bluuebunny/crossref_metadata_2025 huggingface dataset:
A Method for Materials Knowledge Extraction from HTML Tables Based on Sibling Comparison
Authors: Zhang Xiaoming , Lv Pengtao , Zhao Chongchong , Wang Jianxian
Published: August 2016

There are rich data resources residing in available materials websites, and most of these data resources are shown in the form of HTML tables. However, it is difficult to distinguish the attributes and values because of the semi-structured feature of HTML tables. Therefore, identifying attributes in HTML tables is the key issue for the information acquisition. In this paper, based on sibling comparison, a method for materials knowledge extraction from HTML tables is proposed, which consists of three steps: acquiring sibling tables, identifying table pattern and extracting table data. We show how to use [Formula: see text]-measure to find the appropriate thresholds for matching of tables from materials websites when acquiring sibling tables. Further, we propose a strategy named FRFC (i.e. the First Row matching and First Column matching) to distinguish attributes and values, so that table pattern is identified. Moreover, the data from HTML tables is extracted based on their corresponding table patterns and mapped to a predefined schema, which will facilitate the population to materials ontology. The proposed approach is applicable to circumstances, where an attribute in the table may span multiple cells and matched attributes in sibling tables are more. We acquire desired accuracy ([Formula: see text]%) through using FRFC for identifying table pattern. The time about extraction may not increase significantly with increasing number of documents and cells in tables, so our approach is effective to process a large number of documents. A prototype named MTES is developed and demonstrates the effectiveness of our proposed approach.
A Modified Hill-Climbing Algorithm for Knowledge Test Assembly Based on Classified Criteria
Authors: Bojić Dragan M. , Bošnjaković Andrija M. , Protić Jelica Ž. , Tartalja Igor I.
Published: August 2016

This paper presents our experience with the development of an automated knowledge test assembler. Items are selected from an item bank on the basis of precisely formulated formal criteria. The focus of our research was on the classification of criteria for item selection and on an algorithm that assembles a test using these criteria. The criteria are expressed through parameters of a heuristic function used to evaluate a test’s quality; they were derived from teaching experience and we consider them to be highly intuitive to teachers. Item selection is performed by searching a state space using modified hill-climbing. The proposed quality function is used to guide the search for the optimal test. The test assembler is implemented inside an in-house software system, developed for preparing and scoring of knowledge tests. We have shown a statistically significant improvement in the mean reliability of the tests assembled by our test assembler, compared to the tests assembled by a widely available state-of-the-art tool. The performance indicators of the test assembler were also measured and analyzed. The experiments’ results encourage both practical use of the assembler and further research.
ComboRT: A New Approach for Generating Regression Test Cases for Evolving Programs
Authors: Sun Xiaobing , Peng Xin , Leung Hareton , Li Bin
Published: August 2016

Regression testing is essential to ensure software quality during software evolution. Two widely-used regression testing techniques, test case selection and prioritization, are used to maximize the value of the continuously enlarging test suite. However, few works consider both these two techniques together, which decreases the usefulness of the independently studied techniques in practice. In the presence of changes during program evolution, regression testing is usually conducted by selecting the test cases that cover the impact results of the changes. It seldom considers the false-positives in the information covered. Hence, the effectiveness of such regression testing techniques is decreased. In this paper, we propose an approach, ComboRT, which combines test case selection and prioritization together to directly generate a ranked list of test cases. It is based on the impact results predicted by the change impact analysis (CIA) technique, FCA–CIA, which generates a ranked list of impacted methods. Test cases which cover these impacted methods are included in the new test suite. As each method predicted by FCA–CIA is assigned with an impact factor value corresponding to the probability of this method to be impacted, test cases are then ordered according to the impact factor values of the impacted methods. Empirical studies on four Java based software systems demonstrate that ComboRT can be effectively used for regression testing in object-oriented Java-based software systems during their evolution.
A Linked Data Visualiser for Finite Element Biosimulations
Authors: Mehdi Muntazir , Khan Yasar , Jares Joao , Freitas Andre , Jha Alok Kumar , Sakellarios Antonis , Sahay Ratnesh
Published: August 2016

Biosimulation models are used to understand the multiple or different causative factors that cause impairment in human organs. Finite Element Method (FEM) provide a mathematical framework to simulate dynamic biological systems, with applications ranging from human ear, cardiovascular, to neurovascular research. Finite Element (FE) Biosimulation experiments produce huge amounts of numerical data. Visualising and analysing this huge numerical biosimulation data is a strenuous task. In this paper, we present a Linked Data Visualiser–called SIFEM Visualiser–to help domain-experts (experts in the field of ear mechanics) and clinical practitioners (otorhinolaryngologists) to Visualise, analyse and compare biosimulation results from heterogeneous, complex, and high volume numerical data. The SIFEM visualiser builds on conceptualising different aspects of biosimulations. In addition to the visualiser, we also propose how biosimulation numerical data can be conceptualised, such that it sustains the visualisation of large numerical data. The SIFEM Visualiser aims to help domain scientists and clinical practitioners exploring and analysing Finite Element (FE) numerical data and simulation results obtained from different aspects of inner ear (Cochlear) model — such as biological, geometrical, mathematical, and physical models. We validate the SIFEM Visualiser in both dimensions of qualitative and quantitative evaluation.
Application of Specific Delay Window Routing for Timing Optimization in FPGA Designs
Authors: Wegley Evan , Yi Yanhua , Zhang Qinhai
Published: August 2016

