LLukas22/scidocs huggingface dataset:
Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA†

BACKGROUND
We characterized the incidence of central nervous system (CNS) metastases after treatment with trastuzumab emtansine (T-DM1) versus capecitabine-lapatinib (XL), and treatment efficacy among patients with pre-existing CNS metastases in the phase III EMILIA study.


PATIENTS AND METHODS
In EMILIA, patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer previously treated with trastuzumab and a taxane were randomized to T-DM1 or XL until disease progression. Patients with treated, asymptomatic CNS metastases at baseline and patients developing postbaseline CNS metastases were identified retrospectively by independent review; exploratory analyses were carried out.


RESULTS
Among 991 randomized patients (T-DM1 = 495; XL = 496), 95 (T-DM1 = 45; XL = 50) had CNS metastases at baseline. CNS progression occurred in 9 of 450 (2.0%) and 3 of 446 (0.7%) patients without CNS metastases at baseline in the T-DM1 and XL arms, respectively, and in 10 of 45 (22.2%) and 8 of 50 (16.0%) patients with CNS metastases at baseline. Among patients with CNS metastases at baseline, a significant improvement in overall survival (OS) was observed in the T-DM1 arm compared with the XL arm [hazard ratio (HR) = 0.38; P = 0.008; median, 26.8 versus 12.9 months]. Progression-free survival by independent review was similar in the two treatment arms (HR = 1.00; P = 1.000; median, 5.9 versus 5.7 months). Multivariate analyses demonstrated similar results. Grade ≥3 adverse events were reported in 48.8% and 63.3% of patients with CNS metastases at baseline administered T-DM1 and XL, respectively; no new safety signals were observed.


CONCLUSION
In this retrospective, exploratory analysis, the rate of CNS progression in patients with HER2-positive advanced breast cancer was similar for T-DM1 and for XL, and higher overall in patients with CNS metastases at baseline compared with those without CNS metastases at baseline. In patients with treated, asymptomatic CNS metastases at baseline, T-DM1 was associated with significantly improved OS compared with XL.
A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs.

BACKGROUND
In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed.


OBJECTIVE
To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs.


METHODS
In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry.


RESULTS
291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients.


CONCLUSIONS
IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs.
Innovative design for wheeled locomotion in rough terrain

In our paper we present an innovative locomotion concept for rough terrain based on six motorized wheels. Using rhombus configuration, the rover named Shrimp has a steering wheel in the front and the rear, and two wheels arranged on a bogie on each side. The front wheel has a spring suspension to guarantee optimal ground contact of all wheels at any time. The steering of the rover is realized by synchronizing the steering of the front and rear wheels and the speed difference of the bogie wheels. This allows for precision maneuvers and even turning on the spot with minimum slippage. The use of parallel articulations for the front wheel and the bogies enables to set a virtual center of rotation at the level of or below the wheel axis. This insures maximum stability and climbing abilities even for very low friction coefficients between the wheel and the ground. A well functioning prototype has been designed and manufactured. It shows excellent performance surpassing our expectations. The robot, measuring only about 60 cm in length and 20 cm in height, is able to passively overcome obstacles of up to two times its wheel diameter and can climb stairs with steps of over 20 cm. © 2002 Elsevier Science B.V. All rights reserved.
Merkel cell polyomavirus in Merkel cell carcinoma of Italian patients

Merkel cell carcinoma (MCC) is a rare but very aggressive human malignancy of elderly or immunosuppressed patients. Clonal integration of a new human polyomavirus, the Merkel cell polyomavirus (MCPyV), has been reported in MCC patients. The main objective of the study was the detection of MCPyV and viral expression in clinical samples of Italian patients who were diagnosed MCC. DNA and RNA were extracted from nine MCCs to detect the presence of MCPyV. Viral large T gene (LT1 and LT3), and viral capsid gene (VP1) were detected by polymerase chain reaction (PCR) based methods, and the amplified PCR products were subjected to direct sequencing. The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in eight of the nine MCC lesions, whereas RNA transcripts were detected in three MCCs. These findings indicate a potential role of MCPyV in the pathogenesis of at least a subset of MCCs.
Youth Gangs : An Overview

