nils-herrmann/clean_scirepeval huggingface dataset:
Longitudinal screening algorithm that incorporates change over time in CA125 levels identifies ovarian cancer earlier than a single-threshold rule.

Longitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels.



We retrospectively evaluated serial preclinical serum CA125 values measured annually in 44 incident ovarian cancer cases identified from participants in the PLCO (Prostate Lung Colorectal and Ovarian) Cancer Screening Trial to determine how frequently and to what extent the parametric empirical Bayes (PEB) longitudinal screening algorithm identifies ovarian cancer earlier than an ST rule.



The PEB algorithm detected ovarian cancer earlier than an ST rule in a substantial proportion of cases. At 99% specificity, which corresponded to the ST-rule CA125 cutoff ≥ 35 U/mL that was used in the PLCO trial, 20% of cases were identified earlier by using the PEB algorithm. Among these cases, the PEB signaled abnormal CA125 values, on average, 10 months earlier and at a CA125 concentration 42% lower (20 U/mL) than the ST-rule cutoff. The proportion of cases detected earlier by the PEB algorithm and the earliness of detection increased as the specificity of the screening rule was reduced.



The PEB longitudinal algorithm identifies ovarian cancer earlier and at lower biomarker concentrations than an ST screening algorithm adjusted to the same specificity. Longitudinal biomarker assessment by using the PEB algorithm may have application for screening other solid tumors in which biomarkers are available.
Maximizing the Adequacy of Medication Treatment in Controlled Trials and Clinical Practice: STAR*D Measurement-Based Care

The success of well-developed protocols has been limited in real-world practice, where even effective strategies have not been sufficient to meet patient needs in routine clinical care owing to Axis I and III comorbidities. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial required that antidepressant medication treatment be optimal regarding dose and duration, yet accommodate flexibility to ensure safety given the wide range of comorbid general medical and psychiatric disorders allowed in the trial. The objective of this study was to develop a measurement-based care (MBC) approach and an automated feedback system to ensure adequate and safe antidepressant treatment delivery suitable for both clinical research and routine practice. Ratings of depressive symptom severity and side-effect frequency, intensity, and burden were obtained at each treatment visit using the MBC system that (1) guided medication dose adjustments and treatment duration, (2) documented clinician adherence to treatment recommendations, and (3) provided prompt feedback to clinicians to enhance appropriate treatment decisions. Physician adherence to protocol-specific treatment was monitored based on measured symptoms and side-effect burden, and dose and duration of antidepressant at each critical decision point during the acute phase treatment of major depression. Feedback was provided at the point of care by the clinical coordinators, assisted by Web-based reports following each treatment visit. On the basis of the first treatment step with citalopram, over 85% of treatment encounters had appropriate fidelity to recommendations. Most deviations from treatment recommendations occurred late in treatment and were often justifiable. MBC proved to be feasible and effective in busy primary and psychiatric settings. This approach signals a paradigm shift toward the use of measurement-based clinical decisions, both at the point of care and following each visit, to deliver optimal pharmacotherapy for depression.
Transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis: results from an intermediate risk propensity-matched population of the Italian OBSERVANT study.

Few studies have yielded information on comparative effectiveness of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) procedures in a real-world setting. The aim of this analysis is to describe procedural and post-procedural outcomes in a TAVI/SAVR intermediate risk propensity-matched population.



OBSERVANT is an observational prospective multicenter cohort study, enrolling AS patients undergoing SAVR or TAVI. Propensity score method was applied to analyze procedural and post-procedural outcomes. Pairs of patients with the same probability score were matched (caliper matching).



The unadjusted enrolled population (N=2108) comprises 1383 SAVR patients, 602 transarterial-TAVI patients and 123 transapical-TAVI patients. Matched population comprised a total of 266 patients (133 patients for each group). A relatively low risk population was selected (mean logistic EuroSCORE 9.4 ± 10.4% vs 8.9 ± 9.5%, SAVR vs TAVI; p=0.650). Thirty-day mortality was 3.8% for both SAVR and TAVI (p=1.000). The incidence of stroke (1.5% SAVR and 0.0% TAVI; p=0.156) and myocardial infarction (0.8% SAVR and 0.8% TAVI; p=1.000) was not statistically different between groups, whereas a higher requirement for blood transfusion was reported across the surgical cohort (49.6% vs 36.1%; p=0.026). A higher incidence of major vascular damage (5.3% vs. 0.0%; p=0.007) and pacemaker implantation(0.8% vs 12.0%; p=0.001) were reported in the TAVI group.



