous muscle. The following motor evoked potential features were measured: (a) active and resting threshold to stimulation; (b) duration of the silent period; (c) amount of intracortical inhibition on paired TMS at the interstimulus intervals of 2 and 3 ms and amount of facilitation at interstimulus intervals of 14 and 16 ms. The whole TMS session was repeated after a sleep deprivation of at least 24 hours. After the sleep deprivation, the threshold to stimulation (in the active and resting muscle), as well as the silent period, did not change significantly. By contrast, the paired stimulus study showed a significant (p<0.05) reduction in both intracortical inhibition and facilitation. Thus, TMS showed that sleep deprivation is associated with changes in inhibition-facilitation balance in the primary motor cortex of normal subjects. These changes might have a link with the background factors of the "activating" effects of sleep deprivation.
A comparison of home measurement and ambulatory monitoring of blood pressure in the adjustment of antihypertensive treatment.

The purpose of this study was to compare home and ambulatory blood pressure (BP) in the adjustment of antihypertensive treatment.



After a 4-week washout period, patients whose untreated daytime diastolic ambulatory BP averaged > or = 85 mm Hg were randomized to be treated according to their ambulatory or home BP. Antihypertensive treatment was adjusted at 6-week intervals according to the mean daytime ambulatory diastolic BP or the mean home diastolic BP, depending on the patient's randomization group. If the diastolic BP stayed above 80 mm Hg, the physician blinded to randomization intensified hypertensive treatment.



Ninety-eight patients completed the study. During the 24-week follow-up period both systolic and diastolic BP decreased significantly within both groups (P < .001). At the end of the study, the systolic/diastolic differences between ambulatory (n = 46) and home (n = 52) BP groups in home, daytime ambulatory, night-time ambulatory, and 24-h ambulatory BP changes averaged 2.6/2.6 mm Hg, 0.6/1.7 mm Hg, 1.0/1.4 mm Hg, and 0.6/1.5 mm Hg, respectively (P range .06 to .75) A nonsignificant trend to more intensive drug therapy in the ambulatory BP group and a nonsignificant trend to larger share of patients reaching (57.7% v 43.5%, P = .16) the target pressure in the home BP group was observed due to the 3.8 mm Hg difference in ambulatory and home diastolic BP at randomization.



The adjustment of antihypertensive treatment based on either ambulatory or home BP measurement led to good BP control. No significant between-group differences in BP changes were seen at the end of the study. Additional research is needed to provide more conclusive results.
The growing gap in hypertension control between insured and uninsured adults: National Health and Nutrition Examination Survey 1988 to 2010.

Hypertension awareness, treatment, and control are lower among uninsured than insured adults. Time trends in differences and underlying modifiable factors are important for informing strategies to improve health equity. National Health and Nutrition Examination Surveys 1988 to 1994, 1999 to 2004, and 2005 to 2010 data in adults aged 18 to 64 years were analyzed to explore this opportunity. The proportion of adults with hypertension who were uninsured increased from 12.3% in 1988 to 1994 to 17.4% in 2005 to 2010. In 1988 to 1994, hypertension awareness, treatment, and control to <140/<90 mm Hg (30.1% versus 26.5%; P=0.27) were similar in insured and uninsured adults. By 2005 to 2010, the absolute gap in hypertension control between uninsured and insured adults of 21.9% (52.5% versus 30.6%; P<0.001) was explained approximately equally by lower awareness (65.2% versus 80.7%), fewer aware adults treated (75.2% versus 88.5%), and fewer treated adults controlled (63.1% versus 73.5%; all P<0.001). Publicly insured and uninsured adults had similar income. Yet, hypertension control was similar across time periods in publicly and privately insured adults, despite lower income and education in the former. In multivariable analysis, hypertension control in 2005 to 2010 was associated with visit frequency (odds ratio, 3.4 [95% confidence interval, 2.4-4.8]), statin therapy (1.8 [1.4-2.3]), and healthcare insurance (1.6 [1.2-2.2]) but not poverty index (1.04 [0.96-1.12]). Public or private insurance linked to more frequent healthcare, greater awareness and effective treatment of hypertension, and appropriate statin use could reverse a long-term trend of growing inequity in hypertension control between insured and uninsured adults.
Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis

This review discusses hemoglobin D-Punjab, also known as hemoglobin D-Los Angeles, one of the most common hemoglobin variants worldwide. It is derived from a point mutation in the beta-globin gene (HBB: c.364G>C; rs33946267) prevalent in the Punjab region, Northwestern Indian. Hemoglobin D-Punjab can be inherited in heterozygosis with hemoglobin A causing no clinical or hematological alterations, or in homozygosis, the rarest form of inheritance, a condition that is commonly not related to clinical symptomatology. Moreover, this variant can exist in association with other hemoglobinopathies, such as thalassemias; the most noticeable clinical alterations occur when hemoglobin D-Punjab is associated to hemoglobin S. The clinical manifestations of this association can be similar to homozygosis for hemoglobin S. Although hemoglobin D-Punjab is a common variant globally with clinical importance especially in cases of double heterozygosis, hemoglobin S/D-Punjab is still understudied. In Brazil, for example, hemoglobin D-Punjab is the third most common hemoglobin variant. Thus, this paper summarizes information about the origin, geographic distribution, characterization and occurrence of hemoglobin D-Punjab haplotypes to try to improve our knowledge of this variant. Moreover, a list of the main techniques used in its identification is provided emphasizing the importance of complementary molecular analysis for accurate diagnosis.
Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD) – a controlled multicenter study of a non-pharmacological treatment approach

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and has often a chronic course persisting into adulthood. However, up to 30% of children treated with stimulants either fail to show an improvement or suffer adverse side effects, including decreased appetite, insomnia and irritability and there is no evidence of long term efficacy of stimulants for ADHD. A series of studies has shown that neurofeedback is an effective additional or alternative treatment for children with ADHD, leading to e.g. significant and stable improvement in behavior, attention and IQ. Significant treatment effects of neurofeedback have also been verified in meta-analyses. Most of the trials, however, have been criticized for methodological difficulties, particularly lacking appropriate control conditions and number of patients included. This randomized study examines the efficacy of slow cortical potentials (SCP) -neurofeedback, controlling unspecific effects of the setting by comparing two active treatment modalities.



A total of 144 patients with ADHD, older than six and younger than ten years, in some cases with additional pharmacological treatment, are included in this trial. In five trial centres patients are treated either with SCP-feedback or electromyographic (EMG) -feedback in 25 sessions within 3 months. A comprehensive test battery is conducted before and after treatment and at follow-up 6 month later, to assess core symptoms of ADHD, general psychopathology, attentional performance, comorbid symptoms, intelligence, quality of life and cortical arousal.



The efficacy of SCP-feedback training for children with ADHD is evaluated in this randomized controlled study. In addition to behavior ratings and psychometric tests neurophysiological parameters serve as dependent variables. Further, the choice of EMG-biofeedback as an active control condition is debated.
Medicine-taking experiences and associated factors: comparison between Arabic-speaking and Caucasian English-speaking patients with Type 2 diabetes.

The aim of this study was to explore and compare medication-taking experiences and associated issues in Arabic-speaking and Caucasian English-speaking patients with Type 2 diabetes in Australia.



Various healthcare settings in metropolitan Melbourne, Australia, were purposefully selected to obtain a diverse group of participants with Type 2 diabetes. Recruitment occurred at diabetes outpatient clinics in two tertiary referral hospitals, six primary care practices and ten community centres. Face-to-face semi-structured individual interviews and group interviews were employed. All interviews were audiotaped, transcribed and coded thematically. Data collection continued until saturation was reached.



In total, 100 participants were recruited into two groups: 60 were Arabic-speaking and 40 were Caucasian English-speaking. Both groups had similar demographic and clinical characteristics. Only 5% of the Arabic-speaking participants had well-controlled diabetes compared with 17.5% of the participants in the English-speaking group. Arabic-speaking participants actively changed medication regimens on their own without informing their healthcare professionals. Arabic-speaking patients had more knowledge gaps about their prescribed treatments, compared with the English-speaking group. Their use of diabetes medicines was heavily influenced by peers with diabetes and family members; conversely, they feared revealing their diagnosis within the wider Arabic community due to stigma and collective negative social labelling of diabetes. Confidence in non-Arabic-speaking healthcare providers was lacking.



Findings yielded new insights into medication-taking practices and associated factors in Arabic-speaking patients with diabetes. It is vital that healthcare professionals working with Arabic-speaking patients adapt their treatment approaches to accommodate different beliefs and views about medicines.