bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of N-terminal pro-B-type natriuretic peptide in patients with three-vessel disease
Authors: Zhang Ce , Jiang Lin , Xu Lianjun , Tian Jian , Liu Junhao , Zhao Xueyan , Feng Xinxing , Wang Dong , Zhang Yin , Sun Kai , Xu Bo , Zhao Wei , Hui Rutai , Gao Runlin , Yuan Jinqing , Song Lei 
Published: May 2019

Abstract

Aims
Risk assessment and treatment stratification for three-vessel disease (3VD) remain challenging. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for prognostication and treatment in heart failure. The present study aimed to evaluate the prognostic value of NT-proBNP beyond the SYNTAX score II (SSII), and its association with long-term outcome after three strategies [percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT)] in a cohort of patients with 3VD.

Methods and results
A total of 6597 patients with available baseline NT-proBNP data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. During a median follow-up of 7.0 years, higher NT-proBNP levels were strongly associated with increased risks of all-cause death, cardiac death, and MACCE (all adjusted P &lt; 0.01). Moreover, NT-proBNP significantly improved discrimination and reclassification of the SSII. Notably, there was a significant interaction between NT-proBNP quartiles and treatment strategies for MACCE (P = 0.004). Revascularization was associated with lower risks of MACCE than MT, except for patients in the lowest quartile wherein no such association was observed. Among patients in the highest quartile, PCI was associated with an increased risk of MACCE compared with CABG (hazard ratio 1.43, 95% confidence interval 1.09–1.87).

Conclusion
N-terminal pro-BNP is a potential biomarker for risk stratification and therapeutic decision-making in patients with 3VD. Further randomized studies are needed to confirm these findings.
Biomarkers to predict the response to cardiac resynchronization therapy
Authors: Heggermont Ward , Auricchio Angelo , Vanderheyden Marc 
Published: May 2019

AbstractCardiac resynchronization therapy (CRT) is an established non-pharmacological treatment for selected heart failure patients with wide QRS duration. However, there is a persistent number of non-responders throughout. The prediction of the CRT response is paramount to adequately select the correct patients for CRT. One of the expanding fields of research is the development of biomarkers that predict the response to CRT. A review of the available literature on biomarkers in CRT patients has been performed to formulate a critical appraisal of the available data. The main conclusion of our review is that biomarker research in this patient population is very fragmented and broad. This results in the use of non-uniform endpoints to define the CRT response, which precludes an in-depth comparison of the available data. To improve research development in this field, a uniform definition of the CRT response and relevant endpoints is necessary to better predict the CRT response.
Recent Secondary Contacts, Linked Selection, and Variable Recombination Rates Shape Genomic Diversity in the Model Species Anolis carolinensis
Authors: Bourgeois Yann , Ruggiero Robert P , Manthey Joseph D , Boissinot Stéphane 
Published: May 2019

AbstractGaining a better understanding on how selection and neutral processes affect genomic diversity is essential to gain better insights into the mechanisms driving adaptation and speciation. However, the evolutionary processes affecting variation at a genomic scale have not been investigated in most vertebrate lineages. Here, we present the first population genomics survey using whole genome resequencing in the green anole (Anolis carolinensis). Anoles have been intensively studied to understand mechanisms underlying adaptation and speciation. The green anole in particular is an important model to study genome evolution. We quantified how demography, recombination, and selection have led to the current genetic diversity of the green anole by using whole-genome resequencing of five genetic clusters covering the entire species range. The differentiation of green anole’s populations is consistent with a northward expansion from South Florida followed by genetic isolation and subsequent gene flow among adjacent genetic clusters. Dispersal out-of-Florida was accompanied by a drastic population bottleneck followed by a rapid population expansion. This event was accompanied by male-biased dispersal and/or selective sweeps on the X chromosome. We show that the interaction between linked selection and recombination is the main contributor to the genomic landscape of differentiation in the anole genome.
Changing Impact of Obesity on Active Life Expectancy of Older Americans
Authors: Zhang Yuan S , Saito Yasuhiko , Crimmins Eileen M 
Published: May 2019

Abstract

Background
The rise in the number and earlier age of onset of obese persons has raised critical concerns about consequences of obesity; however, recent evidence suggests that the impact of obesity on health outcomes may have changed. This study aims to assess the change of the impact of obesity on active life expectancy among Americans aged 70 years and older over almost two decades, 1993–1998 to 2010–2014.

Methods
For each period, we use three waves of data from the Health and Retirement Study to estimate age-specific transition probabilities between health states. The average number of years active and disabled is calculated with Interpolated Markov Chain software based on estimated transition probabilities.

