bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Cytomegalovirus in Liver Tissue by Polymerase Chain Reaction in Infants With Neonatal Cholestasis
Authors: Goel Akshat , Chaudhari Sneha , Sutar Jyoti , Bhonde Gauri , Bhatnagar Sushmita , Patel Vainav , Bhor Vikrant , Shah Ira 
Published: February 2018

Aim:
Cytomegalovirus (CMV) is associated with neonatal cholestasis (NC). Diagnosis of CMV infection is most often based on either positive blood CMV IgM or CMV blood polymerase chain reaction (PCR). Isolation of CMV in liver tissues in patients with NC has rarely been reported. This study was undertaken to see if CMV is present in liver tissues of patients with NC and evaluate the correlation between positive CMV PCR in liver tissue with the serology and blood PCR.

Methods:
This study was conducted in 31 infants with NC from June 2015 to December 2016. All patients underwent blood CMV IgM, blood CMV PCR and liver CMV PCR. Prevalence of CMV in NC based on positive liver CMV PCR was calculated. Sensitivity and specificity of the serologic markers and blood CMV PCR to identify CMV infection in the liver was determined.

Results:
CMV IgM was positive in 13 (42%) patients, CMV IgG was positive in 26 (84%) patients and blood CMV PCR was positive in 23 (74%) patients. Liver CMV PCR was positive in 16 (52%) patients. Fifteen (48%) patients had biliary atresia (BA), 10 (32%) patients had neonatal hepatitis, 5 (16%) had paucity of bile ducts and 1 (3%) had ascending cholangitis. Of the 16 patients with positive liver CMV PCR, 8 (50%) had BA, 4 (25%) had neonatal hepatitis, 3 (19%) had paucity of bile ducts and 1 (6%) had ascending cholangitis. Sensitivity of blood CMV IgM in relation to liver CMV PCR was 69% and specificity was 61%. Sensitivity of blood CMV PCR was 61% and specificity was 71% when compared with liver CMV PCR.

Conclusion:
CMV is present in the liver tissues of more than half the patients with NC. Serology or blood CMV PCR is apparently not an accurate marker of CMV in the liver tissue. Also, CMV infection in children seems to be associated equally with BA or non-BA neonatal hepatitis.
Symptoms, Signs and Long-term Prognosis of Vertically Transmitted Chlamydia trachomatis Infections
Authors: Honkila Minna , Renko Marjo , Pokka Tytti , Wikström Erika , Uhari Matti , Tapiainen Terhi 
Published: February 2018

Background:
Although Chlamydia trachomatis infection is common in pregnant women, such infections are rarely encountered in infants. To clarify the recognition of C. trachomatis infections in infants, we analyzed symptoms and signs of perinatally acquired chlamydial infection, together with its long-term prognosis in a large population-based patient series.

Methods:
A search through 2 national health registries covering 1996–2011, a cohort of 933,823 births, yielded 124 children with a microbiologically confirmed C. trachomatis infection. We then reviewed copies of the children’s medical records up to 16 years of age.

Results:
One-third of the infants with chlamydial conjunctivitis (33/110) had spontaneous blood-stained discharge from the infected eye. The infants with C. trachomatis lower respiratory tract infection were mostly afebrile (30/32), and 15/32 of them had wheezing. Staccato cough was not recorded in any of the infants. The median diagnostic delay from the onset of the symptoms was 13 (range 4–374) days for conjunctivitis and 25 (range 10–149) days for lower respiratory tract infection. One neglected child developed bilateral corneal scars because of an untreated C. trachomatis infection.

Conclusions:
Blood-stained discharge was a typical finding in C. trachomatis conjunctivitis. The C. trachomatis–infected infants had severe and prolonged symptoms, but long-term consequences were rare. The diagnostic delay was long, especially among the infants with a C. trachomatis lower respiratory tract infection.
Is acute kidney injury a harbinger for chronic kidney disease?
Authors: Selewski David T. , Hyatt Dylan M. , Bennett Kevin M. , Charlton Jennifer R. 
Published: February 2018

Purpose of review
Despite abundant evidence in adults, the relationship between acute kidney injury (AKI) and chronic kidney disease (CKD) remains unanswered in pediatrics. Obstacles to overcome include the challenges defining these entities and the lack of long-term follow-up studies. This review focuses on pediatric populations at high-risk for AKI, the evidence of the long-term effect of AKI on renal health, and biomarkers to detect renal disease.

