LLukas22/scidocs huggingface dataset:
Phase I pharmacokinetic and pharmacodynamic study of Carboplatin and topotecan administered intravenously every 28 days to patients with malignant solid tumors.

PURPOSE
Preclinical studies have shown that the combination of topotecan and carboplatin is synergistic. To evaluate the schedule dependency of this interaction, the following phase I trial was designed to determine the safety and maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carboplatin and topotecan in patients with malignant solid tumors.


EXPERIMENTAL DESIGN
In part 1, patients received carboplatin on day 1 and topotecan on days 1, 2, and 3 (C-->T schedule). In part 2, topotecan was administered on days 1, 2, and 3, followed by carboplatin on day 3 (T-->C schedule). Pharmacokinetics were determined in plasma and DNA topoisomerase I catalytic activity and Pt-DNA adducts in WBC and tumor tissue.


RESULTS
Forty-one patients were included. Dose-limiting toxicities during the C-->T schedule were grade 4 thrombocytopenia and febrile neutropenia (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 4 min mg/mL; topotecan, 0.5 mg/m(2)/d). Dose-limiting toxicities during the T-->C schedule included grade 4 neutropenia, thrombocytopenia, neutropenic fever, and grade 4 nausea and vomiting (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 6 min mg/mL; topotecan, 0.9 mg/m(2)/d). One complete response and five partial responses were observed. The clearance of and exposure to carboplatin and topotecan did not depend on the sequence of drug administration. No schedule-dependent effects were seen in Pt-DNA levels and DNA topoisomerase I catalytic activity in WBC and tumor tissue. However, myelotoxicity was clearly more evident in the C-->T schedule.


CONCLUSION
The T-->C schedule was better tolerated because both hematologic and nonhematologic toxicities were milder. Other pharmacodynamic factors than the ones investigated must explain the schedule-dependent differences in toxicities.
Machine Learning Approaches for Failure Type Detection and Predictive Maintenance

With an increasing number of embedded sensing computer systems set up in production plants, machines, cars, etc., there are new possibilities to monitor and log the data from such systems. This development makes it possible to detect anomalies and predict the failures that affect maintenance plans. This thesis divides the field of failure type detection and predictive maintenance into subsections that focus on its realization by a machine learning technique, where each area of failure type detection and predictive maintenance explains and summarizes the most relevant research results in recent years. Each technique introduced is considered from a failure type detection and predictive maintenance perspective, highlighting its assets and drawbacks. An overview in tabular form shows the direction of the current research activities. It will be shown that many issues in the area of feature extraction, feature selection, and data labeling have not been researched so far. Zusammenfassung Die zunehmende Anzahl eingebetteter Sensorsysteme, die in Produktionsanlagen, Maschinen, Autos, usw. implementiert werden, eröffnet neue Möglichkeiten, um ein solches System zu überwachen und Objektdaten zu erfassen. Diese Entwicklung ermöglicht es, Anomalien zu detektieren und Fehler, die wiederum Auswirkungen auf Wartungspläne haben, vor dem eigentlichen Auftreten zu erkennen. Diese Arbeit teilt das Forschungsfeld der Fehlertypenkennung und prädiktiven Wartung in Teilgruppen auf und fokussiert sich auf Umsetzungen mithilfe maschineller Lernverfahren. Jeder Teilbereich der Fehlertypenkennung und prädiktiven Wartung wird erklärt und die Forschungsergebnisse der letzten Jahre in den einzelnen Bereichen zusammengefasst. Jede vorgestellte Technik wird mit deren Vorund Nachteile für die Fehlertypenkennung und prädiktiven Wartung betrachtet. Ein tabellarischer Überblick zeigt die aktuelle Forschungsrichtung der Teilbereiche. Weiter werden Problemstellungen in den Bereichen Feature-Extraction, Feature-Selection und Data-Labeling aufgezeigt, die bislang noch nicht untersucht worden sind. Acknowledgment At first, I would like to thank my thesis advisors, Prof. Johannes Fürnkranz and Dr. Frederik Janssen, who accepted my thesis proposal and made this work possible by offering their advice and support. Furthermore, I would like to express my gratitude to Dr. Immanuel Schweizer for the considerable amount of time that he invested in answering my early questions, as well as for the interesting discussions and organizational support. Moreover, I would like to thank Dr. Andrei Tolstikov, Dipl. Inf. Sebastian Kauschke, Dr. Axel Schulz and Simon Hofmann for their technical support and efforts. Finally, I would like to thank my wife Kerstin and my children, Paul Maximilian and Hendrick Lennard, as well as my parents, who have always stood by me and dealt with my absence from many family occasions with a smile and never-ending support.
A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study.

