bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Sampling of Protein Conformational Transitions via Dynamically Optimized Collective Variables
Authors: Brotzakis Z. Faidon , Parrinello Michele 
Published: August 2018

AbstractProtein conformational transitions often involve many slow degrees of freedom. Their knowledge would give distinctive advantages since it provides chemical and mechanistic insight and accelerates the convergence of enhanced sampling techniques that rely on collective variables. In this study, we implemented a recently developed variational approach to conformational dynamics metadynamics to the conformational transition of the moderate size protein, L99A T4 Lysozyme. In order to find the slow modes of the system we combined data coming from NMR experiments as well as short MD simulations. A Metadynamics simulation based on these information reveals the presence of two intermediate states, at an affordable computational cost.
Genotype patterns in growing solid tumors
Authors: Nanda Mridu , Durrett Rick , Harvard U , Duke U 
Published: August 2018

AbstractOver the past decade, the theory of tumor evolution has largely focused on the selective sweeps model. According to this theory, tumors evolve by a succession of clonal expansions that are initiated by driver mutations. In a 2015 analysis of colon cancer data, Sottoriva et al [34] proposed an alternative theory of tumor evolution, the so-called Big Bang model, in which one or more driver mutations are acquired by the founder gland, and the evolutionary dynamics within the expanding population are predominantly neutral. In this paper we will describe a simple mathematical model that reproduces qualitative features of the observed paatterns of genetic variability and makes quantitative predictions.
The claustrum is required for reward acquisition under high cognitive demand
Authors: White Michael G. , Mu Chaoqi , Zeng Hongkui , Mathur Brian N. 
Published: August 2018

AbstractThe claustrum is proposed to mediate a variety of functions ranging from sensory binding to top-down cognitive control of action, but direct functional assessments of this telencephalic nucleus are lacking. Here we employ the guanine nucleotide-binding subunit beta-4 cre driver line in mice to selectively monitor and manipulate claustrum projection neurons. Using fiber photometry, we find elevated claustrum activity prior to an expected cue during correct performance on a cognitively demanding five-choice response assay relative to a less-demanding one-choice version of the task. Claustrum activity during reward acquisition is also enhanced when cognitive demand is higher. Furthermore, we use optogenetic inhibition of claustrum prior to the expected cue to demonstrate that claustrum is critical for accurate performance on the five-choice, but not the one-choice, task. These results suggest the claustrum supports a cognitive control function necessary for reward acquisition under cognitively demanding conditions.
Actively restoring resilience in selectively logged tropical forests
Authors: Cerullo Gianluca R. , Edwards David P. 
Published: August 2018

Abstract

Huge tracts of tropical forest are selectively logged. Meanwhile, emerging global agendas are providing unprecedented incentives for large‐scale restoration within human‐impacted tropical forest landscapes. Whilst logged forests have high conservation value, their adoption within these agendas remains controversial.

We review the value of restoring logged tropical forests for boosting economic and environmental resilience. Targeted interventions can recover depleted timber stocks, increase saleable carbon stores, and deliver employment and non‐timber forest products (NTFPs) to local communities. Restoration has mixed outcomes for biodiversity but if it improves relogging practices and protects forests from conversion to agricultural plantations may have major positive impacts.

We also examine socio‐economic and political pathways for upscaling logged forest restoration and their incorporation into sustainable forestry, given political and commercial malaise on post‐logging interventions. Spurring these transitions will require strong institutions, executed by policies that enable long‐term concession licences and community land tenure, that leverage commercial involvement and payments for ecosystem services, and that optimise existing interventions.

Research frontiers include: (a) validating the economic and technical feasibility of different interventions; (b) understanding how these interventions impact on synergies and trade‐offs between ecosystem services, NTFPs, and biodiversity; and (c) identifying when to restore a logged forest. This requires establishing long‐term experimental trials that jointly track environmental and socioeconomic outcomes.

