bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution Under Dietary Restriction Decouples Survival From Fecundity in Drosophila melanogaster Females
Authors: Zajitschek Felix , Georgolopoulos Grigorios , Vourlou Anna , Ericsson Maja , Zajitschek Susanne R K , Friberg Urban , Maklakov Alexei A 
Published: April 2018

AbstractOne of the key tenets of life-history theory is that reproduction and survival are linked and that they trade-off with each other. When dietary resources are limited, reduced reproduction with a concomitant increase in survival is commonly observed. It is often hypothesized that this dietary restriction effect results from strategically reduced investment in reproduction in favor of somatic maintenance to survive starvation periods until resources become plentiful again. We used experimental evolution to test this “waiting-for-the-good-times” hypothesis, which predicts that selection under sustained dietary restriction will favor increased investment in reproduction at the cost of survival because “good-times” never come. We assayed fecundity and survival of female Drosophila melanogaster fruit flies that had evolved for 50 generations on three different diets varying in protein content—low (classic dietary restriction diet), standard, and high—in a full-factorial design. High-diet females evolved overall increased fecundity but showed reduced survival on low and standard diets. Low-diet females evolved reduced survival on low diet without corresponding increase in reproduction. In general, there was little correspondence between the evolution of survival and fecundity across all dietary regimes. Our results contradict the hypothesis that resource reallocation between fecundity and somatic maintenance underpins life span extension under dietary restriction.
The Rapid Prediction of Carbapenem Resistance in Patients With Klebsiella pneumoniae Bacteremia Using Electronic Medical Record Data
Authors: Sullivan Timothy , Ichikawa Osamu , Dudley Joel , Li Li , Aberg Judith 
Published: April 2018

Abstract

Background
The administration of active antibiotics is often delayed in cases of carbapenem-resistant gram-negative bacteremia. Using electronic medical record (EMR) data to rapidly predict carbapenem resistance in patients with Klebsiella pneumoniae bacteremia could help reduce the time to active therapy.

Methods
All cases of Klebsiella pneumoniae bacteremia at Mount Sinai Hospital from September 2012 through September 2016 were included. Cases were randomly divided into a “training set” and a “testing set.” EMR data from the training set cases were reviewed, and significant risk factors for carbapenem resistance were entered into a multiple logistic regression model. Performance was assessed by repeated K-fold cross-validation and by applying the training set model to the testing set. All cases were also reviewed to determine the time to effective antibiotic therapy.

Results
A total of 613 cases of Klebsiella pneumoniae bacteremia were included, 61 (10%) of which were carbapenem-resistant. The training and testing sets consisted of 460 and 153 cases, respectively. The regression model derived from the training set correctly predicted 73% of carbapenem-resistant cases and 59% of carbapenem-susceptible cases in the testing set (sensitivity, 73%; specificity, 59%; positive predictive value, 16%; negative predictive value, 95%). The mean area under the receiver operator characteristic curve of the K-fold cross-validation repeats was 0.731. Patients with carbapenem-resistant infections received active antibiotics significantly later than those with susceptible infections (40.4 hours vs 9.6 hours, P &lt; .0001).

Conclusions
A multiple logistic regression model using EMR data can generate rapid, sensitive predictions of carbapenem resistance in patients with Klebsiella pneumoniae bacteremia, which could help shorten the time to effective therapy in these cases.
Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation
Authors: Payne Daniel C , Biggs Holly M , Al-Abdallat Mohammad Mousa , Alqasrawi Sultan , Lu Xiaoyan , Abedi Glen R , Haddadin Aktham , Iblan Ibrahim , Alsanouri Tarek , Al Nsour Mohannad , Sheikh Ali Sami , Rha Brian , Trivedi Suvang U , Rasheed Mohammed Ata Ur , Tamin Azaibi , Lamers Mart M , Haagmans Bart L , Erdman Dean D , Thornburg Natalie J , Gerber Susan I 
Published: April 2018

Abstract

Background
An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology.

Methods
We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization.

Results
Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive.