Results
Overall obesity and severe obesity increased markedly over time yet active life expectancy expanded for all individuals and the increases are greater among the obese and women. Increases in total and active life expectancy occurred because of the changing association of obesity with disability and mortality.

Conclusions
Individuals at age 70 years in the later period in each weight group could expect to live a smaller proportion of remaining life with activities of daily living disability than those in the earlier period. High levels of obesity continue to have significant adverse effects on the quality of life. The increasing prevalence of severe obesity and the growing number of older persons may result in substantial additional health care needs and costs. Continued effort to improve cardiovascular health is required to control the burden of obesity in later life in an era of rising obesity.
Ibuprofen enhances synaptic function and neural progenitors proliferation markers and improves neuropathology and motor coordination in Machado–Joseph disease models
Authors: Mendonça Liliana S , Nóbrega Clévio , Tavino Silvia , Brinkhaus Maximilian , Matos Carlos , Tomé Sandra , Moreira Ricardo , Henriques Daniel , Kaspar Brian K , Pereira de Almeida Luís 
Published: May 2019

AbstractMachado–Joseph disease or spinocerebellar ataxia type 3 is an inherited neurodegenerative disease associated with an abnormal glutamine over-repetition within the ataxin-3 protein. This mutant ataxin-3 protein affects several cellular pathways, leading to neuroinflammation and neuronal death in specific brain regions resulting in severe clinical manifestations. Presently, there is no therapy able to modify the disease progression. Nevertheless, anti-inflammatory pharmacological intervention has been associated with positive outcomes in other neurodegenerative diseases. Thus, the present work aimed at investigating whether ibuprofen treatment would alleviate Machado–Joseph disease.We found that ibuprofen-treated mouse models presented a significant reduction in the neuroinflammation markers, namely Il1b and TNFa mRNA and IKB-α protein phosphorylation levels. Moreover, these mice exhibited neuronal preservation, cerebellar atrophy reduction, smaller mutant ataxin-3 inclusions and motor performance improvement. Additionally, neural cultures of Machado–Joseph disease patients’ induced pluripotent stem cells-derived neural stem cells incubated with ibuprofen showed increased levels of neural progenitors proliferation and synaptic markers such as MSI1, NOTCH1 and SYP. These findings were further confirmed in ibuprofen-treated mice that display increased neural progenitor numbers (Ki67 positive) in the subventricular zone. Furthermore, interestingly, ibuprofen treatment enhanced neurite total length and synaptic function of human neurons. Therefore, our results indicate that ibuprofen reduces neuroinflammation and induces neuroprotection, alleviating Machado–Joseph disease-associated neuropathology and motor impairments. Thus, our findings demonstrate that ibuprofen treatment has the potential to be used as a neuroprotective therapeutic approach in Machado–Joseph disease.
Learning impairments and molecular changes in the brain caused by β-catenin loss
Authors: Wickham Robert J , Alexander Jonathan M , Eden Lillian W , Valencia-Yang Mabel , Llamas Josué , Aubrey John R , Jacob Michele H 
Published: May 2019

AbstractIntellectual disability (ID), defined as IQ<70, occurs in 2.5% of individuals. Elucidating the underlying molecular mechanisms is essential for developing therapeutic strategies. Several of the identified genes that link to ID in humans are predicted to cause malfunction of β-catenin pathways, including mutations in CTNNB1 (β-catenin) itself. To identify pathological changes caused by β-catenin loss in the brain, we have generated a new β-catenin conditional knockout mouse (β-cat cKO) with targeted depletion of β-catenin in forebrain neurons during the period of major synaptogenesis, a critical window for brain development and function. Compared with control littermates, β-cat cKO mice display severe cognitive impairments. We tested for changes in two β-catenin pathways essential for normal brain function, cadherin-based synaptic adhesion complexes and canonical Wnt (Wingless-related integration site) signal transduction. Relative to control littermates, β-cat cKOs exhibit reduced levels of key synaptic adhesion and scaffold binding partners of β-catenin, including N-cadherin, α-N-catenin, p120ctn and S-SCAM/Magi2. Unexpectedly, the expression levels of several canonical Wnt target genes were not altered in β-cat cKOs. This lack of change led us to find that β-catenin loss leads to upregulation of γ-catenin (plakoglobin), a partial functional homolog, whose neural-specific role is poorly defined. We show that γ-catenin interacts with several β-catenin binding partners in neurons but is not able to fully substitute for β-catenin loss, likely due to differences in the N-and C-termini between the catenins. Our findings identify severe learning impairments, upregulation of γ-catenin and reductions in synaptic adhesion and scaffold proteins as major consequences of β-catenin loss.
Taking a Stab at Quantifying the Energetics of Biological Puncture
Authors: Anderson Philip S L , Crofts Stephanie B , Kim Jin-Tae , Chamorro Leonardo P 
Published: May 2019