Youth Gangs: An Overview, the initial Bulletin in this series, brings together available knowledge on youth gangs by reviewing data and research. The author begins with a look at the history of youth gangs and their demographic characteristics. He then assesses the scope of the youth gang problem, including gang problems in juvenile detention and correctional facilities. A review of gang studies provides a clearer understanding of several issues. An extensive list of references is also included for further review.
Georeferencing Wikipedia Documents Using Data from Social Media Sources

Social media sources such as Flickr and Twitter continuously generate large amounts of textual information (tags on Flickr and short messages on Twitter). This textual information is increasingly linked to geographical coordinates, which makes it possible to learn how people refer to places by identifying correlations between the occurrence of terms and the locations of the corresponding social media objects. Recent work has focused on how this potentially rich source of geographic information can be used to estimate geographic coordinates for previously unseen Flickr photos or Twitter messages. In this article, we extend this work by analysing to what extent probabilistic language models trained on Flickr and Twitter can be used to assign coordinates to Wikipedia articles. Our results show that exploiting these language models substantially outperforms both (i) classical gazetteer-based methods (in particular, using Yahoo! Placemaker and Geonames) and (ii) language modelling approaches trained on Wikipedia alone. This supports the hypothesis that social media are important sources of geographic information, which are valuable beyond the scope of individual applications.
Comprehensive Metabolomic Characterization of Coronary Artery Diseases.

BACKGROUND
Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources.


OBJECTIVES
The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD.


METHODS
A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography-quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics.


RESULTS
We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305).


CONCLUSIONS
Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression.
Symptomatic lower extremity vasculitis in giant cell arteritis: a case series.

OBJECTIVE
To describe the clinical features and outcomes of 19 patients with giant cell arteritis (GCA) and symptomatic lower extremity (LE) vasculitis.


METHODS
We reviewed medical records of all patients diagnosed with GCA and symptomatic LE involvement between January 1, 1983, and June 30, 2007, for clinical features, laboratory and radiographic findings, and outcomes.


RESULTS
From 6212 people evaluated for GCA at our institution between 1983 and 2007, we identified 19 cases of GCA with LE vasculitis, all women. Mean age at GCA diagnosis was 70 years (+/- standard deviation 7.99). Sixteen patients (84.2%) had LE symptoms preceding the diagnosis of GCA, median interval 3 months (range 1-48). Three patients (15.8%) had GCA prior to developing LE claudication, median interval 16 months (range 9-34). Cranial symptoms were absent in 42.1%. No patient had permanent visual loss. Erythrocyte sedimentation rate (ESR) was elevated in 16 patients (84.2%), with median ESR 42.5 mm/h (range 8-103). Imaging studies revealed stenotic, occlusive, or aneurysmal disease that was frequently bilateral and consistent with vasculitis. The superficial femoral arteries were most commonly affected. Five patients (26.3%) had upper extremity involvement. Hypertension was the most common cardiovascular risk factor. All patients received glucocorticoid therapy, with clinical improvement in 15 patients (79%). Median length of followup was 41 months (range 11-180 mo). Five patients (26.3%) underwent LE revascularization surgery. Two patients required LE amputation and 1 patient underwent toe amputation. Five patients received additional immunosuppressive therapy.


CONCLUSION
Symptomatic LE vasculitis from GCA is rare. Patients typically present with rapidly progressive LE claudication and elevated inflammatory markers, while cranial symptoms may be absent. GCA with LE involvement is associated with significant morbidity; prompt diagnosis and treatment is essential.
De-differentiation of primary human hepatocytes depends on the composition of specialized liver basement membrane

