bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of Cystatin C–Based e-GFR Measurements to Predict Long-Term Tenofovir Nephrotoxicity in Patients With Hepatitis B
Authors: Koksal Ali Riza , Alkim Huseyin , Boga Salih , Iyisoy Mehmet Sinan , Sen Ilker , Tekin Neijmann Sebnem , Alkim Canan 
Published: October 2016

Background:
Cystatin C is a genuine marker for detecting minor reductions in estimated glomerular filtration rate (e-GFR).

Study Question:
We aimed to investigate the efficiency of cystatin C levels in predicting nephrotoxicity due to antiviral therapy in patients with chronic hepatitis B virus infection.

Study Design:
Seventy-six naive hepatitis B virus patients and 44 controls were enrolled in this prospective cohort study.

Measures and Outcomes:
Serum cystatin C, phosphate and creatinine levels, and urinary albumin/creatinine ratios of all patients were measured at baseline, 3rd, 12th, and 24th months. Nephrotoxicity was determined according to the amount of change in creatinine level at the fourth year of treatment compared with baseline (∆Cr0-4).

Results:
Mean age was 36.1 ± 9.2 years and 40 (52.2%) of patients were women. There was no significant difference between baseline values of tenofovir disoproxil fumarate and entecavir groups. Although the creatinine level at the fourth year of treatment was statistically nonsignificant compared with baseline in the entecavir group, it was significantly higher in the fourth year of tenofovir treatment compared with baseline (0.95 ± 0.27 mg/dL vs. 0.76 ± 0.16 mg/dL, P = 0.002). While the increase in ∆Cr0-4 was ≥0.2 mg/dL in 43.2% of patients in the tenofovir group, this rate was 18.8% in the entecavir group. Diagnostic accuracy in identifying decreased renal function as area under the curve (AUC) was high for baseline serum cystatin C level; furthermore, the highest AUC was calculated for cystatin C plus creatinine–based e-GFR equation (AUC: 0.81, P < 0.001).

Conclusions:
Long-term tenofovir disoproxil fumarate nephrotoxicity can be predicted by serum cystatin C plus creatinine–based e-GFR measured before treatment.
One-Year Outcomes of Diabetes Self-Management Training Among Medicare Beneficiaries Newly Diagnosed With Diabetes
Authors: Strawbridge Larisa M. , Lloyd Jennifer T. , Meadow Ann , Riley Gerald F. , Howell Benjamin L. 
Published: October 2016

Background:
Diabetes is highly prevalent among Medicare beneficiaries, resulting in costly health care utilization. Strategies to improve health outcomes, such as disease self-management, could help reduce the increasing burden of diabetes.

Objectives:
Short-term benefits of diabetes self-management training (DSMT) are established; however, longer-term impacts among Medicare beneficiaries are unknown.

Research Design:
Claims-based observational study with 1-year follow-up beginning 6 months after diabetes diagnosis.

Subjects:
Twenty percent random sample of Medicare beneficiaries newly diagnosed with diabetes during 2009–2011 who used DSMT (N=14,680), matched to a nonuser comparison group.

Measures:
We compared health service utilization and costs between DSMT users and nonusers. Health service utilization included any utilization of the hospital or emergency department (ED) and any hospitalizations due to diabetes-related ambulatory care sensitive conditions as well as the number of hospitalizations and ED visits within the follow-up year. Costs included all Medicare Parts A and B expenditures.

Results:
Multivariate regression results found that DSMT users had 14% reduced odds of any hospitalization, lower numbers of hospitalizations and ED visits (approximately 3 fewer per 100 for each), and approximately $830 lower Medicare expenditures (95% CI, −$1198, −$470) compared with nonusers. Odds of any hospitalization due to diabetes-related ambulatory care sensitive conditions and any ED visit were lower for DSMT users compared with nonusers, but the reductions were not statistically significant.

