nils-herrmann/clean_scirepeval huggingface dataset:
Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial.

The NeoALTTO trial showed that dual HER2 blockade nearly doubles the rate of pathologic complete response (pCR) in patients with primary HER2-positive breast cancer. However, this did not translate into a higher rate of breast-conserving surgery (BCS).



In NeoALTTO, patients with HER2-positive breast cancer were randomly assigned to either trastuzumab, lapatinib or their combination with paclitaxel before surgery with pCR as the primary end point. We investigated the association between the surgery type and clinicopathological factors and response to treatment, adjusting for the treatment arm.



Four hundred and twenty-nine patients were subjected to breast surgery. Two hundred and forty-two (56%) and 187 (44%) patients underwent mastectomy and BCS, respectively. In a logistic regression model, negative estrogen receptor (ER), multicentricity and the presence of a palpable mass before surgery were significantly associated with a low chance of BCS. Conversely, patients with small tumors and those eligible for BCS at diagnosis were managed more with BCS, independent of the treatment arm. Radiological response was not associated with the surgical decision.



Tumor characteristics before neoadjuvant therapy play a main role in deciding the type of surgery calling for a clear consensus on the role of BCS in patients responding to neoadjuvant therapy.
Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients

To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ).  Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension.  This was a multicentre, placebo-controlled, double-blind study with a parallel group design. Subjects with a sitting diastolic blood pressure (DBP) ≥ 95 mmHg were randomized to monotherapy with placebo, moexipril 7.5 mg o.d., moexipril 15 mg o.d. or HCTZ 25 mg o.d. for 8 weeks.  Throughout the study period treatment with moexipril and HCTZ resulted in significant reductions of DBP compared with placebo, but there were no significant differences between the active treatment groups. At end point the adjusted mean reductions were 10.5, 8.7 and 10.1 mmHg in the HCTZ, moexipril 7.5 mg and moexipril 15 mg groups, respectively, compared to 3.9 mmHg in the placebo group. Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels. Otherwise, both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group.  Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension.
Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: a randomized, double-blind, placebo-controlled, crossover trial.

Creatine supplementation has emerged as a promising non-pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. The objective of this study was to examine the efficacy and safety of creatine supplementation in childhood systemic lupus erythematosus (C-SLE).



C-SLE patients with mild disease activity (n = 15) received placebo or creatine supplementation in a randomized fashion using a crossover, double-blind, repeated-measures design. The participants were assessed at baseline and after 12 weeks in each arm, interspersed by an eight-week washout period. The primary outcomes were muscle function, as assessed by a battery of tests including one-maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test, and the handgrip test. Secondary outcomes included body composition, biochemical markers of bone remodeling, aerobic conditioning, quality of life, and physical capacity. Possible differences in dietary intake were assessed by three 24-hour dietary recalls. Muscle phosphorylcreatine content was measured through phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the intervention was assessed by laboratory parameters, and kidney function was measured by (51)Cr-EDTA clearance. Additionally, self-reported adverse events were recorded throughout the trial.



Intramuscular phosphorylcreatine content was not significantly different between creatine and placebo before or after the intervention (creatine-Pre: 20.5 ± 2.6, Post: 20.4 ± 4.1, placebo-Pre: 19.8 ± 2.0; Post: 20.2 ± 3.2 mmol/kg wet muscle; p = 0.70 for interaction between conditions). In addition, probably as a consequence of the lack of change in intramuscular phosphorylcreatine content, there were no significant changes between placebo and creatine for any muscle function and aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of life scores (p > 0.05). The (51)Cr-EDTA clearance was not altered by creatine supplementation and no side effects were noticed.



A 12-week creatine supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse effects but did not affect intramuscular phosphorylcreatine, muscle function, free-fat mass or quality of life in non-active C-SLE patients.
The Multiple Sclerosis Intimacy and Sexuality Questionnaire -- re-validation and development of a 15-item version with a large US sample.

Sexual dysfunction is common in multiple sclerosis (MS) but reliable and valid measurement in this population is needed.



The objective of this research is to re-validate the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 in a large US sample.



A total of 6300 MS patients from the NARCOMS registry completed the MSISQ-19. Unforced principal component analysis utilizing oblique rotation with Kaiser Normalization validated its construct validity.



