nils-herrmann/clean_scirepeval huggingface dataset:
Desmoglein-2-Integrin Beta-8 Interaction Regulates Actin Assembly in Endothelial Cells: Deregulation in Systemic Sclerosis

The inability of endothelial cells of patients affected by the diffuse form of Systemic sclerosis (SSc) to perform angiogenesis is a marker of the disease. We previously demonstrated that desmoglein-2 reduction is a major difference between (SSc)-microvascular endothelial cells (MVECs) and normal (N)-MVECs. Here we investigated the role of desmoglein-2 in human N-MVECs and SSc-MVECs angiogenesis.



Angiogenesis was studied by Matrigel invasion, capillary morphogenesis in vitro and Matrigel plug assay in vivo. Gene profiling was studied by Affymetrix technology and signal transduction by Western blotting. Colocalization was validated by immunoprecipitation and confocal microscopy. SiRNAs were used to validate the roles of specific molecules. We observed that desmoglein-2 co-localizes with integrin-beta8 in N-MVECs. This complex is required to signal through Rac, FAK, SMAD1/5 and MAP-kinases, promoting an angiogenic program. Inhibition of desmoglein-2 by DSG2-siRNA impaired actin stress fibres formation, capillary morphogenesis in vitro and angiogenesis in vivo. Transcriptome profiling after DSG2 inhibition revealed alterations of several genes involved in actin organization. siRNA inhibition of integrin-beta8 and RAC2 also resulted into capillary morphogenesis impairment in N-MVECs, due to reduced expression of the same actin-assembly genes that were down-regulated by DSG2 silencing. SSc-MVECs showed down-regulation of the same genes in DSG2-siRNA treated N-MVECs, suggesting that impairment of desmoglein-2/integrin-beta8 complex contributes to angiogenesis derangement in SSc. Transfection of DSG2 in SSc-MVEC partially restored their angiogenic properties in vitro.



We have shown that impairment of actin assembly as a result of desmoglein-2/integrin-beta8 complex formation is a major factor contributing to angiogenesis deregulation in Systemic sclerosis.
Criterion validity of the BBUSQ-22: a questionnaire assessing bowel and urinary tract symptoms in women

To evaluate the criterion validity of the Birmingham Bowel and Urinary Symptoms Questionnaire (BBUSQ-22). Forty-four women presenting with urinary or bowel symptoms to a urogynaecology/functional bowel clinic, completed three disease-specific questionnaires (Birmingham Bowel and Urinary Symptoms Questionnaire, Sheffield Prolapse Symptoms Questionnaire and King’s Health Questionnaire) and two generic questionnaires (SF-36 and EuroQol). Wilcoxon rank sum tests, Spearman’s rank correlations and multiple regression analyses were undertaken. All clinically hypothesised correlations between the questionnaires’ domains were found significant, and all domains hypothesised to be predictors of the BBUSQ-22 domains were proven to be prognostic, without explaining too much variability to doubt their uniqueness. The similarity among the measures has been proved without such relationships being too strong to call into question the distinctiveness of the concepts being measured. Overall, criterion validity is demonstrated, and the clinical usefulness of the addition this questionnaire makes to the area is highlighted.
[Effects of the nutrition education program on self-efficacy, diet behavior pattern and cardiovascular risk factors for the patients with cardiovascular disease].

This study examined the effects of a nutrition education program on self-efficacy, diet behavior pattern and cardiovascular risk factors for patients with cardiovascular disease (CVD).



Sixty-four CVD subjects (37 experimental, 27 control) were recruited from a cardiac center, at a university hospital located in D city, Korea. All subjects attended a first heart camp where pretest measures were performed, and a second heart camp at 6 months for the posttest measures. During the 6 month study period, the experimental group was required to attend five monthly nutrition education sessions, while the control group received only routine outpatient follow-ups. Data were analyzed by chi(2)-test and independent t-test using the SPSSWIN 11.5 program.



