bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Immune Cell Subtypes and Phenotype With Subsequent Invasive Candidiasis in Patients With Abdominal Sepsis
Authors: Arens Christoph , Kramm Timo , Decker Sebastian , Spannenberger Jens , Brenner Thorsten , Richter Daniel Christoph , Weigand Markus Alexander , Uhle Florian , Lichtenstern Christoph 
Published: August 2018

ABSTRACT

Background:
In nonneutropenic intensive care unit (ICU) patients, current risk stratification scores lack specificity to reliably predict the risk of a prospective invasive candidiasis (IC). We aimed to explore possible associations of distinct immunological markers with different degrees of Candida affection in patients with abdominal sepsis.

Methods:
The presented explorative, noninterventional diagnosis study recruited patients admitted to the surgical ICU at Heidelberg University Hospital with abdominal sepsis. Over 5 days, we determined white blood cell count, 1,3-β-d-glucan, and HLA-DR expression; the amount of Th1, Th17, regulatory T, T helper, and cytotoxic T cells; Dectin-1 and TLR2-expression; the amount of T, B, and NK cells; the ex vivo secretion of IL-8 upon stimulation with LPS, flagellin, and zymosan; and the distribution of distinct T-cell cytokines in a daily manner. On day 21, patients’ Candida infection status was stratified in no colonization or IC, colonization or IC.

Results:
A total of 26 patients were included. On day 21, five patients showed no colonization or IC, in 13 patients a colonization was detected, and eight patients were diagnosed with IC. On study inclusion, the stratification groups showed comparable values in standard laboratory parameters and morbidity scores. Decreased B and NK cell counts, as well as reduced IL-8 secretion after ex vivo stimulation with LPS or flagellin seemed to be associated with a higher risk of subsequent Candida colonization. Even lower values could distinguish the therapy-relevant difference between prospective IC from colonization alone.

Conclusions:
We were able to show distinct immune system impairments in early abdominal sepsis by specific immune-based measurements. A possible association of these impairments with a subsequent Candida affection is shown.
Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a Murine Deceased Criteria Donor Model
Authors: Vemuri Chandu , Upadhya Gundumi A. , Arif Batool , Jia Jianluo , Lin Yiing , Gaut Joseph P. , Fazal Jawad , Pan Hua , Wickline Samuel A. , Chapman William C. 
Published: August 2018

Background
Over 100 000 patients await renal transplantation and 4000 die per year. Compounding this mismatch between supply and demand is delayed graft function which contributes to short-term and long-term graft failures. Previously, we reported that thrombin-targeted perfluorocarbon nanoparticles (PFC-NP) protect kidneys from ischemic renal injury after transient arterial occlusion. Here we hypothesize that perfusion of renal allografts with PFC-NP similarly can protect graft function after an ischemic interval.

Methods
After 60 minutes of warm ischemia, male Lewis rats underwent left renal explantation followed by renal perfusion with 5 mL of standard perfusate alone (N = 3) or with 0.3 mL of untargeted PFC-NP (N = 5) or 0.3 mL thrombin-targeted of PFC NP functionalized with phenylalanine-proline-arginine-chloromethylketone (PPACK) (PFC-PPACK), an irreversible thrombin inhibitor (N = 5). Kidneys underwent 6 hours of cold storage, followed by transplantation into recipients and native nephrectomy. Animals were euthanized at 24 hours for tissue collection or at 48 hours for blood and renal tissue collection. A survival experiment was performed using the same protocol with saline control (N = 3), PFC-NP (N = 3) or PFC-PPACK (N = 6).

Results
Serum creatinine was improved for the PFC-PPACK groups as compared with control groups (P < 0.04). Kaplan-Meier survival curves also indicated increased longevity (P < 0.05). Blinded histologic scoring revealed markedly attenuated renal damage in the PFC-PPACK group compared to untreated animals (2.75 ± 1.60 versus 0.83 ± 3.89; P = 0.0001) and greater preservation of renal vasculature.