Recent findings
AKI in critically ill children and neonates is common and independently associated with adverse outcomes. Patients with diabetes and sickle cell disease along with neonates with necrotizing enterocolitis have been identified as high-risk for AKI. Preterm birth and neonates with AKI have signs of renal dysfunction early in childhood. Urinary biomarkers may identify AKI and CKD earlier than traditional biomarkers, but more work is necessary to determine their clinical utility. Promising technological advances including the ability to determine nephron number noninvasively will expand our ability to characterize the AKI to CKD transition.

Summary
AKI is common and associated with poor outcomes. It is probable that AKI is a harbinger to CKD in pediatric populations. However, we currently lack the tools to definitely answer this question and more research is needed.
Eosinophil Counts in the Small Intestine and Colon of Children Without Apparent Gastrointestinal Disease
Authors: Kiss Zoltán , Tél Bálint , Farkas Nelli , Garami András , Vincze Áron , Bajor Judit , Sarlós Patrícia , Márta Katalin , Erős Adrienn , Mikó Alexandra , Szakács Zsolt , Pécsi Dániel , Mátrai Péter , Hegyi Péter , Veres Gábor 
Published: February 2018

ABSTRACTThe aim of the current study was to review the available data regarding eosinophil density in healthy tissue specimen originating from lower gastrointestinal segments to support suggested diagnostic cutoffs widely used in clinical practice. A systematic search was performed in 3 different databases. Calculations were made with Comprehensive MetaAnalysis software using random‐effects model. Cell number measurements were pooled using the random‐effects model and displayed on forest plots. Summary point estimations, 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated. The cumulative mean cell numbers were 8.26 (95% CI 4.71‐11.80) with PI of 0‐25.32 for the duodenum, 11.52 (95% CI 7.21‐15.83) with PI 0‐60.64 for the terminal ileum, and 11.10/ high‐power field (HPF) (95% CI 9.11–13.09) with PI of 0.96 to 21.23 in the large intestine and the rectum (HPF area = 0.2 mm2). Previous studies included control patients with irritable bowel syndrome and functional gastrointestinal disorders. As mucosal eosinophils have a role in their pathomechanism, those patients should have been excluded. A critical point of interpreting reported data is that HPF is relative to the technical parameters of the microscopes; therefore, it is important to report findings in cell/mm2. The present meta‐analysis does not support the higher (>20) or lower (<10) cutoff values for healthy tissue eosinophil number. In contrast to the esophagus, there is no normal cutoff eosinophil density in the small intestine and the colon. A prospective, multicenter study to establish normal mucosal eosinophil density is clearly needed.
The Value of Regional Cerebral Blood Flow SPECT and FDG PET in Operculoinsular Epilepsy
Authors: Fei Phillip , Soucy Jean-Paul , Obaid Sami , Boucher Olivier , Bouthillier Alain , Nguyen Dang Khoa 
Published: February 2018

Purpose
Operculoinsular epilepsy (OIE) can be challenging to diagnose. While the value of SPECT cerebral blood flow and PET 18F-FDG studies for presurgical evaluation of patients with medial temporal lobe epilepsy (MTLE) is well established, it remains unclear whether they can help identify an operculoinsular epileptic focus. This study assesses the value of interictal/ictal regional cerebral blood flow (rCBF) SPECT and FDG PET for OIE diagnosis.

Methods
Eighteen patients with proven OIE who underwent interictal/ictal rCBF SPECT and/or FDG-PET prior to epilepsy surgery were identified from our clinical database and were compared with a group of 18 patients who underwent MTLE surgery. Regional cerebral blood flow SPECT and FDG PET images were reevaluated visually by an expert reader blind to clinical data.

Results
Interictal/ictal rCBF SPECT correctly identified an operculoinsular focus in 11 (65%) of 17 OIE patients and was misleading in 3 cases (18%). Secondary activation in areas connected to the insula was often observed. In the MTLE group, the area of maximal increased perfusion was congruent in 12 (75%) of 16 patients and extended to the ipsilateral insula in 1 patient. FDG PET findings were concordant with the epileptic focus in 8 (47%) of 17 OIE patients and were misleading in 4 (24%), whereas they were concordant in all MTLE patients.

