bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Complement-binding Donor-specific Antibodies, Not IgG-antibody Strength Nor C4d Status, at Antibody-mediated Rejection Diagnosis Is an Independent Predictor of Kidney Graft Failure
Authors: Malheiro Jorge , Santos Sofia , Tafulo Sandra , Dias Leonídio , Martins La Salete , Fonseca Isabel , Almeida Manuela , Pedroso Sofia , Beirão Idalina , Castro-Henriques António , Cabrita António 
Published: May 2018

Background
Antibody-mediated rejection (AMR) remains associated with reduced kidney graft survival and no clear prognostic marker is available.

Methods
We investigated whether donor-specific antibodies (DSA) ability to bind C1q in comparison with AMR C4d status, both indirect signs of complement activation, improve risk stratification at time of AMR. Hence, among 467 patients in whom 1 or more graft biopsies were performed between 2008 and 2015, we included 56 with AMR according to Banff '15 criteria. Using concurrent sera, we prospectively identified DSA by single-antigen beads (IgG and C1q) assays.

Results
Antibody-mediated rejection C4d (+) (n = 28) was associated with preformed DSA (P = 0.007), whereas DSA C1q (+) (n = 25) cases had stronger IgG-DSA (P < 0.001). At AMR, graft function was similar between DSA C1q groups, but in the first year after, it improved in DSA C1q (−), whereas a steady decline was observed in DSA C1q (+) cases, remaining significantly lower from 1 year until 4 years after AMR. DSA C1q (+) was significantly associated with reduced graft survival (P = 0.021), whereas AMR C4d (+) was not (P = 0.550). Importantly, a similar negative impact of DSA C1q (+) on graft survival was observed within AMR C4d (+) (P = 0.040) and (−) (P = 0.036), cases. In multivariable analysis, DSA C1q (+) (hazard ratio, 3.939, P = 0.005) and de novo DSA (hazard ratio, 4.409, P = 0.033) were independent predictors of graft failure, but stronger IgG-DSA was not. Similar results were obtained considering C1q-DSA and IgG-DSA strength as continuous variables.

Conclusions
C1q-DSA assessment at AMR can be a valuable tool in detecting patients with higher risk of graft failure.
A Novel Technique in the Treatment of Lymphoceles After Renal Transplantation: C-Arm Cone Beam CT-Guided Percutaneous Embolization of Lymphatic Leakage After Lymphangiography
Authors: Yildirim İsmail Okan , Pişkin Turgut , Duman Enes , Firat Ali , Dogan Murat , Taskapan Hülya , Sahin Idris , Sarac Kaya 
Published: May 2018

Background
We aimed to evaluate the efficacy of percutaneous embolization after lymphangiography using C-arm cone-beam computed tomography (CBCT) performed at the site of lymphatic leakage in patients with postrenal transplant lymphocele.

Methods
Between July 2014 and August 2017, 13 patients not responding to percutaneous ethanol sclerotherapy and conservative treatment for recurrent lymphocele after renal transplant were included. The mean age of the patients was 56.38 ± 9.91 (range, 36-70) years, and it comprised 9 men and 4 women. All patients underwent intranodal lymphangiography. C-arm CBCT-guided percutaneous embolization was performed in patients with confirmed lymphatic leakage. Patients who had no lymphatic leakage underwent drainage with fibrin glue injection.

Results
Lymphatic leakage was observed in 9 patients after lymphangiography, and they underwent CBCT-guided percutaneous N-butyl-2-cyanoacrylate embolization. The volume of lymphatic drainage reduced to less than 10 mL in 8 patients. One patient who was not responding to embolization was treated surgically, after percutaneous drainage and fibrin glue injection. Lymphatic leakage was not observed in 4 patients after lymphangiography. Of these, 3 patients showed a reduction in the amount of lymphatic drainage after lymphangiography. All 4 patients underwent percutaneous drainage and fibrin glue injection. One patient did not respond to the treatment and was treated surgically. Prelymphangiography and postlymphangiography and embolization, the volume of lymphatic drainage was 113.07 ± 21.75 mL, and 53.84 ± 30.96 mL, respectively, and statistically significant decrease was detected (P < 0.005).

