bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALDH1A1 Contributes to PARP Inhibitor Resistance via Enhancing DNA Repair in BRCA2−/− Ovarian Cancer Cells
Authors: Liu Lu , Cai Shurui , Han Chunhua , Banerjee Ananya , Wu Dayong , Cui Tiantian , Xie Guozhen , Zhang Junran , Zhang Xiaoli , McLaughlin Eric , Yin Ming , Backes Floor J. , Chakravarti Arnab , Zheng Yanfang , Wang Qi-En 
Published: September 2019

Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved to treat recurrent ovarian cancer with BRCA1 or BRCA2 mutations, and as maintenance therapy for recurrent platinum-sensitive ovarian cancer (BRCA wild-type or mutated) after treatment with platinum. However, the acquired resistance against PARPi remains a clinical hurdle. Here, we demonstrated that PARP inhibitor (olaparib)–resistant epithelial ovarian cancer (EOC) cells exhibited an elevated aldehyde dehydrogenase (ALDH) activity, mainly contributed by increased expression of ALDH1A1 due to olaparib-induced expression of BRD4, a member of bromodomain and extraterminal (BET) family protein. We also revealed that ALDH1A1 enhanced microhomology-mediated end joining (MMEJ) activity in EOC cells with inactivated BRCA2, a key protein that promotes homologous recombination (HR) by using an intrachromosomal MMEJ reporter. Moreover, NCT-501, an ALDH1A1-selective inhibitor, can synergize with olaparib in killing EOC cells carrying BRCA2 mutation in both in vitro cell culture and the in vivo xenograft animal model. Given that MMEJ activity has been reported to be responsible for PARPi resistance in HR-deficient cells, we conclude that ALDH1A1 contributes to the resistance to PARP inhibitors via enhancing MMEJ in BRCA2−/− ovarian cancer cells. Our findings provide a novel mechanism underlying PARPi resistance in BRCA2-mutated EOC cells and suggest that inhibition of ALDH1A1 could be exploited for preventing and overcoming PARPi resistance in EOC patients carrying BRCA2 mutation.
Intermittent Dosing Regimens of Aspirin and Naproxen Inhibit Azoxymethane-Induced Colon Adenoma Progression to Adenocarcinoma and Invasive Carcinoma
Authors: Mohammed Altaf , Janakiram Naveena B. , Madka Venkateshwar , Zhang Yuting , Singh Anil , Biddick Laura , Li Qian , Lightfoot Stanley , Steele Vernon E. , Lubet Ronald A. , Suen Chen S. , Miller Mark Steven , Sei Shizuko , Rao Chinthalapally V. 
Published: September 2019

Abstract
Chronic use of aspirin and related drugs to reduce cancer risk is limited by unwanted side effects. Thus, we assessed the efficacy associated with different dosing regimens of aspirin and naproxen. Azoxymethane (AOM)-rat colon cancer model was used to establish the pharmacodynamic efficacy of aspirin and naproxen under different dosing regimens. Colon tumors were induced in rats (36/group) by two weekly doses of AOM. At the early adenoma stage, rats were fed diets containing aspirin (700 and 1,400 ppm) or naproxen (200 and 400 ppm), either continuously, 1 week on/1 week off, or 3 weeks on/3 weeks off, or aspirin (2,800 ppm) 3 weeks on/3 weeks off. All rats were euthanized 48 weeks after AOM treatment and assessed for efficacy and biomarkers in tumor tissues. Administration of aspirin and naproxen produced no overt toxicities. Administration of different treatment regimens of both agents had significant inhibitory effects with clear dose-response effects. Aspirin suppressed colon adenocarcinoma multiplicity (both invasive and noninvasive) by 41% (P &lt; 0.003) to 72% (P &lt; 0.0001) and invasive colon adenocarcinomas by 67%–91% (P &lt; 0.0001), depending on the treatment regimen. Naproxen doses of 200 and 400 ppm inhibited invasive adenocarcinoma multiplicity by 53%–88% (P &lt; 0.0001), depending on the dosing regimen. Colonic tumor biomarker analysis revealed that proliferation (proliferating cell nuclear antigen and p21), apoptosis (p53 and Caspase-3), and proinflammatory mediators (IL1β and prostaglandin E2) were significantly correlated with the tumor inhibitory effects of aspirin and naproxen. Overall, our results suggest that intermittent dosing regimens with aspirin or naproxen demonstrated significant efficacy on the progression of adenomas to adenocarcinomas, without gastrointestinal toxicities.
Effects of 7-Methylxanthine on Deprivation Myopia and Retinal Dopamine Release in Chickens
Authors: Liu Hong , Schaeffel Frank , Trier Klaus , Feldkaemper Marita 
Published: September 2019

