bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased rates of atrial fibrillation recurrence following pulmonary vein isolation in overweight and obese patients
Authors: Sivasambu Bhradeev , Balouch Muhammad A. , Zghaib Tarek , Bajwa Rizma J. , Chrispin Jonathan , Berger Ronald D. , Ashikaga Hiroshi , Nazarian Saman , Marine Joseph E. , Calkins Hugh , Spragg David D. 
Published: November 2017

AbstractIntroductionCatheter ablation is common for patients with symptomatic, drug‐refractory atrial fibrillation (AF). Obesity is a known risk factor for incident AF. The impact of obesity on AF ablation outcomes is incompletely understood. We sought to determine the impact of elevated body mass index (BMI) on pulmonary vein isolation (PVI) procedural outcomes and associated complications.Methods and resultsWe evaluated patients undergoing PVI from 2001 to 2015, dividing them into four groups: normal weight (BMI ≥ 18.5 to < 25), overweight (BMI ≥ 25 to < 30), obese (BMI > 30 to < 40), and morbidly obese (BMI ≥ 40). Demographic and procedural characteristics, complications, and ablation outcomes were compared among groups.A total of 701 patients (146 time‐matched controls, 227 overweight, 244 obese, and 84 morbidly obese) with complete demographic, procedural, and follow‐up data were included. Increasing BMI correlated positively with HTN, OSA, CHA2DS2‐VASC score, and persistent AF (P ≤ 0.001 for all associations). Radiofrequency application time and intraprocedural heparin dose increased with BMI (P ≤ 0.001). Arrhythmia recurrence at 1 year was 39.9% in controls, while higher in all high‐BMI groups (overweight, 51.3%; obese, 57%; morbidly obese, 58.1 %; P = 0.007 for all versus controls). Impact of BMI on AF recurrence was not seen in persistent AF patients. Complication rates across groups were similar.Conclusions AF recurrence after catheter ablation is higher in overweight, obese, and morbidly obese patients comparing to normal‐weight controls, driven primarily by outcomes differences in paroxysmal AF patients. Complications were not associated with increased BMI.
Multiple strategies for pathogen perception by plant immune receptors
Authors: Cesari Stella 
Published: November 2017

Contents

Summary
17

I.
Introduction
17

II.
Pathogen perception by NLRs: from direct recognition to integrated decoys
18

III.
Multiple activation and signaling pathways for NLRs
18

IV.
How to engineer NLR‐mediated disease resistance?
21

V.
Conclusion
23

Acknowledgements
23

References
23

SummaryPlants have evolved a complex immune system to protect themselves against phytopathogens. A major class of plant immune receptors called nucleotide‐binding domain and leucine‐rich repeat‐containing proteins (NLRs) is ubiquitous in plants and is widely used for crop disease protection, making these proteins critical contributors to global food security. Until recently, NLRs were thought to be conserved in their modular architecture and functional features. Investigation of their biochemical, functional and structural properties has revealed fascinating mechanisms that enable these proteins to perceive a wide range of pathogens. Here, I review recent insights demonstrating that NLRs are more mechanistically and structurally diverse than previously thought. I also discuss how these findings provide exciting future prospects to improve plant disease resistance.
Body fatness at a young age, body fatness gain and risk of breast cancer: systematic review and meta‐analysis of cohort studies
Authors: Hidayat K. , Yang C.‐M. , Shi B.‐M. 
Published: November 2017

