bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atraumatic Spinal Epidural Hematoma as Initial Presentation of Hemophilia A in an Infant
Authors: Crumm Caitlin E. , Crotty Erin E. , Albert Catherine M. , Blair Amanda B. , Otjen Jeffrey P. , Feldman Kenneth W. 
Published: March 2019

Abstract
Hemophilia A is characterized by deficiency of factor VIII. We present a unique, illustrative case of an infant with a short history of neck pain and irritability without neurological deficits who was found to have a spinal epidural hematoma. The subsequent investigation for the etiology, including workup for nonaccidental trauma, led to a diagnosis of severe hemophilia A.
3 Cases of Inflicted Skull Crush Injuries in Infants
Authors: Brown Emily C.B. , Donaruma-Kwoh Marcella M. , Otjen Jeffrey P. , Feldman Kenneth W. 
Published: March 2019

Abstract
We describe 3 infants with skull fractures that involved more than 1 skull bone. On further evaluation, 2 of the 3 infants had additional fractures at other sites of the body and the third infant had concerning bruising of the face. Although an accidental mechanism of injury was initially given as the history in each case, law enforcement investigations led all 3 fathers to confess to crushing their infants' skulls out of frustration. These crushes were caused by their arms or hands. Bilateral skull fractures or those involving more than 1 skull bone can be seen in falls as well as in crush injuries. A crush-like pattern of injury, in the absence of a clear and plausible accidental mechanism, should raise concerns for possible physical abuse especially in nonambulatory infants.
Roller Coaster–Induced Subdural Hematoma in a Previously Healthy Teenager
Authors: Tseng Peggy , Kearl Yvette Liza , Ansari Ashkon 
Published: March 2019

Abstract
Of the multitude of neurologic injuries related to roller-coaster rides, a majority of them are reported about adults. In this case, we present a patient who presented to the pediatric emergency department with new-onset seizure and hemiplegia 2 days after a roller-coaster ride. She was ultimately diagnosed with a subdural hematoma. The acceleration and G forces of roller coasters are hypothesized to cause enough stress and shearing forces that are thought to directly cause subdural hemorrhage.
Advances in roller-coaster technology may surpass the passenger's physical capacity for acceleration and rotary forces, and we may see an increased number of medical complications after these rides. We recommend that emergency and pediatric health care providers consider amusement park thrill rides as a possible cause of subdural hematomas in previously healthy patients with new neurologic complaints.
Austere Foreign Body Injuries in Children and Adolescents
Authors: Fischer Julie , Krishnamurthy Jayasree , Hansen Shana , Reeves Patrick T. 
Published: March 2019

Background
Pediatric foreign body (FB) injuries to the nasal, aural, and/or oral cavities are well documented. Description of austere foreign body (AFB) injuries involving the rectum, vagina, or penis eludes the current pediatric literature. Austere FBs can be difficult to identify and have the potential to cause serious consequences. We aim to characterize AFB injuries by children and adolescents presenting to emergency departments (EDs) in the United States.

Methods
The National Electronic Injury Surveillance System was queried to include subjects aged 0 to 25 years using a primary search term for diagnosis of foreign body from the period of January 2008 to January 2017. The consumer product and the body part involved (ie, rectal, vaginal, penile) were analyzed. Taylor series linearization generated national estimates. A trend analysis was performed using the Cochrane Armitage test of trend.

Results
There were 27,755 (95% confidence interval, 21,170–34,338) national estimated childhood ED visits for suspected AFB injuries during 2008 to 2017 including an estimated 7756 vaginal FBs, 7138 penile FBs, and 8359 rectal FBs (RFBs). Over the timeline, there was a significant up trend in the frequency of annual RFBs (P < 0.01).

Conclusion
Austere FB injuries appear to cluster around age of 7 years. Most AFB injuries are able to be treated and released from the ED. It appears that RFB injury frequencies are rising and tend to require more frequent admission. Providers must be vigilant in the diagnosis and management of these potentially hazardous injury types.
Capturing Patients' Perspectives on Medication Safety: The Development of a Patient-Centered Medication Safety Framework
Authors: Giles Sally J. , Lewis Penny J. , Phipps Denham L. , Mann Faith , Avery Anthony J. , Ashcroft Darren M. 
Published: March 2019

Objectives
Medication safety incidents are common in primary care and contributory factors frameworks can assist in our understanding of their causes. A framework that is positioned from the perspective of patients would be advantageous in practice when seeking patient insights into medication safety. The aim of this study was to develop a patient-centered contributory factors framework for examining medication safety incidents.

