bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quadratic function between arterial partial oxygen pressure and mortality risk in sepsis patients: an interaction with simplified acute physiology score
Authors: Zhang Zhongheng , Ji Xuqing 
Published: October 2016

AbstractOxygen therapy is widely used in emergency and critical care settings, while there is little evidence on its real therapeutic effect. The study aimed to explore the impact of arterial oxygen partial pressure (PaO2) on clinical outcomes in patients with sepsis. A large clinical database was employed for the study. Subjects meeting the diagnostic criteria of sepsis were eligible for the study. All measurements of PaO2 were extracted. The primary endpoint was death from any causes during hospital stay. Survey data analysis was performed by using individual ICU admission as the primary sampling unit. Quadratic function was assumed for PaO2 and its interaction with other covariates were explored. A total of 199,125 PaO2 samples were identified for 11,002 ICU admissions. Each ICU stay comprised 18 PaO2 samples in average. The fitted multivariable model supported our hypothesis that the effect of PaO2 on mortality risk was in quadratic form. There was significant interaction between PaO2 and SAPS-I (p = 0.007). Furthermore, the main effect of PaO2 on SOFA score was nonlinear. The study shows that the effect of PaO2 on mortality risk is in quadratic function form, and there is significant interaction between PaO2 and severity of illness.
Tetrameric structure of the restriction DNA glycosylase R.PabI in complex with nonspecific double-stranded DNA
Authors: Wang Delong , Miyazono Ken-ichi , Tanokura Masaru 
Published: October 2016

AbstractR.PabI is a type II restriction enzyme that recognizes the 5′-GTAC-3′ sequence and belongs to the HALFPIPE superfamily. Although most restriction enzymes cleave phosphodiester bonds at specific sites by hydrolysis, R.PabI flips the guanine and adenine bases of the recognition sequence out of the DNA helix and hydrolyzes the N-glycosidic bond of the flipped adenine in a similar manner to DNA glycosylases. In this study, we determined the structure of R.PabI in complex with double-stranded DNA without the R.PabI recognition sequence by X-ray crystallography. The 1.9 Å resolution structure of the complex showed that R.PabI forms a tetrameric structure to sandwich the double-stranded DNA and the tetrameric structure is stabilized by four salt bridges. DNA binding and DNA glycosylase assays of the R.PabI mutants showed that the residues that form the salt bridges (R70 and D71) are essential for R.PabI to find the recognition sequence from the sea of nonspecific sequences. R.PabI is predicted to utilize the tetrameric structure to bind nonspecific double-stranded DNA weakly and slide along it to find the recognition sequence.
Novelty during a late postacquisition time window attenuates the persistence of fear memory
Authors: Katche Cynthia , Tomaiuolo Micol , Dorman Guido , Medina Jorge H. , Viola Haydee 
Published: October 2016

AbstractLearning to avoid threats in the environment is highly adaptive. However, sometimes a dysregulation of fear memories processing may underlie fear-related disorders. Despite recent advances, a major question of how to effectively attenuate persistent fear memories in a safe manner remains unresolved. Here we show experiments employing a behavioural tool to target a specific time window after training to limit the persistence of a fear memory in rats. We observed that exposure to a novel environment 11 h after an inhibitory avoidance (IA) training that induces a long-lasting memory, attenuates the durability of IA memory but not its formation. This effect is time-restricted and not seen when the environment is familiar. In addition, novelty-induced attenuation of IA memory durability is prevented by the intrahippocampal infusion of the CaMKs inhibitor KN-93. This new behavioural approach which targets a specific time window during late memory consolidation, might represent a new tool for reducing the durability of persistent fear memories.
Modelling Methane Production and Sulfate Reduction in Anaerobic Granular Sludge Reactor with Ethanol as Electron Donor
Authors: Sun Jing , Dai Xiaohu , Wang Qilin , Pan Yuting , Ni Bing-Jie 
Published: October 2016

