nils-herrmann/clean_scirepeval huggingface dataset:
Smoking withdrawal dynamics: I. Abstinence distress in lapsers and abstainers.

Smoking withdrawal reports from a clinical trial (n = 893) were submitted to hierarchical linear modeling as a cross-method replication of a heterogeneity approach to withdrawal measurement and to clarify the influence of postcessation smoking on symptom reports. Five individual difference parameters tapping distinct facets of withdrawal were derived: intercepts (mean severity), linear slope (direction and rate of change), quadratic trend (curvature), volatility (scatter) and, among lapsers, a cigarette coefficent (smoking-related deflections of symptoms). All parameters were highly variable across persons. Lapsers had more aversive symptom patterns than abstainers, and symptoms tended to be higherthan otherwise predicted on lapse days. These results reinforce the conclusion that withdrawal symptoms are highly variable and argue against discarding withdrawal data from participants who lapse.
Effect of hepatic or renal impairment on the pharmacokinetics of casopitant, a NK-1 receptor antagonist

Two studies were conducted in subjects with mild or moderate hepatic or renal impairment and subjects with normal organ function to evaluate the pharmacokinetics of casopitant and to assess its safety in these populations. A total of 26 subjects were enrolled in the hepatic impairment study and 18 subjects in the renal impairment study. All subjects received oral casopitant 100 mg once-daily for 5 days. Casopitant area under the concentration-time curve (AUC) increased 11% and 24% in subjects with mild or moderate hepatic impairment, respectively, on Day 1, compared with subjects with normal hepatic function; a similar increase was observed on Day 5. The AUC of the active major metabolite, GSK525060, was reduced 29% and 19% on Days 1 and 5, respectively, in subjects with moderate hepatic impairment, but not altered by mild hepatic impairment. Casopitant AUC increased 34% and 22% on Day 1 in subjects with mild or moderate renal impairment, respectively, and 28% and 11% on Day 5, respectively, compared with subjects with normal renal function. GSK525060 AUC was increased 17% and 24% on Days 1 and 5, respectively, in subjects with mild renal impairment; but did not significantly change in subjects with moderate renal impairment. Further age-adjusted analysis showed no meaningful effect of renal impairment on casopitant or GSK525060 AUC. Plasma protein binding of casopitant and GSK525060 was similar in all subjects. The pharmacokinetics of casopitant is not altered to a clinically significant extent in subjects with mild or moderate, hepatic or renal impairment. The impact of severe hepatic or renal impairment was not evaluated.
Quantitative analysis of the effects of donepezil on regional cerebral blood flow in Alzheimer’s disease by using an automated program, 3DSRT

Donepezil, an acetylcholinesterase inhibitor, has been reported to have an effect that improves cerebral blood flow (CBF) alongside its primary effect on memory function. The aim of this study was to investigate the effects of long-term, low-dose donepezil therapy on blood perfusion in Alzheimer’s disease (AD) by using a fully automated regional CBF quantification program named 3DSRT. Fifteen subjects with mild to moderate AD according to NINCDS/ADRDA criteria underwent 99mTc-ethylcysteinate dimer (ECD) brain perfusion single photon emission computed tomography (SPECT) twice with an interval of 55.1 ± 11.0 weeks. The dose of donepezil was fixed at 5 mg/day following the induction period (3 mg/day) of 2 weeks. Clinical efficacy of donepezil was assessed by using the Mini-Mental State Examination (MMSE). The results of SPECT imaging under exactly identical conditions were analyzed by 3DSRT, which enables us to perform a very objective assessment. Despite a decrease of the MMSE score from 20.9 ± 4.7 to 18.7 ± 5.7, CBF was increased in almost all cerebral areas except the left temporal segment. The increase was statistically significant in the left callosomarginal, right central, and bilateral pericallosal and lenticular nucleus segments. Thus far, no direct cerebrovascular effects have been reported for donepezil. We hypothesize that these CBF-promoting effects of donepezil might be related to increased neuronal activity and enhanced connection of neurons.
Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients

Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients. A column switching technique combined with high performance liquid chromatography (HPLC) enabled automated analyses of plasma for simultaneous determination of fluvoxamine, tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run. The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine, clomipramine, amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine. In patients under fluvoxamine monotherapy before comedication, plasma concentrations of fluvoxamine increased after administration of a tricyclic antidepressant, thus indicating bidirectional drug interactions. The inhibitory effects of fluvoxamine on the metabolism of classical antidepressants disappeared after discontinuation of concomitant fluvoxamine treatment within at least 1–2 weeks. The reported alterations in drug metabolism observed in depressed patients who were under fluvoxamine/tricyclic antidepressant comedication suggested that careful supervision and regular drug monitoring are necessary in such patients.
Variability in social reasoning: the influence of attachment security on the attribution of goals

