bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and Outcomes of Staphylococcus aureus Bacteriuria: A Population-based Study
Authors: Stokes William , Parkins Michael D , Parfitt Elizabeth C T , Ruiz Juan C , Mugford Gerry , Gregson Daniel B 
Published: November 2018

Abstract

Background
Staphylococcus aureus bacteriuria (SABU) may represent multiple processes ranging from asymptomatic colonization to a marker of S. aureus bacteremia (SAB). Our objective was to describe SABU at a population-based level and determine patient characteristics associated with SAB.

Methods
A retrospective study was performed using electronic databases. All urine cultures positive for S. aureus between 2010 and 2013 within the Calgary Health Zone were included. Patient characteristics were compared among patients with and without SAB and risk factors identified using multiple logistic regression modeling.

Results
A total of 2540 urine cultures positive for S. aureus from 2054 patients were analyzed. The incidence of SABU was greatest among geriatric males with multiple comorbidities. SAB occurred in 175 (6.9%) of SABU patients. Those with SAB were more likely to be hospitalized, male, have a recent urinary procedure, have pure S. aureus culture in urine, and have laboratory findings suggesting systemic infection. Patients with isolated SABU were more likely to be ≥65 years, have dementia, and have abnormal urinalyses with pyuria and urine nitrites. In-hospital mortality in patients with SABU and SABU+SAB was 9.2% and 17.5%, respectively. Patients with SABU detected ≥48 hours before SAB had the highest risk of death.

Conclusions
Less than 7% of patients with SABU have or will develop SAB. Characteristics associated with SABU were identified that established higher risk for systemic infection. Investigating SABU patients with these characteristics for systemic infection is warranted because a delay in diagnosis is associated with increased mortality.
Thymus machinery for T-cell selection
Authors: Kondo Kenta , Ohigashi Izumi , Takahama Yousuke 
Published: November 2018

AbstractAn immunocompetent and self-tolerant pool of naive T cells is formed in the thymus through the process of repertoire selection. T cells that are potentially capable of responding to foreign antigens are positively selected in the thymic cortex and are further selected in the thymic medulla to help prevent self-reactivity. The affinity between T-cell antigen receptors expressed by newly generated T cells and self-peptide–major histocompatibility complexes displayed in the thymic microenvironments plays a key role in determining the fate of developing T cells during thymic selection. Recent advances in our knowledge of the biology of thymic epithelial cells have revealed unique machinery that contributes to positive and negative selection in the thymus. In this article, we summarize recent findings on thymic T-cell selection, focusing on the machinery unique to thymic epithelial cells.
Birth weight is not causally associated with adult asthma: results from instrumental variable analyses
Authors: Zeng Ping , Yu Xinghao , Zhou Xiang 
Published: November 2018

AbstractThe association between lower birth weight and childhood asthma is well established by observational studies. However, it remains unclear whether the influence of lower birth weight on asthma can persist into adulthood. Here, we conducted a Mendelian randomization analysis to assess the causal relationship of birth weight on the risk of adult asthma. Specifically, we carefully selected genetic instruments based on summary statistics obtained from large-scale genome-wide association meta-analyses of birth weight (up to ~160,000 individuals) and adult asthma (up to ~62,000 individuals). We performed Mendelian randomization using two separate approaches: a genetic risk score approach and a two-sample inverse-variance weighted (IVW) approach. With 37 genetic instruments for birth weight, we estimated the causal effect per one standard deviation (SD) change of birth weight to be an odds ratio (OR) of 1.00 (95% CI 0.98~1.03, p=0.737) using the genetic risk score method. We did not observe nonlinear relationship or gender difference for the estimated causal effect. In addition, with the IVW method, we estimated the causal effect of birth weight on adult asthma was observed (OR=1.02, 95% CI 0.84~1.24, p=0.813). Additionally, the iMAP method provides no additional genome-wide evidence supporting the causal effects of birth weight on adult asthma. The result of the IVW method was robust against various sensitivity analyses, and MR-PRESSO and the Egger regression showed that no instrument outliers and no horizontal pleiotropy were likely to bias the results. Overall, this Mendelian randomization study provides no evidence for the fetal origins of diseases hypothesis for adult asthma, implying that the impact of birth weight on asthma in years of children and adolescents does not persist into adult and previous findings may be biased by confounders.
Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide
Authors: Dingens Adam S. , Arenz Dana , Overbaugh Julie , Bloom Jesse D. 
Published: November 2018