The scree plot supported a three-component solution, with 63% of total variance explained. The components mirrored the original validation study measuring primary, secondary, and tertiary sexual dysfunction. PCA suggested the scale could be shortened to 15 items, which were found to apply equally well to males and females (with one primary item specific for each sex). The components were moderately intercorrelated (Pearson rs ranged from 0.5 to 0.67). The secondary subscale correlated most highly with self-reported disability (r (6081) = 0.44, p < 0.001), whereas the tertiary subscale correlated most highly with psychological distress (r (5992) = -.37, p < 0.001). Cronbach's alpha for the total scale (0.92) and the subscales (primary, 0.87; secondary, 0.82; tertiary, 0.91) demonstrated good reliability.



The revised 15-item MSISQ is a reliable and valid measure of sexual dysfunction in men and women with MS.
A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer

This phase I/II study of saracatinib in combination with gemcitabine in patients with advanced pancreatic cancer was conducted by the NCIC Clinical Trials Group. The aims were to define the recommended phase II dose (RP2D) of saracatinib when combined with gemcitabine, and assess the efficacy of this combination in advanced pancreatic cancer.  Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and no prior chemotherapy. In phase I saracatinib was escalated in combination with gemcitabine (1000 mg/m2) to determine the recommended phase II dose (RP2D). The study was then expanded to a single arm phase II trial using a Simon 2-stage design. The primary endpoint was objective tumor response (OR) plus stable disease ≥4 months (SD4) rate; if ≥8 patients had OR+SD4, the study would proceed to stage 2.  Thirteen patients were enrolled into the phase I portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in combination with gemcitabine. Twenty-one additional patients were then enrolled at the RP2D (phase II). Of the 22 response evaluable patients treated at the RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%) had a partial response to treatment. Objective criteria for continuing to stage 2 were thus not met and the trial was closed following the accrual of 34 patients.  Saracatinib 175 mg daily in combination with gemcitabine is well tolerated but the combination did not improve efficacy over what would be expected from gemcitabine alone.
Urinary CD133+ Extracellular Vesicles Are Decreased in Kidney Transplanted Patients with Slow Graft Function and Vascular Damage

Extracellular vesicles (EVs) present in the urine are mainly released from cells of the nephron and can therefore provide information on kidney function. We here evaluated the presence of vesicles expressing the progenitor marker CD133 in the urine of normal subjects and of patients undergoing renal transplant. We found that EV expressing CD133 were present in the urine of normal subjects, but not of patients with end stage renal disease. The first day after transplant, urinary CD133+ EVs were present at low levels, to increase thereafter (at day 7). Urinary CD133(+) EVs significantly increased in patients with slow graft function in respect to those with early graft function. In patients with a severe pre-transplant vascular damage of the graft, CD133(+) EVs did not increase at day 7. At variance, the levels of EVs expressing the renal exosomal marker CD24 did not vary in the urine of patients with end stage renal disease or in transplanted patients in respect to controls. Sorted CD133(+) EVs were found to express glomerular and proximal tubular markers. These data indicate that urinary CD133(+) EVs are continuously released during the homeostatic turnover of the nephron and may provide information on its function or regenerative potential.
Prediction of aromatase inhibitory activity using the efficient linear method (ELM)

Aromatase inhibition is an effective treatment strategy for breast cancer. Currently, several in silico methods have been developed for the prediction of aromatase inhibitors (AIs) using artificial neural network (ANN) or support vector machine (SVM). In spite of this, there are ample opportunities for further improvements by developing a simple and interpretable quantitative structure-activity relationship (QSAR) method. Herein, an efficient linear method (ELM) is proposed for constructing a highly predictive QSAR model containing a spontaneous feature importance estimator. Briefly, ELM is a linear-based model with optimal parameters derived from genetic algorithm. Results showed that the simple ELM method displayed robust performance with 10-fold cross-validation MCC values of 0.64 and 0.56 for steroidal and non-steroidal AIs, respectively. Comparative analyses with other machine learning methods (i.e. ANN, SVM and decision tree) were also performed. A thorough analysis of informative molecular descriptors for both steroidal and non-steroidal AIs provided insights into the mechanism of action of compounds. Our findings suggest that the shape and polarizability of compounds may govern the inhibitory activity of both steroidal and non-steroidal types whereas the terminal primary C(sp3) functional group and electronegativity may be required for non-steroidal AIs. The R code of the ELM method is available at http://dx.doi.org/10.6084/m9.figshare.1274030.
Retinal Arteriolar Morphometry Based on Full Width at Half Maximum Analysis of Spectral-Domain Optical Coherence Tomography Images

In this study, we develop a microdensitometry method using full width at half maximum (FWHM) analysis of the retinal vascular structure in a spectral-domain optical coherence tomography (SD-OCT) image and present the application of this method in the morphometry of arteriolar changes during hypertension.