Patients undergoing transcatheter and surgical treatment of severe aortic stenosis are still extremely distinct populations. In the relatively low-risk propensity-matched population analyzed, despite similar procedural and 30-day mortality, SAVR was associated with a higher risk for blood transfusion, whereas TAVI showed a significantly increased rate of vascular damage, permanent AV block and residual aortic valve regurgitation.
Proton pump inhibitor influence on reflux in Barrett's oesophagus.

It is important to identify factors responsible for the development of Barrett's oesophagus (BO). The effect of proton pump inhibitors (PPIs) on oesophageal clearance of both acid and alkaline reflux in these patients is uncertain and studies comparing BO patients and healthy controls (HCs) have not been performed earlier.



Two groups of patients were studied: 18 HCs and 12 BO patients. Oesophageal motility, acid reflux and duodenogastro-oesophageal reflux (DGOR) were measured using a three-pressure transducer catheter with an antimony pH tip, connected to a sodium ion selective electrode. All patients were studied both on and off PPIs.



Without PPI therapy, BO patients had significantly more upright and supine acid reflux and upright DGOR compared with HCs. During acid reflux, HC demonstrated more peristalsis than BO [HC, % peristalsis=64 (9), BO=53 (8), P<0.01], but this was not seen during DGOR. [HC, % peristalsis=68 (14), BO=56 (11)]. In Barrett's patients, DGOR was significantly reduced with PPIs [off PPI, % upright DGOR=61 (17), on PPIs=19 (15), P<0.01], and no oesophageal motility differences were seen compared with results without PPIs.



HCs demonstrate better oesophageal motility compared with BO patients to prevent acid and alkaline reflux. When acid reflux occurred, HCs had better coordinated motility to remove it. This increased coordination did not occur during DGOR, suggesting different stimulation mechanisms. PPI reduced DGOR in BO patients, without any change in oesophageal motility.
Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data

To assess the value of monitoring response to bisphosphonate treatment by means of measuring bone mineral density.



Secondary analysis of trial data using mixed models.  The Fracture Intervention Trial, a randomised controlled trial that compared the effects of alendronate and placebo in 6459 postmenopausal women with low bone mineral density recruited between May 1992 and May 1993. Bone density measurements of hip and spine were obtained at baseline and at one, two, and three years after randomisation.



Between-person (treatment related) variation and within-person (measurement related) variation in hip and spine bone mineral density.



The mean effect of three years' treatment with alendronate was to increase hip bone mineral density by 0.030 g/cm(2). There was some between-person variation in the effects of alendronate, but this was small in size compared with within-person variation. Alendronate treatment is estimated to result in increases in hip bone density >or=0.019 g/cm(2) in 97.5% of patients.



Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent bisphosphonate is unnecessary and may be misleading. Routine monitoring should be avoided in this early period after bisphosphonate treatment is commenced.
Pilot randomised trial of a healthy eating behavioural intervention in uncontrolled asthma.

Rigorous research on the benefit of healthy eating patterns for asthma control is lacking.We randomised 90 adults with objectively confirmed uncontrolled asthma and a low-quality diet (Dietary Approaches to Stop Hypertension (DASH) scores <6 out of 9) to a 6-month DASH behavioural intervention (n=46) or usual-care control (n=44). Intention-to-treat analyses used repeated-measures mixed models.Participants were middle-aged, 67% female and multiethnic. Compared with controls, intervention participants improved on DASH scores (mean change (95% CI) 0.6 (0, 1.1) versus -0.3 (-0.8, 0.2); difference 0.8 (0.2, 1.5)) and the primary outcome, Asthma Control Questionnaire scores (-0.2 (-0.5, 0) versus 0 (-0.3, 0.3); difference -0.2 (-0.5, 0.1)) at 6 months. The mean group differences in changes in Mini Asthma Quality of Life Questionnaire overall and subdomain scores consistently favoured the intervention over the control group: overall 0.4 (95% CI 0, 0.8), symptoms 0.5 (0, 0.9), environment 0.4 (-0.1, 1.0), emotions 0.4 (-0.2, 0.9) and activities 0.3 (0, 0.7). These differences were modest, but potentially clinical significant.The DASH behavioural intervention improved diet quality with promising clinical benefits for better asthma control and functional status among adults with uncontrolled asthma. A full-scale efficacy trial is warranted.
Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study