In addition to optimizing for long-path timing and routability, commercial FPGA routing engines must also optimize for various timing constraints, enabling users to fine tune their designs. These timing constraints involve both long- and short-path timing requirements. The intricacies of commercial FPGA architectures add difficulty to the problem of supporting such constraints. In this work, we introduce specific delay window routing as a general method for optimization during the routing stage of the FPGA design flow, which can be applied to various timing constraints constituting both long- and short-path requirements. Furthermore, we propose a key adjustment to standard FPGA routing technology for the purposes of specific delay window routing. By using dual-wave expansion instead of traditional single-wave expansion, we solve the critical issue of inaccurate delay estimation in our wave search, which would otherwise make routing according to a specific delay window difficult. Our results show that this dual-wave method can support stricter timing constraints than the standard single-wave method. For a suite of designs with constraints requiring connections to meet a target delay within 250ps, our dual-wave method could satisfy the requirement for all designs, whereas the single-wave method failed for more than two thirds of the designs.
10 Optimizations on Linear Search
Authors: Limoncelli Thomas A.
Published: August 2016

System administrators (DevOps engineers or SREs or whatever your title) must deal with the operational aspects of computation, not just the theoretical aspects. Operations is where the rubber hits the road. As a result, operations people see things from a different perspective and can realize opportunities outside of the basic O() analysis. Let’s look at the operational aspects of the problem of trying to improve something that is theoretically optimal already.
Presence of dipalmitoylphosphatidylcholine from the lungs at the active hydrophobic spots in the vasculature where bubbles are formed on decompression
Authors: Arieli Ran , Khatib Soliman , Vaya Jacob
Published: August 2016

Most severe cases of decompression illness are caused by vascular bubbles. We showed that there are active hydrophobic spots (AHS) on the luminal aspect of ovine blood vessels where bubbles are produced after decompression. It has been suggested that AHS may be composed of lung surfactant. Dipalmitoylphosphatidylcholine (DPPC) is the main component of lung surfactants. Blood samples and four blood vessels, the aorta, superior vena cava, pulmonary vein, and pulmonary artery, were obtained from 11 slaughtered sheep. Following exposure to 1,013 kPa for 20.4 h, we started photographing the blood vessels 15 min after the end of decompression for a period of 30 min to determine AHS by observing bubble formation. Phospholipids were extracted from AHS and from control tissue and plasma for determination of DPPC. DPPC was found in all blood vessel samples and all samples of plasma. The concentration of DPPC in the plasma samples ( n = 8) was 2.04 ± 0.90 μg/ml. The amount of DPPC in the AHS which produced four or more bubbles ( n = 16) was 1.59 ± 0.92 μg. This was significantly higher than the value obtained for AHS producing less than four bubbles and for control samples ( n = 19) (0.97 ± 0.61 μg, P = 0.027). DPPC leaks from the lungs into the blood, settling on the luminal aspect of the vasculature to create AHS. Determining the constituents of the AHS might pave the way for their removal, resulting in a dramatic improvement in diver safety.
Responses of cerebellar Purkinje cells during fictive optomotor behavior in larval zebrafish
Authors: Scalise Karina , Shimizu Takashi , Hibi Masahiko , Sawtell Nathaniel B.
Published: August 2016

Although most studies of the cerebellum have been conducted in mammals, cerebellar circuitry is highly conserved across vertebrates, suggesting that studies of simpler systems may be useful for understanding cerebellar function. The larval zebrafish is particularly promising in this regard because of its accessibility to optical monitoring and manipulations of neural activity. Although several studies suggest that the cerebellum plays a role in behavior at larval stages, little is known about the signals conveyed by particular classes of cerebellar neurons. Here we use electrophysiological recordings to characterize subthreshold, simple spike, and climbing fiber responses in larval zebrafish Purkinje cells in the context of the fictive optomotor response (OMR)—a paradigm in which fish adjust motor output to stabilize their virtual position relative to a visual stimulus. Although visual responses were prominent in Purkinje cells, they lacked the direction or velocity sensitivity that would be expected for controlling the OMR. On the other hand, Purkinje cells exhibited strong responses during fictive swim bouts. Temporal characteristics of these responses are suggestive of a general role for the larval zebrafish cerebellum in controlling swimming. Climbing fibers encoded both visual and motor signals but did not appear to encode signals that could be used to adjust OMR gain, such as retinal slip. Finally, the observation of diverse relationships between simple spikes and climbing fiber responses in individual Purkinje cells highlights the importance of distinguishing between these two types of activity in calcium imaging experiments.
Synchronization of the Fractional-Order Brushless DC Motors Chaotic System
Authors: Shen Shiyun , Zhou Ping
Published: August 2016

