bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cabergoline-induced manic episode: case report
Authors: Yüksel Rabia Nazik , Elyas Kaya Zeynep , Dilbaz Nesrin , Cingi Yirün Merve 
Published: January 2016

Cabergoline is an orally administered synthetic dopamine agonist that is used for the treatment of hyperprolactinemia, Parkinson’s disease and antipsychotic-induced prolactin elevation. One of the main characteristics of cabergoline is its long duration of effect. It is highly effective in suppressing prolactin levels up to 21 days after a single 1 mg oral dose. The prolonged elimination half-life offers an advantage of once-daily dosing, but it might be a handicap in terms of washout of adverse effects such as psychosis. Cabergoline has been associated with adverse reactions consistent with other dopaminergic agonists including cardiovascular, gastrointestinal and neuropsychiatric effects. It is known that dopaminergic treatment is a remarkable risk factor for psychosis. A number of reports implicate dopamine agonists in the development of psychosis, but there is no knowledge in the literature of dopamine agonist-induced mania. In this case, we report the first manic episode occurring after cabergoline use for hyperprolactinemia treatment. In susceptible individuals, cabergoline can cause manic episodes and cabergoline should be used more carefully considering the risk–benefit ratio.
Serum-resistant CpG-STAT3 decoy for targeting survival and immune checkpoint signaling in acute myeloid leukemia
Authors: Zhang Qifang , Hossain Dewan Md Sakib , Duttagupta Priyanka , Moreira Dayson , Zhao Xingli , Won Haejung , Buettner Ralf , Nechaev Sergey , Majka Marcin , Zhang Bin , Cai Qi , Swiderski Piotr , Kuo Ya-Huei , Forman Stephen , Marcucci Guido , Kortylewski Marcin 
Published: January 2016

Key PointsSTAT3 decoy conjugated to TLR9 ligand targets survival and immune checkpoint signaling in all acute myeloid leukemia cell compartments. Serum-resistant CpG-STAT3dODN conjugates induce direct killing and/or immune-mediated eradication of AML, including stem/progenitor cells.
Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma
Authors: Zweegman Sonja , van der Holt Bronno , Mellqvist Ulf-Henrik , Salomo Morten , Bos Gerard M. J. , Levin Mark-David , Visser-Wisselaar Heleen , Hansson Markus , van der Velden Annette W. G. , Deenik Wendy , Gruber Astrid , Coenen Juleon L. L. M. , Plesner Torben , Klein Saskia K. , Tanis Bea C. , Szatkowski Damian L. , Brouwer Rolf E. , Westerman Matthijs , Leys M. (Rineke) B. L. , Sinnige Harm A. M. , Haukås Einar , van der Hem Klaas G. , Durian Marc F. , Mattijssen E. (Vera) J. M. , van de Donk Niels W. C. J. , Stevens-Kroef Marian J. P. L. , Sonneveld Pieter , Waage Anders 
Published: January 2016

Key Points
In a multicenter, randomized phase 3 trial, MPR-R was not superior over MPT-T with respect to response rate, PFS, and OS. Grade 3/4 hematologic toxicity requiring growth factor support occurred with MPR-R vs clinically significant neuropathy with MPT-T.
Traffic-related air pollution and alveolar nitric oxide in southern California children
Authors: Eckel Sandrah P. , Zhang Zilu , Habre Rima , Rappaport Edward B. , Linn William S. , Berhane Kiros , Zhang Yue , Bastain Theresa M. , Gilliland Frank D. 
Published: January 2016