INTRODUCTION
Patients presenting with advanced, recurrent, or metastatic endometrial cancer have limited treatment options. On behalf of the Gynecologic Oncology Group, we conducted this phase II trial of nintedanib (BIBF 1120), a potent small molecule triple receptor tyrosine kinase inhibitor of PDGFR α and β, FGFR 1/3, and VEGFR 1-3, in this population.


OBJECTIVES
The primary objectives were to estimate event-free survival (EFS) at 6 months and the proportion of patients who have an objective tumor response. In addition, we sought to determine the nature and degree of toxicity. Secondary objectives were to estimate progression-free and overall survival.


METHODS
This was a two-stage, single-arm phase II study. Eligible patients were treated with single-agent nintedanib at a dose of 200mg twice daily.


RESULTS
Of 37 patients enrolled, 32 were eligible. There were zero complete and three partial responses for an overall response rate of 9.4% (90% 2-sided CI=2.6-22.5%). Seven patients (21.9%; 90% 2-sided CI=10.7-37.2%) were EFS at 6 months, with one patient continuing on study at the time of this writing. Serious toxicity included the following grade 3 events: gastrointestinal toxicity (5), neutropenia (1), edema (1), hypertension (1), and liver function abnormalities (5).


CONCLUSIONS
Nintedanib lacked sufficient activity as a single agent to warrant enrollment to second stage. However, preclinical data indicate it may be synergistic with paclitaxel in a population of patients enriched for specific p53 mutations that result in loss of function. Subsequent studies may evaluate this agent in combination with paclitaxel.
Emerging Points of the Supraorbital and Supratrochlear Nerves in the Supraorbital Margin With Reference to the Lacrimal Caruncle: Implications for Regional Nerve Block in Upper Eyelid and Dermatologic Surgery.

BACKGROUND
Blocking the supraorbital nerve (SON) and supratrochlear nerve (STN) by injecting anesthetic distal to the surgical site has the advantage in upper eyelid surgery that avoids obscuring the surgical landmarks and compromising the levator function.


OBJECTIVE
To identify the emerging points of the SON and STN in the supraorbital margin with reference to the lacrimal caruncle.


METHODS
Forty-nine orbits from 27 embalmed Korean cadavers were dissected. The lacrimal caruncle and facial midline were used as landmarks. The emerging points of the SON and STN in the supraorbital margin were determined.


RESULTS
The emerging points of the SON and STN were, respectively, located at 3.0 mm lateral and 3.3 mm medial to the vertical line through the apex of the lacrimal caruncle along the supraorbital margin. The horizontal distances from the facial midline to the emerging points of the SON and STN were 22.8 and 15.2 mm, respectively.


CONCLUSION
The optimum sites for achieving SON and STN block are, respectively, located approximately 3 mm lateral and 3 mm medial to the vertical line through the apex of lacrimal caruncle along the supraorbital margin. This knowledge will help the surgeon achieve an easy and accurate approach for regional nerve block.
An examination of eating patterns in community women with bulimia nervosa and binge eating disorder.

OBJECTIVE
To better understand the eating patterns of persons with eating disorders.


METHOD
This study investigated typical eating behavior (meal frequency and snacking) and atypical eating behavior among 311 community women with on-line questionnaires. Participants were classified with bulimia nervosa (BN; n =39), binge eating disorder (BED; n = 69), or controls (CON; n = 203).


