nils-herrmann/clean_scirepeval huggingface dataset:
Validation of the Japanese Severe Respiratory Insufficiency Questionnaire in hypercapnic patients with noninvasive ventilation.

The Severe Respiratory Insufficiency (SRI) Questionnaire was originally developed in German to assess health-related quality of life (HRQL) and was validated as a multidimensional instrument with high psychometric properties in chronic hypercapnic respiratory failure (CHRF) patients receiving noninvasive ventilation (NIV). We aimed to investigate the intercultural adaptation of the Japanese SRI Questionnaire and whether it is a reliable and valid HRQL questionnaire to administer to those patients.



The SRI Questionnaire was adapted to Japanese using a translation and back-translation procedure, followed by equivalency assessment. It was validated in 56 stable outpatients receiving NIV for CHRF, primarily due to chronic obstructive pulmonary disease (COPD) and/or pulmonary tuberculosis sequelae.



Examination of the frequency distribution of the Japanese SRI Questionnaire showed that the subscales and summary were approximately normally distributed and well balanced. There were no significant differences in SRI scores between patients with COPD and pulmonary tuberculosis sequelae. Cronbach׳s α values representing internal consistency of seven SRI subscales ranged from 0.56 to 0.80; attendant symptoms and sleep had the lowest values. Cronbach׳s α value was 0.92 for the SRI summary. The SRI summary score was significantly related to all eight subscales of the Medical Outcomes Study 36-item short form, with correlation coefficients of 0.41-0.66.



The Japanese SRI Questionnaire was produced using a standardized procedure and an equivalency study. It has high psychometric properties with internal consistency and concurrent validity. The Japanese SRI Questionnaire can be used to assess HRQL in patients on NIV for CHRF.
Bad dream frequency in older adults with generalized anxiety disorder: prevalence, correlates, and effect of cognitive behavioral treatment for anxiety.

This study investigated the relation between generalized anxiety disorder (GAD) and frequency of bad dreams in older adults. A secondary analysis from a randomized clinical trial comparing cognitive behavioral therapy (CBT) for anxiety to enhanced usual care (EUC) assessed bad dream frequency at baseline, post treatment (3 months), and at 6, 9, 12, and 15 months. Of 227 participants (mean age = 67.4), 134 met GAD diagnostic criteria (CBT = 70, EUC = 64), with the remaining 93 serving as a comparison group. Patients with GAD had significantly more bad dreams than those without, and bad dream frequency was significantly associated with depression, anxiety, worry, and poor quality of life. CBT for anxiety significantly reduced bad dream frequency at post treatment and throughout follow up compared to EUC.
Over-Expression of hNGF in Adult Human Olfactory Bulb Neural Stem Cells Promotes Cell Growth and Oligodendrocytic Differentiation

The adult human olfactory bulb neural stem/progenitor cells (OBNC/PC) are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases, however effective delivery of NGF into the CNS parenchyma is still challenging due mainly to its limited ability to cross the blood-brain barrier, and intolerable side effects if administered into the brain ventricular system. An effective method to ensure delivery of NGF into the parenchyma of CNS is the genetic modification of NSC to overexpress NGF gene. Overexpression of NGF in adult human OBNSC is expected to alter their proliferation and differentiation nature, and thus might enhance their therapeutic potential. In this study, we genetically modified adult human OBNS/PC to overexpress human NGF (hNGF) and green fluorescent protein (GFP) genes to provide insight about the effects of hNGF and GFP genes overexpression in adult human OBNS/PC on their in vitro multipotentiality using DNA microarray, immunophenotyping, and Western blot (WB) protocols. Our analysis revealed that OBNS/PC-GFP and OBNS/PC-GFP-hNGF differentiation is a multifaceted process involving changes in major biological processes as reflected in alteration of the gene expression levels of crucial markers such as cell cycle and survival markers, stemness markers, and differentiation markers. The differentiation of both cell classes was also associated with modulations of key signaling pathways such MAPK signaling pathway, ErbB signaling pathway, and neuroactive ligand-receptor interaction pathway for OBNS/PC-GFP, and axon guidance, calcium channel, voltage-dependent, gamma subunit 7 for OBNS/PC-GFP-hNGF as revealed by GO and KEGG. Differentiated OBNS/PC-GFP-hNGF displayed extensively branched cytoplasmic processes, a significant faster growth rate and up modulated the expression of oligodendroglia precursor cells markers (PDGFRα, NG2 and CNPase) respect to OBNS/PC-GFP counterparts. These findings suggest an enhanced proliferation and oligodendrocytic differentiation potential for OBNS/PC-GFP-hNGF as compared to OBNS/PC-GFP.
Evaluation of a self-management patient education program for patients with chronic heart failure undergoing inpatient cardiac rehabilitation: study protocol of a cluster randomized controlled trial

Chronic heart failure requires a complex treatment regimen on a life-long basis. Therefore, self-care/self-management is an essential part of successful treatment and comprehensive patient education is warranted. However, specific information on program features and educational strategies enhancing treatment success is lacking. This trial aims to evaluate a patient-oriented and theory-based self-management educational group program as compared to usual care education during inpatient cardiac rehabilitation in Germany.



