bluuebunny/crossref_metadata_2025 huggingface dataset:
Exogenous putrescine affects polyamine and arginine metabolism in rat liver following bile ductus ligation
Authors: Mladenović Bojan , Mladenović Nikola , Brzački Vesna , Petrović Nemanja , Kamenov Aleksandar , Golubović Mladjan , Ničković Vanja , Stojanović Nikola M. , Sokolović Dušan T.
Published: September 2018

Rat bile duct ligation (BDL) represents a useful method that mimics obstructive extrahepatic cholestasis, which is known to be a frequent disorder in humans. Polyamines (putrescine, spermidine, and spermine) are one of the key molecules regulating cell proliferation and differentiation. This work aimed to evaluate the potential beneficial properties of putrescine in rat BDL model by studying several biochemical parameters reflecting liver function and polyamine metabolism. Rats that were subjected to BDL were injected with putrescine (150 mg/kg) for 9 days, while in parallel another group with BDL remained untreated. Two control groups were included as well, sham-opened and putrescine-treated group. The following plasma parameters: ALT, AST, γ-GT, ALP, bilirubin, bile acids, as well as liver malondialdehyde and polyamine concentration and the activity of enzymes involved in polyamine metabolism were studied. After BDL, significant alterations in plasma biochemical parameters occurred, where a 9-day putrescine treatment significantly alleviated liver function deterioration. Putrescine also increased liver polyamines’ concentrations and polyamine and diamine oxidase activities in rats submitted to BDL. Our results demonstrated, for the first time, that putrescine plays an important role in preserving liver tissue function in rats with experimentally induced cholestasis.
Cellular Automata Based Test Design for Coherence Verification in 3D Caches
Authors: Chakraborty Bidesh , Dalui Mamata , Sikdar Biplab K.
Published: September 2018

To provide high vertical interconnection density between device tiers, Through Silicon Via (TSV) offers a promising solution in 3D caches. It reduces the length of global interconnection and ensures high speed cache memory access. Maintaining coherency of shared data in such caches is, however, very crucial and, therefore, demands that the reliability and accuracy of TSVs as well as the cache coherence controller (CC) are to be ensured. In the current work, we propose an elegant test solution for at-speed detection of stuck-at-faults in TSVs (offline test) as well as verification for the functioning of CC (online test). The proposed test structure is designed around the modular and cascadable structure of Cellular Automata (CA) to achieve a cost-effective realization of test and coherence verification in 3D caches with high degree of scalability. It ensures correct decisions in more than 71% cases even if the test hardware is subjected to single stuck-at-fault.
A Comprehensive Query Language for Provenance Information
Authors: Jabal Amani Abu , Bertino Elisa
Published: September 2018

We design and implement a query language for a secure, interoperable, and multi-granular provenance framework, referred to as QL-SimP. Our language supports two provenance representations (relational and graph-based) due to its independence from the underlying provenance representation. It also supports various queries that can be utilized for difference provenance applications. We integrate Computational Research Infrastructure for Science (CRIS) — a real-world system for managing scientific data — with our provenance framework, thus making it possible to query CRIS provenance information by using our provenance language. We have also evaluated our provenance queries based on relational and graph databases.
Analytical and Experimental Flutter Analysis of a Typical Wing Section Carrying a Flexibly Mounted Unbalanced Engine
Authors: Mirabbashi A. S. , Mazidi A. , Jalili M. M.
Published: September 2018

In this paper, both experimental and analytical flutter analyses are conducted for a typical 5-degree of freedon (5DOF) wing section carrying a flexibly mounted unbalanced engine. The wing flexibility is simulated by two torsional and longitudinal springs at the wing elastic axis. One flap is attached to the wing section by a torsion spring. Also, the engine is connected to the wing by two elastic joints. Each joint is simulated by a spring and damper unit to bring the model close to reality. Both the torsional and longitudinal motions of the engine are considered in the aeroelastic governing equations derived from the Lagrange equations. Also, Peter’s finite state model is used to simulate the aerodynamic loads on the wing. Effects of various engine parameters such as position, connection stiffness, mass, thrust and unbalanced force on the flutter of the wing are investigated. The results show that the aeroelastic stability region is limited by increasing the engine mass, pylon length, engine thrust and unbalanced force. Furthermore, increasing the damping and stiffness coefficients of the engine connection enlarges the stability domain.
q-Analogs of Lidstone expansion theorem, two-point Taylor expansion theorem, and Bernoulli polynomials
Authors: Ismail Mourad E. H. , Mansour Zeinab S. I.
Published: September 2018

In this paper, we introduce a generalization of the [Formula: see text]-Taylor expansion theorems. We expand a function in a neighborhood of two points instead of one in three different theorems. The first is a [Formula: see text]-analog of the Lidstone theorem where the two points are 0 and 1 and we expand the function in [Formula: see text]-analogs of Lidstone polynomials which are in fact [Formula: see text]-Bernoulli polynomials as in the classical case. The definitions of these [Formula: see text]-Bernoulli polynomials and numbers are introduced. We also introduce [Formula: see text]-analogs of Euler polynomials and numbers. On the other two expansion theorems, we expand an analytic function around arbitrary points [Formula: see text] and [Formula: see text] either in terms of the polynomials [Formula: see text] or in terms of the polynomials [Formula: see text]. As an application, we introduce a new series expansion for the basic hypergeometric series [Formula: see text].
Vibration Analysis and Control of Nuclear Power Crane with MRFD
Authors: Qin Yi Xiao , Li Bo Lun , Li Xin , Li Yan Qing , De Zhang Zhi , Gu Cui Yun , Ze Gu Hong
Published: September 2018