Conclusions
The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.
The Hospital Antimicrobial Use Process: From Beginning to End
Authors: Truong William R , Yamaki Jason 
Published: April 2018

Abstract
Hospital antimicrobial stewardship (AMS) programs are responsible for ensuring that all antimicrobials are utilized in the most appropriate and safe manner to improve patient outcomes, prevent adverse drug reactions, and prevent the development of antimicrobial resistance. This Perspectives article outlines the hospital antimicrobial use process (AUP), the foundational system that ensures that all antimicrobials are utilized in the most appropriate and safe manner. The AUP consists of the following steps: antimicrobial ordering, order verification, preparation and delivery, administration, monitoring, and discharge prescribing. AMS programs should determine how each step contributes to how an antimicrobial is used appropriately or inappropriately at their institution. Through this understanding, AMS programs can integrate stewardship activities at each step to ensure that every opportunity is taken to optimize antimicrobial use during a patient’s treatment course. Hence, approaching AMS through the framework of a hospital’s AUP is essential to improving appropriate antimicrobial use.
Recovery after stroke: not so proportional after all?
Authors: Hope Thomas M.H. , Friston Karl , Price Cathy J. , Leff Alex P. , Rotshtein Pia , Bowman Howard 
Published: April 2018

ABSTRACTBackgroundThe proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. Reports that the rule can be used to predict recovery, extraordinarily accurately, are rapidly accumulating. Here, we show that the rule may not be as powerful as it seems.MethodsWe provide a formal analysis of the relationship between baseline scores (X), outcomes (Y) and recovery (Y-X), to highlight the shortcomings of the proportional recovery rule, and illustrate those problems with simulations in which synthetic recovery data are derived from different types of recovery processes.FindingsWhen the correlation between baseline scores and recovery is stronger than that between baselines scores and outcomes, the former can create an inflated impression of how predictable outcomes really are given baseline scores. This often happens when outcomes are less variable than baseline scores, as is common in empirical studies of recovery after stroke. Moreover, we cannot use the results of these correlations to distinguish proportional recovery from recovery which is either not consistently proportional, or not proportional at all.InterpretationAnalyses relating baseline scores to subsequent change are a minefield: our formal analysis applies as consistently outside the area of stroke as it does within it. One implication of our analysis is that the proportional recovery rule is not as predictive of real recovery after stroke as recent empirical studies suggest. Another is that different analytical methods will be required to ascertain whether recovery is even proportional at all.
AAV-mediated progranulin delivery to a mouse model of progranulin deficiency causes T cell-mediated hippocampal degeneration
Authors: Amado Defne A. , Rieders Julianne M. , Diatta Fortunay , Hernandez-Con Pilar , Singer Adina , Zhang Junxian , Lancaster Eric , Davidson Beverly L. , Chen-Plotkin Alice S. 
Published: April 2018

AbstractAdeno-associated virus (AAV)-mediated gene replacement is emerging as a safe and effective means of correcting single-gene mutations, and use of AAV vectors for treatment of diseases of the CNS is increasing. AAV-mediated progranulin gene (GRN) delivery has been proposed as a treatment for GRN-deficient frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL), and two recent studies using focal intraparenchymal AAV-Grn delivery to brain have shown moderate success in histopathologic and behavioral rescue in mouse FTD models. Here, we used AAV9 to deliver GRN to the lateral ventricle to achieve widespread expression in the Grn null mouse brain. We found that despite a global increase in progranulin throughout many brain regions, overexpression of GRN resulted in dramatic and selective hippocampal toxicity and degeneration affecting both neurons and glia. Histologically, hippocampal degeneration was preceded by T cell infiltration and perivascular cuffing, suggesting an inflammatory component to the ensuing neuronal loss. GRN delivery with an ependymal-targeting AAV for selective secretion of progranulin into the cerebrospinal fluid (CSF) similarly resulted in T cell infiltration as well as ependymal hypertrophy. Interestingly, overexpression of GRN in wild-type animals also provoked T cell infiltration. These results call into question the safety of GRN overexpression in the CNS, with evidence for both a region-selective immune response and cellular proliferative response following GRN gene delivery. Our results highlight the importance of careful consideration of target gene biology and cellular response to overexpression in relevant animal models prior to progressing to the clinic.Significance StatementGene therapies using adeno-associated viral (AAV) vectors show great promise for many human diseases, including diseases that affect the central nervous system (CNS). Frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL) are neurodegenerative diseases resulting from loss of one or both copies of the gene encoding progranulin (GRN), and gene replacement has been proposed for these currently untreatable disorders. Here, we used two different AAV vectors to induce widespread brain GRN expression in mice lacking the gene, as well as in wild-type mice. Unexpectedly, GRN overexpression resulted in T cell infiltration, followed by marked hippocampal neurodegeneration. Our results call into question the safety of GRN overexpression in the CNS, with wider implications for development of CNS gene therapies.
Discovery of a Streptococcus pneumoniae serotype 33F capsular polysaccharide locus that lacks wcjE and contains a wcyO pseudogene
Authors: Manna Sam , Dunne Eileen M. , Ortika Belinda D. , Pell Casey L. , Kama Mike , Russell Fiona M. , Mungun Tuya , Mulholland E. Kim , Hinds Jason , Satzke Catherine 
Published: April 2018