Conclusions:
Findings demonstrate benefits from DSMT use, including lower health service utilization and costs. The low cost of DSMT relative to the reduction in Medicare expenditures highlights an opportunity to reduce the burden of diabetes on both individuals and the health care system.
Identifying Specific Combinations of Multimorbidity that Contribute to Health Care Resource Utilization
Authors: Schiltz Nicholas K. , Warner David F. , Sun Jiayang , Bakaki Paul M. , Dor Avi , Given Charles W. , Stange Kurt C. , Koroukian Siran M. 
Published: October 2016

Background:
Multimorbidity affects the majority of elderly adults and is associated with higher health costs and utilization, but how specific patterns of morbidity influence resource use is less understood.

Objective:
The objective was to identify specific combinations of chronic conditions, functional limitations, and geriatric syndromes associated with direct medical costs and inpatient utilization.

Design:
Retrospective cohort study using the Health and Retirement Study (2008–2010) linked to Medicare claims. Analysis used machine-learning techniques: classification and regression trees and random forest.

Subjects:
A population-based sample of 5771 Medicare-enrolled adults aged 65 and older in the United States.

Measures:
Main covariates: self-reported chronic conditions (measured as none, mild, or severe), geriatric syndromes, and functional limitations. Secondary covariates: demographic, social, economic, behavioral, and health status measures. Outcomes: Medicare expenditures in the top quartile and inpatient utilization.

Results:
Median annual expenditures were $4354, and 41% were hospitalized within 2 years. The tree model shows some notable combinations: 64% of those with self-rated poor health plus activities of daily living and instrumental activities of daily living disabilities had expenditures in the top quartile. Inpatient utilization was highest (70%) in those aged 77–83 with mild to severe heart disease plus mild to severe diabetes. Functional limitations were more important than many chronic diseases in explaining resource use.

Conclusions:
The multimorbid population is heterogeneous and there is considerable variation in how specific combinations of morbidity influence resource use. Modeling the conjoint effects of chronic conditions, functional limitations, and geriatric syndromes can advance understanding of groups at greatest risk and inform targeted tailored interventions aimed at cost containment.
Lack of Evidence for Racial Disparity in 30-Day All-Cause Readmission Rate for Older US Veterans Hospitalized with Heart Failure
Authors: Kheirbek Raya Elfadel , Wojtusiak Janusz , Vlaicu Sorina O. , Alemi Farrokh 
Published: October 2016

Background:
Heart failure is the leading cause for 30-day all-cause readmission. Although racial disparities in health care are well documented, their impact on 30-day all-cause readmission rate is inconclusive.

Objective:
We examined the impact of racial disparity on 30-day readmission for hospitalized patients with heart failure.

Methods:
This is a retrospective secondary data analysis for a large veteran cohort in 130 Veterans Affairs Medical Centers. Propensity scores were used to reduce differences in age, gender, survival days, and comorbidities in index hospitalization among 46 524 whites and 14 124 African Americans (AA).

Results:
At index hospitalization, AA patients were younger (73.04 vs 67.10 years, t = −54.58, P < .000) and less likely to have myocardial infarcts (8.02% vs 9.80%, t = −6.36, P = .000), peripheral vascular disease (15.25% vs 22.51%, t = −18.68, P = .000), chronic obstructive pulmonary disease (39.59% vs 50.05%, t = −21.89, P < .000), and complicated diabetes (23.42% vs 26.24%, t = −6.73, P = .000). AA patients had lower mortality 30 days post–index hospitalization (3.51% vs 5.69%, t = −10.23, P = .000). In contrast, AA patients were more likely to have renal disease (44.03% vs 38.71%, t = 11.32, P < .000) and HIV/AIDS (1.56% vs 0.20%, t = 19.71, P < .000). The 30-day all-cause readmission rate before adjustments was 17.82% for AA patients versus 18.72% for white patients. There was no difference in the 2 rates after adjustments (18% vs 18%; odds of readmission = 1.002, z = 0.08, P = .937).

