bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway
Authors: Liang Xue-hai , Nichols Joshua G , Hsu Chih-Wei , Vickers Timothy A , Crooke Stanley T 
Published: June 2019

Abstract
Antisense technology can reduce gene expression via the RNase H1 or RISC pathways and can increase gene expression through modulation of splicing or translation. Here, we demonstrate that antisense oligonucleotides (ASOs) can reduce mRNA levels by acting through the no-go decay pathway. Phosphorothioate ASOs fully modified with 2′-O-methoxyethyl decreased mRNA levels when targeted to coding regions of mRNAs in a translation-dependent, RNase H1-independent manner. The ASOs that activated this decay pathway hybridized near the 3′ end of the coding regions. Although some ASOs induced nonsense-mediated decay, others reduced mRNA levels through the no-go decay pathway, since depletion of PELO/HBS1L, proteins required for no-go decay pathway activity, decreased the activities of these ASOs. ASO length and chemical modification influenced the efficacy of these reagents. This non-gapmer ASO-induced mRNA reduction was observed for different transcripts and in different cell lines. Thus, our study identifies a new mechanism by which mRNAs can be degraded using ASOs, adding a new antisense approach to modulation of gene expression. It also helps explain why some fully modified ASOs cause RNA target to be reduced despite being unable to serve as substrates for RNase H1.
Coding palindromes in mitochondrial genes of Nematomorpha
Authors: Mikhailov Kirill V , Efeykin Boris D , Panchin Alexander Y , Knorre Dmitry A , Logacheva Maria D , Penin Aleksey A , Muntyan Maria S , Nikitin Mikhail A , Popova Olga V , Zanegina Olga N , Vyssokikh Mikhail Y , Spiridonov Sergei E , Aleoshin Vladimir V , Panchin Yuri V 
Published: June 2019

AbstractInverted repeats are common DNA elements, but they rarely overlap with protein-coding sequences due to the ensuing conflict with the structure and function of the encoded protein. We discovered numerous perfect inverted repeats of considerable length (up to 284 bp) embedded within the protein-coding genes in mitochondrial genomes of four Nematomorpha species. Strikingly, both arms of the inverted repeats encode conserved regions of the amino acid sequence. We confirmed enzymatic activity of the respiratory complex I encoded by inverted repeat-containing genes. The nucleotide composition of inverted repeats suggests strong selection at the amino acid level in these regions. We conclude that the inverted repeat-containing genes are transcribed and translated into functional proteins. The survey of available mitochondrial genomes reveals that several other organisms possess similar albeit shorter embedded repeats. Mitochondrial genomes of Nematomorpha demonstrate an extraordinary evolutionary compromise where protein function and stringent secondary structure elements within the coding regions are preserved simultaneously.
Age-Related Differences in Hospitalization Rates, Clinical Presentation, and Outcomes Among Older Adults Hospitalized With Influenza—U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET)
Authors: Czaja Christopher A , Miller Lisa , Alden Nisha , Wald Heidi L , Cummings Charisse Nitura , Rolfes Melissa A , Anderson Evan J , Bennett Nancy M , Billing Laurie M , Chai Shua J , Eckel Seth , Mansmann Robert , McMahon Melissa , Monroe Maya L , Muse Alison , Risk Ilene , Schaffner William , Thomas Ann R , Yousey-Hindes Kimberly , Garg Shikha , Herlihy Rachel K 
Published: June 2019

AbstractBackgroundRates of influenza hospitalizations differ by age, but few data are available regarding differences in laboratory-confirmed rates among adults aged ≥65 years.MethodsWe evaluated age-related differences in influenza-associated hospitalization rates, clinical presentation, and outcomes among 19 760 older adults with laboratory-confirmed influenza at 14 FluSurv-NET sites during the 2011–2012 through 2014–2015 influenza seasons using 10-year age groups.ResultsThere were large stepwise increases in the population rates of influenza hospitalization with each 10-year increase in age. Rates ranged from 101–417, 209–1264, and 562–2651 per 100 000 persons over 4 influenza seasons in patients aged 65–74 years, 75–84 years, and ≥85 years, respectively. Hospitalization rates among adults aged 75–84 years and ≥85 years were 1.4–3.0 and 2.2–6.4 times greater, respectively, than rates for adults aged 65–74 years. Among patients hospitalized with laboratory-confirmed influenza, there were age-related differences in demographics, medical histories, and symptoms and signs at presentation. Compared to hospitalized patients aged 65–74 years, patients aged ≥85 years had higher odds of pneumonia (aOR, 1.2; 95% CI, 1.0–1.3; P = .01) and in-hospital death or transfer to hospice (aOR, 2.1; 95% CI, 1.7–2.6; P &lt; .01).ConclusionsAge-related differences in the incidence and severity of influenza hospitalizations among adults aged ≥65 years can inform prevention and treatment efforts, and data should be analyzed and reported using additional age strata.
Will China’s H7N9 Control Strategy Continue to Be Effective?
Authors: Wang Guo-Lin , Gray Gregory C , Chen Ji-Ming , Ma Mai-Juan 
Published: June 2019

