bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential of Human Nucleus Pulposus-Like Cells Derived From Umbilical Cord to Treat Degenerative Disc Disease
Authors: Perez-Cruet Mick , Beeravolu Naimisha , McKee Christina , Brougham Jared , Khan Irfan , Bakshi Shreeya , Chaudhry G Rasul 
Published: January 2018

Abstract

BACKGROUND
Degenerative disc disease (DDD) is a common spinal disorder that manifests with neck and lower back pain caused by the degeneration of intervertebral discs (IVDs). Currently, there is no treatment to cure this debilitating ailment.

OBJECTIVE
To investigate the potential of nucleus pulposus (NP)-like cells (NPCs) derived from human umbilical cord mesenchymal stem cells (MSCs) to restore degenerated IVDs using a rabbit DDD model.

METHODS
NPCs differentiated from MSCs were characterized using quantitative real-time reverse transcription polymerase chain reaction and immunocytochemical analysis. MSCs and NPCs were labeled with fluorescent dye, PKH26, and transplanted into degenerated IVDs of a rabbit model of DDD (n = 9 each). Magnetic resonance imaging of the IVDs was performed before and after IVD degeneration, and following cell transplantation. IVDs were extracted 8 wk post-transplantation and analyzed by various biochemical, immunohistological, and molecular techniques.

RESULTS
NPC derivatives of MSCs expressed known NP-specific genes, SOX9, ACAN, COL2, FOXF1, and KRT19. Transplanted cells survived, dispersed, and integrated into the degenerated IVDs. IVDs augmented with NPCs showed significant improvement in the histology, cellularity, sulfated glycosaminoglycan and water contents of the NP. In addition, expression of human genes, SOX9, ACAN, COL2, FOXF1, KRT19, PAX6, CA12, and COMP, as well as proteins, SOX9, ACAN, COL2, and FOXF1, suggest NP biosynthesis due to transplantation of NPCs. Based on these results, a molecular mechanism for NP regeneration was proposed.

CONCLUSION
The findings of this study demonstrating feasibility and efficacy of NPCs to regenerate NP should spur interest for clinical studies to treat DDD using cell therapy.
Cohesive Polydensified Matrix Hyaluronic Acid for the Treatment of Etched-In Fine Facial Lines: A 6-Month, Open-Label Clinical Trial
Authors: Black Jeanette M. , Gross Todd M. , Murcia Crystal L. , Jones Derek H. 
Published: January 2018

BACKGROUND
Available hyaluronic acid dermal fillers have unique biophysical properties that influence their clinical utility, longevity, and aesthetic outcomes.

OBJECTIVE
To evaluate the effectiveness and durability of a cohesive polydensified matrix hyaluronic acid dermal filler (CPM-HA) for the treatment of etched-in fine facial lines.

MATERIALS AND METHODS
Subjects with etched-in fine lines of the forehead, cutaneous lip, melolabial folds, nasolabial folds, and/or radial cheek received treatment with CPM-HA mixed with lidocaine and epinephrine, with an optional touch-up treatment at Week 2, if deemed necessary. Response to treatment (as measured by the Merz Aesthetics Scales, Lemperle Facial Wrinkle Scales, and subject self-assessment) and safety/tolerability were monitored over the course of 26 weeks.

RESULTS
Thirty-one subjects received treatment with CPM-HA to 1 or more facial areas. All 5 treatment areas showed clinically meaningful and statistically significant improvements in average clinician rating scale scores at all study visits (p < .001 vs baseline). Most subjects reported maintained improvement from baseline of 50% or more throughout the 26-week study. Injection site reactions were mild and resolved without intervention.

CONCLUSION
Cohesive polydensified matrix hyaluronic acid dermal filler treatment was well tolerated and provided consistent and durable improvement in the appearance of a diverse range of etched-in fine facial lines.
The Infectious and Noninfectious Etiology, Clinical Picture and Outcome of Neutropenia in Immunocompetent Hospitalized Children
Authors: David Odeya , Fruchtman Yariv , Sergienko Ruslan , Kapelushnik Joseph , Leibovitz Eugene 
Published: January 2018

Background:
Acquired neutropenia in immunocompetent children is common, and its differential diagnosis ranges from benign causes to life-threatening diseases. We described the etiology, clinical picture and outcome of new-onset neutropenia in immunocompetent children assessed in the emergency department and hospitalized at our medical center.

Methods:
Previously healthy children admitted with neutropenia (absolute neutrophil count <1.5 × 109/L) were included. Serious bacterial infections were defined as culture-positive blood, urine, cerebrospinal fluid, articular fluid or stool infections, pneumonia, Brucellosis and Rickettsiosis.