Conclusions:
In a large Department of Veterans Affairs (VA) cohort, white and AA veterans hospitalized for heart failure had similar 30-day all-cause readmission rates after adjustments were made for age, gender, survival days, and comorbidities. However, the 30-day all-cause mortality rate was higher for white patients than for AA patients. Future prospective studies are needed to validate results and test generalizability outside the VA system of care.
Incremental Prognostic Value of Quantified Vulnerable Plaque by Cardiac Computed Tomography
Authors: Dwivedi Girish , Liu Yingwei , Tewari Shrankhala , Inacio Joao , Pelletier-Galarneau Matthieu , Chow Benjamin J.W. 
Published: October 2016

Background:
Coronary computed tomography (CT) angiography (CCTA) has the ability to detect, characterize, and quantify atherosclerotic plaques. The aim of our study was to evaluate the prognostic power of CCTA-quantified plaque subtypes.

Materials and Methods:
A total of 36 patients with adverse events and 36 Morise score–matched patients who remained event free on follow-up were identified. Using CCTA images, plaque subtype volumes in the major epicardial arteries were analyzed using predetermined attenuation ranges in Hounsfield units (HU): 1 to 30 HU (low attenuating), 31 to 70 HU (intermediate attenuating), 71 to 150 HU (high attenuating), and mean coronary lumen+2 SD to 1000 HU (calcified). Each epicardial artery was divided into proximal, mid, and distal segments, and plaque volumes were normalized for arterial segment length.

Results:
The baseline characteristics of the 2 cohorts were similar. Low-attenuation and intermediate-attenuation plaque volumes were greater in the proximal segments as well as in the entire length in the adverse event compared with the event-free group. High-attenuation plaque volume was increased only in the proximal segments in the adverse event group. There was no difference in the volume of calcified plaque between the 2 groups. The log rank test using a cutoff of 3.99 mm3/mm for combined intermediate and low plaque volume showed more adverse events in patients with a plaque volume of ≥3.99 mm3/mm.

Conclusions:
Adverse events appear to be associated with greater volumes of low-attenuation and intermediate-attenuation plaques that reflect lipid and fibrous atherosclerosis. The difference between the 2 groups is most apparent in the proximal epicardial arteries.
Predicting off-target effects for end-to-end CRISPR guide design
Authors: Listgarten Jennifer , Weinstein Michael , Elibol Melih , Hoang Luong , Doench John , Fusi Nicolo 
Published: October 2016

AbstractThe CRISPR-Cas9 system provides unprecedented genome editing capabilities. However, off-target effects lead to sub-optimal usage and additionally are a bottleneck in development of therapeutic uses. Herein, we introduce the first machine learning-based approach to this problem, yielding a state-of-the-art predictive model for CRISPR-Cas9 off-target effects which outperforms all other guide design services. Our approach, Elevation, consists of two inter-related machine learning models—one for scoring individual guide-target pairs and another which aggregates guide-target scores into a single, overall guide summary score. Through systematic investigation, we demonstrate that Elevation performs substantially better than competing approaches on both of these tasks. Additionally, we are the first to systematically evaluate approaches on the guide summary score problem; we show that the most widely-used method (and one re-implemented by several other servers) performs no better than random at times, whereas Elevation consistently outperformed it, sometimes by an order of magnitude. In our analyses, we also introduce a method to balance errors on truly active guides with those which are truly inactive, encapsulating a range of practical use cases, thereby showing that Elevation is consistently superior across the entire range. We thus contribute a new evaluation metric for benchmarking off-target modeling. Finally, because of the large computational demands of our tasks, we have developed a cloud-based service for end-to-end guide design which incorporates our previously reported on-target model, Azimuth, as well as our new off-target model, Elevation.
The non-stationary dynamics of fitness distributions: asexual model with epistasis and standing variation
Authors: Martin Guillaume , Roques Lionel 
Published: October 2016

