nils-herrmann/clean_scirepeval huggingface dataset:
Phase II study of the histone deacetylase inhibitor MGCD 0103 in patients with previously treated chronic lymphocytic leukaemia

Historically, loss of tumour suppressor genes and genomic silencing via DNA mutation or deletion have been thought to contribute to tumorigenesis by permitting apoptotic escape, sustained growth, limitless replication, immunological evasion, and metastasis of the malignant cell. However, epigenetic modifications that favour transcriptionally repressive chromatin are also common in neoplastic transformation, particularly in B-cell malignancies (Koduru et al, 1995; Baur et al, 1999; Costello et al, 2000). CpG island promoter methylation and post-translational modifications of histone proteins alter chromatin conformation, favouring transcriptional repression and genomic silencing. Eukaryotic DNA is condensed 10 000fold via the nucleosome, a histone octamer consisting of a histone H3 and H4 tetramer and two histone H2A and H2B dimers. Post-translational modifications of histone proteins including histone acetylation are critical to transcriptional regulation of genes. Histone acetylation and histone deacyetylation regulated by histone acetyltransferases and histone deacetylases (HDACs) leads to either transcriptionally active hyperacetylated chromatin or transcriptionally repressive hypoacetylated chromatin, respectively. Four classes of HDACs remove acetyl groups from lysine residues in the N-terminal tails of core histones in protein repressor and chromatin remodelling complexes including HDACs 1, 2, 3 and 8 (class I isotypes located within the nucleus); HDACs 4, 5, 6, 7, 9 and 10 (class II isotypes which shuttle between the cytoplasm and the nucleus), Sirt 1–7 (class III istoypes), and HDAC 11 (class IV isotype) (de Ruijter et al, 2003). While genomic deletions and mutations irreversibly alter the sequence of a gene, histone modifications can be readily targeted by therapies that inhibit histone deacetylation. In addition to nuclear modification of histone proteins, several of the class II HDAC enzymes can also Kristie A. Blum, Anjani Advani, Louis Fernandez, Richard Van Der Jagt, Joseph Brandwein, Suman Kambhampati, Jeannine Kassis, Melanie Davis, Claire Bonfils, Marja Dubay, Julie Dumouchel, Michel Drouin, David M. Lucas, Robert E. Martell and John C. Byrd The Ohio State University Medical Center, Columbus, OH, The Cleveland Clinic Foundation, Cleveland, OH, USA, Queen Elizabeth II Health Sciences Center, Halifax, NS, Ottawa Hospital-General Campus, Ottawa, ON, Princess Margaret Hospital, Toronto, ON, Canada, Veteran Affairs Medical Center, Kansas City, MO, USA, University of Montreal, QC, and MethylGene Inc., Montreal, QC, Canada
Influence of preventive dental treatment on mutans streptococci counts in patients undergoing head and neck radiotherapy

The aim of this study was to evaluate the influence of chlorhexidine gluconate, sodium fluoride and sodium iodine on mutans streptococci counts in saliva of irradiated patients.



Forty-five patients were separated into three experimental groups and received chlorhexidine (0.12%), sodium fluoride (0.5%) or sodium iodine (2%), which were used daily during radiotherapy and for 6 months after the conclusion of the treatment. In addition, a fourth group, composed by 15 additional oncologic patients, who did not receive the mouthwash or initial dental treatment, constituted the control group. Clinical evaluations were performed in the first visit to dental clinic, after initial dental treatment, immediately before radiotherapy, after radiotherapy and 30, 60, 90 days and 6 months after the conclusion of radiotherapy. After clinical examinations, samples of saliva were inoculated on SB20 selective agar and incubated under anaerobiosis, at 37ºC for 48 h. Total mutans streptococci counts were also evaluated by using real-time PCR, through TaqMan system, with specific primers and probes for S. mutans and S. sobrinus.



All preventive protocols were able to reduce significantly mutans streptococci counts, but chlorhexidine gluconate was the most effective, and induced a significant amelioration of radiotherapy side effects, such as mucositis and candidosis.