Conclusions
Interictal/ictal rCBF SPECT can identify a concordant operculoinsular focus in a significant proportion of OIE patients and offers a valuable diagnostic tool in nonlesional cases. By contrast, the value of interictal FDG PET in this population is more equivocal.
Genome-wide translating mRNA analysis following ketamine reveals novel targets for antidepressant treatment
Authors: Miller Oliver H. , Grabole Nils , Wells Isabelle , Hall Benjamin J. 
Published: February 2018

AbstractLow-dose ketamine is an efficacious antidepressant for treatment-resistant unipolar and bipolar depressed patients. Major Depression Disorder patients receiving a single infusion report elevated mood within two hours, and ketamine’s antidepressant effects have been observed as long as seven days post-treatment. In light of this remarkable observation, efforts have been undertaken to “reverse-translate” ketamine’s effects to understand its mechanism of action. Major advances have been achieved in understanding the molecular, cellular, and circuit level changes that are initiated by low-dose ketamine. Although enhancement of protein synthesis clearly plays a role, the field lacks a comprehensive understanding of the protein synthesis program initiated after ketamine treatment. Here, using ribosome-bound mRNA footprinting and deep sequencing (RiboSeq), we uncover a genome-wide set of actively translated mRNAs (the translatome) in medial prefrontal cortex after an acute antidepressant-like dose of ketamine. Gene Ontology analysis confirmed that initiation of protein synthesis is a defining feature of antidepressant-dose ketamine in mice and Gene Set Enrichment Analysis points to a role for GPCR signaling, metabolism, vascularization, and structural plasticity in ketamine’s effects. One gene, VIPR2, whose protein product VPAC2 acts as a GPCR for the neuropeptide vasoactive intestinal peptide, was characterized in cortex and identified as a potential novel target for antidepressant action.
Ecological advantages and evolutionary limitations of aggregative multicellular development
Authors: Pentz Jennifer T. , Márquez-Zacarías Pedro , Yunker Peter J. , Libby Eric , Ratcliff William C. 
Published: February 2018

AbstractAll multicellular organisms develop through one of two basic routes: they either aggregate from free-living cells, creating potentially-chimeric multicellular collectives, or they develop clonally via mother-daughter cellular adhesion. While evolutionary theory makes clear predictions about trade-offs between these developmental modes, these have never been experimentally tested in otherwise genetically-identical organisms. We engineered unicellular baker’s yeast (Saccharomyces cerevisiae) to develop either clonally (‘snowflake’, Δace2), or aggregatively (‘floc’,GAL1p::FLO1), and examined their fitness in a fluctuating environment characterized by periods of growth and selection for rapid sedimentation. When cultured independently, aggregation was far superior to clonal development, providing a 35% advantage during growth, and a 2.5-fold advantage during settling selection. Yet when competed directly, clonally-developing snowflake yeast rapidly displaced aggregative floc. This was due to unexpected social exploitation: snowflake yeast, which do not produce adhesive FLO1, nonetheless become incorporated into flocs at a higher frequency than floc cells themselves. Populations of chimeric clusters settle much faster than floc alone, providing snowflake yeast with a fitness advantage during competition. Mathematical modeling suggests that such developmental cheating may be difficult to circumvent; hypothetical ‘choosy floc’ that avoid exploitation by maintaining clonality pay an ecological cost when rare, often leading to their extinction. Our results highlight the conflict at the heart of aggregative development: non-specific cellular binding provides a strong ecological advantage – the ability to quickly form groups – but this very feature leads to its exploitation.
Relationships between Human Brain Structural Connectomes and Traits
Authors: Zhang Zhengwu , Allen Genevera I. , Zhu Hongtu , Dunson David 
Published: February 2018

AbstractAdvanced brain imaging techniques make it possible to measure individuals’ structural connectomes in large cohort studies non-invasively. However, due to limitations in image resolution and pre-processing, questions remain about whether reconstructed connectomes are measured accurately enough to detect relationships with human traits and behaviors. Using a state-of-the-art structural connectome processing pipeline and a novel dimensionality reduction technique applied to data from the Human Connectome Project (HCP), we show strong relationships between connectome structure and various human traits. Our dimensionality reduction approach uses a tensor characterization of the connectomes and relies on a generalization of principal components analysis. We analyze over 1100 scans for 1076 subjects from the HCP and the Sherbrooke test-retest data set as well as 175 human traits that measure domains including cognition, substance use, motor, sensory and emotion. We find that brain connectomes are associated with many traits. Specifically, fluid intelligence, language comprehension, and motor skills are associated with increased cortical-cortical brain connectivity, while the use of alcohol, tobacco, and marijuana are associated with decreased cortical-cortical connectivity.
The evolutionary dynamics of microRNAs in domestic mammals
Authors: Penso-Dolfin Luca , Moxon Simon , Haerty Wilfried , Di Palma Federica 
Published: February 2018