AbstractResistance to enfuvirtide, the only clinically approved HIV-1 entry inhibitor, has primarily been mapped to the binding site in the N-terminal heptad repeat (NHR) of the Env transmembrane domain and a limited number of allosteric sites. To better delineate the genotypic determinants of resistance, we used deep mutational scanning to quantify how all mutations to HIV-1 Env affect enfuvirtide sensitivity. We identified numerous additional resistance mutations in the NHR and other regions of Env, including the co-receptor binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and can inform clinical monitoring of patients.
Spatial scale moderates the shape of the biodiversity-disease relationship
Authors: Halliday Fletcher W. , Rohr Jason R. 
Published: November 2018

AbstractDiverse host communities commonly inhibit the spread of parasites in studies at small and intermediate scales, leading some to suggest that conserving biodiversity could help control infectious diseases. However, the generality of this “dilution effect” remains controversial. First, most studies assume a linear, monotonic relationship between biodiversity and disease, though the actual shape is unknown. Second, most studies are conducted at a single spatial scale, though biotic interactions are often-scale-dependent, thus spatial scale might determine the direction of biodiversity-disease relationships. Third, most studies focus only on a small range of possible diversity levels, though the direction of biodiversity-disease relationships may change outside of this range. By analyzing 231 biodiversity-disease relationships on 77 parasite species, we provide broad evidence that biodiversity-disease relationships are generally non-linear and moderated by spatial scale; biodiversity generally inhibits disease at local scales (<100 km2) and amplifies disease at regional scales (>1,000,000 km2). These effects did not depend on any tested host, parasite, or study characteristics, though the spatial scale of a study was often related to study design and parasite type, highlighting the need for additional multiscale research. Few studies were missing substantial data at low diversity, but missing data at low diversity could result in underreporting of amplification. Experiments might be missing data at high diversity, which could result in underreporting of dilution. Despite context-dependence in biodiversity-disease relationships, most conservation is implemented at local scales where biodiversity appears to inhibit disease and thus these results suggest that local conservation actions could reduce disease risk.Significance statementIt has been suggested that diverse ecological communities limit disease spread, but the generality of this pattern is contentious. Therefore, the degree to which biodiversity conservation can limit harmful epidemics remains unresolved. We address this fundamental question by analyzing 231 published relationships between biodiversity and disease. We find evidence that most biodiversity-disease relationships are nonlinear and scale-dependent with biodiversity generally associated with reduced disease at small and intermediate scales, but increased disease at large scales. Moreover, these results were generally robust to missing data at low and high biodiversity levels and variation in host, parasite, and study characteristics. This suggests that conservation efforts aimed at reducing the impacts of human and wildlife diseases will be most successful at local scales.
Tracing diagnosis trajectories over millions of inpatients reveal an unexpected association between schizophrenia and rhabdomyolysis
Authors: Paik Hyojung , Kan Matthew J. , Rappoport Nadav , Hadley Dexter , Sirota Marina , Chen Bin , Manber Udi , Cho Seong Beom , Butte Atul J. 
Published: November 2018

AbstractWhile it has been technically feasible to create longitudinal representations of individual health at a nationwide scale, the use of these techniques to identify novel disease associations for the risk stratification of patients has had limited success. Here, we created a large-scale US longitudinal disease network of traced readmission patterns (i.e., disease trajectories), merging data from over 10.4 million inpatients from 350 California hospitals through the Healthcare Cost and Utilization Project between 1980 and 2010. We were able to create longitudinal representations of disease progression mapping over 300 common diseases, including the well-known complication of heart failure after acute myocardial infarction. Surprisingly, out of these generated disease trajectories, we discovered an unknown association between schizophrenia, a chronic mental disorder, and rhabdomyolysis, a rare disease of muscle breakdown. It was found that 92 of 3674 patients (2.5%) with schizophrenia were readmitted for rhabdomyolysis (relative risk, 2.21 [1.80–2.71, confidence interval = 0.95] P-value 9.54E-15), which has a general population incidence of 1 in 10,000. We validated this association using independent electronic health records from over 830,000 patients treated over seven years at the University of California, San Francisco (UCSF) medical center. A case review of 29 patients at UCSF who were treated for schizophrenia and who went on to develop rhabdomyolysis demonstrated that the majority of cases (62%) are idiopathic, which suggests a biological connection between these two diseases. Together, these findings demonstrate the power of using public disease registries in combination with electronic medical records to discover novel disease associations.One Sentence SummaryBased on the longitudinal health records from millions of California inpatient discharges, we created a temporal network that enabled us to understand statewide patterns of hospital readmissions, which led to the novel finding that hospitalization for schizophrenia is significantly associated with rehospitalization for rhabdomyolysis.
On the objectivity, reliability, and validity of deep learning enabled bioimage analyses
Authors: Segebarth Dennis , Griebel Matthias , Stein Nikolai , von Collenberg Cora R. , Martin Corinna , Fiedler Dominik , Comeras Lucas B. , Sah Anupam , Schoeffler Victoria , Lüffe Theresa , Dürr Alexander , Gupta Rohini , Sasi Manju , Lillesaar Christina , Lange Maren D. , Tasan Ramon O. , Singewald Nicolas , Pape Hans-Christian , Flath Christoph M. , Blum Robert 
Published: November 2018