AbstractObjectivesAs part of large on-going vaccine impact studies in Fiji and Mongolia, we identified 25/2750 (0.9%) of nasopharyngeal swabs by microarray that were positive for Streptococcus pneumoniae contained pneumococci with a divergent 33F capsular polysaccharide locus (designated ‘33F-1’). We investigated the 33F-1 capsular polysaccharide locus to better understand the genetic variation and its potential impact on serotyping results.MethodsWhole genome sequencing was conducted on ten 33F-1 pneumococcal isolates. Initially, sequence reads were used for molecular serotyping by PneumoCaT. Phenotypic typing of 33F-1 isolates was then performed using the Quellung reaction and latex agglutination. Genome assemblies were used in phylogenetic analyses of each gene in the capsular locus to investigate genetic divergence.ResultsAll ten pneumococcal isolates with the 33F-1 cps locus typed as 33F by Quellung and latex agglutination. Unlike the reference 33F capsule locus sequence, DNA microarray and PneumoCaT analyses found that 33F-1 pneumococci lack the wcjE gene, and instead contain wcyO with a frameshift mutation. Phylogenetic analyses found the wzg, wzh, wzd, wze, wchA, wciG and glf genes in the 33F-1 cps locus had higher DNA sequence similarity to homologues from other serotypes than to the 33F reference sequence.ConclusionsWe have discovered a novel genetic variant of serotype 33F, which lacks wcjE and contains a wcyO pseudogene. This finding adds to the understanding of molecular epidemiology of pneumococcal serotype diversity, which is poorly understood in low and middle-income countries.
Disturbance macroecology: integrating disturbance ecology and macroecology with different-age post-fire stands of a closed-cone pine forest
Authors: Newman Erica A. , Wilber Mark Q. , Kopper Karen E. , Moritz Max A. , Falk Donald A. , McKenzie Don , Harte John 
Published: April 2018

AbstractMacroecological studies have generally restricted their scope to relatively steady-state systems, and as a result, how biodiversity and abundance metrics are expected to scale in disturbance-dependent ecosystems is unknown. We examine macroecological patterns in a fire-dependent forest of Bishop pine (Pinus muricata). We target two different-aged stands in a stand-replacing fire regime, one a characteristically mature stand with a diverse understory, and one more recently disturbed by a stand-replacing fire (17 years prior to measurement). We compare the stands using macroecological metrics of species richness, abundance and spatial distributions that are predicted by the Maximum Entropy Theory of Ecology (METE), an information-entropy based theory that has proven highly successful in predicting macroecological metrics across a wide variety of systems and taxa. Ecological patterns in the mature stand more closely match METE predictions than do data from the recently disturbed stand. This suggests METE’s predictions are more robust in late-successional, slowly changing, or steady-state systems than those in rapid flux with respect to species composition, abundances, and organisms’ sizes. Our findings highlight the need for a macroecological theory that incorporates natural disturbance and other ecological perturbations into its predictive capabilities, because most natural systems are not in a steady state.
Morphological variation and strain identification of insects using wings and I3S
Authors: Vyas-Patel Nayna , Mumford John D 
Published: April 2018

AbstractNovel insect identification techniques often lead to speculation on whether the method could cope with any intraspecific variation that might occur in a species. Using I3S Classic (Interactive Individual Identification System, Classic) and images of mosquito wings, different mosquito strains were tested with a copy of the strain present or absent from the database which contained images of other strains of the test species. When a wing image of the exact species, strain and sex was present in the database, there was 100% (or near 100%) retrieval of the correct species and strain at rank one. When the exact strain was absent from the database, but other strains of the same species were present, the retrieval rates at rank one were again high (100%) in the majority of cases and when they were not, the correct species was generally retrieved at rank two. Out of 40 different species and strains tested, only three were significantly different at rank one when the exact strain was absent from the database. In general, images of field strains selected for each other and therefore were similar to each other in greater numbers and instances than for the laboratory strains tested. When a copy of a strain was absent from the database, but other strains/sibling species were present, I3S retrieved the correct strains/sibling species at rank one in the majority of cases. In the one case of transgenic mosquitoes tested, I3S could reliably be used to identify transgenic mosquitoes from the parent stock as they were retrieved 100% at rank one when both the transgenic and unmodified parent strains were present in the database. This indicates the potential of using I3S to distinguish transgenic or other selectively bred strains from a parent strain, also selectively bred and wild mosquitoes, at least in the first phase after field release. Similarly, hybrid strains, sibling species and members of species complexes as in theAnopheles gambiaespecies complex could also be correctly identified when copies of all the relevant species/strains/siblings were in the database. This contradicts the belief that only molecular characterisation could separateA. gambiaes.s. fromA. coluzzii, orA. arabiensis; I3S could accurately separate them all. I3S worked as it was set up to do, retrieving closely resembling images of the test insects from the database and ranking them in order of similarity. Dealing with any intraspecific variation was therefore not an issue if the software (I3S) was used systematically. I3S complements molecular and traditional taxonomic methods for species identification and the separation of sibling complexes and strains. In future, it should become the norm to maintain databases of insect wings and other body part images for use in image recognition.
Studies on squalene biosynthesis and the standardization of its extraction methodology fromSaccharomyces cerevisiae
Authors: Paramasivan Kalaivani , Rajagopal Kavya , Mutturi Sarma 
Published: April 2018