Conclusions
These results validate an NP-based approach to improve renal graft function as antithrombin NPs improved allograft function, decreased renal damage, protected vasculature, and improved longevity.
Identification and Validation of the Predictive Capacity of Risk Factors and Models in Liver Transplantation Over Time
Authors: Blok Joris J. , Putter Hein , Metselaar Herold J. , Porte Robert J. , Gonella Federica , de Jonge Jeroen , van den Berg Aad P. , van der Zande Josephine , de Boer Jacob D. , van Hoek Bart , Braat Andries E. 
Published: August 2018

Background
Outcome after liver transplantation (LT) is determined by donor, transplant and recipient risk factors. These factors may have different impact on either patient or graft survival (outcome type). In the literature, there is wide variation in the use of outcome types and points in time (short term or long term). Objective of this study is to analyze the predictive capacity of risk factors and risk models in LT and how they vary over time and per outcome type.

Methods
All LTs performed in the Netherlands from January 1, 2002, to December 31, 2011, were analyzed with multivariate analyses at 3-month, 1-year, and 5-year for patient and (non-)death-censored graft survival. The predictive capacity of the investigated risk models was compared with concordance indices.

Results
Recipient age, model for end-stage liver disease sodium, ventilatory support, diabetes mellitus, hepatocellular carcinoma, previous malignancy, hepatitis C virus antibody, hepatitis B virus antibody, perfusion fluid, and Eurotransplant donor risk index (ET-DRI) had significant impact on outcome (graft or patient survival) at 1 or multiple points in time. Significant factors at 3-month patient survival (recipient age, model for end-stage liver disease sodium, ventilatory support) were used to compose a concept model. This model, had a higher c-index than the balance-of-risk score, DRI, ET-DRI, donor-recipient model and simplified recipient risk index for long-term patient and non–death-censored graft survival.

Conclusions
In this study, the effects of recipient risk factors and models on different outcome types and time points were shown. Short-term patient survival mainly depends on recipient risk factors, long-term graft survival on donor risk factors and is more difficult to predict. Next to the concept model, the donor-recipient model has a higher predictive capacity to other risk models for (long-term) patient and non–death-censored graft survival. The DRI and ET-DRI best predicted death-censored graft survival. Knowledge about risk factors and models is critical when using these for waitlist management and/or help in organ allocation and decision-making.
Anti-HLA Donor-Specific IgG Subclasses and C1q-binding Evolution in Posttransplant Monitoring
Authors: Ponsirenas Renata von Glehn , Cazarote Helena B. , Araújo Stanley de Almeida , Wanderley David Campos , Shimakura Silvia , Valdameri Joana S. , Contieri Fabiana L. C. , von Glehn Cristina C. Q. C. , Susin Michelle F. , Sotomaior Vanessa Santos 
Published: August 2018

Background
The identification of low-level antibodies by single-antigen bead methodology has brought advancements to risk evaluation of kidney transplant recipients. However, the use of mean fluorescence intensity (MFI) to quantify antibodies and to guide therapy is not enough. Notably, immunoglobulin G (IgG) subclass switching is hypothesized to follow a programmed sequence after an emergency signal from the germinal center. In transplantation this process is not clear yet. In the present study, we sequentially evaluate anti-HLA donor specific antibody (DSA) subclasses, their profile changes, and C1q-binding ability and the influence of those characteristics on antibody mediated rejection (AMR) occurrence and allograft function.

Methods
A total of 30 DSA-positive patients were tested for IgG subclass content and C1q-binding in sequential serum samples.

Results
Twenty-one patients were DSA-positive before transplant; patients sensitized only by transfusion or pregnancies had IgG1 and/or IgG3, and patients sensitized by both transfusion and pregnancies or previous transplant showed a broader range of IgG subclasses. C1q binding was detected in high MFI made up of IgG1 or multiple IgG subclasses. Only 4 patients were positive for C1q posttransplantation and 3 of these showed an increase in MFI, changes in subclasses patterns, AMR, and allograft dysfunction.

