bluuebunny/crossref_metadata_2025_split huggingface dataset:
Murine models of autoimmune hemolytic anemia
Authors: Howie Heather L. , Hudson Krystalyn E. 
Published: August 2018

Purpose of review
Pathogenic autoantibodies directed against red blood cells (RBCs) may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Much of what is known about the etiology and pathogenesis of AIHA has been learned from observations made in human patients and murine models, but many questions remain; importantly, it is still unclear why some people generate RBC-specific autoantibodies. The combination of technological advancements applied to existing models and the development of new AIHA murine models will continue to provide considerable insight into the initiation of AIHA and provide a platform for the design of more effective therapies.

Recent findings
Advancements in well described murine models of AIHA show that reticulocytes are preferentially targeted by anti-RBC autoantibodies and an increase in oxidative stress may trigger autoantibody production. Additionally, a new murine model of erythrocyte autoreactivity demonstrates that T cell tolerance is the stopgap for autoimmunity. Moreover, unlike many self-antigens, data suggest that RBC self-antigens are not presented in the thymus thereby escaping the scrutiny of T cell central tolerance mechanisms and placing emphasis on peripheral tolerance instead. Information gained from this new model provide novel insight into how the immune system responds to RBC autoantigens and provides a tractable platform to discover new therapies for AIHA.

Summary
Murine models of AIHA have provided significant understanding into the risk factors for AIHA. The application of new technologies and models of erythrocyte autoreactivity is a pathway with the potential to elucidate how tolerance to RBC autoantigens is established, maintained, and broken down.
Anxiety and Salivary Cortisol Levels in Children Undergoing Esophago‐Gastro‐Duodenoscopy Under Sedation
Authors: Kara Duygu , Bayrak Nevzat Aykut , Volkan Burcu , Uçar Cihat , Cevizci Mehmet Nuri , Yildiz Sedat 
Published: August 2018

ABSTRACTObjectives:Esophagogastroduodenoscopy (EGD) can cause fear and anxiety in children. Cortisol, which is the most important glucocorticoid hormone in humans, can increase under physiological stress. The purpose of this study was to measure the salivary cortisol level (SCL) and anxiety level in patients undergoing EGD and evaluate their effects on the procedure.Methods:Children undergoing EGD under sedoanalgesia with propofol for various reasons were included. Their basal SCLs were compared with those of healthy age‐ and sex‐matched controls. Moreover, SCL of the patient group at 30 minutes before EGD and 2 hours after the procedure were measured. Their anxiety scores were calculated using the modified Yale Preoperative Anxiety Scale before EGD. Duration of endoscopy, sedation, and recovery and total propofol doses were recorded.Results:Demographic properties of the patient group (n = 119; 10.9 ± 3.2 years; 43.7% boys) and control group (n = 85; 11.8 ± 2.8 years; 45.1% boys) were not significantly different. Basal SCLs of both groups were similar (16.9 ± 0.7 vs 19.7 ± 1.8 ng/mL, P = 0.16). SCL before EGD in the patient group was significantly higher than basal and post‐EGD values (P < 0.001 for each). Pre‐EGD SCL was positively correlated with anxiety level, propofol dose, and duration of sedation, procedure, and recovery. Anxiety levels of patients were positively correlated with propofol dose and duration of sedation and recovery, and negatively correlated with age.Conclusions:Childhood EGD is a significant stress factor, which was reflected by the pre‐procedural SCL in this study. Increased anxiety resulted in increased propofol doses and sedoanalgesia‐related procedural durations, which may cause potential complications.
No Useful Field Expansion with Full-field Prisms
Authors: Jung Jae-Hyun , Peli Eli 
Published: August 2018

SIGNIFICANCE
Full-field prisms that fill the entire spectacle eye wire have been considered as field expansion devices for homonymous hemianopia (HH) and acquired monocular vision (AMV). Although the full-field prism is used for addressing binocular dysfunction and for prism adaptation training after brain injury as treatment for spatial hemineglect, we show that the full-field prism for field expansion does not effectively expand the visual field in either HH or AMV.