ABSTRACTMicroRNAs are crucial regulators of gene expression found across both the plant and animal kingdoms. While the numberof annotated microRNAs deposited in miRBase has greatly increased in recent years, few studies provided comparative analyses across sets of related species, or investigated the role of microRNAs in the evolution of gene regulation.We generated small RNA libraries across 5 mammalian species (cow, dog, horse, pig and rabbit) from 4 different tissues (brain, heart, kidney and testis). We identified 1675 miRBase and 413 novel microRNAs by manually curating the set of computational predictions obtained frommiRCatandmiRDeep2.Our dataset spanning five species has enabled us to investigate the molecular mechanisms and selective pressures driving the evolution of microRNAs in mammals. We highlight the important contributions of intronic sequences (366 orthogroups), duplication events (135 orthogroups) and repetitive elements (37 orthogroups) in the emergence of new microRNA loci.We use this framework to estimate the patterns of gains and losses across the phylogeny, and observe high levels of microRNA turnover. Additionally, the identification of lineage-specific losses enables the characterisation of the selective constraints acting on the associated target sites.Compared to the miRBase subset, novel microRNAs tend to be more tissue specific. 20 percent of novel orthogroups are restricted to the brain, and their target repertoires appear to be enriched for neuron activity and differentiation processes. These findings may reflect an important role for young microRNAs in the evolution of brain expression plasticity.Many seed sequences appear to be specific to either the cow or the dog. Analyses on the associated targets highlightthe presence of several genes under artificial positive selection, suggesting an involvement of these microRNAs in the domestication process.Altogether, we provide an overview on the evolutionary mechanisms responsible for microRNA turnover in 5 domestic species, and their possible contribution to the evolution of gene regulation.
A Survey of Orbitrap All Ion Fragmentation Analysis Assessed by an R MetaboList Package to Study Small-molecule Metabolites
Authors: Sentandreu Enrique , Peris-Díaz Manuel D , Sweeney Shannon R , Chiou Jennifer , Muñoz Nathalie , Tiziani Stefano 
Published: February 2018

ABSTRACTLeukemia cell and melanoma tumor tissue extracts were studied for small (mostly m/z <250) polar metabolites by LC-ESI-HRMSn analysis powered by a hybrid Quadrupole-Orbitrap. MS data was simultaneously acquired in fast polarity switching mode operating in MS1 and MS/MS (All Ion Fragmentation, AIF) full-scan analyses at high mass resolution. Positive assignments were achieved by AIF analysis considering at least two characteristic transitions of metabolites. A targeted metabolite profiling was achieved by the relative quantification of 18 metabolites through spiking their respective deuterated counterparts. Manual data processing of MS1 and AIF scans were compared for accurate determination of natural metabolites and their deuterated analogs by chromatographic alignment and peak area integration. Evaluation of manual and automated (MetaboList R package) AIF data processing yielded comparable results. The versatility of AIF analysis also enabled the untargeted metabolite profiling of leukemia and melanoma samples in which 22 and 53 compounds were respectively identified outside those studied by labeling. The main limitation of the method was that low abundance metabolites with scan rates below 8 scans/peak could not be accurately quantified by AIF analysis. Combination of AIF analysis with MetaboList R package represents an opportunity to move towards automated, faster and more global metabolomics approaches supported by an entirely flexible open source automated data processing platform freely available from Comprehensive R Archive Network (CRAN, https://CRAN.R-project.org/package=MetaboList).
Rapid multiplex small DNA sequencing on the MinION nanopore sequencing platform
Authors: Wei Shan , Weiss Zachary R. , Williams Zev 
Published: February 2018

AbstractReal-time sequencing of short DNA reads has a wide variety of clinical and research applications including screening for mutations, target sequences and aneuploidy. We recently demonstrated that MinION, a nanopore-based DNA sequencing device the size of a USB drive, could be used for short-read DNA sequencing. In this study, an ultra-rapid multiplex library preparation and sequencing method for the MinION is presented and applied to accurately test normal diploid and aneuploidy samples’ genomic DNA in under three hours, including library preparation and sequencing. This novel method shows great promise as a clinical diagnostic test for applications requiring rapid short-read DNA sequencing.
Anatomical, Physiological, and Functional Heterogeneity of the Dorsal Raphe Serotonin System
Authors: Ren Jing , Friedmann Drew , Xiong Jing , Liu Cindy D. , DeLoach Katherine E. , Ran Chen , Pu Albert , Sun Yanwen , Weissbourd Brandon , Neve Rachael L. , Horowitz Mark , Luo Liqun 
Published: February 2018

