bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated model for end-stage liver disease maybe superior to some other model for end-stage liver disease-based systems in addition to Child-Turcotte-Pugh and albumin-bilirubin scores in patients with hepatitis B virus-related liver cirrhosis and spontaneous bacterial peritonitis
Authors: Chen Pin-Cheng , Chen Bo-Huan , Huang Chien-Hao , Jeng Wen-Juei , Hsieh Yi-Chung , Teng Wei , Chen Yi-Cheng , Ho Yu-Pin , Sheen I-Shyan , Lin Chun-Yen 
Published: September 2019

Objectives
For mortality prediction of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis, no direct comparisons have been made among the eight models, Child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD), MELD-Na, integrated MELD (iMELD) score, MELD to sodium (MESO) index, modification of the MELD scoring system (Refit MELD), Refit MELD-Na and Albumin-Bilirubin (ALBI) score.

Materials and methods
Between January 2005 and July 2017, 314 patients who met the criteria for liver cirrhosis with the first episode of SBP were enrolled in this retrospective study. Clinical and laboratory data were obtained at diagnosis. Patients were followed up until February 2018 or death.

Results
Patients were predominantly middle-aged male. Hepatitis B virus (HBV) infection accounted for the majority of the etiologies (41.7%) with 33.6% of the patients received antivirals. The in-hospital mortality rate was 39.8%. The cumulative 3-month and 6-month mortality rates were 51.6 and 60.2%, respectively. For patients with HBV related, not hepatitis C virus or alcohol related, liver cirrhosis, iMELD had the highest area under receiver operating characteristic curve (AUC) and was significantly superior to MELD, MESO, and Refit MELD in addition to CTP and ALBI scores in predicting 3-month and 6-month mortality.

Conclusion
For patients with HBV-related liver cirrhosis and SBP, iMELD had the highest AUC among these eight models and was significantly superior to MELD, MESO, and Refit MELD in addition to CTP and ALBI scores in predicting 3-month and 6-month mortalities.
Fostering Civility in Learning Conversations
Authors: Clark Cynthia M. , Fey Mary K. 
Published: September 2019

Background
Civility, psychological safety, and effective stress management are essential for meaningful learning conversations.

Problem
Incivility triggers fear and humiliation, impairs clinical judgment and learning, reduces psychological safety, and increases cognitive load. These factors converge to make learners less likely to incorporate feedback, speak up when there is a problem, and discuss practice errors and patient safety issues.

Approach
The authors combined the Basic Assumption and the PAAIL (Preview, Advocacy1, Advocacy2, Inquiry, and Listen) conversational strategy to help surface (rather than obscure) both educators' and learners' thinking. The synergy of these 2 strategies allows educators to identify individual learning needs and develop the learners' clinical judgment skills. This process improves learning by reducing incivility and cognitive load, improving psychological safety, and strengthening clinical judgment skills.

Conclusion
This conversational strategy can minimize stress and anxiety in learners and optimize learning.
Quality Improvement Project to Evaluate Discharge Prescriptions in Children With Cystic Fibrosis
Authors: Merino Sanjuán Matilde , Chorro-Mari Veronica , Nwokoro Chinedu , Christiansen Nanna , Pao Caroline , Gomez-Pastrana Duran David , Climente Marti Monica 
Published: September 2019

Introduction:
Cystic Fibrosis (CF) requires multiple pharmaceutical treatments, elevating the risk of medication errors (ME), which may compromise patient safety. This study aimed to improve the quality of discharge prescriptions (DPs) using indicators following admissions for IV antibiotics in pediatric CF patients.

Methods:
This project involved a longitudinal observational retrospective descriptive study followed by a longitudinal quasi-experimental prospective phase between January 2013 and December 2016 in CF patients admitted to a London Children’s Hospital. The CF pharmacist reviewed DPs. Six rights of medication administration were defined (6R): dose, drug, frequency, duration of treatment, pharmaceutical form, and route of administration. We classified ME according to 6R, including subtype of error: committed/omitted. We calculated quality indicators by dividing the number of each correct parameter defined by 6R by number of DPs. Retrospective results were used prospectively to describe and implement improvement strategies and safety actions.