PURPOSE
Full-field prisms may shift a portion of the blind side to the residual seeing side. However, foveal fixation on an object of interest through a full-field prism requires head and/or eye rotation away from the blind side, thus negating the shift of the field toward the blind side.

METHODS
We fit meniscus and flat full-field 7Δ and 12Δ yoked prisms and conducted Goldmann perimetry in HH and AMV. We compared the perimetry results with ray tracing calculations.

RESULTS
The rated prism power was in effect at the primary position of gaze for all prisms, and the meniscus prisms maintained almost constant power at all eccentricities. To fixate on the perimetry target, the subjects needed to turn their head and/or eyes away from the blind side, which negated the field shift into the blind side. In HH, there was no difference in the perimetry results on the blind side with any of the prisms. In AMV, the lower nasal field of view was slightly shifted into the blind side with the flat prisms, but not with the meniscus prisms.

CONCLUSIONS
Full-field prisms are not an effective field expansion device owing to the inevitable fixation shift. There is potential for a small field shift with the flat full-field prism in AMV, but such lenses cannot incorporate refractive correction. Furthermore, in considering the apical scotoma, the shift provides a mere field substitution at best.
An Unusual Murder
Authors: Barranco Rosario , Molinelli Andrea , Ventura Francesco 
Published: August 2018

AbstractFatalities due to stabbings are usually caused by large blood vessels or organs injuries resulting in hemorrhagic shock. Vagal inhibition from a stab to the neck is an undeniably exceptional event, infrequently described in the literature. In our case report, we describe one such fatality.The body of a deceased 38-year-old man was found near a public garden. According to a bystander, the victim had been assaulted by 2 individuals, sustaining a stab wound to the neck with a broken glass bottle. At the autopsy, there was a large, inverted L–shaped cut wound in the left cervical region, measuring approximately 4.5 × 3 cm. The carotid artery and the jugular vein, as well as their main branches, were uninjured. The trachea and bronchi contained no exudate or blood. There was a hematoma near the trunk of the vagus nerve and its branches.The cause of death was attributed to the deep stab wound to the neck via vasovagal inhibition and parasympathetic nervous system stimulation.
Recommendations on RBC Transfusion Support in Children With Hematologic and Oncologic Diagnoses From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative
Authors: Steiner Marie E. , Zantek Nicole D. , Stanworth Simon J. , Parker Robert I. , Valentine Stacey L. , Lehmann Leslie E. , Josephson Cassandra D. , Bateman Scot T. , Luban Naomi L. C. 
Published: August 2018

Objectives:To present the recommendations and supporting evidence for RBC transfusions in critically ill children with hematologic and oncologic disease from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.Design:Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children.Methods:The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations and research priorities for RBC transfusions in critically ill children. The hematologic/oncologic subgroup included seven experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.Results:The hematologic/oncologic subgroup developed 14 recommendations (seven clinical, seven research); all achieved greater than 80% agreement. In patients with sickle cell disease, Transfusion and Anemia Expertise Initiative recommends: 1) RBC transfusion to achieve a target hemoglobin concentration of 10 g/dL rather than hemoglobin of less than 30% prior to surgical procedures requiring general anesthesia and 2) exchange transfusion over simple (nonexchange) transfusion if the child’s condition is deteriorating (based on clinical judgment), otherwise a simple, nonexchange RBC transfusion is recommended. There is insufficient evidence to make recommendations on transfusion thresholds for patients with sickle cell disease prior to minor procedures, with acute stroke or with pulmonary hypertension. For patients with oncologic disease or undergoing hematopoietic stem cell transplant, a hemoglobin concentration of 7–8 g/dL is recommended. Due to lack of evidence, research is needed to clarify the appropriate transfusion thresholds in these patients.Conclusions:Transfusion and Anemia Expertise Initiative developed specific pediatric recommendations regarding RBC transfusion management in critically ill children with sickle cell disease, oncologic disease, and hematopoietic stem cell transplant and recommendations to help guide future research priorities.
Retinal Hemorrhages
Authors: Hansen Jennifer B. , Killough Emily F. , Moffatt Mary E. , Knapp Jane F. 
Published: August 2018

