bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal Patient Blood Management Program Based on a Three-pillar Strategy
Authors: Althoff Friederike C. , Neb Holger , Herrmann Eva , Trentino Kevin M. , Vernich Lee , Füllenbach Christoph , Freedman John , Waters Jonathan H. , Farmer Shannon , Leahy Michael F. , Zacharowski Kai , Meybohm Patrick , Choorapoikayil Suma 
Published: November 2018

Objectives:
To determine whether a multidisciplinary, multimodal Patient Blood Management (PBM) program for patients undergoing surgery is effective in reducing perioperative complication rate, and thereby is effective in improving clinical outcome.

Background:
PBM is a medical concept with the focus on a comprehensive anemia management, to minimize iatrogenic (unnecessary) blood loss, and to harness and optimize patient-specific physiological tolerance of anemia.

Methods:
A systematic review and meta-analysis was performed. Eligible studies had to address each of the 3 PBM pillars with at least 1 measure per pillar, for example, preoperative anemia management plus cell salvage plus rational transfusion strategy. The study protocol has been registered with PROSPERO (CRD42017079217).

Results:
Seventeen studies comprising 235,779 surgical patients were included in this meta-analysis (100,886 pre-PBM group and 134,893 PBM group). Implementation of PBM significantly reduced transfusion rates by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55–0.68, P < 0.00001], 0.43 red blood cell units per patient (mean difference −0.43, 95% CI −0.54 to −0.31, P < 0.00001), hospital length of stay (mean difference −0.45, 95% CI −0.65 to −0.25, P < 0,00001), total number of complications (RR 0.80, 95% CI 0.74–0.88, P <0.00001), and mortality rate (RR 0.89, 95% CI 0.80–0.98, P = 0.02).

Conclusions:
Overall, a comprehensive PBM program addressing all 3 PBM pillars is associated with reduced transfusion need of red blood cell units, lower complication and mortality rate, and thereby improving clinical outcome. Thus, this first meta-analysis investigating a multimodal approach should motivate all executives and health care providers to support further PBM activities.
Tamsulosin to Prevent Postoperative Urinary Retention After Female Pelvic Reconstructive Surgery
Authors: Chapman Graham C. , Sheyn David , Petrikovets Andrey , Mahajan Sangeeta T. , El-Nashar Sherif , Pollard Robert , Mangel Jeffrey M. 
Published: November 2018

Objective
This study aimed to determine the effect of tamsulosin on postoperative urinary retention in female patients after pelvic reconstructive surgery.

Methods
Data were obtained from a retrospective, matched cohort of female patients who were admitted after pelvic reconstructive surgery at a single academic institution. Patients who received tamsulosin were compared with those who did not at a 1:4 ratio, matched by surgical procedure. Patients were excluded if they were discharged on the day of surgery or if an intraoperative complication necessitated prolonged postoperative bladder drainage. Information on demographics, preoperative diagnoses, prolapse stage, preoperative voiding dysfunction, urodynamic findings, intraoperative details, postoperative complications, and voiding outcomes up to 6 weeks after surgery was gathered. The primary outcome was postoperative urinary retention, defined by failure of an active voiding trial.

Results
Patients underwent surgery between January 2016 and March 2018. We identified 35 patients who received tamsulosin and matched to 140 controls. Patients in the tamsulosin group were younger; groups were otherwise similar. Patients who received tamsulosin after surgery were less likely to develop postoperative urinary retention (2.9% vs 24.3%, P = 0.004). After controlling for confounders, multivariable logistic regression identified tamsulosin use as the only independent predictor of postoperative urinary retention with a significant protective effect (odds ratio, 0.09; 95% confidence interval, 0.01–0.67; P = 0.03).