AbstractIn this work, a mathematical model based on growth kinetics of microorganisms and substrates transportation through biofilms was developed to describe methane production and sulfate reduction with ethanol being a key electron donor. The model was calibrated and validated using experimental data from two case studies conducted in granule-based Upflow Anaerobic Sludge Blanket reactors. The results suggest that the developed model could satisfactorily describe methane and sulfide productions as well as ethanol and sulfate removals in both systems. The modeling results reveal a stratified distribution of methanogenic archaea, sulfate-reducing bacteria and fermentative bacteria in the anaerobic granular sludge and the relative abundances of these microorganisms vary with substrate concentrations. It also indicates sulfate-reducing bacteria can successfully outcompete fermentative bacteria for ethanol utilization when COD/SO42− ratio reaches 0.5. Model simulation suggests that an optimal granule diameter for the maximum methane production efficiency can be achieved while the sulfate reduction efficiency is not significantly affected by variation in granule size. It also indicates that the methane production and sulfate reduction can be affected by ethanol and sulfate loading rates, and the microbial community development stage in the reactor, which provided comprehensive insights into the system for its practical operation.
Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans
Authors: Park Dong Ik , Dournes Carine , Sillaber Inge , Uhr Manfred , Asara John M. , Gassen Nils C. , Rein Theo , Ising Marcus , Webhofer Christian , Filiou Michaela D. , Müller Marianne B. , Turck Christoph W. 
Published: October 2016

AbstractSelective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature.
Efficient detection of differentially methylated regions using DiMmeR
Authors: Almeida Diogo , Skov Ida , Silva Artur , Vandin Fabio , Tan Qihua , Röttger Richard , Baumbach Jan 
Published: October 2016

AbstractMotivationEpigenome-wide association studies (EWAS) generate big epidemiological datasets. They aim for detecting differentially methylated DNA regions that are likely to influence transcriptional gene activity and, thus, the regulation of metabolic processes. The by far most widely used technology is the Illumina Methylation BeadChip, which measures the methylation levels of 450 (850) thousand cytosines, in the CpG dinucleotide context in a set of patients compared to a control group. Many bioinformatics tools exist for raw data analysis. However, most of them require some knowledge in the programming language R, have no user interface, and do not offer all necessary steps to guide users from raw data all the way down to statistically significant differentially methylated regions (DMRs) and the associated genes.ResultsHere, we present DiMmeR (Discovery of Multiple Differentially Methylated Regions), the first free standalone software that interactively guides with a user-friendly graphical user interface (GUI) scientists the whole way through EWAS data analysis. It offers parallelized statistical methods for efficiently identifying DMRs in both Illumina 450K and 850K EPIC chip data. DiMmeR computes empirical P-values through randomization tests, even for big datasets of hundreds of patients and thousands of permutations within a few minutes on a standard desktop PC. It is independent of any third-party libraries, computes regression coefficients, P-values and empirical P-values, and it corrects for multiple testing.Availability and ImplementationDiMmeR is publicly available at http://dimmer.compbio.sdu.dk.Supplementary informationSupplementary data are available at Bioinformatics online.
Atrial fibrillation septal pacing: translation of modelling results
Authors: Luca Adrian , Kallmyer Todd , Virag Nathalie 
Published: October 2016

AimsAtrial fibrillation (AF) septal pacing consists of rapid pacing from a ring of electrodes around the atrial septum, leading to local capture of both atria during AF. The present model-based study evaluated the impact of the number of stimulation electrodes in the septal ring on AF capture for different types of sustained AF dynamics.Methods and resultsUsing a biophysical model of AF based on CT scans from an AF patient, models with different AF substrates (Cholinergic AF and Meandering Wavelets) were created by varying the atrial membrane kinetics. Rapid pacing was applied from the septum area with a ring of 1, 2, 3, 4, 6, 8, or 12 electrodes during 20 seconds at a pacing cycle lengths (PCLs) in the range 60–100% of AF cycle length (AFCL), in 4% steps. Percentage of captured tissue during rapid pacing was determined using 24 sensing electrode pairs evenly distributed on the atrial surface. Results were averaged over 10 AF simulations. For Cholinergic AF, the number of stimulation electrodes on the septal ring had no significant impact on AF capture independently of AF dynamics. For Meandering Wavelets, more electrodes were needed to achieve AF capture in the presence of complex AF.ConclusionChanges in AF substrate significantly impacted septal pacing outcomes and response to rapid AF pacing may similarly vary patient-to-patient. The number of stimulation electrodes had a lesser impact, suggesting that the design of a ring with 3–4 electrodes around the septum would be sufficient for most AF dynamics.
Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas
Authors: Showler Kaye , Nishimura Mayumi , Daino Kazuhiro , Imaoka Tatsuhiko , Nishimura Yukiko , Morioka Takamitsu , Blyth Benjamin J. , Kokubo Toshiaki , Takabatake Masaru , Fukuda Maki , Moriyama Hitomi , Kakinuma Shizuko , Fukushi Masahiro , Shimada Yoshiya 
Published: October 2016

