bluuebunny/crossref_metadata_2025_split huggingface dataset:
c‐Met inhibition enhances chemosensitivity of human ovarian cancer cells
Authors: Wang Jing , Cheng Jian‐Xin 
Published: September 2016

SummaryIn clinical practice, human ovarian cancer shows considerable resistance to chemotherapy. This study aimed to investigate the role of c‐Met in the chemoresistance of ovarian cancer. Ovarian cancer cell line SKOV3 and OVCAR‐3 were pretreated with c‐Met inhibitor INCB28060, and then treated with paclitaxel. Cell survival, cell cycle and apoptosis were analyzed by MTT assay, flow cytometry analysis and TUNEL assay, respectively. The activation of c‐Met signalling was detected by western blot analysis. INCB28060 inhibited the survival of SKOV3 and OVCAR‐3 cells and enhanced the chemosensitivity of SKOV3 and OVCAR‐3 cells to paclitaxel. INCB28060 inhibited c‐Met signalling, caused mitochondrial membrane depolarization and DNA repair, and induced the apoptosis of SKOV3 and OVCAR‐3 cells. c‐Met plays an important role in mediating the chemoresistance of ovarian cancer. The combination of c‐Met inhibitor and chemotherapy is a promising strategy to human ovarian cancer.
Bone metabolism markers: Indicators of loading dose intravenous ibandronate treatment for bone metastases from breast cancer
Authors: Wang Ruliang , Zhang Shaohua , Jiang Zefei , Tian Jizheng , Wang Tao , Song Santai 
Published: September 2016

SummaryTo investigate the changes in bone metabolism markers after second‐line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second‐line loading dose ibandronate for advanced breast cancer with BM and moderate‐to‐severe bone pain. Ibandronate (6 mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3‐4 weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty‐two patients were included in the final analysis. Compared with their pre‐treatment scores, patients exhibited significantly increased KPS scores (P < .01) and a reduced dose of analgesic medication (oxycodone) (P < .01) after 3 and 6 weeks’ post‐treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate‐resistant acid phosphatase (TRACP‐5b), and cross‐linked carboxy‐terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6 weeks’ post‐treatment (P < .001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.
Vertical Integration, Firms’ Entry, Exit, Strategic Shifts, Age, and The Productivity Growth in Korea's Core Growth‐Leading Industries
Authors: Pai Mi Kyung 
Published: September 2016

AbstractThis study attempts to measure the impact of firms’ entry, exit, strategic shifts, and age on the productivity growth of Korea's three core growth‐leading industries and their vertical integration with capital share (VI) firms and non‐VI (NVI) firms in view of the 2008 global financial crisis and the institutional push by the Korean Government. A stochastic frontier production model was applied to firm‐level panel data from 2006 to 2011 for Korea's automobile, electronics and general machinery industries. The results show that exogenous shocks to the market triggered large‐scale resource reallocations from firms with declining productivity to firms with less declining or rising productivity, and market share reallocation between VI firms and NVI firms. The Korean Government's institutional push led the productivity growth of NVI firms to reach their highest levels in 2010. In a VI structure, a structure comprising VI firms only, the agency problem dominated the synergies of secure supply chains and saving on transaction costs, while NVI firms endeavoured to raise their productivity to step into a VI structure to secure stable supply chains, only to find their R&D initiatives stagnated once they took on the VI structure. Therefore, efficient resource reallocation is hindered by the agency problem within the bounds of vertically integrated industrial structures.
Comparing Homicide‐Suicides in the United States and Sweden
Authors: Regoeczi Wendy C. , Granath Sven , Issa Rania , Gilson Thomas , Sturup Joakim 
Published: September 2016

AbstractResearch on homicides followed by suicides has largely relied on very localized samples and relatively short time spans of data. As a result, little is known about the extent to which patterns within cases of homicide‐suicides are geographically specific. The current study seeks to help fill this gap by comparing twenty years of homicide‐suicide data for Sweden and a large U.S. county. Although some of the underlying patterns in the two countries are similar (e.g., decreasing rates), a number of important differences emerge, particularly with respect to incidence, weapons used, perpetrator age, and relationship of the perpetrator to the victim.
Institutional Constraints on Cost‐Effective Water Management: Selenium Contamination in Colorado's Lower Arkansas River Valley
Authors: Sharp Misti D. , Hoag Dana L.K. , Bailey Ryan T. , Romero Erica C. , Gates Timothy K. 
Published: September 2016

