nils-herrmann/clean_scirepeval huggingface dataset:
Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses.

The T790M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management.



As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA).



T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples, and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47% to 50% of patients using each of the genotyping assays, with concordance among them ranging from 57% to 74%. Although CTC- and ctDNA-based genotyping were each unsuccessful in 20% to 30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate.



Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient's cancer, which should be validated in predicting response to T790M-targeted inhibitors.
Initiate Insulin by Aggressive Titration and Education (INITIATE): a randomized study to compare initiation of insulin combination therapy in type 2 diabetic patients individually and in groups.

Insulin is often postponed for years because initiation is time-consuming. We sought to compare initiation of insulin individually and in groups with respect to change in A1C and several other parameters in type 2 diabetic patients.



A randomized (1:1), multicenter, two-arm, parallel design study with a recruiting period of up to 14 weeks and a 24-week treatment period. Either in groups of 4-8 or individually, using the same personnel and education program, 121 insulin-naive type 2 diabetic patients with an A1C of 7.0-12.0% were randomized to initiate bedtime insulin glargine. The patients visited the treatment center before and at the time of insulin initiation and at 6, 12, and 24 weeks. Patients self-adjusted the insulin dose to achieve a fasting plasma glucose 4.0-5.5 mmol/l.



At 24 weeks, mean +/- SE A1C had decreased from 8.7 +/- 0.2 to 6.9 +/- 0.1% in those treated individually and from 8.8 +/- 0.2 to 6.8 +/- 0.1% in those in groups (not significant [NS]). Insulin doses averaged 62 +/- 5 IU and 56 +/- 5 IU at 24 weeks (NS), respectively. The frequency of hypoglycemia was similar. The total time (visits and phone calls) spent in initiating insulin in the patients in groups (2.2 +/- 0.1 h) was 48% less than in those treated individually (4.2 +/- 0.2 h). Diabetes treatment satisfaction improved significantly in both sets of patients.



Similar glycemic control and treatment satisfaction can be achieved by initiating insulin in groups and individually. Starting insulin in groups takes one-half as much time as individual initiation.
Dopamine transporter imaging and the effects of deep brain stimulation in patients with Parkinson’s disease

Single-photon emission computed tomography (SPECT) with [123I]FP-CIT is a marker for loss of presynaptic dopamine transporters in the striatum in Parkinson’s disease (PD). We used [123I]FP-CIT SPECT in order to evaluate binding to the dopamine transporter before and after neurosurgical treatment with bilateral stimulation in the subthalamic nucleus (STN). Thirty-five patients with levodopa-responsive PD were examined with [123I]FP-CIT SPECT pre-operatively (baseline scan: mean 3 months before surgery), and 3 and 12 months after surgery. Pre-operatively, all patients already had substantial signs of severe nigrostriatal neuronal loss as determined from the [123I]FP-CIT SPECT scans. One year after surgery the specific [123I]FP-CIT binding to the striatum was significantly reduced by 10.3% compared with the pre-operative baseline scan. The mean time span from the baseline scan before surgery to the follow-up scan 1 year after surgery was 16.2 months. Hence, the rate of reduction equals a mean annual reduction of 7.7%. A comparable control group of patients with PD who did not undergo surgery was also examined longitudinally. In this group the specific binding of [123I]FP-CIT was reduced by 6.7% per year. The specific binding of [123I]FP-CIT was reduced equally in the STN-stimulated patients and a group of non-operated PD patients with advanced disease. Our study does not support the notion that electrode implantation and STN stimulation exert a neuroprotective effect by themselves.
Application of intraoperative indocyanine green videoangiography to brain tumor surgery

Videoangiography using indocyanine green (ICG) has been used in the ophthalmologic field for a long time. It was introduced to the neurosurgical field several years ago but has been limited to vascular surgeries. We applied ICG videoangiography to brain tumor surgery and evaluated the usefulness. Twenty-three patients with a brain tumor who underwent microsurgical resection were analyzed. The pathological diagnosis was meningioma in 15 patients, metastasis in three, glioma in three, and hemangioblastoma in two. A microscope with a special filter and infrared excitation light to illuminate the operating field was used in this study. The intravascular fluorescence was imaged with a video camera attached to the microscope. ICG was injected intravenously with the dose of 5–25 mg, and overall, ICG was injected intraoperatively 32 times. ICG videoangiography allowed for an excellent evaluation of blood flow in the tumoral and peri-tumoral vessels both before and after the resection in all cases. ICG videoangiography is a useful method for monitoring blood flow in the exposed vessels during microsurgery for a brain tumor. This noninvasive method is simple, safe, cost-effective, and easily repeatable. Before resection, it provides information on the tumoral and peri-tumoral circulation including sequential visualization of vessels or direction of the blood flow. After resection, it checks the patency of the peri-tumoral vessels and is especially useful for the vein. This ICG videoangiography can be an alternative tool to intraoperative angiography or Doppler ultrasonography in selective cases.
A comparison of unsedated colonoscopy and flexible sigmoidoscopy in the family medicine setting: an LA Net study.