These results highlights the importance of the initial dental treatment for patients who will be subjected to radiotherapy for head and neck cancer treatment.
Stiffness Analysis Of Multi-Chain Parallel Robotic Systems

The paper presents a new stiffness modelling method for multi-chain parallel robotic manipulators with flexible links and compliant actuating joints. In contrast to other works, the method involves a FEA-based link stiffness evaluation and employs a new solution strategy of the kinetostatic equations, which allows computing the stiffness matrix for singular postures and to take into account influence of the internal forces. The advantages of the developed technique are confirmed by application examples, which deal with stiffness analysis of the Orthoglide manipulator.
Validation of the Bleeding Academic Research Consortium definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention.

The Bleeding Academic Research Consortium (BARC) has recently proposed a unified definition of bleeding in patients receiving antithrombotic therapy. We investigated the relationship between bleeding events as defined by BARC and 1-year mortality in patients undergoing percutaneous coronary intervention (PCI) and assessed whether the BARC bleeding definition is superior to existing bleeding definitions in regard to mortality prediction in patients after PCI procedures.



This study represents a patient-level pooled analysis of 12 459 patients recruited in 6 randomized trials of patients undergoing PCI. Bleeding events were assessed with the use of BARC, Thrombolysis in Myocardial Infarction (TIMI), and Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial criteria. The primary outcome was 1-year mortality. Bleeding occurred in 1233 patients (9.9%) according to BARC (679 patients or 5.4% with BARC class ≥2 bleeding), in 374 patients (3.0%) according to TIMI, and in 491 patients (3.9%) according to REPLACE-2 criteria. There were 340 deaths (2.7%) over the first year after PCI. BARC class ≥2 bleeding was associated with a significant increase in 1-year mortality (adjusted hazard ratio 2.72; 95% confidence interval, 2.03-3.63). The predictivity of a multivariable model for 1-year mortality was significantly improved after inclusion of bleeding defined according to BARC to an extent comparable to that provided by TIMI and REPLACE-2 criteria.



The present study demonstrated a close association between bleeding events defined according to BARC and 1-year mortality after PCI.
Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes.

We determined whether insulin therapy changes liver fat content (LFAT) or hepatic insulin sensitivity in type 2 diabetes. Fourteen patients with type 2 diabetes (age 51+/-2 yr, body mass index 33.1+/-1.4 kg/m2) treated with metformin alone received additional basal insulin for 7 mo. Liver fat (proton magnetic resonance spectroscopy), fat distribution (MRI), fat-free and fat mass, and whole body and hepatic insulin sensitivity (6-h euglycemic hyperinsulinemic clamp combined with infusion of [3-(3)H]glucose) were measured. The insulin dose averaged 75+/-10 IU/day (0.69+/-0.08 IU/kg, range 24-132 IU/day). Glycosylated hemoglobin A1c (Hb A1c) decreased from 8.9+/-0.3 to 7.4+/-0.2% (P<0.001). Whole body insulin sensitivity increased from 2.21+/-0.38 to 3.08+/-0.40 mg/kg fat-free mass (FFM).min (P<0.05). This improvement could be attributed to enhanced suppression of hepatic glucose production (HGP) by insulin (HGP 1.04+/-0.28 vs. 0.21+/-0.19 mg/kg FFM.min, P<0.01). The percent suppression of HGP by insulin increased from 72+/-8 to 105+/-11% (P<0.01). LFAT decreased from 17+/-3 to 14+/-3% (P<0.05). The change in LFAT was significantly correlated with that in hepatic insulin sensitivity (r=0.56, P<0.05). Body weight increased by 3.0+/-1.1 kg (P<0.05). Of this, 83% was due to an increase in fat-free mass (P<0.01). Fat distribution and serum adiponectin concentrations remained unchanged while serum free fatty acids decreased significantly.



insulin therapy improves hepatic insulin sensitivity and slightly but significantly reduces liver fat content, independent of serum adiponectin.
Association between indices of obesity and fasting hyperglycemia in Taiwan