<b><i>Introduction:</i></b> Intake of 7-methylxanthine (7-MX), an adenosine receptor (AR) antagonist, has been shown to inhibit school myopia in children and deprivation myopia in rhesus monkeys, but the underlying mechanisms are not known. Also retinal dopamine seems to be involved in the control of eye growth, and in the brain, ARs and dopamine receptors interact widely by heteromerization. We have studied whether 7-MX can inhibit deprivation myopia also in chickens and whether inhibition may involve the retinal dopamine system. <b><i>Methods:</i></b> 7-MX was applied by either tube-feeding (100 µg/g body weight, twice a day) or intravitreal injection (12.5 µg, every other day). Forty-eight 2-week-old chicks wore unilateral diffusers and were randomly assigned to either the tube-feeding group (involving 7-MX, vehicle [xanthan gum], or no feeding, for 13 days) or the intravitreal injection group (involving 7-MX, vehicle, or DMSO, for 8 days). Refractions (REs), ocular biometry (AL, VCD), and scleral and choroidal thickness (ChT) were measured before and after treatment. Dopamine and dihydroxyphenylacetic acid (DOPAC) content were determined in retina and vitreous by HPLC at the end of the experiments. <b><i>Results:</i></b> No matter how 7-MX was applied, it did not inhibit deprivation myopia in chicks. No significant differences were observed in RE, VCD, AL, and scleral fibrous layer thickness. Feeding 7-MX produced more choroidal thinning in the open contralateral eye compared to control eyes in the vehicle-fed group (–40 ± 14 vs. –1 ± 7 µm, unpaired <i>t</i> test, <i>p</i> &#x3c; 0.05). DOPAC and dopamine concentration in vitreous and DOPAC concentration in retina did not change with 7-MX. Vitreal dopamine content was significantly decreased in deprived eyes in the groups fed with the vehicle xanthan gum (paired <i>t</i> test, <i>p</i> &#x3c; 0.01) but not in 7-MX-treated eyes, perhaps indicating a small effect of 7-MX on dopamine. <b><i>Conclusions:</i></b> In our study, 7-MX had no effect on DM in chicks and only minor effects on ChT and retinal dopamine. It remains unclear whether 7-MX inhibits myopia through a retinal mechanism or whether it acts directly on choroid and sclera. In the latter case, the finding that myopia is suppressed in mammals but not birds might be explained by differences in scleral structure.
Investigating the role of life-history traits in mammalian genomes
Authors: Tang Yun , Mai Chun Lan , Yu Jian Ping , Li Da Yong 
Published: September 2019

Abstract
Genome size evolution has intrigued many evolutionary biologists. Ultimately, the reasons that genomes have become large are proliferation of non-coding elements and/or duplication events. The proximate causes are related to phylogeny, life-history traits and environmental factors. Genome size in mammals exhibits little interspecific variation compared with other taxa. The proximate causes and the evolutionary patterns shaped by phylogeny or life-history traits are largely unknown for mammals. Here, with a dataset of 121 species of mammals, we studied the variations of genome size associated with life history using a comparative quantitative analysis. The results showed that the genome size was positively associated with body size, but not with four other life-history traits (i.e., gestation period, weaning age, litter size, and longevity) in these species. For Primates, Rodentia and Chiroptera, the genome size was not correlated with life-history traits. Our results suggest that evolution of a large genome may result from increased cell size and thus facilitate the evolution of large bodies.
The Role of the Non-state Film Industry in Promoting China’s Soft Power
Authors: Yang Yanling 
Published: September 2019