Over the last half decade there has been a growing move to apply the methods and theory of cognitive development to questions regarding infants' social understanding. Though this combination has afforded exciting opportunities to better understand our species' unique social cognitive abilities, the resulting findings do not always lead to the same conclusions. For example, a growing body of research has found support for both universal similarity and individual differences in infants' social reasoning about others' responses to incomplete goals. The present research examines this apparent contradiction by assessing the influence of attachment security on the ability of university undergraduates to represent instrumental needs versus social-emotional distress. When the two varieties of goals were clearly differentiated, we observed a universally similar pattern of results (Experiments 1A/B). However, when the goals were combined, and both instrumental need and social-emotional distress were presented together, individual differences emerged (Experiments 2 and 3). Taken together, these results demonstrate that by integrating the two perspectives of shared universals and individual differences, important points of contact can be revealed supporting a deeper, more nuanced understanding of the nature of human social reasoning.
Hyperhidrosis treatment with bornaprine in the acute phase of spinal cord-injured patients

Original article.To test the use of bornaprine in the hyperhidrosis treatment in the acute phase of spinal cord-injured patients.Patients with acute spinal cord lesions in the Spinal Unit of Pietra Ligure, Savona, Italy.In 4 years, 12 patients have been treated, for a maximum period of 75 days, with dosages ranging from 2 to 4 mg day−1.Results:All of them reported long-lasting subjective benefits, without side effects, even after the interruption of the therapy.The bornaprine treatment, at 2 or 4 mg day−1 dosage, has been effective and safe to contrast hyperhidrosis, in the acute phase of spinal cord-injured patients. This positive experience would require additional trials and a larger number of cases to gain a more solid support.
Body Weight, Not Insulin Sensitivity or Secretion, May Predict Spontaneous Weight Changes in Nondiabetic and Prediabetic Subjects

Previous studies have found that high insulin sensitivity predicts weight gain; this association has not been confirmed. Our aim was to systematically analyze metabolic predictors of spontaneous weight changes.



In 561 women and 467 men from the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort (mean age 44 years, BMI range 19-44 kg/m(2), 9% impaired glucose tolerance) followed up for 3 years, we measured insulin sensitivity (by a euglycemic clamp) and β-cell function (by modeling of the C-peptide response to oral glucose and by acute insulin response to intravenous glucose).



Insulin sensitivity was similar in weight gainers (top 20% of the distribution of BMI changes), weight losers (bottom 20%), and weight stable subjects across quartiles of baseline BMI. By multiple logistic or linear regression analyses controlling for center, age, sex, and baseline BMI, neither insulin sensitivity nor any β-cell function parameter showed an independent association with weight gain; this was true in normal glucose tolerance, impaired glucose tolerance, and whether subjects progressed to dysglycemia or not. Baseline BMI was significantly higher in gainers (26.1 ± 4.1 kg/m(2)) and losers (26.6 ± 3.7 kg/m(2)) than in weight stable subjects (24.8 ± 3.8 kg/m(2), P<0.0001 for both gainers and losers). Baseline waist circumference (or equivalently, BMI or weight) was a positive, independent predictor of both weight gain and weight loss (odds ratio 1.48 [95% CI 1.12-1.97]) in men and (1.67 [1.28-2.12]) in women. In men only, better insulin sensitivity was an additional independent predictor of weight loss.



Neither insulin sensitivity nor insulin secretion predicts spontaneous weight gain. Individuals who have attained a higher weight are prone to either gaining or losing weight regardless of their glucose tolerance.
The Lung Image Database Consortium (LIDC) data collection process for nodule detection and annotation

The Lung Image Database Consortium (LIDC) is developing a publicly available database of thoracic computed tomography (CT) scans as a medical imaging research resource to promote the development of computer-aided detection or characterization of pulmonary nodules. To obtain the best estimate of the location and spatial extent of lung nodules, expert thoracic radiologists reviewed and annotated each scan. Because a consensus panel approach was neither feasible nor desirable, a unique two-phase, multicenter data collection process was developed to allow multiple radiologists at different centers to asynchronously review and annotate each CT scan. This data collection process was also intended to capture the variability among readers.



Four radiologists reviewed each scan using the following process. In the first or "blinded" phase, each radiologist reviewed the CT scan independently. In the second or "unblinded" review phase, results from all four blinded reviews were compiled and presented to each radiologist for a second review, allowing the radiologists to review their own annotations together with the annotations of the other radiologists. The results of each radiologist's unblinded review were compiled to form the final unblinded review. An XML-based message system was developed to communicate the results of each reading.