Mechanisms for the adverse respiratory effects of traffic-related air pollution (TRAP) have yet to be established. We evaluated the acute effects of TRAP exposure on proximal and distal airway inflammation by relating indoor nitric oxide (NO), a marker of TRAP exposure in the indoor microenvironment, to airway and alveolar sources of exhaled nitric oxide (FeNO).FeNOwas collected online at four flow rates in 1635 schoolchildren (aged 12–15 years) in southern California (USA) breathing NO-free air. Indoor NO was sampled hourly and linearly interpolated to the time of theFeNOtest. Estimated parameters quantifying airway wall diffusivity (DawNO) and flux (J′awNO) and alveolar concentration (CANO) sources ofFeNOwere related to exposure using linear regression to adjust for potential confounders.We found that TRAP exposure indoors was associated with elevated alveolar NO. A 10 ppb higher indoor NO concentration at the time of theFeNOtest was associated with 0.10 ppb higher averageCANO(95% CI 0.04–0.16) (equivalent to a 7.1% increase from the mean), 4.0% higherJ′awNO(95% CI −2.8–11.3) and 0.2% lowerDawNO(95% CI −4.8–4.6).These findings are consistent with an airway response to TRAP exposure that was most marked in the distal airways.
Treatment of Gram-negative pneumonia in the critical care setting: is the beta-lactam antibiotic backbone broken beyond repair?
Authors: Bassetti Matteo , Welte Tobias , Wunderink Richard G. 
Published: January 2016

AbstractBeta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta-lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram-negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs.
The effects of immunomodulation by macrophage subsets on osteogenesis in vitro
Authors: Loi Florence , Córdova Luis A. , Zhang Ruth , Pajarinen Jukka , Lin Tzu-hua , Goodman Stuart B. , Yao Zhenyu 
Published: January 2016

AbstractBackgroundBone formation and remodeling are influenced by the inflammatory state of the local microenvironment. In this regard, macrophages are postulated to play a crucial role in modulating osteogenesis. However, the differential effects of macrophage subsets and their plasticity on bone formation are currently unknown.MethodsPolarized primary murine macrophages and preosteoblastic MC3T3 cells were co-cultured to investigate the effect of non-activated M0, pro-inflammatory M1, and tissue-regenerative M2 macrophages on the osteogenic ability of MC3T3-E1 cellsin vitro. Furthermore, to model the physiological transition from inflammation to tissue regeneration, M1-MC3T3 co-cultures were treated with interleukin-4 (IL-4) at different time points to modulate the M1 phenotype towards M2. Macrophage phenotypic markers were assessed by flow cytometry and enzyme-linked immunosorbent assay. A time course study of osteogenic markers at different time points was conducted: alkaline phosphatase (ALP) mRNA levels were evaluated at week 1, ALP activity and osteocalcin and osteopontin mRNA levels at week 2, and matrix mineralization and osteocalcin and osteopontin protein concentrations at week 3. Supernatant collected 72 hours after seeding or IL-4 treatment, whichever was later, was analyzed for oncostatin M, a cytokine released by macrophages that has been recognized to enhance osteogenesis. Unpaired t test or one-way ANOVA with Tukey’s or Dunnett’s post hoc tests were used for statistical comparison of the groups.ResultsCo-culture with any of the macrophage subtypes increased the osteogenic ability of MC3T3 cells as indicated by increases in ALP activity and matrix mineralization. Increased ALP activity, osteocalcin concentration, and matrix mineralization demonstrated that osteogenesis by M1-MC3T3 co-cultures was further enhanced by macrophage phenotype modulation to M2 via IL-4 treatment 72 hours after seeding. Increased oncostatin M protein concentration in untreated M1-MC3T3 co-cultures and M1-MC3T3 co-cultures treated with IL-4 at 72 hours correlated with greater ALP activity and matrix mineralization.ConclusionsThese results suggest that a transient inflammatory phase is crucial for enhanced bone formation. Macrophage plasticity may offer new strategies for modulating the local inflammatory microenvironment with the aim of potentially enhancing bone repair.
Mesenchymal stem cell-based therapy in kidney transplantation
Authors: Chen Cheng , Hou Jianquan 
Published: January 2016