Based on the extension of Lyapunov direct method for nonlinear fractional-order systems, chaos synchronization for the fractional-order Brushless DC motors (BLDCM) is discussed. A chaos synchronization scheme is suggested. By means of Lyapunov candidate function, the theoretical proof of chaos synchronization is addressed. The numerical results show that the chaos synchronization scheme is valid.
Problems on Solving Matrix Aggregation in Group Decision-Making by Glowworm Swarm Optimization
Authors: Li Yaping
Published: August 2016

Judgment matrix aggregation, as an important part of group decision-making, has been widely and deeply studied due to the universality and importance of group decision-making in the management field. For the variety of judgment matrix in group decision-making, the matrix aggregation result can be obtained by using the mode of glowworm swarm optimization. First, this paper introduces the basic principle of the glowworm swarm optimization (GSO) algorithm and gives the improved GSO algorithm to solve the matrix aggregation problems. In this approach, the consistency ratio is introduced to the objective function of the glowworm swarm optimization, thus reducing the subjectivity and information loss in the aggregation process. Then, the improved GSO algorithm is applied to the solution of the deterministic matrix and the fuzzy matrix. The method optimization can provide an effective and relatively uniform aggregation method for matrix aggregation. Finally, through comparative analysis, it is shown that the method of this paper has certain advantages in terms of adaptability, accuracy, and stability to solving the matrix aggregation problems.
Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury
Authors: Mo Yu-ping , Yao Hai-jiang , Lv Wei , Song Liang-yu , Song Hong-tao , Yuan Xiao-chen , Mao Ying-qiu , Jing Quan-kai , Shi Su-hua , Li Zhi-gang
Published: August 2016

In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen’s weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats’ hind limbs among groups, and EA was shown to promote the recovery of SCI rats’ motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3.
Successful Treatment of Suspected Cannabinoid Hyperemesis Syndrome Using Haloperidol in the Outpatient Setting
Authors: Jones Jennifer L. , Abernathy Karen E.
Published: August 2016

Chronic use of cannabis can result in a syndrome of hyperemesis characterized by cyclical vomiting without any other identifiable causes. Cannabinoid hyperemesis syndrome (CHS) is seldom responsive to traditional antiemetic therapies. Despite frequent nausea and vomiting, patients may be reluctant to discontinue use of cannabis. We report a case of severe, refractory CHS with complete resolution of nausea and vomiting after treatment with haloperidol in the outpatient setting. After review of the literature, we believe this is the first reported successful outpatient treatment of CHS and suggests a potential treatment for refractory patients.
Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study
Authors: Levada Oleg A. , Cherednichenko Nataliya V. , Trailin Andriy V. , Troyan Alexandra S.
Published: August 2016

Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer’s disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy.
Differential Regulatory Analysis Based on Coexpression Network in Cancer Research
Authors: Li Junyi , Li Yi-Xue , Li Yuan-Yuan
Published: August 2016

With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA) based on gene coexpression network (GCN) increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.
Periodic Epidemic Spreading over Complex Systems: Modeling and Analysis
Authors: Wang Zhe , Yao Hong , Han Haiyan , Du Jun , Ding Chao
Published: August 2016

It is well observed that some infectious diseases show a feature of periodicity; that is, the disease may prevail during a certain season and vanish afterwards. In the effort of understanding this specific phenomenon, in this paper, we propose a spreading model with a time-variant infectivity function considering both the features of periodicity and agent variability. We apply the modified model to a scale-free network frame with tunable power-law coefficient to find out the characteristics of periodic spreading dynamics. Our work consists of both theoretical derivation and a series of corresponding numerical simulations in order to find out the influence of the parameters of both network topology and the modified model on spreading dynamics in the underlined networks. The experiments prove the success of our model in producing a periodic behavior of spreading, and the results agree well with theoretical calculations.
Trabectedin Is Active against Malignant Pleural Mesothelioma Cell and Xenograft Models and Synergizes with Chemotherapy and Bcl-2 Inhibition In Vitro
Authors: Hoda Mir A. , Pirker Christine , Dong Yawen , Schelch Karin , Heffeter Petra , Kryeziu Kushtrim , van Schoonhoven Sushilla , Klikovits Thomas , Laszlo Viktoria , Rozsas Anita , Ozsvar Judit , Klepetko Walter , Döme Balazs , Grusch Michael , Hegedüs Balazs , Berger Walter
Published: August 2016

