bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation Exposure and Attributable Cancer Risk in Patients With Esophageal Atresia
Authors: Yousef Yasmine , Baird Robert 
Published: July 2017

ABSTRACTObjectives:Cases of esophageal carcinoma have been documented in survivors of esophageal atresia (EA). Children with EA undergo considerable amounts of diagnostic imaging and consequent radiation exposure potentially increasing their lifetime cancer mortality risk. This study evaluates the radiological procedures performed on patients with EA and estimates their cumulative radiation exposure and attributable lifetime cancer mortality risk.Methods:Medical records of patients with EA managed at a tertiary care center were reviewed for demographics, EA subtype, and number and type of radiological investigations. Existing normative data were used to estimate the cumulative radiation exposure and lifetime cancer risk per patient.Results:The present study included 53 patients with a mean follow‐up of 5.7 years. The overall median and maximum estimated effective radiation dose in the neonatal period was 5521.4 μSv/patient and 66638.6 μSv/patient, respectively. This correlates to a median and maximum estimated cumulative lifetime cancer mortality risk of 1:1530 and 1:130, respectively. Hence, radiation exposure in the neonatal period increased the cumulative cancer mortality risk a median of 130‐fold and a maximum of 1575‐fold in EA survivors.Conclusions:Children with EA are exposed to significant amounts of radiation and an increased estimated cumulative cancer mortality risk. Efforts should be made to eliminate superfluous imaging.
The Patient–Healthcare Professional Relationship and Communication in the Oncology Outpatient Setting
Authors: Prip Anne , Møller Kirsten Alling , Nielsen Dorte Lisbet , Jarden Mary , Olsen Marie-Helene , Danielsen Anne Kjaergaard 
Published: July 2017

Background:
Today, cancer care and treatment primarily take place in an outpatient setting where encounters between patients and healthcare professionals are often brief.

Objective:
The aim of this study was to summarize the literature of adult patients’ experiences of and need for relationships and communication with healthcare professionals during chemotherapy in the oncology outpatient setting.

Methods:
The systematic literature review was carried out according to PRISMA guidelines and the PICO framework, and a systematic search was conducted in MEDLINE, CINAHL, The Cochrane Library, and Joanna Briggs Institute Evidence Based Practice Database.

Results:
Nine studies were included, qualitative (n = 5) and quantitative (n = 4). The studies identified that the relationship between patients and healthcare professionals was important for the patients’ ability to cope with cancer and has an impact on satisfaction of care, that hope and positivity are both a need and a strategy for patients with cancer and were facilitated by healthcare professionals, and that outpatient clinic visits framed and influenced communication and relationships.

Conclusions:
The relationship and communication between patients and healthcare professionals in the outpatient setting were important for the patients’ ability to cope with cancer.

Implications for Practice:
Healthcare professionals need to pay special attention to the relational aspects of communication in an outpatient clinic because encounters are often brief. More research is needed to investigate the type of interaction and intervention that would be the most effective in supporting adult patients’ coping during chemotherapy in an outpatient clinic.
Management of Scaphoid Fractures
Authors: Ko Jason H. , Pet Mitchell A. , Khouri Joseph S. , Hammert Warren C. 
Published: July 2017

Learning Objectives:
After reading this article, the participant should be able to: 1. Understand the epidemiology, classification, and anatomy pertinent to the scaphoid. 2. Appropriately evaluate a patient with suspected scaphoid fracture, including appropriate imaging. 3. Understand the indications for operative treatment of scaphoid fractures, and be familiar with the various surgical approaches. 4. Describe the treatment options for scaphoid nonunion and avascular necrosis of the proximal pole.

Summary:
The goal of this continuing medical education module is to present the preoperative assessment and the formation and execution of a surgical treatment plan for acute fractures of the scaphoid. In addition, secondary surgical options for treatment of scaphoid nonunion and avascular necrosis are discussed.
Extended Transconjunctival Lower Eyelid Blepharoplasty with Release of the Tear Trough Ligament and Fat Redistribution
Authors: Wong Chin-Ho , Mendelson Bryan 
Published: July 2017

Background:
The transconjunctival lower eyelid blepharoplasty is advantageous for its quick recovery and low complication rates. Conventional techniques rely on fat removal to contour the lower eyelid. This article describes the authors’ extended transconjunctival lower eyelid blepharoplasty technique that takes dissection beyond the orbital rim to address aging changes on the midcheek.