Basement membrane (BM) is a highly specialized extracellular matrix (ECM), which is associated with epithelia and endothelia. BM provide epithelia with structural support and also regulate cell behavior. The liver contains a unique ECM within the space of Disse, which consists of basement membrane constituents as well as fibrillar ECM molecules. Changes in composition of this ECM are considered detrimental for viability of hepatocytes during progression of liver disease. Mouse tumor-derived BM preparations, such as MatrigelTM, which are commonly used as a model for BM in vitro, differ significantly in their composition from liver BM present in vivo. In order to gain further insights into the role of BM in the regulation of hepatocyte behavior in health and disease, we generated a liver-derived basement membrane matrix (LBLM). LBLM allowed investigation of BM-hepatocyte interactions in vitro. Here we report a novel approach of generating a liver-derived basement membrane matrix by separate isolation of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans, and subsequent reconstitution into a matrix-like gel. Adhesion of primary human hepatocytes to LBLM was increased and the rate of de-differentiation was decreased compared to hepatocyte cultivation on MatrigelTM or type I collagen matrix. Primary human hepatocytes maintained their differentiated epithelial phenotype on LBLM isolated from normal human livers for more than 21 days, whereas they de-differentiated rapidly on LBLM isolated from cirrhotic human livers. Normal human LBLM contains a unique isoform composition of type IV collagen, namely α1 (IV), α2(IV), α4(IV), and α6(IV) chains, whereas cirrhotic LBLM contains only α1(IV) and α2(IV) isoforms, albeit present in increased amounts. These findings suggest that the composition of liver basement membrane is important for the maintenance of hepatocyte viability and provide anti-de-differentiation clues.
Effects of ad types, positions, animation lengths, and exposure times on the click-through rate of animated online advertisings

In this study, we focus on the click-through rate for the advertising effectiveness to examine the effects of design factors on animated online advertisings. A factorial experiment with repeated measuring was designed to collect a set of serially correlated click-through data. Ad types, positions, animation lengths, and exposure times were considered as the independent factors in this study. The generalized estimating equations (GEE) approach is introduced to the logistic regression models with correlated binary data. A goodness-of-fit statistic, quasi-likelihood information criterion (QIC) for data correlated models will be used for evaluating GEE-constructed models. The results showed a logistic regression model with order effect, two-factor interaction effect of ad types and ad positions, as well as ad positions and animation lengths are statistically significant. In addition, the GEE model with AR(1) correlation structures was well verified by the data. 2008 Elsevier Ltd. All rights reserved.
Subclinical neuropathy among Diabetes Control and Complications Trial participants without diagnosable neuropathy at trial completion: possible predictors of incident neuropathy?

OBJECTIVE
We sought to evaluate the prevalence of subclinical neuropathy in intensive and conventional treatment groups at completion of the Diabetes Control and Complications Trial (DCCT).


RESEARCH DESIGN AND METHODS
We assessed neuropathy using nerve conduction results obtained at DCCT completion after stratifying the DCCT cohort to exclude subjects with progressively less severe degrees of diagnosable neuropathy. We began with those who had confirmed clinical neuropathy (the primary DCCT end point) and eventually excluded all subjects with any clinical or electrodiagnostic evidence of neuropathy.


RESULTS
After excluding subjects with confirmed clinical neuropathy at DCCT completion, 8 of 10 nerve conduction measures (including all lower-extremity measures) were significantly improved in the intensive treatment group (O'Brien rank-sum test across all nerve conduction measures, P < 0.0001). Conduction velocity group differences were substantial, and the peroneal conduction velocity averaged 3.1 m/s faster in the intensive compared with the conventional treatment group (45.1 vs. 42.0 m/s, P < 0.0001). Numerous significant differences in median and peroneal motor conduction velocities favoring the intensive treatment group persisted, regardless of the exclusion criteria applied.


CONCLUSIONS
Intensive and conventional treatment group subjects without diagnosable neuropathy at DCCT completion had significant differences in electrophysiologic measurements favoring the intensive treatment group. Differences in subsequent incident neuropathy between the original treatment groups may reflect, in part, their levels of subclinical neuropathy at DCCT completion, rather than persistent metabolic effects.
Twenty Fraction Prostate Radiotherapy with Intra-prostatic Boost: Results of a Pilot Study.

AIMS
For patients with high-risk, locally bulky prostate cancer, an intra-prostatic boost to tumour volumes (dose-painting) offers a risk-adapted dose escalation. We evaluated the feasibility of hypofractionated dose-painting radiotherapy and the associated toxicity. The possibility to streamline a radiobiologically optimised planning protocol was also investigated.


MATERIALS AND METHODS
Twenty-eight patients were treated using a dose-painting approach; boost volumes were identified with functional magnetic resonance imaging scans. The prostate dose outside the boost volume was 60 Gy in 20 fractions, and the maximum integrated boost dose was set to 68 Gy, provided that the dose constraints to the organs at risk could be fulfilled. Rotational intensity-modulated radiotherapy was used with daily image guidance and fiducial markers.