Two raters using manual and FWHM methods measured retinal vessel outer and lumen diameters in SD-OCT images. Inter-rater reproducibility was measured using coefficients of variation (CV), intraclass correlation coefficient and a Bland-Altman plot. OCT images from forty-three eyes of 43 hypertensive patients and 40 eyes of 40 controls were analyzed using an FWHM approach; wall thickness, wall cross-sectional area (WCSA) and wall to lumen ratio (WLR) were subsequently calculated.



Mean difference in inter-rater agreement ranged from -2.713 to 2.658 μm when using a manual method, and ranged from -0.008 to 0.131 μm when using a FWHM approach. The inter-rater CVs were significantly less for the FWHM approach versus the manual method (P < 0.05). Compared with controls, the wall thickness, WCSA and WLR of retinal arterioles were increased in the hypertensive patients, particular in diabetic hypertensive patients.



The microdensitometry method using a FWHM algorithm markedly improved inter-rater reproducibility of arteriolar morphometric analysis, and SD-OCT may represent a promising noninvasive method for in vivo arteriolar morphometry.
On the complexity of halfspace area queries

Given a non convex simple polygon $P$, is it possible to construct a d ata structure which after preprocessing can answer halfspace area queries (i.e. given a line, determine the area of the portion of the polygon above the line) in $o(n)$ time? We answer negatively, proving a $\Omega(n)$ lower bound on the query time of any data structure performing this task. We then consider the batched version of the same problem: given a polygon $P$ with $n$ vertices, and $k$ query lines, we present an algorithm that computes the area of $P$ on both sides of each line in $O^{*}(n^{3/5}k^{4/5}+n+k)$ time. Variants of our method allow the query of a collection of weighted polygons with or without holes, and solve several other related problems within the same time bounds.
Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease.

Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease-related death in relation to an underlying inflammatory response.



coronary angiography was performed in 1134 subjects, and 989 patients with documented coronary artery disease were studied prospectively. CMV-IgG titers and interleukin (IL)-6 levels were measured before angiography. Increasing titers of CMV correlated with the elevation of IL-6 levels (P<0.001) after adjustment for possible confounders. All patients were followed up for a median of 3.1 years (maximum 4.3 years). During follow-up, 96 patients died, 70 of cardiac disease. Overall, CMV seropositivity was not related to cardiac mortality after adjustment for confounding variables (P=0.19). In contrast, in patients with elevated IL-6 levels (>/=11.9 pg/mL, median level), CMV seropositivity was independently associated with a 3.2-fold (95% CI 1.4 to 7.3, P=0.007) increase in risk of future cardiac death, whereas in individuals without IL-6 elevation, previous CMV infection had no effect on cardiac mortality.



MV seropositivity in patients with an inflammatory response is independently associated with future cardiac mortality, whereas this association is lost in patients who do not demonstrate an inflammatory response. These data support the hypothesis that the atherosclerotic effects of CMV are mediated through an underlying inflammatory response.
Intra-articular hyaluronic acid compared with corticoid injections for the treatment of rhizarthrosis.

Prospective assessment of the efficacy and tolerability of intra-articular sodium hyaluronate (SH; Ostenil mini) and triamcinolone acetonide (TA; Volon A10) for treatment of osteoarthritis (OA) of the carpometacarpal (CMC) joint of the thumb in a 26-week, controlled, randomized, on an intention to treat, masked-observer study.



Patients were treated with three intra-articular injections of either SH (n = 28) or TA (n = 28). Primary assessments were pain according to a 100mm visual analogue scale and extensive clinical and functional parameters such as swelling, grip power and range of motion. The population was analysed using one- and two-sided Mann-Whitney (MW) estimators.