The nuclear power crane is required to have high security and stability, as its lifting mechanism and span structure are needed to perform predominantly in serious working conditions. A new vibration analysis and control method on the nuclear power crane is proposed to improve its stability, which is based on magneto rheological fluid damper (MRFD) and switch algorithm control strategy. The simulation is completed through dynamic model and control model. The experiment is accomplished in a serving crane. Both numerical simulated and experimental results show that the vibration of nuclear power crane is suppressed significantly with MRFD. It is proved that MRFD should be taken into consideration in the vibration control of nuclear power crane.
Application of a Cyclic Degradation Model for Pore Pressure Accumulation in Loose Sands and Silts Subjected to Dynamic Loading
Authors: Juneja A. , Mohammed-Aslam A. K.
Published: September 2018

Most cyclic soil models which are used to estimate strain and pore pressure accumulations, are soil specific and, often evaluate the accumulation model either as a function of the number of load cycles or they tend to utilize parameters which can only be obtained by using detailed laboratory tests. This paper attempts to enhance the capabilities of a simple plasticity model which can approximate the trend of pore pressure accumulation. This function uses a stress dependent degradation parameter which allows the yield loci to adjust and reduce its size at the end of each load cycle. The cyclic degradation model which was originally developed for clays, was adapted for sands and silts in this work with the use of two new parameters. The model was tested by using the cyclic triaxial data of three non-plastic soils. These samples were subjected to cyclic load amplitudes which are normally used in most seismic studies. The modified degradation model could predict fairly well the pore pressure accumulation in high-load amplitude tests but lead to over-prediction in low-load amplitude tests, unless the function was allowed to taper off at large cycles. Notwithstanding the above, the above cyclic model using the degraded yield surface, was incapable of correctly predicting the stress paths which were close to the sample’s ultimate state as it failed to permit phase transformation which is generally observed in sands and silts.
A near-infrared small molecule acceptor based on the quinoidal form for organic solar cells
Authors: Sun Shi-Xin , Xu Jia-Wei , Chen Xiao-Long , Zhang You-Wen , Chen Yang , Chen De-Yin , Ren Tian-Hua , Xing Rong
Published: September 2018

A novel non-fullerene small molecule acceptor named DPPMDPC6 with diketopyrrolopyrrole (DPP) as central moiety and methyl-dioxocyano-pyridine (MDP) units as two branches has been designed and synthesized. Benefitted from the quinoidal MDP segment, the molecule exhibits effective electron delocalization extending to the near infrared (NIR) region absorption with narrow bandgap of 1.42[Formula: see text]eV. The acceptor also displayed intrinsic properties with good thermal stability, and matched energy levels with various donor materials especially for the commercial polymer PTB7. Under optimized condition, the devices fabricated by forming PTB7:DPPMDPC6 blend films yield a moderate PCE of 5.80% with a [Formula: see text] of 0.84[Formula: see text]V, a [Formula: see text] of 12.94[Formula: see text]mA[Formula: see text]cm[Formula: see text], and an FF of 53.4%. This preliminary study demonstrates that the new acceptor tailored with quinoidal MDP units could lead to enhancement on the low energy absorption band that is favorable for the photovoltaic performances.
BotMap
Authors: Ducasse Julie , Macé Marc , Oriola Bernard , Jouffrais Christophe
Published: September 2018

The development of novel shape-changing or actuated tabletop tangible interfaces opens new perspectives for the design of physical and dynamic maps, especially for visually impaired (VI) users. Such maps would allow non-visual haptic exploration with advanced functions, such as panning and zooming. In this study, we designed an actuated tangible tabletop interface, called BotMap, allowing the exploration of geographic data through non-visual panning and zooming. In BotMap, small robots represent landmarks and move to their correct position whenever the map is refreshed. Users can interact with the robots to retrieve the names of the landmarks they represent. We designed two interfaces, named Keyboard and Sliders, which enable users to pan and zoom. Two evaluations were conducted with, respectively, ten blindfolded and eight VI participants. Results show that both interfaces were usable, with a slight advantage for the Keyboard interface in terms of navigation performance and map comprehension, and that, even when many panning and zooming operations were required, VI participants were able to understand the maps. Most participants managed to accurately reconstruct maps after exploration. Finally, we observed three VI people using the system and performing a classical task consisting in finding the more appropriate itinerary for a journey.
On the Convergence of the TTL Approximation for an LRU Cache under Independent Stationary Request Processes
Authors: Jiang Bo , Nain Philippe , Towsley Don
Published: September 2018

The modeling and analysis of an LRU cache is extremely challenging as exact results for the main performance metrics (e.g., hit rate) are either lacking or cannot be used because of their high computational complexity for large caches. As a result, various approximations have been proposed. The state-of-the-art method is the so-called TTL approximation, first proposed and shown to be asymptotically exact for IRM requests by Fagin [13]. It has been applied to various other workload models and numerically demonstrated to be accurate but without theoretical justification. In this article, we provide theoretical justification for the approximation in the case where distinct contents are described by independent stationary and ergodic processes. We show that this approximation is exact as the cache size and the number of contents go to infinity. This extends earlier results for the independent reference model. Moreover, we establish results not only for the aggregate cache hit probability but also for every individual content. Last, we obtain bounds on the rate of convergence.
Race Detection in Two Dimensions
Authors: Dimitrov Dimitar , Vechev Martin , Sarkar Vivek
Published: September 2018

Dynamic race detection is a program analysis technique for detecting errors caused by undesired interleavings of concurrent tasks. A primary challenge when designing efficient race detection algorithms is to achieve manageable space requirements.