Sugar substitutes are important in the dietary management of diabetes mellitus. Erythritol is a non-caloric dietary bulk sweetener that reverses endothelial dysfunction in diabetic rats. We completed a pilot study to examine the effects of erythritol on vascular function in patients with type 2 diabetes mellitus. Participants (n = 24) consumed erythritol 36 g/day as an orange-flavored beverage for 4 weeks and a single dose of 24 g during the baseline and final visits. We assessed vascular function before and after acute (2 h) and chronic (4 weeks) erythritol consumption. Acute erythritol improved endothelial function measured by fingertip peripheral arterial tonometry (0.52 ± 0.48 to 0.87 ± 0.29 au, P = 0.005). Chronic erythritol decreased central pulse pressure (47 ± 13 to 41 ± 9 mmHg, P = 0.02) and tended to decrease carotid-femoral pulse wave velocity (P = 0.06). Thus, erythritol consumption acutely improved small vessel endothelial function, and chronic treatment reduced central aortic stiffness. Erythritol may be a preferred sugar substitute for patients with diabetes mellitus.
A Functional Co-Design towards Safe and Secure Vehicle Platooning

Cooperative adaptive cruise control (CACC) or platooning recently becomes promising as vehicles can learn of nearby vehicles? intentions and dynamics through wireless vehicle to vehicle (V2V) communication and advanced on-board sensing technologies. Violation of cybersecurity often results in serious safety issues as been demonstrated in recent studies. However, safety and security in a vehicle platoon so far have been considered separately by different sets of experts. Consequently no existing solution solves both safety and security in a coherent way. In this paper, we show cyber attacks on an automated platoon system could have the most severe level of safety impact with large scale car crash and argue the importance of safety-security co-design for safety critical cyber physical systems (CPS). We propose a safety-security co-design engineering process to derive functional security requirements for a safe automated vehicle platoon system based on a deep comprehension on the interrelation of safety and security. To our best knowledge, we are the first to apply the safety-security co-design concept to a concrete application. Through this engineering process, we propose a general approach for designing a safe and secure platooning. Following the general approach, we come up with a new platoon control algorithm that takes into account both safety and security. Our defense mechanism implicitly defends against safety-related cyber-attacks and greatly shortens the safe distance required when the platoon is not protected.
Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10−8 to P = 2.7 × 10−24). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.
The effects of an arm ergometer training programme on wheelchair subjects

The purpose of the present investigation was to study the effects of an arm ergometer training programme on several physiological variables of recreational wheelchair subjects. Ten paraplegics (5 experimental, 5 control) were tested prior to and immediately after a 2 month exercise regimen at 80% of peak heart rate (30 min per day, 5 days per week, for 8 consecutive weeks at 50 rev/min). The results demonstrated significant increases (P<0.05) in VO2max (1 min-1 & ml kg-1 min-1) and workload but only mild improvements in maximal heart rate and post exercise blood lactates. Body fat, vital capacity and forced expiratory volume did not change with training. Triceps lateralis fibre distribution and fast twitch (FT) fibre area were unaffected by the endurance training programme. However, slow twitch (ST) fibre area increased (P < 0·05) with training. The results indicate that physiological variables of paraplegic subjects following an arm ergometer endurance training programme react similarly to changes previously observed in non-handicapped subjects. The values when compared with normals are low as a result of the relative inactivity of the subjects due to the lack of available exercise programmes for wheelchair people.
Detection of circulating melanoma cells by a two-marker polymerase chain reaction assay in relation to therapy.

Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanin biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination in evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.
Effect of heliox on heart rate kinetics and dynamic hyperinflation during high-intensity exercise in COPD

Respiratory mechanical abnormalities in patients with chronic obstructive pulmonary disease (COPD) may impair cardiodynamic responses and slow down heart rate (HR) kinetics compared with normal resulting in reduced convective oxygen delivery during exercise. We reasoned that heliox breathing (79% helium–21% oxygen) and the attendant reduction of operating lung volumes should accelerate HR kinetics in the transition from rest to high-intensity exercise. Eleven male ambulatory patients with clinically stable COPD undertook constant work-rate cycle testing at 80% of each individuals’ maximum work capacity while breathing room air (RA) or heliox (HX), randomly. Mean response time (MRT) for HR and dynamic end-expiratory lung volume (EELV) were measured. Resting EELV was not affected by HX breathing, while exercise EELV decreased significantly by 0.23 L at isotime during HX breathing compared with RA. During HX breathing, MRT for HR significantly accelerated (p = 0.002) by an average of 20 s (i.e., 17%). Speeded MRT for HR correlated with indices of reduced lung hyperinflation, such as EELV at isotime (r = 0.88, p = 0.03), and with improved exercise endurance time (r = −0.64, p = 0.03). The results confirm that HX-induced reduction of dynamic lung hyperinflation is associated with consistent improvement in indices of cardio-circulatory function such as HR kinetics in the rest-to-exercise transition in COPD patients.
Hybrid Therapy with Right Atrial Catheter Ablation and Previously Ineffective Antiarrhythmic Drugs for the Management of Atrial Fibrillation