Summary
This article explores the role of non-state actors from the film industry in promoting China’s soft power. Much research on non-state actors has emphasised the Anglophone world, while little research has been undertaken in the context of non-democratic regimes such as China. Therefore, following scholarly reviews on soft power and the role of its key actors, this article analyses China’s approach to soft power, based on semi-structured interviews conducted with film experts to explore the role of non-state actors in generating soft power. The study reveals that although China has consistently privileged state-owned actors over non-state actors, non-state actors have actually played an increasingly important role in disseminating soft power. The article argues that the more powerfully the Chinese authorities emphasise China’s state actors, the less likely it is that China will win hearts and minds — because of China’s domestic political ideology and censorship mechanism in the field.
Germany’s Excessive Agricultural Nitrogen Emissions and the Need for Improving Existing Regulatory Concepts
Authors: Möckel Stefan 
Published: September 2019

For decades, German agriculture has been responsible for high nitrogen inputs into the environment. Recent reductions in nitrogen surpluses that were originally caused by fertilization are not sufficient to meet European requirements. In the case of ammonia emissions, there has even been an upward trend despite contradicting national emission targets due to the expansion of animal husbandry. Both developments are not surprising, since German agricultural policy has for years been unable to adopt stricter measures that would reduce nitrogen surpluses and ammonia emissions and modernise existing regulatory concepts in line with European requirements. This paper presents the state of current emissions in section 1. Subsequently, sections 2 to 4 present the regulatory concepts for livestock facilities, agricultural fertilisation as well as the protection of Natura 2000 areas from agricultural intervention and identify their shortcomings in the light of recent rulings by the European Court of Justice. The paper offers a summary assessment that includes the most important areas for improvement.
A Region-Dependent Seasonal Forecasting Framework for Tropical Cyclone Genesis Frequency in the Western North Pacific
Authors: Wang Chao , Wang Bin , Wu Liguang 
Published: September 2019

ABSTRACTIt has been a common practice to predict total tropical cyclone (TC) genesis frequency over the entire western North Pacific (WNP). Here we show that TC genesis (TCG) exhibits distinct regional variability and sources of predictability. Therefore, we divide the WNP into four quadrants with 140°E and 17°N being dividing lines plus the South China Sea (SCS) to predict five subregional TCG frequencies as well as the entire WNP TCG frequency. Besides the well-known ENSO-induced seesaw relationship between the TCGs in the southeast and northwest quadrants, we found that 1) an enhanced TCG in the northeast WNP is associated with a pronounced anomalous cyclonic circulation, which is maintained through its interaction with the underlying sea surface temperature (SST) anomalies; 2) an active TCG in the southwest WNP is accompanied by a zonally elongated positive vorticity anomaly and SST warming over the equatorial eastern Pacific; and 3) the SCS TCG is influenced by the upper-level South Asia high through modulating large-scale environmental parameters. Physically meaningful predictors are identified and a set of empirical prediction models for TCG frequency is established for each subregion. Both the cross-validated reforecast for 1965–2000 and independent forecast for 2001–16 show significant temporal correlation skills. Moreover, the sum of the predicted TCG frequency in five subregions yields a basinwide TCG frequency prediction with a temporal correlation skill of 0.76 for the independent forecast period of 2001–16. The results indicate its potential utility to improve the TC forecasting in the WNP.
Mesoscale Air–Sea Interaction and Its Role in Eddy Energy Dissipation in the Kuroshio Extension
Authors: Yang Haiyuan , Chang Ping , Qiu Bo , Zhang Qiuying , Wu Lixin , Chen Zhaohui , Wang Hong 
Published: September 2019