RESULTS
In terms of typical eating behaviors, the BN group ate significantly fewer meals, particularly lunches, than the other two groups. Atypical eating, such as nibbling, eating double meals and nocturnal eating, was significantly more common in the eating disorder groups. More frequent breakfast consumption was associated with lower BMI in the BED and CON groups, and more frequent meal consumption was associated with less binge eating in the BED group only.


DISCUSSION
Our study revealed differences in typical and atypical eating patterns, and associations with weight and eating disorder behaviors among eating disorder and control groups.
Anatomy, Physiology, and Function of Auditory End-Organs in the Frog Inner Ear

The vertebrate ear is a highly sensitive frequency analyzer that receives sound through a specialized accessory apparatus (the external and middle ears) prior to its transmission to discrete end-organs containing sensory hair cells (the inner ear). Although there are significant differences in the structures used to receive and analyze sound, amphibian and mammalian ears function very similarly to each other. With few exceptions, the amphibian ear consists of a middle ear and an inner ear, but no external ear. As schematized in Figure 7.1, the amphibian middle ear has an exposed eardrum (tympanic membrane) overlying a funnelshaped tympanic cavity that connects to the inner ear near the base of the skull (see Mason, Chapter 6, for a review of the amphibian middle ear). The amphibian inner ear or otic labyrinth is unique among vertebrate animals in that it has two sensory organs specialized for the reception of airborne sound, the amphibian papilla (AP) and the basilar papilla (BP). These sensory papillae reside within the posterior portion of the otic labyrinth and are contained in ventrally located recesses of the large, fluid-filled saccular chamber shared with two vibration-sensitive macular organs, the sacculus and lagena (Fig. 7.1). Both the AP and BP chambers have a thin contact membrane that separates periotic perilymph from the endolymph fluid of the saccular chamber. Sound energy captured by the eardrum as well as other areas along the body of a frog is converted into fluid displacements and travels along pathways of the otic labyrinth that lead into the endolymphatic spaces of the inner ear (Hetherington et al. 1986; Lewis and Lombard 1988; Purgue and Narins 2000a). The sound path eventually leads into the AP and BP recesses before exiting into the caudal portion of the periotic canal and the round window (Purgue and Narins 2000a). Similar to the mammalian ear, the amphibian ear demonstrates exquisite intensity sensitivity and sharp frequency selectivity that are likely to arise from nonlinear, active amplification processes. How theories of mammalian auditory function apply to amphibian hearing is not known. Mechanisms of tuning and sensitivity have been extensively studied in the mammalian cochlea. It is generally agreed that the initial stage of inner ear
Extending automatic theorem proving by planning

A general concept for combining planning with automatic theorem provingis introduced. From this a system architecture based on the notion of planningtrees, methods and sensors is developed. It is illustrated by examples taken fromthe domain of sorting algorithms.
Descriptors for antimicrobial peptides.

INTRODUCTION
A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class of antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates.


AREAS COVERED
This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which of these are currently being used in quantitative structure-activity relationship (QSAR) studies for AMP optimization. Additionally, some key commercial computational tools are discussed, and both successful and less successful studies are referenced, illustrating some of the challenges facing AMP scientists. Through examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion.


EXPERT OPINION
Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge to peptide drug discovery, enabling successful design of a new generation anti-infective drug molecules. However, if this wonderful scenario is to play out, computational chemists and peptide microbiologists would need to start playing together and not just side by side.
Safety and efficacy of neoadjuvant FOLFIRINOX treatment in a series of patients with borderline resectable pancreatic ductal adenocarcinoma.