Colonoscopy visualizes more of the colon than flexible sigmoidoscopy. This study compares the outcomes of an unsedated modified colon endoscopy (MCE) with flexible sigmoidoscopy (FS) in family medicine practice.



We conducted a retrospective chart review of existing clinical data to compare outcomes for 48 patients undergoing MCE and 35 patients undergoing FS at 3 family medicine practices in Los Angeles. Outcomes of interest included completion rates, number of complications, depth reached, anatomic site visualized, and information about the number and nature of clinical findings.



No significant differences were found between MCE and FS regarding completion rates (83.3% vs 75%, respectively). Expected statistically significant differences were found between the 2 procedures in the anatomic site visualized (P<.01) and depth reached (P<.01). Clinical pathologies were identified in 58% of MCE patients and 37% of FS patients. Four adenocarcinomas were identified in the MCE group in the proximal region of the colon that could not have been detected by FS.



Findings from this study suggest that MCE can be an acceptable alternative to FS in office settings for colorectal cancer screening.
Adaptive Scheduling under Memory Pressure on Multiprogrammed SMPs

We present a simple scheduling strategy that copes with the adverse effects of paging on multiprogrammed SMPs. We consider open, multiuser SMP servers, typically found in academic or industrial environments. Our strategy incorporates four uniquely combined features. It is adaptive, in the sense that the programs themselves take scheduling actions upon detecting memory pressure; it is dynamic, since programs detect the likelihood of paging at runtime by communicating with the operating system through a lightweight interface; it is preventive, because it takes scheduling actions before paging occurs; and it is non-intrusive, because the local scheduling actions taken by a program do not affect adversely, but act to the benefit of other programs sharing the system. We present an efficient implementation of our strategy in Linux and show with a realistic production workload that it can improve the response time of the Linux kernel under memory pressure by up to a factor of eight and the throughput by up to a factor of four.
Adverse parenting as a risk factor in the occurrence of anxiety disorders

The aim of the study was to test the homogeneity of the association between adverse parenting and anxiety disorders within these disorders as well as among six European countries. Based on data from 8,232 respondents (part II sample) originating from the European study of the epidemiology of mental disorders (ESEMeD), we examined the association between three dimensions of parental rearing (care, overprotection, authoritarianism) measured by a short form of the parental bonding instrument (PBI) and anxiety disorders by computing one logistic regression model per disorder. A similar pattern of recalled parenting behaviour across the four anxiety disorders assessed was found, with care and overprotection having the strongest associations. There were only minor country-specific variations of this pattern. Our results suggest an association between adverse parenting and the risk of anxiety disorders in particular as well as psychiatric disorders in general that is rather non-disorder specific.
Practice-linked online personal health records for type 2 diabetes mellitus: a randomized controlled trial.

Web-based personal health records (PHRs) have been advocated as a means to improve type 2 diabetes mellitus (DM) care. However, few Web-based systems are linked directly to the electronic medical record (EMR) used by physicians.



We randomized 11 primary care practices. Intervention practices received access to a DM-specific PHR that imported clinical and medications data, provided patient-tailored decision support, and enabled the patient to author a "Diabetes Care Plan" for electronic submission to their physician prior to upcoming appointments. Active control practices received a PHR to update and submit family history and health maintenance information. All patients attending these practices were encouraged to sign up for online access.



We enrolled 244 patients with DM (37% of the eligible population with registered online access, 4% of the overall population of patients with DM). Study participants were younger (mean age, 56.1 years vs 60.3 years; P < .001) and lived in higher-income neighborhoods (median income, $53,784 vs $49,713; P < .001) but had similar baseline glycemic control compared with nonparticipants. More patients in the intervention arm had their DM treatment regimens adjusted (53% vs 15%; P < .001) compared with active controls. However, there were no significant differences in risk factor control between study arms after 1 year (P = .53).