AbstractKidney transplantation is the best treatment for end-stage renal disease, but its implementation is limited by organ shortage and immune rejection. Side effects of current immunosuppressive drugs, such as nephrotoxicity, opportunistic infection, and tumorigenic potential, influence long-term graft outcomes. In recent years, continued research and subsequent discoveries concerning the properties and potential utilization of mesenchymal stem cells (MSCs) have aroused considerable interest and expectations. Biological characteristics of MSCs, including multi-lineage differentiation, homing potential, paracrine effect and immunomodulation, have opened new horizons for applications in kidney transplantation. However, many studies have shown that the biological activity of MSCs depends on internal inflammatory conditions, and the safety and efficacy of the clinical application of MSCs remain controversial. This review summarizes the findings of a large number of studies and aims to provide an objective viewpoint based on a comprehensive analysis of the presently established benefits and obstacles of implementing MSC-based therapy in kidney transplantation, and to promote its clinical translation.
Duration of depressive symptoms and mortality risk: The English Longitudinal Study of Ageing (ELSA)
Authors: White James , Zaninotto Paola , Walters Kate , Kivimäki Mika , Demakakos Panayotes , Biddulph Jane , Kumari Meena , De Oliveira Cesar , Gallacher John , Batty G. David 
Published: January 2016

BackgroundThe relationship between the duration of depressive symptoms and mortality remains poorly understood.AimsTo examine whether the duration of depressive symptoms is associated with mortality risk.MethodData (n= 9560) came from the English Longitudinal Study of Ageing (ELSA). We assessed depressive symptom duration as the sum of examinations with an eight-item Center for Epidemiologic Studies Depression Scale score of ⩾3; we ascertained mortality from linking our data to a national register.ResultsRelative to those participants who never reported symptoms, the age- and gender-adjusted hazard ratios for elevated depressive symptoms over 1, 2, 3 and 4 examinations were 1.41 (95% CI 1.15–1.74), 1.80 (95% CI 1.44–2.26), 1.97 (95% CI 1.57–2.47) and 2.48 (95% CI 1.90–3.23), respectively (Pfor trend <0.001). This graded association can be explained largely by differences in physical activity, cognitive function, functional impairments and physical illness.ConclusionsIn this cohort of older adults, the duration of depressive symptoms was associated with mortality in a dose–response manner.
Glucose modulates Drosophila longevity and immunity independent of the microbiota
Authors: Galenza Anthony , Hutchinson Jaclyn , Campbell Shelagh D. , Hazes Bart , Foley Edan 
Published: January 2016

ABSTRACT
The acquisition of nutrients is essential for maintenance of metabolic processes in all organisms. Nutritional imbalance contributes to myriad metabolic disorders that include malnutrition, diabetes and even cancer. Recently, the importance of macronutrient ratio of food has emerged as a critical factor to determine health outcomes. Here we show that individual modifications to a completely defined diet markedly impact multiple aspects of organism wellbeing in Drosophila melanogaster. Through a longitudinal survey of several diets we demonstrate that increased levels of dietary glucose significantly improve longevity and immunity in adult Drosophila. Our metagenomic studies show that relative macronutrient levels not only influence the host, but also have a profound impact on microbiota composition. However, we found that elevated dietary glucose extended the lifespan of adult flies even when raised in a germ-free environment. Furthermore, when challenged with a chronic enteric infection, flies fed a diet with added glucose had increased survival times even in the absence of an intact microbiota. Thus, in contrast to known links between the microbiota and animal health, our findings uncover a novel microbiota-independent response to diet that impacts host wellbeing. As dietary responses are highly conserved in animals, we believe our results offer a general understanding of the association between glucose metabolism and animal health.
The role of oncogenic Ras in human skin tumorigenesis depends on the clonogenic potential of the founding keratinocytes
Authors: Maurelli Riccardo , Tinaburri Lavinia , Gangi Fabio , Bondanza Sergio , Severi Anna Lisa , Scarponi Claudia , Albanesi Cristina , Mesiti Giuseppe , Guerra Liliana , Capogrossi Maurizio C. , Dellambra Elena 
Published: January 2016