Results:
The retrospective study phase included 42 CF children (100 hospital admissions and 1,343 drugs). The prospective phase included thirty-five children (55 admissions and 822 drugs). The total number of ME identified was 148 (78 committed; 70 omitted) in retrospective phase and 135 (19 committed; 116 omitted) in prospective phase. Quality indicators for drug and dose showed significant improvement after implementing safety strategies. The global quality indicator increased from 22% (retrospective) to 41.82% (prospective), but we did not achieve the previously defined quality standard value (50%).

Conclusions:
A retrospective review of DP by a CF Pharmacist identified failures in DP quality. Implementing improvement strategies improved prescribing. Integrating pharmacist within multidisciplinary team improves DP reducing errors.
Ten Years of Kidney Paired Donation at Mayo Clinic: The Benefits of Incorporating ABO/HLA Compatible Pairs
Authors: Basu Arpita , Prieto Mikel , Kosberg Catherine , Mai Martin L. , Khamash Hasan A. , Jadlowiec Caroline C. , Issa Naim S. , Dean Patrick G. , Lorenz Elizabeth C. , Stegall Mark D. , Schinstock Carrie A. 
Published: September 2019

Background.
We examined the 10-year experience of Mayo Clinic's kidney paired donation (KPD).We aimed to determine the benefits for the recipients of enrolled ABO/HLA compatible pairs and determine the factors associated with prolonged KPD waiting time.

Methods.
We performed a retrospective study of 332 kidney transplants facilitated by the Mayo 3-site KPD program from September 2007 to June 2018.

Results.
The median (interquartile range) time from KPD entry to transplantation was 89 days (42-187 days). The factors independently associated with receiving a transplant >3 months after KPD entry included recipient blood type O and calculated panel reactive antibodies ≥98%. Fifty-four ABO/HLA compatible pairs participated in KPD for the following reasons: cytomegalovirus mismatch (18.5% [10/54]), Epstein-Barr virus (EBV) mismatch (EBV) (9.3% [5/54]), age/size mismatch (51.9% [28/54]), or altruistic reasons (20.3% [11/54]). Cytomegalovirus and EBV mismatch were avoided in 90% (9/10) and 100% (5/5) of cases. Recipients who entered KPD for age/size mismatch and altruistic reasons received kidneys from donors with lower Living Kidney Donor Profile Index scores than their actual donor (median [interquartile range] 31.5 [12.3-47]; P < 0.001 and 26 (-1 to 46); P = 0.01 points lower, respectively). Median time to transplant from KPD entry for compatible pair recipients was 70 days (41-163 days), and 44.4% (24/54) of these transplants were preemptive. All chains/swaps incorporating compatible pairs included ABO/HLA incompatible pairs.

Conclusions.
KPD should be considered for all living donor/recipient pairs because the recipients of these pairs can derive personal benefit from KPD while increasing the donor pool for difficult to match pairs.
Serotonergic modulation of walking inDrosophila
Authors: Howard Clare E. , Chen Chin-Lin , Tabachnik Tanya , Hormigo Rick , Ramdya Pavan , Mann Richard S. 
Published: September 2019