AbstractVarious models describe asexual evolution by mutation, selection and drift. Some focus directly on fitness, typically modelling drift but ignoring or simplifying both epistasis and the distribution of mutation effects (travelling wave models). Others follow the dynamics of quantitative traits determining fitness (Fisher’s geometrical model), imposing a complex but fixed form of mutation effects and epistasis, and often ignoring drift. In all cases, predictions are typically obtained in high or low mutation rate limits and for long-term stationary regimes, thus loosing information on transient behaviors and the effect of initial conditions. Here, we connect fitness-based and trait-based models into a single framework, and seek explicit solutions even away from stationarity. The expected fitness distribution is followed over time via its cumulant generating function, using a deterministic approximation that neglects drift. In several cases, explicit trajectories for the full fitness distribution are obtained, for arbitrary mutation rates and standing variance. For non-epistatic mutation, especially with beneficial mutations, this approximation fails over the long term but captures the early dynamics, thus complementing stationary stochastic predictions. The approximation also handles several diminishing return epistasis models (e.g. with an optimal genotype): it can then apply at and away from equilibrium. General results arise at equilibrium, where fitness distributions display a ‘phase transition’ with mutation rate. Beyond this phase transition, in Fisher’s geometrical model, the full trajectory of fitness and trait distributions takes simple form, robust to details of the mutant phenotype distribution. Analytical arguments are explored for why and when the deterministic approximation applies.Significance statementHow fast do asexuals evolve in new environments? Asexual fitness dynamics are well documented empirically. Various corresponding theories exist, to which they may be compared, but most typically describe stationary regimes, thus losing information on the shorter timescale of experiments, and on the impact of the initial conditions set by the experimenter. Here, a general deterministic approximation is proposed that encompasses many previous models as subcases, and shows surprising accuracy when compared to stochastic simulations. It can yield predictions over both short and long timescales, hopefully fostering the quantitative test of alternative models, using data from experimental evolution in asexuals.
A Neural Locus for Perceptually-Relevant Saccadic Suppression in Visual-Motor Neurons of the Primate Superior Colliculus
Authors: Chen Chih-Yang , Hafed Ziad M. 
Published: October 2016

AbstractSaccadic eye movements cause rapid retinal-image shifts that go perceptually unnoticed several times per second. The mechanisms for perceptual saccadic suppression have been controversial, in part due to sparse understanding of neural substrates. Here we uncovered an unexpectedly specific neural locus for saccadic suppression in the primate superior colliculus (SC). We first developed a sensitive behavioral measure of perceptual suppression in two male macaque monkeys (Macaca mulatta), demonstrating known selectivity to low spatial frequencies. We then investigated visual responses in either purely visual SC neurons or anatomically-deeper visual-motor neurons, which are also involved in saccade generation commands. Surprisingly, visual-motor neurons showed the strongest visual suppression, and the suppression was dependent on spatial frequency like in perception. Most importantly, visual-motor neuron suppression selectivity was highly predictive of behavioral suppression effects in each individual animal, with our recorded population explaining up to ~74% of behavioral variance even on completely different experimental sessions. In contrast, purely visual SC neurons only had mild and unselective suppression (only explaining up to ~48% of behavioral variance). These results run contrary to a hypothesized SC mechanism for saccadic suppression, in which a motor command in the visual-motor and motor neurons is relayed to the more superficial purely visual neurons to suppress them, and to then potentially be fed back to cortex. Instead, our results indicate that an extra-retinal modulatory signal mediating perceptual suppression is already established in visual-motor neurons.New & NoteworthySaccades, which repeatedly re-align the line of sight, introduce spurious signals in retinal images that normally go unnoticed. In part, this happens because of peri-saccadic suppression of visual sensitivity. Here we discovered that a specific sub-type of superior colliculus (SC) neurons may play a critical role in saccadic suppression. Curiously, it is the neurons that help mediate the saccadic command itself that exhibit perceptually-relevant changes invisualsensitivity, not the previously hypothesized purely visual neurons.
Portable and Error-Free DNA-Based Data Storage
Authors: Tabatabaei Yazdi S. M. Hossein , Gabrys Ryan , Milenkovic Olgica 
Published: October 2016