The study is a multicenter cluster randomized controlled trial in four cardiac rehabilitation clinics. Clusters are patient education groups that comprise HF patients recruited within 2 weeks after commencement of inpatient cardiac rehabilitation. Cluster randomization was chosen for pragmatic reasons, i.e. to ensure a sufficient number of eligible patients to build large-enough educational groups and to prevent contamination by interaction of patients from different treatment allocations during rehabilitation. Rehabilitants with chronic systolic heart failure (n = 540) will be consecutively recruited for the study at the beginning of inpatient rehabilitation. Data will be assessed at admission, at discharge and after 6 and 12 months using patient questionnaires. In the intervention condition, patients receive the new patient-oriented self-management educational program, whereas in the control condition, patients receive a short lecture-based educational program (usual care). The primary outcome is patients' self-reported self-management competence. Secondary outcomes include behavioral determinants and self-management health behavior (symptom monitoring, physical activity, medication adherence), health-related quality of life, and treatment satisfaction. Treatment effects will be evaluated separately for each follow-up time point using multilevel regression analysis, and adjusting for baseline values.



This study evaluates the effectiveness of a comprehensive self-management educational program by a cluster randomized trial within inpatient cardiac rehabilitation in Germany. Furthermore, subgroup-related treatment effects will be explored. Study results will contribute to a better understanding of both the effectiveness and mechanisms of a self-management group program as part of cardiac rehabilitation.
Cyclic GMP and Cilia Motility

Motile cilia of the lungs respond to environmental challenges by increasing their ciliary beat frequency in order to enhance mucociliary clearance as a fundamental tenant of innate defense. One important second messenger in transducing the regulable nature of motile cilia is cyclic guanosine 3',5'-monophosphate (cGMP). In this review, the history of cGMP action is presented and a survey of the existing data addressing cGMP action in ciliary motility is presented. Nitric oxide (NO)-mediated regulation of cGMP in ciliated cells is presented in the context of alcohol-induced cilia function and dysfunction.
Cardiovascular and gastrointestinal function of IRAG

Signalling by NO/cGMP is very important for regulation of vascular tone and gastrointestinal motility. One important signalling pathway of cGMP-dependent protein kinase type I (cGKI) is mediated by IRAG (IP3 Receptor Associated cGKI substrate) which is highly expressed in smooth muscle of cardiovascular and gastrointestinal tissue. In order to elucidate the physiological role of IRAG we generated IRAG knockout mice by targeted deletion of exon 3. These mice show an enlarged gastrointestinal tract including pylorus stenosis.
Language choice for safety critical applications

The programming languages currently most popular among software engineers for writing safety critical applications are C and, more recently, C++. The Ada language has been designed with software safety in mind. Although Ada is not perfect concerning safety critical programming, it is far better than C or C++. There have been definitions of subsets of C for safety critical applications, such as MISRA C. Similarly, there are several attempts at defining a safe subset of C++, including MISRA C++ and the Joint Strike Fighter (JSF) Avionics C++ coding standards. The most commonly used safety critical subset of Ada is SPARK. SPARK provides a statically provable fully deterministic subset of Ada. The C and C++ safety critical subsets attempt to achieve a level of safety similar to the full Ada language. That attempt generally fails. This paper concentrates on a comparing the C++ language, including portions of the JSF C++ standard and those features inherited from C, with the full Ada language.
Does the method of treatment affect the outcome in soft-tissue sarcomas of the adductor compartment?

We have investigated the significance of the method of treatment on the oncological and functional outcomes and on the complications in 184 patients with soft-tissue sarcomas of the adductor compartment managed at three international centres. The overall survival at five years was 65% and was related to the grade at diagnosis and the size of the tumour. There was no difference in overall survival between the three centres. There was, however, a significant difference in local control with a rate of 28% in Centre 1 compared with 10% in Centre 2 and 5% in Centre 3. The overall mean functional score using the Toronto Extremity Salvage Score in 70 patients was 77% but was significantly worse in patients with wound complications or high-grade tumours. The scores were not affected by the timing of radiotherapy or the use of muscle flaps. This large series of soft-tissue sarcomas of the adductor compartment has shown that factors influencing survival do not vary across the international boundaries studied, but that methods of treatment affect complications, local recurrence and function.
Exploring the reliability of the modified rankin scale.

The modified Rankin Scale (mRS) is the most prevalent outcome measure in stroke trials. Use of the mRS may be hampered by variability in grading. Previous estimates of the properties of the mRS have used diverse methodologies and may not apply to contemporary trial populations. We used a mock clinical trial design to explore inter- and intraobserver variability of the mRS.