AbstractFluorescent labeling of biomolecules is widely used for bioimage analyses throughout the life sciences. Recent advances in deep learning (DL) have opened new possibilities to scale the image analysis processes through automation. However, the annotation of fluorescent features with a low signal-to-noise ratio is frequently based on subjective criteria. Training on subjective annotations may ultimately lead to biased DL models yielding irreproducible results. An end-to-end analysis process that integrates data annotation, ground truth estimation, and model training can mitigate this risk. To highlight the importance of this integrated process, we compare different DL-based analysis approaches. Based on data from different laboratories, we show that ground truth estimation from multiple human annotators is indispensable to establish objectivity in fluorescent feature annotations. We demonstrate that ensembles of multiple models trained on the estimated ground truth establish reliability and validity. Our research provides guidelines for reproducible and transparent bioimage analyses using DL methods.
A clinal polymorphism in the insulin signaling transcription factorfoxocontributes to life-history adaptation inDrosophila
Authors: Durmaz Esra , Rajpurohit Subhash , Betancourt Nicolas , Fabian Daniel K. , Kapun Martin , Schmidt Paul , Flatt Thomas 
Published: November 2018

AbstractA fundamental aim of adaptation genomics is to identify polymorphisms that underpin variation in fitness traits. InD. melanogasterlatitudinal life-history clines exist on multiple continents and make an excellent system for dissecting the genetics of adaptation. We have previously identified numerous clinal SNPs in insulin/insulin-like growth factor signaling (IIS), a pathway known from mutant studies to affect life history. However, the effects of natural variants in this pathway remain poorly understood. Here we investigate how two clinal alternative alleles atfoxo, a transcriptional effector of IIS, affect fitness components (viability, size, starvation resistance, fat content). We assessed this polymorphism from the North American cline by reconstituting outbred populations, fixed for either the low- or high-latitude allele, from inbred DGRP lines. Since diet and temperature modulate IIS, we phenotyped alleles across two temperatures (18°C, 25°C) and two diets differing in sugar source and content. Consistent with clinal expectations, the high-latitude allele conferred larger body size and reduced wing loading. Alleles also differed in starvation resistance and expression ofInR, a transcriptional target of FOXO. Allelic reaction norms were mostly parallel, with few GxE interactions. Together, our results suggest that variation in IIS makes a major contribution to clinal life-history adaptation.
Overly strong priors for socially meaningful visual signals in psychosis proneness
Authors: Stuke Heiner , Kress Elisabeth , Weilnhammer Veith Andreas , Sterzer Philipp , Schmack Katharina 
Published: November 2018

ABSTRACTPredictive coding accounts of psychosis state that an overweighing of high-level priors relative to sensory information may lead to the misperception of meaningful signals underlying the experience of auditory hallucinations and delusions. However, it is currently unclear whether the hypothesized overweighing of priors (1) represents a pervasive alteration that also affects the visual modality, and, (2) takes already effect at early automatic processing stages.Here, we addressed these questions by studying visual perception of socially meaningful stimuli in healthy individuals with varying degrees of psychosis proneness (n=39). In a first task, we quantified participants’ prior for detecting faces in visual noise. In a second task, we measured participants’ prior for detecting direct gaze stimuli that were rendered invisible by continuous flash suppression. We found that the prior for detecting faces in noise correlated with hallucination proneness (rho=0.50, p=0.001) as well as delusion proneness (rho=0.44, p=0.005). Similarly, the prior for detecting invisible direct gaze was significantly associated with hallucination proneness (rho = 0.42, p = 0.010) and trend-wise with delusion proneness (rho = 0.29, p = 0.087). Our results provide evidence for the idea that overly strong high-level priors for automatically detecting socially meaningful stimuli might constitute a generic processing alteration in psychosis.
A spatial code in the dorsal lateral geniculate nucleus
Authors: Hok Vincent , Jacob Pierre-Yves , Bordiga Pierrick , Truchet Bruno , Poucet Bruno , Save Etienne 
Published: November 2018