State-of-the-art algorithms for unstructured parallelism require Θ (
n
) space per monitored memory location, where
n
is the total number of tasks. This is a serious drawback when analyzing programs with many tasks. In contrast, algorithms for programs with a series-parallel (SP) structure require only Θ (1) space. Unfortunately, it is currently not well understood if there are classes of parallelism beyond SP that can also benefit from and be analyzed with Θ (1) space complexity.

In this work, we show that structures richer than SP graphs, namely, that of two-dimensional (2D) lattices, can also be analyzed in Θ (1) space. Toward that (a) we extend Tarjan’s algorithm for finding lowest common ancestors to handle 2D lattices; (b) from that extension we derive a serial algorithm for race detection that can analyze arbitrary task graphs with a 2D lattice structure; (c) we present a restriction to fork-join that admits precisely the 2D lattices as task graphs (e.g., it can express pipeline parallelism).

Our work generalizes prior work on structured race detection and aims to provide a deeper understanding of the interplay between structured parallelism and program analysis efficiency.
How do students deal with difficult physiological knowledge?
Authors: Colthorpe Kay Louise , Abe Haruna , Ainscough Louise
Published: September 2018

Physiology courses are considered to be challenging for students to master due to the highly conceptual nature of the discipline and the substantial cognitive effort required to understand disciplinary knowledge. Students must choose appropriate learning strategies to develop their understanding, as their choices may influence both their understanding and their academic achievement. The primary aim of this study was to develop an understanding of why students experience difficulties with physiology and how they respond when facing the challenge of learning this discipline. Undergraduate allied health students ( n = 231) studying physiology were asked to identify the topics they had difficulty understanding, the strategies they used to deal with that difficult knowledge, and the reasons for their difficulties. Consenting students’ responses were subjected to inductive and deductive thematic analyses, and their performance on examinations were collated. Students reported that they found physiology difficult due to their lack of familiarity with it and the level of detail required. To aid their understanding of difficult topics, students commonly reported reviewing information, seeking further information, and seeking social assistance, with more high-achieving students reporting reviewing records, and fewer reporting seeking social assistance than poor-achieving students. Most notably, a disconnect was found between students’ reporting of difficult modules and their academic achievement on those modules, with students who cited difficulties performing equally well, if not better, than those who do not. Importantly, these findings suggest that students, in recognizing their difficulties and the reasons for them, can implement effective learning strategies to overcome them.
Recall of physiology knowledge among medical interns: an exploratory study in Riyadh, Saudi Arabia
Authors: AlMohanna Asmaa M. , Suliman Mohammed E. , AlEssa Noran A. , Khatib Said Y. , Saeed Abdallah A. , Hamza Muaawia A.
Published: September 2018

The aim of the study was to explore the factors associated with the recall of basic medical physiology knowledge among medical interns and to determine the level of retained basic science knowledge. Two hundred and four interns, 114 women and 90 men, working in two major tertiary medical care centers, King Fahad Medical City (KFMC; 29 students) and King Khalid University Hospital (KKUH; 117 students), in Riyadh city, participated in the study. An anonymous knowledge test with 10 validated multiple-choice questions was developed specifically for this purpose. One hundred and forty-six interns (117 working at KKUH and 29 at KFMC) had graduated from medical schools adopting a conventional instructional system, whereas 58 (3 from KKUH and 55 from KFMC had graduated from schools adopting an integrated system (hybrid problem-based learning). Fifty-two students (26%) gained a score ≥60%, whereas 152 students (74%) obtained <60% of the score. Higher scores were associated with younger age ( P < 0.01), traditional curriculum ( P < 0.001), interns from KKUH ( P < 0.001), and candidates for postgraduate studies ( P < 0.02). There was no significant association between recall of physiology knowledge and all other variables studied, including sex. Multivariate analyses show that age and traditional curriculum are the only significant predictors of knowledge retention. Almost three-fourths of the interns scored <60%, and higher scores were significantly associated with younger interns, traditional curriculum, working in KKUH, and interns preparing for graduate studies. However, the difference between the two curricula disappears when the influence of hospital training is considered.
Fetal growth restriction shortens cardiac telomere length, but this is attenuated by exercise in early life
Authors: Booth S. A. , Wadley G. D. , Marques F. Z. , Wlodek M. E. , Charchar F. J.
Published: September 2018