SummaryHigher body fatness in adulthood has been consistently associated with an increased risk of postmenopausal breast cancer, as well as a tendency towards a lower risk of premenopausal breast cancer. However, the association between body fatness at a young age (≤30 years), body fatness gain and the risk of breast cancer is less defined. PubMed and Web of Science databases were searched to identify relevant publications. Risk estimates with 95% confidence intervals from each study were transformed into a continuous variable for each 5 kg m−2 increase in body mass index (BMI) and were pooled under a random‐effects model. Each 5 kg m−2 increase in BMI was significantly associated with a 14%, 12% and 17% lower risk of breast cancer later in life among all women, premenopausal women and postmenopausal women, respectively. Significant heterogeneity and publication bias were observed. The results remained unchanged after the trim and fill method was applied to correct the bias. Each 5 kg m−2 increase in BMI from a young age until cohort entry was significantly associated with a 13% and 14% higher risk of breast cancer in all women and postmenopausal women, respectively. In summary, higher body fatness at a young age may have a protective role in the later development of breast cancer in both premenopausal and postmenopausal women. However, this potential benefit should not be overemphasized, as our findings suggest that increased body fatness gain from a young age is positively associated with postmenopausal breast cancer risk. These findings further justify the need to maintain a steady weight throughout life.
Intelligent feeding control methods in aquaculture with an emphasis on fish: a review
Authors: Zhou Chao , Xu Daming , Lin Kai , Sun Chuanheng , Yang Xinting 
Published: November 2017

AbstractIn aquaculture, feeding is the primary factor determining efficiency and cost, so it is important to know when to stop feeding to maximize efficiency. Until now, fish feeding has been mostly based on artificial discrimination, which is usually time‐consuming and laborious. In recent years, intelligent feeding control according to changes in behaviour and growth status has gained increasing attention. This approach involves many methods as well as monitoring and feedback equipment and can automatically determine the feeding demands of fish. This review summarizes the development of intelligent feeding control methods, such as mathematical models, acoustic methods and computer vision, in aquaculture over the past three decades. All methods have unique application scenarios and models for the culture to which they are most suitable, and the advantages and disadvantages of each method in the laboratory as well as in pond, cage and recirculating aquaculture systems are analysed. Studies show that improvements in sensor accuracy and hardware and software processing speed have promoted the development of new technologies and methods, providing effective or potential support for intelligent feeding control. However, its accuracy and intelligent are still need to be improved to meet the needs of actual feeding scenarios. Through close collaborations between engineers and fish behaviourists, the feeding machine and system will be more elaborate and precise on the basis of the above methods, and the level of intelligence will be further improved.
A critical analysis of the international legal framework regulating the microbiological classification of bivalve shellfish production areas
Authors: de Souza Robson Ventura , Campos Carlos , Garbossa Luis Hamilton Pospissil , Vianna Luiz Fernando de Novaes , Vanz Argeu , Rupp Guilherme Sabino , Seiffert Walter 
Published: November 2017

AbstractThis study presents a review of the microbiological standards and associated monitoring practices for classification of commercial shellfish production areas in force in Brazil, European Union and United States of America. The classification systems are not immediately comparable principally because some regulations are based on the monitoring of water and others of shellfish flesh. To create a common baseline to compare these regulations, regression models were developed based on monitoring data and used to correlate levels of faecal indicator bacteria in water and in shellfish. The classification system used in the European Union was found to provide the highest level of shellfish safety for classification categories that do not require post‐harvest treatments prior to marketing, while the United States system provides higher level of shellfish safety for classification categories that require these treatments. The Brazilian legislation prescribes depuration as the post‐harvest treatment for shellfish with much higher levels of coliforms than the United States and European Union systems. Evidence was found that the microbiological limits for sea water set out in the Brazilian Resolution 357 – CONAMA are more stringent than the regulations used in the European Union and United States. The results also suggest that the Brazilian Shellfish Sanitation Programme and the European Union legislation are the least stringent concerning maximum faecal contamination tolerated. This assessment provides information on margins of safety for shellfish products traded internationally.
Translation and validation of the Danish version of the brief family assessment measure III in a sample of acutely admitted elderly medical patients
Authors: Shamali Mahdi , Konradsen Hanne , Lauridsen Jørgen T. , Østergaard Birte 
Published: November 2017