AbstractDNA-based data storage is an emerging nonvolatile memory technology of potentially unprecedented density, durability, and replication efficiency1,2,3,4,5,6. The basic system implementation steps include synthesizing DNA strings that contain user information and subsequently reading them via high-throughput sequencing technologies. All existing architectures enable reading and writing, while some also allow for editing3and elementary sequencing error correction3,4. However, none of the current architectures offers error-free and random-access readouts from a portable device. Here we show through experimental and theoretical verification that such a platform may be easily implemented in practice using MinION sequencers. The gist of the approach is to design an integrated pipeline that encodes data to avoid synthesis and sequencing errors, enables random access through addressing, and leverages efficient portable nanopore sequencing via new anchored iterative alignment and insertion/deletion error-correcting codes. Our work represents the only known random access DNA-based data storage system that uses error-prone MinION sequencers and produces error-free readouts with the highest reported information rate and density.
Polyphyletic ancestry of expanding Patagonian Chinook salmon populations
Authors: Correa Cristian , Moran Paul 
Published: October 2016

AbstractChinook salmon native to North America are spreading through South America’s Patagonia and have become the most widespread anadromous salmon invasion ever documented. To better understand the colonization history and role that genetic diversity might have played in the founding and radiation of these new populations, we characterized ancestry and genetic diversity across latitude (39-48°S). Samples from four distant basins in Chile were genotyped for 13 microsatellite loci, and allocated, through probabilistic mixture models, to 148 potential donor populations in North America representing 46 distinct genetic lineages. Patagonian Chinook salmon clearly had a diverse and heterogeneous ancestry. Lineages from the Lower Columbia River were introduced for salmon open-ocean ranching in the late 1970s and 1980s, and were prevalent south of 43°S. In the north, however, a diverse assembly of lineages was found, associated with net-pen aquaculture during the 1990s. Finally, we showed that possible lineage admixture in the introduced range can confound allocations inferred from mixture models, a caveat previously overlooked in studies of this kind. While we documented high genetic and lineage diversity in expanding Patagonian populations, the degree to which diversity drives adaptive potential remains unclear. Our new understanding of diversity across latitude will guide future research.
Population‐level variation in senescence suggests an important role for temperature in an endangered mollusc
Authors: Hassall C. , Amaro R. , Ondina P. , Outeiro A. , Cordero‐Rivera A. , San Miguel E. 
Published: October 2016

AbstractAge‐related declines in survival and function (senescence) were thought not to exist in wild populations, as organisms, and particularly in invertebrates, do not live long enough. While recent evidence has demonstrated that senescence is both common and measurable even in wild populations under field conditions, there are still organisms that are thought to exhibit ‘negligible senescence’. We explore variation in rates and patterns of senescence in the biogerontological model organism, the freshwater pearl mussel Margaritifera margaritifera, across five populations, which differ in their age profile. In particular, we tested the theory of negligible senescence using time‐at‐death records for 1091 specimens of M. margaritifera. There is clear evidence of senescence in all populations, as indicated by an increase in mortality with age, but the nature of the relationship varies subtly between populations. We find strong evidence of a mortality plateau at later ages in some populations, but this is unequivocally absent from others. We then demonstrate that the temporal scaling of the rates of senescence between five populations of M. margaritifera can be explained by the variation in the thermal environment of the population. Hence, climate change may pose a threat to the demography of this long‐lived, endangered species, and a greater understanding of the relationship between river temperature and population structure will be essential to secure the species against global temperature increases. Our findings demonstrate that useful insights can be drawn from a non‐invasive monitoring method to derive demographic data, and we suggest a wide‐scale application of this method to monitor populations across the whole latitudinal (and, hence, thermal) range of the species.