SummaryThe dorsal raphe (DR) constitutes a major serotonergic input to the forebrain, and modulates diverse functions and brain states including mood, anxiety, and sensory and motor functions. Most functional studies to date have treated DR serotonin neurons as a single, homogeneous population. Using viral-genetic methods, we found that subcortical-vs. cortical-projecting serotonin neurons have distinct cell body distributions within the DR and different degrees of coexpressing a vesicular glutamate transporter. Further, the amygdala-and frontal cortex-projecting DR serotonin neurons have largely complementary whole-brain collateralization patterns, receive biased inputs from presynaptic partners, and exhibit opposite responses to aversive stimuli. Gain-and loss-of-function experiments suggest that amygdala-projecting DR serotonin neurons promote anxiety-like behavior, whereas frontal cortex-projecting neurons promote active coping in face of challenge. These results provide compelling evidence that the DR serotonin system contains parallel sub-systems that differ in input and output connectivity, physiological response properties, and behavioral functions.
N6-methyladenosine binding proteins negatively regulate HIV-1 infectivity and viral production
Authors: Lu Wuxun , Tirumuru Nagaraja , Koneru Pratibha C. , Liu Chang , Kvaratskhelia Mamuka , He Chuan , Wu Li 
Published: February 2018

AbstractBackgroundThe internalN6-methyladenosine (m6A) modification of cellular mRNA regulates post-transcriptional gene expression. The YTH domain family proteins (YTHDF1-3, or Y1-3) bind to m6A-modified cellular mRNA and modulate its metabolism and processing, thereby affecting protein translation in cells. We previously reported that HIV-1 RNA contains m6A modification and that Y1-3 proteins inhibit HIV-1 infection by decreasing HIV-1 reverse transcription. Here we extended our studies to further understand the mechanisms of Y1-3-mediated inhibition of HIV-1 infection and viral production.ResultsOverexpression of Y1-3 proteins in HIV-1 target cells decreased viral genome RNA (gRNA) levels and inhibited early and late reverse transcription. Purified recombinant Y1-3 proteins preferentially bound to the m6A-modified 5’ leader sequence of gRNA compared with its unmodified RNA counterpart, consistent with the strong binding of Y1-3 to HIV-1 gRNA in infected cells. HIV-1 mutants with two altered m6A modification sites in the 5’ leader sequence of gRNA demonstrated significantly lower infectivity compared with wild-type HIV-1, confirming that these sites are important for viral infection. HIV-1 produced from cells with knockdown of endogenous Y1, Y3, or Y1-3 proteins together showed increased viral infectivity compared with HIV-1 produced from control cells. Interestingly, we found that Y1-3 proteins and HIV-1 Gag formed a complex with RNA in HIV-1-infected target cells.ConclusionsOur results suggest the inhibitory effects of Y1-3 proteins on HIV-1 infection and provide new insight into the mechanisms of m6A modification of HIV-1 RNA in regulating viral replication, which clarify some discrepancies in the previously published studies in this area.
Crystal structure of chromo barrel domain of RBBP1
Authors: Lei Ming , Feng Yue , Zhou Mengqi , Yang Yuan , Loppnau Peter , Li Yanjun , Yang Yi , Liu Yanli 
Published: February 2018

AbstractRBBP1 is a retinoblastoma protein (pRb) binding protein acting as a repressor of gene transcription. RBBP1 is a multidomain protein including a chromo barrel domain, and its chromo barrel domain has been reported to recognize histone H4K20me3 weakly, and this binding is enhanced by the simultaneous binding of DNA. However, the molecular basis of this DNA-mediated histone binding by the chromo barrel domain of RBBP1 is unclear. Here we attempted to co-crystallize the chromo barrel domain of RBBP1 with either a histone H4K20me3 peptide alone or with both a histone H4K20me3 peptide and DNA, but only solved the peptide/DNA unbound crystal structure. Our structural analysis indicates that RBBP1 could interact with histone H4K20me3 similar to other histone binding chromo barrel domains, and the surface charge representation analysis of the chromo barrel domain of RBBP1 suggests that the chromo barrel domain of RBBP1 does not have a typical DNA binding surface, indicating that it might not bind to DNA. Consistently, our ITC assays also showed that DNA does not significantly enhance the histone binding ability of the chromo barrel domain of RBBP1.