nils-herrmann/clean_scirepeval huggingface dataset:
The -48 C/T polymorphism in the presenilin 1 promoter is associated with an increased risk of developing Alzheimer's disease and an increased Abeta load in brain.

Mutations in the presenilin 1 gene (PS1) account for the majority of early onset, familial, autosomal dominant forms of Alzheimer's disease (AD), whereas its role in other late onset forms of AD remains unclear. A -48 C/T polymorphism in the PS1 promoter has been associated with an increased genetic risk in early onset complex AD and moreover has been shown to influence the expression of the PS1 gene. This raises the possibility that previous conflicting findings from association studies with homozygosity for the PS1 intron 8 polymorphism might be the result of linkage disequilibrium with the -48 CC genotype. Here we provide further evidence of increased risk of AD associated with homozygosity for the -48 CC genotype (odds ratio=1.6). We also report a phenotypic correlation with Abeta(40), Abeta(42(43)), and total Abeta load in AD brains. The -48 CC genotype was associated with 47% greater total Abeta load (p<0.003) compared to CT + TT genotype bearers. These results suggest that the -48 C/T polymorphism in the PS1 promoter may increase the risk of AD, perhaps by altering PS1 gene expression and thereby influencing Abeta load.
Identifying Distinct Healthcare Pathways During Episodes of Chronic Obstructive Pulmonary Disease Exacerbations

Healthcare pathways are important to measure because they are expected to affect outcomes. However, they are challenging to define because patients exhibit heterogeneity in their use of healthcare services. The objective of this study was to identify and describe healthcare pathways during episodes of chronic obstructive pulmonary disease (COPD) exacerbations. Linked administrative databases from Saskatchewan, Canada were used to identify a cohort of newly diagnosed COPD patients and their episodes of healthcare use for disease exacerbations. Latent class analysis (LCA) was used to classify the cohort into homogeneous pathways using indicators of respiratory-related hospitalizations, emergency department (ED) visits, general and specialist physician visits, and outpatient prescription drug dispensations. Multinomial logistic regression models tested patients' demographic and disease characteristics associated with pathway group membership. The most frequent healthcare contact sequences in each pathway were described. Tests of mean costs across groups were conducted using a model-based approach with χ² statistics. LCA identified 3 distinct pathways for patients with hospital- (n = 963) and ED-initiated (n = 364) episodes. For the former, pathway group 1 members followed complex pathways in which multiple healthcare services were repeatedly used and incurred substantially higher costs than patients in the other pathway groups. For patients with an ED-initiated episode, pathway group 1 members also had higher costs than other groups. Pathway groups differed with respect to patient demographic and disease characteristics. A minority of patients were discharged from ED or hospital, but did not have any follow-up care during the remainder of their episode.Patients who followed complex pathways could benefit from case management interventions to streamline their journeys through the healthcare system. The minority of patients whose pathways were not consistent with recommended follow-up care should be further investigated to fully align COPD treatment in the province with recommended care practices.
Newborn infant characteristics and risk of future rheumatoid arthritis: a twin-control study

Low birth weight has been proposed as a risk factor for rheumatoid arthritis (RA). The twin-control study design provides an opportunity to investigate the significance of potential prenatal determinants for adult morbidity by accounting for maternal characteristics and early environmental and genetic factors. We investigated the association between birth weight and RA in a sample of 42 twin pairs discordant for rheumatoid arthritis in which valid information on birth weight, birth length, and order was available from midwife records. Difference plot and conditional logistic regression were used to investigate the relationship between RA and birth weight or birth order adjusting for birth length and sex. The intra-pairwise birth weight differences, i.e., RA twin minus co-twin, ranged from −750 to 1,100 g, mean 78 g (95 % CI −13 to 70), 146 g (95 % CI (−36 to 329) in monozygotic, 32 g (95 % CI −90 to 154) in dizygotic, same sex and 69 g (95 % CI −122 to 260) in dizygotic, opposite sex twin pairs. The odds ratio for birth weight as risk factor for RA was 1.00 (95 % CI 0.997–1.003) when adjusting for birth length, birth order, and sex, irrespective of ACPA status. The odds ratio for developing RA as first born twin was 2.33 (95 % CI 0.97–5.60) when adjusting for birth length, birth weight, and sex, irrespective of ACPA status. In this twin-control study, birth weight was not associated with the development of RA in adult life. Being born first may predispose to RA.
Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study.

