nils-herrmann/clean_scirepeval huggingface dataset:
Beta1-Adrenoceptor Polymorphism Predicts Flecainide Action in Patients with Atrial Fibrillation

Antiarrhythmic action of flecainide is based on sodium channel blockade. Beta(1)-adrenoceptor (beta(1)AR) activation induces sodium channel inhibition, too. The aim of the present study was to evaluate the impact of different beta(1)AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation.



In 145 subjects, 87 with atrial fibrillation, genotyping was performed to identify the individual beta(1)AR Arg389Gly and Ser49Gly polymorphism. Resting heart rate during atrial fibrillation and success of flecainide-induced cardioversion were correlated with beta(1)AR genotype. The overall cardioversion rate with flecainide was 39%. The Arg389Arg genotype was associated with the highest cardioversion rate (55.5%; OR 3.30; 95% CI; 1.34-8.13; p = 0.003) compared to patients with Arg389Gly (29.5%; OR 0.44; 95% CI; 0.18-1.06; p = 0.066) and Gly389Gly (14%; OR 0.24; 95% CI 0.03-2.07; p = 0.17) variants. The single Ser49Gly polymorphism did not influence the conversion rate. In combination, patients with Arg389Gly-Ser49Gly genotype displayed the lowest conversion rate with 20.8% (OR 0.31; 95% CI; 0.10-0.93; p = 0.03). In patients with Arg389Arg variants the heart rate during atrial fibrillation was significantly higher (110+/-2.7 bpm; p = 0.03 vs. other variants) compared to Arg389Gly (104.8+/-2.4 bpm) and Gly389Gly (96.9+/-5.8 bpm) carriers. The Arg389Gly-Ser49Gly genotype was more common in patients with atrial fibrillation compared to patients without atrial fibrillation (27.6% vs. 5.2%; HR 6.98; 95% CI; 1.99-24.46; p<0.001).



The beta(1)AR Arg389Arg genotype is associated with increased flecainide potency and higher heart rate during atrial fibrillation. The Arg389Gly-Ser49Gly genotype might be of predictive value for atrial fibrillation.
Characterization of aneurysm remnants after endovascular treatment: contrast-enhanced MR angiography versus catheter digital subtraction angiography.

A substantial percentage of coiled aneurysms are associated with persistent filling of an aneurysmal component due to incomplete initial treatment or re-growth. Traditionally follow-up of coiled aneurysms has consisted of repeated intra-arterial cerebral catheter angiography, an invasive procedure with associated risks. Hence, many authors have advocated the use of non-invasive imaging techniques for this purpose. Our aim was to compare contrast-enhanced MR angiography (CE-MRA) with digital subtraction angiography (DSA) for depiction of aneurysmal remnants of coiled cerebral aneurysms.



Aneurysms coiled between September 2003 and October 2006 were retrospectively reviewed. We included patients meeting the following criteria: 1) residual/recurrent aneurysm measuring 2 mm or greater, and 2) CE-MRA and DSA performed no more than 60 days apart. Three readers were asked to determine which technique was superior for characterization of the aneurysmal remnant: CE-MRA, DSA, or indeterminate. Statistical analysis included most rule and kappa statistics.



Of 232 patients who underwent coiling, 44 met the inclusion criteria (33 women and 11 men; 24-72 years of age). Sixteen patients had neck remnants and 28 had body remnants. The first study to identify the remnant was DSA in 35 patients and CE-MRA in 9. In 32 patients (32/44, 73%), the readers indicated that CE-MRA was superior to DSA for remnant characterization. CE-MRA and DSA were thought to be equivalent in 7 (16%), and DSA was preferred in 3 (7%). Two cases (5%) yielded ambiguous results. Of the 28 body remnants, 22 (78.6%) were characterized by remnant protrusion into the coil mass: In 20 of these (91%), the readers preferred CE-MRA over DSA, and in 2 cases (9%), the techniques were thought to be equivalent.



In patients with known aneurysm remnants, CE-MRA is at least equivalent to DSA for characterization of aneurysmal remnants after coiling. Contrast filling within the coil mass was more clearly seen with CE-MRA than with DSA.
Efficient Certification and Zero-Knowledge Proofs of Knowledge on Infrastructure Topology Graphs

Digital signature schemes are a foundational cryptographic building block in certification and the projection of trust. Based on a signature scheme on committed graphs, we propose a framework of certification and proof methods to sign topology graphs and to prove properties of their certificates in zero-knowledge. This framework allows an issuer, such as an auditing system, to sign the topology representation of an infrastructure. The prover, such as an infrastructure provider, can then convince a verifier of topology properties including connectivity and isolation without disclosing the blueprint of the topology itself. By that, we can certify the structure of critical systems while still maintaining confidentiality. We offer zero-knowledge proofs of knowledge for a general specification language of security goals for virtualized infrastructures such that high-level security goals can be proven over topology certificates. We offer an efficient and practical construction, built upon the Camenisch-Lysyanskaya signature scheme, honest-verifier proofs and the strong RSA assumption.
Comparison of cardiovascular mortality in the Great East Japan and the Great Hanshin-Awaji Earthquakes　- a large-scale data analysis of death certificates.