adamantinoma). Case report and review of literature . J Cancer Res Clin Oncol 2008 ; 134 : 427 – 31 . Qureshi AA , Shott S , Mallin BA , Gitelis S . Current trends in the [2] management of adamantinoma of long bones. An international study . J Bone Joint Surg Am 2000 ; 82-A : 1122 – 31 . Hazelbag HM , Taminiau AH , Fleuren GJ , Hogendoorn PC . [3] Adamantinoma of the long bones. A clinicopathological study of thirty-two patients with emphasis on histological subtype, precursor lesion, and biological behavior . J Bone Joint Surg Am 1994 ; 76 : 1482 – 99 . Lokich J . Metastatic adamantinoma of bone to lung. A case [4] report of the natural history and the use of chemotherapy and radiation therapy . Am J Clin Oncol 1994 ; 17 : 157 – 9 . Dudek AZ , Murthaiah PK , Franklin M , Truskinovsky AM . [5] Metastatic adamantinoma responds to treatment with receptor tyrosine kinase inhibitor . Acta Oncol 2010 ; 49 : 101 – 4 . Van Der Graaf WT , Blay JY , Chawla SP , Kim DW , Bui-Nguyen [6] B , Casali PG , et al . Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebocontrolled phase 3 trial . Lancet 2012 ; 379 : 1879 – 86 . Motzer R , Hutson TE , Reeves J , Hawkins R , Guo J , Nathan [7] P , et al . Randomized, open-label, phase III trial of pazopanib versus sunitinib in fi rst-line treatment of patients with metastatic renal cell carcinoma (MRCC): Results of the COMPARZ trial. 37th ESMO Congress ; 2012 Sep 28 – Oct 2 ; Vienna, Austria . ing to manufacturer instructions). The cancer panel also included SMARCB1, a gene that when mutated is associated with hypersensitivity to pazopanib in cell cultures (see the ‘ Genomics of Drug Sensitivity in Cancer ’ database; (http://www.cancerrxgene.org/translation/Drug/199); this, however, was also found to be un-mutated. We suggest that treatment with pazopanib should be considered in the setting of metastatic AD. Further molecular profi ling of AD may identify the specifi c pathway and shed light on the mechanisms involved in sensitivity to pazopanib.
Lessons learned from the past on mental health care of refugee children in Serbia

102 unaccompanied asylum-seeking adolescents showed a high prevalence of infections (58.8 %; 20 % with parasites), iron deficiency anemia (17.6 %), and a very low prevalence of non-communicable diseases (<2.0 %) [3]. The vast majority of exile children are traveling with their parents. Stress levels of parents have significantly increased which in turn negatively impacts children that are now significantly more traumatized. The number of unattended minors is rapidly rising, for instance in Germany the total number of unaccompanied minors in 2015 exceeded 60,000 [1]. Unaccompanied minors are at higher risk to develop mental health problems. Unfortunately, a significant proportion of them may be at risk of trafficking, abuse or neglect. In the above study, mental illness was present in 13.7 % of adolescents and females were more frequently affected [3]. Studies showed higher rates of depression, post-traumatic stress disorder and anxiety disorders among war refugees [4, 5]. A recent Sweden survey pointed out that neurotic disorders are more common in the unaccompanied refugees [6]. A Greek study showed an increase in the incidents of deaths of unaccompanied minors during 2014–2015 compared to previous years 2011–2013; more than 70 children have drowned trying to rich a Greek island and majority of others are often soaking wet, freezing, suffering from hypothermia due to a winter conditions [7].
Preparation by radio-frequency magnetron co-sputtering and characterization of thin films of lanthanum–strontium ferromanganites

Abstract (La 0.8 Sr 0.2 )(Mn 1 −  y Fe y )O 3 ± δ films with y  = 0, 0.2, 0.5, 0.8 and 1, a few hundred nanometers thick, were deposited onto polycrystalline yttria-stabilized zirconia YSZ by a magnetron co-sputtering technique using individual targets of La 0.8 Sr 0.2 MnO 3 and La 0.8 Sr 0.2 FeO 3 . The deposition parameters, substrate temperature and gas pressure, were studied by scanning electron microscopy, energy dispersive X-ray spectrometry, X-ray diffraction and interferential microscopy for their effects on the morphological, chemical, topographic and crystallographic properties of films and YSZ-film interfaces. (La 0.8 Sr 0.2 )(Mn 1 −  y Fe y )O 3 ±  δ thin films were found to be homogeneous, dense and crystallized in the perovskite structure after deposition at 600 °C. Profilometry by secondary ion mass spectrometry and observations by Auger electron spectrometry after selective dissolution of the films were also used to investigate both morphology and quality of the YSZ-film interface after deposition.
Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection.