Conclusions
Posttransplant evaluation of DSA subclasses and the ability to bind C1q may be informative for both AMR occurrence and allograft dysfunction. Monitoring these events may help to better define risk and interventional time points.
Uneven missing data skews phylogenomic relationships within the lories and lorikeets
Authors: Smith Brian Tilston , Mauck William M. , Benz Brett , Andersen Michael J. 
Published: August 2018

AbstractThe resolution of the Tree of Life has accelerated with advances in DNA sequencing technology. To achieve dense sampling, it is often necessary to obtain DNA from historical museum specimens to supplement modern genetic samples. However, DNA from historical material is generally degraded and fragmented, which presents various challenges. In this study, we evaluated how the coverage at variant sites and missing data among historical and modern sample types impacts phylogenomic inference. We explored these patterns in the brush-tongued parrots (lories and lorikeets) of Australasia by sampling ultraconserved elements in 105 taxa. Trees estimated with low coverage sites had several clades where historical or modern samples clustered together, which were not observed in trees with more stringent filtering. To assess if the aberrant relationships were affected by missing data, we performed a targeted outlier analysis of sites and loci and a more general data reduction approach where we excluded sites based on a percentage of data completeness. The outlier analyses showed that 6.6% of total sites were driving the topological differences among trees built with and without low coverage sites, and at these sites, historical samples had 7.5x more missing data than modern ones. An examination of subclades identified loci biased by missing data, and the exclusion of these loci shifted phylogenetic relationships. Predictive modeling found that outlier analysis scores were not correlated with summary statistics of locus alignments, indicating that outlier loci do not have characteristics differing from other loci. Excluding missing data by percentage completeness indicated that sites with 70% completeness were necessary to avoid spurious relationships, but more stringent conditions of data completeness produced less-resolved trees. After accounting for biased loci and understanding the stability of relationships, we inferred a more robust phylogenetic hypothesis for lories and lorikeets.
Group Based Trajectory Analysis of Cognitive Outcomes in Children with Perinatal HIV
Authors: Patel Payal B. , Apornpong Tanakorn , Kerr Stephen J. , Puthanakit Thanyawee , Thongpibul K. , Kosalaraksa P. , Ounchanum P. , Kanjanavanit S. , Ngampiyaskul C. , Luesomboon W. , Penhusun L. , Chettra K. , Mellins Claude , Malee Kay , Spudich Serena , Ananworanich Jintanat , Paul Robert ,   On behalf of the PREDICT/Resilience Study Group
Published: August 2018

AbstractBackgroundCognitive impairment is common in children with perinatally-acquired HIV (pHIV). It is not known whether exposure to HIV-related neuropathogenic mechanisms during vulnerable periods of neurodevelopment may produce distinct long-term cognitive phenotypes as children age. We used group based trajectory modeling to identify clusters of children with pHIV following a unique developmental trajectory across age and predictors of belonging to select cognitive trajectory groups.MethodsParticipants included children aged 1 to 17 enrolled in the PREDICT resilience study, a cohort study of children with pHIV in Thailand and Cambodia. Cognitive testing was conducted semi-annually over three years. Group based trajectory analyses determined subgroups of children with differing cognitive trajectories using maximum likelihood estimates and Bayesian statistics. Multiple logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group.ResultsThree distinct cognitive phenotypes were identified for each neurocognitive test categorized as high, medium and low scoring groups. A subgroup of children demonstrated normal developmental patterns for Color Trails Test 1 and 2. Children in the low trajectory group were more likely to present at an older age (>8 years, OR: 2.72; p 0.01) and report lower household income level (OR: 0.33-0.42; p<0.005). Neither CD4 nadir nor treatment arm was associated with cognitive trajectory status.ConclusionOur study reflects the benefit of using group based trajectory modeling to classify the heterogeneity in cognitive outcomes of children with pHIV. Children were described as belonging to three distinct subgroups determined at study onset alluding to the fact that cognitive outcomes are likely to be determined at an early age with little variability over time in children with pHIV. Demographic variables, including older age at presentation and household income, were associated with low scoring cognitive trajectories, whereas HIV related variables were not. These findings mirror other studies and demonstrate the impact of socioeconomic factors on cognitive development in children with pHIV.
Shared behavioral mechanisms underlieC. elegansaggregation and swarming
Authors: Ding S Serena , Schumacher Linus J. , Javer Avelino E. , Endres Robert G. , Brown André EX 
Published: August 2018