Background and aims: Fetal and postnatal growth restriction cause a predisposition to cardiovascular disease (CVD) in adulthood. Telomeres are repetitive DNA-protein structures that protect chromosome ends, and the loss of these repeats (a reduction in telomere length) is associated with CVD. As exercise preserves telomere length and cardiovascular health, the aim of this study was to determine the effects of growth restriction and exercise training on cardiac telomere length and telomeric genes. Methods and results: Pregnant Wistar Kyoto rats underwent bilateral uterine vessel ligation to induce uteroplacental insufficiency and fetal growth restriction (“Restricted”). Sham-operated rats had either intact litters (“Control”) or their litters reduced to five pups with slowed postnatal growth (“Reduced”). Control, Restricted, and Reduced male rats were assigned to Sedentary, Early exercise (5–9 wk of age), or Late exercise (20–24 wk of age) groups. Hearts were excised at 24 wk of age for telomere length and gene expression measurements by quantitative PCR. Growth restriction shortened cardiac telomere length ( P < 0.001), but this was rescued by early exercise ( P < 0.001). Early and Late exercise increased cardiac weight index ( P < 0.001), but neither this nor telomere length was associated with expression of the telomeric genes Tert, Terc, Trf2, Pnuts, or Sirt1. Discussion and conclusions: Growth restriction shortens cardiac telomere length, reflecting the cardiac pathologies associated with low birth weight. Exercise in early life may offer long-term protective effects on cardiac telomere length, which could help prevent CVD in later life.
Specific Targeting of Oncogenes Using CRISPR Technology
Authors: Oppel Felix , Schürmann Matthias , Goon Peter , Albers Andreas E. , Sudhoff Holger
Published: September 2018

In recent decades, tools of molecular biology have enabled researchers to genetically modify model organisms, including human cells. RNAi, zinc-finger nucleases, transcription activator–like effector nucleases, CRISPR-Cas9 (clustered regularly-interspaced short palindromic repeats and CRISPR-associated protein 9), retro- or lentiviral gene transfer, and many other methods can be utilized to remove genes, add genes, or change their expression. Within the same timeframe, survival rates for many highly malignant tumor diseases have not improved substantially. If modern medicine could apply even a subset of research methods in clinical management, which are already well established and controllable in basic research laboratories, this could strongly impact patients' prognosis. CRISPR-Cas9 is a method to precisely target and manipulate genomic loci and recent studies have attempted to use this method as a genetic treatment for Duchenne muscular dystrophy, blood disorders, autosomal-dominant hearing loss, and cancer. Some of these approaches target mutant genomic sequences specifically and try to avoid affecting the respective normal loci. Considering obvious genetic risks opposing the objected benefits, data are needed to show whether CRISPR technology is suitable as a future cancer therapy approach or not. Here, we develop strategies for the specific targeting of viral cancer drivers and oncogenes activated by mutation, using the latest CRISPR technology. Cancer Res; 78(19); 5506–12. ©2018 AACR.
MERTK Promotes Resistance to Irreversible EGFR Tyrosine Kinase Inhibitors in Non–small Cell Lung Cancers Expressing Wild-type EGFR Family Members
Authors: Yan Dan , Parker Rebecca E. , Wang Xiaodong , Frye Stephen V. , Earp H. Shelton , DeRyckere Deborah , Graham Douglas K.
Published: September 2018

Purpose:

Lung cancer is the leading cause of cancer-related death. Non–small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and over 60% express wild-type EGFR (wtEGFR); however, EGFR tyrosine kinase inhibitors (TKIs) have limited effect in most patients with wtEGFR tumors. We previously identified MERTK tyrosine kinase as a potential therapeutic target in NSCLC and developed MRX-2843, a novel MERTK-selective inhibitor with favorable properties for clinical translation. The goal of this study was to determine whether MERTK and EGFR inhibitor combination therapy could provide antitumor efficacy against wtEGFR NSCLC.

Experimental Design:

An unbiased screen of 378 kinase inhibitors was conducted to identify synergistic interactions with MRX-2843 and biochemical and therapeutic effects were determined in vitro and in vivo.

Results:

Numerous irreversible EGFR TKIs, including CO-1686 and osimertinib, synergized with MRX-2843 to inhibit wtEGFR NSCLC cell expansion, irrespective of driver oncogene status. CO-1686 and MRX-2843 combination therapy inhibited MERTK, wtEGFR, and ERBB2/ERBB3 and decreased downstream PI3K-AKT, MAPK-ERK, and AURORA kinase (AURK) signaling more effectively than single agents. Inhibition of PI3K, AKT or AURK, but not MEK, synergized with CO-1686 to inhibit tumor cell expansion, suggesting their roles as key redundant resistance pathways. Treatment with MRX-2843 and CO-1686 or osimertinib prevented xenograft growth while single agents had limited effect. Tumor growth inhibition was durable even after treatment with combination therapy was stopped.

Conclusions:

Our data support the application of MRX-2843 in combination with an irreversible EGFR TKI as a novel strategy for treatment of patients with wtEGFR NSCLC.
Complementary Feeding in Developed Countries: The 3 Ws (When, What, and Why?)
Authors: Campoy Cristina , Campos Daniel , Cerdó Tomás , Diéguez Estefanía , García-Santos José Antonio
Published: September 2018

While a wide knowledge exists on the effects of breast milk or infant formula on growth and infant development, less attention has been paid to the importance of complementary feeding (CF). This review focuses on current recommendations for optimal introduction of CF in healthy full-term European infants and discusses the potential impact of this type of feeding on health outcomes. Overall, exclusive breastfeeding is recommended at least for 4 months and preferable for 6 months, followed by the introduction of CF alongside breast milk; infants’ nutrient requirements must meet the differences between nutrients provided by breast milk and the estimated total needs. There is growing evidence that healthy feeding practices during the CF period have positive short- and long-term effects on optimal growth, body composition, neurodevelopment, healthy food preferences, and gut microbiota composition and function; adequate and healthy CF may also diminish the risk of infections, allergies, type 1 diabetes mellitus, as well as celiac and non-communicable diseases. Following the expert recommendations, the design of nutritional strategies must encourage parents to provide a healthy lifestyle for their offspring. Future research should aim to optimize timing, content, and methods of CF; furthermore, it is necessary to explore future CF-targeted health-promoting strategies in early life (appetite regulation, eating patterns, eating behavior, gut dysbiosis, etc.) to prevent growth/obesity outcomes, immune system related-diseases or non-communicable diseases in later life.
What Is the Best Management of cN0pN1(sn) Breast Cancer Patients
Authors: de Boniface Jana , Schmidt Marcus , Engel Jutta , Smidt Marjolein L. , Offersen Birgitte Vrou , Reimer Toralf
Published: September 2018