Methods
A purposive sample of 106 members of the public, patients, and carers were recruited to take part in focus groups (n = 18). Focus groups were audio recorded, transcribed, and analyzed using a thematic framework. A patient and public involvement group was set up to undertake multiple roles in the research process, including the development of the focus group schedule, analysis of the data, and the construction of a patient-centered framework of contributory factors (patient-centered medication safety) and implementation checklist.

Results
The findings highlighted the importance of communication, supplies of medication and appliances, patient- and carer-related factors, healthcare professional factors, and computer systems and programs in the safe use of medicines. Some contributory factors were unique to primary care patients such as access to services and continuity of care. In conjunction with a patient and public involvement group, a framework of factors that patients believe contribute to medication safety incidents in primary care was developed that could be used by patients and healthcare professionals.

Conclusions
The patient-centered medication safety framework and implementation checklist provides a novel tool to examine contributory factors that can lead to medication safety incidents from patients' perspective.
Differential Uptake of 68Ga-PSMA-HBED-CC (PSMA-11) in Low-Grade Versus High-Grade Gliomas in Treatment-Naive Patients
Authors: Verma Priyanka , Malhotra Gaurav , Goel Atul , Rakshit Sutapa , Chandak Ashok , Chedda Rupal , Banerjee Sharmila , Asopa Ramesh V. 
Published: March 2019

Purpose of the Report
Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein, which is not only overexpressed in prostate cancers but also in variety of solid tumors including glioblastoma multiforme. The aim of the present study was to demonstrate PSMA expression in gliomas using 68Ga-PSMA-HBED-CC(PSMA 11) PET/CT.

Patients and Methods
Ten patients with initially MRI suspected and eventually histopathologically proven gliomas [8 males (age range 30–73 yr; mean age 51.8 yr); 2 females aged 39 and 55 years] were subjected preoperatively to regional brain PET scan with 68Ga-PSMA-11 and 18F-FDG PET/CT. Final histopathology of brain lesions, their MIB-1 proliferation index (MIB-1 PI) were compared with PSMA and FDG PET findings.

Results
FDG PET/CT showed distinct FDG uptake in high-grade gliomas, whereas low-grade gliomas were non-FDG-avid amidst physiological tracer uptake. In vivo PSMA expression was seen in all patients with glioma. Of these, the 7 patients of glioblastoma harboring 8 lesions showed significantly higher PSMA expression than those with low-grade gliomas, average SUVmax being 16.93 and 2.93, respectively. Similarly, average tumor-to-background ratios (13.95 and 3.42, respectively) and MIB-1 PI (17.31 and 3.3, respectively) were substantially more in high-grade versus low-grade gliomas.

Conclusions
The results of this pilot study show that 68Ga-HBED-CC-PSMA PET/CT can be used to characterize the PSMA expression in gliomas, high-grade ones demonstrating higher SUVmax, MIB-1 PI tumor-to-background ratio than the low-grade ones. With these results as basis, certain patients may benefit from potential PSMA-targeted radionuclide therapy.
68Ga-DOTANOC PET/CT in an Atypical Extraskeletal Paravertebral Hemangioma Mimicking as Neurogenic Tumor in a Known Case of Breast Cancer
Authors: Vadi Shelvin Kumar , Mittal Bhagwant Rai , Parihar Ashwin Singh , Kumar Rajender , Singh Harmandeep , Singh Gurpreet 
Published: March 2019