Methods:
From December of 2012 to December of 2015, 54 patients underwent this procedure. Through a transconjunctival incision, the preseptal space was entered and excess orbital fat pads were excised. Medially, the origins of the palpebral part of the orbicularis oculi, the tear trough ligament, and orbital part of the orbicularis oculi were sequentially released, connecting the dissection with the premaxillary space. More laterally, the orbicularis retaining ligament was released, connecting the dissection with the prezygomatic space. Excised orbital fat was then grafted under the released tear trough ligament to correct the tear trough deformity. When the patients had significant maxillary retrusion, structural fat grafting was performed at the same time.

Results:
The mean follow-up was 10 months. High satisfaction was noted among the patients treated with this technique. The revision rate was 2 percent. Complication rates were low. No chemosis, prolonged swelling, lower eyelid retraction, or ectropion was seen in any patients.

Conclusion:
The extended transconjunctival lower blepharoplasty using the midcheek soft-tissue spaces is a safe and effective approach for treating patients presenting with eye bags and tear trough deformity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Assessment of clonal kinetics reveals multiple trajectories of dendritic cell development
Authors: Lin Dawn , Kan Andrey , Gao Jerry , Crampin Edmund , Hodgkin Philip D. , Naik Shalin H. 
Published: July 2017

SUMMARYA thorough understanding of cellular development is incumbent on assessing the complexities of fate and kinetics of individual clones within a population. Here, we develop a system for robust periodical assessment of lineage outputs of thousands of transient clones and establishment ofbona fidecellular trajectories. We appraise the development of dendritic cells (DCs) from barcode-labeled hematopoietic stem and progenitor cells (HSPCs) by serially measuring barcode signatures, and visualize this multidimensional data using novel developmental interpolated t-distributed stochastic neighborhood embedding (Di-SNE) time-lapse movies. We identify multiple cellular trajectories of DC development that are characterized by distinct fate bias and expansion kinetics, and determine that these are intrinsically programmed. We demonstrate that conventional DC and plasmacytoid DC trajectories are largely separated already at the HSPC stage. This framework allows systematic evaluation of clonal dynamics and can be applied to other steady-state or perturbed developmental systems.
Maternal alcohol consumption during pregnancy and offspring epigenome-wide DNA methylation: findings from six general population-based birth cohorts
Authors: Sharp Gemma C , Arathimos Ryan , Reese Sarah E , Page Christian M , Felix Janine , Küpers Leanne K , Rifas-Shiman Sheryl L , Liu Chunyu ,   The Cohorts for Heart and Aging Research in Genomic Epidemiology plus (CHARGE +) methylation alcohol working group, Burrows Kimberley , Zhao Shanshan , Magnus Maria C , Duijts Liesbeth , Corpeleijn Eva , DeMeo Dawn L , Litonjua Augusto , Baccarelli Andrea , Hivert Marie-France , Oken Emily , Snieder Harold , Jaddoe Vincent , Nystad Wenche , London Stephanie J , Relton Caroline L , Zuccolo Luisa 
Published: July 2017

AbstractSome evidence suggests that light-to-moderate alcohol consumption during pregnancy is associated with adverse outcomes in the offspring, but the precise biological mechanisms underlying such associations are currently unknown. Epigenetic modifications have been suggested as one potential explanation.Within the Pregnancy and Childhood Epigenetics (PACE) consortium, we performed meta-analysis to combine information from six population-based birth cohort studies to investigate DNA methylation at over 450,000 sites in the cord blood of newborns differentially exposed to alcoholin utero. We were primarily interested in the effects of sustained consumption throughout pregnancy (data available for five cohorts, 3,075 mother-child pairs), which represents a prolonged prenatal exposure to alcohol, but we also explored binge-drinking and timing-specific exposures. In addition to looking for differential methylation at individual CpG sites, we also used two different methods, Comb-P and DMRcate, to identify differentially methylated regions (DMRs).We found no strong evidence of association between any of our alcohol exposure measures and DNA methylation at any individual CpG site. Using Comb-P, we identified 19 DMRs in the offspring of mothers who drank throughout pregnancy compared to the offspring of mothers who gave up drinking at the start of pregnancy, but these were not validated using DMRcate.In this multi-cohort study of the general population we found no evidence that maternal alcohol consumption during pregnancy is associated with offspring cord blood DNA methylation, which is in stark contrast to the multiple, strong associations that previous studies have found for maternal smoking. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure and a more global assessment of genomic DNA methylation might show evidence of association.
c-Myc Represses Transcription of the Epstein-Barr Virus Latent Membrane Protein 1 Early After Primary B Cell Infection
Authors: Price Alexander M. , Messinger Joshua E. , Luftig Micah A. 
Published: July 2017