To evaluate reasons for discontinuing intraperitoneal (IP) chemotherapy, and to compare characteristics of patients who did versus did not successfully complete six cycles of IP chemotherapy.



In a phase III trial, women with optimal stage III ovarian or peritoneal carcinoma were randomly allocated to receive IP therapy (paclitaxel 135 mg/m(2) intravenously (IV) over 24 h, cisplatin 100 mg/m(2) IP day 2, paclitaxel 60 mg/m(2) IP day 8) every 21 days for six cycles. Patients unable to receive IP therapy were treated with the alternate (IV) regimen. Variables compared included surgical procedures prior to enrollment, timing of IP catheter insertion, and primary and contributing reasons for discontinuing IP therapy.



Among 205 eligible patients randomly allocated to the IP arm, 119 (58%) did not complete six cycles of IP therapy. Forty (34%) patients discontinued IP therapy primarily due to catheter complications and 34 (29%) discontinued for unrelated reasons. Hysterectomy, appendectomy, small bowel resection, and ileocecal resection were not associated with failure to complete six cycles. IP therapy was not initiated in 16% of patients who did versus 5% of those who did not have a left colon or rectosigmoid colon resection (P = 0.015). There was no association between timing of catheter insertion and failure to complete IP therapy.



In this multi-institutional setting, it was difficult to deliver six cycles of IP therapy without complications. There appears to be an association between rectosigmoid colon resection and the inability to initiate IP therapy. Catheter choice, timing of insertion, and how surgical treatment of ovarian cancer influences the successful completion of intraperitoneal chemotherapy require further study.
Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia.

To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg in insomnia patients.



Adults (18-64 y) with chronic primary insomnia (DSM-IV) were randomly assigned to one of four sequences of 1 mg, 3 mg, and 6 mg of doxepin, and placebo in a crossover study. Treatment periods consisted of 2 polysomnographic assessment nights with a 5-day or 12-day drug-free interval between periods. Efficacy was assessed using polysomnography (PSG) and patient-reported measures. Safety analyses included measures of residual sedation and adverse events.



Sixty-seven patients were randomized. Wake time during sleep, the a priori defined primary endpoint, was statistically significantly improved at the doxepin 3 mg and 6 mg doses versus placebo. All three doses had statistically significant improvements versus placebo for PSG-defined wake after sleep onset, total sleep time, and overall sleep efficiency (SE). SE in the final third-of-the-night also demonstrated statistically significant improvement at all doses. The doxepin 6 mg dose significantly reduced subjective latency to sleep onset. All three doxepin doses had a safety profile comparable to placebo. There were no statistically significant differences in next-day residual sedation, and sleep architecture was generally clinically preserved.



In adults with primary insomnia, doxepin 1 mg, 3 mg, and 6 mg was well-tolerated and produced improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. The side-effect profile was comparable to placebo, with no reported anticholinergic effects, no memory impairment, and no significant hangover/next-day residual effects. These data demonstrate that doxepin 1 mg, 3 mg, and 6 mg is efficacious in improving the sleep of patients with chronic primary insomnia.
An Assessment of the Relationship between Condom Labels and HIV-Related Beliefs and Intentions

The aim of this article is to examine the impact of the FDA’s proposed condom package labeling on HIV-related beliefs about condom effectiveness, on intentions to recommend condoms for friends to use, and intentions to use condoms. Using a nationally representative survey we randomized 1,194 adults ages 18–65 years into one of three condom label conditions: the current label on condom packaging; a label with the proposed FDA language; and a label with CDC language on condom effectiveness. In short, there are no significant differences between the proposed FDA label and the current label on HIV-related beliefs and intentions. In contrast, from an HIV prevention perspective, the CDC condom language appears to offer a better alternative to the current condom label for unmarried populations.
Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study.

To assess the effects of turmeric (Curcuma longa) extract on irritable bowel syndrome (IBS) symptomology in otherwise healthy adults.



Partially blinded, randomized, two-dose, pilot study.



Five hundred (500) volunteers were screened for IBS using the Rome II criteria. Two hundred and seven (207) suitable volunteers were randomized.



One or two tablets of a standardized turmeric extract taken daily for 8 weeks.



IBS prevalence, symptom-related quality of life (IBSQOL) and self-reported effectiveness.



