nils-herrmann/clean_scirepeval huggingface dataset:
Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme

The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ε2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301 (SORT1) from eight cohorts of adults aged between 44 and 90 + years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ε4 effect on semantic fluency z score = −0.02; 95 % CI = −0.05 to 0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within studies that negative effects of APOE ε4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits.
Does feeding alter arterial oxygen saturation in patients with acute stroke?

We measured arterial oxygen saturation (SaO(2)) during eating in acute stroke patients to establish the frequency of any meal-related hypoxemia, which could further damage already vulnerable brain tissue.



Stroke patients (</=12 days from stroke onset) classified as "safe to feed orally" were compared with elderly hospitalized (for nonneurological causes) and young healthy controls. SaO(2) was measured noninvasively at the bedside by pulse oximetry continuously for 10 minutes before the patient ate a meal, during the meal, and for 10 minutes after completion of the meal.



The median baseline SaO(2) was significantly lower in stroke patients (n=106, 95.7%) than elderly (n=50, 96.7%) or young control subjects (n=20, 97.9%; P:<0.001). There was a small decrease in the median SaO(2) during eating in stroke and elderly patients (95.6%, P:=0.08, and 96.3%, P:=0.004, respectively) but not in young controls. Only stroke patients had a significantly lower median SaO(2) after completion of the meal (95. 4%, P:<0.001). SaO(2) of </=90% during and after eating occurred in 24% of stroke and 16% of elderly patients but not in young controls, and it was significantly more common in those who had SaO(2) of </=90% during the baseline recordings (P:</=0.003).



Eating a meal was associated with a small fall in median SaO(2) among stroke and elderly patients, but only in stroke patients did this persist for at least 10 minutes after eating. A quarter of stroke patients had episodes in which the SaO(2) fell to </=90% saturation (ie, hypoxemia) during or after eating, although this rarely coincided exactly with swallowing and was more common in patients who also experienced desaturation during the baseline recordings. Further studies are required to establish whether these changes are clinically important.
A Phase I Trial of High-Dose Chemotherapy Combining Topotecan plus Cyclophosphamide with Hematopoietic Stem Cell Transplantation for Ovarian Cancer: The ITOV 01bis Study.

Dose-intensive chemotherapy with hematopoietic stem cell transplantation has been evaluated as a salvage treatment for recurrent ovarian cancer, but its benefit has not yet been demonstrated. In a previous phase I trial, we reported the feasibility of administering topotecan as a salvage regimen.



Twenty-one patients were treated with escalating doses of topotecan associated with a fixed dose of cyclophosphamide.



The maximum tolerated dose was established at 9.0 mg/m2 on a 5-day regimen, analogously to what was reported for topotecan monotherapy. One toxic death from septic shock and multiorgan failure occurred. Although hematopoietic toxicities were overcome by peripheral blood stem cell transplantation, superior nonhematological toxicities were observed as compared to the initial trial.



Response rates were generally short and survival rates were poor. Results of the ITOV 01bis study demonstrate that, in the setting of recurrent ovarian cancer, intensive chemotherapy based on topotecan-cyclophosphamide association is not currently clinically indicated.
Assessment of >/=50% and <50% intracranial stenoses by transcranial color-coded duplex sonography.

A favorable risk-benefit ratio for warfarin compared with aspirin has been reported for the prevention of major vascular events in symptomatic >/=50% intracranial stenoses. Transcranial color-coded duplex sonography (TCCS) criteria providing an accurate detection of >/=50% and <50% stenoses of the anterior, middle, and posterior cerebral arteries and basilar and vertebral arteries were evaluated retrospectively with angiography used as the standard of reference.



Prospectively collected TCCS, extracranial color-coded duplex sonography, and intra-arterial digital subtraction angiography data of 310 patients were reviewed. The patients had angiography for confirmation of symptomatic extracranial >/=70% carotid stenoses, symptomatic stenoses (peak systolic velocity higher than the corresponding mean value +2 SDs of 104 normal subjects), and occlusions of the middle cerebral or basilar artery previously assessed by ultrasound. The sonographer was not aware of angiographic findings.



TCCS would have detected all 31 of >/=50% intracranial stenoses with 1 false-positive and 35 of 38 <50% stenoses with 3 false-positives. One of 69 stenoses (1%) and 280 of 2741 normal arteries (10%) were missed because of inadequate insonation windows. The corresponding peak systolic velocity cutoffs for >/=50%/<50% stenoses were >/=155/>/=120 cm/s (anterior cerebral artery), >/=220/>/=155 cm/s (middle cerebral artery), >/=145/>/=100 cm/s (posterior cerebral artery), >/=140/>/=100 cm/s (basilar artery), and >/=120/>/=90 cm/s (vertebral artery).