Although the majority of breast cancer patients are clinically node-negative (cN0) at diagnosis, 15-20% will have a metastatic sentinel lymph node (SLN, pN1(sn)). While a less radical approach regarding axillary surgery in cN0 patients with a positive SLN biopsy is advocated, the limitations of 5 published trials on axillary management in pN1(sn) are discussed intensely in the literature and support the performance of ongoing validation and extension trials, especially considering the lack of data in the setting of mastectomy. As locoregional radiotherapy has a significant effect on both recurrence and survival, a standardization of locoregional radiotherapy in the situation of SLN biopsy alone in pN1(sn) patients has to be defined in the future, and de-escalation trials should embrace a truly multidisciplinary approach. This is also of utmost importance considering the fact that high-volume nodal disease requires an intensified adjuvant chemotherapy strategy to which patients omitting axillary dissection cannot be stratified. Finally, there is mounting evidence that the therapeutic role of extensive axillary surgery in low-volume nodal disease is negligible, and multidisciplinary and translational efforts must be undertaken to individualize treatment in order to gain a reasonable balance between necessary staging information and unnecessary treatment-related morbidity.
Häufigkeit und Risikofaktoren des Therapieabbruchs in einer verhaltenstherapeutischen Hochschulambulanz: Der Einfluss von riskantem Alkoholkonsum zu Therapiebeginn
Authors: Schawohl Anne , Odenwald Michael
Published: September 2018

Hintergrund: Zu Therapieabbrüchen in der ambulanten Verhaltenstherapie und damit verbundenen Risikofaktoren existieren bisher nur wenige und gemischte Ergebnisse. In dieser Studie wurden Risikofaktoren für Therapieabbrüche erfasst und untersucht, ob sich ein riskanter Alkoholkonsum (bei Therapiebeginn) auf die Therapieabbrüche in einer verhaltenstherapeutischen Hochschulambulanz auswirkt. Patienten und Methoden: 178 Patienten wurden unterteilt in a) Completer (reguläre Beendigung der Psychotherapie) und b) Dropouts (vorzeitiger Abbruch). Als Risikofaktoren wurden soziodemografische und klinische Variablen untersucht (z.B. Brief-Symptom-Inventar, Beck-Depressions-Inventar, Alcohol Use Disorders Identification Test (AUDIT) usw.). Ergebnisse: 93 Patienten (52%) schlossen die Psychotherapie regulär ab (Completer), 85 (48%) brachen vorzeitig ab (Dropouts; davon 45 in Probatorik und 40 danach). Die Dropouts waren bei Therapiebeginn älter als die Completer (M = 35,33 vs. M = 29.08 Jahre; p = 0,001), waren häufiger beschäftigt (64 vs. 45%; p = 0,014), hatten häufiger komorbide Diagnosen (55 vs. 34%; p = 0,005), waren stärker psychisch belastet (Global Severity Index: M = 1,25 vs. 1,01; p = 0,007) und wiesen einen riskanteren Alkoholkonsum auf (AUDIT: M = 10,49 vs. M = 5,01; p ≤ 0,001). Das Alkoholkonsum-Verhalten bei Therapiebeginn prädizierte einen vorzeitigen Therapieabbruch (b = 0,11; p = 0,001). Ein riskantes Alkoholkonsum-Verhalten war mit einem Dropout in der Probatorik assoziiert (p = 0,005). Schlussfolgerungen: Ein riskanter Alkoholkonsum ist bei ambulanten Psychotherapiepatienten mit vorzeitigem Therapieabbruch korreliert. Komorbides riskantes Trinkverhalten sollte zu Beginn der ambulanten Psychotherapie erfasst und inhaltlich thematisiert werden.
Prognostic Significance of Asymptomatic Brain Natriuretic Peptide Elevation at Nephrology Referral in Patients with Chronic Kidney Disease
Authors: Hayashi Terumasa , Yasuda Keiko , Kimura Tomonori , Sasaki Koichi , Shimada Karin , Hashimoto Nobuhiro , Isaka Yoshitaka
Published: September 2018