Abstract
Since the first outbreak of avian influenza A(H7N9) virus in China in early 2013, several interventions to control the transmission of H7N9 virus from poultry to humans have been implemented. Temporarily closing live poultry markets reduced the risk of human infection to an extent, but it did not prevent the spread of the H7N9 virus among poultry, and this spread eventually led to more human cases. Nevertheless, the mass vaccination of poultry after September 2017 has been highly effective in preventing the H7N9 virus infection in both poultry and humans. In light of the emergence of highly pathogenic H7N9 and H7N2 viruses in unimmunized ducks, vaccination among poultry, especially for ducks, should be accompanied with continued surveillance of H7N9 variants and other avian influenza A viruses that could signal a heightened pandemic risk.
Development of High-Level Echinocandin Resistance in a Patient With Recurrent Candida auris Candidemia Secondary to Chronic Candiduria
Authors: Biagi Mark J , Wiederhold Nathan P , Gibas Connie , Wickes Brian L , Lozano Victoria , Bleasdale Susan C , Danziger Larry 
Published: June 2019

Abstract

Objective
Candida auris is a globally emerging pathogen associated with significant mortality. This pathogen frequently is misidentified by traditional biochemical methods and is resistant to commonly used antifungals. The echinocandins currently are recommended as the first-line treatment for C. auris infections. The objective of this work is to demonstrate the challenges associated with C. auris in the real-world setting.

Methods
A 54-year-old male presented to our institution for concerns of sepsis on multiple occasions over a 5-month period. Eleven urine cultures were positive over this timeframe for yeast (9 unidentified Candida isolates and 2 C. lusitaniae isolates). On day 27, the patient developed echinocandin-susceptible candidemia, which was initially identified as C. haemulonii but later accurately identified as C. auris at an outside mycology reference laboratory. Approximately 10 weeks later, the patient had a recurrence of candidemia, this time caused by an echinocandin-resistant C. auris strain.

Results
Genomic DNA sequencing performed at the outside mycology reference laboratory identified a single serine to proline base pair change at position 639 (S639P) in the hotspot 1 region of the FKS1 gene of the echinocandin-resistant strain.

Conclusions
Our experiences highlight 4 major concerns associated with C. auris: misidentification, persistent colonization, infection recurrence despite the receipt of appropriate initial therapy, and development of resistance.
Null geodesics and repulsive behavior of gravity in $(2+1)$D massive gravity
Authors: Nakashi Keisuke , Kobayashi Shinpei , Ueda Shu , Saida Hiromi 
Published: June 2019

Abstract
We study the null geodesics in a static circularly symmetric (SCS) black hole spacetime, which is a solution in the $(2+1)$D massive gravity proposed by Bergshoeff, Hohm, and Townsend (BHT massive gravity). We obtain analytic solutions for the null geodesic equation in the SCS black hole background and find the explicit form of deflection angles. We see that, for various values of the impact parameter, the deflection angle can be positive, negative, or even zero in this black hole spacetime. The negative deflection angle indicates the repulsive behavior of the gravity that comes from the gravitational hair parameter that is the most characteristic quantity of the BHT massive gravity.
EVALUATING SHORT-TERM EXPOSURE TO WI-FI SIGNALS ON STUDENTS’ REACTION TIME, SHORT-TERM MEMORY AND REASONING ABILITY
Authors: Hosseini M A , Hosseini A , Jarideh S , Argasi H , Shekoohi-Shooli F , Zamani A , Taeb S , Haghani M 
Published: June 2019

AbstractThis study investigated the effect of short-term exposure to Wi-Fi signals on the cognitive functions of the mind. After obtaining permission from the local Ethics Committee of Shiraz University of Medical Sciences and approval by the Iranian Registry of Clinical Trials (IRCT2017041233398N1), 45 male and female students from Shiraz University of Medical Sciences volunteered to participate in this study. They were exposed to Wi-Fi signals in two sham and exposure sessions, each for 2 hours. After completion, they took part in reaction time, short-term memory, and reasoning ability tests. After scoring, the data were analysed by SPSS software. In addition, the electric field strength and power density were calculated. The results showed no statistically significant differences between the mean scores of reaction time, short-term memory, and reasoning ability in sham and exposure. Also, the obtained values from the electric field strength and power density (E = 4.1 Vm−1, P = 0.446 Wm−2) were lower than that of threshold values by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Our results can greatly reduce concerns regarding the effects of short-term exposure to Wi-Fi waves on cognitive functions.
Hot flashes and awakenings among midlife women
Authors: Thurston Rebecca C , Chang Yuefang , Buysse Daniel J , Hall Martica H , Matthews Karen A 
Published: June 2019

Abstract

Study Objectives
For most women, the menopause is accompanied by hot flashes and sleep problems. Although hot flashes reportedly wake women from sleep, in the few studies that have used objective measures of both sleep and hot flashes, links between hot flashes and nocturnal awakening have been inconsistent. In a well-characterized cohort of midlife women, we examined the association between objectively assessed hot flashes and actigraphically defined wake from sleep. We hypothesized that wake episodes would be more likely during an objective hot flash relative to minutes without a hot flash.

Methods
Peri- and postmenopausal midlife women underwent simultaneous objective measurement of hot flashes (sternal skin conductance) and sleep (actigraphy) over 24 hours in the home. The likelihood of waking in the minutes during the hot flash relative to the minutes preceding the hot flash was compared using generalized estimating equations.

Results
We studied 168 women with at least one objective nocturnal hot flash and actigraphy data. Actigraphy-assessed wake episodes were concurrent with 78% of the objective hot flashes. We found an increased likelihood of wake in the minutes during the objective hot flash (0 to +5 min: OR [95% CI] = 5.31 (4.46 to 6.33); p &lt; .0001) relative to the minutes preceding it (–10 to –1 min). The increased likelihood of wake occurred irrespective of whether the women reported the objective hot flash.

Conclusion
Among these women who underwent objective measurement of sleep and hot flashes, nocturnal wakefulness was observed with the majority of hot flashes.
Demyelination-remyelination in the Central Nervous System: Ligand-dependent Participation of the Notch Signaling Pathway
Authors: Mathieu Patricia A , Almeira Gubiani María F , Rodríguez Débora , Gómez Pinto Laura I , Calcagno María de Luján , Adamo Ana M 
Published: June 2019

AbstractMultiple sclerosis (MS) is an immune-mediated central nervous system disease mostly affecting young people. Multiple sclerosis and other neurodegenerative and white matter disorders involve oligodendrocyte (OL) damage and demyelination. Therefore, elucidating the signaling pathways involved in the remyelination process through the maturation of OL progenitor cells (OPCs) may contribute to the development of new therapeutic approaches. In this context, this paper further characterizes toxic cuprizone (CPZ)-induced demyelination and spontaneous remyelination in rats and investigates the role of ligand-dependent Notch signaling activation along demyelination/remyelination both in vivo and in vitro. Toxic treatment generated an inflammatory response characterized by both microgliosis and astrogliosis. Interestingly, early demyelination revealed an increase in the proportion of Jagged1+/GFAP+ cells, which correlated with an increase in Jagged1 transcript and concomitant Jagged1-driven Notch signaling activation, particularly in NG2+ OPCs, in both the corpus callosum (CC) and subventricular zone (SVZ). The onset of remyelination then exhibited an increase in the proportion of F3/contactin+/NG2+ cells, which correlated with an increase in F3/contactin transcript during ongoing remyelination in the CC. Moreover, neurosphere cultures revealed that neural progenitor cells present in the brain SVZ of CPZ-treated rats recapitulate in vitro the mechanisms underlying the response to toxic injury observed in vivo, compensating for mature OL loss. Altogether, the present results offer strong evidence of cell-type and ligand-specific Notch signaling activation and its time- and area-dependent participation in toxic demyelination and spontaneous remyelination.
Location, seasonal and functional characteristics of water-holding containers with juvenile Aedes albopictus in urban southern Taiwan: a cross-sectional study
Authors: Lin Chia-Hsien , Schiøler Karin L , Konradsen Flemming 
Published: June 2019