Abstract
Abusive head trauma is an important cause of morbidity and mortality in infants and young children. Retinal hemorrhages (RHs) are frequently seen, particularly during dilated eye examination of these children. This review focuses on the evaluation of children with RH, with emphasis on the differential diagnosis, pathophysiology, and distinguishing features of RHs due to abusive head trauma. Many causes exist for RHs in infants and children. Most medical and accidental traumatic causes result in a pattern of RH that is nonspecific and not typical of the pattern and distribution of RHs seen in children with abusive head trauma. In children with intracranial hemorrhage and concerns for abuse, the finding of severe, multilayered RHs extending to the periphery of the retina is very specific for abuse as the cause of the findings, especially if retinoschisis is present. There are few other accidental traumatic mechanisms associated with retinoschisis, and the history of such a traumatic event is readily apparent. The indications for ophthalmologic consult, optimal timing of the eye examination, and significance of the findings are specifically discussed.
Ultrasound Elastography Applications in Pediatrics
Authors: Thumar Vishal , Squires Judy H. , Spicer Paul J. , Robinson Amie L. , Chan Sherwin S. 
Published: August 2018

Abstract
Ultrasound is one of the most important imaging modalities in pediatric imaging because of its accessibility, portability, lack of ionizing radiation, and ability to generally perform examinations without need for sedation. Ultrasound elastography can measure the stiffness of various tissues. This review article aims to discuss how ultrasound elastography has performed in evaluating multiple pathologies in the pediatric population. The best studied pediatric applications are in liver diseases such as fibrosis, biliary atresia, and hepatic vascular congestion. Measuring muscle stiffness in cerebral palsy is the most promising pediatric musculoskeletal application, but many other applications are in the early stages of research. Other applications in pediatric small organ imaging have been explored and still need more study before gaining clinical relevance.
Dupuytren’s Contracture
Authors: Mella Juan Rodolfo , Guo Lifei , Hung Virginia 
Published: August 2018

Abstract
Dupuytren’s contracture, a benign condition characterized by fibrosis of the palmar and digital fascia, may be a debilitating condition that limits daily function. Several techniques exist for managing symptomatic contractures of the hand related to Dupuytren’s. These techniques include the more invasive open fasciotomy or fasciectomy. More recently, less invasive techniques including administration of collagenase Clostridium histolyticum (CCH) or percutaneous needle aponeurotomy (PNA) have become part of the treatment armamentarium. A comprehensive review of the literature is performed and an algorithm for management of Dupuytren’s contracture is proposed.
Chrysalis: A new method for high-throughput histo-cytometry analysis of images and movies
Authors: Kotov Dmitri I. , Pengo Thomas , Mitchell Jason S. , Gastinger Matthew J. , Jenkins Marc K. 
Published: August 2018

AbstractAdvances in imaging have led to the development of powerful multispectral, quantitative imaging techniques, like histo-cytometry. The utility of this approach is limited, however, by the need for time consuming manual image analysis. We therefore developed the software Chrysalis and a group of Imaris Xtensions to automate this process. The resulting automation allowed for high-throughput histo-cytometry analysis of 3D confocal microscopy and two-photon time-lapse images of T cell-dendritic cell interactions in the spleen. It was also applied to epi-fluorescence images to quantify T cell localization within splenic tissue by using a ‘signal absorption’ strategy that avoids computationally intensive distance measurements. In summary, this image processing and analysis software makes histo-cytometry more useful for immunology applications by automating image analysis.
Comparing adult hippocampal neurogenesis across species: translating time to predict the tempo in humans
Authors: Charvet Christine J. , Finlay Barbara L 
Published: August 2018