AbstractTo navigate complex environments, animals must generate highly robust, yet flexible, locomotor behaviors. For example, walking speed must be tailored to the needs of a particular environment: Not only must animals choose the correct speed and gait, they must also rapidly adapt to changing conditions, and respond to sudden and surprising new stimuli. Neuromodulators, particularly the small biogenic amine neurotransmitters, allow motor circuits to rapidly alter their output by changing their functional connectivity. Here we show that the serotonergic system in the vinegar fly,Drosophilamelanogaster, can modulate walking speed in a variety of contexts and in response to sudden changes in the environment. These multifaceted roles of serotonin in locomotion are differentially mediated by a family of serotonergic receptors with distinct activities and expression patterns.
DirectMS1: MS/MS-free identification of 1000 proteins of cellular proteomes in 5 minutes
Authors: Ivanov Mark V. , Bubis Julia A. , Gorshkov Vladimir , Tarasova Irina A. , Levitsky Lev I. , Lobas Anna A. , Solovyeva Elizaveta M. , Pridatchenko Marina L. , Kjeldsen Frank , Gorshkov Mikhail V. 
Published: September 2019

AbstractProteome characterization relies heavily on tandem mass spectrometry (MS/MS) and is thus associated with instrumentation complexity, lengthy analysis time, and limited duty-cycle. It was always tempting to implement approaches which do not require MS/MS, yet, they were constantly failing in achieving meaningful depth of quantitative proteome coverage within short experimental times, which is particular important for clinical or biomarker discovery applications. Here, we report on the first successful attempt to develop a truly MS/MS-free and label-free method for bottom-up proteomics. We demonstrate identification of 1000 protein groups for a standard HeLa cell line digest using 5-minute LC gradients. The amount of loaded sample was varied in a range from 1 ng to 500 ng, and the method demonstrated 10-fold higher sensitivity compared with the standard MS/MS-based approach. Due to significantly higher sequence coverage obtained by the developed method, it outperforms all popular MS/MS-based label-free quantitation approaches.
Causal adaptation to visual input dynamics governs the development of complex cells in V1
Authors: Matteucci Giulio , Zoccolan Davide 
Published: September 2019

AbstractVisual perception relies on cortical representations of visual objects that remain relatively stable with respect to the variation in object appearance typically encountered during natural vision (e.g., because of position changes). Such stability, known as transformation tolerance, is built incrementally along the ventral stream (the cortical hierarchy devoted to shape processing), but early evidence of position tolerance is already found in primary visual cortex (V1) for complex cells1. To date, it remains unknown what mechanisms drive the development of this class of neurons, as well as the emergence of tolerance across the ventral stream. Leading theories suggest that tolerance is learned, in an unsupervised manner, either from the temporal continuity of natural visual experience2–10 or from the spatial statistics of natural scenes11,12. However, neither learning principle has been empirically proven to be at work in the postnatal developing cortex. Here we show that passive exposure to temporally continuous visual inputs during early postnatal life is essential for normal development of complex cells in rat V1. This was causally demonstrated by rearing newborn rats with frame-scrambled versions of natural movies, resulting in temporally unstructured visual input, but with unaltered, natural spatial statistics. This led to a strong reduction of the fraction of complex cells, which also displayed an abnormally fast response dynamics and a reduced ability to support stable decoding of stimulus orientation over time. Conversely, our manipulation did not prevent the development of simple cells, which showed orientation tuning and multi-lobed, Gabor-like receptive fields as sharp as those found in rats reared with temporally continuous natural movies. Overall, these findings causally implicate unsupervised temporal learning in the postnatal development of transformation tolerance but not of shape tuning, in agreement with theories that place the latter under the control of unsupervised adaptation to spatial, rather than temporal, image statistics13–16.
A small family business: synergistic and additive effects of the queen and the brood on worker reproduction in a primitively eusocial bee
Authors: Orlova Margarita , Starkey Jesse , Amsalem Etya 
Published: September 2019