AbstractBackgroundUrban Kaohsiung City (KC), in southern Taiwan, has experienced annual dengue epidemics for decades despite considerable vector control efforts. Substantial research has been undertaken to characterize Aedes aegypti breeding habitats, but no systematic assessment has been completed for Aedes albopictus present in KC.MethodsA cross-sectional survey was conducted from 2013 to 2015 in a predefined area of KC. Each identified container was characterised by season, location, ownership, function and number of juvenile A. aegypti. Negative binomial hurdle analyses were applied to evaluate the association between the number of juvenile A. albopictus and the characteristics of each identified container.ResultsFor all containers, high numbers of A. albopictus were significantly predicted by containers identified during the wet season (vs dry), located on government (vs private) property and classified as a discarded item (vs water storage). For outdoor containers, more A. albopictus were significantly predicted by wet season (vs dry) and discarded item (vs container in use).ConclusionsIn order to improve dengue prevention in KC, we propose that vector control efforts be expanded to include A. albopictus through an increased focus during the wet season on discarded containers that are located outdoors and on government property.
StrainHub: A phylogenetic tool to construct pathogen transmission networks
Authors: de Bernardi Schneider Adriano , Ford Colby T. , Hostager Reilly , Williams John , Cioce Michael , Çatalyürek Ümit V. , Wertheim Joel O. , Janies Daniel 
Published: June 2019

SummaryIn exploring the epidemiology of infectious diseases, networks have been used to reconstruct contacts among individuals and/or populations. Summarizing networks using pathogen metadata (e.g., host species and place of isolation) and a phylogenetic tree is a nascent, alternative approach. In this paper, we introduce a tool for reconstructing transmission networks in arbitrary space from phylogenetic information and metadata. Our goals are to provide a means of deriving new insights and infection control strategies based on the dynamics of the pathogen lineages derived from networks and centrality metrics. We created a web-based application, called StrainHub, in which a user can input a phylogenetic tree based on genetic or other data along with characters derived from metadata using their preferred tree search method. StrainHub generates a transmission network based on character state changes in meta-data, such as place or source of isolation, mapped on the phylogenetic tree. The user has the option to calculate centrality metrics on the nodes including betweenness, closeness, degree, and a new metric, the source/hub ratio. The outputs include the network with values for metrics on its nodes and the tree with characters reconstructed. All of these results can be exported for further analysis.Availabilityhttps://github.com/abschneider/StrainHub and strainhub.io
Genotyping structural variants in pangenome graphs using the vg toolkit
Authors: Hickey Glenn , Heller David , Monlong Jean , Sibbesen Jonas A. , Sirén Jouni , Eizenga Jordan , Dawson Eric T. , Garrison Erik , Novak Adam M. , Paten Benedict 
Published: June 2019

AbstractStructural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmarked vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated by recent long-read sequencing studies. In addition, we use assemblies from 12 yeast strains to show that graphs constructed directly from aligned de novo assemblies improve genotyping compared to graphs built from intermediate SV catalogs in the VCF format.
Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure
Authors: Ward Joey , Lyall Laura M. , Bethlehem Richard A. I. , Ferguson Amy , Strawbridge Rona J. , Lyall Donald M. , Cullen Breda , Graham Nicholas , Johnston Keira J.A. , Bailey Mark E.S. , Murray Graham K. , Smith Daniel J. 
Published: June 2019

AbstractAnhedonia is a core feature of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including nucleus accumbens, caudate and medial frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this trait as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for anhedonia influences brain structure, particularly in regions associated with reward and pleasure processing.
Rapid Online Changes of Mind during Value-based Action Decisions
Authors: Martí-Marca Angela , Deco Gustavo , Cos Ignasi 
Published: June 2019

AbstractWhile the principles of decision-making are often expressed in terms of benefit-cost trade-off, reasonable doubt remains as to how the cognitive value and motor cost associated to several options may be computed across several brain areas, ultimately leading to a decision. Furthermore, does the assessment of non-chosen options continue after the decision has been made and the selected movement is already ongoing? Does the planning of several motor options depend on a unique parallel process or are there some elements within the sensorimotor loop requiring a sequential processing? Our hypothesis is that a change of available prospects at any point in time should dynamically adjust the desirability for each option, implying a fast reassessment of values and costs across prefrontal and motor cortical areas, even after an initial decision has been made and its associated response movement is ongoing. To test this, we performed a decision-making task in which human participants were instructed to select a reaching path trajectory from an origin to a wide rectangular target to gain the most reward. Reward delivery was contingent upon the distribution of value and upon precise target arrival. The original value distribution was altered during the ongoing movement in one third of the trials. Our results show that participants changed their movement trajectories towards the target position offering a better prospect, as presented by the second distribution. The changes of mind occurred more frequently for slow movements, had a duration in average inferior to the reaction time, and altered the initial timing and movement velocity. Although reward is the main factor guiding the selection of a specific movement in our experiment, our results indicate that the motor system was biased towards early changes of mind, given that the amplitude of the first acceleration and velocity peaks was significantly smaller in trials in which the participant switched target side and those in which they stuck to their original choice. Finally, the short latency of the recorded changes of mind strongly supports the hypothesis that, for the experimental conditions hereby considered, value considerations occur in parallel to motor planning.