To examine the association of body mass index (BMI), waist–hip ratio (WHR), and waist circumference (WC) with fasting hyperglycemia after adjustment for age, cigarette smoking, and alcohol use. A cross-sectional survey was conducted among individuals visiting four health-screening centers across Taiwan. A total of 61 568 subjects (28 734 men and 32 834 women) between 25 and 64 years of age were included. Fasting hyperglycemia was defined as fasting plasma glucose ≥6.1 mmol/l or current diagnosis and use of insulin or hypoglycemic agent. Fasting hyperglycemia was found in 11.0% of men and 8.3% of women. The factors significantly associated with fasting hyperglycemia in men were age, BMI, WHR, and heavy drinking, while for women these factors were age, educational level, BMI, WHR, and heavy smoking. For men, increased risk of fasting hyperglycemia started from age 30 to 34 years, BMI ≥25 kg/m2, and WHR ≥0.82. For women, increased risk of fasting hyperglycemia started from age 35 to 39 years, BMI ≥24 kg/m2, and WHR ≥0.74. WC lost its significance as a predictor of fasting hyperglycemia when WHR included in the model. This study found that central obesity and general obesity were both independently associated with increased risk of fasting hyperglycemia in Taiwanese. The relationship between fasting hyperglycemia and central fat accumulation (WHR) begins to appear at levels that would not be regarded as representing obesity in Western populations, suggesting the need to redefine cutoffs for central obesity in this population.
Influence of exercise training on proangiogenic TIE-2 monocytes and circulating angiogenic cells in patients with peripheral arterial disease

Inflammation is the driving force in atherosclerosis. One central strategy in the treatment of peripheral arterial disease (PAD) is the promotion of angiogenesis. Here, proangiogenic Tie-2 expressing monocytes (TEM) and circulating angiogenic cells (CAC) play a crucial role. Exercise training (ET) is recommended in PAD patients at Fontaine stage II to promote angiogenesis. 40 patients with intermittend claudication (IC) [2 groups: supervised ET (SET) vs. non-supervised ET (nSET), each n = 20] and 20 healthy controls were included in the study. Analysis of TEM and CAC was performed from whole blood by flow-cytometry. TEM were identified via CD45, CD86, CD14, CD16 and analysed for the expression of Tie-2. CAC were identified via their expression of CD45 (CD45dim), CD34 and VEGF-R2 (CD309/KDR). Follow up was performed after mean of 7.65 ± 1.62 months. In comparison to healthy controls, we found increased proportions of CAC (p < 0.0001) and similar TEM numbers in both ET groups. At follow-up (FU) TEM poroportions increased (p < 0.001) and CAC proportions decreased (p < 0.01), but both more significantly in SET (p < 0.001) than nSET (p = 0.01). Only in SET fibrinogen levels decreased and VEGF-A increased (both p < 0.05). Finally, we found in both ET groups a significant increase in absolute walking distance but with a higher individual increase in SET (p < 0.01). TEM and CAC proportions correlated inversely with the absolute walking distance (CAC: r = −0.296, p = 0.02; TEM: r = −0.270, p = 0.04) as well as with ABI (CAC: r = −0.394, p < 0.01; TEM: r = −0.382, p < 0.01). ET influences the distribution of CAC and TEM proportions. nSET, although still effective in regard to an improved walking distance, is less effective in the influence of proangiogenic cells and inflammatory burden than SET. Our results indicate SET to be a more preferential exercise form, supporting the necessity to establish more SET programs.
Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity.

To characterise RA in a sample of Spanish patients by estimating mean clinical activity, functional ability, and radiological damage, and current and cumulative prevalence of extra-articular manifestations.



Cross sectional analysis of a cohort of patients with RA randomly selected from the clinical databases of 34 centres. Standard definitions and measurements were used, and radiographs read centrally. Estimates and confidence intervals were adjusted to sampling.



Data were available for 788 patients. Extra-articular RA was present in 285 (36.2%) patients. Cumulative prevalence and 95% confidence intervals of extra-articular manifestations were estimated: nodules 24.5% (21.5 to 27.5), Sjögren's syndrome 17.0% (14.4 to 19.6), atlantoaxial subluxation 12.1% (9.8 to 14.4), carpal tunnel syndrome 10.7% (7.8 to 13.6), interstitial lung disease 3.7% (2.4 to 5.0), serositis 2.5% (1.4 to 3.5), eye disease 2.5% (1.1 to 3.9), vasculitis 1.3% (0.5 to 2.1), amyloidosis 0.6% (0.1 to 1.2), and Felty's syndrome 0.3% (<0.6). Mean (SD) activity/progression indexes were: DAS28-3 3.4 (1.2), HAQ 1.6 (0.4), Larsen score 54.7 (26.4). Less than 5% of the patients were in remission. 205 (72%) patients were receiving disease modifying antirheumatic drugs (DMARDs).