ABSTRACT
Using the high-resolution Community Earth System Model (CESM) output, this study investigates air–sea interaction and its role in eddy energy dissipation in the Kuroshio Extension (KE) region. Based on an eddy energetics analysis, it is found that the baroclinic pathway associated with temperature variability is the main eddy energy source in this region. Both the air–sea heat flux and wind stress act as eddy killers that remove energy from oceanic eddies. Heat exchange between atmosphere and oceanic eddies dominates the dissipation of eddy temperature variance within the surface layer and accounts for 36% of the total dissipation in the upper 350-m layer. Compared to the heat exchange, the role of wind power in damping the eddy kinetic energy (EKE) is relatively small. Only 18% of EKE dissipation in the upper 350 m is attributed to eddy wind power. Misrepresentation of the damping role of mesoscale ocean–atmosphere interaction can result in an incorrect vertical structure of eddy energy dissipation, leading to an erroneous representation of vertical mixing in the interior ocean.
Nautical Collision Avoidance
Authors: Wickens Christopher D. , Williams Adam , Clegg Benjamin A. , Smith C. A. P. 
Published: September 2019

Objective Experimentally investigate maneuver decision preferences in navigating ships to avoid a collision. How is safety (collision avoidance) balanced against efficiency (deviation from path and delay) and rules of the road under conditions of both trajectory certainty and uncertainty. Background Human decision error is a prominent factor in nautical collisions, but the multiple factors of geometry of collisions and role of uncertainty have been little studied in empirical human factors literature. Approach Eighty-seven Mechanical Turk participants performed in a lower fidelity ship control simulation, depicting ownship and a cargo ship hazard on collision or near-collision trajectories of various conflict geometries, while controlling heading and speed with the sluggish relative dynamics. Experiment 1 involved the hazard on a straight trajectory. In Experiment 2, the hazard could turn on unpredictable trials. Participants were rewarded for efficiency and penalized for collisions or close passes. Results Participants made few collisions, but did so more often when on a collision path. They sometimes violated the instructed rules of the road by maneuvering in front of the hazard ship’s path. They preferred speed control to heading control. Performance degraded in conditions of uncertainty. Conclusion Data reveal an understanding of maneuver decisions and conditions that affect the balance between safety and efficiency. Application The simulation and data highlight the degrading role of uncertainty and provide a foundation upon which more complex questions can be asked, asked of more trained navigators, and decision support tools examined.
Predicting Design-Induced Error on the Flight Deck
Authors: Parnell Katie J. , Banks Victoria A. , Plant Katherine L. , Griffin Thomas G. C. , Beecroft Peter , Stanton Neville A. 
Published: September 2019

Objective To explore the types of errors that commercial pilots may make when trying to resolve a suspected engine oil leak using the interfaces currently available. Background The decisions that pilots make often have to be made quickly and under time pressure, with the emphasis on avoiding critical situations from arising. To make the correct decisions, it is vital that pilots have accurate and up-to-date information available. However, interaction with flight deck interfaces may lead to error if they are not effectively designed. Method A hierarchical task analysis was conducted using evidence from pilot interview data to understand the pilots’ typical response to a suspected engine oil leak scenario. This was used as the primary input into the Systematic Human Error Reduction and Prediction Approach (SHERPA). Results A total of 108 possible errors were identified. The most common error type was a retrieval error, in which flight crews may retrieve the wrong information about the engine. A number of remedial measures are proposed to try and overcome such issues. Conclusion This analysis provides an initial starting point for identifying potential future design ideas that can assist the pilots in dealing with oil leaks. Application This work has identified the value of applying human error identification methodologies to the assessment of current flight deck processes surrounding engine oil leaks. The method presented permits the operational analysis of possible errors on the flight deck and facilitates the proposition of remedial measures to implement technological innovations that can mitigate error.
Hepatitis C Virus Infection in the Dallas County Jail: Implications for Screening, Prevention, and Linkage to Care
Authors: Abe Caroline M. , Aguwa Merilyne , Zhao Michelle , Sullivan Jacqueline , Porsa Esmaeil , Nijhawan Ank E. 
Published: September 2019