Conclusions
Prophylactic tamsulosin use may be effective in preventing postoperative urinary retention in female patients undergoing pelvic reconstructive surgery.
Steatosis in Liver Transplantation: Current Limitations and Future Strategies
Authors: Linares Ivan , Hamar Matyas , Selzner Nazia , Selzner Markus 
Published: November 2018

AbstractIn parallel with the pandemic of obesity and diabetes, the prevalence of nonalcoholic fatty liver disease has progressively increased. Nonalcoholic steatohepatitis (NASH), a subtype of nonalcoholic fatty liver disease has also augmented considerably being currently cirrhosis due to NASH the second indication for liver transplantation in the United States. Innovative treatments for NASH have shown promising results in phase 2 studies and are being presently evaluated in phase 3 trials. On the other hand, the high mortality on the liver transplant waitlist and the organ shortage has obligated the transplant centers to consider suboptimal grafts, such as steatotic livers for transplantation. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary nonfunction, early allograft dysfunction and posttransplant vascular and biliary complications. Macrosteatosis of more than 30% in fact is an independent risk factor for graft loss. Therefore, it needs to be considered into the risk assessment scores. Growing evidence supports that moderate and severe macrosteatotic grafts can be successfully used for liver transplantation with careful recipient selection. Protective strategies, such as machine-based perfusion have been developed in experimental setting to minimize preservation-related injury and are now on the verge to move into the clinical implementation. This review focuses on the current and potential future treatment of NASH and the clinical practice in fatty liver transplantation, highlights its limitations and optimal allocation, and summarizes the advances of experimental protective strategies, and their potential for clinical application to increase the acceptance and improve the outcomes after liver transplantation with high-grade steatotic livers.
Ethnic and Age Disparities in Outcomes Among Liver Transplant Waitlist Candidates
Authors: Mustian Margaux N. , Shelton Brittany A. , MacLennan Paul A. , Reed Rhiannon D. , White Jared A. , Eckhoff Devin E. , Locke Jayme E. , Allman Richard M. , Gray Stephen H. 
Published: November 2018

Background.
Despite the increasing prevalence of end-stage liver disease in older adults, there is no consensus to determine suitability for liver transplantation (LT) in the elderly. Disparities in LT access exist, with a disproportionately lower percentage of African Americans (AAs) receiving LT. Understanding waitlist outcomes in older adults, specifically AAs, will identify opportunities to improve LT access for this vulnerable population.

Methods.
All adult, liver-only white and AA LT waitlist candidates (January 1, 2003 to October 1, 2015) were identified in the Scientific Registry of Transplant Recipients. Age and race categories were defined: younger white (age <60 years), younger AA, older white (age, ≥60 years), and older AA. Outcomes were delisting, transplantation, and mortality and were modeled using Fine and Gray competing risks.

Results.
Among 101 805 candidates, 58.4% underwent transplantation, 14.7% died while listed, and 21.4% were delisted. Among those delisted, 36.1% died, whereas 7.4% were subsequently relisted. Both older AAs and older whites were more likely than younger whites to be delisted and to die after delisting. Older whites had higher incidence of waitlist mortality than younger whites (subdistribution hazard ratio, 1.07; 95% confidence interval, 1.01-1.13). All AAs and older whites had decreased incidence of LT, compared with younger whites.

Conclusions.
Both older age and AA race were associated with decreased cumulative incidence of transplantation. Independent of race, older candidates had increased incidences of delisting and mortality after delisting than younger whites. Our findings support the need for interventions to ensure medical suitability for LT among older adults and to address disparities in LT access for AAs.
Nanopore native RNA sequencing of a human poly(A) transcriptome
Authors: Workman Rachael E. , Tang Alison D. , Tang Paul S. , Jain Miten , Tyson John R. , Zuzarte Philip C. , Gilpatrick Timothy , Razaghi Roham , Quick Joshua , Sadowski Norah , Holmes Nadine , Goes de Jesus Jaqueline , Jones Karen L. , Snutch Terrance P. , Loman Nicholas , Paten Benedict , Loose Matthew , Simpson Jared T. , Olsen Hugh E. , Brooks Angela N. , Akeson Mark , Timp Winston 
Published: November 2018