Synthesis and applications. Post‐logging interventions can deliver various timber, carbon, socioeconomic and potentially biodiversity benefits but are underemployed and undervalued pantropically. Opportunities exist to optimise interventions by tailoring incentives, policies, and management to ecological and social circumstances. Governments, conservation bodies and the private sector must underscore restoration of production forests as a major future objective, including via greater adoption in global initiatives, including forest and landscape restoration under the Bonn Challenge and the Reducing Emissions from Deforestation and Forest Degradation (REDD+) agenda.
Distinct responses of niche and fitness differences to water availability underlie variable coexistence outcomes in semi‐arid annual plant communities
Authors: Wainwright Claire E. , HilleRisLambers Janneke , Lai Hao R. , Loy Xingwen , Mayfield Margaret M. 
Published: August 2018

Abstract

Climate change is predicted to have profound consequences for multispecies coexistence, and thus, patterns of biological diversity. These consequences will be mediated by direct and indirect impacts of environmental change on species’ vital rates and interactions. While the impacts of environmental change on individual species has received much attention to date, the consequences for coexistence mediated by changes in the strength and direction of multispecies interactions are not as well understood.

To investigate how coexistence dynamics may be sensitive to environmental change, we conducted a field experiment in a diverse semi‐arid annual plant system. We imposed a water manipulation treatment in two sites that vary in aridity and associated rainfall. Focusing on four common annual plant species in these sites, we quantified the fecundity (seed production) of individuals in response to a gradient of intra‐ and interspecific competitor densities and aridity. We then used these fecundities to parameterize an annual plant population model and examine the influence of aridity and species identity on resultant coexistence dynamics (as a function of stabilizing niche differences and fitness inequalities).

While the responses of some vital rates and competitive impacts to watering varied somewhat predictably across sites, coexistence metrics encapsulating changes in these vital rates and interaction strengths did not. Fitness inequalities among our focal species were driven largely by differences in sensitivity to competition, which were almost always much greater than the magnitude of stabilizing niche differences. These findings were surprising given observational evidence suggesting that these species do coexist at local scales in these natural communities.

Synthesis. Our study is one of the first to explicitly consider the influence of environmental variation on the individual components of coexistence outcomes. We show that environmental change has the ability to influence coexistence not only through direct pathways (i.e., vital rates), but also indirect pathways (i.e., species interactions). Despite the consistency of many of the responses of these individual components to environmental variation, their combined influence on predictions of both current and future coexistence remains unclear.
Upregulation of C/EBPβ and TSC2 by an HDAC inhibitor CG200745 protects heart from DOCA‐induced hypertrophy
Authors: Lee Eunjo , Lee Hae‐Ahm , Kim Mina , Do Ga young , Cho Hyun‐Min , Kim Gun Jik , Jung Hanna , Song Jung Hup , Cho Joong Myung , Kim Inkyeom 
Published: August 2018

SummaryHistone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor‐mediated upregulation of TSC2 is unclear. We hypothesized that an HDAC inhibitor, CG200745 (CG), ameliorates cardiac hypertrophy through the inhibition of mTORC1 signaling by upregulating of the CCAAT/enhancer‐binding protein‐β (C/EBP‐β)/TSC2 pathway. To establish a cardiac hypertrophy model, deoxycorticosterone acetate (DOCA, 40 mg/kg/wk) was subcutaneously injected for 4 weeks into Sprague‐Dawley rats. All rats were unilaterally nephrectomized and had free access to drinking water containing 1% NaCl with or without CG of different concentrations. The expression level of TSC2 and C/EBP‐β was measured by quantitative real‐time PCR (qRT‐PCR) and western blot analysis. Acetylation of C/EBP‐β was analyzed by immunoprecipitation. The recruitment of C/EBP‐β and polymerase II (Pol II) on TSC2 promoter region was analyzed by chromatin immunoprecipitation (ChIP). CG treatment increased the expression of TSC2. In addition, CG treated rats showed an increased in the expression and acetylation of C/EBP‐β, owing to the increase in the recruitment of C/EBP‐β and Pol II at Tsc2 gene promoter. Thus, CG ameliorates cardiac hypertrophy through the inhibition of mTORC1 signaling via upregulation of the C/EBP‐β/TSC2 pathway in DOCA‐induced hypertensive rats.
Adolescent parenthood associated with adverse socio‐economic outcomes at age 30 years in women and men of the Pelotas, Brazil: 1982 Birth Cohort Study
Authors: Gigante DP , de França GVA , De Lucia Rolfe E , Lima NP , dos Santos Motta JV , Gonçalves H , Horta BL , Barros FC , Ong KK 
Published: August 2018