Abstract

68Ga-DOTANOC PET/CT is well documented in evaluation of well-differentiated neuroendocrine tumors and in other lesions with somatostatin receptor expression such as pheochromocytoma, paraganglioma, neuroblastoma, meningioma, and mesenchymal tumors causing oncogenic osteomalacia. Causes of interpretative pitfalls include prominent pancreatic uncinate process activity, inflammation, osteoblastic activity (degenerative bone disease/fracture/vertebral hemangioma), splenunculi/splenosis, and others. We present a case of extraskeletal paravertebral lesion detected in a known case of breast cancer with increased 68Ga-DOTANOC uptake later proved to be hemangioma. This is a novel finding and should be kept as a rare benign differential in evaluation of lesions with somatostatin receptor expression.
Intravesical Extrusion of a Single-Incision Midurethral Sling Anchor With a Simple Transurethral Resection Technique: A Case Report
Authors: Gabriel Iwona M. , Chiang H. Abraham , Kalousdian Anthony , Minassian Vatche A. 
Published: March 2019

Abstract
Single-incision midurethral slings were introduced in 2006 with the goal of providing shorter operative time, less postoperative pain, and decreased rates of injury to surrounding structures (eg, bladder and/or obturator nerve). Although unrecognized bladder injury during SIMS placement is a rare complication, it can lead to irritative voiding symptoms and recurrent urinary tract infections. We present the case of minimally invasive approach to remove an extruded sling.
Increasing Age Predicts Increasing Residual Urine Volume
Authors: Wolff Birte Johanna , Brennan Katelyn , Joyce Cara Jean , Shannon Megan B. , Brincat Cynthia Ann 
Published: March 2019

Objectives
To determine reference values for postvoid residual (PVR) volume for patients referred to a tertiary urogynecology center.

Methods
After Institutional Review Board approval, we performed a retrospective chart review of all new patients presenting to our referral center. We assessed associations between PVR and patient demographics, pelvic floor symptoms, and physical examination by Wilcoxon rank sum or Kruskal-Wallis tests as appropriate. A multivariable logistic regression model was used to calculate odds ratios for patient characteristics associated with PVR in the top age range-specific decile.

Results
Three hundred sixty-one patients were included in the analysis. The median PVR was 20 mL (interquartile range, 1st, 3rd quartiles, 10, 50). Older age was associated with higher PVR (P < 0.001). The median PVR in participants younger than 40 years was 10 mL, ages 40 to 49 years was 18 mL, 50 to 69 years was 20 mL, 70 to 79 years was 38 mL and in women older than 79 years was 50 mL. A multivariable analysis showed that prolapse stage (odds ratio [OR], 3.46 with prolapse stage 2–4 vs stage 0–1; P = 0.001), history of stroke (OR, 7.62; [95% CI 2.17–26.77, P = 0.002]), narcotic use (OR, 2.45; [95% CI 1.01–5.92; P = 0.047]), and urinary frequency (OR, 2.61; [95% CI, 1.14–5.98; P = 0.024]) were risk factors for increased PVR (as defined at >90%ile for age), independent of the age-related elevation.

Conclusions
The majority of patients presenting for urogynecologic evaluation had a low PVR with a median of 20 mL. Postvoid residual was higher for older age groups but nearly all volumes were less than 100 mL. The utility of a PVR measurement is highest for patients with pelvic organ prolapse, urinary frequency, narcotic use, or history of stroke.
Improving the clinical performance of blood-based DNA methylation biomarkers utilizing locus-specific epigenetic heterogeneity
Authors: Miller Brendan F. , Pisanic Thomas R. , Margolin Gennady , Petrykowska Hanna M. , Athamanolap Pornpat , Goncearenco Alexander , Osei-Tutu Akosua , Annunziata Christina M. , Wang Tza-Huei , Elnitski Laura 
Published: March 2019