Background: It is unclear whether asymptomatic elevation of brain natriuretic peptide (BNP) is associated with cardiovascular events (CVEs) or heart failure (HF) in predialysis chronic kidney disease (CKD) patients. Methods: We measured BNP in 482 asymptomatic predialysis patients with CKD stages 2–5 at nephrology referral between August 2004 and October 2010, and followed them prospectively to investigate the prognostic significance of BNP using Cox models and receiver operating characteristic (ROC) analyses. The primary composite end point was the time to death or the first nonfatal CVEs. Secondary end points included CVEs including sudden death, HF and all-cause death. Results: The median age was 67 years (male, 67.4%; diabetic nephropathy, 33.4%), and estimated glomerular filtration rate was 20.1 mL/min/1.73 m2. The primary end point occurred in 92 patients. CVEs including sudden death, HF and all-cause death occurred in 66, 35, and 54 patients, respectively during a median follow-up period of 37.7 months. Multivariate analyses showed that BNP level was significantly associated with the primary end point (hazard ratio [HR] 1.241; 95% CI 1.020–1.511; p = 0.031), CVEs (HR 1.337; 95% CI 1.067–1.675; p = 0.012) and HF (HR 1.489; 95% CI 1.059–2.091; p = 0.022), but not associated with all-cause death (HR 1.081; 95% CI 0.829–1.410; p = 0.565). The ROC curves showed that the optimal predictive BNP levels for the primary end point, CVEs and HF were 92.5, 127.0, and 274.6 (pg/mL) respectively. Conclusion: Asymptomatic elevation of BNP is strongly predictive for CVEs and HF, which might help to integrate cardio-renal risk stratification in predialysis CKD patients.
Rechallenge with First-Line Platinum Chemotherapy for Sensitive-Relapsed Small-Cell Lung Cancer
Authors: Shiozawa Toshihiro , Sekine Ikuo , Aida Yuka , Watanabe Hiroko , Nakazawa Kensuke , Kurishima Koichi , Satoh Hiroaki , Hizawa Nobuyuki
Published: September 2018

Background: Sensitive-relapsed small-cell lung cancer (SCLC) is thought to be sensitive to chemotherapy; therefore, second-line chemotherapy is recommended. Although platinum rechallenge is performed in the second-line chemotherapy for sensitive-relapsed SCLC, it remains unclear whether such a strategy is effective. Methods: We retrospectively analyzed the outcome of rechallenge chemotherapy for sensitive-relapsed SCLC. The endpoints of this study were progression-free survival from the time of relapse (PFS-Re) and overall survival from the time of relapse (OS-Re). We also compared the toxicity profile of rechallenge chemotherapy to that of first-line chemotherapy. Results: Of the 133 SCLC patients who received first-line treatment, 20 patients satisfied the definition of sensitive relapse and received rechallenge chemotherapy. Combined carboplatin and etoposide was the most commonly used rechallenge regimen, and 17 (85%) received it at a reduced dose due to hematological toxicity during the first-line treatment. Median PFS-Re and OS-Re were 4.5 months (95% CI: 3.5–5.4) and 10.5 months (95% CI: 7.9–13.0), respectively. There was no association between dose adjustment and survival. The frequency of hematologic toxicity tended to be lower with rechallenge than first-line treatment. The incidence of grade 3 febrile neutropenia decreased from 40% in first-line treatment to 15% in rechallenge. Conclusion: Platinum rechallenge could be a useful second-line option for sensitive-relapsed SCLC, having favorable efficacy and safety. Dose adjustment at rechallenge based on the toxicity profile during the first-line chemotherapy could reduce toxicity without weakening efficacy.
Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2 Diabetes Mellitus
Authors: Fang Zhao-hui  , Duan Xian-chun , Zhao Jin-dong , Wu Yuan-jie , Liu Meng-meng
Published: September 2018

Background/Aims: To investigate the potential therapeutic effect of novel polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes Mellitus (T2DM) and elucidate the underling molecular mechanisms. Methods: Relative expression of HIF1α and Sirt1 in T2DM patients was determined via real-time PCR. The direct binding of HIF1α on Sirt1 promoter was validated by ChIP assay. The inhibitory regulation of Sirt1 by HIF1α was analyzed using luciferase reporter assay. The endogenous protein of HIF1α and Sirt1 in response to H-1-2 treatment was quantified by western blotting. The blood glucose, secreted insulin and serous lipid profiles were measured with ELISA kits. Results: We consolidated that HIF1α and Sirt1 was dysregulated in T2DM patients and subjected to H-1-2 modulation. H-1-2 significantly inhibited hypoxia and up-regulated Sirt1 expression in EndoC-βH1 cells. Accordingly, H-1-2 enhanced glucose-stimulation insulin secretion and improved blood glucose and lipid profiles in T2DM cells, and elevated the glucose and insulin tolerance simultaneously. Furthermore, we demonstrated that H-1-2 alleviated T2DM via inhibition of hypoxia and up-regulation of Sirt1 in isolated pancreatic β-cells from T2DM rats. Conclusion: Our data unambiguously demonstrated H-1-2 administration alleviated T2DM by enhancing Sirt1 expression through inhibition of hypoxia.
Label-Free Spectral Imaging Unveils Biochemical Mechanisms of Low-Level Laser Therapy on Spinal Cord Injury
Authors: Gong Yuze , Wang Shuang , Liang Zhuowen , Wang Zhe , Zhang Xu , Li Jie , Song Jiwei , Hu Xueyu , Wang Kaige , He Qingli , Bai Jintao
Published: September 2018