Malignant pleural mesothelioma (MPM) is characterized by widespread resistance to systemic therapy. Trabectedin is an antineoplastic agent targeting both the malignant cells and the tumor microenvironment that has been approved for the treatment of advanced soft tissue sarcoma and ovarian cancer. In this preclinical study, we evaluated the antineoplastic potential of trabectedin as a single agent and in drug combination approaches in human MPM. Therefore, we utilized an extended panel of MPM cell lines (n = 6) and primary cell cultures from surgical MPM specimens (n = 13), as well as nonmalignant pleural tissue samples (n = 2). Trabectedin exerted a dose-dependent cytotoxic effect in all MPM cell cultures in vitro when growing as adherent monolayers or nonadherent spheroids with IC50 values ≤ 2.6 nmol/L. Nonmalignant mesothelial cells were significantly less responsive. The strong antimesothelioma activity was based on cell-cycle perturbation and apoptosis induction. The activity of trabectedin against MPM cells was synergistically enhanced by coadministration of cisplatin, a drug routinely used for systemic MPM treatment. Comparison of gene expression signatures indicated an inverse correlation between trabectedin response and bcl-2 expression. Accordingly, bcl-2 inhibitors (Obatoclax, ABT-199) markedly synergized with trabectedin paralleled by deregulated expression of the bcl-2 family members bcl-2, bim, bax, Mcl-1, and bcl-xL as a consequence of trabectedin exposure. In addition, trabectedin exerted significant antitumor activity against an intraperitoneal MPM xenograft model. Together, these data suggest that trabectedin exerts strong activity in MPM and synergizes with chemotherapy and experimental bcl-2 inhibitors in vitro. Thus, it represents a promising new therapeutic option for MPM. Mol Cancer Ther; 15(10); 2357–69. ©2016 AACR.
BPR1J373, an Oral Multiple Tyrosine Kinase Inhibitor, Targets c-KIT for the Treatment of c-KIT–Driven Myeloid Leukemia
Authors: Chen Li-Tzong , Chen Chiung-Tong , Jiaang Weir-Torn , Chen Tsai-Yun , Butterfield Joseph H. , Shih Neng-Yao , Hsu John Tsu-An , Lin Hui-You , Lin Sheng-Fung , Tsai Hui-Jen
Published: August 2016

Acute myelogenous leukemia (AML) carrying t(8;21)(q22;q22) or inv(16)/t(16;16)(p13;q22) is classified as core binding factor (CBF)-AML and accounts for approximately 15% of AML. c-KIT mutation can be detected in 17%∼46% of CBF-AML and is associated with poor prognosis. c-KIT mutation is a crucial hit and cooperates with AML1-ETO resulting from t(8;21)(q22;q22) to cause overt AML. Tyrosine kinase inhibitors (TKI) targeting c-KIT, such as imatinib, has been used successfully to treat c-KIT driven gastrointestinal stromal tumors. However, the effect of TKI on c-KIT–driven leukemia, including CBF-AML and systemic mastocytosis (SM), has not been satisfactory. BPR1J373 is a 5-phenylthiazol-2-ylamine-pyriminide derivative targeting multiple tyrosine kinases. It was shown to inhibit cell proliferation and induce apoptosis in AML cells with constitutively activated c-KIT via inhibiting c-KIT phosphorylation and its downstream signals. The compound induced apoptosis by the mitochondrial intrinsic pathway through upregulation of proapoptotic proteins Bax and Bak and caspase 8 and 9 activation in c-KIT mutant Kasumi-1 cells. Furthermore, it induced cell-cycle arrest via targeting aurora kinase B in c-KIT wild-type KG-1 cells. The antitumor response of BPR1J373 was also shown in subcutaneously grafted SCID mice. BPR1J373 was shown to effectively suppress c-KIT phosphorylation of D816V mutation by treating c-KIT–null COS-1 cells transfected with c-KIT D816V mutant plasmid. In conclusion, BPR1J373 inhibits cell proliferation of c-KIT–driven AML cells via induction of apoptosis and cell-cycle arrest. It is also effective for multiple drug–resistant c-KIT D816V mutation. BPR1J373 deserves further development for clinical use in c-KIT–driven myeloid leukemia. Mol Cancer Ther; 15(10); 2323–33. ©2016 AACR.
Hypertensive/mikrovaskuläre Erkrankung und COPD: Eine Fall-Kontroll-Studie
Authors: Lang Susanne M.
Published: August 2016