Previsit use of online PHR linked to the EMR increased rates of DM-related medication adjustment. Low rates of online patient account registration and good baseline control among participants limited the intervention's impact on overall risk factor control.
Predicting Mortality in Non-Variceal Upper Gastrointestinal Bleeders: Validation of the Italian PNED Score and Prospective Comparison With the Rockall Score

We sought (i) to validate a new prediction rule of mortality (Progetto Nazionale Emorragia Digestiva (PNED) score) on an independent population with non-variceal upper gastrointestinal bleeding (UGIB) and (ii) to compare the accuracy of the Italian PNED score vs. the Rockall score in predicting the risk of death.We conducted prospective validation of analysis of consecutive patients with UGIB at 21 hospitals from 2007 to 2008. Outcome measure was 30-day mortality. All the variables used to calculate the Rockall score as well as those identified in the Italian predictive model were considered. Calibration of the model was tested using the χ2 goodness-of-fit and performance characteristics with receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of the two predictive models.Over a 16-month period, data on 1,360 patients were entered in a national database and analyzed. Peptic ulcer bleeding was recorded in 60.7% of cases. One or more comorbidities were present in 66% of patients. Endoscopic treatment was delivered in all high-risk patients followed by high-dose intravenous proton pump inhibitor in 95% of them. Sixty-six patients died (mortality 4.85%; 3.54–5.75). The PNED score showed a high discriminant capability and was significantly superior to the Rockall score in predicting the risk of death (AUC 0.81 (0.72–0.90) vs. 0.66 (0.60–0.72), P<0.000). Positive likelihood ratio for mortality in patients with a PNED risk score >8 was 16.05.CONCLUSIONS:The Italian 10-point score for the prediction of death was successfully validated in this independent population of patients with non-variceal gastrointestinal bleeding. The PNED score is accurate and superior to the Rockall score. Further external validation at the international level is needed.
Group education on asthma for children and caregivers: a randomized, controlled trial addressing effects on morbidity and quality of life.

To establish the efficacy in terms of morbidity and quality of life of a group education program on asthma aimed at children and caregivers.



An open, randomized, controlled trial was undertaken in 13 primary health care centers in Spain, Cuba, and Uruguay and involved 245 children with active asthma aged 9 to 13 years and their caregivers. The intervention consisted of 3 educational sessions lasting 45 to 60 minutes each and was performed with 3 intervention groups: children alone, caregivers alone, and both children and caregivers. The outcome measures were difference between intervention and control groups in the rate of asthma attacks and hospital admission, as well as the quality of life of children and caregivers in the 6 months following the intervention.



The rate of asthma attacks per patient-year decreased when the intervention was given only to children (mean difference, -1.61; 95% confidence interval [CI], -2.87 to -0.34) or to both children and caregivers (-1.60; 95% CI, -2.88 to -0.31). Hospital admissions per patient-year decreased in the intervention groups children alone (-0.28; 95% CI, -0.51 to -0.05) and both children and caregivers (-0.25; 95% CI, -0.49 to -0.02). Education provided to caregivers alone was not associated with any changes in morbidity. No differences were observed in terms of quality of life between controls and any of the intervention groups.



Group education on asthma reduces morbidity but does not improve quality of life. The benefits are apparent when education is aimed at children but no additional benefit is obtained if the intervention is also aimed at their caregivers. Finally, group education for adult caregivers alone is not effective.
Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy.

This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy. MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4 cm. In conclusion, the data show that radiotherapy has a potent clastogenic effect in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm.
Placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes: The effect of vitamin C and E supplementation.

In view of the increased rates of pre-eclampsia observed in diabetic pregnancy and the lack of ex vivo data on placental biomarkers of oxidative stress in T1 diabetic pregnancy, the aim of the current investigation was to examine placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes. A further objective of the study was to investigate the putative impact of vitamin C and E supplementation on antioxidant enzyme activity and lipid peroxidation in type 1 diabetic placentae.



The current study measured levels of antioxidant enzyme [glutathione peroxidase (Gpx), glutathione reductase (Gred), superoxide dismutase (SOD) and catalase] activity and degree of lipid peroxidation (aqueous phase hydroperoxides and 8-iso-prostaglandin F2α) in matched central and peripheral samples from placentae of DAPIT (n=57) participants. Levels of vitamin C and E were assessed in placentae and cord blood.



Peripheral placentae demonstrated significant increases in Gpx and Gred activities in pre-eclamptic in comparison to non-pre-eclamptic women. Vitamin C and E supplementation had no significant effect on cord blood or placental levels of these vitamins, nor on placental antioxidant enzyme activity or degree of lipid peroxidation in comparison to placebo-supplementation.