ABSTRACTHigh throughput cDNA sequencing technologies have dramatically advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and because modifications are not carried forward in cDNA. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies (ONT). Our study focused on poly(A) RNA from the human cell line GM12878, generating 9.9 million aligned sequence reads. These native RNA reads had an aligned N50 length of 1294 bases, and a maximum aligned length of over 21,000 bases. A total of 78,199 high-confidence isoforms were identified by combining long nanopore reads with short higher accuracy Illumina reads. We describe strategies for assessing 3′ poly(A) tail length, base modifications and transcript haplotypes from nanopore RNA data. Together, these nanopore-based techniques are poised to deliver new insights into RNA biology.DISCLOSURESMA holds shares in Oxford Nanopore Technologies (ONT). MA is a paid consultant to ONT. REW, WT, TG, JRT, JQ, NJL, JTS, NS, AB, MA, HEO, MJ, and ML received reimbursement for travel, accommodation and conference fees to speak at events organised by ONT. NL has received an honorarium to speak at an ONT company meeting. WT has two patents (8,748,091 and 8,394,584) licensed to Oxford Nanopore. JTS, ML and MA received research funding from ONT.
Novel autoregulatory cases of alternative splicing coupled with nonsense-mediated mRNA decay
Authors: Pervouchine Dmitri , Popov Yaroslav , Berry Andy , Borsari Beatrice , Frankish Adam , Guigó Roderic 
Published: November 2018

AbstractNonsense-mediated decay (NMD) is a eukaryotic mRNA surveillance system that selectively degrades transcripts with premature termination codons (PTC). Many RNA-binding proteins (RBP) regulate their expression levels by a negative feedback loop, in which RBP binds its own pre-mRNA and causes alternative splicing to introduce a PTC. We present a bioinformatic framework to identify novel such autoregulatory feedback loops by combining eCLIP assays for a large panel of RBPs with the data on shRNA inactivation of NMD pathway, and shRNA-depletion of RBPs followed by RNA-seq. We show that RBPs frequently bind their own pre-mRNAs and respond prominently to NMD pathway disruption. Poison and essential exons, i.e., exons that trigger NMD when included in the mRNA or skipped, respectively, respond oppositely to the inactivation of NMD pathway and to the depletion of their host genes, which allows identification of novel autoregulatory mechanisms for a number of human RBPs. For example, SRSF7 binds its own pre-mRNA and facilitates the inclusion of two poison exons; SFPQ binding promotes switching to an alternative distal 3’-UTR that is targeted by NMD; RPS3 activates a poison 5’-splice site in its pre-mRNA that leads to a frame shift; U2AF1 binding activates one of its two mutually exclusive exons, leading to NMD; TBRG4 is regulated by cluster splicing of its two essential exons. Our results indicate that autoregulatory negative feedback loop of alternative splicing and NMD is a generic form of post-transcriptional control of gene expression.
Consequences of breed formation on patterns of genomic diversity and differentiation: the case of highly diverse peripheral Iberian cattle
Authors: da Fonseca Rute R. , Ureña Irene , Afonso Sandra , Pires Ana Elisabete , Jørsboe Emil , Chikhi Lounes , Ginja Catarina 
Published: November 2018

AbstractBackgroundIberian primitive breeds exhibit a remarkable phenotypic diversity over a very limited geographical space. While genomic data are accumulating for most commercial cattle, it is still lacking for these primitive breeds. Whole genome data is key to understand the consequences of historic breed formation and the putative role of earlier admixture events in the observed diversity patterns.ResultsWe sequenced 48 genomes belonging to eight Iberian native breeds and found that the individual breeds are genetically very distinct with FST values ranging from 4 to 16% and have levels of nucleotide diversity similar or larger than those of their European counterparts, namely Jersey and Holstein. All eight breeds display significant gene flow or admixture from African taurine cattle and include mtDNA and Y‐chromosome haplotypes from multiple origins. Furthermore, we detected a very low differentiation of chromosome X relative to autosomes within all analyzed taurine breeds, potentially reflecting male‐biased gene flow.ConclusionsOur results show that an overall complex history of admixture resulted in unexpectedly high levels of genomic diversity for breeds with seemingly limited geographic ranges that are distantly located from the main domestication center for taurine cattle in the Near East. This is likely to result from a combination of trading traditions and breeding practices in Mediterranean countries. We also found that the levels of differentiation of autosomes vs sex chromosomes across all studied taurine and indicine breeds are likely to have been affected by widespread breeding practices associated with male-biased gene flow.
Mesenchymal stem cell derived exosomes enhance lymphangiogenesis via exosomal transfer of Ang-2/Tie2
Authors: Zhao Ting , Yan Zhixin , Liu Jinwen , Sun Hui , Chen Yifei , Tao Yan , Xu Wenrong , Qian Hui , Yan Yongmin 
Published: November 2018

