nils-herrmann/clean_scirepeval huggingface dataset:
Cervical Acid Phosphatase: A Biomarker of Cervical Dysplasia and a Potential Surrogate Endpoint for Colposcopy

In 2000, cervical acid phosphatase (CAP) has been recently described as a biomarker labeling abnormal squamous cells on Pap smears (USPTO #6,143,512). The enzyme activity is presented as a red, granular deposit on a modified Papanicolaou background. This unique property was utilized for development of MarkPap technology intended for cervical cancer screening.



We conduct a multicenter, random assignment, assessor blinded, 2-group (test and control), split-sample designed clinical trial on 1,500 subject/specimens to assess safety and efficacy of the new test, in comparison with the control, for cervical cancer screening in standard Pap test environment. Safety is measured with frequency, severity and relation of adverse events. Efficacy is measured with primary endpoints (portion of positive/abnormal specimens detected, and the false negative rate). At the end of the follow-up period (two years) when the study will be completed, other efficacy endpoints such as accuracy (sensitivity/specificity) and predictive values will be added to the method evaluation. Here we present in interim analysis.



In April 2003, the recruitment was completed and the first twelve hundred cases have been evaluated. There was no serious or related adverse event in both groups. Minor, unrelated adverse events were rare and insignificantly distributed in both groups.  Portion of positive/abnormal specimens detected: Pe (new test) = 0.166, Ps (Pap control): 0.082; Ps' (ACS reported value for US in year 2000): 0.07. Pe >/= Ps + delta, for delta = 0.5Ps. B. False negative rate: Pe = 0.05, Ps' = 0.10. Confidence intervals: 95% CI: Test [0.148-0.193], Pap control [0.068-0.098]. OR = 2.26. chi2 = 40.69101 is greater than the critical value of 3.841 (P < 0.01).



We concluded that CAP had added to visibility of Pap test and has enabled cytoscreeners to significantly improve the detection of positive/abnormal specimens and reduce false negative rate. We discuss this unique property of CAP with emphasis on using it as a surrogate endpoint for colposcopy and eventual removal of a cervical lesion that, if untreated, could progress into cancer.
Improving Dietary Habits in Disadvantaged Women With HIV/AIDS: The SMART/EST Women's Project

There is a lack of information on whether brief nutrition education can succeed in improving longer-term dietary patterns in disadvantaged populations with HIV/AIDS. In the SMART/EST II Women's Project 466 disadvantaged women with HIV/AIDS were randomized to one of four groups and received a two-phase training consisting of a coping skills/stress management and nutrition education provided either in a group or individually. At baseline the majority of participants had excessive fat and sugar consumption and suboptimal intakes of vegetables, fruits, calcium-rich foods and whole grains. Dietary patterns for all participants improved after the nutrition intervention primarily due to decreases in high fat and high sugar foods such as soda and fried foods and were still significantly better 18 months later. There were only short-term differences in improvements between the four groups. These findings support the value of even brief nutrition education for disadvantaged women living with HIV/AIDS.
Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.

Tenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue reverse transcriptase inhibitor.



To evaluate the efficacy and safety of tenofovir DF compared with stavudine in antiretroviral-naive patients.



A prospective, randomized, double-blind study conducted at 81 centers in the United States, South America, and Europe from June 9, 2000, to January 30, 2004. A total of 753 patients infected with HIV who were antiretroviral naive were screened and 602 patients entered the study.



Patients were randomized to receive either tenofovir DF (n = 299) or stavudine (n = 303), with placebo, in combination with lamivudine and efavirenz.



Proportion of patients with HIV RNA levels of less than 400 copies/mL at week 48.