Hintergrund/Ziele: In dieser Studie untersuchten wir die Hypothese, dass bei Personen mit chronisch-obstruktiver Lungenerkrankung (COPD) Erkrankungen der kleinen Gefäße häufiger und mit höherem Schweregrad vorliegen als in einer nach Lebensalter und Geschlecht gepaarten Vergleichsgruppe von Krankenhauspatienten. Methoden: Monozentrische Fall-Kontroll-Studie mit 151 Teilnehmern mit COPD (FEV1/VC < 0,7), die an einem Lehrkrankenhaus in Melbourne über 4 Monate im Jahr 2010 jeweils unmittelbar nach einer Lungenfunktionsprüfung konsekutiv rekrutiert wurden. Die Kontrollgruppe bestand aus Personen mit normalen Lungenfunktionswerten, die zeitgleich im selben Zentrum rekrutiert wurden. Auf die Bildgebung der Netzhaut mit einer Funduskamera ohne Mydriasis (KOWA oder Canon CR5-45NM) folgte die Beurteilung der anonymisierten Aufnahmen durch zwei geschulte Grader im Hinblick auf mikrovaskuläre Retinopathie (Klassifikation nach Wong und Mitchell) und Gefäßkaliber (computergestütztes Verfahren und nach Knudtson modifizierte Parr-Hubbard-Formel). Unterschiede zwischen COPD-Patienten und Vergleichsgruppe wurden mittels Fisher-Exact-Test oder t-Test (StataCorp, Texas) untersucht. Ergebnisse: Bei den COPD-Patienten trat mikrovaskuläre Retinopathie insgesamt häufiger auf (121, 80% vs. 76, 50 %; OR 3,98; 95%-KI 2,39-6,64) und häufiger mit hohem Schweregrad (42, 28% vs. 18, 12%; OR 2,85; 95%-KI 1,55-5,23) als bei den anderen Krankenhauspatienten. COPD war auch nach Adjustierung für Geschlecht, Hypertonie, Rauchen und Diabetesdauer eine unabhängige Determinante für mikrovaskuläre Retinopathie (OR 4,56; 95%-KI 2,49-8,36). Die Netzhautarteriolen und -venulen waren bei den COPD-Patienten weiter als bei den anderen Krankenhauspatienten (mittlere Differenz: +6,5 µm; 95%-KI 1,4-11,6 bzw. +17,4 µm; 95%-KI 9,4-25,5). Weitere Venulen lagen insbesondere bei jüngeren Personen (+0,6 µm; 0,1-1,17) mit höherem Zigarettenkonsum (+0,3 µm; 0,2-0,5) oder niedrigerem Serumalbumin vor (+23,0 µm; 6,0-40,0). Es bestand kein Unterschied im Venendurchmesser zwischen aktiven und ehemaligen Rauchern (p = 0,77). Tendenziell waren die Venulen weiter bei Patienten mit höherem COPD-Schweregrad (niedriger FEV1/VC; p = 0,09) und im CT nachgewiesenen Emphysem (p = 0,06). Schlussfolgerungen: Hypertonie/mikrovaskuläre Erkrankungen treten insgesamt häufiger und mit höherem Schweregrad bei Patienten mit COPD auf. Das trägt wahrscheinlich zum erhöhten kardialen Risiko bei, das mit der Krankheit einhergeht. Übersetzung aus Kidney Blood Press Res 2016;41:29-39 (DOI:10.1159/000368544)
Ingenol Mebutate 500 µg on the Cheekbones with Concomitant Conjunctivitis
Authors: Gaide Olivier , Cattin Vincent
Published: August 2016

Ingenol mebutate induces strong inflammation after a single application already. This must be taken into account when prescribing the drug, as mistakes in the application may results in severe side effects. Here, we report the case of a 72-year-old woman who applied ingenol mebutate on the cheekbones and developed a pronounced conjunctivitis, needing topical corticosteroids. The treatment was intended for the actinic keratosis she had on the chest, and the regimen of 2 consecutive once daily applications of ingenol mebutate at 500 µg/g had been prescribed as registered. The inadvertent application on the thin skin of the cheekbones led to a pronounced inflammation. With topical steroids followed by fusidic acid, both conjunctivitis and skin inflammation resolved within a few days. The skin showed erythema for a few weeks, but after 3 months, the patient presented a perfectly smooth skin and was very happy with the cosmetic outcome. This suggests that the cheekbones are a sensitive site for ingenol mebutate, but that intense inflammation should not scare physician or patient, as clinical remission with excellent healing can still be expected.
Bowenoid Actinic Keratosis and Bowen's Disease Treated Successfully with Ingenol Mebutate
Authors: Mohanna Mosab T. , Hofbauer Günther F.L.
Published: August 2016

Ingenol mebutate (IM) is a topical pharmacotherapy approved in Switzerland since 2012 for treating non-hypertrophic, non-hyperkeratotic actinic keratosis (AK). We report 2 cases with off-label use of IM. The first case of bowenoid AK was treated with 150 μg IM for 3 consecutive days with an almost complete clinical remission of the lesion. The second case of Bowen's disease was treated with 500 μg IM for 2 consecutive days leading to complete clinical remission.
Ingenol Mebutate for Lentigo Maligna: A Case Report
Authors: Gadaldi Karolina , Feldmeyer Laurence , Yawalkar Nikhil , Hunger Robert E.
Published: August 2016