AbstractMesenchymal stem cell derived exosomes (MSC-Ex) are nanosized membrane-bound extracellular vesicles found in MSC conditioned medium, that have yielded beneficial effects in several experimental models of organ injury. However, the therapeutic value and mechanism of MSC-Ex in lymphedema is poorly understood. Here we find that human umbilical cord MSCs derived exosomes (hucMSC-Ex) treatment contributed to the regeneration of LYVE-1 positive lymphatic vessels and reduction of lymphedema in a mouse model of tail lymphedema. Following uptake, exosomal lymphangiogenic factors (angiopoietin (Ang)-2 and Tie2) are taken up by HDLECs and promoted HDLECs proliferation, migration, and tube formation in vitro. We also find that exosomal Ang-2 and Tie2 exert a prolymphangiogenic effect on HDLECs through upregulating Prox1 and VEGFR3/p-Akt expression. In conclusion, our result unravel a previously unappreciated prolymphangiogenic role of hucMSC-Ex in lymphedema therapy and provide a new mechanism of Ang-2 in therapeutic lymphangiogenesis.
Dynamic Graphical Models of Molecular Kinetics
Authors: Olsson Simon , Noé Frank 
Published: November 2018

AbstractMost current molecular dynamics simulation and analysis methods rely on the idea that the molecular system can be characterized by a single global state, e.g., a Markov State in a Markov State Model (MSM). In this approach, molecules can be extensively sampled and analyzed when they only possess a few metastable states, such as small to medium-sized proteins. However this approach breaks down in frustrated systems and in large protein assemblies, where the number of global meta-stable states may grow exponentially with the system size. Here, we introduce Dynamic Graphical Models (DGMs), which build upon the idea of Ising models, and describe molecules as assemblies of coupled subsystems. The switching of each sub-system state is only governed by the states of itself and its neighbors. DGMs need many fewer parameters than MSMs or other global-state models, in particular we do not need to observe all global system configurations to estimate them. Therefore, DGMs can predict new, previously unobserved, molecular configurations. Here, we demonstrate that DGMs can faithfully describe molecular thermodynamics and kinetics and predict previously unobserved metastable states for Ising models and protein simulations.
A Neurophysiological Measure of Reward Sensitivity and its Limited Association with Anhedonia in Adolescents and Young Adults
Authors: Frank David W. , Stevens Elise M. , Versace Francesco 
Published: November 2018

AbstractAnhedonia (i.e., the attenuated ability to enjoy pleasurable stimuli) characterizes multiple mood disorders, but its neurophysiological underpinnings are not yet clear. Here, we measured event-related potentials in 116 adolescents and young adults engaged in a signal detection task designed to objectively characterize the anhedonic phenotype. In line with previous studies, the behavioral results showed that approximately 35% of the sample did not develop a response bias towards the more frequently rewarded stimuli (a sign of low hedonic capacity). The event-related potentials (ERPs) evoked by the reward feedback stimuli delivered during the task showed that individuals that did not develop a response bias had significantly less cortical positivity at Fz from 224 ms to 316 ms post feedback onset compared to those that developed a response bias during the task. However, further analyses showed that this between groups difference was relatively weak, as it disappeared when we controlled for response-locked ERPs. Furthermore, the response bias observed in the signal detection task was not strongly associated with self-reported ratings of hedonic capacity. We conclude that even though the signal detection task may be used as a reward sensitivity measure in neurotypical adolescents and young adults, this task may only be able to detect clinically significant levels of anhedonia in this particular population.
ChIPulate : A comprehensive ChIP-seq simulation pipeline
Authors: Datta Vishaka , Hannenhalli Sridhar , Siddharthan Rahul 
Published: November 2018