AbstractComparison of neurodevelopmental sequences between species whose initial period of brain organization may vary from one hundred days to one thousand days, and whose progress is intrinsically nonlinear presents large challenges in normalization. Comparing adult timelines when lifespans stretch from one year to seventy-five, when underlying cellular mechanisms under scrutiny do not scale similarly, presents challenges to simple detection and comparison. The question of adult hippocampal neurogenesis has generated numerous controversies regarding its simple presence or absence in humans versus rodents, whether it is best described as the tail of a distribution centered on early neural development, or is several distinct processes. In addition, adult neurogenesis may have substantially changed in evolutionary time in different taxonomic groups. Here we extend and adapt a model of the cross-species transformation of early neurodevelopmental events which presently reaches up to the equivalent of the third human postnatal year for 18 mammalian species (www.translatingtime.net) to address questions relevant to hippocampal neurogenesis, which permit extending the database to adolescence or perhaps to the whole lifespan. We acquired quantitative data delimiting the envelope of hippocampal neurogenesis from cell cycle markers (i.e., Ki67, DCX) and RNA sequencing data for two primates (macaque, humans) and two rodents (rat, mouse). To improve species coverage in primates, we gathered the same data from marmosets (Callithrix jacchus), but additionally gathered data on a number of developmental milestones to find equivalent developmental time points between marmosets and other species. When all species are so modeled, and represented in a common time frame, the envelopes of hippocampal neurogenesis are essentially superimposable. Early developmental events involving the olfactory and limbic system start and conclude possibly slightly early in primates than rodents, and we find a comparable early conclusion of primate hippocampal neurogenesis (as assessed by the relative number of Ki67 cells) suggesting a plateau to low levels at approximately 2 years of age in humans. Marmosets show equivalent patterns within neurodevelopment, but unlike macaque and humans may have wholesale delay in the initiation of neurodevelopment processes previously observed in some precocial mammals such as the guinea pig and multiple large ungulates.
Elevated pyrimidine dimer formation at distinct genomic bases underlie promoter mutation hotspots in UV-exposed cancers
Authors: Elliott Kerryn , Boström Martin , Filges Stefan , Lindberg Markus , den Eynden Jimmy Van , Ståhlberg Anders , Clausen Anders R. , Larsson Erik 
Published: August 2018

ABSTRACTSequencing of whole cancer genomes has revealed an abundance of recurrent mutations in gene-regulatory promoter regions, in particular in melanoma where strong mutation hotspots are observed adjacent to ETS-family transcription factor (TF) binding sites. While sometimes interpreted as functional driver events, these mutations have also been suggested to be due to locally inhibited DNA repair or, alternatively, locally increased propensity for UV damage. Here, we provide evidence that base-specific elevations in the efficacy of UV lesion formation underlie these mutations. First, we find that low-dose UV light induces mutations preferably at a known ETS promoter hotspot in cultured cells even in the absence of global or transcription-coupled nucleotide excision repair (NER), ruling out inhibited repair. Further, by genome-wide mapping of cyclobutane pyrimidine dimers (CPDs) shortly after UV exposure and thus before DNA repair, we find that ETS-related mutation hotspots exhibit a strong base-specific increase in CPD formation frequency. Analysis of a large whole genome cohort illustrates the widespread contribution of this effect to recurrent mutations in melanoma. While inhibited NER underlies a general increase in somatic mutation burden in regulatory regions, we conclude that the most recurrently mutated individual DNA bases arise instead due to locally favorable conditions for UV damage formation, thus explaining a key phenomenon in whole-genome cancer analyses.
Validation of the protein kinase PfCLK3 as a multi-stage cross species malarial drug target
Authors: Alam Mahmood M , Sanchez-Azqueta Ana , Janha Omar , Flannery Erika L. , Mahindra Amit , Mapesa Kopano , Brancucci Nicolas , Antonova-Koch Yevgeniya , Crouch Kathryn , Simwela Nelson Victor , Akinwale Jude , Mitcheson Deborah , Solyakov Lev , Dudek Kate , Jones Carolyn , Zapatero Cleofé , Doerig Christian , Nwakanma Davis C. , Jesús Vázquez Maria , Colmenarejo Gonzalo , Jesús Lafuente Maria , Leon Maria Luisa , Waters Andrew P. , Jamieson Andrew G. , Fernandez Alvaro León Elena , Marti Matthias , Winzeler Elizabeth A. , Gamo Francisco Javier , Tobin Andrew B. 
Published: August 2018