TCCS may reliably assess >/=50% and <50% basal cerebral artery narrowing and prove useful for noninvasive management of patients with symptomatic intracranial stenoses.
The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults1234

Popular beliefs that breakfast is the most important meal of the day are grounded in cross-sectional observations that link breakfast to health, the causal nature of which remains to be explored under real-life conditions.



The aim was to conduct a randomized controlled trial examining causal links between breakfast habits and all components of energy balance in free-living humans.



The Bath Breakfast Project is a randomized controlled trial with repeated-measures at baseline and follow-up in a cohort in southwest England aged 21-60 y with dual-energy X-ray absorptiometry-derived fat mass indexes ≤11 kg/m² in women (n = 21) and ≤7.5 kg/m² in men (n = 12). Components of energy balance (resting metabolic rate, physical activity thermogenesis, energy intake) and 24-h glycemic responses were measured under free-living conditions with random allocation to daily breakfast (≥700 kcal before 1100) or extended fasting (0 kcal until 1200) for 6 wk, with baseline and follow-up measures of health markers (eg, hematology/biopsies).



Contrary to popular belief, there was no metabolic adaptation to breakfast (eg, resting metabolic rate stable within 11 kcal/d), with limited subsequent suppression of appetite (energy intake remained 539 kcal/d greater than after fasting; 95% CI: 157, 920 kcal/d). Rather, physical activity thermogenesis was markedly higher with breakfast than with fasting (442 kcal/d; 95% CI: 34, 851 kcal/d). Body mass and adiposity did not differ between treatments at baseline or follow-up and neither did adipose tissue glucose uptake or systemic indexes of cardiovascular health. Continuously measured glycemia was more variable during the afternoon and evening with fasting than with breakfast by the final week of the intervention (CV: 3.9%; 95% CI: 0.1%, 7.8%).



Daily breakfast is causally linked to higher physical activity thermogenesis in lean adults, with greater overall dietary energy intake but no change in resting metabolism. Cardiovascular health indexes were unaffected by either of the treatments, but breakfast maintained more stable afternoon and evening glycemia than did fasting.
Development and validation of the Italian version of the Spinal Cord Independence Measure III.

To provide a translation and cultural adaptation of the Spinal Cord Independence Measure version III scale for Italy (i-SCIM3) and to validate this version of the scale.



i-SCIM3 was developed involving a forward-backward translation and administered to patients with spinal cord lesions (SCL) admitted to two centers. Two raters for each center evaluated patients at admission and discharge. Psychometric testing included reliability by internal consistency (Cronbach's alpha) and test-retest reliability. The validity of i-SCIM3 was assessed by comparing it with the Italian version of Functional Independence Measure (FIM).



One hundred three adult patients with SCL (84 males) with a mean age of 50.33+/-15.35 years were recruited. Seventy-four patients were paraplegic and 29 patients were tetraplegic. The median time elapsed between the two evaluations was 77.5 days (interquartile range, 53-144 days). Internal consistency, inter-rater reliability, and test-retest reliability were satisfactory overall, showing values higher than 0.90. The validity of i-SCIM3 was confirmed by the close correlation with FIM results both at admission and discharge (r=0.91, p<0.01). The sensitivity to change of i-SCIM3 was similar to that of FIM.



i-SCIM3 was found to be a consistent, reliable, and valid scale for use in the clinical setting. It is the first validated scale in Italian for patients with SCL.
Optimal detection of faulty traffic sensors used in route planning

In a smart city, real-time traffic sensors may be deployed for various applications, such as route planning. Unfortunately, sensors are prone to failures, which result in erroneous traffic data. Erroneous data can adversely affect applications such as route planning, and can cause increased travel time. To minimize the impact of sensor failures, we must detect them promptly and accurately. However, typical detection algorithms may lead to a large number of false positives (i.e., false alarms) and false negatives (i.e., missed detections), which can result in suboptimal route planning. In this paper, we devise an effective detector for identifying faulty traffic sensors using a prediction model based on Gaussian Processes. Further, we present an approach for computing the optimal parameters of the detector which minimize losses due to false-positive and false-negative errors. We also characterize critical sensors, whose failure can have high impact on the route planning application. Finally, we implement our method and evaluate it numerically using a real- world dataset and the route planning platform OpenTripPlanner.
Risk of venous thromboembolic disease in postmenopausal women taking oral or transdermal hormone replacement therapy