Conclusions
Lymphangiography and CBCT-guided percutaneous embolization procedures might be an effective treatment method for patients with lymphocele refractory to treatment.
Immunosuppression Is Associated With Clinical Features and Relapse Risk of B Cell Posttransplant Lymphoproliferative Disorder: A Retrospective Analysis Based on the Prospective, International, Multicenter PTLD-1 Trials
Authors: Zimmermann Heiner , Babel Nina , Dierickx Daan , Morschhauser Franck , Mollee Peter , Zaucha Jan M. , Dreyling Martin H. , Dührsen Ulrich , Reinke Petra , Verhoef Gregor , Subklewe Marion , Hüttmann Andreas , Tousseyn Thomas , Bachy Emmanuel , Hauser Ingeborg A. , Tarella Corrado , Van Den Neste Eric , Gheysens Olivier , Anagnostopoulos Ioannis , Leblond Veronique , Riess Hanno , Choquet Sylvain , Trappe Ralf U. 
Published: May 2018

Background
Current guideline recommendations for immunosuppression reduction after diagnosis of posttransplant lymphoproliferative disorder (PTLD) include stopping antimetabolites, reducing calcineurin inhibitors, and maintaining corticosteroids. However, the effect of immunosuppression on PTLD relapse risk after up-to-date therapy is unclear.

Methods
This is a retrospective analysis of immunosuppression, patient baseline characteristics, and relapse risk measured as landmark time to progression (TTP) starting 1 year after start of therapy in 159 patients with B cell PTLD after solid organ transplantation treated in the prospective, international, multicenter PTLD-1 trials with either sequential treatment (rituximab followed by cyclophosphamide (CHOP-21 chemotherapy) 750 mg/m2 intravenously [IV] day (d) 1, doxorubicin 50 mg/m2 IV d1, vincristine 1.4 mg/m2 (maximum, 2 mg) IV d1, and prednisone 50 mg/m2 PO d1-5, every 21 days) or risk-stratified sequential treatment (rituximab followed by rituximab or rituximab (R-CHOP-21 immunochemotherapy) 375 mg/m2 IV day (d) 1, cyclophosphamide 750 mg/m2 IV d1, doxorubicin 50 mg/m2 IV d1, vincristine 1.4 mg/m2 (max. 2 mg) IV d1, and prednisone 50 mg/m2 PO d1-5, every 21 days).

Results
Patient baseline characteristics at diagnosis of PTLD differed significantly depending on immunosuppression before diagnosis. Compared with immunosuppression before diagnosis, significantly fewer patients received an antimetabolite or a calcineurin inhibitor (CNI) after diagnosis of PTLD. Relapse risk measured as landmark TTP was significantly higher for patients on corticosteroids compared to all others (P = 0.010) as well as for patients on ciclosporin compared with those on tacrolimus (P = 0.002), but similar for those on antimetabolites compared with all others (P = 0.912). In a Cox regression analysis of landmark TTP, corticosteroid-containing immunosuppression after diagnosis of PTLD (P = 0.002; hazard ratio, 11.195) and age (P = 0.001; hazard ratio, 1.076/year) were identified as independent, significant risk factors for PTLD relapse.

Conclusions
In the prospective PTLD-1 trials, corticosteroid use after diagnosis of PTLD is associated with an increased risk of relapse, whereas the use of antimetabolites is not. These findings require prospective validation.
Impact of Early Initiated Everolimus on the Recurrence of Hepatocellular Carcinoma After Liver Transplantation
Authors: Rodríguez-Perálvarez Manuel , Guerrero Marta , Barrera Lydia , Ferrín Gustavo , Álamo Jose M. , Ayllón María D. , Artacho Gonzalo Suarez , Montero José L. , Briceño Javier , Bernal Carmen , Padillo Javier , Marín-Gómez Luis M. , Pascasio Juan M. , Poyato Antonio , Gómez-Bravo Miguel A. , De la Mata Manuel 
Published: May 2018

Background
Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation.