AbstractThe mechanisms that maintain reproductive division of labor in social insects are still incompletely understood. Most studies focus on the relationship between adults, overlooking another important stakeholder in the game – the juvenile offspring. Recent studies from various social species show that not only the queen, but also the brood regulates reproductive division of labor between females, but how the two coordinate to maintain reproductive monopoly remained unexplored.Our study aims at disentangling the roles of the brood and the queen in regulating worker reproduction in primitively eusocial bees. We examined the effects induced by the brood and queen, separately and together, on the behavioral, physiological and brain gene expression of Bombus impatiens workers. We found that young larvae induce a releaser effect in workers, decreasing egg laying and aggressive behaviors, while the queen induces both releaser and primer effects, modifying worker aggressive and egg laying behavior and reproductive physiology. The expression of reproduction- and aggression-related genes was altered in the presence of both queen and brood, but the effect was stronger or the same in the presence of the queen.We identified two types of interactions between the queen and the brood in regulating worker reproduction: (1) synergistic interactions regulating worker physiology, where the combined effect of the queen and the brood was greater than each of them separately; (2) additive interactions regulating worker behavior, where the combined effects of the queen and the brood are the gross sum of their separated effects. In these interactions the brood acted in a manner similar to the queen but to a much smaller extent and improved the quality of the effect induced by the queen. Our results suggest that the queen and the brood of primitively eusocial bees coordinate synergistically, additively, and sometimes even redundantly to regulate worker behavior and reproduction, and the interaction between them exists in multiple regulatory levels.
Field manipulation of competition among hybrids reveals dynamic and highly stable features of a complex fitness landscape driving adaptive radiation
Authors: Martin Christopher H. , Gould Katelyn 
Published: September 2019

AbstractThe effect of the environment on fitness in natural populations is a fundamental question in evolutionary biology. However, experimental manipulations of environment and phenotype are rare. Thus, the relative importance of the competitive environment versus intrinsic organismal performance in shaping the location, height, and fluidity of fitness peaks and valleys remains largely unknown. We experimentally tested the effect of competitive environment on the fitness landscape driving the evolution of novelty in a sympatric adaptive radiation of a generalist and two trophic specialist pupfishes, a scale-eater and molluscivore, endemic to San Salvador Island, Bahamas. We manipulated phenotypes, by generating 2,611 F4/F5 lab-reared hybrids, and competitive environment, by altering frequencies of rare phenotypes between high- and low-frequency field enclosures, then tracked hybrid survival in two natural lake populations on San Salvador. We found no evidence of frequency-dependent effects on survival fitness landscapes, indicating robustness to the competitive environment. Although survival surfaces favored alternate phenotypes between lakes, joint fitness estimation across lake environments supported multiple fitness peaks for generalist and molluscivore phenotypes and a large fitness valley isolating the most divergent scale-eater phenotype, strikingly similar to a previous independent field experiment. The consistency of this complex fitness landscape across competitive environments, multivariate trait axes, and spatiotemporal heterogeneity provides surprising evidence of stasis in major features of fitness landscapes despite substantial environmental variance, possibly due to absolute biomechanical constraints on diverse prey capture strategies within this radiation. These results challenge competitive speciation theory and highlight the interplay between organism and environment underlying static and dynamic features of the adaptive landscape.
Deep learning for brains?: Different linear and nonlinear scaling in UK Biobank brain images vs. machine-learning datasets
Authors: Schulz Marc-Andre , Yeo B.T. Thomas , Vogelstein Joshua T. , Mourao-Miranada Janaina , Kather Jakob N. , Kording Konrad , Richards Blake , Bzdok Danilo 
Published: September 2019

AbstractIn recent years, deep learning has unlocked unprecedented success in various domains, especially in image, text, and speech processing. These breakthroughs may hold promise for neuroscience and especially for brain-imaging investigators who start to analyze thousands of participants. However, deep learning is only beneficial if the data have nonlinear relationships and if they are exploitable at currently available sample sizes. We systematically profiled the performance of deep models, kernel models, and linear models as a function of sample size on UK Biobank brain images against established machine learning references. On MNIST and Zalando Fashion, prediction accuracy consistently improved when escalating from linear models to shallow-nonlinear models, and further improved when switching to deep-nonlinear models. The more observations were available for model training, the greater the performance gain we saw. In contrast, using structural or functional brain scans, simple linear models performed on par with more complex, highly parameterized models in age/sex prediction across increasing sample sizes. In fact, linear models kept improving as the sample size approached ∼10,000 participants. Our results indicate that the increase in performance of linear models with additional data does not saturate at the limit of current feasibility. Yet, nonlinearities of common brain scans remain largely inaccessible to both kernel and deep learning methods at any examined scale.
Tracking infection dynamics at single-cell level reveals highly resolved expression programs of a large virus infecting algal blooms
Authors: Ku Chuan , Sheyn Uri , Sebé-Pedrós Arnau , Ben-Dor Shifra , Schatz Daniella , Tanay Amos , Rosenwasser Shilo , Vardi Assaf 
Published: September 2019