Large earthquakes have been associated with cardiovascular disease (CVD) mortality. In Japan, the 1995 Great Hanshin-Awaji (H-A) Earthquake was an urban-underground-type earthquake, whereas the 2011 Great East Japan (GEJ) Earthquake was an ocean-trench type. In the present study, we examined how these different earthquake types affected CVD mortality.



We examined death certificate data from 2008 to 2012 for 131 municipalities in Iwate, Miyagi, and Fukushima prefectures (n=320,348) and from 1992 to 1996 for 220 municipalities in Hyogo, Osaka, and Kyoto prefectures (n=592,670). A Poisson regression model showed significant increases in the monthly numbers of acute myocardial infarction (AMI)-related deaths (incident rate ratio [IRR] GEJ=1.34, P=0.001; IRR of H-A=1.57, P<0.001) and stroke-related deaths (IRR of GEJ=1.42, P<0.001; IRR of H-A=1.33, P<0.001) after the earthquakes. Two months after the earthquakes, AMI deaths remained significant only for H-A (IRR=1.13, P=0.029). When analyzing the standardized mortality ratio (SMR) after the earthquakes using the Cochran-Armitage trend test, seismic intensity was significantly associated with AMI mortality for 2 weeks after both the GEJ (P for trend=0.089) and H-A earthquakes (P for trend=0.005).



Following the GEJ and H-A earthquakes, there was a sharp increase in CVD mortality. The effect of the disaster was sustained for months after the H-A earthquake, but was diminished after the GEJ Earthquake.
Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period(P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss(P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss(P < 0.001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.
Pre-operative Diagnosis of Pancreatic Neuroendocrine Tumors with Endoscopic Ultrasonography and Computed Tomography in a Large Series.

Diagnosis of pancreatic neuroendocrine tumors (p-NETs) is frequently challenging. We describe a large series of patients with p-NETs in whom both pre-operative Computed Tomography (CT) and Endoscopic Ultrasonography (EUS) were performed.



This was a retrospective analysis of prospectively collected sporadic p-NET cases. All patients underwent both standard multidetector CT study and EUS with fine-needle aspiration (FNA). The final histological diagnosis was achieved on a post-surgical specimen. Chromogranin A (CgA) levels were measured.



A total of 80 patients (mean age: 58 +/- 14.2 years; males: 42) were enrolled. The diameter of functioning was significantly lower than that of non-functioning p-NETs (11.2 +/- 8.5 mm vs 19.8 +/- 12.2 mm; P = 0.0004). The CgA levels were more frequently elevated in non-functioning than functioning pNET patients (71.4% vs 46.9%; P = 0.049). Overall, the CT study detected the lesion in 51 (63.7%) cases, being negative in 26 (68.4%) patients with a tumor </=10 mm, and in a further 3 (15%) cases with a tumor diameter </=20 mm. CT overlooked the pancreatic lesion more frequently in patients with functioning than non-functioning p-NETs (46.5% vs 24.3%; P = 0.002). EUS allowed a more precise pre-operative tumor measurement, with an overall incorrect dimension in only 9 (11.2%) patients. Of note, the EUS-guided FNA suspected the neuroendocrine nature of tumor in all cases.



Data of this large case series would suggest that the EUS should be included in the diagnostic work-up in all patients with a suspected p-NET, even when the CT study was negative for a primary lesion in the pancreas.
Variability in the prevalence of premenstrual asthma.

Our aim is to analyse the differences in the prevalence of premenstrual asthma (PMA) according to a set of criteria, the relationship between them and the influence of asthma severity. The answer "Yes" to "Does your asthma get worse before menstruation?" was considered subjective PMA. A daily respiratory symptoms register of fertile asthmatic females was taken during two consecutive menstrual cycles. For the semi-objective diagnosis, an exacerbation of > or =20% was required in the symptoms register.  diagnosis was a premenstrual worsening of > or =20% of peak flow. We selected 103 patients. Subjective premenstrual deterioration was perceived in 43.7%. The semi-objective deterioration of symptoms in the first cycle occurred in 44.7%, and in 22.3% in both cycles. A total of 54.3% of females with semi-objective criteria in the first cycle perceived a subjective deterioration of symptoms, versus 35.1% of those without semi-objective criteria (p = 0.05). PMA was present at all levels of asthma severity, with no clear link to the degree of severity. The detection of PMA prevalence, the subjective perception of this deterioration and its presence at all levels of asthma severity lead us to urge research into possible premenstrual deterioration in all fertile asthmatic females.
The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension

The aim of this study was to compare 80 mg telmisartan/5 mg amlodipine/12.5 mg hydrochlorothiazide (T80/A5/H12.5) with 80 mg telmisartan/12.5 mg hydrochlorothiazide (T80/H12.5) to determine their relative blood pressure (BP) lowering effects in essential hypertensive patients with inadequate control and to evaluate the long-term safety of T80/A5/H12.5 in a 52-week extension period. Patients (n=132) were randomly assigned to receive double-blind treatment with T80/A5/H12.5 or T80/H12.5 for 8 weeks after a 6-week run-in-period of T80/H12.5. All 126 patients who completed the double-blind period entered the 52-week open-label extension and received T80/A5/H12.5. The adjusted mean changes from the reference baseline of the trough-seated systolic and diastolic BP (SBP/DBP) at week 8 were significantly larger in the T80/A5/H12.5 group (−10.6/−8.8 mm Hg) than in the T80/H12.5 group (−2.3/−1.3 mm Hg) (P<0.0001). The BP-lowering effect of T80/A5/H12.5 was maintained over the 52-week extension period. The adverse events (AEs) during both treatment periods were generally mild. Drug-related AEs were reported in one patient in each group in the double-blind period and in five patients exposed to T80/A5/H12.5 in the double-blind and/or open-label extension period. T80/A5/H12.5 therapy was clinically and statistically superior to T80/H12.5 therapy for the reduction of BP in patients with essential hypertension uncontrolled with T80/H12.5, and its BP-lowering effect was maintained in the long term. T80/A5/H12.5 was generally well-tolerated.
The effect of formulation and food consumption on the bioavailability of dovitinib (TKI258) in patients with advanced solid tumors

This 2-arm, phase 1, crossover study compared the relative bioavailability of two dovitinib (TKI258) capsule formulations [anhydrate clinical service form (CSF) and monohydrate final market image (FMI); Arm 1] and determined the effect of food on dovitinib exposure (Arm 2). Patients with advanced solid tumors were enrolled in one of the 2 arms. Arm 1 randomized patients to a single 500-mg dose of either CSF or FMI followed by 7 days of rest and 500 mg of the other formulation. Arm 2 patients received 300 mg of FMI once daily and were randomized to follow one of six meal sequences, each with three prandial conditions: low fat (LF), high fat (HF), or no meal (NM). Twenty-three and 37 patients were enrolled and 19 and 21 were evaluable in Arms 1 and 2, respectively. In Arm 1, the adjusted geometric means for FMI had small reductions relative to CSF [area under the plasma concentration–time curve (AUClast) decreased by 12 %, maximum concentration (C max) decreased by 3 %]. In Arm 2, the HF meal versus NM showed a 2 % increase in the adjusted geometric mean for AUClast and a 5 % decrease for C max. The LF meal versus NM comparison showed 9 and 6 % increases for AUClast and C max, respectively. Overall, common adverse events included nausea, vomiting, diarrhea, and fatigue. Systemic exposure to dovitinib was similar for the FMI and CSF capsule formulations. Additionally, since prandial conditions did not affect the systemic exposure, dovitinib can be taken with or without food.
Posterolateral versus interbody fusion in isthmic spondylolisthesis: functional results in 52 cases with a minimum follow-up of 6 years.

Posterolateral fusion has long been considered the "gold standard" technique for surgical treatment of adult spondylolisthesis. Superior results have subsequently been reported with interbody fusion with cages and posterior instrumentation. The goal of this prospective study was to compare the two techniques regarding their clinical outcomes and fusion rates. Fifty-two patients with isthmic spondylolisthesis were operated by the same surgeon. One group (25 patients) had decompression and posterolateral fusion (PLF) with a pedicle screw system ; patients in the other group were treated by decompression, posterior interbody fusion (PLIF) and a pedicle screw system. The two groups were similar with respect to grade of slipping, age, and activity. Seventy-seven percent of the patients had a good or very good result with PLIF and 68% with posterolateral fusion. However, there was no statistical difference in cases with low grade slipping, whereas the difference was significant for cases with high grade slipping. The fusion rate was 93% with PLIF and 68% with PLF, but without any significant incidence on the functional outcome. Based on these findings, we now use posterior interbody fusion for high grade spondylolisthesis which requires reduction or if the disc space is still high. When the slip grade is low, or the disc space is narrow, we prefer posterolateral fusion.
Comparison of pharmacy-based measures of medication adherence

Pharmacy databases are commonly used to assess medication usage, and a number of measures have been developed to measure patients' adherence to medication. An extensive literature now supports these measures, although few studies have systematically compared the properties of different adherence measures.