In the primary intent-to-treat analysis in which patients with missing data or who added or switched antiretroviral medications before week 48 were considered as failures, the proportion of patients with HIV RNA of less than 400 copies/mL at week 48 was 239 (80%) of 299 in patients receiving tenofovir DF and 253 (84%) of 301 in patients receiving stavudine (95% confidence interval, -10.4% to 1.5%), exceeding the predefined -10% limit for equivalence. However, equivalence was demonstrated in the secondary analyses (HIV RNA <50 copies/mL) at week 48 and through 144 weeks. Virologic failure was associated most frequently with efavirenz and lamivudine resistance. Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups, respectively (P =.06). A more favorable mean change from baseline in fasting lipid profile was noted in the tenofovir DF group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n = 170] vs +134 mg/dL for stavudine [n = 162], P<.001), total cholesterol (+30 mg/dL [n = 170] vs +58 mg/dL [n = 162], P<.001), direct low-density lipoprotein cholesterol (+14 mg/dL [n = 169] vs +26 mg/dL [n = 161], P<.001), and high-density lipoprotein cholesterol (+9 mg/dL [n = 168] vs +6 mg/dL [n = 154], P =.003). Investigator-reported lipodystrophy was less common in the tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58 [19%] of 301, P<.001). The number of bone fractures and the renal safety profile were similar between the 2 groups.



Through 144 weeks, the combination of tenofovir DF, lamivudine, and efavirenz was highly effective and comparable with stavudine, lamivudine, and efavirenz in antiretroviral-naive patients. However, tenofovir DF appeared to be associated with better lipid profiles and less lipodystrophy.
Dihydrofolate-Reductase Mutations in Plasmodium knowlesi Appear Unrelated to Selective Drug Pressure from Putative Human-To-Human Transmission in Sabah, Malaysia

Malaria caused by zoonotic Plasmodium knowlesi is an emerging threat in Eastern Malaysia. Despite demonstrated vector competency, it is unknown whether human-to-human (H-H) transmission is occurring naturally. We sought evidence of drug selection pressure from the antimalarial sulfadoxine-pyrimethamine (SP) as a potential marker of H-H transmission.



The P. knowlesi dihdyrofolate-reductase (pkdhfr) gene was sequenced from 449 P. knowlesi malaria cases from Sabah (Malaysian Borneo) and genotypes evaluated for association with clinical and epidemiological factors. Homology modelling using the pvdhfr template was used to assess the effect of pkdhfr mutations on the pyrimethamine binding pocket.



Fourteen non-synonymous mutations were detected, with the most common being at codon T91P (10.2%) and R34L (10.0%), resulting in 21 different genotypes, including the wild-type, 14 single mutants, and six double mutants. One third of the P. knowlesi infections were with pkdhfr mutants; 145 (32%) patients had single mutants and 14 (3%) had double-mutants. In contrast, among the 47 P. falciparum isolates sequenced, three pfdhfr genotypes were found, with the double mutant 108N+59R being fixed and the triple mutants 108N+59R+51I and 108N+59R+164L occurring with frequencies of 4% and 8%, respectively. Two non-random spatio-temporal clusters were identified with pkdhfr genotypes. There was no association between pkdhfr mutations and hyperparasitaemia or malaria severity, both hypothesized to be indicators of H-H transmission. The orthologous loci associated with resistance in P. falciparum were not mutated in pkdhfr. Subsequent homology modelling of pkdhfr revealed gene loci 13, 53, 120, and 173 as being critical for pyrimethamine binding, however, there were no mutations at these sites among the 449 P. knowlesi isolates.



Although moderate diversity was observed in pkdhfr in Sabah, there was no evidence this reflected selective antifolate drug pressure in humans.
Erratum to: Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study

