LLukas22/scidocs huggingface dataset:
Phase I pharmacokinetic and pharmacodynamic study of lapatinib in combination with sorafenib in patients with advanced refractory solid tumors.

BACKGROUND
The epidermal growth factor receptor (EGFR) and ERBB2 (HER2) pathways and vascular endothelial growth factor (VEGF)-dependent angiogenesis have a pivotal role in cancer pathogenesis and progression. Robust experimental evidence has shown that these pathways are functionally linked and implicated in acquired resistance to targeted therapies making them attractive candidates for joined targeting. We undertook this phase I trial to assess the safety, the recommended dose for phase II trials (RPTD), pharmacokinetics (PK), pharmacodynamics (PD), and the preliminary antitumour activity of the combination of lapatinib and sorafenib in patients with advanced refractory solid tumours.


METHODS
Four cohorts of at least three patients each received lapatinib once daily and sorafenib twice daily together on a continuous schedule. Doses of lapatinib and sorafenib were escalated based on dose-limiting toxicities (DLTs) in the first treatment cycle following a traditional 3+3 design until the RPTD was reached. Additional patients were treated at the RPTD to characterise PK profiles of this combination and to investigate the potential interaction between lapatinib and sorafenib. Serum samples were collected at baseline and then prospectively every two cycles to assess changes in PD parameters. This trial is registered with ClinicalTrials.gov, number NCT00984425.


FINDINGS
Thirty patients with advanced refractory solid tumours were enroled. DLTs were grade three fatigue and grade 3 atypical skin rash observed at dose levels 3 and 4, respectively. The higher dose level explored (lapatinib 1250mg/day and sorafenib 400mg twice daily) represented the RPTD of the combination. The most common drug-related adverse events were fatigue (68%), hypocalcemia (61%), diarrhoea (57%), lymphopaenia (54%), anorexia (50%), rash (50%), and hypophosphatemia (46%). PK analysis revealed no significant effect of sorafenib on the PK profile of lapatinib. Of the 27 assessable patients for clinical activity, one achieved a confirmed complete response, four (15%) had a partial response, and 12 (44%) achieved disease stabilisation. The disease control rate overall was 63%.


INTERPRETATION
Combination treatment with lapatinib and sorafenib was feasible with promising clinical activity and without significant PK interactions. Long term tolerability seems to be challenging.
Why Google stores billions of lines of code in a single repository

Google's monolithic repository provides a common source of truth for tens of thousands of developers around the world.
Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer.

BACKGROUND
Patients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer.


OBJECTIVE
To determine cRR in CSI testicular cancer.


DESIGN, SETTING, AND PARTICIPANTS
We reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time.


RESULTS AND LIMITATIONS
At orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size <3cm, respectively. However, for patients without relapse within the first 2 yr of follow-up, the corresponding risk of relapse within the next 5 yr in the groups was 0.0%, 1.0% (95% confidence interval [CI] 0.3-1.7%), 5.6% (95% CI 3.1-8.2%), and 3.9% (95% CI 1.4-6.4%). Over time, cRR decreased (p≤0.021) in all models. Limitations include changes to surveillance protocols over time and few late relapses.


CONCLUSIONS
After 2 yr, the risk of relapse on surveillance for CSI testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients.


PATIENT SUMMARY
Our study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time.
A new image denoising method based on the bilateral filter

In this paper we propose a new method to reduce noise in digital images. The method is based on the bilateral filter. The bilateral filter is a nonlinear filter that does spatial averaging without smoothing edges. The spatial averaging aspect of the bilateral filter is very crucial; the bilateral filter has been shown to work better than wavelet thresholding in some recent papers. The proposed method improves the bilateral filter through decomposing a signal into its frequency components. In this way, noise in different frequency components can be eliminated. Experimental results with both simulated and real images are given. In addition to this new method, we also provide an empirical study of the optimal parameter selection for the bilateral filter.
Characterizing the evolving research on enterprise content management