AbstractGround and surface water selenium (Se) contamination is problematic throughout the world, leading to harmful impacts on aquatic life, wildlife, livestock, and humans. A groundwater reactive transport model was applied to a regional‐scale irrigated groundwater system in the Lower Arkansas River Basin in southeastern Colorado to identify management practices that remediate Se contamination. The system has levels of surface water and groundwater Se concentrations exceeding the respective chronic standard and guidelines. We evaluate potential solutions by combining the transport model with an assessment of the cost to employ those practices. We use a framework common in economics and engineering fields alike, the Pareto frontier, to show the impact of four different best management practices on the tradeoffs between Se and cost objectives. We then extend that analysis to include institutional constraints that affect the economic feasibility associated with each practice. Results indicate that although water‐reducing strategies have the greatest impact on Se, they are the hardest for farmers to implement given constraints common to western water rights institutions. Therefore, our analysis shows that estimating economic and environmental tradeoffs, as is typically done with a Pareto frontier, will not provide an accurate picture of choices available to farmers where institutional constraints should also be considered.
Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients
Authors: Petersson J. , Giske C. G. , Eliasson E. 
Published: September 2016

BackgroundControversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta‐lactam antibiotics.MethodsWe studied ICU patients treated with either antibiotic, excluding patients on renal replacement therapy. Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2–3 days when feasible. Glomerular filtration rate (GFR) was estimated from plasma creatinine and cystatin C, GFR calculated from cystatin C (eGFR) and measured creatinine clearance (CrCl). Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/l for piperacillin and meropenem respectively.ResultsWe analysed 33 and 31 paired samples from 20 and 19 patients treated with piperacillin–tazobactam and meropenem respectively. Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27.0 (14.7–52.9) and 8.6 (2.7–30.3); and for meropenem, 7.5 (4.7–10.2) and 2.4 (1.0–3.5). All values median (interquartile range) and concentrations in mg/l. The percentage of measured concentrations below the breakpoint at the mid and end of the dosing interval were for piperacillin, 27% and 61%; and for meropenem, 6% and 48%. Lower estimates of GFR were associated with higher concentrations but concentrations varied greatly between patients with similar GFR. The correlation with terminal concentration half‐life was similar for eGFR and CrCl.ConclusionsWith standard doses of meropenem and piperacillin–tazobactam, plasma concentrations in ICU patients vary > 10‐fold and are suboptimal in a significant percentage of patients. The variation is large also between patients with similar renal function.
Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
Authors: Wu Ryan T. , Cao Lei , Mattson Elliot , Witwer Kenneth W. , Cao Jay , Zeng Huawei , He Xin , Combs Gerald F. , Cheng Wen‐Hsing 
Published: September 2016

SummarySelenium (Se) is a trace metalloid essential for life, but its nutritional and physiological roles during the aging process remain elusive. While telomere attrition contributes to replicative senescence mainly through persistent DNA damage response, such an aging process is mitigated in mice with inherently long telomeres. Here, weanling third generation telomerase RNA component knockout mice carrying short telomeres were fed a Se‐deficient basal diet or the diet supplemented with 0.15 ppm Se as sodium selenate to be nutritionally sufficient throughout their life. Dietary Se deprivation delayed wound healing and accelerated incidence of osteoporosis, gray hair, alopecia, and cataract, but surprisingly promoted longevity. Plasma microRNA profiling revealed a circulating signature of Se deprivation, and subsequent ontological analyses predicted dominant changes in metabolism. Consistent with this observation, dietary Se deprivation accelerated age‐dependent declines in glucose tolerance, insulin sensitivity, and glucose‐stimulated insulin production in the mice. Moreover, DNA damage and senescence responses were enhanced and Pdx1 and MafA mRNA expression were reduced in pancreas of the Se‐deficient mice. Altogether, these results suggest a novel model of aging with conceptual advances, whereby Se at low levels may be considered a hormetic chemical and decouple healthspan and longevity.
Emergency Department Utilization in Children <36 Months Is Not an Independent Risk Factor for Maltreatment
Authors: MacNeill Emily C. , Cabey Whitney , Kluge Robert , Norton James , Mitchell Alice M. 
Published: September 2016

AbstractBackground and ObjectivesEarly childhood high‐frequency use (HFU) of the emergency department (ED) has been endorsed as a marker for increased risk of child maltreatment. In a prior analysis of pediatric ED (PED) visits by 16,664 children, 0–36 months old, we defined early childhood HFU (the 90th percentile) as five or more visits. The purpose of this study was to follow HFU patients to determine if they had a higher likelihood of reported maltreatment.MethodsThis is a single‐center, cross‐sectional, observational study of the association between PED use in early life and subsequent intervention by child protective services (CPS). CPS data were obtained from a Department of Social Services database for subjects meeting criteria for PED HFU as well as sex, race, and ethnicity‐matched controls. Multivariable analyses were performed to assess if HFU was independently associated with child maltreatment.ResultsWhile CPS involvement was more highly represented in the group with PED HFU, so were many confounding variables such as African American race, history of hospital admissions, and social work consultations in the PED for any reason. HFU, by itself, is not a risk factor for a major intervention by CPS.ConclusionsIn efforts to identify children at risk for maltreatment, objective assessments such as PED utilization are potential markers to utilize to aid in recognition. Unfortunately, there are many risk factors for increased PED utilization that act as confounders for this marker. Future work is necessary to identify children at risk for maltreatment in the ED.
Parameters of Context‐Induced Ethanol (EtOH)‐Seeking in Alcohol‐Preferring (P) Rats: Temporal Analysis, Effects of Repeated Deprivation, and EtOH Priming Injections
Authors: Hauser Sheketha R. , Deehan Gerald A. , Knight Christopher P. , Toalston Jamie E. , McBride William J. , Rodd Zachary A. 
Published: September 2016