Pasireotide has a broader somatostatin receptor binding profile than other somatostatin analogues. A 16-week, Phase II trial showed that pasireotide may be an effective treatment for acromegaly. An extension to this trial assessed the long-term efficacy and safety of pasireotide. This study was an open-label, single-arm, open-ended extension study (primary efficacy and safety evaluated at month 6). Patients could enter the extension if they achieved biochemical control (GH B 2.5 lg/L and normal IGF-1) or showed clinically relevant improvements during the core study. Thirty of the 60 patients who received pasireotide (200–900 lg bid) in the core study entered the extension. At extension month 6, of the 26 evaluable patients, six were biochemically controlled, of whom five had achieved control during the core study. Normal IGF-1 was achieved by 13/26 patients and GH B 2.5 lg/L by 12/26 at month 6. Nine patients received pasireotide for C24 months in the extension; three who were biochemically controlled at month 24 had achieved control during the core study. Of 29 patients with MRI data, nine had significant (C20 %) tumor volume reduction during the core study; an additional eight had significant reduction during the extension. The most common adverse events were transient gastrointestinal disturbances;  Electronic supplementary material The online version of this article (doi:10.1007/s11102-013-0478-0) contains supplementary material, which is available to authorized users. S. Petersenn (&) ENDOC Center for Endocrine Tumors, Altonaer Str. 59, 20357 Hamburg, Germany e-mail: stephan.petersenn@endoc-med.de A. J. Farrall Brain Research Imaging Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK C. Block Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium S. Melmed Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA J. Schopohl Medizinische Klinik und Poliklinik IV, Campus Innenstadt, University of Munich, Munich, Germany P. Caron Service d’Endocrinologie, Maladies Métaboliques et Nutrition, Centre Hospitalier Universitaire Larrey, Toulouse, France R. Cuneo Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia D. Kleinberg Neuroendocrine Unit, New York University School of Medicine, New York, NY, USA A. Colao Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Naples, Italy M. Ruffin G. Hughes Novartis Pharma AG, Basel, Switzerland K. Hermosillo Reséndiz K. Hu Novartis Pharmaceuticals, East Hanover, NJ, USA A. Barkan Pituitary and Neuroendocrine Center, University of Michigan, Ann Arbor, MI, USA 123 Pituitary (2014) 17:132–140 DOI 10.1007/s11102-013-0478-0
Prostate cancer detected by methylated gene markers in histopathologically cancer-negative tissues from men with subsequent positive biopsies.

The goal of this retrospective, multicenter study was to evaluate the ability of a newly developed refinement of a quantitative methylation-specific PCR assay to detect prostate cancer in histopathologically negative biopsy samples collected from men who were later positively diagnosed during a follow-up biopsy procedure. Biomarkers tested in the assay included the much-studied glutathione-S-transferase P1 gene and others reported to be frequently methylated in prostate cancer. Core biopsy tissue from subjects with serial negative biopsies served as a negative control to assess assay specificity. As a positive control, biopsy core tissue from patients histopathologically diagnosed with prostate cancer was used to gauge true marker sensitivity in known cancer-containing specimens. Testing was completed in 971 archived paraffin-embedded tissue blocks from 264 men screened for prostate cancer. More samples were initially tested, but due to the advanced age of the paraffinized tissue, DNA quality for quantitative methylation-specific PCR analysis was insufficient in 34% of the available blocks. The glutathione-S-transferase P1 gene has been confirmed as a powerful indicator of the presence of prostate cancer cells. A sensitivity of 52% was observed in the "potentially false-negative first biopsies," with a corresponding specificity of 85% and the sensitivity in biopsy tissue cores containing histopathologically confirmed prostate cancer was 95%. An even higher sensitivity can be reached with RAR-2beta (84%) and APC (72%), with respective specificities of 48% and 50%. Gene methylation was detected in initial, negative biopsy tissue in men who were later diagnosed with prostate cancer. Testing for methylation in histopathologically negative biopsies could improve the early detection of prostate cancer.
Does artificial UV use prior to spring break protect students from sunburns during spring break?

Dark-skinned individuals are less likely than light-skinned individuals to become sunburned or develop skin cancer. Some have extrapolated this relationship and surmised that developing and maintaining a tan will reduce the risk of sunburns and melanoma. In order to examine whether this strategy indeed protects against sunburns, we surveyed college students about both their tanning habits prior to spring break and their spring break activities.



Sorority and fraternity students were recruited after spring break. Analyses examined associations between potential risk factors and the development of one or more sunburns during spring break.



As expected, the risk of obtaining a sunburn increased with: time spent in the sun during spring break; light complexion, as assessed by various sun-sensitivity factors; and lack of sunscreen use. We also found that tanning using an artificial UV source during the 10 weeks prior to spring break was not associated with reduced risk of sunburns during spring-break, but rather with a marginal increase in this risk.