Abstract
The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis.
Tumor regression patterns by follow-up duration in patients with nasopharyngeal carcinoma treated with concurrent chemoradiotherapy
Authors: Kong Moonkyoo , Hong Seong Eon 
Published: October 2016

Abstract
The aim of this study was to describe the patterns of tumor regression with respect to follow-up duration after chemoradiotherapy in patients with nasopharyngeal carcinoma. A total of 27 patients with nasopharyngeal carcinoma were included and received definitive concurrent chemoradiotherapy. Patterns of primary tumor regression and development of locoregional recurrences were evaluated by imaging studies every 1 to 2 months. Primary tumors gradually regressed over the period of follow-up. The median time to full regression was 4.9 months (range, 1.5–19.4). In 61.5% of patients, the primary tumor continued to regress for &gt;4 months after completion of chemoradiotherapy. Six patients experienced locoregional recurrence during follow-up, all of which occurred after full regression of the primary tumor. A patient group with delayed regression did not have poorer prognosis than a patient group with early regression. Older age, non-current-smoker status, advanced T stage, and higher daily radiation dose were significantly associated with delayed primary tumor regression. Nasopharyngeal carcinoma continued to regress for &gt;4 months after chemoradiotherapy in a considerable number of patients. We recommend waiting for &gt;4 months for full regression of nasopharyngeal carcinomas after chemoradiotherapy, if signs of persistent or recurrent disease are not evident on follow-up examination.
The Role of Risk-Reducing Surgery in Hereditary Breast and Ovarian Cancer
Authors: Hartmann Lynn C. , Lindor Noralane M. 
Published: October 2016

(Abstracted from N Engl J Med 2016;374:454–468)
This review article addresses issues associated with the care of women in families with hereditary breast and ovarian cancer syndrome who have not had cancer themselves. Issues addressed include optimal risk assessment for breast and ovarian cancers, the effectiveness of risk-reducing surgery, side effects of the procedures and alternative strategies for cancer prevention as well as the best ways to help with the decision-making process.
Gestational Alloimmune Liver Disease
Authors: Anastasio Hannah B. , Grundy Maureen , Birsner Meredith L. , Blakemore Karin J. 
Published: October 2016

BACKGROUND:
Gestational alloimmune liver disease, a form of profound liver failure in the newborn, is the main underlying cause of the entity formerly known as neonatal hemochromatosis. Antepartum maternal intravenous immunoglobulin (IVIG) has been shown to prevent gestational alloimmune liver disease, which otherwise has a recurrence risk above 90% in subsequent pregnancies.

CASE:
A 30-year-old woman, gravida 3 para 0120, presented early in gestation. Her previous pregnancy had been complicated by fetal growth restriction, oligohydramnios, and ultimately fatal fulminant neonatal liver failure. With gestational alloimmune liver disease recognized as the primary diagnosis for the liver failure, we began maternal weekly IVIG therapy. She delivered a healthy newborn at term without evidence of hepatic dysfunction.

CONCLUSION:
Recognition of gestational alloimmune liver disease enables antepartum treatment that dramatically alters the course of disease.
Body Mass Index and the Spontaneous Onset of Parturition
Authors: Hermesch Amy C. , Allshouse Amanda A. , Heyborne Kent D. 
Published: October 2016

OBJECTIVE:
To investigate the relationship between body mass index (BMI) and the onset of parturition throughout gestation.

METHODS:
This was a secondary analysis of the Maternal-Fetal Medicine Units Network Preterm Prediction Study. Time-to-spontaneous-birth-event (ie, “survival”) methods were used to study the association of BMI with the timing of spontaneous onset of labor throughout gestation with indicated births censored at delivery. A Kaplan-Meier estimate of the probability of spontaneous labor was compared with a log rank test across five categories of BMI (kg/m2): underweight (less than 18.5), normal weight (18.5–24.99), preobese (25–29.99), obese I (30–34.99), and obese II+ (35 or greater). A proportional hazards model was estimated to compare time to spontaneous onset of labor adjusted for multiple variables known to be associated with the onset of labor.

RESULTS:
Normal-weight women (n=1,054) had a median delivery gestational age of 39 3/7 weeks. Obese II+ women (n=178) had a median delivery gestational age 5 days later than normal-weight women (P<.001). Delivery gestational age of preobese (n=866) and obese I (n=548) women was not significantly different from normal-weight women. Underweight women (n=41) had a median delivery gestational age 5 days earlier than normal-weight women (P<.001). Compared with women with normal BMIs, obese II+ women were significantly less likely and underweight women significantly more likely to enter spontaneous labor at all gestational ages. In the multivariable model, BMI was significantly associated with spontaneous onset of labor throughout pregnancy (BMI [five-unit] adjusted hazard ratio 0.874, 0.829–0.921).