AbstractIn complex biological systems, simple individual-level behavioral rules can give rise to emergent group-level behavior. While such collective behavior has been well studied in cells and larger organisms, the mesoscopic scale is less understood, as it is unclear which sensory inputs and physical processes mattera priori. Here, we investigate collective feeding in the roundwormC. elegansat this intermediate scale, using quantitative phenotyping and agent-based modeling to identify behavioral rules underlying both aggregation and swarming—a dynamic phenotype only observed at longer timescales. Using fluorescent multi-worm tracking, we quantify aggregation behavior in terms of individual dynamics and population-level statistics. Based on our quantification, we use agent-based simulations and approximate Bayesian inference to identify three key behavioral rules that give rise to aggregation: cluster-edge reversals, a density-dependent switch between crawling speeds, and taxis towards neighboring worms. Our simulations suggest that swarming is simply driven by local food depletion but otherwise employs the same behavioral mechanisms as the initial aggregation. Hence, mesoscopicC. elegansuses mechanisms familiar from microscopic systems for aggregation, but implemented via more complex behaviors characteristic of macroscopic organisms.
Isolated individuals and groups show opposite preferences toward humidity
Authors: Martín Mariano Calvo , Nicolis Stamatios C. , Planas-Sitjà Isaac , de Biseau Jean-Christophe , Deneubourg Jean-Louis 
Published: August 2018

AbstractCockroaches, like most social arthropods, are led to choose collectively among different alternative resting places. These decisions are modulated by different factors, such as environmental conditions (temperature, relative humidity) and sociality (groups size, nature of communications). The aim of this study is to establish the interplay between environmental conditions and the modulation of the interactions between individuals within a group leading to an inversion of preferences. We show that the preferences of isolated cockroaches and groups of 16 individuals, on the selection of the relative humidity of a shelter are inversed and shed light on the mechanisms involved. We suggest that the relative humidity has a multi-level influence on cockroaches, manifested as an attractant effect at the individual level and as a negative effect at the group level, modulating the interactions.
Sex-specific migration strategies of ospreys (Pandion haliaetus) from Germany
Authors: Meyburg Bernd-Ulrich , Roepke Dietrich , Meyburg Christiane , van Wijk Rien E. 
Published: August 2018

AbstractBirds exhibit a wide variety of migration strategies, not only between species, but also within species. Populations might migrate to specific sites outside of the breeding season, but individuals within populations may also exhibit different migration strategies. Young, unexperienced birds may take different routes, visit different sites, and time their annual cycle differently than adults. In turn, within groups of adult birds, there may be a division between the sexes whereby males and females migrate to different sites or, more commonly, at different times. We investigated differences in the migration strategies of male and female ospreys (Pandion haliaetus) from a breeding population in northeastern Germany. An important difference between the sexes was the much earlier leaving of the breeding place by the females compared to the males. The difference in the timing of departure was much more pronounced compared to most other raptor species. The other main difference between the male and female ospreys was the distance that the birds accumulated over the annual cycle, with males generally moving more while at the breeding ground compared with the non-breeding grounds, and the opposite in females. An exception to this observation was two males that migrated to the Iberian Peninsula, that covered longer distances during the non-breeding season. Consequently, individuals accumulated the same distances over the course of an annual cycle, regardless of sex or migration strategy. Unexpectedly, a difference in the timing of the annual cycle between the sexes occurred at the breeding grounds with females leaving 2 to 3 months before the males, long before the young had fledged. Because males migrated much faster and, unlike the females, did not make prolonged stops, their arrival times at the non-breeding grounds were not different. Return migration to the breeding grounds was very similar between the sexes, and even the two males that spent the non-breeding season on the Iberian Peninsula did not arrive before any of the other birds. Thus, a shorter migration distance is not necessarily associated with an advantage with respect to a timely return to the breeding grounds.
Which osteoarthritic gait features recover following Total Knee Replacement surgery?
Authors: Biggs Paul Robert , Whatling Gemma Marie , Wilson Chris , Metcalfe Andrew John , Holt Cathy Avril 
Published: August 2018