These data provide evidence that maintaining a tan may not provide protection from sunburns. Public health messages need to address this misconception, stating clearly that a tan does not protect against or reduce the chances of developing a sunburn.
Signs and symptoms from nicotine gum abstinence

This study examined and compared withdrawal signs and symptoms from cessation of 0, 2 and 4 mg nicotine gum. In addition, a comparison was made between nicotine gum versus cigarette withdrawal symptoms. Smokers first underwent cigarette deprivation for 4 days and then were randomly assigned to 0 (N=16), 2 (N=25), and 4 (N=21) mg gum. They were asked to chew the gum for 1 month and then to undergo a 4-day nicotine gum deprivation period. The results showed a number of significant changes occurring after deprivation from 4 mg gum, one change from 2 mg gum, and no changes from 0 mg gum. There were no significant differences in severity of withdrawal among the various doses of nicotine gum. There were more severe symptoms of withdrawal from cigarette as opposed to 4 mg nicotine gum deprivation.
Evaluation of oxprenolol slow release and osmotic release by exercise testing and ambulatory electrocardiographic monitoring in patients with chronic stable angina pectoris

We have treated eleven patients with chronic stable angina pectoris with slow-release oxprenolol (160 mg and 320 mg) in a double-blind crossover study and evaluated its efficacy objectively by exercise testing between 180 and 240 min after dosing. The mean exercise time increased significantly from 6.2 min on placebo to 7.2 min and 7.3 min on oxprenolol 160 mg and 320 mg respectively. No overall beneficial effects could be demonstrated for the higher dose. A further 20 patients received slow release oxprenolol 160 mg and 10/170 mg “Oros” (osmotic release) oxprenolol in a double-blind crossover study using exercise testing and ambulatory electrocardiographic monitoring at 21–23 h after dosing. The mean exercise time increased significantly from 7.0 min on placebo to 8.3 min on slow-release oxprenolol and to 8.1 min on “Oros” oxprenolol. The effects of the 2 treatments on exercise and ambulatory heart rates were comparable. Two patients were withdrawn during the doubleblind treatment period while receiving oxprenolol slow-release, one because of unstable angina and another becaues of throbbing headache. These findings confirm that slow-release oxprenolol is effective in treating chronic stable angina pectoris at the 160-mg dose. “Oros” oxprenolol 10/170 mg has a profile of action closely similar to but without any additional benefit over slow-release oxprenolol 160 mg.
Effects of smoking on thermal pain threshold in deprived and minimally-deprived habitual smokers

This study examined the antinociceptive effects of smoking in nine habitual smokers under deprived (12 h) and minimally-deprived (<30 min) conditions. Pain threshold for thermal stimuli, heart rate, blood pressure and ratings of mood, arousal, dominance and well-being were assessed before and after smoking a cigarette. Overall, smoking affected all measured variables in the expected direction, leading to increased physiological activity, elevated pain threshold and improved mood. However, most of these effects depended on the deprivation status of the subjects, such that smoking after deprivation increased pain threshold whereas smoking after minimal deprivation did not. Pain threshold before smoking was the same for both groups. Deprived subjects had lower pre-smoke diastolic blood pressure, heart rate, and arousal levels, which rose to equal minimally-deprived subjects' scores after smoking.
Detection of Minimal Residual Disease in Acute Lymphoblastic Leukemia by In Vitro Amplification of Rearranged T-Cell Receptor Chain Sequences

Human T-cell receptor (TCR) b-chain diversity mainly originates from high junctional variability. since only a limited number of germline elements is available. This extraordinary diversity at the V.J junction, due to the use of two D elements and extensive incorporation of N nucleotides. constitutes a specific clonal marker for cell populations exhibiting rearranged TCR genes. To this end we amplifled in vitro by polymerase chain reaction (PCR) the TCR#{212} junctional region of five acute lymphoblastic leukemias (ALL). isolated respective DNA fragments. and used them directly as clonospecific probes. The combination of PCR technology and hybridization to clonospecific probes per-
Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes.

