nils-herrmann/clean_scirepeval huggingface dataset:
Fitting single-cell models to voltage- and current-clamp data: Bayesian filtering

We have incorporated into the NEURON simulation environment parameter estimation by maximizing the log-likelihood function. For linear models, we use an optimal Bayesian filter, the Kalman filter , to compute the log-likelihood. For non-linear models, likelihood cannot be computed exactly and we have explored several approximate Bayesian filters including an extended Kalman filter  and a particle filter . Bayesian filtering iteratively implements two steps for each data point: prediction and update. The first step uses the model to predict the state of the cell at the next time data is collected. The second step updates the prediction based on the new data point. Even when the model is deterministic, both the “predicted state” and the “updated state” are actually joint distributions for all components of state, even hidden components that are not measured. To give a deterministic model a probabilistic structure, we add Gaussian white noise to one or more of its states. The update step implements Bayes Rule to force the model to better follow the data. Bayes rule selects the optimal tradeoff between measurement noise and process noise. It is assumed by the method that it is actually the noise that forces the model; the log-likelihoods of the required noise are tallied. A graphical interface allows the user to obtain an intuitive understanding of how the standard deviations of the state estimates propagate and are modified by Bayes rule forcing the model to follow the data. The likelihood can be used to generate 95% confidence regions for the parameters using the chi-squared statistic . We test the validity of this construction using simulated data where 95% of the confidence regions drawn should cover the true values of the parameters. We similarly test the validity of our confidence regions under the often inevitable situation that the model being fitted has been misspecified. Finally we compare the log-likelihood objective function with the square norm objective function in terms of location of minima and the efficiency of search methods such as Praxis in finding the minima when starting from reasonable parameter values that are not close to their true value.
Anxious–Retarded Depression: Relation with Plasma Vasopressin and Cortisol

Recently, we published a report on the effects of repetitive transcranial magnetic stimulation (rTMS) on plasma levels of neuroactive steroids in major depression (Padberg et al, 2002). We meanwhile noticed that the progesterone levels reported in Figure 2 in this paper were above those usually found in human plasma. We therefore have reanalyzed our GC/MS data. By doing so we found that, when switching from steroid analysis by GC/MS from the electron impact (EI) mode that was employed in our previous study in depression (Romeo et al, 1998) to the negative chemical ionization (NCI) mode, we made a mistake with the calculation of progesterone concentrations. In our paper (Padberg et al, 2002) we reported on calculations based on Neuropsychopharmacology (2003) 28, 610–611 & 2003
Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes.

Given its critical role in T-cell signaling, interleukin-2-inducible kinase (ITK) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and neoplastic diseases. Ablation of ITK subverts Th2 immunity, thereby potentiating Th1-based immune responses. While small-molecule ITK inhibitors have been identified, none have demonstrated clinical utility. Ibrutinib is a confirmed irreversible inhibitor of Bruton tyrosine kinase (BTK) with outstanding clinical activity and tolerability in B-cell malignancies. Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an immunomodulatory inhibitor of both ITK and BTK. Our comprehensive molecular and phenotypic analysis confirms ITK as an irreversible T-cell target of ibrutinib. Using ibrutinib clinical trial samples along with well-characterized neoplastic (chronic lymphocytic leukemia), parasitic infection (Leishmania major), and infectious disease (Listeria monocytogenes) models, we establish ibrutinib as a clinically relevant and physiologically potent ITK inhibitor with broad therapeutic utility.
Advances in the Conceptualization and Measurement of Health Care Empowerment: Development and Validation of the Health Care Empowerment Inventory

The Health Care Empowerment Model offers direction for the investigation of patient-controlled engagement and involvement in health care. At the core of the model is the construct of Health Care Empowerment (HCE), for which there exist no validated measures. A set of 27 candidate self-report survey items was constructed to capture five hypothesized inter-related facets of HCE (informed, engaged, committed, collaborative, and tolerant of uncertainty). The full item set was administered to 644 HIV-infected persons enrolled in three ongoing research studies. Exploratory and confirmatory factor analyses resulted in a two factor solution comprising four items each on two subscales: (1) HCE: Informed, Committed, Collaborative, and Engaged HCE ICCE) and (2) HCE Tolerance of Uncertainty (HCE TU). Subscale scores were evaluated for relationships with relevant constructs measured in the three studies, including depression, provider relationships, medication adherence, and HIV-1 viral load. Findings suggest the utility of this 8-item Health Care Empowerment Inventory (HCEI) in efforts to measure, understand, and track changes in the ways in which individuals engage in health care.
Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response

To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus (SLE) and further analyse clinical efficacy in various patient subsets.



The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus standard SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect.



Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA-SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA-SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits regarding severe flares, corticosteroid use and health-related quality of life.



These findings suggest that belimumab has greater therapeutic benefit than standard therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline.
A 24-week comparison of low-dose ciclesonide and fluticasone propionate in mild to moderate asthma.

To compare the efficacy of ciclesonide (80 microg/day) with fluticasone propionate (200 microg/day) in mild to moderate persistent asthma.



Patients aged 12-75 years and previously treated with low doses of inhaled corticosteroid (fluticasone propionate 250 microg/day or equivalent) entered a 2-4 week run-in period during which only rescue medication was permitted. For inclusion into the double-blind, 24-week treatment period, patients had to show a forced expiratory volume in 1s (FEV(1)) of 61-90% predicted and a decrease in FEV(1) during run-in of >or=10%. Patients (n = 480) were randomized to ciclesonide 80 microg (ex-actuator) once daily in the evening or fluticasone propionate 100 microg (ex-valve) twice daily. The primary efficacy variable was the change from baseline in FEV(1). Secondary efficacy variables included asthma control and asthma-specific quality of life.



Both treatments significantly increased FEV(1) and other lung function variables from baseline (p < 0.0001, both groups, all variables). The least squares mean increases in FEV(1) were 0.46L (ciclesonide) and 0.52L (fluticasone propionate); non-inferiority of ciclesonide to fluticasone propionate was demonstrated (p = 0.0002, per-protocol analysis). Five patients in each group experienced asthma exacerbations. Improvements in the percent of days with asthma control (days with no asthma symptoms and no use of rescue medication) and asthma-specific quality of life were comparable between treatments.



The study confirmed similar efficacy of ciclesonide 80 microg once daily and fluticasone propionate 100 microg twice daily in mild to moderate persistent asthma. The low dose of ciclesonide was efficacious during long-term treatment. EudraCT number: 2004-001072-39.
Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial

The impact of intraocular involvement (IOL) in primary CNS lymphoma (PCNSL) has not been sufficiently evaluated. Here, we present the analysis of IOL in the only completed randomized phase III trial in PCNSL. The G-PCNSL-SG1 study evaluated the role of whole-brain radiotherapy in primary therapy of PCNSL. Data of the 526 eligible study patients were checked, and clinical characteristics, therapy, and outcome of patients with IOL diagnosed at study inclusion were analyzed. Ophthalmologic examination at study inclusion was performed in 297 patients (56.5 %) of whom IOL was diagnosed in 19 (6.4 %). Clinical characteristics did not significantly differ between patients with IOL (IOL+) and those without (IOL−). The median progression-free survival (PFS) in the IOL+ group was 3.5 months (95 % CI 0.0–7.07) as compared to 8.3 months (95 % CI 4.78–11.78) in the IOL− group (P = 0.004), the median overall survival (OS) was 13.2 months (95 % CI 0.86–25.62) and 20.5 months (95 % CI 15.56–25.5), respectively (P = 0.155). In multivariate analysis, a significantly inferior PFS and OS for IOL+ patients were found. IOL at diagnosis of PCNSL was an independent negative prognostic indicator for PFS and OS in this analysis.
Cost-effectiveness of cardiovascular risk management by practice nurses in primary care

Cardiovascular disease (CVD) is largely preventable and prevention expenditures are relatively low. The randomised controlled SPRING-trial (SPRING-RCT) shows that cardiovascular risk management by practice nurses in general practice with and without self-monitoring both decreases cardiovascular risk, with no additional effect of self-monitoring. For considering future approaches of cardiovascular risk reduction, cost effectiveness analyses of regular care and additional self-monitoring are performed from a societal perspective on data from the SPRING-RCT.



Direct medical and productivity costs are analysed alongside the SPRING-RCT, studying 179 participants (men aged 50-75 years, women aged 55-75 years), with an elevated cardiovascular risk, in 20 general practices in the Netherlands. Standard cardiovascular treatment according to Dutch guidelines is compared with additional counselling based on self-monitoring at home (pedometer, weighing scale and/ or blood pressure device) both by trained practice nurses. Cost-effectiveness is evaluated for both treatment groups and patient categories (age, sex, education).



Costs are €98 and €187 per percentage decrease in 10-year cardiovascular mortality estimation, for the control and intervention group respectively. In both groups lost productivity causes the majority of the costs. The incremental cost-effectiveness ratio is approximately €1100 (95% CI: -5157 to 6150). Self-monitoring may be cost effective for females and higher educated participants, however confidence intervals are wide.