Group comparisons revealed that the experimental group had significantly more improved self-efficacy, frequency of food selection, gustation of salt, systolic blood pressure, and serum total-cholesterol compared to the control group.



A nutrition education program may be effective in improving self-efficacy, diet behavior pattern and cardiovascular risk factors for patients with cardiovascular disease.
Improved Survival of HIV-1-Infected Patients with Progressive Multifocal Leukoencephalopathy Receiving Early 5-Drug Combination Antiretroviral Therapy

Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery.



All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008).



The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death.
A Pilot Study of Dose Intense Doxorubicin and Cyclophosphamide Followed by Infusional Paclitaxel in High-Risk Primary Breast Cancer

We conducted a pilot study of dose dense doxorubicin and cyclophosphamide (AC) combination chemotherapy followed by infusional paclitaxel (T) in primary breast cancer to determine its safety and feasibility. Twenty-two subjects (10 with stage II and ≥4 positive lymph nodes, and 12 with stage III disease) were treated with AC (A 60 mg/m2 and C 2000 mg/m2) with filgrastim every 14 days for three cycles followed by infusional paclitaxel (140 mg/m2 over 96 h) every 14 days for three cycles. Mean overall cycle length was 15.3 days and mean duration of therapy was 92 days. Dose reductions of C or T were required in 7/132 (5.3%) cycles for mucositis, diarrhea, or failure to recover platelets by day 15. Ninety-five percent of subjects had grade 4 neutropenia and 1 subject had a platelet nadir of <20,000. Actual delivered dose intensity (DI) over six cycles was: A 27 mg/m2 per week; C 892 mg/m2 per week; T 64 mg/m2 per week (90.6, 89.2, and 91.4% of planned DI, respectively). Average total dose administered was: A 180 mg/m2; C 5880 mg/m2; T 403 mg/m2 (100, 98, and 96% of planned total doses, respectively). Clinical response rate in 10 subjects receiving neoadjuvant therapy was 100% (4 complete response, 6 partial response). Four subjects had a pathologic complete response (three subjects without evidence of malignancy and one subject with ductal carcinoma in situ.) Administration of dose dense AC followed by infusional paclitaxel in 14-day cycles is feasible and this regimen is active in breast cancer.
Heart failure assessment at the community pharmacy level: a feasibility pilot study.

A key element missing in disease-management programs for heart failure (HF) is participation of the community pharmacist. The purpose of this study is to determine if a simple and efficient clinical tool will allow community pharmacists to identify patients at risk for worsening HF.



The One Minute Clinic for Heart Failure (TOM-C HF) was developed as a simple six-item symptom screening tool to be used during routine patient/customer interactions.



Ten community pharmacies located in the upper Midwest.



Self-identified HF patients.



121 unique patients were evaluated over a 12-month period. The application of this clinical tool took between 1 and 5 minutes in over 80% of the interactions. Seventy-five patients (62%) had one or more signs or symptoms of worsening HF. The most common symptoms detected included edema (39%) and increased shortness of breath (17%). Self-reported weight gain of more than 5 pounds was seen in 19% of patients.



The TOM-C HF tool was used to identify patients in a time-efficient manner in the community pharmacy setting who appear to be developing worsening HF. Inclusion of the community pharmacists as an early screen for HF decompensation may be an important link in disease-management programs to help reduce hospital readmission rates.
MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin

We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis. Positive WT1 MRD (defined as > 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as > 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39 % versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels. Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment.
Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy.

The Southwest Oncology Group conducted a study of acute lymphoblastic leukemia (ALL) in adults over a 5-year period, testing the utility of the L-10M regimen initially described by the group from Memorial Sloan-Kettering Cancer Center. One hundred sixty-eight eligible patients were treated with this intensive combination chemotherapy regimen. One hundred fifteen (68%) achieved complete remission. With the current median follow-up time of 34.5 months, the median durations of remission, relapse-free survival, and overall survival were 22.9, 20.9, and 17.7 months, respectively. Only 35% of the patients over 50 years of age achieved a complete remission. Age was a significant prognostic factor for complete response, survival, relapse-free survival, and remission duration. In addition, a low initial WBC count was found to have a statistically significant association with longer remission duration. Responders between the ages of 20 and 49 years with WBC counts of less than 15,000 appear to have an exceptionally good prognosis.
Reliability of tissue Doppler wall motion monitoring after heart transplantation for replacement of invasive routine screenings by optimally timed cardiac biopsies and catheterizations.