This two-phase data collection process was designed, tested, and implemented across the LIDC. More than 500 CT scans have been read and annotated using this method by four expert readers; these scans either are currently publicly available at http://ncia.nci.nih.gov or will be in the near future.



A unique data collection process was developed, tested, and implemented that allowed multiple readers at distributed sites to asynchronously review CT scans multiple times. This process captured the opinions of each reader regarding the location and spatial extent of lung nodules.
Effects of polydextrose supplementation on different faecal parameters in healthy volunteers.

The beneficial effects of prebiotics on bowel health were thoroughly investigated. The aim of the study was to show prebiotic effects of polydextrose (PDX). A placebo-controlled, randomized intervention study with PDX supplementation (8 g/day) was conducted in 45 healthy subjects. The effects of PDX on stool weight, orofaecal transit time, consistency of stool (Bristol stool form scale), short-chain fatty acid production, pH value, neutral sterol and bile acid excretion and faecal microbiota were evaluated. It was found that supplementation of PDX shortened the orofaecal transit time significantly. Furthermore, ingestion of PDX resulted in a decreased pH value and in significant changes in bile acid and neutral sterol excretion. PDX had no effects on stool weight, concentrations of the main short-chain fatty acids (acetate, propionate) and faecal contents of lactic acid bacteria and bifidobacteria. In conclusion, PDX is able to shorten the orofaecal transit time and to improve stool consistency in subjects suffering from constipation.
Oncoproteomic Analysis Reveals Co-Upregulation of RELA and STAT5 in Carboplatin Resistant Ovarian Carcinoma

Ovarian cancer is one of the most lethal types of female malignancy. Although most patients are initially responsive to platinum-based chemotherapy, almost all develop recurrent chemoresistant tumors and succumb to their diseases. Elucidating the pathogenesis underlying drug resistance is fundamental to the development of new therapeutics, leading to improved clinical outcomes in these patients.



We compared the proteomes of paired primary and recurrent post-chemotherapy ovarian high-grade serous carcinomas from nine ovarian cancer patients using CIEF/Nano-RPLC coupled with ESI-Tandem MS. As compared to their primary tumors, more than half of the recurrent tumors expressed higher levels of several proteins including CP, FN1, SYK, CD97, AIF1, WNK1, SERPINA3, APOD, URP2, STAT5B and RELA (NF-kappaB p65), which were also validated by quantitative RT-PCR. Based on shRNA screening for the upregulated genes in in vitro carboplatin-resistant cells, we found that simultaneous knockdown of RELA and STAT5B was most effective in sensitizing tumor cells for carboplatin treatment. Similarly, the NF-kappaB inhibitor, BMS-345541, and the STAT5 inhibitor, Dasatinib, significantly enhanced cell sensitivity to carboplatin. Moreover, both RELA and STAT5 are known to bind to the promoter region of Bcl-X, regulating its promoter activity. In this regard, augmented Bcl-xL expression was detected in carboplatin-resistant cells. Combined ectopic expression of RELA and STAT5B enhanced Bcl-xL promoter activity while treatment with BMS-345541 and Dasatinib decreased it. Chromatin immunoprecipitation of the Bcl-X promoter region using a STAT5 antibody showed induction of RELA and STAT5 DNA-binding segments both in naïve cells treated with a high concentration of carboplatin as well as in carboplatin-resistant cells.



Proteomic analysis identified RELA and STAT5 as two major proteins associated with carboplatin resistance in ovarian tumors. Our results further showed that NF-kappaB and STAT5 inhibitor could sensitize carboplatin-resistant cells and suggest that such inhibitors can be used to benefit patients with carboplatin-resistant recurrent ovarian cancer.
Pharmacotherapy for self-injurious behavior: Preliminary tests of the D1 hypothesis

1. The D1 dopamine hypersensitivity model of self-injurious behavior leads to a testable clinical hypothesis: that the mixed D1/D2 dopamine antagonist fluphenazine may improve the symptoms of self-injurious patients. 2. The hypothesis was tested in an open pilot trial in six patients and a partially controlled trial in nine patients. 3. Some degree of clinical improvement was observed in eleven of the fifteen. 4. The trials represent a partial affirmation of the D1 hypothesis. However, it is also clear that conventional methodology for psychopharmacologic research is inappropriate for the proper clinical evaluation of self-injurious patients. The proper method should include the following elements: i) An epidemiologically representative sample ii) A naturalistic study environment iii) A longitudinal design with long-term follow-up iv) Concurrent behavioral ratings using direct observations and a reliable, treatment-sensitive rating scale. 5. Before subjects enter a clinical trial of an experimental medication, a neuropsychiatric differential diagnosis should be applied to limit the diversity of the sample.
Rice policosanol does not have any effects on blood coagulation factors in hypercholesterolemic patients.