BackgroundDrug‐paired environments can act as stimuli that elicit drug craving. In humans, drug craving is influenced by the amount of time abstinent, number of past periods of abstinence, and inadvertent exposure to the previously abused drug. The current experiments were designed to determine the effects of (i) the duration of abstinence on expression of ethanol (EtOH)‐seeking; (ii) EtOH priming following a short and long abstinence period; and (iii) repeated deprivation cycles on relapse drinking and EtOH‐seeking.MethodsRats were allowed to self‐administer 15% EtOH, processed through extinction training, maintained in a home cage for a designated EtOH‐free period, and then reintroduced to the operant context in the absence of EtOH. The experiments examined the effects of: (i) various home‐cage duration periods (1 to 8 weeks), (ii) priming injections of EtOH in the Pavlovian spontaneous recovery (PSR; 14 days after extinction) and reinstatement of responding (RoR; 1 day after extinction) models, and (iii) exposure to repeated cycles of EtOH access‐deprivation on relapse drinking and EtOH‐seeking behavior.ResultsHighest expression of EtOH‐seeking was observed following 6 weeks of home‐cage maintenance. Priming injections of EtOH were more efficacious at stimulating/enhancing EtOH‐seeking in the PSR than RoR model. Exposure to repeated cycles of EtOH deprivation and access enhanced and prolonged relapse drinking and the expression of EtOH‐seeking (318 ± 22 responses), which was not observed in rats given equivalent consistent exposure to EtOH (66 ± 11 responses).ConclusionsOverall, the data indicated that the PSR model has ecological validity; factors that enhance EtOH craving in humans enhance the expression of EtOH‐seeking in the PSR test. The data also detail factors that need to be examined to determine the biological basis of EtOH‐seeking (e.g., neuroadaptations that occur during the incubation period and following repeated cycles of EtOH drinking and abstinence).
Immediate Neural Plasticity Involving Reaction Time in a Saccadic Eye Movement Task is Intact in Children With Fetal Alcohol Spectrum Disorder
Authors: Paolozza Angelina , Munoz Douglas P. , Brien Donald , Reynolds James N. 
Published: September 2016

BackgroundSaccades are rapid eye movements that bring an image of interest onto the retina. Previous research has found that in healthy individuals performing eye movement tasks, the location of a previous visual target can influence performance of the saccade on the next trial. This rapid behavioral adaptation represents a form of immediate neural plasticity within the saccadic circuitry. Our studies have shown that children with fetal alcohol spectrum disorder (FASD) are impaired on multiple saccade measures. We therefore investigated these previous trial effects in typically developing children and children with FASD to measure sensory neural plasticity and how these effects vary with age and pathology.MethodsBoth typically developing control children (n = 102; mean age = 10.54 ± 3.25; 48 males) and children with FASD (n = 66; mean age = 11.85 ± 3.42; 35 males) were recruited from 5 sites across Canada. Each child performed a visually guided saccade task. Reaction time and saccade amplitude were analyzed and then assessed based on the previous trial.ResultsThere was a robust previous trial effect for both reaction time and amplitude, with both the control and FASD groups displaying faster reaction times and smaller saccades during alternation trials (visual target presented on the opposite side to the previous trial). Children with FASD exhibited smaller overall mean amplitude and smaller amplitude selectively on alternation trials compared with controls. The effect of the previous trial on reaction time and amplitude did not differ across childhood and adolescent development.ConclusionsChildren with FASD did not display any significant reaction time differences, despite exhibiting numerous deficits in motor and higher level cognitive control over saccades in other studies. These results suggest that this form of immediate neural plasticity in response to sensory information before saccade initiation remains intact in children with FASD. In contrast, the previous trial effect on amplitude suggests that the motor component of saccades may be affected, signifying differential vulnerability to prenatal alcohol exposure.
Legacy effects of top–down disturbances on woody plant species composition in semi‐arid systems
Authors: Scholtz R. , Smit I. P. J. , Coetsee C. , Kiker G. A. , Venter F. J. 
Published: September 2016