Consenting patients with stroke attending for outpatient review had the mRS performed by 2 independent assessors with pairs of assessors selected from a team of 3 research nurses and 4 stroke physicians. Before formal assessment, interviewers estimated disability based only on initial patient observation. Each patient was then randomized to undergo the mRS using standard assessment or a prespecified structured interview. The second interviewer in the pair reassessed the patient using the same method blinded to the colleague's score. For each patient assessed, one rater was randomly assigned to video record their interview. After 3 months, this interviewer reviewed and regraded their original video assessment.



Across 100 paired assessments, interobserver agreement was moderate (k=0.57). Intraobserver variability was good (k=0.72) but less than would be expected from previous literature. Forty-nine assessments were performed using the structured interview approach with no significant difference between structured and standard mRS. Researchers were unable to reliably predict mRS from initial limited patient assessment (k=0.16).



Despite availability of training and structured interview, there remains substantial interobserver variability in mRS grades awarded even by experienced researchers. Additional methods to improve mRS reliability are required.
Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer

The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 53.8% (95% CI=39.5–67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 50.0% (95% CI=35.8–64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3–21.0) before, 3.2% (95% CI=1.9–5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1–22.5) before, 3.2% (95% CI=1.8–5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.
Building a MARC-to-OLAC crosswalk: repurposing library catalog data for the language resources community

The Open Language Archives Community (OLAC) is an international partnership of institutions which are building a network of interoperating repositories and services to create a worldwide virtual library of language resources (that is, resources that document, describe, or develop the more than 7,000 known languages of the world). OLAC uses a community-specific refinement of qualified Dublin Core [http://www.language-archives.org/OLAC/metadata.htm] along with a community-specific refinement of the OAI Protocol for Metadata Harvesting [http://www.language-archives.org/OLAC/repositories.htm] to maintain an aggregated catalog of the holdings of the 35 participating archives. OLAC recognizes that the language resources of interest to the community come not only from sources within the community but also from many sources outside the community. This poster describes one approach we have developed for addressing this issue, namely, a crosswalk that transforms the MARC21 catalog for a library or archive into an OAI static repository that holds an OLAC metadata record for each MARC record identified as describing a language resource.
Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria.

In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease.



Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data.



The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition.
A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.

Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse.



We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival.



Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported--183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04).



Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.
Outcome predictors in guided and unguided self-help for social anxiety disorder.

Internet-based self-help with therapist guidance has shown promise as an effective treatment and may increase access to evidence-based psychological treatment for social anxiety disorder (SAD). Although unguided self-help has been suggested primarily as a population-based preventive intervention, some studies indicate that patients with SAD may profit from unguided self-help. Gaining knowledge about predictors of outcome in guided and unguided self-help for SAD is important to ensure that these interventions can be offered to those who are most likely to respond. Utilizing a sample of 245 patients who received either guided or unguided self-help for SAD, the present study examined pre-treatment symptoms and program factors as predictors of treatment adherence and outcome. The results were in line with previous findings from the face-to-face treatment literature: namely, the intensity of baseline SAD symptoms, but not depressive symptoms, predicted treatment outcomes in both unguided and guided self-help groups. Outcomes were unrelated to whether a participant has generalized versus specific SAD. Furthermore, for the unguided self-help group, higher credibility ratings of the treatment program were associated with increased treatment adherence. The findings suggest that guided and unguided self-help may increase access to SAD treatment in a population that is more heterogeneous than previously assumed.
Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma.

Limited data exist regarding the activity of bendamustine in Hodgkin lymphoma (HL). This phase II study evaluated the efficacy of bendamustine in relapsed and refractory HL.



Patients with relapsed and refractory HL who were ineligible for autologous stem-cell transplantation (ASCT), or for whom this treatment failed, received bendamustine 120 mg/m(2) as a 30-minute infusion on days 1 and 2 every 28 days with growth factor support. The primary end point was overall response rate (ORR). A secondary end point was referral rate to allogeneic stem-cell transplantation (alloSCT) for patients deemed eligible for alloSCT at the time of enrollment.



Of the 36 patients enrolled, 34 were evaluable for response. Patients had received a median of four prior treatments, and 75% had relapsed after ASCT. The ORR by intent-to-treat analysis was 53%, including 12 complete responses (33%) and seven partial responses (19%). The response rate among evaluable patients was 56%. Responses were seen in patients with prior refractory disease, prior ASCT, and prior alloSCT; however, no responses were seen in patients who relapsed within 3 months of ASCT. The median response duration was 5 months. Five patients (20% of those eligible) proceeded to alloSCT after treatment with bendamustine. Grade ≥ 3 adverse events were infrequent and most commonly included thrombocytopenia (20%), anemia (14%), and infection (14%).



This study confirms the efficacy of bendamustine in heavily pretreated patients with HL. These results support current and future studies evaluating bendamustine combinations in relapsed and refractory HL.