Background/Aims: Low-level laser therapy (LLLT) leads to complex photochemical responses during the healing process of spinal cord injury (SCI). Confocal Raman Microspectral Imaging (in combination with multivariate analysis) was adopted to illustrate the underlying biochemical mechanisms of LLLT treatment on a SCI rat model. Methods: Using transversal tissue sections, the Raman spectra can identify areas neighboring the injury site, glial scar, cavity, and unharmed white matter, as well as their correlated cellular alterations, such as demyelination and up-regulation of chondroitin sulfate proteoglycans (CSPGs). Multivariate data analysis methods are used to depict the underlying therapeutic effects by highlighting the detailed content and distribution variations of the biochemical constituents. Results: It is confirmed that photon-tissue interactions might lead to a decay of the inhibitory response to remyelination by suppressing CSPG expression, as also morphologically demonstrated by reduced glial scar and cavity areas. An inter-group comparison semi-quantitatively confirms changes in lipids, phosphatidic acid, CSPGs, and cholesterol during SCI and its LLLT treatment, paving the way for in vitro and in vivo understanding of the biochemical changes accompanying pathobiological SCI events. Conclusion: The achieved results in this work not only have once again proved the well-known cellular mechanisms of SCI, but further illustrate the underlying biochemical variability during LLLT treatment, which provide a sound basis for developing real-time Raman methodologies to monitor the efficacy of the SCI LLLT treatment.
Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation
Authors: Liu Xianglan , Sun Yong , Zheng Yang , Zhang Maomao , Jin Xiangyuan , Kang Kai , Wang Yongshun , Li Shuang , Zhang Hanlu , Zhao Qi , Zhang Shengnan , Wu Jian , Yu Bo
Published: September 2018

Background/Aims: IL-35, a powerful suppressor of inflammation and autoimmunity, is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote Treg differentiation. However, the precise effect of IL-35 on dendritic cells (DCs) remains to be clarified. Methods: In this study, we investigated the expression of IL-35 in DCs after stimulation with LPS utilizing enzyme linked immunosorbent assay(ELISA), quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, and the influence of IL-35 on the maturation and function of DCs by mixed lymphocyte reaction assay and flow cytometry. We further examined the regulation of IL-35 in DCs by the microRNA let-7i (let-7i) via transfected with let-7i mimic, inhibitor or suppressor of cytokine signalling 1 (SOCS1) siRNA. IL-35-overexpressing DCs were transfused into BALB/c recipients with C57BL/6 heart transplantations to verify the role of immune tolerance in transplantation. Results: The results showed that IL-35 expression was significantly up-regulated following lipopolysaccharide (LPS)-induced DC maturation. Overexpression of IL-35 suppressed DC maturation, promoted the secretion of anti-inflammatory cytokines, and subsequently affected the balance between Treg and Th17 cells. IL-35 expression in DCs was regulated by let-7i, which targets SOCS1. The transfusion of IL-35-transfected DCs induced Treg generation in mice and prolonged cardiac allograft survival. Conclusion: Our data demonstrated that IL-35 induces tolerogenic DCs which are capable of alleviating allograft rejection. Clinical application of IL-35-treated DCs might be a promising approach for eliciting cardiac allograft immune tolerance.
ОСОБЛИВОСТІ ДЕФЕКТІВ МЕДИЧНОЇ ДОПОМОГИ В АНЕСТЕЗІОЛОГІЇ-РЕАНІМАТОЛОГІЇ (ЗА МАТЕРІАЛАМИ СУДОВО-СЛІДЧИХ СПРАВ)
Authors: Franchuk V. V.
Published: September 2018

Medical malpractice litigations have become a serious social and public health problem in contemporary Ukraine, however peculiarities of improper medical care in anesthesiology is little known inside the country.The aim of the study – to evaluate the medical malpractice litigations provided by anesthesiologists in Ukraine.Materials and Methods. A retrospective review of all alleged medical malpractice cases (350 in total) between 2007 and 2016 handled at Ternopil, Zhytomyr and Chernivtsi Regional Bureaus of Forensic Medical Examination, was performed. The paper analyses official data of court verdicts in cases of medical malpractice litigations taken from Ukrainian State Register of court decisions for the same time period.Results and Discussion. 32.5 % of all of medical malpractice litigations were initiated against anesthesiologists. Lacks of health care provision committed by anesthesiologists were detected in 70.2 % of the cases. Unreasonable medical care occurred in cases of serious Unintentional medical care was confirmed by forensic medical expert commission as a rule in diagnostics (33.8 %) and medical procedures or medical treatment (26.4 %). Mistakes in medical records were detected in (24.7 %) of the cases, institutional errors – (11.1 %), ethical errors – (4.0 %). Insufficient or incomplete medical care provided by anesthesiologists seemed more frequently (44.5 %), inopportune medical care – 33.6 %, unskillful medical care 20.3 %. Severe consequences for the patients took place in all of the cases. A causal relationship between the damage claimed by the patient or his family and improper medical care were found in 30.0 % cases.Conclusions. Anesthesiologists lead the top list of physician specialties involved in claims in Ukraine. Diagnostic and institutional errors, improper performance of medical procedures and medication errors are seemed most frequently in medical malpractice cases in anesthesiology. The majority of the medical mistakes became due to different objective reasons. Approximately a half of all of the studied cases faced together with breach of standards of care followed by the poor quality of the medical personnel.
АНАЛІЗ СТОМАТОЛОГІЧНОГО СТАТУСУ ШКОЛЯРІВ МІСТА СТРИЯ ЗАЛЕЖНО ВІД РЕЖИМУ ТА РАЦІОНУ ХАРЧУВАННЯ
Authors: Lebid O. I. , Duda K. M. , Stoikevych H. V.
Published: September 2018