Spanish patients with RA ever seen by a rheumatologist have, on average, a moderate degree of activity, despite widespread use of DMARDs. Measures of the degree of progression do not show a benign disease. The proportion of extra-articular manifestations in Spanish patients with RA is similar to that found in other Mediterranean populations, and lower than that reported in Anglo Saxon countries.
Qualitative process evaluation of a problem-solving guided self-help manual for family carers of young people with first-episode psychosis

Caring for a young person experiencing first-episode psychosis is challenging and can affect carers' well-being adversely. While some face-to-face approaches have achieved promising outcomes, they are costly and resource-intensive to provide, restricting their reach and penetration. Guided self-help in book-form (or bibliotherapy) is an alternative but untested approach in these circumstances. In this study, we aimed to evaluate carers' beliefs about the usefulness of problem-solving guided self-help manual for primary carers of young people with first-episode psychosis.



A qualitative process evaluation nested in a randomised controlled trial, conducted across two early intervention psychosis services in Melbourne, Australia. 124 carers were randomised to problem-solving guided self-help intervention or treatment as usual. We also undertook a qualitative process evaluation, using individual interviews, with a random sample of 24 of the intervention group. A thematic analysis of the qualitative data was undertaken, which is the subject of this paper. Interviews were conducted between January 2009 and September 2010.



Three themes were abstracted from the data, reflecting carers' beliefs about the usefulness of the manual: promoting carers' well-being, increasing carers' understanding of and support for the young person with first-episode psychosis, and accessibility and delivery modes of the programme.



This process evaluation highlights that guided self-help is useful in informing and supporting carers of affected young people. While there is scope for broadening the delivery modes, the approach is easy to use and accessible, and can be used as a cost-effective adjunct to standard support provided to carers, by community mental health nurses and other clinicians.
First-in-Human Phase I Study of PRS-050 (Angiocal), an Anticalin Targeting and Antagonizing VEGF-A, in Patients with Advanced Solid Tumors

To report the nonrandomized first-in-human phase I trial of PRS-050, a novel, rationally engineered Anticalin based on human tear lipocalin that targets and antagonizes vascular endothelial growth factor A (VEGF-A).



Patients with advanced solid tumors received PRS-050 at 0.1 mg/kg to 10 mg/kg by IV in successive dosing cohorts according to the 3+3 escalation scheme. The primary end point was safety.



Twenty-six patients were enrolled; 25 were evaluable. Two patients experienced dose-limiting toxicity, comprising grade (G) 3 hypertension and G3 pyrexia, respectively. The maximum tolerated dose was not reached. Most commonly reported treatment-emergent adverse events (AEs) included chills (52%; G3, 4%), fatigue (52%; G3, 4%), hypertension (44%; G3, 16%), and nausea (40%, all G1/2). No anti-PRS-050 antibodies following multiple administration of the drug were detected. PRS-050 showed dose-proportional pharmacokinetics (PK), with a terminal half-life of approximately 6 days. Free VEGF-A was detectable at baseline in 9/25 patients, becoming rapidly undetectable after PRS-050 infusion for up to 3 weeks. A/PRS-050 complex was detectable for up to 3 weeks at all dose levels, including in patients without detectable baseline-free VEGF-A. We also detected a significant reduction in circulating matrix metalloproteinase 2, suggesting this end point could be a pharmacodynamic (PD) marker of the drug's activity.



PRS-050, a novel Anticalin with high affinity for VEGF-A, was well-tolerated when administered at the highest dose tested, 10 mg/kg. Based on target engagement and PK/PD data, the recommended phase II dose is 5 mg/kg every 2 weeks administered as a 120-minute infusion.
Dendritic cells and T lymphocyte interactions in patients with lymphoid malignancies.