Invasive screenings at predefined time intervals for acute rejection and transplant coronary artery disease (TxCAD) are standard procedures. However, cardiac biopsies and catheterizations are distressing and risky for the patients and are also costly. We assessed the reliability of pulsed-wave tissue Doppler imaging (PW-TDI) for the timing of invasive examinations in heart recipients in an attempt to avoid unnecessary endomyocardial biopsies (EMBs) and catheterizations.



PW-TDI obtained at the basal left ventricular posterior wall before 408 EMBs and 293 catheterizations was tested for its diagnostic value regarding rejection and TxCAD with the use of International Society of Heart and Lung Transplantation biopsy grading, coronary angiography, and intravascular ultrasound as standards. Early diastolic peak wall motion velocity and relaxation time showed high sensitivities for clinically relevant rejection diagnosis (90.0% and 93.3%, respectively). The negative and positive predictive values for rejection of diastolic parameter changes appeared high enough (up to 96% and 92%, respectively) to allow a reliable noninvasive PW-TDI monitoring with efficiently timed, instead of routinely scheduled, EMBs. At definite cutoff values for systolic parameters, the probability for TxCAD reached 92% to 97%. The Fisher classification functions allowed TxCAD exclusion with 80% probability.



Without diastolic parameter changes, acute rejection can be practically excluded, and serial PW-TDI can save patients from routine EMBs. The high specificity and negative predictive value for TxCAD of reduced systolic peak velocities and extended systolic time allow optimized timed catheterizations. Peak systolic velocity and systolic time allow diagnostic classifications that enable patients without known TxCAD but with high risk for catheterization to be spared routine angiographies.
Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL)

TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18–64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2–15%). Acute GvHD grade II–IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24–48) and 51% (90% confidence interval: 37–65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).
Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression

The aim of this study was to determine the predictive value of whole-brain voxel-based regional cerebral blood flow (rCBF) for repetitive transcranial magnetic stimulation (rTMS) response in patients with pharmacoresistant depression. Thirty-three right-handed patients who met DSM-IV criteria for major depressive disorder (unipolar or bipolar depression) were included before rTMS. rTMS response was defined as at least 50% reduction in the baseline Beck Depression Inventory scores. The predictive value of 99mTc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) for rTMS response was studied before treatment by comparing rTMS responders to non-responders at voxel level using Statistical Parametric Mapping (SPM) (p < 0.001, uncorrected). Of the patients, 18 (54.5%) were responders to rTMS and 15 were non-responders (45.5%). There were no statistically significant differences in demographic and clinical characteristics (p > 0.10). In comparison to responders, non-responders showed significant hypoperfusions (p < 0.001, uncorrected) in the left medial and bilateral superior frontal cortices (BA10), the left uncus/parahippocampal cortex (BA20/BA35) and the right thalamus. The area under the curve for the combination of SPECT clusters to predict rTMS response was 0.89 (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value for the combination of clusters were: 94, 73, 81 and 92%, respectively. This study shows that, in pharmacoresistant depression, pretreatment rCBF of specific brain regions is a strong predictor for response to rTMS in patients with homogeneous demographic/clinical features.
Comparison of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease.

This study aimed to assess and compare the effectiveness of lidocaine and bronchodilator inhalation treatments for rapid cough suppression in patients with chronic obstructive pulmonary disease (COPD).