University of Jyväskylä, Department of Computer Science and Information Systems, PO Box 35, FIN-40014, Finland; Agder University College, Department of Information Systems, PO Box 422, 4604, Kristiansand, Norway; University of Toronto, Faculty of Information Studies, 140 St. George Street, Toronto, ON M5S 3G6, Canada; University of Oulu, Department of Information Processing Science, University of Oulu, PO Box 3000, FIN-90014, Finland Abstract Innovations in network technologies in the 1990’s have provided new ways to store and organize information to be shared by people and various information systems. The term Enterprise Content Management (ECM) has been widely adopted by software product vendors and practitioners to refer to technologies used to manage the content of assets like documents, web sites, intranets, and extranets In organizational or inter-organizational contexts. Despite this practical interest ECM has received only little attention in the information systems research community. This editorial argues that ECM provides an important and complex subfield of Information Systems. It provides a framework to stimulate and guide future research, and outlines research issues specific to the field of ECM. European Journal of Information Systems (2006) 15, 627–634. doi:10.1057/palgrave.ejis.3000648
Hydro thermal scheduling using particle swarm optimization

This paper presents a new approach of particle swarm optimization (PSO) algorithm for short term hydro thermal scheduling (HTS) problems. Various possible particle selections have been studied and its effects on the global optima have been discussed. The effectiveness and stochastic nature of proposed algorithm has been tested with standard test case and the results have been compared with earlier works. This paper also describes software developed for short term hydro-thermal scheduling by considering hydro economic dispatch and thermal unit commitment. The proposed algorithm is ideally suitable for hydro-thermal co-ordination problems, hydro economic dispatch problems with unit commitment, thermal economic dispatch with unit commitment problems and scheduling of hydraulically coupled plants.
Incidence of amyloidosis over 3 years: the AMYPRO study.

OBJECTIVES
There is a lack of epidemiological information concerning amyloidosis, particularly in France. We started a 3-year prospective study (AMPYRO) to analyze the epidemiological features of amyloidosis in the eastern part of France.


METHODS
From 2003 to 2005, all patients with a tissue sample showing amyloid deposits, were included in this study. Immunohistochemistry using anti-P component, anti-SAA, anti-light chains immunoglobulins and anti-transthyretin was applied for each tissue sample. For each patient, past and present medical histories along with biological features were recorded.


RESULTS
Seventy-six patients with amyloid were identified over 3 years. The age-standardized incidence rate of amyloidosis was estimated at 14 cases per million person-years. The final entire population included in the AMYPRO study was composed of 66 patients with a mean age of 71.7+/-11.5 years old. The amyloid typing after clinical, biological and immunohistochemistry revealed senile amyloid in 40 cases (60.6%), AL amyloid in 13 (19.7%) and AA amyloid in 9 (13.6%). Neither clinical nor biological features differed significantly between the transthyretin-positive and transthyretin-negative populations.


CONCLUSION
Regarding only tissue samples, senile amyloid was the most prominent amyloid type identified. Therefore, the clinician needs to be aware that in most of the amyloid cases identified on the pathologic examination there is no need for additional examination unless there are clinical or biological signs of a primary or secondary amyloidosis.
Joyce's love stories

Contents: Introduction love and socialism in 'A Painful Case' The strange friendly pity of 'The Dead' Stephen Dedalus's market place of love The artist's amatory aesthetics Abjection and amor matris in Ulysses Richard Rowan's deep wound of doubt The Blooms' amatory metempsychosis Molly's return to Howth The politics of the new Bloomusalem Amatory Darwinism in Finnegans Wake Arrah Na Plurabelle Joyce's amorous collideorscape Afterword Bibliography Index.
Treatment options for insomnia--pharmacodynamics of zolpidem extended-release to benefit next-day performance.