ObjectiveTo investigate the potential long‐term effects of adolescent parenthood on completed education and income.DesignPopulation‐based birth cohort study.SettingAll live births in 1982, whose mothers lived in the urban area of Pelotas, southern Brazil.SampleA total of 3701 participants: 1914 women and 1787 men at age 30 years.MethodsQuestionnaires were completed by the mothers in the early phases of this study, and by the cohort members in adolescence and adulthood. Linear regression models and G‐computation were used in the analyses.Main outcome measuresEducational attainment and income at age 30 years.ResultsIn women, adolescent parenthood was associated with lower attained education compared with women without adolescent maternity: by −2.8 years [95% confidence interval (CI) −3.2 to −2.3] if their first birth was at age 16–19, and by −4.4 years (−5.5 to −3.3) at age 11–15. These effects were greater among women who had three or more children. Women with adolescent parenthood also had 49 or 33% lower income at age 30 if their first child was born when aged 16–19 or 11–15, respectively. In men, the adverse effect of adolescent parenthood on education appeared to be mediated by a higher number of children and there was no effect of adolescent paternity on income at age 30 years.ConclusionThese findings suggest lasting socio‐economic disadvantages of adolescent parenthood, with larger effects being apparent in women than in men.Tweetable abstractAdolescent parenthood has an adverse effect on educational attainment later in life, and on household income among women.
MRI measurement of residual cervical length after radical trachelectomy for cervical cancer and the risk of adverse pregnancy outcomes: a blinded imaging analysis
Authors: Alvarez RM , Biliatis I , Rockall A , Papadakou E , Sohaib SA , deSouza NM , Butler J , Nobbenhuis M , Barton DJP , Shepherd JH , Ind TEJ 
Published: August 2018

ObjectiveTo determine the association between the residual cervix measured on postoperative MRI after radical vaginal trachelectomy (RVT) and adverse obstetrical outcomes.DesignObservational study.SettingReferral Cancer centre.PopulationWomen who conceived after RVT for cervical cancer at the Royal Marsden Hospital, London, between 1995 and 2015.MethodsPostoperative MRI scans were analysed by three researchers. The agreement between researchers was assessed by Pearson's correlation coefficient and Bland–Altman plot. Patients were divided into two groups (<10 and ≥10 mm residual cervix) for the analysis of adverse obstetrical outcomes.Main outcome measuresLate miscarriage, premature delivery, premature rupture of membranes (PROM) and chorioamnionitis.ResultsThirty‐one MRI scans were available; 29 of these women had a pregnancy that progressed beyond the first trimester. There was a strong reproducibility of the measurement of residual cervix (P < 0.001). Nineteen women (65.5%) had <10 mm residual cervix and 10 (34.5%) had ≥10 mm. Among women with <10 mm residual cervix, seven (36.8%) experienced PROM and ten (66.7%) had a preterm birth; No women with ≥10 mm residual cervix had PROM and two (22.2%) had a preterm birth (P = 0.028 and P = 0.035, respectively). Overall, there were nine (16.7%) first‐trimester miscarriages, six (11.1%) late fetal losses, 12 (31.6%) preterm births and 36 (66.7%) live births. After a mean follow up of 78.1 months, 36 women were disease‐free and one woman had died.ConclusionsMRI measurements of the residual cervix are reproducible between observers. The incidence of PROM and premature delivery is higher when the residual cervix after RVT is <10 mm.Tweetable abstractThe risk of prematurity after RVT can be predicted from measurements of residual cervical length on postoperative MRI scan.
Varying 10‐year off‐treatment responses to nucleos(t)ide analogues in patients with chronic hepatitis B according to their pretreatment hepatitis B e antigen status
Authors: Liu Feng , Liu Zhi Rong , Li Tao , Liu You De , Zhang Meng , Xue Yan , Zhang Li Xin , Ye Qian , Fan Xiao Ping , Wang Lei 
Published: August 2018