Islet transplantation can improve metabolic control for type 1 diabetes (T1D), an effect anticipated to improve insulin sensitivity. However, current immunosuppression regimens containing tacrolimus and sirolimus have been shown to induce insulin resistance in rodents.



The objective of the study was to evaluate the effect of islet transplantation on insulin sensitivity in T1D using euglycemic clamps with the isotopic dilution method to distinguish between effects at the liver and skeletal muscle.



Twelve T1D subjects underwent evaluation in the Clinical and Translational Research Center before and between 6 and 7 months after the transplant and were compared with normal control subjects.



The intervention included intrahepatic islet transplantation according to a Clinical Islet Transplantation Consortium protocol under low-dose tacrolimus and sirolimus immunosuppression.



Total body (M/Δinsulin), hepatic (1/endogenous glucose production ·basal insulin) and peripheral [(Rd - endogenous glucose production)/Δinsulin] insulin sensitivity assessed by hyperinsulinemic (1 mU·kg(-1)·min(-1)) euglycemic (∼90 mg/dL) clamps with 6,6-(2)H2-glucose tracer infusion were measured.



Glycosylated hemoglobin was reduced in the transplant recipients from 7.0% ± 0.3% to 5.6% ± 0.1% (P < .01). There were increases in total (0.11 ± 0.01 to 0.15 ± 0.02 dL/min·kg per microunit per milliliter), hepatic [2.3 ± 0.1 to 3.7 ± 0.4 × 10(2) ([milligrams per kilogram per minute](-1)·(microunits per milliliter)(-1))], and peripheral (0.08 ± 0.01 to 0.12 ± 0.02 dL/min·kg per microunit per milliliter) insulin sensitivity from before to after transplantation (P < .05 for all). All insulin sensitivity measures were less than normal in T1D before (P ≤ .05) and not different from normal after transplantation.



Islet transplantation results in improved insulin sensitivity mediated by effects at both the liver and skeletal muscle. Modern dosing of glucocorticoid-free immunosuppression with low-dose tacrolimus and sirolimus does not induce insulin resistance in this population.
A decision tree to assess short-term mortality after an emergency department visit for an exacerbation of COPD: a cohort study

Creating an easy-to-use instrument to identify predictors of short-term (30/60-day) mortality after an exacerbation of chronic obstructive pulmonary disease (eCOPD) could help clinicians choose specific measures of medical care to decrease mortality in these patients. The objective of this study was to develop and validate a classification and regression tree (CART) to predict short term mortality among patients evaluated in an emergency department (ED) for an eCOPD.



We conducted a prospective cohort study including participants from 16 hospitals in Spain. COPD patients with an exacerbation attending the emergency department (ED) of any of the hospitals between June 2008 and September 2010 were recruited. Patients were randomly divided into derivation (50%) and validation samples (50%). A CART based on a recursive partitioning algorithm was created in the derivation sample and applied to the validation sample.



Two thousand four hundred eighty-seven patients, 1252 patients in the derivation sample and 1235 in the validation sample, were enrolled in the study. Based on the results of the univariate analysis, five variables (baseline dyspnea, cardiac disease, the presence of paradoxical breathing or use of accessory inspiratory muscles, age, and Glasgow Coma Scale score) were used to build the CART. Mortality rates 30 days after discharge ranged from 0% to 55% in the five CART classes. The lowest mortality rate was for the branch composed of low baseline dyspnea and lack of cardiac disease. The highest mortality rate was in the branch with the highest baseline dyspnea level, use of accessory inspiratory muscles or paradoxical breathing upon ED arrival, and Glasgow score <15. The area under the receiver-operating curve (AUC) in the derivation sample was 0.835 (95% CI: 0.783, 0.888) and 0.794 (95% CI: 0.723, 0.865) in the validation sample. CART was improved to predict 60-days mortality risk by adding the Charlson Comorbidity Index, reaching an AUC in the derivation sample of 0.817 (95% CI: 0.776, 0.859) and 0.770 (95% CI: 0.716, 0.823) in the validation sample.



We identified several easy-to-determine variables that allow clinicians to classify eCOPD patients by short term mortality risk, which can provide useful information for establishing appropriate clinical care.