ABSTRACTRecent evidence has shown that the EBV oncogene LMP1 is not expressed at high levels early after EBV-infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased fifty-fold between seven days post infection and the LCL state. Metabolic labeling of nascently transcribed mRNA indicated this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to early-infected B cells. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc expression both in LCLs and early after primary B-cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B-cell infection directly represses LMP1 transcription.IMPORTANCEEBV is a highly successful pathogen that latently infects greater than 90% of adults worldwide and is also causally associated with a number of B-cell malignancies. EBV expresses a set of viral oncoproteins and non-coding RNAs during the latent life cycle with the potential to promote cancer. Critical among these is the viral latent membrane protein, LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here, we show that the transcription of LMP1 can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV-encoded oncogenes will allow us to better treat cancers that rely on these viral products for survival.
Acute stress induces long-lasting alterations in the dopaminergic system of female mice
Authors: Wichmann Romy , Vander Weele Caitlin M. , Yosafat Ariella S. , Schut Evelien H.S. , Verharen Jeroen P. H. , Sridharma Suganya , Siciliano Cody A. , Izadmehr Ehsan M. , Farris Kathryn M. , Wildes Craig P. , Kimchi Eyal Y. , Tye Kay M. 
Published: July 2017

AbstractStress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how a non-social stressor impacts the effect of DA neurotransmission on social and reward-related behaviors in female mice. Acute stress exposure attenuated the anti-social effects of photoinhibiting ventral tegmental area (VTA) DA neurons and transformed photoactivation of these cells into an anti-social signal. Fast-scan cyclic voltammetry (FSCV) revealed an enhancement in optogenetically-induced DA release after stress. 60 days after stress, mice showed distinct patterns of intra-cranial self-stimulation of VTA DA neurons. Our results reveal the impact stress exerts on females and show that neural and behavioral changes induced by acute stress exposure are still present months later.
Experimental evolution and genome data analysis ofCandida albicansreveals cryptic bacteria in single yeast colonies
Authors: Carmo Ferreira Bruno Danielle do , Fernanda Bartelli Thais , Ronqui Rodrigues Camila , Briones Marcelo R. S. 
Published: July 2017

ABSTRACTAt least 25% of patients with positiveCandida albicansbloodstream infection also have one or more bacterial species associated with the infection. These polymicrobial infections are usually caused by coagulase-negative staphylococci, most commonlyStaphylococcus epidermidisand are associated with significantly worse clinical outcomes as compared to monomicrobial infections. Here we show bacteria are present inC. albicanscultures started from isolated single colony platting. These co-evolving bacteria can only be detected by the use of specific selective medium and/or long periods of incubation from 8 days up to 48 weeks (approximately 4,000 generations), used in experimental evolution methods. The detection of these co-evolving bacteria is highly dependent on the type of enzyme used for 16S rRNA gene amplification and is often missed in clinical laboratory analysis because of short incubation periods, media and temperatures, used in mycology clinical routine, that are unfavorable for bacterial growth. In this study, we identified bacteria in cultures of differentC. albicansisolates from long term, continuous growth by molecular analysis and microscopy. Also, we confirmed the presence of these co-evolving bacteria by identification ofS. epidermidisgenome segments in sequencing reads of theC. albicansreference strain SC5314 genome sequencing project raw data deposited in GenBank. This result rules out the possibility of laboratory specific contamination. Also, we show that the presence of associated bacteria correlates with antifungal resistance alterations observed in growth under hypoxia. Our findings show the intense interaction betweenC. albicansyeasts and bacteria and have direct implications in yeast clinical procedures, especially concerning patient treatment.
Anin vivobinding assay for RNA-binding proteins based on repression of a reporter gene
Authors: Katz Noa , Cohen Roni , Solomon Oz , Kaufmann Beate , Eden Noa , Atar Orna , Yakhini Zohar , Goldberg Sarah , Amit Roee 
Published: July 2017