Dendritic cell (DC) vaccination is an attractive approach to the treatment of patients with lymphoid tumors. To evaluate its feasibility, we have tested the functional properties of DC and T-lymphocytes in patients with treated and untreated chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). Healthy volunteers were used both as controls and as a source of cells for allogeneic mixed leukocyte reaction (MLR). In these reactions, dendritic cells from both untreated and treated patients were comparable to dendritic cells from healthy volunteers. In all the untreated patients studied, autologous dendritic cells promoted the survival and proliferation of both CD4 and CD8 lymphocytes (though the proliferation response was much better in the CD4 subset), whereas only 3 out of 5 treated patients were able to mount this response with CD4 lymphocytes and 4 out of 5 with CD8 lymphocytes. In 3 out of 5 untreated patients, pulsing of DCs with tetanus toxoid promoted a better CD4 response than was achieved with unpulsed DCs, while none of 5 treated patients had an additional response after pulsing with tetanus toxoid. None of patients studied, either treated or untreated, had a better CD8 response to pulsed DCs than to unpulsed ones. During CD4 lymphocyte proliferation, more CD4(+)CD25(hi) lymphocytes were generated in both treated and untreated patients than in healthy controls. Poor proliferation of cytotoxic cells and preferential proliferation of CD4(+)CD25(hi) T-regulatory cells in response to self and/or foreign antigens might be one of the mechanisms responsible for immunosuppression and impaired tumor surveillance in patients with lymphoid malignancies.
Surgical trends for benign ovarian tumors among hospitals of different accreditation levels: an 11-year nationwide population-based descriptive study in Taiwan.

Using a population-based nationwide database, we describe the changing surgical trends for laparoscopy or laparotomy for benign ovarian tumors among hospitals of different accreditation levels in Taiwan (medical centers, regional hospitals, and local hospitals).



Women who had National Health Insurance and received either laparoscopy or laparotomy as the primary surgery for benign ovarian tumors in Taiwan during 1999-2009 were identified for analysis.



In total, 135,793 women who received either laparotomic (39,779) or laparoscopic surgery (96,014) for benign ovarian pathology were identified. The increase in annual laparoscopy number from 7176 in 1999 to 11,046 in 2009 was significant according to a log-linear regression test (p < 0.0001). The decrease in laparotomies from 3845 to 3567 was not significant (p = 0.190). Service volume shifts from local hospitals to regional hospitals were noted, with a concomitant decrease in the numbers of local hospitals. Laparoscopy was used more often than laparotomy among all three hospital accreditation levels. An increasing trend for choosing laparoscopy was observed for medical centers and local hospitals (p < 0.0001), but not regional hospitals (p = 0.0745). Laparoscopy was used more often in younger patients, by younger surgeons, and by male surgeons among hospitals at all three accreditation levels.



Laparoscopy was preferentially used over laparotomy at all three hospital levels. An increasing trend for choosing laparoscopy was observed for medical centers and local hospitals, but not regional hospitals. Service volume shifts from local hospitals to regional hospitals were noted. Use of laparoscopy differed according to patient age, surgeon age, and surgeon gender among different hospital levels.
The other side of recovery: validation of the Portuguese version of the subjective experiences of psychosis scale

The aim of this study was to develop and validate a Portuguese version of The Subjective Experiences of Psychosis Scale (SEPS) for use in Portuguese-speaking populations in order to provide a self-report instrument to assess and monitor dimensions of psychotic experiences, translating patient's perspective and experience in terms of recovery from psychosis.



The sample consisted of 30 participants with psychotic disorders who had recently experienced delusions or hallucinations. The SEPS was completed along with other observer-based assessments and self-report questionnaires, such as the Brief Psychiatric Rating Scale, the Insight and Treatment Attitudes Questionnaire and the Function Assessment Short Test.



Two main factors representing the positive and negative components of each subscale were identified. We obtained good internal consistency and test-retest reliability for the positive and negative components of all subscales. The subscales of SEPS correlated with observer-based assessments and self-report questionnaires.



The Portuguese version of the SEPS is a useful tool in the assessment and monitoring of psychotic symptoms.