BACKGROUND
The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial first demonstrated that implantation of left ventricular assist devices (LVADs) as destination therapy (DT) can provide survival superior to any known medical treatment in patients with end-stage heart failure who are ineligible for transplantation. In the present study, we describe outcomes of DT in the post-REMATCH era in the United States.


METHODS AND RESULTS
The present study included 280 patients who underwent HeartMate XVE LVAD implantation between November 2001 and December 2005. A preoperative risk score for in-hospital mortality after LVAD implantation was established in 222 patients with complete data. All patients were followed up until death or December 2006. The 1-year survival after LVAD implantation was 56%. The in-hospital mortality after LVAD surgery was 27%. The main causes of death included sepsis, right heart failure, and multiorgan failure. The most important determinants of in-hospital mortality were poor nutrition, hematological abnormalities, markers of end-organ or right ventricular dysfunction, and lack of inotropic support. Stratification of DT candidates into low (n=65), medium (n=111), high (n=28), and very high (n=18) risk on the basis of the risk score calculated from these predictors corresponded with 1-year survival rates of 81%, 62%, 28%, and 11%, respectively.


CONCLUSIONS
Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Patients with advanced heart failure who are referred for DT before major complications of heart failure develop have the best chance of achieving an excellent 1-year survival with LVAD therapy.
WordNet-based user profiles for neighborhood formation in hybrid recommender systems

Recommender systems help to reduce information overload and provide customized information access for targeted domains. Such systems take input from users and, based on their needs and preferences, provide personalized advices that help people to filter useful information. Collaborative filtering and content-based filtering are the most widely recommendation techniques adopted to date. The paper presents a new hybrid recommendation technique based on the combination of classic collaborative filtering and user profiles inferred using content-based methods.
A fast and memory-efficient Discrete Focal Stack Transform for plenoptic sensors

Article history: Available online 23 December 2014
Role of conventional angiography in evaluation of patients with carotid artery stenosis demonstrated by Doppler ultrasound in general practice.

BACKGROUND AND PURPOSE
Previous studies have suggested that patients with carotid stenosis who are candidates for endarterectomy can be effectively identified on the basis of carotid Doppler ultrasound alone. Before widespread acceptance of this policy, the accuracy of carotid Doppler ultrasound outside selected centers and clinical trials needs to be evaluated. We performed a 12-month prospective study to evaluate the accuracy of Doppler ultrasound in identifying patients for carotid intervention in general practice settings.


METHODS
Each patient referred to our endovascular service for diagnostic angiography to evaluate for carotid stenosis was interviewed and examined by a neurologist. Subjects consisted of symptomatic patients with >/=50% stenosis and asymptomatic patients with >/=60% stenosis by Doppler ultrasound. Information pertaining to demographic and cerebrovascular risk factors and the results of the carotid Doppler ultrasound were recorded. The severity of stenosis on angiograms was measured with North American Symptomatic Carotid Endarterectomy Trial criteria by a blinded observer. The results of both studies were compared to determine the relative accuracy of ultrasound results.


RESULTS
Of 130 patients (mean age, 69+/-8.8 years) who met Doppler ultrasound criteria, 22 (17%) and 8 patients (6%) were found to have 30% to 49% or <30% stenosis by angiography, respectively. The positive predictive value of carotid Doppler ultrasound for identifying appropriate symptomatic candidates for carotid intervention (angiographic stenosis >/=50%) was 80%, with a false-positive value of 20%. The positive predictive value of carotid Doppler ultrasound for identifying appropriate asymptomatic candidates for carotid intervention (angiographic stenosis >/=60%) was 59%, with a false-positive value of 41%. Carotid endarterectomy or angioplasty and stent placement were undertaken subsequently in 60 (46%) of the patients. In 94 patients who underwent cerebral angiography alone, no complications were observed.


CONCLUSIONS
The present accuracy of carotid Doppler ultrasound in general practice does not justify its use as the sole basis of selecting appropriate patients for carotid intervention. Given the relatively low rate of associated morbidity with present day techniques, additional confirmatory studies such as angiography should be performed in every patient before a decision regarding intervention is made.