AbstractThe requirement for next generation anti-malarials to be both curative and transmission blockers necessitate the identification of molecular pathways essential for viability of both asexual and sexual parasite life stages. Here we identify a selective inhibitor to the Plasmodium falciparum protein kinase PfCLK3 which we use in combination with chemogenetics, whole genome sequencing and transcriptomics to validate PfCLK3 as a druggable target acting at multiple parasite life stages. Consistent with the proposed role of PfCLK3 as a regulator of RNA splicing, inhibition results in the down-regulation of >400 genes essential for parasite survival. Through this mechanism, blocking PfCLK3 activity not only results in rapid killing of asexual blood stage parasites but is also effective on sporozoites and gametocytes as well as showing parasiticidal activity in all Plasmodium species tested. Hence, our data establishes PfCLK3 as a target with the potential to deliver both symptomatic treatment and transmission blocking in malaria.
Single-molecule imaging reveals the interplay between transcription factors, nucleosomes, and transcriptional bursting
Authors: Donovan Benjamin T. , Huynh Anh , Ball David A. , Poirier Michael G. , Larson Daniel R. , Ferguson Matthew L. , Lenstra Tineke L. 
Published: August 2018

SummaryTranscription factors show rapid and reversible binding to chromatin in living cells, and transcription occurs in sporadic bursts, but how these phenomena are related is unknown. Using a combination of in vitro and in vivo single-molecule imaging approaches, we directly correlated binding of the transcription factor Gal4 with the transcriptional bursting kinetics of the Gal4 target genes GAL3 and GAL10 in living yeast cells. We find that Gal4 dwell times sets the transcriptional burst size. Gal4 dwell time depends on the affinity of the binding site and is reduced by orders of magnitude by nucleosomes. Using a novel imaging platform, we simultaneously tracked transcription factor binding and transcription at one locus, revealing the timing and correlation between Gal4 binding and transcription. Collectively, our data support a model where multiple polymerases initiate during a burst as long as the transcription factor is bound to DNA, and a burst terminates upon transcription factor dissociation.
Troponin-I localizes selected apico-basal cell polarity signals
Authors: Casas-Tintó Sergio , Ferrús Alberto 
Published: August 2018

AbstractBeyond its well characterized role in muscle contraction,DrosophilaTroponin I (TnI) is expressed in other cell types where it plays a role in proliferation control. TnI traffics between the nucleus and the cytoplasm through a sumoylation-dependent mechanism. We address here the role of TnI in the cytoplasm. TnI accumulates in the apical region of epidermal cells and neuroblasts. TnI helps to localize and co-immunoprecipitates with Par-3/Bazooka and with disc large (Dlg), two components of the apico-basal polarity system. By contrast, Scribbled is not affected by TnI depletion. In neuroblasts, TnI is required for the polar localization of Miranda while non-polar Dlg is not affected. TnI loss-of-function triggers genome instability, cell apoptosis and extrusion from wing disc epithelia. However, rescue from apoptosis by p35 does not prevent genome instability demonstrating that both features, apoptosis and genome instability, are mechanistically independent. While PI3K is known to contribute to apico-basal polarity of epithelia in vertebrates,DrosophilaPI3K depletion alters neither the apical localization of TnI or Par3/Bazooka, nor the basal localization of Dlg. However, the overexpression of PI3K prevents the polarity defects caused by TnI depletion. Thus, TnI binds certain apico-basal polarity signals in a cell type dependent context, and it unveils a hitherto unsuspected diversity of mechanisms to allocate cell polarity factors.