nils-herrmann/clean_scirepeval huggingface dataset:
Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients

Atypical antipsychotics induce pre-diabetic symptoms in some but not all patients, characterized most notably by elevated weight. The side effect profiles of the various drugs in the class differ, however, raising the possibility of drug-specific mechanisms for similar side effects. We used physiogenomic analysis, an approach previously employed to study the genetics of drug and diet response, to discover and compare genetic associations with weight profiles observed in patients treated with olanzapine and risperidone as an approach to unraveling contrasting mechanistic features of both drugs. A total of 29 single nucleotide polymorphisms (SNPs) were selected from 13 candidate genes relevant to two potential pharmacological axes of psychotropic-related weight profiles, appetite peptides and peripheral lipid homeostasis. We applied physiogenomic analysis to a cross-section of 67 and 101 patients being treated with olanzapine and risperidone, respectively, and assessed genetic associations with the weight profiles. Weight profiles in patients treated with olanzapine were significantly associated with SNPs in the genes for apolipoprotein E, apolipoprotein A4 and scavenger receptor class B, member 1. Weight profiles in patients treated with risperidone were significantly associated with SNPs in the genes for leptin receptor, neuropeptide Y receptor Y5 and paraoxonase 1. These results are consistent with contrasting mechanisms for the weight profile of patients treated with these drugs. Genes associated with olanzapine weight profiles may be related to peripheral lipid homeostatic axes, whereas those associated with risperidone's may be related to brain appetite peptide regulation. Future physiogenomic studies will include neurotransmitter receptor SNPs and validation in independent samples.
Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD).

The Health of the Nation Outcomes Scales (HoNOS) have been developed to measure outcomes in people with mental health problems.



Frequent impaired social functioning, problems with communication and associated physical conditions meant that a bespoke instrument was needed for people with learning disabilities. We describe the development of the Health of the Nation Outcomes Scales for People with Learning Disabilities (HoNOS-LD).



HoNOS-LD was piloted at 26 sites. Two raters, at two points in time, rated 372 subjects. Analysis determined acceptability, ease of use, interrater reliability, sensitivity to change and reliability with the Aberrant Behavior Checklist (ABC).



The resulting 18-item instrument demonstrated good reliability and validity characteristics and is generally acceptable to clinicians.



HoNOS-LD is an appropriate instrument for measuring outcome in people with learning disabilities with additional mental health needs.
Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes

The pharmacokinetic and pharmacodynamic properties of biphasic insulin aspart (BIAsp 30) (30% soluble, 70% protaminated insulin aspart [IAsp]) and insulin glargine (IGlarg) were compared. Twelve people with type 2 diabetes took part in two 24-h isoglycaemic clamp studies, 1 week apart. Patients were randomised to treatment with 0.5 U/kg of BIAsp 30 (0.25 U/kg at 08.30 h and 0.25 U/kg at 20.30 h) or 0.50 U/kg IGlarg at 08.30 h. Both insulins were given by subcutaneous injection into the anterior abdominal wall. The plasma glucose, glucose infusion rates, plasma insulin and C-peptide concentrations were measured. All 12 patients were men; mean (±SD) age was 58.8 (8.9) years, BMI 31.0 (3.0) kg/m2 and HbA1c 7.1 (0.6)%. Plasma glucose was constant throughout the 24-h clamp period. After each injection of BIAsp 30, glucose infusion rates increased, reaching a distinct peak approximately 3–5 h after injection. A much flatter postinjection profile was observed following IGlarg administration. Plasma insulin concentrations rose rapidly after each injection of BIAsp 30, reaching a distinct peak after approximately 2–3 h. A flatter plasma insulin profile reached a plateau approximately 6–16 h after IGlarg administration. Plasma C-peptide fell below baseline after both injections of BIAsp 30 but remained unaltered after IGlarg injection. The pharmacodynamic and pharmacokinetic profiles were 34 and 28%, respectively, higher following equivalent doses (0.5 U/kg) of BIAsp 30 given as two split doses than following IGlarg given as a single daily dose.
Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity

Invasive ductal carcinomas (IDC) of the breast with the triple negative phenotype (steroid hormone receptor absent, negative HER2 status) are characterized by poor clinical outcome. Additional tumor markers might allow identification of patients at higher risk. We evaluated clinical and biological features of 284 consecutive patients with pT1-3, pN1-3 M0 triple-negative IDC. Median follow-up was 70 months (interquartile range 59–94 months). Statistically significant worse disease-free and overall survival were observed in multivariate analysis, for patients with EGFR immunoreactivity in ≥50% invasive tumor cells (HR 2.39, 95% CI, 1.32–4.34, P = 0.004 for DFS; HR 2.34, 95% CI, 1.20–4.59 P = 0.01 for OS). Age ≥ 70 years and PVI were additional independent predictors of reduced overall survival. EGFR immunoreactivity significantly correlates with worse prognosis in patients with triple-negative IDC, supporting further studies on the correlation between the degree of EGFR expression and outcome of triple negative breast cancer.
Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer.

To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer.



Forty-eight patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response.



Eight of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T(1) tumors more frequently exhibited clinical complete response (P = 0.05) and showed a trend to exhibit pCR (P = 0.07). Five (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR (n = 3) versus nonresponse (n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T(4) stage (P = 0.02) and express basal markers (P < 0.00001), growth factors, and growth factor receptors. Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate (50% versus 97%; P = 0.001).



Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen.
Comparison of MMF efficacy and safety in paediatric vs. adult renal transplantation: subgroup analysis of the randomised, multicentre FDCC trial.

Mycophenolate mofetil (MMF) is widely used for immunosuppressive therapy in renal transplantation, but comparative data regarding efficacy and safety in paediatric vs. adult kidney allograft recipients in one and the same study are lacking.



We therefore performed this subgroup analysis of the FDCC trial, a 12-month, prospective, randomised study, comparing fixed-dose (FD) with concentration-controlled (CC) MMF dosing in paediatric and adult renal transplant recipients. Sixty-two paediatric and 839 adult de novo patients in 19 countries were randomised 1:1 to receive fixed-dose or concentration-controlled MMF therapy in combination with calcineurin inhibitors and corticosteroids.



Both patient and allograft survival proved to be excellent in paediatric patients (98.4% and 90.3%) and adults (96.8% and 95.0%). The rates of biopsy-proven acute rejections (BPAR) and treated acute rejection episodes (ARE) were comparable between paediatric (12.9% and 17.7%) and adult patients (15.5% and 20.7%). Transplant function at 12 months post-transplant was similar in paediatric (67.8 ± 45.6 mL/min/1.73 m2;) and adult recipients (64.7 ± 23.3 mL/min/1.73 m2;). Children < 6 years (n = 10) exhibited a numerically higher frequency of leucocytopaenia (20%), diarrhoea (40%) and weight loss (10%) than older children (6-18 years; 5.8%, 28.8% and 1.9%) and adults (16.1%, 24.7% and 1.5%). On the whole, the percentage of patients who experienced adverse events causing interruption of MMF therapy were numerically lower in children (4.8%) than in adults (12.5%).  The overall efficacy and tolerability of MMF appear to be comparable between paediatric and adult patients. Further studies are needed to validate these results.
Psychomotor retardation is a scar of past depressive episodes, revealed by simple cognitive tests

The cumulative duration of depressive episodes, and their repetition, has a detrimental effect on depression recurrence rates and the chances of antidepressant response, and even increases the risk of dementia, raising the possibility that depressive episodes could be neurotoxic. Psychomotor retardation could constitute a marker of this negative burden of past depressive episodes, with conflicting findings according to the use of clinical versus cognitive assessments. We assessed the role of the Retardation Depressive Scale (filled in by the clinician) and the time required to perform the neurocognitive d2 attention test and the Trail Making Test (performed by patients) in a sample of 2048 depressed outpatients, before and after 6 to 8 weeks of treatment with agomelatine. From this sample, 1140 patients performed the TMT-A and -B, and 508 performed the d2 test, at baseline and after treatment. At baseline, we found that with more past depressive episodes patients had more severe clinical level of psychomotor retardation, and that they needed more time to perform both d2 and TMT. When the analyses were performed again after treatment, and especially when the analyses were restricted to patients with clinical remission, the cognitive tests were the only ones correlated with past depressive episodes. Psychomotor retardation tested at a cognitive level was therefore systematically revealing the burden of past depressive episodes, with an increased weight for patients with less remaining symptoms. If prospectively confirmed, interventions such as cognitive remediation therapy could benefit from a more specific focus on neurocognitive retardation.
Collaborative modeling and negotiation