The finding that maternal supplementation with vitamin C/E does not augment cord or placental levels of these vitamins is likely to explain the lack of effect of such supplementation on placental indices including antioxidant enzymes or markers of lipid peroxidation.
The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients

Oral tacrolimus therapy is effective for refractory ulcerative colitis (UC), but dose adjustment according to the trough concentrations which varies largely among individuals, is required. This study aimed to identify factors to predict the tacrolimus dose required for achieving the target trough level for remission induction of UC.



Forty-seven consecutive UC patients who were treated with tacrolimus were retrospectively analyzed. Tacrolimus doses were adjusted every 2 or 3 days to achieve trough concentrations of 10-15 ng/mL. The dose required for reaching the target trough level was analyzed based on disease characteristics, course of trough concentrations, and gene polymorphism related to tacrolimus metabolism.



Median daily dose of tacrolimus required for achieving the target trough level was 0.19 (0.07-0.42) mg/kg, and patients were divided into high or low dose group (< 0.2 mg/kg or > 0.2 mg/kg). The value of initial trough concentration/starting dose was higher in the low dose group than in the high dose group (1.35 ng/mL/mg vs. 0.78 ng/mL/mg, p < 0.0001). Although presence of CYP3A5 *1 was more frequently observed in the high dose group, initial trough concentration was the only significant factor for determining requirement of high dose of tacrolimus (OR = 28.0, 95% confidence interval 3.20 - 631).



The most practical predictor of the dose required for achieving the target trough concentration was the trough concentration measured 2 or 3 days after starting tacrolimus therapy. Our findings would make tarcolimus administration for UC safer, easier and more effective.
Aerobic and Combined Exercise Sessions Reduce Glucose Variability in Type 2 Diabetes: Crossover Randomized Trial

To evaluate the effects of aerobic (AER) or aerobic plus resistance exercise (COMB) sessions on glucose levels and glucose variability in patients with type 2 diabetes. Additionally, we assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS).



Fourteen patients with type 2 diabetes (56±2 years) wore a CGMS during 3 days. Participants randomly performed AER and COMB sessions, both in the morning (24 h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods).



Baseline fasting glycemia was 139±05 mg/dL and HbA1c 7.9±0.7%. Glucose levels decreased immediately after AER and COMB protocols by ∼16%, which was sustained for approximately 3 hours. Comparing the two exercise modalities, responses over a 24-h period after the sessions were similar for glucose levels, glucose variance and glucose coefficient of variation. In the symbolic analysis, increases in 0 V pattern (COMB, 67.0±7.1 vs. 76.0±6.3, P = 0.003) and decreases in 1 V pattern (COMB, 29.1±5.3 vs. 21.5±5.1, P = 0.004) were observed only after the COMB session.



Both AER and COMB exercise modalities reduce glucose levels similarly for a short period of time. The use of non-conventional analysis indicates reduction of glucose variability after a single session of combined exercises.
Is painless synovitis different from painful synovitis? A controlled, ultrasound, radiographic, clinical trial

This study compares the clinical, ultrasonography, radiography, and laboratory outcomes of painless and painful chronic synovitis in patients with established rheumatoid arthritis.



This cross-sectional study involved 60 patients with rheumatoid arthritis and synovitis in the metacarpophalangeal joints; 30 of the patients did not experience pain, and 30 had experienced pain for at least 6 months prior to the study. The radiocarpal, distal radioulnar, and metacarpophalangeal joints were evaluated using the ultrasound gray scale, power Doppler, and radiography. Past and present clinical and laboratory findings were also evaluated.



There were no statistically significant differences between the groups for most of the outcomes. The group with pain scored worse on the disease activity indices (e.g., DAS 28 and SDAI), function questionnaires (HAQ and Cochin), and pinch strength test. A logistic regression analysis revealed that the use of an immunobiological agent was associated with a 3-fold greater chance of belonging to the group that experienced pain. The painless group had worse erosion scores in the second and fifth metacarpophalangeal with odd ratios (ORs) of 6.5 and 3.5, respectively. The painless group had more cartilage with grade 4 damage in the third metacarpophalangeal.



The rheumatoid arthritis patients with both painless and painful synovitis exhibited similar disease histories and radiographic and ultrasound findings. However, the ultrasonography evaluation revealed worse scores in the second and fifth metacarpophalangeal of the synovitis patients who did not experience pain.