IBS prevalence decreased significantly in both groups between screening and baseline (41% and 57%), with a further significant drop of 53% and 60% between baseline and after treatment, in the one- and two-tablet groups respectively (p < 0.001). A post-study analysis revealed abdominal pain/discomfort score reduced significantly by 22% and 25% in the one- and two-tablet group respectively, the difference tending toward significance (p = 0.071). There were significant improvements in all bar one of the IBSQOL scales of between 5% and 36% in both groups, approximately two thirds of all subjects reported an improvement in symptoms after treatment, and there was a favorable shift in self-reported bowel pattern. There were no significant differences between groups.



Turmeric may help reduce IBS symptomology. Placebo controlled trials are now warranted to confirm these findings.
The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia.

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.
Aerosol granulocyte macrophage-colony stimulating factor: a low toxicity, lung-specific biological therapy in patients with lung metastases.

The objective was to study the feasibility of granulocyte macrophage-colony stimulating factor (GM-CSF) delivery to the lung using an aerosol in humans. A Phase I dose escalation study provided GM-CSF at three dose levels as a twice-a-day (BID) x 7 days schedule. Pulmonary functions were monitored using a remote spirometry device. Blood counts were checked at the beginning and end of each week of GM-CSF nebulization. If no toxicity was encountered, patients rested for 7 days and then were treated at the next dose level. Six of seven patients were successfully dose escalated from 60 microg/dose BID x 7 days, to 120 microg/dose BID x 7 days, then 240 microg/dose BID x 7 days. No toxicity was seen. Comparison of day 0 and day 7 blood leukocyte counts showed no significant increases in either leukocyte numbers or percentage of neutrophils. Pulmonary functions test changes were minor. No significant change in forced vital capacity, FEV1, peak flow, or FEF 25-75 related to either time or dose level was observed. One patient's lung metastases progressed. The other five patients received an additional 2-6 months of intermittent aerosol GM-CSF at dose level 3 without side effects. One patient with Ewing's sarcoma has a complete response, and a patient with melanoma had a partial response; the other three had stabilization of pulmonary metastases for 2-6 months. Aerosol delivery of GM-CSF is feasible, safe, and possibly effective. Aerosol cytokine delivery may achieve effective immunological activation against cancer in the lung and is worthy of further study.
A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study.

This study was designed to test a rapid protocol of intravenous acetylcysteine for prevention of radiocontrast-induced nephropathy (RCIN).



Oral acetylcysteine (NAC) may provide better prophylaxis against RCIN than intravenous (i.v.) hydration alone. Current protocols preclude prophylaxis of same-day or emergency patients owing to the need for prolonged pretreatment.



We prospectively randomized 80 patients with stable renal dysfunction undergoing cardiac catheterization/intervention to a rapid protocol of i.v. NAC (150 mg/kg in 500 ml N/saline over 30 min immediately before contrast followed by 50 mg/kg in 500 ml N/saline over 4 h, n = 41, 67 +/- 10 years, 90% men) or i.v. hydration (1 ml/kg/h N/saline for 12 h pre- and post-contrast, n = 39, 71 +/- 8.8 years, 85% men).



Radiocontrast-induced nephropathy occurred in 2 of the 41 patients in the NAC group (5%) and in 8 of the 39 patients in the hydration group (21%; p = 0.045; relative risk: 0.28; 95% confidence interval 0.08 to 0.98). In the NAC group, mean serum creatinine fell from 1.85 +/- 0.59 to 1.77 +/- 0.73 and 1.79 +/- 0.73 mg/dl 48 h and four days post-contrast (p = 0.02 and 0.023 vs. baseline, respectively). In the hydration group, serum creatinine increased from 1.75 +/- 0.41 to 1.81 +/- 0.6 48 h and 1.80 +/- 0.50 mg/dl four days post-contrast (p = 0.99 and 0.23, respectively). NAC infusion was ceased after the bolus in three patients (7%) due to flushing, itching, or a transient rash.



Administration of i.v. NAC should be considered in all patients at risk of RCIN before contrast exposure when time constraints preclude adequate oral prophylaxis, provided the patient is able to tolerate this degree of volume loading.
Design and Evaluation of a Person-Centric Heart Monitoring System over Fog Computing Infrastructure

Heart disease and stroke are becoming the leading cause of death worldwide. Electrocardiography monitoring devices (ECG) are the only tool that helps physicians diagnose cardiac abnormalities. Although the design of ECGs has followed closely the electronics miniaturization evolution over the years, existing wearable ECG have limited accuracy and rely on external resources to analyze the signal and evaluate heart activity. In this paper, we work towards empowering the wearable device with processing capabilities to locally analyze the signal and identify abnormal behavior. The ability to differentiate between normal and abnormal heart activity significantly reduces (a) the need to store the signals, (b) the data transmitted to the cloud and (c) the overall power consumption. Based on this concept, the HEART platform is presented that combines wearable embedded devices, mobile edge devices, and cloud services to provide on-the-spot, reliable, accurate and instant monitoring of the heart. The performance of the system is evaluated concerning the accuracy of detecting abnormal events and the power consumption of the wearable device. Results indicate that a very high percentage of success can be achieved in terms of event detection ratio and the device being operative up to a several days without the need for a recharge.
PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies.