Many patients with paroxysmal atrial fibrillation (AF) become refractory to antiarrhythmic drugs (AADs). Early studies suggested that linear catheter ablation in the right atrium may provide sufficient substrate modification to reestablish therapeutic efficacy of previously ineffective AADs.  This prospective before-after multicenter trial evaluated the safety and effectiveness of hybrid therapy that included right atrial catheter ablation coupled with a regimen of previously ineffective AADs on AF episode frequency and symptoms in drug refractory patients with paroxysmal AF. A standard linear lesion set (lateral, septal, isthmus) was used in all subjects. AF episode frequency, clinical arrhythmia symptoms, condition-specific (AFSS) and global health-related quality of life (SF-36) were assessed prior to ablation and at 6 months.  Ninety-three subjects, refractory to an average 2.9 AADs at baseline, qualified for inclusion and underwent right atrial catheter ablation. Eighty-four subjects (90%) provided 6 month AF episode frequency data which demonstrated a significant decrease compared to baseline (3.4 vs. 9.5, p < 0.0001). Forty-nine subjects (58%) were considered a clinical success by virtue of achieving a pre-specified target level episode frequency reduction of 50% or greater. Substantial and statistically significant improvements were realized almost uniformly for all measured arrhythmia symptoms as well as for both quality of life measures. The incidence of major complications was 5.4%.  The addition of right atrial catheter ablation to a regimen of previously ineffective AADs is associated with a significant reduction in the frequency, duration and severity of AF episodes and symptoms.
Performance of Hispanic inmates on the Spanish Miller Forensic Assessment of Symptoms Test (M-FAST).

The few psychological assessment measures commercially available for the assessment of Spanish-speaking populations lack strong empirical foundation. This is concerning given the rising numbers of Spanish speakers entering the forensic and correctional systems for whom valid assessment is difficult without linguistically and culturally appropriate measures. In this study, we translated and adapted the Miller Forensic Assessment of Symptoms Test (M-FAST) into Spanish. The general purpose of this study was to investigate the psychometric, linguistic, and conceptual equivalence of the English- and Spanish-language versions of the M-FAST in a sample of 102 bilingual Hispanic incarcerated males. Participants were randomly assigned to one of three feigning conditions (honest, uncoached, or coached) and completed the M-FAST in both English and Spanish on two separate occasions. Both language versions were psychometrically, linguistically, and conceptually equivalent.
The effect of high plasma levels of angiotensin-converting enzyme (ACE) and plasminogen activator inhibitor (PAI-1) on the reperfusion after thrombolytic therapy in patients presented with acute myocardial infarction

The resistance to thrombolytic agents and delays in reperfusion occur in more than 30% after acute myocardial infarction. This may play an important role in the unsuccessful recanalization after thrombolytic therapy. The aim of this study is to assess the clinical and biochemical markers of reperfusion after different types of thrombolytic therapy and to find out the relationship between PAI-1 and ACE serum levels and the short-term outcome. Pretreatment ACE and PAI-1 plasma levels of 184 patients with acute myocardial infarction, treated with thrombolytic therapy were determined. Failure of thrombolysis was considered when reperfusion was delayed as assessed by noninvasive reperfusion criteria, reinfarction, and impaired left ventricular function. High plasma level of ACE (> 50 U/L), PAI-1 (> 43 ng/ml) and both was found in 57, 108 and 32 patients respectively. Subjects with high ACE plasma levels were characterized by impaired LV systolic function (79.0% vs. 75.0%), new Q-wave (88.4% vs. 74.2%), less reperfusion arrhythmia (19.3% vs. 22.8%) and prolonged hospitalization (70% vs. 66%) but no statistical significance was observed. High enzymes levels of PAI-1 were observed with higher incidence of anterior myocardial infarction (50.0% vs. 41.0%), lesser ST segment resolution (65.6% vs. 58.8%), reinfarction (6.3% vs. 5.9%), and impaired LV systolic function (90.6% vs. 76.0%), and prolonged hospitalization (70.4% vs. 63.4). There was a statistically significant difference between thrombolytic agents in the presence of high ACE regarding hospital overstay (p = 0.02). While the presence of high PAI-1 was significantly affect the degree of ST-segment resolution (p = 0.03).  High plasma ACE and/or PAI-1 plays a considerable role in the higher incidence of unsuccessful reperfusion and impaired left ventricular function after thrombolytic therapy. A rapid diagnostic tool that enables physician of detecting those enzymes before giving thrombolytic therapy may change the strategy of treatment to offer another effective revascularization method.