Methods
This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders.

Results
Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation.

Conclusion
Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.
Does internal metabolic state determine our motor coordination strategy?
Authors: Taylor Scott V. , Faisal A. Aldo 
Published: May 2018

AbstractMotor coordination requires the orchestration of multiple degrees of freedom in order to perform actions. Humans display characteristic and predictable reaching trajectories even though multiple trajectories are possible. Computational theories of motor control can explain these reaching trajectories by assuming that subjects orchestrate their movements to minimise a cost function, such as end-point variability or movement effort. However, how internal metabolic states influence decision making and sensorimotor control is not well understood. Here we measure human behaviour during a centre out reaching task in two distinct metabolic conditions in the morning – after having had breakfast and not. We find that humans alter their patterns of motor coordination according to their internal metabolic state and that this change in behaviour results in a 20% lower task-related energy expenditure when fasted. We suggest that movements are orchestrated according to different criteria in different metabolic states so that metabolic costs are reduced in low metabolic states. We also predict that motor coordination strategies take the metabolic costs of specific muscle groups into account when planning and executing movements. Thus, metabolic state may alter the computational strategies of decision making between animal-based experiments (in typically low metabolic conditions) and human psychophysics experiments (in typically high metabolic conditions).
Palaeobiological inferences based on long bone epiphyseal and diaphyseal structure - the forelimb of xenarthrans (Mammalia)
Authors: Amson Eli , Nyakatura John A 
Published: May 2018

ABSTRACTTrabecular architecture (i.e., the main orientation of the bone trabeculae, their number, mean thickness, spacing, etc.) has been shown experimentally to adapt with great accuracy and sensitivity to the loadings applied to the bone during life. However, the potential of trabecular parameters used as a proxy for the mechanical environment of an organism’s organ to help reconstruct the lifestyle of extinct taxa has only recently started to be exploited. Furthermore, these parameters are rarely combined to the long-used mid-diaphyseal parameters to inform such reconstructions. Here we investigate xenarthrans, for which functional and ecological reconstructions of extinct forms are particularly important in order to improve our macroevolutionary understanding of their main constitutive clades, i.e., the Tardigrada (sloths), Vermilingua (anteaters), and Cingulata (armadillos and extinct close relatives). The lifestyles of modern xenarthrans can be classified as fully terrestrial and highly fossorial (armadillos), arboreal (partly to fully) and hook-and-pull digging (anteaters), or suspensory (fully arboreal) and non-fossorial (sloths). The degree of arboreality and fossoriality of some extinct forms, “ground sloths” in particular, is highly debated. We used high-resolution computed tomography to compare the epiphyseal 3D architecture and mid-diaphyseal structure of the forelimb bones of extant and extinct xenarthrans. The comparative approach employed aims at inferring the most probable lifestyle of extinct taxa, using phylogenetically informed discriminant analyses. Several challenges preventing the attribution of one of the extant xenarthran lifestyles to the sampled extinct sloths were identified. Differing from that of the larger “ground sloths”, the bone structure of the small-sized Hapalops (Miocene of Argentina), however, was found as significantly more similar to that of extant sloths, even when accounting for the phylogenetic signal.
On Signalling and Estimation Limits for Molecular Birth-Processes
Authors: Parag Kris V 
Published: May 2018