BACKGROUND
Insomnia can manifest as difficulty in falling asleep, in maintaining sleep throughout the night, or waking up too early, with symptoms often unpredictably changing over time. Pharmacologic options for insomnia treatment include prescription hypnotics, such as gamma-amino butyric acid-receptor agonists, sedating antidepressants, over-the-counter antihistamines, melatonin-receptor agonists, and alternative therapies. A concern with insomnia medications is the risk of next-day residual effects, which can impair memory and ability to perform certain tasks, such as driving, and may increase the risk of accidents and falls, especially in the elderly.


OBJECTIVES
To describe the impact of current insomnia treatments on next-day performance.


RESULTS
The longer-acting benzodiazepines are associated with next-day "hangover" effects and, as a result, have been largely replaced by agents in the nonbenzodiazepine class, which typically have shorter half-lives. The hypnotic, sedative activities of these classes of drugs depend on variations in binding characteristics to the alpha1 subunit of the gamma-amino butyric acidA-receptor, which inhibits neuronal activity in broad areas of the brain and is found in areas of the brain responsible for sleep/wakefulness and sedation. However, nonbenzodiazepines with a rapid onset of action and short half-life have shown limited efficacy for maintaining sleep throughout the night. These properties have contributed to the development of modified-release formulations. Zolpidem extended-release is a bilayer tablet that retains the fast onset of action of its parent compound zolpidem while extending the duration of hypnotic activity, owing to a slower-release portion of the tablet.


CONCLUSIONS
Based on clinical evidence, the risk of residual next-day effects of zolpidem extended-release is limited, mainly due to the similarly short half-life in its extended-release formulation.
Generalized Multiclass AdaBoost and Its Applications to Multimedia Classification

AdaBoost has received considerable attention in the vision and multimedia research community in recent years. It is originally designed for two-class classification problems. To handle multiple classes, many AdaBoost extensions have been developed primarily based on various schemes for reducing multiclass classification to multiple two-class problems. From a statistical prospective, AdaBoost can be viewed as a forward stepwise additive model using an exponential loss function. In this paper, we derive a generalized form of AdaBoost for multiclass classification based on a multiclass exponential loss function. To prove its effectiveness, we benchmarked a number of multimedia problems of different nature. Experimental results show that the new boosting algorithm outperforms other multiclass alternatives. In addition, the generalized boosting algorithm can be used to either boost a multiclass classifier, or build a multiclass classifier from a binary one.
Subgroups of patients with cancer with different symptom experiences and quality-of-life outcomes: a cluster analysis.

PURPOSE/OBJECTIVES
To identify subgroups of outpatients with cancer based on their experiences with the symptoms of fatigue, sleep disturbance, depression, and pain; to explore whether patients in the subgroups differed on selected demographic, disease, and treatment characteristics; and to determine whether patients in the subgroups differed on two important patient outcomes: functional status and quality of life (QOL).


DESIGN
Descriptive, correlational study.


SETTING
Four outpatient oncology practices in northern California.


SAMPLE
191 outpatients with cancer receiving active treatment.


METHODS
Patients completed a demographic questionnaire, Karnofsky Performance Status scale, Lee Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies Depression Scale, Multidimensional Quality-of-Life Scale Cancer, and a numeric rating scale of worst pain intensity. Medical records were reviewed for disease and treatment information. Cluster analysis was used to identify patient subgroups based on patients symptom experiences. Differences in demographic, disease, and treatment characteristics as well as in outcomes were evaluated using analysis of variance and chi square analysis.


MAIN RESEARCH VARIABLES
Subgroup membership, fatigue, sleep disturbance, depression, pain, functional status, and QOL.


FINDINGS
Four relatively distinct patient subgroups were identified based on patients experiences with four highly prevalent and related symptoms.


CONCLUSIONS
The subgroup of patients who reported low levels of all four symptoms reported the best functional status and QOL.