Policosanol is an agent that includes mixtures of aliphatic primary alcohols extracted primarily from sugercane wax. Policosanol has been shown to lower total and LDL cholesterol in animal models, healthy volunteers and hypercholesterolemic patients. However, these findings have been challanged recently. Up to now, there has been no study investigating the effects ofpolicosanol on blood coagulation factors. This study investigated the effects of rice policosanol (Oryza sp.) 10 mg/day on blood coagulation factors in 66 hypercholesterolemic patients of both sexes aged 20 to 78 years in a single center, randomized, double-blind, placebo-controlled, crossover trial. After an 8-week run-in period in which patients were placed on therapeutic lifestyle changes, in particular a cholesterol-lowering diet, they were randomly assigned to receive rice policosanol 10 mg tablets or placebo tablets once daily with the evening meal for 8 weeks. During next 8 weeks those receiving policosanol during the first 8 weeks, received placebo and those taking placebo during the first 8 weeks, received policosanol. Plasma fibrinogen, factors VII, VIII, XII and XIII were measured before and after the treatment. Rice policosanol treatment did not change significantly neither fibrinogen nor factors VII, VIII, XII and XIII.
A real-world stepped wedge cluster randomized trial of practice facilitation to improve cardiovascular care

Practice facilitation has been associated with meaningful improvements in disease prevention and quality of patient care. Using practice facilitation, the Improved Delivery of Cardiovascular Care (IDOCC) project aimed to improve the delivery of evidence-based cardiovascular care in primary care practices across a large health region. Our goal was to evaluate IDOCC's impact on adherence to processes of care delivery.



A pragmatic stepped wedge cluster randomized trial recruiting primary care providers in practices located in Eastern Ontario, Canada ( Participants were randomly assigned by region to one of three steps. Practice facilitators were intended to visit practices every 3-4 (year 1-intensive) or 6-12 weeks (year 2-sustainability) to support changes in practice behavior. The primary outcome was mean adherence to indicators of evidence-based care measured at the patient level. Adherence was assessed by chart review of a randomly selected cohort of 66 patients per practice in each pre-intervention year, as well as in year 1 and year 2 post-intervention.



Eighty-four practices (182 physicians) participated. On average, facilitators had 6.6 (min: 2, max: 11) face-to-face visits with practices in year 1 and 2.5 (min: 0 max: 10) visits in year 2. We collected chart data from 5292 patients. After adjustment for patient and provider characteristics, there was a 1.9 % (95 % confidence interval (CI): -2.9 to -0.9 %) and 4.2 % (95 % CI: -5.7 to -2.6 %) absolute decrease in mean adherence from baseline to intensive and sustainability years, respectively.



IDOCC did not improve adherence to best-practice guidelines. Our results showed a small statistically significant decrease in mean adherence of questionable clinical significance. Potential reasons for this result include implementation challenges, competing priorities in practices, a broad focus on multiple chronic disease indicators, and use of an overall index of adherence. These results contrast with findings from previously reported facilitation trials and highlight the complexities and challenges of translating research findings into clinical practice.
Pharmacist intervention program to enhance hypertension control: a randomised controlled trial

Studies have demonstrated that hypertension remains inadequately managed throughout the world, with lack of adherence to BP-lowering medication being a major factor. The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control.  This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre, Covilhã, located in the Eastern Central Region of Portugal.  This report evaluates the pharmacist’s interventions during a prospective randomised controlled trial, from July 2009 to June 2010. Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were randomly allocated either to a control group (no pharmaceutical care) or to an intervention group (quarterly follow-up by a hospital pharmacist during a 9-month period). The pharmacist interventions, aimed to increase medication adherence and blood pressure control, involved educational interventions and counselling tips directed to the patient.  Systolic blood pressure, diastolic blood pressure and blood pressure control (according to JNC 7 guidelines) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures. Blood pressure measurements were performed by blinded nurses. Medication adherence was also evaluated, using a validated questionnaire at baseline and at the end of investigation.  A total of 197 hypertensive patients were randomly assigned to the study (99 in the control group and 98 in the intervention group). Although there were no significant differences (P > 0.05) in both groups concerning mean age, gender, body mass index, and antihypertensive pharmacotherapy, blood pressure control was higher in the intervention group (P = 0.005) at the end of the study. Significant lower systolic blood pressure (−6.8 mmHg, P = 0.006) and diastolic blood pressure (−2.9 mmHg, P = 0.020) levels were observed in the intervention group. Medication adherence was also significantly higher in the intervention group at the end of the study (74.5% vs. 57.6%, P = 0.012).Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents.