nils-herrmann/clean_scirepeval huggingface dataset:
Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer

We evaluated the use of sorafenib to overcome resistance to aromatase inhibitors (AIs) in patients with metastatic breast cancer who had disease recurrence or progression while on AIs. We performed a multi-institution phase I/II study of sorafenib and anastrozole 1 mg daily in 35 postmenopausal females with hormone receptor positive metastatic breast cancer resistant to AIs. Primary objectives were to determine the dose of sorafenib in conjunction with anastrozole and the clinical benefit rate (CBR) (complete response [CR], partial response [PR], or stable disease [SD] ≥ 24 weeks). Secondary objectives were to determine toxicity and to evaluate if response was associated with change in number of circulating endothelial cells or circulating endothelial progenitor cells. Based on the phase I portion, sorafenib 400 mg twice daily was selected as the phase II dose. Among 35 patients, 7 had SD ≥ 24 weeks, 1 had PR ≥ 24 weeks, and 14 had progressive disease (PD) ≤ 24 weeks, corresponding to a CBR of 23%. The most common adverse events (all; Grade 3/4) were fatigue (66%; 17%), diarrhea (63%; 6%), nausea (60%; 9%), and hand-foot syndrome (57%; 34%). Dose reduction occurred in 77% of the patients and 31% came off study due to toxicity. The combination of sorafenib and anastrozole demonstrated a 23% CBR in patients with hormone receptor positive, AI-resistant metastatic breast cancer, which may be attributable to the restoration of sensitivity to AIs. Toxicities occurred frequently resulting in a high rate of discontinuation.
Motivational interviewing with hazardous drinkers.

PURPOSES
To test the effectiveness of motivational interviewing in a population of hazardous drinkers utilizing community health care centers in rural southeastern Idaho.



This study targeted rural people at risk for alcohol dependence utilizing low-income community health care centers in rural southeastern Idaho. The Alcohol Use Disorders Identification Test (AUDIT) was used to screen interested clients' alcohol use. Clients achieving an AUDIT score indicating hazardous alcohol use were recruited into the study and randomized into a control or treatment group. Twenty-six hazardous drinkers attending five low-income community health centers participated in the study. The experimental group participated in one motivational interviewing session with the investigator, a family nurse practitioner (NP). The comparison group received no treatment. Alcohol use was tracked for 6 weeks after successful recruitment into the program.



Participants in the study significantly decreased their average number of drinks per day. At time 1 (pretreatment), the control group drank 4.37 drinks per day and the treatment group drank 4.65 drinks per day. At time 2 (posttest), the control group drank 3.77 drinks per day and the treatment group drank 1.95 drinks per day. The effects of the motivational interviewing treatment on hazardous drinking also were measured by serum gamma-glutamyltransferase (GGT), a liver function test. There was also a significant decrease in the GGT from pretest to posttest in the treatment group.



The results of this investigation found that motivational interviewing shows promise as an effective intervention for hazardous drinkers attending low-income community clinics. Although other possible explanations could be postulated for the positive changes in sample participants, the data indicate that the motivational interviewing approach was responsible for a significant portion of the positive changes within the current sample. The information collected from the study adds to the literature on hazardous drinking, research, and treatment of this significant problem. Negotiating change in behavior is part of the practice of NPs. People struggling with alcohol use are more likely to encounter NPs, family doctors, or social workers than counselors specializing in alcohol treatment. Motivational interviewing is specifically designed for preparing people for change. Because most people resist being told what to do, that is, "you have to stop drinking," use of motivational interviewing principles can decrease resistance and optimize change. Additionally, identifying and intervening with hazardous drinking in a primary care setting can reduce healthcare costs and reduce the stigma of specialist care. Adding this valuable communication skill to the competencies of NPs is important to both clients and NPs.
Functional topography of early periventricular brain lesions in relation to cytoarchitectonic probabilistic maps

Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we asked whether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matter damage. Eight patients with pre- and perinatally acquired left-sided periventricular brain lesions underwent focal transcranial magnetic stimulation to assess the integrity of cortico-spinal hand motor projections, and functional MRI to determine the hemispheric organization of language production. MRI lesion-symptom mapping revealed that two distinct portions of the periventricular lesions were critically involved in the disruption of cortico-spinal hand motor projections on the one hand and in the induction of language reorganization into the contra-lesional right hemisphere on the other hand. Both regions are located in a position compatible with the course of cortico-spinal/cortico-nuclear projections of the primary motor cortex in the periventricular white matter, as determined by the stereotaxic probabilistic cytoarchitectonic atlas developed by the Jülich group.
Multi-Site Clinical Evaluation of DW-MRI as a Treatment Response Metric for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

To evaluate diffusion weighted MRI (DW-MR) as a response metric for assessment of neoadjuvant chemotherapy (NAC) in patients with primary breast cancer using prospective multi-center trials which provided MR scans along with clinical outcome information.



A total of 39 patients with locally advanced breast cancer accrued from three different prospective clinical trials underwent DW-MR examination prior to and at 3-7 days (Hull University), 8-11 days (University of Michigan) and 35 days (NeoCOMICE) post-treatment initiation. Thirteen patients, 12 of which participated in treatment response study, from UM underwent short interval (<1hr) MRI examinations, referred to as "test-retest" for examination of repeatability. To further evaluate stability in ADC measurements, a thermally controlled diffusion phantom was used to assess repeatability of diffusion measurements. MRI sequences included contrast-enhanced T1-weighted, when appropriate, and DW images acquired at b-values of 0 and 800 s/mm2. Histogram analysis and a voxel-based analytical technique, the Parametric Response Map (PRM), were used to derive diffusion response metrics for assessment of treatment response prediction.



Mean tumor apparent diffusion coefficient (ADC) values generated from patient test-retest examinations were found to be very reproducible (|ΔADC|<0.1x10-3mm2/s). This data was used to calculate the 95% CI from the linear fit of tumor voxel ADC pairs of co-registered examinations (±0.45x10-3mm2/s) for PRM analysis of treatment response. Receiver operating characteristic analysis identified the PRM metric to be predictive of outcome at the 8-11 (AUC = 0.964, p = 0.01) and 35 day (AUC = 0.770, p = 0.05) time points (p<.05) while whole-tumor ADC changes where significant at the later 35 day time interval (AUC = 0.825, p = 0.02).



This study demonstrates the feasibility of performing a prospective analysis of DW-MRI as a predictive biomarker of NAC in breast cancer patients. In addition, we provide experimental evidence supporting the use of sensitive analytical tools, such as PRM, for evaluating ADC measurements.
Health-related quality of life in women with newly diagnosed polycystic ovary syndrome randomized between clomifene citrate plus metformin or clomifene citrate plus placebo.

What is the health-related quality of life (HRQoL) in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomifene citrate (CC) combined with metformin compared with those using CC combined with placebo?



Overall quality of life in women with PCOS treated with CC plus metformin was significantly lower than in women treated with CC plus placebo.



There are no data on HRQoL in adult women who receive ovulation induction with the purpose of conceiving. Women with PCOS have higher scores on depression and anxiety scales and lower QoL scores than women without PCOS.



This study was a secondary analysis of a multi-centre RCT completed between June 2001 and May 2004. The randomization was stratified per centre, and the centres received blinded, numbered containers with medication. There were172 women available for the HRQoL assessment: 85 were allocated to metformin and 87 were allocated to placebo.



The Rotterdam Symptom Checklist (RSCL), a standard self-administered questionnaire, was used to assess physical symptoms, psychological distress, activity levels and overall HRQoL.



In the intention to treat analysis, we found differences between the treatment groups with respect to physical symptoms and overall HRQoL. Physical well-being was significantly impaired in women allocated to metformin but not in women allocated to placebo. The increase in physical symptoms in the metformin group was caused by side-effects typical of metformin, and was most pronounced at Week 1 (mean difference 12 [95% confidence interval (CI): 8-16] and still apparent at Week 16 [mean difference 7 (95% CI 2-12]. Overall well-being was significantly impaired in the metformin group compared with the placebo group [mean difference 13 (95% CI 6-20)].



RSCL measurements were available only for three quarters of the participants. Although the number of missing questionnaires and the baseline measurements, were comparable between the treatment groups, some form of selection bias cannot be ruled out.



Our finding that metformin was more burdensome than placebo, strengthens the recommendation that CC only and not CC plus metformin should be the drug of choice in this patient population.



None of the authors declared a conflict of interest. There was no study funding.
Private Incremental Regression

Data is continuously generated by modern data sources, and a recent challenge in machine learning has been to develop techniques that perform well in an incremental (streaming) setting. A variety of offline machine learning tasks are known to be feasible under differential privacy, where generic construction exist that, given a large enough input sample, perform tasks such as PAC learning, Empirical Risk Minimization (ERM), regression, etc. In this paper, we investigate the problem of private machine learning, where as common in practice, the data is not given at once, but rather arrives incrementally over time.
 We introduce the problems of private incremental ERM and private incremental regression where the general goal is to always maintain a good empirical risk minimizer for the history observed under differential privacy. Our first contribution is a generic transformation of private batch ERM mechanisms into private incremental ERM mechanisms, based on a simple idea of invoking the private batch ERM procedure at some regular time intervals. We take this construction as a baseline for comparison. We then provide two mechanisms for the private incremental regression problem. Our first mechanism is based on privately constructing a noisy incremental gradient function, which is then used in a modified projected gradient procedure at every timestep. This mechanism has an excess empirical risk of ≈√d where d the input and constraint set can be used to derive significantly better results for certain interesting regression problems. Our second mechanism which achieves this is based on the idea of projecting the data to a lower dimensional space using random projections, and then adding privacy noise in this low dimensional space. The mechanism overcomes the issues of adaptivity inherent with the use of random projections in online streams, and uses recent developments in high-dimensional estimation to achieve an excess empirical risk bound of ≈ T1/3 W2/3, where T is the length of the stream and W is the sum of the Gaussian widths of the input domain and the constraint set that we optimize over.
A dose-response study with formoterol Turbuhaler as maintenance therapy in asthmatic patients.

The aim of this randomized, double-blind, parallel group study was to determine the lowest effective dose of 6, 12 and 24 microg formoterol fumarate dihydrate Turbuhaler b.i.d. compared with placebo. The 4 week treatment was preceded by a 1 week run-in period. Morning peak expiratory flow (PEF) before intake of the study drug was the primary variable. Patients recorded PEF, prior to and 15 min after intake of the study drug (immediate response), asthma symptoms, and use of rescue medication morning and evening. Of 221 patients (71 females and 150 males), 194 were included in the efficacy per protocol (PP) analysis; mean age 47 yrs, mean forced expiratory volume in one second (FEV1) 2.01 L (58% of predicted), mean FEV1 reversibility 27% at entry. Ninety percent used inhaled steroids. Compared with placebo, 6 microg formoterol b.i.d was found to be the lowest effective dose in the morning (p=0.008) and evening p=0.0041) PEF. The mean increases in PEF were 22 and 23 L x min-1 respectively, compared with placebo. After 6 microg formoterol, the mean immediate increase in morning PEF was 42 L x min-1 compared to an increase of only 9 L x min-1 after placebo (<0.0001). All doses produced a statistically significant decrease in asthma symptoms, day and night, and the need for rescue medication at night. All doses were well-tolerated. In conclusion, the lowest effective dose in this study was formoterol Turbuhaler 6 microg b.i.d.
Measuring health status in chronic airflow limitation.

A health status instrument for use in clinical trials must be valid (measuring what it is supposed to measure) and responsive (able to detect clinically important change). Approaches to measuring health status in clinical trials include using a battery of instruments, a general instrument which provides a profile of the patient's health, an instrument that generates a health utility, or an instrument that focuses on the problems associated with a particular disease. Disease-specific instruments have been used in clinical trials in chronic airflow limitation (CAL). The Oxygen Cost Diagram is simple and easy to administer, but responsiveness and validity are unproven. The Transition Dyspnoea Index is valid and responsive, but is difficult to use in trials in which multiple measurements are desired. The Chronic Respiratory Disease Questionnaire has proved valid and responsive in controlled trials in CAL patients. Health status measures should be included in all clinical trials in CAL.
Comparison of Effect of Two Exercise Programs on Activities of Daily Living in Individuals with Dementia: A 9-Week Randomized, Controlled Trial.

To compare the effects of two exercise programs on proxy- and performance-based measures of activities of daily living (ADLs) and to explore potential motor and cognitive mediators underlying ADL improvements in individuals with dementia.



A parallel, three-group, single-blind, randomized, controlled trial.



Psychogeriatric wards.



Individuals with dementia (mean age 85.6 ± 5.1).



Each 9-week intervention consisted of thirty-six 30-minute sessions. A combined group (n = 35) participated in two strength and two walking sessions, an aerobic group (n = 35) participated in four walking sessions, and a social control group (n = 35) participated in four nonexercise social visits per week. The social group was used as a reference for the mediation analysis, which was performed in the combined and aerobic groups.



ADLs were assessed using the Katz index (proxy-reported ADL performance), Erlangen-ADL test (E-ADL) (instrumental ADL performance), and 7-item Physical Performance Test (PPT-7) (physical ADL performance).



There was a group effect for Katz index (P = .02), E-ADL (P < .001), and PPT-7 (P = .003). Differences from baseline to after the intervention were similar in the combined and aerobic groups. Exercise-induced changes in global cognition mediated changes in Katz index (95% confidence interval (CI) = 0.05-0.41), leg muscle strength mediated changes in E-ADL (95% CI = 0.03-0.43), and leg muscle strength (95% CI = 0.01-0.36) and walking endurance (95% CI = 0.01-0.43) mediated changes in PPT-7 only in the combined group.



Physical exercise can improve ADL levels in individuals with dementia, but improvements are small and seem independent of exercise type. Additional analyses suggest that combined aerobic and strength exercise may be more effective than aerobic-only exercise to effectively target ADL dysfunction in individuals with dementia. Future research is warranted to justify these exercise-specific findings.
Nonlinear nonstationary Wiener model of infant EEG seizures

This paper presents the estimation of a nonstationary nonlinear model of seizures in infants based on parallel Wiener structures. The model comprises two parts and is partly derived from the Roessgen et al. seizure model. The first part consists of a nonlinear Wiener model of the pure background activity, and the second part in a nonlinear Wiener model of the pure seizure activity with a time-varying deterministic input signal. The two parts are then combined in a parallel structure. The Wiener model consists of an autoregressive moving average filter followed by a nonlinear shaping function to take into account the non-Gaussian statistical behavior of the data. Model estimation was performed on 64 infants of whom four showed signs of clinical and electrical seizures. Model validation is performed using time-frequency-based entropy distance and shows an averaged improvement of 50% in modeling performance compared with the Roessgen model.
Improved prediction of salvage antiretroviral therapy outcomes using ultrasensitive HIV-1 drug resistance testing.

The clinical relevance of ultrasensitive human immunodeficiency virus type 1 (HIV-1) genotypic resistance testing in antiretroviral treatment (ART)-experienced individuals remains unknown.



This was a retrospective, multicentre, cohort study in ART-experienced, HIV-1-infected adults who initiated salvage ART including, at least 1 ritonavir-boosted protease inhibitor, raltegravir or etravirine. Presalvage ART Sanger and 454 sequencing of plasma HIV-1 were used to generate separate genotypic sensitivity scores (GSS) using the HIVdb, ANRS, and REGA algorithms. Virological failure (VF) was defined as 2 consecutive HIV-1 RNA levels ≥200 copies/mL at least 12 weeks after salvage ART initiation, whereas subjects remained on the same ART. The ability of Sanger and 454-GSS to predict VF was assessed by receiver operating characteristic (ROC) curves and survival analyses.



The study included 132 evaluable subjects; 28 (21%) developed VF. Using HIVdb, 454 predicted VF better than Sanger sequencing in the ROC curve analysis (area under the curve: 0.69 vs 0.60, Delong test P = .029). Time to VF was shorter for subjects with 454-GSS < 3 vs 454-GSS ≥ 3 (Log-rank P = .003) but not significantly different between Sanger-GSS < 3 and ≥3. Factors independently associated with increased risk of VF in multivariate Cox regression were a 454-GSS < 3 (HR = 4.6, 95 CI, [1.5, 14.0], P = .007), and the number of previous antiretrovirals received (HR = 1.2 per additional drug, 95 CI, [1.1, 1.3], P = .001). Equivalent findings were obtained with the ANRS and REGA algorithms.



Ultrasensitive HIV-1 genotyping improves GSS-based predictions of virological outcomes of salvage ART relative to Sanger sequencing. This may improve the clinical management of ART-experienced subjects living with HIV-1.
Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

Cognitive impairment is a major problem in elderly, affecting quality of life. Pre-clinical studies show that MMFS-01, a synapse density enhancer, is effective at reversing cognitive decline in aging rodents.



Since brain atrophy during aging is strongly associated with both cognitive decline and sleep disorder, we evaluated the efficacy of MMFS-01 in its ability to reverse cognitive impairment and improve sleep.



We conducted a randomized, double-blind, placebo-controlled, parallel-designed trial in older adult subjects (age 50-70) with cognitive impairment. Subjects were treated with MMFS-01 (n = 23) or placebo (n = 21) for 12 weeks and cognitive ability, sleep quality, and emotion were evaluated. Overall cognitive ability was determined by a composite score of tests in four major cognitive domains.



With MMFS-01 treatment, overall cognitive ability improved significantly relative to placebo (p = 0.003; Cohen's d = 0.91). Cognitive fluctuation was also reduced. The study population had more severe executive function deficits than age-matched controls from normative data and MMFS-01 treatment nearly restored their impaired executive function, demonstrating that MMFS-01 may be clinically significant. Due to the strong placebo effects on sleep and anxiety, the effects of MMFS-01 on sleep and anxiety could not be determined.



The current study demonstrates the potential of MMFS-01 for treating cognitive impairment in older adults.
Towards topological consistency and similarity of multiresolution geographical maps

Several application contexts require the ability to use together and compare different geographic datasets (maps) concerning the same or overlapping areas. This is for example the case of mediator systems, integrating distinct data sources for query processing, and GISs dealing with multi-resolution maps. In both cases, distinct maps may represent the same geographic feature with different geometry type (a road can be a region in one map and a line in another one). An important issue is therefore determining whether two multi-resolution maps are consistent, i.e., they represent the same area without contradictions, and, if not, if they are at least similar. In this paper we consider consistency and similarity of multi-resolution maps with respect to topological information. Existing approaches do not take feature geometry type into account. In this paper, we extend them with two notions of topological consistency, the first requiring the same topological relation between pairs of common features, the second `relaxing' the first one by considering similarity between topological relations. A similarity function for multi-resolution maps is then provided, taking into account both feature geometry types and topological relations of map objects. We finally discuss how the proposed consistency and similarity concepts can be significantly used in GIS applications. Some experimental results are also reported to show the effectiveness of the proposed approach.