RESULTS
The boost dose was escalated to 68 Gy for 25 patients (median dose 69 Gy, range 68-70 Gy); for three patients the boost dose was 67 Gy, due to the proximity of the urethra and/or the rectum. The mean normal tissue complication probability for rectal bleeding was 4.7% (range 3.4-5.8%) and was 3.5% for faecal incontinence (range 2.3-5.0%). At a median follow-up of 38 months (range 32-45) there was no grade 3 toxicity. Two patients developed grade 2 genitourinary toxicity (7.1%) and none developed grade 2 gastrointestinal toxicity. The mean prostate-specific antigen (PSA) for 23 patients who had stopped the adjuvant hormone therapy with a normal testosterone was 0.27 ng/ml (0.02-0.72) at follow-up; two patients have suppressed PSA and testosterone after stopping 3 year adjuvant hormone and three patients have relapsed (one pelvic node, two PSA only) at 36, 12 and 42 months, respectively.


CONCLUSIONS
A hypofractionated radiotherapy schedule, 60 Gy in 20 fractions with intra-prostatic boost dose of 68 Gy, can be achieved without exceeding dose constraints for organs at risk. Hypofractionated dose-painting escalated radiotherapy has an acceptable safety profile. The same planning protocol was used in a phase II single-arm trial (BIOPROP20: ClinicalTrials.gov identifier NCT02125175) and will further be used in a large phase III randomised trial (PIVOTALboost): patients will be randomised standard radiotherapy (60 Gy in 20 fractions) with or without lymph node radiotherapy versus dose-painting radiotherapy with or without lymph node radiotherapy; the trial will be opened for recruitment in summer 2017.
Individualized quality of life in patients with low back pain: reliability and validity of the Patient Generated Index.

OBJECTIVE
To evaluate the reliability and validity of the improved version of the Patient Generated Index (PGI) in patients with low back pain.


METHODS
The PGI was administered to 90 patients attending care in 1 of 6 institutions in Norway and evaluated for reliability and validity. The questionnaire was given out to 61 patients for re-test purposes.


RESULTS
The PGI was completed correctly by 80 (88.9%) patients and, of the 61 patients responding to the re-test, 50 (82.0%) completed both surveys correctly. PGI scores were approximately normally distributed, with a median of 40 (range 80), where 100 is the best possible quality of life. There were no floor or ceiling effects. The 5 most frequently listed areas affecting quality of life were pain, sleep, stiffness, socializing and housework. The test-retest intraclass correlation coefficient was 0.73. The smallest detectable changes for individual and group purposes were 32.8 and 4.6, respectively. The correlations between PGI scores and other instrument scores followed a priori hypotheses of low to moderate correlations.


DISCUSSION
The PGI has evidence for reliability and validity in Norwegian patients with low back pain at the group level and may be considered for application in intervention studies when a comprehensive evaluation of quality of life is important. However, the smallest detectable change, of approximately 30 points, may be considered too large for individual purposes in clinical applications.
Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES
This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder.


METHODS
Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response. Heart rate, systolic blood pressure (BP), diastolic BP, and electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase.


RESULTS
During acute titration, GUAN-IR decreased heart rate, systolic BP, and diastolic BP; DMPH increased heart rate, systolic BP, diastolic BP, and corrected QT (QTc) interval; COMB increased diastolic BP, but had no effects on heart rate, systolic BP, or QTc. During maintenance, GUAN-IR-associated decreases in heart rate and DMPH-associated increases in systolic BP returned to baseline values. Other variables across the three groups remained unchanged from the end of blinded titration. There were no discontinuations due to CV adverse events.


CONCLUSION
GUAN-IR, DMPH, and COMB were well tolerated and safe. Expected changes in CV parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB values falling intermediately between the two other treatment groups. No serious CV events occurred in any participant. GUAN-IR- and DMPH-associated CV changes generally returned to baseline with sustained therapy. These data suggest that COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant monotherapy, possibly reducing risk of the small but statistically significant changes associated with either single treatment. Clinicaltrials.gov Identifier: NCT00429273.