In this study population, regular treatment is more cost effective than counselling based on self-monitoring, with the majority of costs caused by lost productivity.
Treatment and outcomes of urethral recurrence of urinary bladder cancer in women after radical cystectomy and orthotopic neobladder: a series of 12 cases.

The incidence, treatment, and outcome of urethral recurrence (UR) after radical cystectomy (RC) for muscle-invasive bladder cancer with orthotopic neobladder in women have rarely been addressed in the literature.



A total of 12 patients (median age at recurrence: 60 years) who experienced UR after RC with an orthotopic neobladder were selected for this study from a cohort of 456 women from participating institutions. The primary clinical and pathological characteristics at RC, including the manifestation of the UR and its treatment and outcome, were reviewed.



The primary bladder tumors in the 12 patients were urothelial carcinoma in 8 patients, squamous cell carcinoma and adenocarcinoma in 1 patient each, and mixed histology in 2 patients. Three patients (25%) had lymph node-positive disease at RC. The median time from RC to the detection of UR was 8 months (range 4-55). Eight recurrences manifested with clinical symptoms and 4 were detected during follow-up or during a diagnostic work-up for clinical symptoms caused by distant metastases. Treatment modalities were surgery, chemotherapy, radiotherapy, and bacillus Calmette-Guérin urethral instillations. Nine patients died of cancer. The median survival after the diagnosis of UR was 6 months.



UR after RC with an orthotopic neobladder in females is rare. Solitary, noninvasive recurrences have a favorable prognosis when detected early. Invasive recurrences are often associated with local and distant metastases and have a poor prognosis.
Upper limb children action-observation training (UP-CAT): a randomised controlled trial in Hemiplegic Cerebral Palsy

Rehabilitation for children with hemiplegic cerebral palsy (HCP) aimed to improve function of the impaired upper limb (UL) uses a wide range of intervention programs. A new rehabilitative approach, called Action-Observation Therapy, based on the recent discovery of mirror neurons, has been used in adult stroke but not in children. The purpose of the present study is to design a randomised controlled trial (RCT) for evaluating the efficacy of Action-Observation Therapy in improving UL activity in children with HCP.



The trial is designed according to CONSORT Statement. It is a randomised, evaluator-blinded, match-pair group trial. Children with HCP will be randomised within pairs to either experimental or control group. The experimental group will perform an Action-Observation Therapy, called UP-CAT (Upper Limb-Children Action-Observation Training) in which they will watch video sequences showing goal-directed actions, chosen according to children UL functional level, combined with motor training with their hemiplegic UL. The control group will perform the same tailored actions after watching computer games. A careful revision of psychometric properties of UL outcome measures for children with hemiplegia was performed. Assisting Hand Assessment was chosen as primary measure and, based on its calculation power, a sample size of 12 matched pairs was established. Moreover, Melbourne and ABILHAND-Kids were included as secondary measures. The time line of assessments will be T0 (in the week preceding the onset of the treatment), T1 and T2 (in the week after the end of the treatment and 8 weeks later, respectively). A further assessment will be performed at T3 (24 weeks after T1), to evaluate the retention of effects. In a subgroup of children enrolled in both groups functional Magnetic Resonance Imaging, exploring the mirror system and sensory-motor function, will be performed at T0, T1 and T2.



The paper aims to describe the methodology of a RCT for evaluating the efficacy of Action-Observation Therapy in improving UL activity in children with hemiplegia. This study will be the first to test this new type of treatment in childhood. The paper presents the theoretical background, study hypotheses, outcome measures and trial methodology.
Radiosynovectomy using yttrium-90, phosphorus-32 or rhenium-188 radiocolloids versus corticoid instillation for rheumatoid arthritis of the knee.

Radiosynovectomy (RSO) is widely used in rheumatoid arthritis (RA). Commercially available radiopharmaceuticals are costly, and therefore new agents may be of interest. Radiocolloids labelled with less costly and more accessible radionuclides are of interest to developing countries. We investigated the efficacy of different formulations in RA.



In a multicentre effort, a cohort of 99 RA patients with knee involvement underwent RSO. Sixty-eight patients were treated with 184 ± 4 MBq Y-90 silicate (Y-90), 15 patients with 53 ± 11 MBq P-32 colloid (P-32), and 16 patients with 451 ± 110 MBq of Re-188 tin colloid (Re-188). Corticosteroid group (CSG) consisting of 46 patients received an intra-articular instillation of 20-40 mg triamcinolone. Pain response was evaluated by a 10-step visual analogue scale (VAS) before, 1 month, 3 months, 6 months and 12 months following the procedure.