Background: Lentigo maligna (LM) is a melanoma in situ on sun-damaged skin, with a strong predilection to the head and neck area of the elderly. Many therapeutic modalities have been proposed in the treatment of this pathology, including surgery, cryotherapy, radiotherapy and topical imiquimod. Up to date surgical excision remains the treatment of choice with the lowest recurrence rate. Recently, a new topical treatment with ingenol mebutate has been described to be efficacious and well tolerated in the treatment of melanoma in situ. Objective: We sought to demonstrate that ingenol mebutate might be an efficacious and well-tolerated treatment in a patient suffering from LM on an aesthetically challenging location. Methods: Case report. Results: After therapeutic failure with imiquimod 5% cream, a new topical treatment with ingenol mebutate gel 0.015% once daily on 3 consecutive days was initiated. Despite visible inflammation, no macroscopic lesion clearance was observed. While the first follow-up using reflectance confocal microscopy (RCM) performed at 6 weeks after the completion of the therapy showed no signs of LM, the second follow-up examination at 12 weeks using RCM and biopsy confirmed recurrence of the lesion. Conclusion: Ingenol mebutate cannot be considered a standard treatment modality for all types of LM. Further studies are needed to evaluate the prerequisites that can ensure therapeutic success.
Ingenol Mebutate Treatment in a Patient with Gorlin Syndrome
Authors: Stieger Marco , Hunger Robert E.
Published: August 2016

Background: Gorlin syndrome, also known as the basal cell nevus syndrome (OMIM #109400), is a rare autosomal-dominant genetic disease. The disease, which shows mutation of the patched receptor gene (PTCH1) of the sonic hedgehog pathway, is characterized by developing multiple basal cell carcinomas (BCCs) in adolescent patients. Other clinical features include mandibular keratocysts, palmar and plantar pits, skeletal abnormalities and malformations central nervous system and genital tract. Gorlin-Goltz patients need multidisciplinary medical care and follow-up as well as genetic counseling if the patients want to have children. The treatment of multiple BCCs includes conventional surgery, micrographic Mohs surgery, cryotherapy, laser ablation, photodynamic therapy, imiquimod 5% cream, 5-fluorouracil cream as well as the sonic hedgehog pathway inhibitor vismodegib. Case Report: We report the case of a 30-year-old woman seen in our dermatological department since 2003. All the above-mentioned modalities had been employed for her numerous BCCs. The patient grew wary of the surgical procedures because of the countless scars. We successfully treated multiple BCCs with ingenol mebutate without post-inflammatory scarring. At 8-month follow-up, the patient shows no recurrence of the treated lesions. Conclusion: Ingenol mebutate can be used to treat (superficial) BCCs in patients with Gorlin-Goltz syndrome as an additional modality. Close clinical follow-up is recommended.
Giant Interfrontal Encephalocele in an Infant: A Rare Entity
Authors: Faheem Mohd , Singh Sunil Kumar , Ojha Bal Krishna , Chandra Anil , Srivastava Chhitij , Jaiswal Manish , Zeeshan Qazi
Published: August 2016

Interfrontal encephalocele is one of the rare varieties of anterior encephalocele, and a giant interfrontal encephalocele is extremely rare. The authors could find only one case report of giant interfrontal encephalocele in the literature. Anterior encephaloceles are more prevalent in South-East Asia and some northern parts of India. Giant encephalocele poses a great challenge to neurosurgeons and neuroanesthetists during surgery, as these infants usually have a low birth weight and a large sac, thus making the infant prone to hypothermia and blood loss among other risks. We encountered a patient with a giant interfrontal encephalocele aged 1 month. The rarity of this case prompted us to this report.
Cadmium Exposure Enhances Bisphenol A-Induced Genotoxicity through 8-Oxoguanine-DNA Glycosylase-1 OGG1 Inhibition in NIH3T3 Fibroblast Cells
Authors: Chen Zhi-Yu , Liu Chuan , Lu Yong-hui , Yang Ling-Ling , Li Min , He Min-Di , Chen Chun-Hai , Zhang Lei , Yu Zheng-Ping , Zhou Zhou
Published: August 2016

Background: Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in humans' daily activities, but their combined genotoxic effects remain unclear. Methods: In the present study, we exposed a mouse embryonic fibroblast cell line (NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity. The cytotoxicity was evaluated by viability with CCK-8 assay and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was measured by 2′,7′-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (γH2AX) and the comet assay. The flow cytometry was used to detect cell cycle distribution, and apoptosis was determined by TUNEL assay and western blot against poly-ADP-ribose polymerase (PARP). Results: The results showed that Cd or BPA treatments alone (with the exception of BPA exposure at 50 μM) did not alter cell viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in cell viability; increased BPA-induced LDH release, ROS production, DNA damage and G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8-oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the enhancement of Cd on BPA-induced genotoxicity and cytotoxicity. Conclusion: These findings indicate that Cd exposure aggravates BPA-induced genotoxicity and cytotoxicity through OGG1 inhibition.
Progressive Decline in Height Standard Deviation Scores in the First 5 Years of Life Distinguished Idiopathic Growth Hormone Deficiency from Familial Short Stature and Constitutional Delay of Growth
Authors: Rothermel Juliane , Lass Nina , Toschke Christina , Reinehr Thomas
Published: August 2016