Rationale and objectiveFamily functioning plays a pivotal role in the adaptation to illness of both individuals and families, especially among elderly patients. The Brief Family Assessment Measure Third Edition (Brief FAM‐III) is among the most frequently used self‐report instruments that measures family functioning. However, no Danish translation or measure of its psychometric properties in a Danish population is available. The purpose of this study was to translate the Brief FAM‐III into Danish and then evaluate its psychometric properties in elderly patients.MethodsThe Brief FAM‐III was translated into Danish using the forward–backward translation procedure and examined its psychometric properties in 60 elderly patients (aged over 65) consecutively admitted to an acute medical ward. Internal consistency reliability was assessed by Cronbach's alpha coefficients, and confirmatory factor analysis was used to examine the construct validity of the Brief FAM‐III.ResultsEvaluation of the Danish version of the Brief FAM‐III confirmed the three‐factor structure (General Scale, Self‐Rating Scale and Dyadic Relationships Scale) identified in the original instrument. However, goodness‐of‐fit indicators showed a relatively poor model fit. Cronbach's alpha for the total scales of Brief FAM‐III was 0.94 suggesting good internal consistency.ConclusionsThe Danish version of the Brief FAM‐III demonstrated satisfactory validity and reliability to assess family functioning among acutely admitted elderly Danish patients. We suggest that it may also be useful for monitoring family functioning over time or determining the effects of therapeutic interventions in elderly medical patients; however, further testing is recommended.
Influences of age, ethnic group, and skin sites on a provisory skin marking, experimentally induced, in vivo
Authors: Flament F. , Bazin R. 
Published: November 2017

AbstractBackgroundTo study capacity of skin to being imprinted by a marking head rapidly applied (10 seconds) onto the skin under a standardized pressure (15 kPa).Material and MethodsReferential photographs of skin markings, resulting from different times of application serve at grading the extent of skin imprints. The imprinting tool, equipped with 5 linear bulbs of different sizes but same thickness (1 mm), was applied onto the cheeks of 641 women of different ages (18‐80 years) of 3 different ethnic groups. In the cohort of 198 Caucasian women, the marking head was pressed onto 3 different sites (outer arm, cheek, and dorsal forearm) and the kinetics of skin recovery from cheek marking was recorded on a smaller and younger part of this Caucasian cohort, ie, 141 Caucasian women, aged 18‐59 years.ResultsThe recorded intensities of skin markings were found highly correlated with age in all 3 studied ethnic groups (Chinese, African‐American, and Caucasian). Caucasian women seem more sensitive to the marking and the kinetics of recovery from such imprint was found highly dependent from its intensity, ie, the higher the grades, the slower the recovery. In Caucasian women, intensities were different between skin sites, where arm showed higher resistance to marking. Possible impact of photo‐aging on the decreased skin resistance to such provoked deformation is likely of minor amplitude, as compared to the one induced by chronological aging.ConclusionThis method offers a new vision on skin aging, in its variable response to a standard deformation that appears mostly driven by chronological aging.
The Role of the Anterior Cingulate Cortex in Prediction Error and Signaling Surprise
Authors: Alexander William H. , Brown Joshua W. 
Published: November 2017

AbstractIn the past two decades, reinforcement learning (RL) has become a popular framework for understanding brain function. A key component of RL models, prediction error, has been associated with neural signals throughout the brain, including subcortical nuclei, primary sensory cortices, and prefrontal cortex. Depending on the location in which activity is observed, the functional interpretation of prediction error may change: Prediction errors may reflect a discrepancy in the anticipated and actual value of reward, a signal indicating the salience or novelty of a stimulus, and many other interpretations. Anterior cingulate cortex (ACC) has long been recognized as a region involved in processing behavioral error, and recent computational models of the region have expanded this interpretation to include a more general role for the region in predicting likely events, broadly construed, and signaling deviations between expected and observed events. Ongoing modeling work investigating the interaction between ACC and additional regions involved in cognitive control suggests an even broader role for cingulate in computing a hierarchically structured surprise signal critical for learning models of the environment. The result is a predictive coding model of the frontal lobes, suggesting that predictive coding may be a unifying computational principle across the neocortex.
Pharmacokinetic and Pharmacodynamic Analyses To Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Patients with Serious Infections Caused by Gram-Positive Pathogens
Authors: Lodise Thomas P. , Bosso John , Kelly Colleen , Williams Paul J. , Lane James R. , Huang David B. 
Published: November 2017