New problems in negotiation call for a new framework of solutions. Negotiation management, one such framework, has at its heart the application of computer models and related technology to a collaborative effort at dispute resolution. In this paradigm, negotiation is treated as a communicative and knowledge-intensive group problem-solving process. Easily accessible techniques are being developed for modeling both the process and substance of negotiation. In addition, tools are being designed for negotiators to use in risk and decision analysis, optimization, and precedent analysis. This paper outlines a synthesis of these elements in an integrated computer environment for negotiation management.
Forgiving the September 11th terrorists: associations with coping, psychological distress, and religiosity.

Two studies examined how non-interpersonal forgiveness (when there is no social relationship between the transgressor and forgiver) related to coping and involuntary responses to stress, psychological distress, and religiosity. Three to six weeks after September 11th, 2001, forgiveness had non-linear associations with other responses to the terrorist attacks. Among college students (N=488), those who were trying or had forgiven (pro-forgiveness) the terrorists reported less involuntary engagement, more primary and secondary control coping, and more meaning finding than those who were unsure about forgiveness (ambivalent) and those who did not believe the perpetrators should be forgiven (anti-forgiveness). Ambivalent students reported the most distress, even after controlling for religion. Anti-forgiveness students reported less religiosity than ambivalent and pro-forgiveness students. Most findings were consistent among middle schoolers (N=154), particularly regarding psychological distress and responses to stress. Also, forgiveness of strangers for acts against one's community functioned separately from religion.
Quality of life of Danish women: Population-based norms for the EORTC QLQ-C30

The aim of this study was to derive population-based norms for women completing the EORTC QLQ-C30 version 1 which is designed for use with patients who have cancer. The study was conducted using two different questionnaires: one designed for use in female patients with breast cancer, the other for those with gynaecological cancers, but both including the EORTC QLQ-C30. The women were drawn from the Danish Central Population Register without knowledge of their health status and divided at random between the two questionnaires. All procedures for collecting data were identical. The response rate for those receiving the gynaecological cancer (GS) questionnaire was 49% and it was 71% for the breast cancer (BS) questionnaire. Detailed comparison between the two samples revealed several EORTC QLQ-C30 items showing a clear difference in distribution of scores between them. Because of this and the possible bias due to the relative low age-related response rate in GS, only the results from the BS are used for constructing norms. The norms cover all 30 single items on the EORTC QLQ-C30 and the nine derived scales, for women in four 10-year age groups commencing at 30 years and for those aged 70-75. Clear trends in, for example, declining ability to undertake strenuous activity are illustrated and quantified. Levels of certain symptoms, such as pain, are surprisingly high although it is recognized that the population sampled will contain a proportion of women with active disease including cancer. We recommend the use of these norms both as an aid to the clinical assessment of an individual patient, and to assist in the interpretation of clinical trial and longitudinal quality of life data. As a secondary result, we note that a population-based sample will have a lower response rate to a questionnaire with more questions, especially if many of these extra questions are on sexual issues.
Quality versus quantity: acquisition of coping skills following computerized cognitive-behavioral therapy for substance use disorders.

To evaluate the changes over time in quality and quantity of coping skills acquired following cognitive behavioral therapy (CBT), and examine potential mediating effects on substance use outcomes.



A randomized controlled trial (RCT) evaluating the effectiveness of a computerized version of CBT (CBT4CBT) as an adjunct to standard out-patient treatment over an 8-week period.



Data were collected from individuals seeking treatment for substance dependence in an out-patient community setting.



Fifty-two substance abusing individuals (50% African American), with an average age of 42 years, and a majority reporting cocaine as their primary drug of choice.