Background: Familial short stature (FSS) and constitutional delay of growth (CDG) are the most frequent norm variants in children presenting with short stature. Knowing the growth patterns of these entities in the first years of life might be helpful to distinguish them from growth hormone deficiency (GHD) or other chronic diseases. Methods: We studied the height in the first 5 years of life in 26 children with FSS, in 38 children with CDG and in 14 children with idiopathic GHD. Results: Height standard deviation scores (SDS) did not change between birth and 6 months of life, while height SDS decreased significantly afterwards in GHD, FSS, and CDG. The loss of height SDS was higher in the first 2 years of life than between 2 and 5 years of life in children with CDG (-0.92 vs. -0.11; p = 0.003) or FSS (-0.79 vs. -0.01; p = 0.002). In idiopathic GHD, the loss of height SDS did not differ between the first 2 years of life and the next 3 years (-0.78 vs. -0.77; p = 0.821). Conclusion: Children with FSS and CDG showed a decline in height SDS mainly in the first 2 years of life, whereas the height SDS of children with idiopathic GHD decreased almost continuously over the first 5 years of life.
Integrative versus Conventional Therapy of Chronic Otitis Media with Effusion and Adenoid Hypertrophy in Children: A Prospective Observational Study
Authors: Szőke Henrik , Maródi Márta , Sallay Zsuzsa , Székely Balázs , Sterner Martin-Günther , Hegyi Gabriella
Published: August 2016

Background: Chronic otitis media with effusion (COME) and adenoid hypertrophy (AH) are common entities in the pediatric population. The conventional treatment approach (conventional medicine; COM) involved mainly surgery after a period of close observation. In this study, we aimed to introduce an integrative, non-invasive approach (integrative medicine; IM) for COME, AH, and associated episodes of recurrent acute otitis media, and compared outcomes with conventional treatment. Methods: We conducted a prospective, non-randomized study in an integrative primary care pediatric practice and a conventional pediatric otolaryngological clinic, where treatment modality was determined by patient preference. Out of a total 101 patients aged 1-8 years, integrative therapy was chosen by 46, and conventional treatment by 55. All patients had COME and AH diagnosed by an otolaryngologist and had moderate to severe hearing impairment. COM treatment was based on close observation over time, nasal decongestants and surgical intervention. In contrast, the IM involved a complex personalized approach with non-invasive interventions, non-allopathic medications, diet and patient education. Results: The number of surgical interventions (adenoidectomy, pressure-equalization tube insertion, myringotomy) was significantly less in the IM cohort (1 of 28 vs. 15 of 35 in the COM group, p < 0.001). The frequency of antibiotic use was significantly less in the IM group (p < 0.001). The frequency of analgesic use was also significantly less in the IM group (p = 0.029). Improvement in tympanometric measures (normal A-type curve) was higher in IM patients compared to expected spontaneous remission during the observation period. Improvement in audiometric measures (intact hearing) of IM patients was also higher than expected compared to spontaneous remission during the observation period. Conclusion: Compared to conventional treatment, integrative treatment of patients with COME and AH showed significantly lower invasive surgical intervention rates and significantly decreased antibiotic and analgesic use. The integrative treatment was effective, safe and well tolerated.
Self-Reported Adherence to Trifluridine and Tipiracil Hydrochloride for Metastatic Colorectal Cancer: A Retrospective Cohort Study
Authors: Sugita Kazuo , Kawakami Kazuyoshi , Yokokawa Takashi , Sugisaki Takahito , Takiguchi Tomomi , Aoyama Takeshi , Suzuki Kenichi , Suenaga Mitsukuni , Yamaguchi Kensei , Inoue Ayaka , Machida Yoshiaki , Yamaguchi Toshiharu , Hama Toshihiro
Published: August 2016

Background: A novel oral agent that consists of trifluridine and tipiracil hydrochloride (TFTD) has been established as salvage-line treatment for metastatic colorectal cancer (mCRC). Adherence to TFTD is crucial to maintaining appropriate curative effects. This study sought to clarify adherence to TFTD and identify candidate factors deteriorating adherence at our institution. Methods: A total of 50 consecutive mCRC patients who received TFTD monotherapy between June 1, 2014 and July 31, 2015 were analyzed in this study. Adherence to TFTD was checked by pharmacists using a self-reported treatment diary and interviewing nonadherents at a pharmaceutical outpatient clinic. The adherence rate was defined as the number of patient intakes per 20 scheduled intakes in one cycle. We retrospectively surveyed the factors from the electronic patient record associated with reduced adherence. We measured relative dose intensity, defined as the dose intensity divided by the initial dose (each in milligrams per square meter per week). Results: Patient characteristics were as follows: males/females, 20/30; median age, 61 years (range, 34-83 years); performance status 0/1, 37/13. Median relative dose intensity of TFTD was 91.0%. Adherence rates were 95.0% for the first cycle of TFTD, 97.3% for the second cycle, 98.0% for the third cycle, and 98.2% for the fourth cycle. Factors associated with deteriorated adherence to TFTD were nausea/vomiting/decreased appetite (27.1%, 23 instances), pain (25.9%, 22 instances), neutropenia (11.8%, 10 instances), and missed dose (4.7%, 4 instances). Increased nonadherence to TFTD was associated with Eastern Cooperative Oncology Group performance status 1, while increased TFTD adherence in the first cycle was associated with prior regimens ≥4. Conclusions: The high frequency of treatment-related gastrointestinal disorder is the main factor affecting adherence to TFTD. Intensive supportive care in the management of these symptoms could assist adequate adherence to TFTD in mCRC patients.
Chronic Kidney Disease Classification in Systolic Blood Pressure Intervention Trial: Comparison Using Modification of Diet in Renal Disease and CKD-Epidemiology Collaboration Definitions
Authors: Rocco Michael V. , Chapman Arlene , Chertow Glenn M. , Cohen Debbie , Chen Jing , Cutler Jeffrey A. , Diamond Matthew J. , Freedman Barry I. , Hawfield Amret , Judd Eric , Killeen Anthony A. , Kirchner Kent , Lewis Cora E. , Pajewski Nicholas M. , Wall Barry M. , Yee Jerry ,   for the SPRINT Research Group
Published: August 2016