OBJECTIVETo evaluate the long‐term durability and efficacy of nucleos(t)ide analogues (NAs) and to determine the related factors for virological relapse in chronic hepatitis B (CHB) patients.METHODSCHB patients who fulfilled the criteria for discontinuing NAs therapy in accordance with the published guidelines were included in the study from December 2001. Virological relapse was defined as serum hepatitis virus B (HBV) DNA >104 copies/mL twice at least 2 weeks apart.RESULTSA total of 223 CHB patients were enrolled at the time their NAs therapy was discontinued. The 10‐year cumulative relapse rate (CRR) in hepatitis B e antigen (HBeAg)‐positive patients was statistically lower than that in HBeAg‐negative patients (30.9% vs 62.3%, P < 0.001). In the HBeAg‐positive group, Cox regression analysis showed that age at cessation (hazard ratio [HR] 1.067, P < 0.001), consolidation therapy (HR 0.958, P = 0.021), and time to HBeAg seroconversion (HR 0.943, P = 0.019) were predictors for relapse. In the HBeAg‐negative group, age at cessation (HR 1.040, P = 0.004) and time to HBV DNA negativity (HR 1.246, P = 0.010) were potential predictors for virological relapse.CONCLUSIONSThe off‐treatment responses to NAs differ in CHB patients with different pretreatment HBeAg status. NA withdrawal is generally safe and feasible in young patients with CHB. Long consolidation periods should be preferred in HBeAg‐positive patients to achieve better durability. Benefits of cessation of NAs do not last long in HBeAg‐negative CHB patients.
Population attributable fractions of the main type 2 diabetes mellitus risk factors in women: Findings from the French E3N cohort
Authors: Rajaobelina Kalina , Dow Courtney , Romana Mancini Francesca , Dartois Laureen , Boutron‐Ruault Marie‐Christine , Balkau Beverley , Bonnet Fabrice , Fagherazzi Guy 
Published: August 2018

AbstractBackgroundAlthough many type 2 diabetes mellitus (T2DM) risk factors have been identified, little is known regarding their contributions to the diabetes burden at the population level.MethodsThe study included 72 655 French women from the Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort followed between 1993 and 2011. Cox multivariable models including the main T2DM risk factors (metabolic, dietary, clinical, socioeconomic and hormonal) and a healthy lifestyle index combining five characteristics (smoking, body mass index [BMI], alcohol consumption, fruit and vegetable consumption, and physical activity) were used to estimate hazard ratios and population attributable fractions (PAFs) for T2DM.ResultsIn multivariate models, factors with the strongest effect on T2DM risk were, in decreasing order, BMI ≥ 30 kg/m2 (PAF = 43%; 95% confidence interval [CI] 37–47), high adherence to a Western dietary pattern (PAF = 30%; 95% CI 20–40), hypertension (PAF = 26%; 95% CI 20–32), an acidogenic diet (PAF = 24%; 95% CI 16–32), a family history of diabetes (PAF = 20%; 95% CI 17–22), and, with a negative correlation, moderate alcohol consumption (PAF–19%; 95% CI –34, −4). The PAF for an unhealthy lifestyle was 57% (95% CI 50–63).ConclusionsWe have been able to sort out and quantify the effect of various dietary and biological T2DM risk factors simultaneously in a single population, and to highlight the importance of a healthy lifestyle for primary prevention: more than half the T2DM cases could have been prevented through a healthier lifestyle.
Shifts in Alcohol‐Related Diagnoses After the Introduction of International Classification of Diseases, Tenth Revision, Clinical Modification Coding in U.S. Hospitals: Implications for Epidemiologic Research
Authors: Heslin Kevin C. , Barrett Marguerite L. 
Published: August 2018