AbstractUnderstanding and uncovering the mechanisms or motifs that molecular networks employ to regulate noise is a key problem in cell biology. As it is often difficult to obtain direct and detailed insight into these mechanisms, many studies instead focus on assessing the best precision attainable on the signalling pathways that compose these networks. Molecules signal one another over such pathways to solve noise regulating estimation and control problems. Quantifying the maximum precision of these solutions delimits what is achievable and allows hypotheses about underlying motifs to be tested without requiring detailed biological knowledge. The pathway capacity, which defines the maximum rate of transmitting information along it, is a widely used proxy for precision. Here it is shown, for estimation problems involving elementary yet biologically relevant birth-process networks, that capacity can be surprisingly misleading. A time-optimal signalling motif, called birth-following, is derived and proven to better the precision expected from the capacity, provided the maximum signalling rate constraint is large and the mean one above a certain threshold. When the maximum constraint is relaxed, perfect estimation is predicted by the capacity. However, the true achievable precision is found highly variable and sensitive to the mean constraint. Since the same capacity can map to different combinations of rate constraints, it can only equivocally measure precision. Deciphering the rate constraints on a signalling pathway may therefore be more important than computing its capacity.
GLMdenoise improves multivariate pattern analysis of fMRI data
Authors: Charest Ian , Kriegeskorte Nikolaus , Kay Kendrick N. 
Published: May 2018

ABSTRACTGLMdenoise is a denoising technique for task-based fMRI. In GLMdenoise, estimates of spatially correlated noise (which may be physiological, instrumental, motion-related, or neural in origin) are derived from the data and incorporated as nuisance regressors in a general linear model (GLM) analysis. We previously showed that GLMdenoise outperforms a variety of other denoising techniques in terms of cross-validation accuracy of GLM estimates (Kay et al., 2013a). However, the practical impact of denoising for experimental studies remains unclear. Here we examine whether and to what extent GLMdenoise improves sensitivity in the context of multivariate pattern analysis of fMRI data. On a large number of participants (31 participants across 4 experiments; 3 T, gradient-echo, spatial resolution 2–3.75 mm, temporal resolution 1.3–2 s, number of conditions 32–75), we perform representational similarity analysis (Kriegeskorte et al., 2008a) as well as pattern classification (Haxby et al., 2001). We find that GLMdenoise substantially improves replicability of representational dissimilarity matrices (RDMs) across independent splits of each participant’s dataset (average RDM replicability increases from r = 0.46 to r = 0.61). Additionally, we find that GLMdenoise substantially improves pairwise classification accuracy (average classification accuracy increases from 79% correct to 84% correct). We show that GLMdenoise often improves and never degrades performance for individual participants and that GLMdenoise also improves across-participant consistency. We conclude that GLMdenoise is a useful tool that can be routinely used to maximize the amount of information extracted from fMRI activity patterns.
RAVEN 2.0: a versatile toolbox for metabolic network reconstruction and a case
study on Streptomyces coelicolor
Authors: Wang Hao , Marcišauskas Simonas , Sánchez Benjamín J , Domenzain Iván , Hermansson Daniel , Agren Rasmus , Nielsen Jens , Kerkhoven Eduard J 
Published: May 2018

AbstractRAVEN is a commonly used MATLAB toolbox for genome-scale metabolic model (GEM) reconstruction, curation and constraint-based modelling and simulation. Here we present RAVEN Toolbox 2.0 with major enhancements, including: (i) de novo reconstruction of GEMs based on the MetaCyc pathway database; (ii) a redesigned KEGG-based reconstruction pipeline; (iii) convergence of reconstructions from various sources; (iv) improved performance, usability, and compatibility with the COBRA Toolbox. Capabilities of RAVEN 2.0 are here illustrated through de novo reconstruction of GEMs for the antibiotic-producing bacterium Streptomyces coelicolor. Comparison of the automated de novo reconstructions with the iMK1208 model, a previously published high-quality S. coelicolor GEM, exemplifies that RAVEN 2.0 can capture most of the manually curated model. The generated de novo reconstruction is subsequently used to curate iMK1208 resulting in Sco4, the most comprehensive GEM of S. coelicolor, with increased coverage of both primary and secondary metabolism. This increased coverage allows the use of Sco4 to predict novel genome editing targets for optimized secondary metabolites production. As such, we demonstrate that RAVEN 2.0 can be used not only for de novo GEM reconstruction, but also for curating existing models based on up-to-date databases. Both RAVEN 2.0 and Sco4 are distributed through GitHub to facilitate usage and further development by the community.Author summaryCellular metabolism is a large and complex network. Hence, investigations of metabolic networks are aided by in silico modelling and simulations. Metabolic networks can be derived from whole-genome sequences, through identifying what enzymes are present and connecting these to formalized chemical reactions. To facilitate the reconstruction of genome-scale models of metabolism (GEMs), we have developed RAVEN 2.0. This versatile toolbox can reconstruct GEMs fast, through either metabolic pathway databases KEGG and MetaCyc, or from homology with an existing GEM. We demonstrate RAVEN’s functionality through generation of a metabolic model of Streptomyces coelicolor, an antibiotic-producing bacterium. Comparison of this de novo generated GEM with a previously manually curated model demonstrates that RAVEN captures most of the previous model, and we subsequently reconstructed an updated model of S. coelicolor: Sco4. Following, we used Sco4 to predict promising targets for genetic engineering, which can be used to increase antibiotic production.
Selectively increased autofluorescence at fingernails and certain regions of skin: A potential novel diagnostic biomarker for Parkinson’s disease
Authors: Wu Danhong , Tao Yue , Zhang Mingchao , Li Yujia , Shen Liwei , Li Yuzhen , Ying Weihai 
Published: May 2018