Maximum pain relief occurred at 2-3 weeks for TA and at week 26 for SH after the first intra-articular injection. At weeks 2-3 TA was significantly better than SH (MW: 0.3319 and 0.3063; P = 0.9827 and 0.9929). At week 26 a slight superiority of SH could be observed (MW: 0.53; P = 0.3624) and non-inferiority could be proven. After 26 weeks lateral pinch power was significantly better in the SH-group (MW: 0.6331; P = 0.0226). In all, 88.0% of patients treated with SH and 79.1% of the TA-group described pain improvement after 26 weeks. Both agents were well tolerated. No adverse events with causal connection to the investigational products occurred.



A single course of three SH injections is effective in relieving pain and improving joint function in patients with OA of the CMC joint of the thumb. Although in comparison with triamcinolone its effects are achieved more slowly, the results indicate a superior long-lasting effect of hyaluronan at 6 months after end of treatment period.
Novel Gut-Based Pharmacology of Metformin in Patients with Type 2 Diabetes Mellitus

Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK) activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology. We hypothesized that the pharmacology of metformin includes alteration of bile acid recirculation and gut microbiota resulting in enhanced enteroendocrine hormone secretion. In this study we evaluated T2DM subjects on and off metformin monotherapy to characterize the gut-based mechanisms of metformin. Subjects were studied at 4 time points: (i) at baseline on metformin, (ii) 7 days after stopping metformin, (iii) when fasting blood glucose (FBG) had risen by 25% after stopping metformin, and (iv) when FBG returned to baseline levels after restarting the metformin. At these timepoints we profiled glucose, insulin, gut hormones (glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose-dependent insulinotropic peptide (GIP) and bile acids in blood, as well as duodenal and faecal bile acids and gut microbiota. We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates. These effects reversed when metformin was restarted. Effects on circulating PYY were more modest, while GIP changes were negligible. Microbiota abundance of the phylum Firmicutes was positively correlated with changes in cholic acid and conjugates, while Bacteroidetes abundance was negatively correlated. Firmicutes and Bacteroidetes representation were also correlated with levels of serum PYY. Our study suggests that metformin has complex effects due to gut-based pharmacology which might provide insights into novel therapeutic approaches to treat T2DM and associated metabolic diseases.
Prevention of emergency physician migratory contamination in a cluster randomized trial to increase tissue plasminogen activator use in stroke (the INSTINCT trial).

Cluster randomized trials (CRTs) are increasingly used to evaluate quality improvement interventions aimed at health care providers. In trials testing emergency department (ED) interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating EDs would prevent migratory contamination in a CRT designed to increase ED delivery of tissue plasminogen activator (tPA) in stroke (the INSTINCT trial).



INSTINCT was a prospective, cluster randomized, controlled trial. Twenty-four Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as greater than 10% of EPs affected. Nonadherence, total crossover (contamination+nonadherence), migration distance, and characteristics were determined.



Three hundred seven EPs were identified at all sites. Overall, 7 (2.3%) changed study sites. One moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination); and 4 (1.3%) moved from control to intervention (nonadherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites.



The mobile nature of EPs should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design.
[Prevalence of malnutrition in Spanish institutionalized older people: a multicentric nationwide analysis].

Deficient nutritional status has important implications on vulnerable people's health status, such as those with chronic diseases or older people in situation of dependency.



To examine SARquavitae centers users' nutritional status at admission.



Health, cognitive and functional status of people admitted to any company centers during 2012 was studied. Nutritional status was assessed using the short version of the Mini Nutritional Assessment. Finally, an analysis was performed to identify the most influential variables on the sample's nutritional status.



Clinical records of 4,297 admissions were analyzed. The average age was 82.08 years and 66.1% were women with high comorbidity. At admission, 30.4% of the sample was in malnutrition and 49.4% at risk of malnutrition. A higher prevalence of malnutrition is found in women, in those coming from an acute care hospital or its outpatient clinics, with worse functional and cognitive status and those with chronic conditions such as dementia, cerebrovascular disease or dysphagia.



As demonstrated by the study results, people admitted to SARquavitae nursing homes present a high clinical complexity. Comprehensive assessments are needed that allow establishing specific care plans for people with complex care needs in nursing homes.