AbstractBackgroundVariation in intercellular methylation patterns can complicate the use of methylation biomarkers for clinical diagnostic applications such as blood-based cancer testing. Here, we describe development and validation of a methylation density binary classification method called EpiClass (available for download at https://github.com/Elnitskilab/EpiClass), that can be used to predict and optimize the performance of methylation biomarkers, particularly in challenging, heterogeneous samples such as liquid biopsies. This approach is based upon leveraging statistical differences in single-molecule sample methylation density distributions to identify ideal thresholds for sample classification.ResultsWe developed and tested the classifier using reduced representation bisulfite sequencing (RRBS) data derived from ovarian carcinoma tissue DNA and controls. We used these data to perform in silico simulations using methylation density profiles from individual epiallelic copies of ZNF154, a genomic locus known to be recurrently methylated in numerous cancer types. From these profiles, we predicted the performance of the classifier in liquid biopsies for the detection of epithelial ovarian carcinomas (EOC). In silico analysis indicated that EpiClass could be leveraged to better identify cancer-positive liquid biopsy samples by implementing precise thresholds with respect to methylation density profiles derived from circulating cell-free DNA (cfDNA) analysis. These predictions were confirmed experimentally using DREAMing to perform digital methylation density analysis on a cohort of low volume (1-mL) plasma samples obtained from 26 EOC-positive and 41 cancer-free women. EpiClass performance was then validated in an independent cohort of 24 plasma specimens, derived from a longitudinal study of 8 EOC-positive women, and 12 plasma specimens derived from 12 healthy women, respectively, attaining a sensitivity/specificity of 91.7%/100.0%. Direct comparison of CA-125 measurements with EpiClass demonstrated that EpiClass was able to better identify EOC-positive women than standard CA-125 assessment. Finally, we used independent whole genome bisulfite sequencing (WGBS) datasets to demonstrate that EpiClass can also identify other cancer types as well or better than alternative methylation-based classifiers.ConclusionsOur results indicate that assessment of intramolecular methylation density distributions calculated from cfDNA facilitate the use of methylation biomarkers for diagnostic applications. Furthermore, we demonstrated that EpiClass analysis of ZNF154 methylation was able to outperform CA-125 in the detection of etiologically-diverse ovarian carcinomas, indicating the broad utility of ZNF154 for use as a biomarker of ovarian cancer.
A haplotype-aware de novo assembly of related individuals using pedigree graph
Authors: Garg Shilpa , Aach John , Li Heng , Durbin Richard , Church George 
Published: March 2019

AbstractMotivationReconstructing high-quality haplotype-resolved assemblies for related individuals of various species has important applications in understanding Mendelian diseases along with evolutionary and comparative genomics. Through major genomics sequencing efforts such as the Personal Genome Project, the Vertebrate Genome Project (VGP), the Earth Biogenome Project (EBP) and the Genome in a Bottle project (GIAB), a variety of sequencing datasets from mother-father-child trios of various diploid species are becoming available.Current trio assembly approaches are not designed to incorporate long-read sequencing data from parents in a trio, and therefore require relatively high coverages of costly long-read data to produce high-quality assemblies. Thus, building a trio-aware assembler capable of producing accurate and chromosomal-scale diploid genomes in a pedigree, while being cost-effective in terms of sequencing costs, is a pressing need of the genomics community.ResultsWe present a novel pedigree-graph-based approach to diploid assembly using accurate Illumina data and long-read Pacific Biosciences (PacBio) data from all related individuals, thereby generalizing our previous work on single individuals. We demonstrate the effectiveness of our pedigree approach on a simulated trio of pseudo-diploid yeast genomes with different heterozygosity rates, and real data from Arabidopsis Thaliana. We show that we require as little as 30× coverage Illumina data and 15× PacBio data from each individual in a trio to generate chromosomal-scale phased assemblies. Additionally, we show that we can detect and phase variants from generated phased assemblies.Availabilityhttps://github.com/shilpagarg/WHdenovoContactshilpa_garg@hms.harvard.edu, gchurch@genetics.med.harvard.edu
Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons
Authors: Haq Naila , Schmidt-Hieber Christoph , Sialana Fernando J. , Ciani Lorenza , Heller Janosch P. , Stewart Michelle , Bentley Liz , Wells Sara , Rodenburg Richard J. , Nolan Patrick M , Forsythe Elizabeth , Wu Michael C. , Lubec Gert , Häusser Michael , Beales Philip L. , Christou-Savina Sofia 
Published: March 2019