The influence of hormone replacement therapy (HRT) on hemostasis processes depends on the type of hormone, the combination of doses, the time of taking HRT, and the route of administration (oral, transdermal, implanted). The aim of the current study was to assess some parameters of coagulation, especially tissue factor pathway inhibitor (TFPI) and tissue factor (TF) in postmenopausal women using oral or transdermal HRT. The study was conducted on 76 healthy women, including 46 women aged 44–58 years who were taking oral (26) or transdermal (20) HRT, and 30 women aged 44–54 years who did not take HRT as the control group. Plasma concentrations of TF, TFPI, thrombin-antithrombin complex (TAT), and D-dimer were performed by enzyme-linked immunosorbent assay (ELISA). Moreover, the concentration of fibrinogen and activity of protein C were measured by chromogenic and chronometric methods. We observed a significantly higher concentration of TF and a significantly lower concentration of TFPI in women taking oral and transdermal HRT in comparison with the control group. We also found a significantly lower concentration of fibrinogen in women taking oral HRT vs. the control group. Moreover, no statistically significant changes in concentrations of TAT and D-dimer, or activity of protein C were noted. In this study, the occurrence of an increased TF concentration simultaneously with a decreased concentration of TFPI in women taking HRT indicates hypercoagulability. No significant modification of TAT or D-dimer occurred, and thus there may not be increased risk of thrombosis.
Zero-skew clock tree construction by simultaneous routing, wire sizing and buffer insertion

We propose an integrated clock tree construction algorithm which performs simultaneous routing, wire sizing and buffer insertion. In existing approaches, wire sizing and clock buffer insertion are typically applied sequentially after a clock tree is generated and routed, i.e., they are done as post-processing steps. None of the known methods can perform clock routing while simultaneously considering wire sizing and buffer insertion. We introduce wire widths and levels of buffers inserted as variables in forming merging segments in the proposed Integrated Deferred-Merge Embedding (IDME) al gorithm. As a result, more zero-skew merging locations are made possible and the clock trees generated are zero-skew by construction. Our experiments show that by taking the advantage offered by wire sizing, we are able to minimize phase delay as well as to reduce wire length and use less buffers.
The role of oxidative stress and inflammation in the early evaluation of acute non-ST-elevation myocardial infarction: an observational study.

We aimed to assess the role of oxidative stress (OS) and inflammation in the early evaluation of initial acute non -ST -elevation myocardial infarction (NSTEMI) compared with unstable angina pectoris (USAP).



Forty-seven (54%) patients with NSTEMI and 40 (46%) with (USAP) were included in this cross-section observational study. We assessed the oxidative stress and inflammation parameters. Statistical analysis was performed using Fisher's exact test, Chi-square test, Mann-Whitney U test, Student's t-test, and Pearson correlation analysis for assess the correlations between variables.



Plasma total oxidative stress (TOS) and OS index levels were significantly higher (p<0.001 for both comparisons), in patients with NSTEMI. In addition, white blood cell count (WBC) and high-sensitive C-reactive protein (hs-CRP) levels were significantly higher in patients with NSTEMI (respectively; p<0.001, p=0.02). Age, WBC and low- density lipoprotein cholesterol showed positive correlations with TOS level (Pearson correlation coefficient: r=0.290, p=0.006; r=0.431, p<0.001; r=0.219, p=0.042 respectively), and also age showed positive correlation with OS index (Pearson correlation coefficient; r=0.246; p=0.021). However, the values of the troponin I and creatine kinase-MB fraction did not differ between the two groups (p>0.05 for all).



TOS, OSI, WBC and CRP levels are significantly higher in NSTEMI subject. These data suggest that inflammatory processes and oxidative stress together play a role in the pathogenesis of acute NSTEMI.
Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study.

Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protocol, 30 healthy volunteers were randomized in a double-blind fashion to receive oral rosuvastatin (20 mg/day) and placebo, rosuvastatin, and celecoxib (100 mg bid) or placebo alone, all for 21 days. Twenty-four hours after the final administration of study medication, FMD was measured before and after IR. Pre-IR FMD was similar between groups in both protocols. In the acute administration protocol, rosuvastatin significantly prevented the blunting of FMD associated with IR (FMD pre-IR: 8.4 ± 1.3%; post-IR: 6.2 ± 1.3%; P = 0.01 ANOVA, treatment group interaction). In the daily administration protocol, IR significantly blunted FMD in the placebo group (FMD pre-IR: 7.5 ± 0.9%; post-IR: 3.3 ± 0.7%; P < 0.001). Chronic treatment with rosuvastatin did not modify this ischemic injury (FMD pre-IR: 6.9 ± 0.4%; post-IR: 1.6 ± 1.0%; P < 0.001; P = NS ANOVA, treatment group interaction). Similarly, FMD responses post-IR in volunteers receiving rosuvastatin and celecoxib did not significantly differ from placebo (FMD pre-IR: 8.3 ± 0.9%; post-IR: 2.1 ± 0.8%; P < 0.001; P = NS ANOVA, treatment group interaction). In contrast to acute administration, chronic rosuvastatin does not prevent the development of IR-induced endothelial dysfunction in normal humans.
Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training

Insulin-mediated glucose disposal rates (R d) are reduced in type 2 diabetic patients, a process in which intrinsic signalling defects are thought to be involved. Phosphorylation of TBC1 domain family, member 4 (TBC1D4) is at present the most distal insulin receptor signalling event linked to glucose transport. In this study, we examined insulin action on site-specific phosphorylation of TBC1D4 and the effect of exercise training on insulin action and signalling to TBC1D4 in skeletal muscle from type 2 diabetic patients. During a 3 h euglycaemic–hyperinsulinaemic (80 mU min−1 m−2) clamp, we obtained M. vastus lateralis biopsies from 13 obese type 2 diabetic and 13 obese, non-diabetic control individuals before and after 10 weeks of endurance exercise-training. Before training, reductions in insulin-stimulated R d, together with impaired insulin-stimulated glycogen synthase fractional velocity, Akt Thr308 phosphorylation and phosphorylation of TBC1D4 at Ser318, Ser588 and Ser751 were observed in skeletal muscle from diabetic patients. Interestingly, exercise-training normalised insulin-induced TBC1D4 phosphorylation in diabetic patients. This happened independently of increased TBC1D4 protein content, but exercise-training did not normalise Akt phosphorylation in diabetic patients. In both groups, training-induced improvements in insulin-stimulated R d (~20%) were associated with increased muscle protein content of Akt, TBC1D4, α2-AMP-activated kinase (AMPK), glycogen synthase, hexokinase II and GLUT4 (20–75%). Impaired insulin-induced site-specific TBC1D4 phosphorylation may contribute to skeletal muscle insulin resistance in type 2 diabetes. The mechanisms by which exercise-training improves insulin sensitivity in type 2 diabetes may involve augmented signalling of TBC1D4 and increased skeletal muscle content of key insulin signalling and effector proteins, e.g., Akt, TBC1D4, AMPK, glycogen synthase, GLUT4 and hexokinase II.
Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma.

This multicenter phase 2 study of the European Myeloma Network investigated the combination of carfilzomib, thalidomide, and dexamethasone (KTd) as induction/consolidation therapy for transplant-eligible patients with previously untreated multiple myeloma (N = 91). During KTd induction therapy, patients received 4 cycles of carfilzomib 20/27 mg/m(2) (n = 50), 20/36 mg/m(2) (n = 20), 20/45 mg/m(2) (n = 21), or 20/56 mg/m(2) (n = 20) on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle; thalidomide 200 mg on days 1 to 28; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, and 16. After autologous stem cell transplantation, patients proceeded to KTd consolidation therapy, where the target doses of carfilzomib were 27 mg/m(2), 36 mg/m(2), 45 mg/m(2), or 56 mg/m(2), respectively, and thalidomide 50 mg. Common grade 3/4 adverse events included respiratory (15%), gastrointestinal (12%), and skin disorders (10%); polyneuropathy was infrequent (1%). Complete response rates after induction and consolidation treatment were 25% and 63%, respectively; rates of very good partial response or better after induction and consolidation were 68% and 89%, respectively. At a median follow-up of 23 months, the 36-month progression-free survival rate was 72%. The KTd induction and consolidation regimens were active, safe, and well tolerated.
Emotional blunting associated with SSRI-induced sexual dysfunction. Do SSRIs inhibit emotional responses?

Anecdotal and published case reports suggest that some patients taking selective serotonin reuptake inhibitors (SSRI) experience diminution in emotional responsiveness. This study aims to define the individual components of emotion disturbed in these patients. Fifteen patients reporting SSRI-induced sexual dysfunction completed the Laukes Emotional Intensity Scale (LEIS), a questionnaire about various emotions. Compared to controls, patients reported significantly (p<0.05) less ability to cry, irritation, care about others' feelings, sadness, erotic dreaming, creativity, surprise, anger, expression of their feelings, worry over things or situations, sexual pleasure, and interest in sex. Total score on the LEIS did not correlate with total score on the Hamilton Depression Rating Scale. In our sample, 80% of patients with SSRI-induced sexual dysfunction also describe clinically significant blunting of several emotions. Emotional blunting may be an under-appreciated side-effect of SSRIs that may contribute to treatment non-compliance and/or reduced quality of life.