AbstractSavanna vegetation is controlled by bottom‐up (e.g. soil and rainfall) and top–down (e.g. fire and herbivory) factors, all of which have an effect on biodiversity. Little is known about the relative contribution of these factors to biodiversity, particularly the long‐term effects of top–down disturbance on patterns of woody plant composition. The aim of this study was to identify if various degrees of disturbance regimes create distinct woody species community assemblages. Data were collected over 1820 plots across Kruger National Park, South Africa. Woody species were identified and categorized into one of three height classes: shrub (0.75–2.5 m), brush (2.5–5.5 m), and tree (>5.5 m). Species richness and composition were calculated for each site and height class. A combination of long‐term fire and elephant density data were used to delineate areas with varying degrees of top–down disturbance (i.e. low, medium and high). Using these degrees of disturbance, species composition was identified and community assemblages constructed according to each disturbance regime. Our results suggest that areas with similar disturbance regimes have similar species composition. Shrub composition was mainly responsive to the number of fires between the years 1941–1990, while tree composition was more responsive to elephant disturbance. A few dominant species were found equally under all degrees of disturbance at all height classes, while others were more regularly found under specific disturbance regimes at particular height classes. This study highlights that while species richness does not appear to be influenced by long‐term, top–down disturbance regimes, species community composition may be responsive to these disturbances. Most species and structural classes persisted across all disturbance regimes, but the long‐term effects of top–down disturbances can influence compositional and structural biodiversity. This information provides context for management policies related to artificial water provision, elephants and fire.
Differences in life‐cycle stage components between native and introduced ranges of five woody Fabaceae species
Authors: Harris Carla J. , Manea Anthony , Moles Angela T. , Murray Brad R. , Leishman Michelle R. 
Published: September 2016

AbstractUnderstanding differences in the components of life‐cycle stages of species between their native and introduced ranges can provide insights into the process of species transitioning from introduction to naturalization and invasion. We examined reproductive variables of the germination (seed predation, seed viability, time to germination), seed output (crown projection, seed production, seed weight) and dispersal (seed weight, dispersal investment) stages of five woody Fabaceae species, comparing native and introduced ranges. We predicted that each species would differ in reproductive variables of at least one life‐cycle stage between their native and introduced ranges, thus allowing us to determine the life‐cycle stage most associated with invasion success in the introduced range. Acacia melanoxylon and Paraserianthes lophantha had reduced seed predation in their introduced ranges while P. lophantha also had higher seed viability indicating that the germination life‐cycle stage is most strongly associated with their invasion success in the introduced range. Only Acacia longifolia varied between ranges for the seed output stage due to larger plant size, greater seed production and smaller seed size in its introduced range. Similar to A. longifolia, Acacia cyclops had smaller seed size in its introduced range but did not have any other variable differences between ranges suggesting that the dispersal stage is best associated with its invasion success in the introduced range. Surprisingly, Acacia saligna was the only species without a clear life‐cycle stage difference between ranges despite it being one of the more invasive acacia species in Australia. Although we found clear differences in reproductive variables associated with life‐cycle stages between native and introduced ranges of these five species, these differences were largely species‐specific. This suggests that a species invasion strategy into a novel environment is complex and varies among species depending on the environmental context, phenotypic plasticity and genotypic variation in particular traits.
A Study of Normothermic Hemoperfusion of the Porcine Pancreas and Kidney
Authors: Kuan Kean Guan , Wee Mau Nam , Chung Wen Yuan , Kumar Rohan , Mees Soeren Torge , Dennison Ashley , Maddern Guy , Trochsler Markus 
Published: September 2016

AbstractNormothermic machine perfusion has enormous potential to improve organ preservation and expand the organ donor pool. It is well established in other organs but not the pancreas, which has especially strict organ acceptance criteria. We established a model of normothermic hemoperfusion of the porcine pancreas with and without addition of the kidney as a dialysis organ.Four pancreases were harvested and perfused for 120 min with autologous whole blood at body temperature, two with parallel perfusion of the kidney and two without. The organs and perfusion circuit were evaluated for gross appearance, pH, histology and perfusion parameters.The organs maintained steadily increasing flow rate and perfusion pressure. Gross appearance of the organs was stable but appeared grossly ischemic toward the end of the perfusion period. Histology demonstrated necrosis centered in acinar tissue but islet cells were preserved. pH was significantly alkalotic toward the end of the perfusion, likely due to pancreatic tissue damage. Addition of the kidney did not result in significant improvement of the acid–base environment in this small series.In conclusion, normothermic perfusion of the pancreas is still in the experimental stages but holds great potential. Further studies to optimize perfusion parameters will significantly improve results. Parallel perfusion of the kidney may facilitate improvement in the acid–base environment.