AbstractChIP-seq (Chromatin Immunoprecipitation followed by sequencing) is a high-throughput technique to identify genomic regions that are bound in vivo by a particular protein, e.g., a transcription factor (TF). Biological factors, such as chromatin state, indirect and cooperative binding, as well as experimental factors, such as antibody quality, cross-linking, and PCR biases, are known to affect the outcome of ChIP-seq experiments. However, the relative impact of these factors on inferences made from ChIP-seq data is not entirely clear. Here, via a detailed ChIP-seq simulation pipeline, ChIPulate, we assess the impact of various biological and experimental sources of variation on several outcomes of a ChIP-seq experiment, viz., the recoverability of the TF binding motif, accuracy of TF-DNA binding detection, the sensitivity of inferred TF-DNA binding strength, and number of replicates needed to confidently infer binding strength. We find that the TF motif can be recovered despite poor and non-uniform extraction and PCR amplification efficiencies. The recovery of the motif is however affected to a larger extent by the fraction of sites that are either cooperatively or indirectly bound. Importantly, our simulations reveal that the number of ChIP-seq replicates needed to accurately measure in vivo occupancy at high-affinity sites is larger than the recommended community standards. Our results establish statistical limits on the accuracy of inferences of protein-DNA binding from ChIP-seq and suggest that increasing the mean extraction efficiency, rather than amplification efficiency, would better improve sensitivity. The source code and instructions for running ChIPulate can be found athttps://github.com/vishakad/chipulate.
Community rescue in experimental phytoplankton communities facing severe herbicide pollution
Authors: V. Fugère , M.-P Hébert , N.B. Costa , C.C.Y. Xu , R.D.H. Barrett , B.E. Beisner , G. Bell , G.F. Fussmann , B.J. Shapiro , V. Yargeau , A. Gonzalez 
Published: November 2018

AbstractEvolutionary rescue occurs when adaptation prevents local extinction in deteriorating environments. Laboratory experiments with microorganisms have shown that the likelihood of evolutionary rescue is greatest in large populations that have previously experienced sublethal doses of stress. To assess this result in natural communities, we conducted a mesocosm experiment with semi-natural phytoplankton communities exposed to glyphosate, a widely used herbicide. We tested whether community biomass and pre-exposure to sublethal stress would facilitate community rescue after severe contamination. Exposure to sublethal stress, but not community biomass, facilitated rescue significantly–even though it led to biodiversity loss. Furthermore, glyphosate had modest effects on community composition, suggesting that community resistance to glyphosate was primarily driven by changes in resistance within taxa, not by community turnover. Our results expand the scope of community evolutionary rescue theory to complex ecosystems and confirm that prior stress exposure is a key predictor of rescue.
Reannotation of the ribonucleotide reductase in a cyanophage reveals life history strategies within the virioplankton
Authors: Harrison Amelia O. , Moore Ryan M. , Polson Shawn W. , Wommack K. Eric 
Published: November 2018

AbstractRibonucleotide reductases (RNRs) are ancient enzymes that catalyze the reduction of ribonucleotides to deoxyribonucleotides. They are required for virtually all cellular life and are prominent within viral genomes. RNRs share a common ancestor and must generate a protein radical for direct ribonucleotide reduction. The mechanisms by which RNRs produce radicals are diverse and divide RNRs into three major classes and several subclasses. The diversity of radical generation methods means that cellular organisms and viruses typically contain the RNR best-suited to the environmental conditions surrounding DNA replication. However, such diversity has also fostered high rates of RNR misannotation within subject sequence databases. These misannotations have resulted in incorrect translative presumptions of RNR biochemistry and have diminished the utility of this marker gene for ecological studies of viruses. We discovered a misannotation of the RNR gene within theProchlorococcusphage P-SSP7 genome, which caused a chain of misannotations within commonly observed RNR genes from marine virioplankton communities. These RNRs are found in marine cyanopodo- and cyanosiphoviruses and are currently misannotated as Class II RNRs, which are O2-independent and require cofactor B12. In fact, these cyanoviral RNRs are Class I enzymes that are O2-dependent and may require a di-metal cofactor made of Fe, Mn, or a combination of the two metals. The discovery of an overlooked Class I β subunit in the P-SSP7 genome, together with phylogenetic analysis of the α and β subunits confirms that the RNR from P-SSP7 is a Class I RNR. Phylogenetic and conserved residue analyses also suggest that the P-SSP7 RNR may constitute a novel Class I subclass. The reannotation of the RNR clade represented by P-SSP7 means that most lytic cyanophage contain Class I RNRs, while their hosts, B12-producingSynechococcusandProchlorococcus, contain Class II RNRs. By using a Class I RNR, cyanophage avoid a dependence on host-produced B12, a more effective strategy for a lytic virus. The discovery of a novel RNR β subunit within cyanopodoviruses also implies that some unknown viral genes may be familiar cellular genes that are too divergent for homology-based annotation methods to identify.