Objectives: Screening for hepatitis C virus (HCV) infection in jail provides an opportunity to educate and offer care to a high-risk population. We aimed to (1) estimate the prevalence of HCV infection in jail; (2) describe the demographic characteristics, risk factors, and pre-incarceration health insurance status associated with HCV infection; and (3) examine the implementation of HCV screening in jail. Methods: We conducted a retrospective analysis of an opt-out HCV screening program with HCV RNA confirmation and patient education at the Dallas County Jail from April 1 through November 2, 2017. We extracted data on test results, demographic characteristics, and release destination from electronic medical records. A nurse navigator recorded data on patient self-reported risk factors and pre-incarceration health insurance status. Results: Of 4089 incarcerated persons screened, 708 (17.3%) had a positive HCV antibody result. Of these, 641 (90.5%) had an HCV RNA test ordered; 576 (89.9%) had RNA tests completed, of whom 413 (71.7%) had a positive HCV RNA result. Of these 413, 352 (85.2%) received patient education. Half of HCV RNA-positive incarcerated persons (n = 207, 50.1%) were born outside the birth cohort (1945-1965). Among those with HCV infection, commonly reported risk factors were injection drug use (168 of 352; 47.8%) and tattoos (82 of 352; 23.4%). Most incarcerated persons with HCV infection (284 of 350; 81.1%) did not have health insurance. HCV antibody prevalence was higher among incarcerated persons released to prison (232 of 961; 24.1%) than to outside agencies (38 of 403; 9.4%) or the community (178 of 1026; 17.4%). Conclusions: Screening for HCV with RNA confirmation in jail provides an opportunity for disease education, transmission prevention, and navigation to HCV treatment. Future efforts should examine post-incarceration linkage to care.
Setting meaningful goals in rehabilitation: rationale and practical tool
Authors: Dekker Joost , de Groot Vincent , ter Steeg Anne Marie , Vloothuis Judith , Holla Jasmijn , Collette Emma , Satink Ton , Post Lenneke , Doodeman Suzan , Littooij Elsbeth 
Published: September 2019

Context: Goal-setting is a key characteristic of modern rehabilitation. However, goals need to be meaningful and of importance to the client. Axioms: Both theories and empirical evidence support the importance of a hierarchy of goals: one or more overall goals that clients find personally meaningful and specific goals that are related to the overall goals. We posit that the client’s fundamental beliefs, goals and attitudes (“global meaning”) need to be explored before setting any rehabilitation goal. A chaplain or other person with similar skills can be involved in doing so in an open-ended way. The client’s fundamental beliefs, goals and attitudes serve as a point of departure for setting rehabilitation goals. Setting goals: We set out a three-stage process to set goals: (1) exploring the client’s global meaning (i.e. fundamental beliefs, goals and attitudes), (2) deriving a meaningful overall rehabilitation goal from the client’s global meaning and (3) setting specific rehabilitation goals that serve to achieve the meaningful overall rehabilitation goal. Conclusion: This is an extension of current practice in many rehabilitation teams, which may help counter the drive toward exclusively functional goals based around independence.
Impact of a mass media campaign on participation in the Australian bowel cancer screening program
Authors: Durkin Sarah , Broun Kate , Guerin Nicola , Morley Belinda , Wakefield Melanie 
Published: September 2019

Objective To examine the effect of a mass media campaign designed to increase bowel cancer screening participation. Methods We assessed weekly participation, from January 2015 to December 2017, in the Australian National Bowel Cancer Screening Program in Victoria, where a seven-week campaign aired in mid-2017, and in the adjacent comparison state of South Australia. Participation, defined as the number of immunochemical faecal occult blood tests returned out of those invited by the Screening Program in the past 16 weeks, was analysed using negative binomial regression. Results Compared with non-campaign weeks, there was an increase in the return rate in the campaign state during campaign weeks (adjusted return rates non-campaign weeks = 34.4% vs. campaign weeks = 45.3%, p < 0.01), not observed in the comparison state (38.3% vs. 40.3%, p > 0.05). The increase in the return rate was significantly greater in the campaign state (Rate Ratio of Campaign/Non-Campaign weeks = 1.31, p < 0.01) than the comparison state (1.05, p > 0.05, interaction p < 0.001), and did not differ significantly by age, sex or socio-economic area. The relative increase was greater among never-participants (Rate Ratio of Campaign/Non-Campaign weeks = 1.24) than previous-participants (1.16), interaction p < 0.001). Conclusions This mass media campaign increased bowel cancer screening participation, including from never and low participation subgroups. To maximize participation and ensure equitable population benefit, repeated campaigns that reach eligible people about bowel cancer risks and potential life-saving benefits of screening should be standard.