AbstractSince their discovery in the early ‘70s1, hippocampal place cells have been studied in numerous animal and human spatial memory paradigms2–4. These pyramidal cells, along with other spatially tuned types of neurons (e.g. grid cells, head direction cells), are thought to provide the mammalian brain a unique spatial signature characterizing a specific environment, and thereby a memory trace of the subject’s place5. While grid and head direction cells are found in various brain regions, only few hippocampal-related structures showing ‘place cell’-like neurons have been identified6,7, thus reinforcing the central role of the hippocampus in spatial memory. Concurrently, it is increasingly suggested that visual areas play an important role in spatial cognition as recent studies showed a clear spatial selectivity of visual cortical (V1) neurons in freely moving rodents8–10. We therefore thought to investigate, in the rat, such spatial correlates in a thalamic structure located one synapse upstream of V1, the dorsal Lateral Geniculate Nucleus (dLGN), and discovered that a substantial proportion (ca. 30%) of neurons exhibits spatio-selective activity. We found that dLGN place cells maintain their spatial selectivity in the absence of visual inputs, presumably relying on odor and locomotor inputs. We also found that dLGN place cells maintain their place selectivity across sessions in a familiar environment and that contextual modifications yield separated representations. Our results show that dLGN place cells are likely to participate in spatial cognition processes, creating as early as the thalamic stage a comprehensive representation of one given environment.
Increased and decreased superficial white matter structural connectivity in schizophrenia and bipolar disorder
Authors: Ji Ellen , Guevara Pamela , Guevara Miguel , Grigis Antoine , Labra Nicole , Sarrazin Samuel , Hamdani Nora , Bellivier Frank , Delavest Marine , Leboyer Marion , Tamouza Ryad , Poupon Cyril , Mangin Jean-François , Houenou Josselin 
Published: November 2018

AbstractSchizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes”, with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from post-mortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labelling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.
Consensus clustering of herpesvirus protein interaction networks provides insights into their evolutionary relationship with bacteriophages
Authors: Hernández Durán Anna , Greco Todd M. , Vollmer Benjamin , Cristea Ileana M. , Grünewald Kay , Topf Maya 
Published: November 2018

AbstractInfections with human herpesviruses are ubiquitous and a public health concern worldwide. Current treatments reduce the morbidity of some manifested symptoms but neither remove the viral reservoir from the infected host nor protect from the recurrent symptom outbreaks that characterize herpetic infections. The difficulty in therapeutically tackling these viral systems stems in part from their remarkably large proteomes and the complex networks of physical and functional associations that they tailor. This study presents our efforts to unravel the complexity of the interactome of herpes simplex virus type 1 (HSV1), the prototypical herpesvirus species. Inspired by our previous work, we present an improved computational pipeline for the protein-protein interaction (PPI) network reconstruction in HSV1, combining both experimentally supported and bioinformatic predictions. Our newly-developed consensus clustering approach allows us to extend the analysis beyond binary physical interactions and reveals higher order functional associations including that of pUS10 with capsid proteins. In-depth bioinformatics sequence analysis unraveled structural features of this 34-36 kDa protein reminiscent of those observed in some capsid-associated proteins in tailed bacteriophages, with which herpesviruses are thought to share a common ancestry. This suggests that pUS10 could represent an evolutionary vestige between these two viral lineages. Using immunoaffinity purification-mass spectrometry we found that pUS10 specifically co-isolated with the inner tegument protein pUL37, which binds cytosolic capsids, contributing to initial tegumentation and eventual virion maturation. In summary, this study unveils new insights at both the system and molecular levels that can help better understand the complexity behind herpesvirus infections.
Dimensional Anhedonia and the Adolescent brain: Reward and Aversion Anticipation, Effort and Consummation: Anhedonia in adolescent depression
Authors: Rzepa Ewelina , McCabe Ciara 
Published: November 2018

AbstractGiven the heterogeneity of depression the Research Domain Criteria Framework suggests a dimensional approach to understanding the nature of mental health and illness. Neural reward function has been suggested as underpinning the symptom of anhedonia in depression but less is known about how anhedonia is related to aversion processing. We examined how anhedonia relates to neural activity during reward and aversion processing in adolescents and emerging adults (N=84) in the age range 13-21yrs. Using a dimensional approach we examined how anhedonia and depression severity correlated with an fMRI task measuring anticipation, effort and consummation of reward and aversion. We show for the first time that the dimensional experience of anhedonia correlated with neural responses during effort to avoid aversion in the precuneus with a trend in the insula and during aversive consummation in the caudate. Using a categorical approach we also examined how the neural responses during each phase of the task differed in those with depression symptoms compared to healthy controls. We found participants with depression symptoms invested less physical effort to gain reward than controls and had blunted neural anticipation of reward and aversion in the precuneus, insula, and prefrontal cortex and blunted neural effort for reward in the putamen. This work highlights blunted neural responses to reward and aversion in depression and how anticipatory and consummatory anhedonia may be enhanced via dysfunctional neural processing of aversion. Future work will assess if these neural mechanisms can be used to predict blunted behavioural approach to reward and avoidance of negative experiences in adolescents at risk of depression.