As part of an 18-month randomized clinical trial to assess the impact of automated telephone reminders on adherence to inhaled corticosteroids (ICS) among 6903 adult members of a managed care organization, we computed eight pharmacy-based measures of ICS adherence using outpatient pharmacy dispensing records obtained from the health plan's electronic medical record. We used simple descriptive statistics to compare the relative performance characteristics of these measures.



Comparative analysis found a relative upward bias in adherence estimates for those measures that require at least one dispensing event to be calculated. Measurement strategies that require a second dispensing event evidence even greater upward bias. These biases are greatest with shorter observation times. Furthermore, requiring a dispensing to be calculated meant that these measures could not be defined for large numbers of individuals (17-32 % of participants in this study). Measurement strategies that do not require a dispensing event to be calculated appear least vulnerable to these biases and can be calculated for everyone. However they do require additional assumptions and data (e.g., pre-intervention dispensing data) to support their validity.



Many adherence measures require one, or sometimes two, dispensings in order to be defined. Since such measures assume all dispensed medication is used as directed, they have a built in upward bias that is especially pronounced when they are calculated over relatively short timeframes (< 9 months). Less biased measurement strategies that do not require a dispensing event are available, but require additional data to support their validity.
The experimental osteoporosis in sheep--clinical approach.

The implementation of new methods of oseoporotic therapy requires tests on an animal model. One of the best is the sheep, whose numerous advantages over other models are described in the literature. The aim of this study was induction of osteoporosis using steroids and ovariorectomy methods in sheep and description of the change in parameters with regard to healthy sheep. The study was performed on female "merino" breed sheep divided into three groups: Negative control (NC) healthy animals, positive control (PC) ovariorectomised animals and steroid group (SC) where methylprednisolone was implemented. Blood tests, diagnostic arthroscopy, quantitative computed tomography and X-Ray micro-tomography of bone were carried out. Blood tests revealed a decreased level of estrogens, progesterone and increased parathormone and cortisol levels in the SC group. A decrease in bone turnover markers and an increase in bone resorption markers in all groups were also noted. Diagnostic arthroscopy revealed osteoarthrosis in PC and SC groups. Radiological density tests showed a slight decrease in PC and NC groups whereas there was more than a triple decrease in SC. Results obtained from microCT showed quickly developing osteoporosis in the SC group, which is reflected in numerous parameters analysed in this study. The best effects for osteoporosis induction were obtained using ovariorectomised sheep with methylprednisolone injections.
Beneficial effect of risedronate for preventing recurrent hip fracture in the elderly Japanese women

A 36-month observational study compared the incidence of unaffected side hip fracture in Japanese female osteoporosis patients with a history of hip fracture between 173 patients receiving risedronate and 356 risedronate-untreated controls. New hip fractures were significantly less frequent in the risedronate group, suggesting a preventive effect in high-risk patients. The purpose of this study was to investigate the preventive effect of risedronate on second hip fracture immediately following a first hip fracture in Japanese female osteoporosis patients with unilateral hip fracture. We conducted a prospective matched cohort study in 184 patients treated with risedronate and 445 patients not receiving risedronate after discharge from hospital. Both groups were followed-up for 36 months, and the incidence of unaffected side hip fracture and the frequency of adverse events were assessed. Efficacy could be investigated in 173 patients from the risedronate group and 356 patients from the control group. Hip fracture was detected in 5 and 32 patients, respectively. Kaplan–Meier estimates of the 36-month fracture incidence were 4.3% in the risedronate group and 13.1% in the control group (P = 0.010, log-rank test). The hazard ratios (95% confidence intervals) obtained by univariate and multivariate analysis were 0.310 (0.121–0.796) and 0.218 (0.074–0.639), respectively, indicating a significantly lower incidence of unaffected side hip fracture in the risedronate group. Adverse events occurred in 38 patients (48 events) from the risedronate group and 94 patients (108 events) from the control group, with serious adverse events in 21 patients (26 events) and 78 patients (88 events), respectively. No significant differences were observed between the two groups. The incidence of unaffected side hip fracture was significantly lower in the risedronate group. Accordingly, risedronate may have a preventive effect on hip fracture in high-risk Japanese female osteoporosis patients for fracture with a history of unilateral hip fracture.
Stress reduces the incorporation of misinformation into an established memory.

Memory can be distorted by misleading post-event information. These memory distortions may have serious consequences, for example in eyewitness testimony. Many situations in which memory reports are solicited, and suggestive or misleading information is presented, are highly stressful for the respondent, yet little is known about how stress affects people's susceptibility to misinformation. Here, we exposed participants to a stressor or a control manipulation before they were presented misinformation about a previous event. We report that stressed participants endorsed misinformation in a subsequent memory test less often than control participants, suggesting that stress reduces distortions of memory by misleading information.