IMPLICATIONS FOR NURSING
The findings from this study need to be replicated before definitive clinical practice recommendations can be made. Until that time, clinicians need to assess patients for the occurrence of multiple symptoms that may place them at increased risk for poorer outcomes.
Ascertaining the validity of individual protocols from Web-based personality inventories

The research described in this article estimated the relative incidence of protocols invalidated by linguistic incompetence, inattentiveness, and intentional misrepresentation in Webbased versus paper-and-pencil personality measures. Estimates of protocol invalidity were derived from a sample of 23,994 protocols produced by individuals who completed an online version of the 300-item IPIP representation of the NEO-PI-R (Goldberg, 1999). Approximately 3.8% of the protocols were judged to be products of repeat participants, many of whom apparently resubmitted after changing some of their answers. Among nonduplicate protocols, about 3.5% came from individuals who apparently selected a response option repeatedly without reading the item, compared to .9% in a sample of paper-and-pencil protocols. The missing response rate was 1.2%, which is 2–10 times higher than the rate found in several samples of paper-and-pencil inventories of comparable length. Two measures of response consistency indicated that perhaps 1% of the protocols were invalid due to linguistic incompetence or inattentive responding, but that Web participants were as consistent as individuals responding to a paper-and-pencil inventory. Inconsistency did not aVect factorial structure and was found to be related positively to neuroticism and negatively to openness to experience. Intentional misrepresentation was not studied directly, but arguments for a low incidence of misrepresentation are presented. Methods for preventing, detecting, and handling invalid response patterns are discussed. Suggested for future research are studies that assess the moderating eVects of linguistic incompetence, inattenPrepared for the special issue of the Journal of Research in Personality 39 (1), February 2005, containing the proceedings of the 2004 meeting of the Association for Research in Personality. E-mail address: j5j@psu.edu. 0092-6566/$ see front matter  2004 Elsevier Inc. All rights reserved. doi:10.1016/j.jrp.2004.09.009 104 J.A. Johnson / Journal of Research in Personality 39 (2005) 103–129 tiveness, and intentional misrepresentation on agreement between self-report and acquaintance judgments about personality.  2004 Elsevier Inc. All rights reserved.
Clinical and radiographic spectrum of septic pulmonary embolism.

AIMS
To review the clinical presentation, radiographic findings, and outcome of therapy in children with septic pulmonary embolism.


METHODS
Retrospective analysis of patients in a tertiary paediatric facility in northern Taiwan.


RESULTS
Ten children were identified with septic pulmonary emboli in a four year retrospective chart review between 1998 and 2001. Seven were immunocompetent, two were premature infants, one had beta thalassemia major. Seven had community acquired staphylococcal infections and bacteraemia, of which six were methicillin resistant Staphylococus aureus (MRSA) isolates. Five had soft tissue infections, two bone infections, one suppurative otitis media, one catheter related infection, and one unknown foci of infection. Multiple and bilateral nodular pulmonary parenchymal lesions were common on plain chest radiographs, but chest computed tomography scans showed the additional findings of a "vessel sign" and central cavitations, confirming the existence of septic pulmonary embolism.


CONCLUSIONS
Community acquired MRSA infections occurred in seven patients with septic pulmonary embolism but without predisposing high risk factors. Critically ill children with skin, soft tissue, or bone infections, when associated with septic pulmonary embolism in an area with a high rate of MRSA, should be empirically treated with glycopeptides (such as vancomycin or teicoplanin) before susceptibility results are known, in order to minimise morbidity and avoid mortality.
A survey on unsupervised outlier detection in high-dimensional numerical data

High-dimensional data in Euclidean space pose special challenges to data mining algorithms. These challenges are often indiscriminately subsumed under the term ‘curse of dimensionality’, more concrete aspects being the so-called ‘distance concentration effect’, the presence of irrelevant attributes concealing relevant information, or simply efficiency issues. In about just the last few years, the task of unsupervised outlier detection has found new specialized solutions for tackling high-dimensional data in Euclidean space. These approaches fall under mainly two categories, namely considering or not considering subspaces (subsets of attributes) for the definition of outliers. The former are specifically addressing the presence of irrelevant attributes, the latter do consider the presence of irrelevant attributes implicitly at best but are more concerned with general issues of efficiency and effectiveness. Nevertheless, both types of specialized outlier detection algorithms tackle challenges specific to high-dimensional data. In this survey article, we discuss some important aspects of the ‘curse of dimensionality’ in detail and survey specialized algorithms for outlier detection from both categories. © 2012 Wiley Periodicals, Inc. Statistical Analysis and Data
Nanoarchitectured Design of Porous Materials and Nanocomposites from Metal-Organic Frameworks.