ABSTRACT

Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection model studies suggest that the pharmacokinetic/pharmacodynamic (PK/PD) drivers for efficacy are area under the concentration-time curve from 0 to 24 h at steady state (AUC
0–24ss
), AUC/MIC, and time above the MIC during the dosing interval (
T
> MIC), while QTc prolongation was associated with the maximal concentration at steady state (
C
maxss
) in a thorough QTc phase 1 study. Using PK data collected from 470 patients from the previously conducted phase 3 complicated skin and skin structure infection (cSSSI) trials, population PK modeling and Monte Carlo simulation (MCS) were used to identify a fixed iclaprim dosage regimen for the ongoing phase 3 ABSSSI studies that maximizes AUC
0–24ss
, AUC/MIC, and
T
> MIC while minimizing the probability of a
C
maxss
of ≥800 ng/ml relative to the values for the previously employed cSSSI regimen of 0.8 mg/kg of body weight infused intravenously over 0.5 h every 12 h. The MCS analyses indicated that administration of 80 mg as a 2-h infusion every 12 h provides 28%, 28%, and 32% increases in AUC
0–24ss
, AUC/MIC, and
T
> MIC, respectively, compared to values for the 0.8-mg/kg cSSSI regimen, while decreasing the probability of a
C
maxss
of ≥800 ng/ml, by 9%. Based on PK/PD analyses, 80 mg iclaprim administered over 2 h every 12 h was selected as the dosing scheme for subsequent phase 3 clinical trials.
A Novel Mechanism of Inactivating Antibacterial Nitro Compounds in the Human Pathogen Staphylococcus aureus by Overexpression of a NADH-Dependent Flavin Nitroreductase
Authors: El-Hossary Ebaa M. , Förstner Konrad U. , François Patrice , Baud Damien , Streker Karin , Schrenzel Jacques , Ohlsen Knut , Holzgrabe Ulrike 
Published: November 2017

ABSTRACT

Recently, the nitro-substituted bisquaternary bisnaphthalimides were reported to have substantial anti-infective activity against Gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus
(MRSA). Here, we selected resistant
S. aureus
clones by cultivation in increasing concentrations of the most active compound, MT02. Interestingly, MT02-resistant variants induced a diffusible red color of the broth. Chromatographic and spectroscopic investigations revealed a stepwise reduction of the bisquaternary bisnaphthalimides' nitro groups to amino groups. The corresponding derivatives were completely inactive against staphylococci. RNA sequencing experiments revealed a strong overexpression of a novel oxidoreductase in MT02-resistant strains. Deletion mutants of this enzyme did not produce the red color and were not able to develop resistance against bisquaternary bisnaphthalimides. Biochemical reactions confirmed an NADH-dependent deactivation of the nitro-substituted compounds. Thus, this is the first report of a nitroreductase-based antibiotic resistance mechanism in the human pathogen
S. aureus
.
Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis
Authors: Denti Paolo , Garcia-Prats Anthony J. , Draper Heather R. , Wiesner Lubbe , Winckler Jana , Thee Stephanie , Dooley Kelly E. , Savic Rada M. , McIlleron Helen M. , Schaaf H. Simon , Hesseling Anneke C. 
Published: November 2017