Background: Interventional trials have used either the Modification of Diet in Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation for determination of estimated glomerular filtration rate (eGFR) to define whether participants have stages 3-5 CKD. The equation used to calculate eGFR may influence the number and characteristics of participants designated as having CKD. Methods: We examined the classification of CKD at baseline using both equations in the Systolic Blood Pressure Intervention Trial (SPRINT). eGFR was calculated at baseline using fasting serum creatinine values from a central laboratory. Results: Among 9,308 participants with baseline CKD classification using the 4-variable MDRD equation specified in the SPRINT protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage (higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage (lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90 ml/min/1.73 m2, participants <75 years were more likely to be reclassified to a less advanced CKD stage; this reclassification was more likely to occur in non-blacks rather than blacks. Participants aged ≥75 years were more likely to be reclassified to a more advanced than a less advanced CKD stage, regardless of baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73 m2) occurred in 3% of participants. Conclusions: Use of the MDRD equation led to a higher percentage of participants being classified as having CKD stages 3-4. Younger and non-black participants were more likely to be reclassified as not having CKD using the CKD-EPI equation.
Bibliotecas, Bibliofilia e Bibliografia: alguns apontamentos
Authors: Araújo Diná Marques Pereira , Reis Alcenir Soares dos
Published: August 2016

Aborda sobre Bibliografia e suas relações com a Bibliofilia e a Biblioteconomia de Livros Raros. Apresenta autores que destacam as várias vozes e significados atribuídos à Bibliografia. Discorre sobre os repertórios bibliográficos apresentando exemplos de bibliografias da Bibliofilia a partir do século XVIII. Aponta um panorama da Bibliografia Material, anglo-saxã e sua influência na Biblioteconomia. Reflete sobre as correntes da bibliografia como campo do conhecimento necessário para a formação do bibliotecário-pesquisador de livros raros, antigos e especiais
Differential Response to Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Reduced or Preserved Ejection Fraction
Authors: Wan Siu-Hin , Stevens Susanna R. , Borlaug Barry A. , Anstrom Kevin J. , Deswal Anita , Felker G. Michael , Givertz Michael M. , Bart Bradley A. , Tang W.H. Wilson , Redfield Margaret M. , Chen Horng H.
Published: August 2016

Background—

The ROSE AHF trial (Renal Optimization Strategies Evaluation in Acute Heart Failure) found that when compared with placebo, neither low-dose dopamine (2 µg/kg per minute) nor low-dose nesiritide (0.005 μg/kg per minute without bolus) enhanced decongestion or preserved renal function in AHF patients with renal dysfunction. However, there may be differential responses to vasoactive agents in AHF patients with reduced versus preserved ejection fraction (EF). This post hoc analysis examined potential interaction between treatment effect and EF (EF ≤40% versus >40%) on the ROSE AHF end points.

Methods and Results—

ROSE AHF enrolled AHF patients (n=360; any EF) with renal dysfunction. The coprimary end points were cumulative urine volume and the change in serum cystatin-C in 72 hours. The effect of dopamine (interaction
P
=0.001) and nesiritide (interaction
P
=0.039) on urine volume varied by EF group. In heart failure with reduced EF, urine volume was higher with active treatment versus placebo, whereas in heart failure with preserved EF, urine volume was lower with active treatment. The effect of dopamine and nesiritide on weight change, sodium excretion, and incidence of AHF treatment failure also varied by EF group (interaction
P
<0.05 for all). There was no interaction between vasoactive treatment’s effect and EF on change in cystatin-C. Compared with placebo, dopamine was associated with improved clinical outcomes in heart failure with reduced EF and worse clinical outcomes in heart failure with preserved EF. With nesiritide, there were no differences in clinical outcomes when compared with placebo in both heart failure with reduced EF and heart failure with preserved EF.

Conclusions—

In this post hoc analysis of ROSE AHF, the response to vasoactive therapies differed in patients with heart failure with reduced EF and heart failure with preserved EF. Investigations of AHF therapies should assess the potential for differential responses in AHF with preserved versus reduced EF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01132846.