AbstractAn organism’s ability to control the timing and direction of energy flow both within its body and out to the surrounding environment is vital to maintaining proper function. When physically interacting with an external target, the mechanical energy applied by the organism can be transferred to the target as several types of output energy, such as target deformation, target fracture, or as a transfer of momentum. The particular function being performed will dictate which of these results is most adaptive to the organism. Chewing food favors fracture, whereas running favors the transfer of momentum from the appendages to the ground. Here, we explore the relationship between deformation, fracture, and momentum transfer in biological puncture systems. Puncture is a widespread behavior in biology requiring energy transfer into a target to allow fracture and subsequent insertion of the tool. Existing correlations between both tool shape and tool dynamics with puncture success do not account for what energy may be lost due to deformation and momentum transfer in biological systems. Using a combination of pendulum tests and particle tracking velocimetry (PTV), we explored the contributions of fracture, deformation and momentum to puncture events using a gaboon viper fang. Results on unrestrained targets illustrate that momentum transfer between tool and target, controlled by the relative masses of the two, can influence the extent of fracture achieved during high-speed puncture. PTV allowed us to quantify deformation throughout the target during puncture and tease apart how input energy is partitioned between deformation and fracture. The relationship between input energy, target deformation and target fracture is non-linear; increasing impact speed from 2.0 to 2.5 m/s created no further fracture, but did increase deformation while increasing speed to 3.0 m/s allowed an equivalent amount of fracture to be achieved for less overall deformation. These results point to a new framework for examining puncture systems, where the relative resistances to deformation, fracture and target movement dictate where energy flows during impact. Further developing these methods will allow researchers to quantify the energetics of puncture systems in a way that is comparable across a broad range of organisms and connect energy flow within an organism to how that energy is eventually transferred to the environment.
Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study
Authors: Harris Holly R , Cushing-Haugen Kara L , Webb Penelope M , Nagle Christina M , Jordan Susan J ,   Australian Ovarian Cancer Study Group, Risch Harvey A , Rossing Mary Anne , Doherty Jennifer A , Goodman Marc T , Modugno Francesmary , Ness Roberta B , Moysich Kirsten B , Kjær Susanne K , Høgdall Estrid , Jensen Allan , Schildkraut Joellen M , Berchuck Andrew , Cramer Daniel W , Bandera Elisa V , Rodriguez Lorna , Wentzensen Nicolas , Kotsopoulos Joanne , Narod Steven A , McLaughlin John R , Anton-Culver Hoda , Ziogas Argyrios , Pearce Celeste L , Wu Anna H , Lindström Sara , Terry Kathryn L 
Published: May 2019

Abstract

Background
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4–21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer.

Methods
Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls).

Results
An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85–0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65–0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations.

Conclusion
Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.
Bias control in the analysis of case–control studies with incidence density sampling
Authors: Cheung Yin Bun , Ma Xiangmei , Lam K F , Li Jialiang , Milligan Paul 
Published: May 2019

AbstractBackgroundPrevious simulation studies of the case–control study design using incidence density sampling, which required individual matching for time, showed biased estimates of association from conditional logistic regression (CLR) analysis; however, the reason for this is unknown. Separately, in the analysis of case–control studies using the exclusive sampling design, it has been shown that unconditional logistic regression (ULR) with adjustment for an individually matched binary factor can give unbiased estimates. The validity of this analytic approach in incidence density sampling needs evaluation.MethodsIn extensive simulations using incidence density sampling, we evaluated various analytic methods: CLR with and without a bias-reduction method, ULR with adjustment for time in quintiles (and residual time within quintiles) and ULR with adjustment for matched sets and bias reduction. We re-analysed a case–control study of Haemophilus influenzae type B vaccine using these methods.ResultsWe found that the bias in the CLR analysis from previous studies was due to sparse data bias. It can be controlled by the bias-reduction method for CLR or by increasing the number of cases and/or controls. ULR with adjustment for time in quintiles usually gave results highly comparable to CLR, despite breaking the matches. Further adjustment for residual time trends was needed in the case of time-varying effects. ULR with adjustment for matched sets tended to perform poorly despite bias reduction.ConclusionsStudies using incidence density sampling may be analysed by either ULR with adjustment for time or CLR, possibly with bias reduction.
Adherence to dietary recommendations and colorectal cancer risk: results from two prospective cohort studies
Authors: Nguyen Sang , Li Honglan , Yu Danxia , Gao Jing , Gao Yutang , Tran Huong , Xiang Yong-Bing , Zheng Wei , Shu Xiao-Ou 
Published: May 2019

Abstract

Background
Understanding the association between diet and colorectal cancer (CRC) risk is essential to curbing the epidemic of this cancer. This study prospectively evaluated adherence to the Chinese Food Pagoda (CHFP), and two American Dietary Guidelines: the Alternative Healthy Eating Index (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) in association with CRC risk among Chinese adults living in urban Shanghai, China.