AbstractBackgroundGait analysis can be used to measure variations in joint function in patients with knee osteoarthritis (OA), and is useful when observing longitudinal biomechanical changes following Total Knee Replacement (TKR) surgery. The Cardiff Classifier is an objective classification tool applied previously to examine the extent of biomechanical recovery following TKR. In this study, it is further developed to reveal the salient features that contribute to recovery towards healthy function.MethodsGait analysis was performed on 30 patients before and after TKR surgery, and 30 healthy controls. Median TKR follow-up time was 13 months. The combined application of principal component analysis (PCA) and the Cardiff Classifier defined 18 biomechanical features that discriminated OA from healthy gait. Statistical analysis tested whether these features were affected by TKR surgery and, if so, whether they recovered to values found for the controls.ResultsThe Cardiff Classifier successfully discriminated between OA and healthy gait in all 60 cases. Of the 18 discriminatory features, only six (33%) were significantly affected by surgery, including features in all three planes of the ground reaction force (p<0.001), ankle dorsiflexion moment (p<0.001), hip adduction moment (p=0.003), and transverse hip angle (p=0.007). All but two (89%) of these features remained significantly different to those of the control group after surgery.ConclusionsThis approach was able to discriminate gait biomechanics associated with knee OA. The ground reaction force provided the strongest discriminatory features. Despite increased gait velocity and improvements in self-reported pain and function, which would normally be clinical indicators of recovery, the majority of features were not affected by TKR surgery. This TKR cohort retained pre-operative gait patterns; reduced sagittal hip and knee moments, decreased knee flexion, increased hip flexion, and reduced hip adduction. The changes that were associated with surgery were predominantly found at the ankle and hip, rather than at the knee.
Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment
Authors: Bezler Alexandra , Braukmann Fabian , West Sean , Duplan Arthur , Conconi Raffaella , Schütz Frédéric , Gönczy Pierre , Piano Fabio , Gunsalus Kristin , Miska Eric A. , Keller Laurent 
Published: August 2018

ABSTRACTBackgroundRNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter-and trans-generational inheritance. In the nematodeCaenorhabditis elegansenvironmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene expression. Notably, transmission efficiency differs between the male and female germline, yet the underlying mechanisms remain elusive.ResultsHere we use high-throughput sequencing of dissected gonads to quantify sex-specific endogenous piRNAs, miRNAs and siRNAs in theC. elegansgermline and the somatic gonad. We identify genes with exceptionally high levels of 22G RNAs that are associated with low mRNA expression, a signature compatible with silencing. We further demonstrate that contrary to the hermaphrodite germline, the male germline, but not male soma, is resistant to environmental RNAi triggers provided by feeding. This sex-difference in silencing efficacy is associated with lower levels of gonadal RNAi amplification products. Moreover, this tissue-and sex-specific RNAi resistance is regulated by the germline, since mutant males with a feminized germline are RNAi sensitive.ConclusionThis study provides important sex-and tissue-specific expression data of miRNA, piRNA and siRNA as well as mechanistic insights into sex-differences of gene regulation in response to environmental cues.
PAVOOC: Designing CRISPR sgRNAs using 3D protein structures and functional domain annotation
Authors: Schaefer Moritz , Clevert Dr. Djork-Arné , Weiss Dr. Bertram , Steffen Dr. Andreas 
Published: August 2018

AbstractSummary: sgRNAs targeting the same gene can significantly vary in terms of efficacy and specificity. PAVOOC (Prediction And Visualization of On- and Off-targets for CRISPR) is a web-based CRISPR sgRNA design tool that employs state-of-the art machine learning models to prioritize most effective candidate sgRNAs. In contrast to other tools, it maps sgRNAs to functional domains and protein structures and visualizes cut sites on corresponding protein crystal structures. Furthermore, PAVOOC supports HDR template generation for gene editing experiments and the visualization of the mutated amino acids in 3D.Availability and Implementation: PAVOOC is available under https://pavooc.me and accessible using current browsers (Chrome/Chromium recommended). The source code is hosted at github.com/moritzschaefer/pavooc under the MIT License. The backend, including data processing steps, and the frontend is implemented in Python 3 and ReactJS respectively. All components run in a simple Docker environment.Contact: mail@moritzs.de