AbstractNucleocytoplasmic large DNA viruses have the largest genomes among all viruses and infect diverse eukaryotes across various ecosystems, but their expression regulation and infection strategies are not well understood. We profiled single-cell transcriptomes of the worldwide-distributed microalga Emiliania huxleyi and its specific coccolithovirus responsible for massive bloom demise. Heterogeneity in viral transcript levels detected among single cells was used to reconstruct the viral transcriptional trajectory and to map cells along a continuum of infection states. This enabled identification of novel viral genetic programs, which are composed of five kinetic classes with distinct promoter elements. The infection substantially changed the host transcriptome, causing rapid shutdown of protein-encoding nuclear transcripts at the onset of infection, while the plastid and mitochondrial transcriptomes persisted to mid- and late stages, respectively. Single-cell transcriptomics thereby opens the way for tracking host-pathogen infection dynamics at high resolution within microbial communities in the marine environment.
The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection
Authors: Giraud-Gatineau Alexandre , Coya Juan Manuel , Maure Alexandra , Biton Anne , Thomson Michael , Bernard Elliott M. , Gutierrez Maximiliano G. , Larrouy-Maumus Gérald , Brosch Roland , Gicquel Brigitte , Tailleux Ludovic 
Published: September 2019

AbstractAntibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed macrophages into potent bactericidal phagocytes. We found that 1,495 genes were differentially expressed in M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of genes involved in metabolism, lysosome biogenesis and activation. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including nitric oxide production, phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB (TFEB), involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections.
Parallel evolution of tobramycin resistance across species and environments
Authors: Scribner Michelle R. , Santos-Lopez Alfonso , Marshall Christopher W. , Deitrick Christopher , Cooper Vaughn S. 
Published: September 2019

AbstractAn important problem in evolution is identifying the genetic basis of how different species adapt to similar environments. Understanding how various bacterial pathogens evolve in response to antimicrobial treatment is a pressing example of this problem, where discovery of molecular parallelism could lead to clinically useful predictions. Evolution experiments with pathogens in environments containing antibiotics combined with periodic whole population genome sequencing can be used to characterize the evolutionary dynamics of the pathways to antimicrobial resistance. We separately propagated two clinically relevant Gram-negative pathogens,Pseudomonas aeruginosaandAcinetobacter baumannii, in increasing concentrations of tobramycin in two different environments each: planktonic and biofilm. Independent of the pathogen, populations adapted to tobramycin selection by parallel evolution of mutations infusA1, encoding elongation factor G, andptsP, encoding phosphoenolpyruvate phosphotransferase. As neither gene is a direct target of this aminoglycoside, both are relatively novel and underreported causes of resistance. Additionally, both species acquired antibiotic-associated mutations that were more prevalent in the biofilm lifestyle than planktonic, in electron transport chain components inA. baumanniiand LPS biosynthesis enzymes inP. aeruginosapopulations. Using existing databases, we discovered bothfusA1andptsPmutations to be prevalent in antibiotic resistant clinical isolates. Additionally, we report site-specific parallelism offusA1mutations that extend across several bacterial phyla. This study suggests that strong selective pressures such as antibiotic treatment may result in high levels of predictability in molecular targets of evolution despite differences between organisms’ genetic background and environment.