ABSTRACT
The role of Ras in human skin tumorigenesis induction is still ambiguous. Overexpression of oncogenic Ras causes premature senescence in cultured human cells and hyperplasia in transgenic mice. Here, we investigated whether the oncogenic insult outcome might depend on the nature of the founding keratinocyte. We demonstrate that overexpression of the constitutively active Ras-V12 induces senescence in primary human keratinocyte cultures, but that some cells escape senescence and proliferate indefinitely. Ras overexpression in transient-amplifying- or stem-cell-enriched cultures shows that p16 (encoded by CDKN2A) levels are crucial for the final result. Indeed, transient-amplifying keratinocytes expressing high levels of p16 are sensitive to Ras-V12-induced senescence, whereas cells with high proliferative potential, but that do not display p16, are resistant. The subpopulation that sustains the indefinite culture growth exhibits stem cell features. Bypass of senescence correlates with inhibition of the pRb (also known as RB1) pathway and resumption of telomerase reverse transcriptase (TERT) activity. Immortalization is also sustained by activation of the ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1) and Akt pathways. Moreover, only transduced cultures originating from cultures bearing stem cells induce tumors in nude mice. Our findings demonstrate that the Ras overexpression outcome depends on the clonogenic potential of the recipient keratinocyte and that only the stem cell compartment is competent to initiate tumorigenesis.
REV1 promotes PCNA monoubiquitylation through interacting with ubiquitylated RAD18
Authors: Wang Zhifeng , Huang Min , Ma Xiaolu , Li Huiming , Tang Tieshan , Guo Caixia 
Published: January 2016

ABSTRACT
Translesion DNA synthesis (TLS) is a mode of DNA damage tolerance which plays an important role in genome mutagenesis and chromatin integrity maintenance. Proliferating cell nuclear antigen (PCNA) monoubiquitylation is one of the key factors for TLS pathway choice. So far, it remains unclear how the TLS pathway is elaborately regulated. Here, we report that TLS polymerase REV1 can promote PCNA monoubiquitylation after UV radiation. Further studies revealed that this stimulatory effect is mediated through the enhanced interaction between REV1 and ubiquitylated RAD18, which facilitates the release of nonubiquitylated RAD18 from ubiquitylated RAD18 trapping, after which RAD18 is recruited to chromatin for its TLS function. Furthermore, we found that this stimulatory effect could also be detected after exposure to hydroxyurea or mitomycin C, but not methyl methanesulfonate (MMS), which is in line with the fact that ubiquitylated RAD18 could not be detected after exposure to MMS.
Absence of diurnal variation in visceromotor response to colorectal distention in normal Long Evans rats
Authors: Botschuijver Sara , Yu Zhumei , Welting Olaf , Cailotto Cathy , Kalsbeek Andries , van den Wijngaard Rene 
Published: January 2016

Background: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity) is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS). In healthy men a circadian variation in rectal perception to colonic distention was described. Disturbed day and night rhythms, which occur in shift work and trans meridian flights, are associated with the prevalence of IBS. This raises the question whether disruptions of circadian control are responsible for the observed pathology in IBS. Prior to investigating altered rhythmicity in relation to visceral hypersensitivity in a rat model for IBS, it is relevant to establish whether normal rats display circadian variation similar to healthy men. Methodology and findings: In rodents colorectal distension leads to reproducible contractions of abdominal musculature. We used quantification of this so called visceromotor response (VMR) by electromyography (EMG) to assess visceral sensitivity in rats. We assessed the VMR in normal male Long Evans rats at different time points of the light/dark cycle. Although a control experiment with male maternal separated rats confirmed that intentionally inflicted (i.e. stress induced) changes in VMR can be detected, normal male Long Evans rats showed no variation in VMR along the light/dark cycle in response to colorectal distension.Conclusions: In the absence of a daily rhythm of colorectal sensitivity in normal control rats it is not possible to investigate possible aberrancies in our rat model for IBS.
On Implementing the Model of General Education Quality Management in Orenburg Oblast
Authors: Масликова  , Maslikova E. 
Published: January 2016

The paper concerns the issue of researching the quality of the regional-level education and mechanisms for improving education quality in the
frameworks of implementing the state strategy for modernizing education. The paper lays special accent on the experience of employing the state-ofthe-
art means and know-how for studying the system of education quality assessment, undertaken in Orenburg Oblast; also comprised are the unique
experiences of conducting the regional assessment of the 4th-, 7th- and 8th-graders and high school monitoring. Also the author highlights the challenges
and advantages, revealed through these experiences.
Time-Consistent Decisions and Temporal Decomposition of Coherent Risk Functionals
Authors: Pflug Georg Ch. , Pichler Alois 
Published: January 2016