AbstractAimsThe present work focuses on studies on squalene improvement in theS. cerevisiaeand development of squalene extraction procedure based on mechanical disruption of cells.Methods and ResultsIn this study, a homogenization-based extraction method was developed and was compared to five conventional methods of squalene extraction. Squalene recovered from this novel procedure gave 3.5– fold, 10-fold, 16-fold and 8.1-fold higher yield than standard procedures viz., saponification with 60% KOH, acidic saponification, saponification with 18% KOH and glass beads method, respectively. Furthermore, this procedure has been evaluated on laboratoryS. cerevisiaestrains such as BY4742 and CEN.PK2-1C (native), deletion strains (ERG6andERG11) andtHMGloverexpressedS. cerevisiaestrains. When sonication method of cell lysis was replaced with homogenization it was found that the yields were significantly higher and reached a value of 9 mg/g DCW in case of BY4742. In addition, Squalene yield in ergosterol mutant strains has been analyzed and was found to be 1.8-fold and 3.4-fold higher inERG6andERG11deletion strains, respectively, than BY4742. Squalene was also found to be higher at the optimized temperature of 30°C and pH 6.0. Furthermore, tolerance ofS. cerevisiaeto external squalene at various concentration has been carried and found that the organism was tolerant up to 25 g/L of squalene.ConclusionsHomogenization based mechanical disruption was observed to yield higher squalene and the SEM analysis corroborates these findings. The synergistic effect ofERG11downregulation andtHMG1over-expression has led to significant increase in squalene yield.Significance and Impact of the StudySonication and homogenization has been used as a cell-disruption method for the first time in squalene extraction and squalene yield from homogenization method of cell lysis in BY4742 has been found to be 9 mg/g DCW which is the highest reported so far in a wild-type strain.
Multi-omics approach identifies novel pathogen-derived prognostic biomarkers in patients withPseudomonas aeruginosabloodstream infection
Authors: Willmann Matthias , Götting Stephan , Bezdan Daniela , Maček Boris , Velic Ana , Marschal Matthias , Vogel Wichard , Flesch Ingo , Markert Uwe , Schmidt Annika , Kübler Pierre , Haug Maria , Javed Mumina , Jentzsch Benedikt , Oberhettinger Philipp , Schütz Monika , Bohn Erwin , Sonnabend Michael , Klein Kristina , Autenrieth Ingo B , Ossowski Stephan , Schwarz Sandra , Peter Silke 
Published: April 2018

AbstractPseudomonas aeruginosais a human pathogen that causes health-care associated blood stream infections (BSI). AlthoughP. aeruginosaBSI are associated with high mortality rates, the clinical relevance of pathogen-derived prognostic biomarker to identify patients at risk for unfavorable outcome remains largely unexplored. We found novel pathogen-derived prognostic biomarker candidates by applying a multi-omics approach on a multicenter sepsis patient cohort. Multi-level Cox regression was used to investigate the relation between patient characteristics and pathogen features (2298 accessory genes, 1078 core protein levels, 107 parsimony-informative variations in reported virulence factors) with 30-day mortality. Our analysis revealed that presence of thehelPgene encoding a putative DEAD-box helicase was independently associated with a fatal outcome (hazard ratio 2.01, p = 0.05).helPis located within a region related to the pathogenicity island PAPI-1 in close proximity to apilgene cluster, which has been associated with horizontal gene transfer. BesideshelP, elevated protein levels of the bacterial flagellum protein FliL (hazard ratio 3.44, p < 0.001) and of a bacterioferritin-like protein (hazard ratio 1.74, p = 0.003) increased the risk of death, while high protein levels of a putative aminotransferase were associated with an improved outcome (hazard ratio 0.12, p < 0.001). The prognostic potential of biomarker candidates and clinical factors was confirmed with different machine learning approaches using training and hold-out datasets. ThehelPgenotype appeared the most attractive biomarker for clinical risk stratification due to its relevant predictive power and ease of detection.