Despite their nearly universal activation of mammalian target of rapamycin (mTOR) signaling, glioblastomas (GBMs) are strikingly resistant to mTOR-targeted therapy. We analyzed GBM cell lines, patient-derived tumor cell cultures, and clinical samples from patients in phase 1 clinical trials, and find that the promyelocytic leukemia (PML) gene mediates resistance to mTOR-targeted therapies. Direct mTOR inhibitors and EGF receptor (EGFR) inhibitors that block downstream mTOR signaling promote nuclear PML expression in GBMs, and genetic overexpression and knockdown approaches demonstrate that PML prevents mTOR and EGFR inhibitor-dependent cell death. Low doses of the PML inhibitor, arsenic trioxide, abrogate PML expression and reverse mTOR kinase inhibitor resistance in vivo, thus markedly inhibiting tumor growth and promoting tumor cell death in mice. These results identify a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy to overcome it.
Results of a randomized trial of HERMES-assisted vs non-HERMES-assisted laparoscopic antireflux surgery

Speech recognition technology is a recent development in minimally invasive surgery. This study was designed to assess the impact of HERMES on operating room efficiency and user satisfaction. Patients undergoing laparoscopic antireflux operations by surgeons experienced in minimally invasive surgery were randomized to HERMES-assisted or standard laparoscopic operations. The variables of interest were circulating nurse’s time spent adjusting devices that are voice-controlled by HERMES, number of adjustments to devices requested, and surgeon and nurse satisfaction measured on a scale from 1 (dissatisfied) to 10 (satisfied). A total of 30 cases were studied. In the non-HERMES cases, nurses were interrupted to make device adjustments an average of 15.3 times per case versus 0.33 times per case in the with-HERMES cases (p<0.01). The interruptions during the non-HERMES cases averaged 4.35 min per case versus 0.16 min per case in the with-HERMES cases (p=0.03). Average satisfaction scores for HERMES operations as opposed to non-HERMES operations were 9.2 versus 5.3 for nurses (p<0.01) and 9.0 versus 5.1 for surgeons (p<0.01). Physician and nurse acceptance of HERMES was very high because of the smoother interruption-free environment.
Effect of an Intermittent Weekly Dose of Human Parathyroid Hormone (1-34) on Osteoporosis: A Randomized Double-Masked Prospective Study Using Three Dose Levels

To test the effect of amino-terminal peptide 1–34 of human parathyroid hormone (hPTH (1–34)) as a possible bone anabolic agent in the treatment of osteoporosis, weekly subcutaneous injection of 50 units (L group), 100 units (M group) or 200 units (H group) of hPTH (1–34) was started in 220 patients with osteoporosis at 71 institutions randomly divided into three groups in a double-masked system. Lumbar spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) increased by 0.6%, 3.6% and 8.1% after 48 weeks in groups L, M and H respectively, responses in groups M and H being significantly higher than in L (p<0.05, Mann–Whitney U-test). Since the coefficient of variation for lumbar spine measurement stayed at 1–2.5%, increases of 3.6% and 8.1% appeared significant. Metacarpal BMD and cortical thickness measured by radiogrammetry did not change significantly. Serum calcium decreased in each group and serum phosphorus decreased in groups M and H. Urinary calcium/creatinine decreased at the 12th week in group H and at the 24th and 48th weeks in groups M and L. Serum 25(OH) vitamin D and 1,25(OH)2 vitamin D decreased in each group at the 48th week (p<0.05). Serum bone-type alkaline phosphatase was increased at the fourth week in groups H and M and decreased at the 48th week in group H. Urinary hydroxyproline, pyridinoline and deoxypyridinoline declined significantly in each group. Backache improved in 30–40% of each group. No serious adverse effects were found during the test period. Intermittent weekly injection of hPTH (1–34) increased lumbar BMD in osteoporosis, suggesting usefulness in the treatment of osteoporosis.
Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial.

To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid-modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy.



A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status.



Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001).



Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.