In management and planning it is commonplace for additional information to become available gradually over time. It is well known that most risk measures (risk functionals) are time inconsistent in the following sense: it may happen that at a given time period, some loss distribution appears to be less risky than another one, but looking at the conditional distribution at a later time, the opposite relation holds almost surely.The extended conditional risk functionals introduced in this paper enable a temporal decomposition of the initial risk functional that can be used to ensure consistency between past and future preferences. The central result is a decomposition theorem, which allows recomposing the initial coherent risk functional by compounding the conditional risk functionals without losing information or preferences. It follows from our results that the revelation of partial information in time must change the decision maker’s preferences—for consistency reasons—among the remaining courses of action. Further, in many situations, the extended conditional risk functional allows ranking of different policies, even based on incomplete information.In addition, we use counterexamples to show that without change-of-measures, the only time-consistent risk functionals are the expectation and the essential supremum.
Native Morphology of Hydrated Spheroidal Halloysite Observed by Environmental Transmission Electron Microscopy
Authors: Berthonneau Jeremie , Grauby Olivier , Jeannin Charlotte , Chaudanson Damien , Joussein Emmanuel , Baronnet Alain 
Published: January 2016

AbstractNatural mineral materials such as tabular and spheroidal halloysites have recently been suggested as candidates for intercalating metal ions or organic molecules. Their potential use as nanoadsorbents is related to their porous structure and water content. Although the two morphologies can coexist in natural deposits, spheroidal halloysites remain poorly characterized whereas much literature exists on tubular halloysites. The present study investigates the native morphology, internal porous structure, and behavior upon dehydration of spheroidal halloysite from Opotiki (New Zealand). This mineral was characterized in its natural hydrated state using a transmission electron microscope equipped with an environmental cell (EC-TEM). The sample was placed in a sealed block in which water vapor-saturated air circulated at a pressure of 30 Torr. The observed particles consisted of almost complete spheroids displaying polyhedral external surfaces. 1:1 layers stack concentrically as a pore-free, onion-like structure. The dynamic processes of dehydration created by slow depressurization of the cell resulted in a decrease in the layer-to-layer distance (d001) from ~10 Å to ~7 Å due to the loss of interlayer water molecules. Irreversible formation of spurious ‘internal pores’ was recorded during this process. These pores were not indigenous to the hydrated 10 Å halloysite and resulted from the collapse of the native layers. They cannot account for the physical chemical properties of spheroidal halloysite. Spheroidal halloysites would have a lower propensity for intercalating ions or molecules than tubular halloysites. Isolated facets were also observed in high-resolution-TEM and displayed a pseudo-hexagonal morphology. The three-dimensional microstructure of the spheroid appeared bent along the three pseudo equivalent yi directions of the kaolinite-like single layers. An analogy with polyhedral serpentine has allowed the proposal of a formation process of hydrated spheroidal halloysite triggered by enrichment in divalent ions in the growth system.
Modified Mineral Phases During Clay Ceramic Firing
Authors: El Ouahabi M. , Daoudi L. , Hatert F. , Fagel N. 
Published: January 2016

AbstractCeramic clays are among the most complicated of ceramic systems because of the very intricate relationship between the behavior of minerals during ceramic processing and their modifications during heating. A major challenge is to predict the phase changes in clay ceramics. The aims of this study were to establish reference data of ceramic products that can be formed based on the mineralogical compositions of the local raw materials. These data, in turn, can be compared with archeological ceramics in order to study their origins.The mineralogical compositions and modifications during firing (550–1100°C under oxidizing conditions) of seven clayey materials sampled from the main clay deposits of northern Morocco were evaluated by X-ray powder diffraction. Two groups of clays were distinguished according to the type of neoformed high-temperature minerals: non-calcareous clays and calcareous clays. For the non-calcareous raw materials, spinel was produced at 950°C. Cristobalite and mullite were formed at temperatures in excess of 1000°C from clays that contain illite, kaolinite, and chlorite. In clays containing vermiculite and large amounts of chlorite, hematite was formed at temperatures in excess of 950°C. Firing of calcareous clays at temperatures >950°C yielded Ca-silicates (diopside, gehlenite and wollastonite), spinel, cristobalite, hematite, and feldspars. Mullite may also form in the calcareous clay products when the carbonate content exceeds 10%.