The analysis of the stomatological status of schoolchildren in the city of Stryi shows the influence of the regime and diet, physical activity of students in conjunction with other factors, to metabolic disorders that are trigger in the development of generalsomatic diseases and diseases of hard tissues of teeth.The aim of the study – to analyze the results of the questionnaire and dental examination, on the effect of diet on the stomatological status of schoolchildren in the city of Stryi.Materials and Methods. 96 children aged 14–16 participated in the studies. Among the schoolchildren in the city of Stryi, Lviv oblast, a sociological survey on diet and motor activity was conducted by questionnaire on the poll developed by us. The obtained data were compared with the results of the dental examination, which included the determination of the intensity of caries of the teeth according to the CPI index. The examination of oral hygiene was carried out using the Green-Vermillion (OH I-S) Hygiene Index. The results were summarized into a common table to facilitate statistical processing of information.Results and Discussion. As a result of our research, we have established a clear link between the diet and the diet of schoolchildren on their dental health. So, we found that in the diet of schoolchildren decreased the consumption of dairy products, fish and meat, and on the contrary increased the use of "fast foods", sweets, sweet beverages. Our definition of dental status has shown that the prevalence of caries is 93.69 % for schoolchildren who do not adhere to the regime and diet, and only 6.31 % of the surveyed have intact dental rows.Conclusions. The according to the results of our research, it can be concluded that inappropriate nutrition, violation of its mode and structure, sedentary lifestyle, lack of oral hygiene, in our opinion, together with other factors, lead to metabolic disorders that are trigger in the development of general-somatic diseases, and diseases of hard tissues of teeth.
Victorian Science
Authors: Nixon Jude V.
Published: September 2018

Now virtually unknown, Anne Pratt (1806–1893) remains an important Victorian illustrator, naturalist, and popularizer of science, whose Wild Flowers (1852) made a strong impression on Queen Victoria. While Pratt’s works addressed a largely female audience, their generic appeal, reflecting her profound botanical knowledge and astute insights into flower study, had an ever broader reach into the general public. Pratt authored over twenty books, among them Chapters on the Common Things of the Sea-Side (1850), which saw four editions in ten years. Hopkins was given a second edition as a gift for his tenth birthday. Though he nowhere acknowledges Pratt but for an obscure reference in a letter to his mother, a precocious Hopkins would have found in Chapters the keen attention to nature he would later observe in Ruskin. Pratt’s study would have been an important precursor for Hopkins’s detailed observations of nature in his journals, diaries, and notebooks. Especially pronounced are their attempts to connect the beauty in nature to a benevolent Creator and a natural theology in which everything in nature, to use a Hopkins expression, “speaks and spells” Christ. In their theology of the aesthetics, the divine plays in “ten thousand places.”
Gerard Manley Hopkins, an Environmentalist Poet with a Trinitarian Dimension and Even Trinitarian Humor
Authors: Feeney Joseph J.
Published: September 2018

Hopkins’s environmental poem “Ribblesdale” (1882) shows his creative processes as it celebrates nature and language. It even visualizes God the Father creating the world as a fisherman casting his line and making the River Ribble flow through Lancashire—a river beautiful at Hopkins’s Stonyhurst College, but downriver, treeless and grassless, polluted and surrounded by factories. As a child and young man, Hopkins loved nature, later cherishing even nature’s shapes and selfhood and celebrating nature in his poems. But he grieved for the environment, presenting the earth as a huge nest on which a very large Holy Ghost still sits, warming and protecting her earth-egg. Hopkins mourns earth’s loss of trees and grass, of a clear sky, of “a rural scene,” even of “the weeds and the wilderness.” And Christ, as a human, was implicated in this loss, and as human was just a “Jack, joke, poor potsherd, patch, matchwood.” Yet, as Trinitarian God, he is an “immortal diamond” and, grandly, offers and shares this bright sparkling life with his fellow humans. Such is Gerard Manley Hopkins, lover of God and God’s earth—and grieving environmentalist poet.
Network size, structure, and pathogen transmission: a simulation study comparing different community detection algorithms
Authors: Sumner Kelsey M. , McCabe Collin M. , Nunn Charles L.
Published: September 2018

Social substructure can influence pathogen transmission. Modularity measures the degree of social contact within versus between “communities” in a network, with increasing modularity expected to reduce transmission opportunities. We investigated how social substructure scales with network size and disease transmission. Using small-scale primate social networks, we applied seven community detection algorithms to calculate modularity and subgroup cohesion, defined as individuals’ interactions within subgroups proportional to the network. We found larger networks were more modular with higher subgroup cohesion, but the association’s strength varied by community detection algorithm and substructure measure. These findings highlight the importance of choosing an appropriate community detection algorithm for the question of interest, and if not possible, using multiple algorithms. Disease transmission simulations revealed higher modularity and subgroup cohesion resulted in fewer infections, confirming that social substructure has epidemiological consequences. Increased subdivision in larger networks could reflect constrained time budgets or evolved defences against disease risk.
The British Record Commission, Its Secretary C. P. Cooper, and Two of His German Correspondents during the 1830s
Authors: Bock Oliver
Published: September 2018

This paper presents previously unknown pieces of correspondence between C. P. Cooper (1793–1873), the secretary of the British Record Commission, and two German scholars who supported the Commission’s search for sources concerning the history of the English language and its literature. The letters illustrate how the Commission’s research effort on the Continent was organised by Cooper and his German partners. Their course of action will be contextualised within the Commission’s history up to its abrupt end in 1837 in order to show to what extent these research endeavours and the correspondences were determined by adversarial circumstances that led first to a Parliamentary inquiry into the Commission’s work and finally to its termination.