Methods
Participants included 60 161 men and 72 445 women aged 40–74, from two ongoing population-based prospective cohort studies. Associations between dietary guideline compliance scores and CRC risk were evaluated by Cox proportional hazard regression analyses, with age as time metric, and potential confounders were adjusted.

Results
We identified 1670 CRC incidence cases (691 males and 979 females) during an average 8.1 years of follow-up for men and 13.4 years for women. CHFP score was inversely associated with risk of CRC, with hazard ratios (HRs) (95% confidence intervals) of 0.88 (0.77, 1.00), 0.86 (0.75, 0.98) and 0.84 (0.73, 0.96) for the 2nd, 3rd and 4th quartiles versus 1st quartile, respectively (Ptrend= 0.01). The inverse association appeared stronger for rectal cancer, individuals at younger age (&lt; 50 years), with a lower BMI (&lt;25 kg/m2) or without any metabolic conditions at baseline, although no multiplicative interactions were noted. No consistent association pattern was observed for the modified DASH score and the modified AHEI-2010.

Conclusions
Compliance with the Dietary Guidelines for Chinese was associated with reduced risk of CRC among Chinese adults. To maximize health impacts, dietary recommendations need to be tailored for specific populations.
Parameters influencing the pharmacokinetics/pharmacodynamics of piperacillin/tazobactam in patients with febrile neutropenia and haematological malignancy: a prospective study
Authors: Benech Nicolas , Dumitrescu Oana , Conrad Anne , Balsat Marie , Paubelle Etienne , Ducastelle-Lepretre Sophie , Labussière-Wallet Hélène , Salles Gilles , Cohen Sabine , Goutelle Sylvain , Ader Florence ,   Lyon HEMINF Study Group, Ader F , Alcazer V , Bachy E , Balsat M , Barraco F , Boccard M , Billaud G , Chidiac C , Conrad A , Ducastelle-Leprêtre S , Dumitrescu O , Dupont D , Escuret V , Ferry T , Frobert E , Ghesquières H , Heiblig M , Labussière-Wallet H , Larcher M-V , Laurent F , Lina B , Lina G , Menotti J , Miailhes P , Monneret G , Morfin-Sherpa F , Paubelle E , Perpoint T , Rabodonirina M , Renault M , Roure-Sobas C , Salles G , Thomas X , Valour F , Venet F , Wallet F , Wallon M 
Published: May 2019

Abstract

Objectives
To assess population pharmacokinetics (PK) and pharmacodynamics (PD) of both piperacillin and tazobactam in neutropenia patients and examine dosage requirements related to the MIC distribution for Gram-negative bacteria involved in bloodstream infections (BSIs).

Methods
We conducted a prospective study including adult haematological malignancy patients with febrile neutropenia receiving piperacillin/tazobactam as short (30 min) or prolonged (4 h) intravenous infusions. Concentration data were analysed using a population approach. Dosing simulations with the final model investigated factors influencing the PK/PD of piperacillin/tazobactam quantified by fT>MIC or PTA for piperacillin and tazobactam, respectively. In parallel, the local MIC distribution of β-lactams was documented for Gram-negative bacteria involved in BSIs.

Results
Over 10 months, 31 patients were enrolled, with 11 (35.5%) short and 20 (64.5%) prolonged infusion regimens. A one-compartment model adequately described the data for both drugs. Prolonged infusion, increased serum alkaline phosphatase (ALP) values and renal function impairment were associated with increased piperacillin fT>MIC. For patients with normal or augmented renal CL, dosing regimens q8h or q6h with 30 min of infusion were insufficient to achieve acceptable PTA for piperacillin/tazobactam at the median MIC value of 8 mg/L. Prolonged infusion of large doses was associated with the best PTA for both piperacillin and tazobactam.

Conclusions
In a population of haematological malignancy patients with neutropenia, renal function and ALP influenced the PK of piperacillin/tazobactam. Prolonged intravenous infusion would optimize the PK of piperacillin/tazobactam, especially in the case of augmented renal CL and/or low-range bacterial susceptibility.