Participants' responses to behavioral role-plays of situations associated with high risk for drug and alcohol use were audio-taped and rated independently to assess their coping responses.



There were statistically significant increases in mean ratings of the quality of participants' coping responses for those assigned to CBT4CBT compared to treatment as usual, and these differences remained significant 3 months after treatment completion. Moreover, quality of coping responses mediated the effect of treatment on participants' duration of abstinence during the follow-up period.



These findings suggest that assignment to the computerized CBT program improved participants' coping skills, as measured by independent ratings of a role-playing task. It is also the first study to test and support quality of coping skills acquired as a mediator of the effect of CBT for substance use.
On-demand treatment with alverine citrate/simeticone compared with standard treatments for irritable bowel syndrome: results of a randomised pragmatic study

In routine practice, irritable bowel syndrome (IBS) symptoms are often difficult to be relieved and impair significantly patients' quality of life (QoL). A randomised, double-blind, placebo-controlled study has shown the efficacy of alverine citrate/simeticone (ACS) combination for IBS symptom relief.



As IBS symptoms are often intermittent, this pragmatic study was designed to compare the efficacy of an on-demand ACS treatment vs. that of usual treatments.



Rome III IBS patients were enrolled by 87 general practitioners who were randomly allocated to one of two therapeutic strategies: on-demand ACS or usual treatment chosen by the physician. The primary outcome measure was the improvement of the IBSQoL score between inclusion and month 6.



A total of 436 patients (mean age: 54.4 years; women: 73.4%) were included, 222 in the ACS arm and 214 patients in the usual treatment arm, which was mainly antispasmodics. At 6 months, improvement of IBSQoL was greater with ACS than with the usual treatment group (13.8 vs. 8.4; p < 0.0008). The IBS-severity symptom score (IBS-SSS) was lower with ACS than in the usual treatment arm with a mean (SE) decrease of 170.0 (6.6) vs. 110.7 (6.7), respectively (p = 0.0001). An IBS-SSS < 75 was more frequent in the ACS group (37.7% vs. 16.0%; p < 0.0001). Improvement of both abdominal pain and bloating severity was also greater with the on-demand ACS treatment, which was associated with both lower direct and indirect costs.



After 6 months, on-demand ACS treatment led to a greater improvement of QoL, reduced the burden of the disease and was more effective for IBS symptom relief than usual treatments.
Introducing Computational Thinking to K-5 in a French Context

Computational Thinking (CT) is beginning to be accepted as one of the fundamental 21st century skills for everyone. Curricula and environments are being developed for different group ages, from kindergarten to university, in several countries. As part of this global tendency, France has recently taken political decisions to integrate CT Education (CTE) in the mandatory national curriculum. However, many challenges remain until a full implementation is achieved. In this paper we report on a partnership between a university, local elementary schools and the county Ministry of Education (MoE), and on an exploratory project of introducing CT to K-5 students. This project has provided us with valuable feedback on the specifics of integrating CT in a national curriculum and the creation of a partnership and a community. These lessons will be used in the following stage of scaling up to more elementary schools in the entire county, but also addressing other school levels such as kindergarten, middle school and high school.
A pilot study for mood-based classification of TV programmes

We report results from a pilot study on mood-based classification of TV programmes. Short video clips from various programmes were labelled on three mood axes, giving the subjects opinion of how happy, serious and exciting each clip was. This data was used for mood classification based on automatically extracted audio and video features in a machine learning framework. Attention was given to the challenges of dealing with a small dataset as commonly obtained from pilot studies, showing that a thorough evaluation was possible and produced useful results. Introducing a new feature based on face detection and combining it with other signal processing features led to good classification accuracies. These lay between 85% and 100% for the most simple setting, and still reached more than 70% accuracy when a finer three point mood scale was used. Overall, the results were promising and showed that automatic mood classification of video material is possible. Moods can therefore be used as additional metadata to facilitate search in large archives.
Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study

To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions.



This open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086). CT-P13 (3 mg/kg) was administered intravenously every 8 weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102 weeks (maintenance group) and for those who received RP for 54 weeks and then switched to CT-P13 (switch group).



Overall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively).



Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years.