nils-herrmann/clean_scirepeval huggingface dataset:
Association between neuropsychiatric and autonomic dysfunction in Alzheimer's disease

We sought to determine whether there was an association between specific neuropsychiatric deficits and autonomic dysfunction in patients with Alzheimer's disease (AD). We studied 20 patients and 20 age-matched control subjects with neuropsychiatric tests (Blessed, Cornell depression and NPI scores) and autonomic tests (Deep breath (HRdb), 30:15 ratio and orthostatic hypotension (Bpoh)). The 30:15 ratio was consistently reduced in AD patients as compared to control subjects (1.05 ± 0.07 for patients and 1.18 ± 0.1 for controls, p 0.001). Whereas there were no significant differences in the HRdb and presence of Bpoh. In AD patients with an abnormal 30:15 ratio, there were significant abnormalities in the Blessed score and in the apathy, delusions and aberrant motor behavior items of the NPI. The other autonomic tests did not correlate with any neuropsychiatric score. The relationship between abnormal cortical function and impaired 30:15 ratio suggested that a lack of cortical modulation of autonomic circuits may underlie cardiovascular instability in these patients.
Cell Segmentation, Tracking, and Mitosis Detection Using Temporal Context

The Large Scale Digital Cell Analysis System (LSDCAS) developed at the University of Iowa provides capabilities for extended-time live cell image acquisition. This paper presents a new approach to quantitative analysis of live cell image data. By using time as an extra dimension, level set methods are employed to determine cell trajectories from 2D + time data sets. When identifying the cell trajectories, cell cluster separation and mitotic cell detection steps are performed. Each of the trajectories corresponds to the motion pattern of an individual cell in the data set. At each time frame, number of cells, cell locations, cell borders, cell areas, and cell states are determined and recorded. The proposed method can help solving cell analysis problems of general importance including cell pedigree analysis and cell tracking. The developed method was tested on cancer cell image sequences and its performance compared with manually-defined ground truth. The similarity Kappa Index is 0.84 for segmentation area and the signed border positioning segmentation error is 1.6 +/- 2.1 microm.
Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea

Ramelteon is a selective MT1/MT2-receptor agonist indicated for insomnia treatment. Because it has no depressant effects on the nervous system, it is not expected to affect the control of breathing. The potential effects of ramelteon on apneic and hypopneic events and arterial oxygen saturation (SaO2) in individuals with obstructive sleep apnea were assessed. In this double-blind, randomized, crossover study, 26 adults with mild to moderate obstructive sleep apnea received ramelteon 16 mg and placebo for one night each, with a 5- to 12-day washout period between treatments. Treatments were administered 30 min before habitual bedtime. Respiratory effort was monitored using respiratory inductance plethysmography, SaO2 was measured by pulse oximetry, and sleep onset and duration were measured by polysomnography and post-sleep questionnaire. Post-sleep questionnaire also measured next-day residual effects. The primary measure was apnea–hypopnea index. Apnea–hypopnea index was similar in ramelteon and placebo groups (11.4 vs 11.1, respectively; CI = −2.1, 2.6, P = 0.812). Ramelteon had no effect on the number of central, obstructive, or mixed apnea episodes. No significant differences were observed in SaO2 for the entire night between ramelteon and placebo (95.1 vs 94.7%; P = 0.070). Ramelteon did not meaningfully affect sleep when evaluated by polysomnography and post-sleep questionnaire. Compared with placebo, ramelteon had no significant effect on next-day residual effects. Adverse events were reported by three subjects in the ramelteon group: headache (n = 2) and urinary tract infection (n = 1). No adverse events were reported with placebo. Ramelteon was well-tolerated and, as expected, did not worsen sleep apnea when administered to subjects with mild to moderate obstructive sleep apnea.
Detection of prostate cancer by integration of line-scan diffusion, T2-mapping and T2-weighted magnetic resonance imaging; a multichannel statistical classifier.

A multichannel statistical classifier for detecting prostate cancer was developed and validated by combining information from three different magnetic resonance (MR) methodologies: T2-weighted, T2-mapping, and line scan diffusion imaging (LSDI). From these MR sequences, four different sets of image intensities were obtained: T2-weighted (T2W) from T2-weighted imaging, Apparent Diffusion Coefficient (ADC) from LSDI, and proton density (PD) and T2 (T2 Map) from T2-mapping imaging. Manually segmented tumor labels from a radiologist, which were validated by biopsy results, served as tumor "ground truth." Textural features were extracted from the images using co-occurrence matrix (CM) and discrete cosine transform (DCT). Anatomical location of voxels was described by a cylindrical coordinate system. A statistical jack-knife approach was used to evaluate our classifiers. Single-channel maximum likelihood (ML) classifiers were based on 1 of the 4 basic image intensities. Our multichannel classifiers: support vector machine (SVM) and Fisher linear discriminant (FLD), utilized five different sets of derived features. Each classifier generated a summary statistical map that indicated tumor likelihood in the peripheral zone (PZ) of the prostate gland. To assess classifier accuracy, the average areas under the receiver operator characteristic (ROC) curves over all subjects were compared. Our best FLD classifier achieved an average ROC area of 0.839(+/-0.064), and our best SVM classifier achieved an average ROC area of 0.761(+/-0.043). The T2W ML classifier, our best single-channel classifier, only achieved an average ROC area of 0.599(+/-0.146). Compared to the best single-channel ML classifier, our best multichannel FLD and SVM classifiers have statistically superior ROC performance (P=0.0003 and 0.0017, respectively) from pairwise two-sided t-test. By integrating the information from multiple images and capturing the textural and anatomical features in tumor areas, summary statistical maps can potentially aid in image-guided prostate biopsy and assist in guiding and controlling delivery of localized therapy under image guidance.
The inferiority of G-PB to rhG-CSF-mobilized blood and marrow grafts as a stem cell source in patients with high-risk acute leukemia who underwent unmanipulated HLA-mismatched/haploidentical transplantation: a comparative analysis

The purpose of this study was to investigate the efficacy and feasibility of unmanipulated haploidentical PBSCT for the treatment of acute leukemia (AL). This study compares the clinical outcomes of high-risk AL patients who received PBSCs harvested from family members sharing at least one common haplotype to outcomes of high-risk AL patients who received a mixture of G-CSF-primed BM (G-BM) and peripheral blood (G-PB) harvests. The results show that PBSCT achieved inferior cumulative myeloid engraftment at 30 days after transplant (89.9±10.1% vs 100%; P=0.04), with lower cumulative incidence of grade II–IV acute GVHD (aGVHD) (37.1±16.5% vs 63.2±6%; P=0.058) compared with G-BM/G-PB transplant. However, both transplant protocols had similar rates of 2-year relapse (29.6±17.1% vs 34.0±5.7%; P=0.954), and PBSCT produced a higher incidence of 2-year non-leukemic mortality (62.5±14.8% vs 35.1±5.1%; P=0.014), as well as lower rates of overall (26.8±12.3% vs 43.2±5.0%; P=0.052) and disease-free survival (26.8±12.3% vs 42.4±5.0%; P=0.071) compared with G-BM/G-PB transplant. These results suggest that haploidentical HSCT is an option for patients with AL who urgently need a graft and do not have matched sibling donors. PBSCT is potentially inferior to G-BM/G-PB transplant, and improvements should be made before PBSCT becomes a routine in unmanipulated mismatched/haploidentical transplant settings.
Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial

NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD). The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.



Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled. Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry. The primary outcome measure was trough FEV1 at Week 12.



A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270). Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001). Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26. FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints. Transition dyspnoea index focal scores and St. George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and -2.81 (p = 0.004), respectively. NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo. NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.



Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.
Socioeconomic Disadvantage Moderates the Association between Peripheral Biomarkers and Childhood Psychopathology

Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF.



Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED.



In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems.
Diagnostic accuracy of urine dipsticks for detecting albuminuria in indigenous and non-indigenous children in a community setting

Albuminuria predicts cardiovascular and end-stage kidney disease in indigenous populations. Early detection in indigenous children may identify those who could benefit from early treatment. Community-based detection of albuminuria needs to be performed using a reliable, inexpensive, and widely available test, such as a proteinuria dipstick. Dipstick accuracy for detecting albuminuria in a community setting has not been evaluated. We assessed the accuracy of Multistix 10 SG dipsticks to detect baseline albuminuria and predict for persistent albuminuria at a 2-year follow-up in a population-based cohort of Australian Aboriginal and non-Aboriginal elementary-school-aged children. Variability in the accuracy of dipsticks in subgroups of higher risk children was analyzed using the relative diagnostic odds ratio (RDOR). Using Multistix 10 SG dipsticks, index-test-positive cases were defined as ≥0.30 g/L (1+) proteinuria and index-test-negative cases as <0.30 g/L (negative or trace) proteinuria. Referent-test-positive cases were defined as spot albumin:creatinine (ACR) ≥3.4 mg/mmol, and referent-test-negative cases as ACR <3.4 mg/mmol. There were 2,266 children (55.1% Aboriginal, 51.0% boys, mean age 8.9 years) enrolled. At the 2-year follow-up, 1,432 (63.0%) children were retested (54.0% Aboriginal, 50.5% boys, mean age 10.5 years). Prevalence of baseline albuminuria was 7.3%, and persistent albuminuria was 1.5%. Dipsticks had a sensitivity of 62% and specificity of 97% at baseline. In predicting persistent albuminuria, sensitivity was 75% and specificity 93%. Accuracy did not vary with ethnicity, gender, or body mass index. Accuracy was less in younger children (4.0–7.9 years), and in those with hematuria. The performance characteristics of Multistix dipsticks make them suitable for albuminuria detection in Aboriginal and other higher-risk groups of children. More than two thirds of children detected at a single test will have transient rather than persistent albuminuria. Multistix dipsticks are particularly useful for detecting children who will have persistent albuminuria.
Characterization of real-world patients with low fractional flow reserve immediately after drug-eluting stents implantation.

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for coronary artery disease has been validated. The present study aimed to identify the variables that influence FFR immediately after drug-eluting stents (DESs) implantation. We retrospectively analyzed 167 patients, who had been implanted with DESs at 6 Japanese institutions and had obtained the FFR values before and immediately after PCI. Intravascular ultrasound (IVUS) was used to build a PCI strategy and to decide the completion of the PCI procedure in all case. Patients were categorized into the following 2 groups according to FFR after PCI: the low FFR (≤0.80) group and the high FFR (>0.80) group. Despite successful PCI evaluated by coronary angiography and IVUS, 18.6 % of real-world patients were in the low FFR group. The proportion of the left anterior descending artery (LAD) was significantly greater in the low FFR group than in the high FFR group (87.1 vs 56.6 %; P < 0.01). Multivariate logistic regression analysis revealed that the LAD-to-non-LAD odds ratio for a low FFR (≤0.80) was 7.34 (95 % CI 1.63-32.95; P < 0.01) after adjustment for FFR value before PCI, suggesting that it is difficult to improve the hemodynamics of the LAD lesions even after successful PCI. The LAD was the strongest contributor to the inadequate recovery of FFR immediately after PCI, thus eliciting heed when treating the LAD lesions.
Effect of intra-articular corticosteroid injections and inflammation on periarticular and generalised bone loss in early rheumatoid arthritis.

To explore the effect of intra-articular corticosteroid (IAST) injections on bone mineral density (BMD) in the hand and at the metacarpophalangeal (MCP) joints in early rheumatoid arthritis (RA).



In the first 3 months of the study, 19 patients with RA received methotrexate (MTX) alone and 21 received MTX and IAST injections into clinically inflamed joints. In the following 9 months, all patients received MTX+IAST. BMD was assessed at the hand and periarticular regions at MCP joints 2-5 at baseline, 3 and 12 months.



In the first 3 months a numerically lower percentage rate of bone loss was seen in MTX+IAST-treated patients compared with MTX-treated patients. This observation was more pronounced at the MCP periarticular regions (eg, partial proximal phalanges: digit 2, -0.45% vs -2.69%, p=0.045; digit 3, -0.34% vs -3.32%, p=0.003; digit 4, -0.39% vs -2.57%, p=0.14; digit 5, -0.59% vs -2.70%, p=0.24) than for the whole hand (-1.53% vs -2.42%, p=0.32). In the 3-12-month period, only minor non-statistically significant differences were seen between the two groups.



IAST given over 3 months protects against periarticular bone loss in inflamed finger joints in RA. These data emphasise the importance of suppressing inflammation in patients with active RA to maintain bone health.
Effects of urban fine particulate matter and ozone on HDL functionality

Exposures to ambient particulate matter (PM) are associated with increased morbidity and mortality. PM2.5 (<2.5 μm) and ozone exposures have been shown to associate with carotid intima media thickness in humans. Animal studies support a causal relationship between air pollution and atherosclerosis and identified adverse PM effects on HDL functionality. We aimed to determine whether brief exposures to PM2.5 and/or ozone could induce effects on HDL anti-oxidant and anti-inflammatory capacity in humans. Subjects were exposed to fine concentrated ambient fine particles (CAP) with PM2.5 targeted at 150 μg/m3, ozone targeted at 240 μg/m3 (120 ppb), PM2.5 plus ozone targeted at similar concentrations, and filtered air (FA) for 2 h, on 4 different occasions, at least two weeks apart, in a randomized, crossover study. Blood was obtained before exposures (baseline), 1 h after and 20 h after exposures. Plasma HDL anti-oxidant/anti-inflammatory capacity and paraoxonase activity were determined. HDL anti-oxidant/anti-inflammatory capacity was assessed by a cell-free fluorescent assay and expressed in units of a HDL oxidant index (HOI). Changes in HOI (ΔHOI) were calculated as the difference in HOI from baseline to 1 h after or 20 h after exposures. There was a trend towards bigger ΔHOI between PM2.5 and FA 1 h after exposures (p = 0.18) but not 20 h after. This trend became significant (p <0.05) when baseline HOI was lower (<1.5 or <2.0), indicating decreased HDL anti-oxidant/anti-inflammatory capacity shortly after the exposures. There were no significant effects of ozone alone or in combination with PM2.5 on the change in HOI at both time points. The change in HOI due to PM2.5 showed a positive trend with particle mass concentration (p = 0.078) and significantly associated with the slope of systolic blood pressure during exposures (p = 0.005). Brief exposures to concentrated PM2.5 elicited swift effects on HDL anti-oxidant/anti-inflammatory functionality, which could indicate a potential mechanism for how particulate air pollution induces harmful cardiovascular effects.
Impact of late calcineurin inhibitor withdrawal on ambulatory blood pressure and carotid intima media thickness in renal transplant recipients.

Calcineurin inhibitors (CNIs) have an unfavorable cardiovascular risk profile in renal transplant recipients. The aim of this substudy was to assess the effects of late CNI or mycophenolate mofetil (MMF) withdrawal on ambulatory blood pressure monitoring and carotid intima media thickness.



A total of 119 stable renal transplant recipients on triple regimen with steroids, a CNI and MMF were randomized into either the concentration-controlled CNI or MMF withdrawal groups. Patients were treated for traditional cardiovascular risk factors according to predefined targets. Ambulatory blood pressure monitoring and measurements of intima media thickness were performed at baseline and after 1, 2, and 3 years after randomization.



CNI withdrawal resulted in a significant decline in both ambulatory day- and nighttime blood pressures (daytime: systolic blood pressure, -1.6 mm Hg/y, P=0.018; diastolic blood pressure, -1.3 mm Hg/y, P=0.002; nighttime systolic blood pressure: -1.9 mm Hg/y, P=0.008; diastolic blood pressure: -1.3 mm Hg/y, P=0.014), which was not observed after MMF withdrawal. There was no difference in the proportion of nocturnal nondippers (both groups, 69%, P=0.95). Despite the reduction in ambulatory blood pressure, no effect of CNI withdrawal on carotid intima media thickness was found.



In stable renal transplant recipients, late CNI withdrawal from a triple drug regimen decreased blood pressure in comparison with MMF withdrawal but had no specific impact on carotid intima media thickness. Considering the high prevalence of hypertension in patients on CNI therapy, most stable renal transplant recipients may benefit from late CNI withdrawal by improved blood pressure control.
Total Fluid and Water Consumption and the Joint Effect of Exposure to Disinfection By-Products on Risk of Bladder Cancer

Findings on water and total fluid intake and bladder cancer are inconsistent; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case-control studies observed a positive association between tap water and bladder cancer but none for nontap fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk.



We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case-control study in Spain.



A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders.



Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0.62; 95% confidence interval (CI), 0.40-0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47; 95% CI, 0.33-0.66; p for trend < 0.0001), but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure; we found no statistical interaction (p for interaction = 0.13).



Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level.