ABSTRACT
Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited pediatric pharmacokinetic data to inform dose selection for children. Children routinely receiving levofloxacin (250-mg adult tablets) for MDR-TB prophylaxis or disease in Cape Town, South Africa, underwent pharmacokinetic sampling following receipt of a dose of 15 or 20 mg/kg of body weight given as a whole or crushed tablet(s) orally or via a nasogastric tube. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Model-based simulations were performed to estimate the doses across weight bands that would achieve adult exposures with 750-mg once-daily dosing. One hundred nine children were included. The median age was 2.1 years (range, 0.3 to 8.7 years), and the median weight was 12 kg (range, 6 to 22 kg). Levofloxacin followed 2-compartment kinetics with first-order elimination and absorption with a lag time. After inclusion of allometric scaling, the model characterized the age-driven maturation of clearance (CL), with the effect reaching 50% of that at maturity at about 2 months after birth and 100% of that at maturity by 2 years of age. CL in a typical child (weight, 12 kg; age, 2 years) was 4.7 liters/h. HIV infection reduced CL by 16%. By use of the adult 250-mg formulation, levofloxacin exposures were substantially lower than those reported in adults receiving a similar dose on a milligram-per-kilogram basis. To achieve adult-equivalent exposures at a 750-mg daily dose, higher levofloxacin pediatric doses of from 18 mg/kg/day for younger children with weights of 3 to 4 kg (due to immature clearance) to 40 mg/kg/day for older children may be required. The doses of levofloxacin currently recommended for the treatment of MDR-TB in children result in exposures considerably lower than those in adults. The effects of different formulations and formulation manipulation require further investigation. We recommend age- and weight-banded doses of 250-mg tablets of the adult formulation most likely to achieve target concentrations for prospective evaluation.
What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi- and Extensively Drug-Resistant Tuberculosis
Authors: Heyckendorf Jan , Andres Sönke , Köser Claudio U. , Olaru Ioana D. , Schön Thomas , Sturegård Erik , Beckert Patrick , Schleusener Viola , Kohl Thomas A. , Hillemann Doris , Moradigaravand Danesh , Parkhill Julian , Peacock Sharon J. , Niemann Stefan , Lange Christoph , Merker Matthias 
Published: November 2017

ABSTRACT

Rapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDR
plus
2.0 and MTBDR
sl
2.0) and whole-genome sequencing (WGS) were translated into individual algorithm-derived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged from just 49% (95% confidence interval [CI], 39 to 59%) for Xpert and 63% (95% CI, 56 to 70%) for LPAs to 93% (95% CI, 88 to 98%) for WGS. Only the WGS regimens did not contain any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high. WGS can be used to rule in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be reexamined to avoid systematic false-susceptible results in low-level resistant isolates.
Role of Calprotectin in Withholding Zinc and Copper from Candida albicans
Authors: Besold Angelique N. , Gilston Benjamin A. , Radin Jana N. , Ramsoomair Christian , Culbertson Edward M. , Li Cissy X. , Cormack Brendan P. , Chazin Walter J. , Kehl-Fie Thomas E. , Culotta Valeria C. 
Published: November 2017

ABSTRACTThe opportunistic fungal pathogenCandida albicansacquires essential metals from the host, yet the host can sequester these micronutrients through a process known as nutritional immunity. How the host withholds metals fromC. albicanshas been poorly understood; here we examine the role of calprotectin (CP), a transition metal binding protein. When CP depletes bioavailable Zn from the extracellular environment,C. albicansstrongly upregulatesZRT1andPRA1for Zn import and maintains constant intracellular Zn through numerous cell divisions. We show for the first time that CP can also sequester Cu by binding Cu(II) with subpicomolar affinity. CP blocks fungal acquisition of Cu from serum and induces a Cu starvation stress response involvingSOD1andSOD3superoxide dismutases. These transcriptional changes are mirrored whenC. albicansinvades kidneys in a mouse model of disseminated candidiasis, although the responses to Cu and Zn limitations are temporally distinct. The Cu response progresses throughout 72 h, while the Zn response is short-lived. Notably, these stress responses were attenuated in CP null mice, but only at initial stages of infection. Thus, Zn and Cu pools are dynamic at the host-pathogen interface and CP acts early in infection to restrict metal nutrients fromC. albicans.