The emergence of metal-organic frameworks (MOFs) as a new class of crystalline porous materials is attracting considerable attention in many fields such as catalysis, energy storage and conversion, sensors, and environmental remediation due to their controllable composition, structure and pore size. MOFs are versatile precursors for the preparation of various forms of nanomaterials as well as new multifunctional nanocomposites/hybrids, which exhibit superior functional properties compared to the individual components assembling the composites. This review provides an overview of recent developments achieved in the fabrication of porous MOF-derived nanostructures including carbons, metal oxides, metal chalcogenides (metal sulfides and selenides), metal carbides, metal phosphides and their composites. Finally, the challenges and future trends and prospects associated with the development of MOF-derived nanomaterials are also examined.
Correlations between acoustic rhinometry, subjective symptoms, and endoscopic findings in symptomatic children with nasal obstruction.

IMPORTANCE
Nasal obstruction is common in children and difficult to quantify objectively. Symptom quantification is paramount for surgical and medical decision making. Acoustic rhinometry is a relatively new technique aimed at the objective assessment of nasal obstruction. There is no standardized method for the objective assessment of the pediatric nasal airway.


OBJECTIVE
To explore the correlations between acoustic rhinometry (AR), subjective symptoms, and endoscopic findings in children presenting with nasal obstruction.


DESIGN, SETTING, AND PARTICIPANTS
A cross-sectional, exploratory, diagnostic study of prospectively collected data from a multidisciplinary airway clinic (pulmonology, orthodontics, and otolaryngology) database at a tertiary academic referral center. Data were collected over a 2-year period (2010-2012) from 65 nonsyndromic children (38 boys) 7 years and older (mean [SD] age, 10.3 [2.5] years [range, 7-14 years]), presenting with persistent nasal obstructive symptoms for at least 1 year, without signs and symptoms of sinus disease.


INTERVENTIONS
We collected patient demographics and medical history information including allergy, asthma, and sleep-disordered breathing. Subjective nasal obstruction was scored using a visual analog scale (VAS). Sleep-disordered breathing was assessed using overnight pulse oximetry. The adenoid size, septal position, and visual severity of chronic rhinitis (endoscopic rhinitis score [ERS]) were rated on nasal endoscopy by 2 independent reviewers and validated by agreement. Acoustic rhinometry (AR) was undertaken before and after use of a decongestant.


MAIN OUTCOMES AND MEASURES
Correlation and multiple regression analyses were performed to explore interrelationships between subjective nasal obstruction VAS, AR, and nasal endoscopy.


RESULTS
Among the 65 patients, 28 (43%) had symptoms of sleep-disordered breathing, 14 (22%) had allergic rhinitis, 10 (15%) had asthma, 27 (41%) had grade 3 or 4 adenoidal obstruction, 28 (43%) had an ERS of 2, 6 (9%) had an ERS of 3, and 19 (29%) had septal deviation. Significant correlations were found between subjective nasal obstruction VAS score and ERS (r = -0.364, P = .003), ERS and minimal cross-sectional area before decongestion (r = -0.278, P = .03), and adenoid size and calculated nasal resistance after decongestion (r = 0.430, P < .001). Multiple regression analysis showed that the ERS was the only significant predictor of VAS score (β of -22.089; 95% CI, -35.56 to -8.61 [P = .002]). No predictors were identified for AR variables.


CONCLUSIONS AND RELEVANCE
Among the evaluated tools, endoscopy appears to be the most reliable tool to estimate the degree of subjective nasal symptoms.