Prospective comparison study carried out in a tertiary emergency department. Consecutive COPD patients presenting with intractable cough were randomly assigned to receive lidocaine or terbutaline inhalation treatments for cough suppression. Patients with dyspnoea, unstable vital signs, and pneumonia or neoplasm on chest x ray were excluded. A subjective, 10 point questionnaire based cough severity score was used for assessing the outcome.



The final study sample included 127 patients (mean (SD) age, 69.2 (12.1) years; 33.1% women) of whom 62 received nebulised lidocaine and 65 nebulised bronchodilator. The cough severity score was significantly reduced one hour after inhalation treatment with both lidocaine and bronchodilator, with no significant difference in efficacy. Common but mild side effects in the lidocaine group included oropharyngeal numbness and bitter taste, and, in the bronchodilator group, tremor and palpitation. Dyspnoea, dizziness, and nausea and vomiting were equally uncommon in both groups. None of these problems caused any of the patients to discontinue their treatments and no allergic reactions were reported.



Both lidocaine and bronchodilator inhalation treatments are equally effective for short term cough suppression in patients with COPD.
UK Renal Registry 13th Annual Report (December 2010): Chapter 14: enhancing access to UK Renal Registry data through innovative online data visualisations.

As the volume of data and analyses grows with time, so does the need to present this increasingly complex information in an accessible and clinically informative manner which is responsive to, and reflects the nature of, the enquiries made by those seeking to access the data.


THE UK RENAL REGISTRY INTERACTIVE DATA PORTAL
The UK Renal Registry (UKRR) now has a bespoke interactive data portal which provides a focussed point of access to a variety of graphical display formats and analyses of UKRR data including: · Centre-specific reports--a distillation of annual UKRR data including a colour-coded dashboard summary as well as both funnel plots and longitudinal statistical process control charts for a range of clinical parameters. · Interactive flash-based longitudinal Statistical Process Control charts on a per-centre and per-parameter basis allowing for a more detailed review of performance over time. These charts are the interactive correlates of those available in the centre-specific reports. · Rosling/Gapminder-style motion charts on a perparameter basis simultaneously detailing performance and activity data from multiple centres interactively over time (more details below). · An interactive graphical pivot chart solution using OLAP technology allowing users to design and export their own charts/analyses in real-time using UKRR data.



This work builds strongly on the wealth of information arising from the high-quality validated UKRR datasets. The portal will empower and engage the UK renal community in the comparative analysis of delivered renal care ultimately leading to enhanced quality improvement over time.
Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: final results from CALGB trial 79809.

Chemotherapy-induced ovarian failure (CIOF) is a frequent side-effect of adjuvant chemotherapy that results in rapid bone loss. We hypothesised that zoledronic acid (ZA), a third-generation amino bisphosphonate, would prevent bone loss in premenopausal women who developed CIOF.



Women (439) were randomised to intravenous (i.v.) ZA 4 mg every 3 months for 2 years starting within 1-3 months after randomization (arm A) or 1 year after randomization (arm B, controls). CIOF was prospectively defined as ≥ 3 months of amenorrhoea, follicle-stimulating hormone (FSH) ≥ 30 MIU/ml and non-pregnant at 1 year. The primary end-point was the percentage change in bone mineral density (BMD) in the lumbar spine (LS) from baseline to 12 months in the ZA and in control groups in women who developed CIOF; the secondary end-point was BMD in LS at 3 years in all randomised women.



One hundred and fifty (56%) met the definition of CIOF at 1 year. Overall, grade 3 toxicities of ZA were fatigue (1%) arthralgias (21%) and pain (84%). The median percent change (interquartile range, IQR) at 1 year was +1.2% (-0.5% to +2.8%) and -6.7% (-9.7% to -2.9%) p<0.001 and at 3 years was +1.0% (-1.6% to +5.2%) and -0.5% (-3.7% to +3.2%) p=0.019 in arms A and B, respectively.



ZA every 3 months is well tolerated and prevents rapid bone loss in premenopausal women that develop CIOF. Giving ZA with rather than 1 year after the start of adjuvant chemotherapy is the preferred sequence to prevent bone loss.