BackgroundIn October 2015, the United States transitioned healthcare diagnosis codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM), to the Tenth Revision (ICD‐10‐CM). Trend analyses of alcohol‐related stays could show discontinuities solely from the change in classification systems. This study examined the impact of the ICD‐10‐CM coding system on estimates of hospital stays involving alcohol‐related diagnoses.MethodsThis analysis used 2014 to 2017 administrative data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project State Inpatient Databases for 17 states. Quarterly ICD‐9‐CM data from second quarter 2014 through third quarter 2015 were concatenated with ICD‐10‐CM data from fourth quarter 2015 through first quarter 2017. Quarterly counts of alcohol‐related stays were examined overall and then by 6 diagnostic subgroups: withdrawal, abuse, dependence, alcohol‐induced mental disorders (AIMD), nonpsychiatric alcohol‐induced disease, and intoxication or toxic effects. Within each group, we calculated the difference in the average number of stays between ICD‐9‐CM and ICD‐10‐CM coding periods.ResultsOn average, the number of stays involving any alcohol‐related diagnosis in the 6 quarters before and after the ICD‐10‐CM transition was stable. However, substantial shifts in stays occurred for alcohol abuse, AIMD, and intoxication or toxic effects. For example, the average quarterly number of stays involving AIMD was 170.7% higher in the ICD‐10‐CM period than in the ICD‐9‐CM period. This increase was driven in large part by 1 ICD‐10‐CM code, Alcohol use, unspecified with unspecified alcohol‐induced disorder.ConclusionsResearchers conducting trend analyses of inpatient stays involving alcohol‐related diagnoses should consider how ongoing modifications in the ICD‐10‐CM code system and coding guidelines might affect their work. An advisable approach for trend analyses across the ICD‐10‐CM transition is to aggregate diagnosis codes into broader, clinically meaningful groups—including a single global group that encompasses all alcohol‐related stays—and then to select diagnostic groupings that minimize discontinuities between the 2 coding systems while providing useful information on this important indicator of population health.
Investor reaction to accounting misstatements under IFRS: Australian evidence
Authors: Goodwin John , Atilgan Yigit , Simsir Serif Aziz , Ahmed Kamran 
Published: August 2018

AbstractWe examine the investor reaction to misstatement news for Australian listed firms from 2006 to 2013. We find 4.1 percent of firm‐years have a misstatement and 79 percent of misstatements are disclosed initially only in the periodic filings (stealth misstatements). We find no investor reaction for the average misstatement, reactions of between −2.3 percent and −2.8 percent (−1.5 and −1.7 percent) for misstatements that reduce prior‐period earnings or equity (affect revenue) and reactions of between −1.3 and −2.7 percent for non‐stealth misstatements. Investor reactions are more negative for non‐stealth misstatements that reduce prior‐period earnings or equity than for stealth misstatements.
Legibility of floor plans and wayfinding satisfaction of residents in Care and Attention homes in Hong Kong
Authors: Tao Yiqi , Gou Zhonghua , Lau Stephen Siu‐Yu , Lu Yi , Fu Jiayan 
Published: August 2018

ObjectiveFocusing on Hong Kong Care and Attention homes which provide residential care, meals, personal care and limited nursing care for older people, this study aimed to understand the impact of floor plans’ legibility (layout and complexity) on residents’ wayfinding satisfaction and self‐reported health status.MethodsA questionnaire survey was conducted in nine Care and Attention homes. Space syntax, a well‐established method, was used to evaluate the legibility of their floor plans via calculating the integration value.ResultsFamiliarity with Care and Attention homes did not influence the residents’ satisfaction with wayfinding. The integration value had a significant impact on residents’ satisfaction with wayfinding. No relationship was observed between integration value and self‐reported health status.ConclusionIncreasing complexity in floor plans appears to negatively affect residents’ wayfinding satisfaction. These data suggest that circulation patterns should be improved for better wayfinding.