AbstractBardet-Biedl syndrome (BBS), a ciliopathy, is a rare genetic condition characterised by retina degeneration, obesity, kidney failure and cognitive impairment. In spite of a progress made in general understanding of BBS aetiology, the molecular mechanism of cognitive impairment remains elusive. Here we report that loss of Bardet-Biedl syndrome proteins causes synaptic dysfunction in principal neurons providing possible explanation for cognitive impairment phenotype in BBS patients. Using synaptosomal proteomics and immunocytochemistry we demonstrate the presence of Bbs in postsynaptic density of hippocampal neurons. Loss of Bbs results in the significant reduction of dendritic spines in principal neurons ofBbsmice models. Furthermore, we demonstrate that spine deficiency correlates with events that destabilize spine architecture, such as, impaired spine membrane receptors signalling known to be involved in the maintenance of dendritic spines. Finally, we show that voluntary exercise rescues spine deficiency in the neurons. Based on our data, we propose a model in which Bbs proteins, similar to their function in primary cilia, regulate trafficking of signalling receptors into and out of the membrane of dendritic spines, thus providing the basis for synaptic plasticity.
Generation of scale-invariant sequential activity in linear recurrent networks
Authors: Liu Yue , Howard Marc W. 
Published: March 2019

AbstractSequential neural activity has been observed in many parts of the brain and has been proposed as a neural mechanism for memory. The natural world expresses temporal relationships at a wide range of scales. Because we cannot know the relevant scales a priori it is desirable that memory, and thus the generated sequences, are scale-invariant. Although recurrent neural network models have been proposed as a mechanism for generating sequences, the requirements for scale-invariant sequences are not known. This paper reports the constraints that enable a linear recurrent neural network model to generate scale-invariant sequential activity. A straightforward eigendecomposition analysis results in two independent conditions that are required for scaleinvariance for connectivity matrices with real, distinct eigenvalues. First, the eigenvalues of the network must be geometrically spaced. Second, the eigenvectors must be related to one another via translation. These constraints are easily generalizable for matrices that have complex and distinct eigenvalues. Analogous albeit less compact constraints hold for matrices with degenerate eigenvalues. These constraints, along with considerations on initial conditions, provide a general recipe to build linear recurrent neural networks that support scale-invariant sequential activity.
Hi-C guided assemblies reveal conserved regulatory topologies on X and autosomes despite extensive genome shuffling
Authors: Renschler Gina , Richard Gautier , Valsecchi Claudia Isabelle Keller , Toscano Sarah , Arrigoni Laura , Ramirez Fidel , Akhtar Asifa 
Published: March 2019

AbstractGenome rearrangements that occur during evolution impose major challenges on regulatory mechanisms that rely on three-dimensional genome architecture. Here, we developed a scaffolding algorithm and generated chromosome-length assemblies from Hi-C data for studying genome topology in three distantly relatedDrosophilaspecies. We observe extensive genome shuffling between these species with one synteny breakpoint after approximately every six genes. A/B compartments, a set of large gene-dense topologically associating domains (TADs) and spatial contacts between high-affinity sites (HAS) located on the X chromosome are maintained over 40 million years, indicating architectural conservation at various hierarchies. Evolutionary conserved genes cluster in the vicinity of HAS, while HAS locations appear evolutionarily flexible, thus uncoupling functional requirement of dosage compensation from individual positions on the linear X chromosome. Therefore, 3D architecture is preserved even in scenarios of thousands of rearrangements highlighting its relevance for essential processes such as dosage compensation of the X chromosome.
Rational nanotoolbox with theranostic potential for medicated pro-regenerative corneal implants
Authors: Patra Hirak K. , Azharuddin Mohammad , Islam Mohammad M. , Papapavlou Georgia , Deb Suryyani , Zhu Geyunjian Harry , Romu Thobias , Dhara Ashis K. , Jafari Mohammad J. , Gadheri Amineh , Hinkula Jorma , Rajan Madhavan S , Slater Nigel 
Published: March 2019

AbstractCornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory made artificial corneas has not been fully realised in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other micorbes, enzyme over-expression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment, counter the effects of inflammation or infection and that are able to track early signs of implant failurein situ. In the present work, we describe a nano toolbox comprising tools for drug release and in addition capable of being infection responsive, promoting regeneration including non-invasive monitoring ofin situcorneal environment. These nano constructs can be incorporated within pro-regenerative biosynthetic implants, transforming them into theranostic devices able to respond to biological changes following implantation.