AbstractDiagnosis of Parkinson’s disease (PD) mainly relies on the judgment of experienced neurologists on the clinical symptoms of patients. Quantitative and specific biomarker tests for PD is greatly needed. In this study we tested our hypothesis that increased autofluorescence (AF) of skin and fingernails may become a novel diagnostic biomarker for PD. Our study has indicated that PD patients have a distinct pattern of AF changes, compared with that of acute ischemic stroke (AIS) patients: First, the AF intensity of PD patients in the fingernails and a part of the examined regions of skin is significantly higher than that of the healthy and Low-Risk group, while the AF intensity of AIS patients is significantly higher than that of the healthy and Low-Risk group in most regions examined; second, there is AF asymmetry at the index fingernails and two regions of the skin of PD patients, while there is AF asymmetry at all examined regions of AIS patients; and third, both the AF intensity and AF asymmetry at Centremetacarpus of PD patients is significantly lower than those of AIS patients. The increased AF may result from the altered keratins’ AF induced by the oxidative stress in the plasma of PD patients. Collectively, our study has indicated that PD patients have a distinct pattern of AF changes compared with those of healthy and Low-Risk persons as well as AIS patients, which may become a novel diagnostic biomarker for PD.
A novel LC system embeds analytes in pre-formed gradients for rapid, ultra-robust proteomics
Authors: Bache Nicolai , Geyer Philipp E. , Bekker-Jensen Dorte B. , Hoerning Ole , Falkenby Lasse , Treit Peter V. , Doll Sophia , Paron Igor , Meier Florian , Olsen Jesper V. , Vorm Ole , Mann Matthias 
Published: May 2018

ABSTRACTTo further integrate mass spectrometry (MS)-based proteomics into biomedical research and especially into clinical settings, high throughput and robustness are essential requirements. They are largely met in high-flow rate chromatographic systems for small molecules but these are not sufficiently sensitive for proteomics applications. Here we describe a new concept that delivers on these requirements while maintaining the sensitivity of current nano-flow LC systems. Low-pressure pumps elute the sample from a disposable trap column, simultaneously forming a chromatographic gradient that is stored in a long storage loop. An auxiliary gradient creates an offset, ensuring the re-focusing of the peptides before the separation on the analytical column by a single high-pressure pump. This simplified design enables robust operation over thousands of sample injections. Furthermore, the steps between injections are performed in parallel, reducing overhead time to a few minutes and allowing analysis of more than 200 samples per day. From fractionated HeLa cell lysates, deep proteomes covering more than 130,000 sequence unique peptides and close to 10,000 proteins were rapidly acquired. Using this data as a library, we demonstrate quantitation of 5200 proteins in only 21 min. Thus, the new system-termed Evosep One-analyzes samples in an extremely robust and high throughput manner, without sacrificing in depth proteomics coverage.