ABSTRACTWe employ a reporter assay and Selective 2′-hydroxyl acylation analysed by primer extension sequencing (SHAPE-seq) to study translational regulation by RNA-binding proteins, in bacteria. We designed 82 constructs, each with a single hairpin based on the binding sites of the RNA-binding coat proteins of phages MS2, PP7, GA, and Qβ, at various positions within the N-terminus of a reporter gene. In the absence of RNA-binding proteins, the translation level depends on hairpin location, and exhibits a three-nucleotide periodicity. For hairpin positions within the initiation region, we observe strong translational repression in the presence of its cognate RNA-binding protein.In vivo SHAPE-seqresults for a representative construct indicate that the repression phenomenon correlates with a wide-swath of protection, including the hairpin and extending past the ribosome binding site. Consequently, our data suggest that the protection provided by the RBP-hairpin complex inhibits ribosomal initiation. Finally, utilizing the repression phenomenon for quantifying protein-RNA binding affinityin vivo, we both observe partially contrasting results to previousin vitroandin situstudies, and additionally, show that this method can be used in a high-throughput assay for a quantitative study of protein-RNA bindingin vivo.
Facilitation of motor excitability during listening to spoken sentences is not modulated by noise or semantic coherence
Authors: Panouillères Muriel T.N. , Boyles Rowan , Chesters Jennifer , Watkins Kate E. , Möttönen Riikka 
Published: July 2017

AbstractComprehending speech can be particularly challenging in a noisy environment and in the absence of semantic context. It has been proposed that the articulatory motor system would be recruited especially in difficult listening conditions. However, it remains unknown how signal-to-noise ratio (SNR) and semantic context affect the recruitment of the articulatory motor system when listening to continuous speech. The aim of the present study was to address the hypothesis that involvement of the articulatory motor cortex increases when the intelligibility and clarity of the spoken sentences decreases, because of noise and the lack of semantic context. We applied Transcranial Magnetic Stimulation (TMS) to the lip and hand representations in the primary motor cortex and measured motor evoked potentials from the lip and hand muscles, respectively, to evaluate motor excitability when young adults listened to sentences. In Experiment 1, we found that the excitability of the lip motor cortex was facilitated during listening to both semantically anomalous and coherent sentences in noise, but neither SNR nor semantic context modulated the facilitation. In Experiment 2, we replicated these findings and found no difference in the excitability of the lip motor cortex between sentences in noise and clear sentences without noise. Thus, our results show that the articulatory motor cortex is involved in speech processing even in optimal and ecologically valid listening conditions and that its involvement is not modulated by the intelligibility and clarity of speech.
A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging
Authors: Zeighami Yashar , Fereshtehnejad Seyed-Mohammad , Dadar Mahsa , Collins D. Louis , Postuma Ronald B. , Mišić Bratislav , Dagher Alain 
Published: July 2017

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even inde novopatients.
Multiplexed nanopore sequencing of HLA-B locus in Māori and Polynesian samples
Authors: Ton K.N.T. , Cree S.L. , Gronert-Sum S.J. , Merriman T.R. , Stamp L.K. , Kennedy M.A 
Published: July 2017

AbstractThe human leukocyte antigen (HLA) system is a gene family that encodes the human major histocompatibility complex (MHC). HLA-B is the most polymorphic gene in the MHC class I region, comprised of 4,765 HLA-B alleles (IPD-IMGT/HLA Database Release 3.28). Many HLA-B alleles have been associated with adverse drug reactions and disease risks, and we are interested in developing efficient methods for analysis of HLA alleles in this context. Here we describe an approach to HLA-B typing using multiplexed next generation sequencing on the MinION™ nanopore sequencer (Oxford Nanopore Technologies), combined with data analysis with the SeqNext-HLA software package (JSI Medical Systems GmbH, Ettenheim, Germany). The nanopore sequencer offers the advantages of long-read capability and single molecule reads, which can facilitate effective haplotyping. We developed this method using reference samples of known HLA-B type as well as individuals of New Zealand Māori or Pacific Island (Polynesian) descent, because HLA-B diversity in these populations is not well understood. We demonstrate here that nanopore sequencing of barcoded, pooled, 943 bp polymerase chain reaction (PCR) amplicons of 49 DNA samples, on one R9.4 flowcell (Oxford Nanopore Technologies), generated ample read depth for all samples. Sequence analysis using SeqNext-HLA software assigned HLA-B alleles to all samples at high-resolution with very little ambiguity. Our PCR-based next generation sequencing method is a scaleable and efficient approach for genotyping HLA-B and potentially any other HLA locus. Finally, we report our findings on HLA-B genotypes of this cohort, which adds to our understanding of HLA-B allele frequencies among Māori and Polynesian people.
INO80 Chromatin Remodelling Coordinates Metabolic Homeostasis with Cell Division
Authors: Gowans Graeme J. , Schep Alicia N. , Wong Ka Man , King Devin A. , Greenleaf William J. , Morrison Ashby J. 
Published: July 2017

ABSTRACTAdaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of allS.cerevisiaegenes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the Yeast Metabolic Cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here we demonstrate that the INO80 chromatin-remodelling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin in order to restrict proliferation to metabolically optimal states.