In the RSO group (n = 99), pain relief by VAS from 6 ± 2 before to 5 ± 3, 4 ± 2, 3 ± 2 and 4 ± 2 at 1, 3, 6, 12 months after RSO was documented (Y-90 group: 6 ± 2 to 3 ± 2; P-32: 5 ± 2 to 3 ± 2, Re-188: 7 ± 2 to 4 ± 2 before vs. 6 months after therapy, respectively). The CSG VAS values were 6 ± 2 before and 5 ± 2, 4 ± 3, 5 ± 2 and 6 ± 2 at 1, 3, 6 and 12 months after corticosteroid instillation, respectively. Pain relief achieved with the three radiocolloid formulations did not differ significantly (P > 0.1). Pain relief at 12 months was more durable in RSO compared to CSG, P < 0.05. At 3 months, pain relief (>2 steps) was reported by 86% of RSO versus 67% of CSG, at 6 months 72 versus 46% and at 12 months 46 versus 21%. Side effects, i.e. swelling or transient pain increase, were recorded in 16% of patients but resolved within 1 month.



Therapeutic efficacy of RSO for RA of the knee applying either P-32, Re-188 or Y-90 provides comparable results. Pain relief by RSO is longer lasting as compared to corticosteroid instillation.
Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: a Children's Oncology Group Pilot Study.

To determine the tolerability and serum concentration of epratuzumab, a humanized monoclonal antibody targeting CD22, administered alone and in combination with reinduction chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL), and to preliminarily assess tumor targeting and efficacy.



Therapy consisted of a single-agent phase (epratuzumab 360 mg/m(2)/dose intravenously twice weekly x four doses), followed by four weekly doses of epratuzumab in combination with standard reinduction chemotherapy. Morphologic and minimal residual disease (MRD) responses were determined at the end of this 6-week period. Serum concentrations of epratuzumab were determined before and 30 minutes after infusions, and CD22 targeting efficiency was determined by quantifying changes in CD22 expression after epratuzumab administration.



Fifteen patients (12 fully assessable for toxicity) with first or later CD22-positive ALL marrow relapse enrolled on the feasibility portion of this study from December 2005 to June 2006. Two dose-limiting toxicities occurred: one grade 4 seizure of unclear etiology and one asymptomatic grade 3 ALT elevation. In all but one patient, surface CD22 was not detected by flow cytometry on peripheral blood leukemic blasts within 24 hours of drug administration, indicating effective targeting of leukemic cells by epratuzumab. Nine patients achieved a complete remission after chemoimmunotherapy, seven of whom were MRD negative.



Treatment with epratuzumab plus standard reinduction chemotherapy is feasible and acceptably tolerated in children with relapsed CD22-positive ALL. CD22 targeting was efficient, and the majority of patients achieved favorable early responses.
Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.

The aim of this study was: 1) to evaluate the acute and late outcomes of a transcatheter aortic valve implantation (TAVI) program including both the transfemoral (TF) and transapical (TA) approaches; and 2) to determine the results of TAVI in patients deemed inoperable because of either porcelain aorta or frailty.



Very few data exist on the results of a comprehensive TAVI program including both TA and TF approaches for the treatment of severe aortic stenosis in patients at very high or prohibitive surgical risk.



Consecutive patients who underwent TAVI with the Edwards valve (Edwards Lifesciences, Inc., Irvine, California) between January 2005 and June 2009 in 6 Canadian centers were included.



A total of 345 procedures (TF: 168, TA: 177) were performed in 339 patients. The predicted surgical mortality (Society of Thoracic Surgeons risk score) was 9.8 +/- 6.4%. The procedural success rate was 93.3%, and 30-day mortality was 10.4% (TF: 9.5%, TA: 11.3%). After a median follow-up of 8 months (25th to 75th interquartile range: 3 to 14 months) the mortality rate was 22.1%. The predictors of cumulative late mortality were peri-procedural sepsis (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.48 to 8.28) or need for hemodynamic support (HR: 2.58, 95% CI: 1.11 to 6), pulmonary hypertension (PH) (HR: 1.88, 95% CI: 1.17 to 3), chronic kidney disease (CKD) (HR: 2.30, 95% CI: 1.38 to 3.84), and chronic obstructive pulmonary disease (COPD) (HR: 1.75, 95% CI: 1.09 to 2.83). Patients with either porcelain aorta (18%) or frailty (25%) exhibited acute outcomes similar to the rest of the study population, and porcelain aorta patients tended to have a better survival rate at 1-year follow-up.



A TAVI program including both TF and TA approaches was associated with comparable mortality as predicted by surgical risk calculators for the treatment of patients at very high or prohibitive surgical risk, including porcelain aorta and frail patients. Baseline (PH, COPD, CKD) and peri-procedural (hemodynamic support, sepsis) factors but not the approach determined worse outcomes.