CONCLUSION:
Body mass index is significantly associated with the likelihood of the spontaneous onset of labor at all gestational ages with gestational age at the time of delivery and BMI being inversely related. This novel observation unifies previous reports focusing on the association of overweight and underweight BMIs and preterm and postterm birth and may inform discussions surrounding elective induction of labor at term.
Safety of Outpatient Surgical Abortion for Obese Patients in the First and Second Trimesters
Authors: Benson Lyndsey S. , Micks Elizabeth A. , Ingalls Carly , Prager Sarah W. 
Published: October 2016

OBJECTIVE:
To evaluate the relationship between obesity and surgical abortion complications in the outpatient setting.

METHODS:
We conducted a retrospective cohort study of 4,968 women undergoing surgical abortion at a large outpatient clinic network from September 2012 to July 2014. We used log-binomial regression to evaluate body mass index (BMI) as an independent risk factor for first- and second-trimester abortion complications. Body mass index was analyzed as both a continuous and categorical predictor. We assessed complications including need for uterine reaspiration (including same-day reaspiration), uterine perforation, cervical laceration, infection, emergency department visit or hospitalization, and excessive blood loss defined as estimated blood loss greater than or equal to 100 mL.

RESULTS:
The majority (77%) of procedures was performed in the first trimester. Forty-seven percent of women were normal weight or underweight, 28% were overweight, and 25% were obese, including 4% with BMI greater than or equal to 40. The overall complication rate was 1.7%; the most common complications were need for uterine reaspiration (1.0%) and excessive blood loss (0.6%). Obesity was not associated with increased risk of surgical complications, including when adjusting for age, gestational age, and history of prior cesarean delivery.

CONCLUSION:
In a high-volume outpatient abortion clinic with experienced health care providers, abortion is very safe. Obesity does not appear to be an independent predictor for abortion complications and should not be used in isolation to refer women to hospital-based facilities for abortion care in the first or second trimester.
Postpartum Blood Loss in Women Treated for Intrahepatic Cholestasis of Pregnancy
Authors: Furrer Romana , Winter Katharina , Schäffer Leonhard , Zimmermann Roland , Burkhardt Tilo , Haslinger Christian 
Published: October 2016

OBJECTIVE:
To evaluate postpartum blood loss in women with treated intrahepatic cholestasis of pregnancy.

METHODS:
In a retrospective case–control study, 15,083 deliveries including 348 women with intrahepatic cholestasis of pregnancy (2.3%) were analyzed from 2004 to 2014. To adjust for differences in baseline characteristics, a propensity analysis was performed and women in the control group were matched to the women in the intrahepatic cholestasis of pregnancy group in a 5:1 ratio. Blood loss was analyzed by estimated blood loss and Δ hemoglobin (Hb, difference between prepartum and postpartum Hb). A subgroup analysis regarding severity of intrahepatic cholestasis of pregnancy based on maximum bile acid level (mild [less than 40 micromoles/L], moderate [40–99 micromoles/L], and severe intrahepatic cholestasis of pregnancy [100 micromoles/L or greater]) was performed. Differences in estimated blood loss, ΔHb, and meconium staining between subgroups were analyzed. A Spearman rank correlation was performed to evaluate the association of bile acid levels and blood loss within subgroups.

RESULTS:
Estimated blood loss (median 400 [300–600] mL compared with 400 [300–600] mL, P=.22), ΔHb (14.0 [5.0–22.0] compared with 12.0 [4.0–21.0] g/L, P=.09), meconium staining (14.5% compared with 11.4%, P=.12), and number of stillbirths after 26 weeks of gestation (0.6% compared with 1.8%, P=.10) were not significantly different in the study compared with the control group. In moderate and severe intrahepatic cholestasis of pregnancy, meconium staining was observed significantly more often compared with that in a control group (23.0% and 32.3% compared with 11.4%, P<.01). There was no correlation between estimated blood loss or ΔHb and severity of intrahepatic cholestasis of pregnancy.

CONCLUSIONS:
In our cohort of women with intrahepatic cholestasis of pregnancy who are treated with ursodeoxycholic acid and have planned delivery (induction of labor or planned cesarean delivery) at 38 weeks of gestation, no differences in postpartum blood loss were seen.