Results:
A total of 601 patients (5 days–202 months old) were enrolled; 3 (0.5%), 48 (8%), 165 (27.5%) and 385 (64%) had absolute neutrophil counts <0.2, 0.2–0.5, 0.5–1.0 and 1.0–1.5 × 109/L, respectively. Associated leukopenia and thrombocytopenia were diagnosed in 186 (39%) and 71 (11.8%) patients. Three hundred sixteen of 601 (52.6%) and 519 of 601 (86.4%) were <2 or 36 months of age, respectively. Fever at admission was present in 27.6% patients. Serious bacterial infections were diagnosed in 106 (17.6%) patients. Brucellosis and rickettsiosis were diagnosed in 8 of 52 (15.4%) and 9 of 39 (23.1%) tests obtained. Respiratory syncytial virus was diagnosed in 17 of 33 (51.5%) nasal washes. An infectious etiology was determined in 171 (28.5%) patients. Acute leukemia was diagnosed in 6 patients. A significant correlation was found between resolution of neutropenia and patient age, infectious etiology and severity of neutropenia.

Conclusions:
(1) Severe neutropenia was rare; (2) More than half of patients were <2 months of age; (3) An infectious etiology was diagnosed in a high number of patients, and serious bacterial infections were frequent and (4) Brucella spp. and rickettsial infections were frequent etiologies associated with neutropenia in our setting.
Novel approach to characterising individuals with low back-related leg pain: cluster identification with latent class analysis and 12-month follow-up
Authors: Stynes Siobhán , Konstantinou Kika , Ogollah Reuben , Hay Elaine M. , Dunn Kate M. 
Published: January 2018

Abstract
Traditionally, low back-related leg pain (LBLP) is diagnosed clinically as referred leg pain or sciatica (nerve root involvement). However, within the spectrum of LBLP, we hypothesised that there may be other unrecognised patient subgroups. This study aimed to identify clusters of patients with LBLP using latent class analysis and describe their clinical course. The study population was 609 LBLP primary care consulters. Variables from clinical assessment were included in the latent class analysis. Characteristics of the statistically identified clusters were compared, and their clinical course over 1 year was described. A 5 cluster solution was optimal. Cluster 1 (n = 104) had mild leg pain severity and was considered to represent a referred leg pain group with no clinical signs, suggesting nerve root involvement (sciatica). Cluster 2 (n = 122), cluster 3 (n = 188), and cluster 4 (n = 69) had mild, moderate, and severe pain and disability, respectively, and response to clinical assessment items suggested categories of mild, moderate, and severe sciatica. Cluster 5 (n = 126) had high pain and disability, longer pain duration, and more comorbidities and was difficult to map to a clinical diagnosis. Most improvement for pain and disability was seen in the first 4 months for all clusters. At 12 months, the proportion of patients reporting recovery ranged from 27% for cluster 5 to 45% for cluster 2 (mild sciatica). This is the first study that empirically shows the variability in profile and clinical course of patients with LBLP including sciatica. More homogenous groups were identified, which could be considered in future clinical and research settings.
Factors Associated With Delayed Discharge on General Medicine Service at an Academic Medical Center
Authors: Rohatgi Nidhi , Kane Marlena , Winget Marcy , Haji-Sheikhi Farnoosh , Ahuja Neera 
Published: January 2018

ABSTRACT
Lack of collaboration between care teams and patients/families has been associated with delayed discharge from the hospital. In this study, we determine whether patients' awareness of the estimated date of discharge (EDD) was associated with a decrease in delayed discharge, and determine the factors associated with a delayed discharge. A total of 221 patients admitted to the General Medicine service between July and September 2014 were included in the study. Estimated date of discharge was identified within 36 hours of admission. The bedside nurse communicated this EDD to the patient/family. Patients were interviewed to identify whether they were aware of their EDD. Bedside nurses were interviewed to identify barriers to discharge. In our study, 49.8% of the patients had a delayed discharge. Patients who were aware of their EDD were less likely to have a delayed discharge (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.1–0.6], p < .001). Patients who were discharged on Saturday or Sunday (OR, 4.8 [95% CI, 1.7–14.6], p < .001) and patients who were waiting for physicians' consult (OR, 4.5 [95% CI, 1.6–14.4], p = .007) were more likely to have a delayed discharge. Early identification of the EDD and communicating it with the care team and the patient/family, mobilizing resources for safe weekend discharges, and creating efficient process for consultations might decrease delayed discharges.
Both α-1-antitrypsin Z phenotypes and low caeruloplasmin levels are over-represented in alcohol and nonalcoholic fatty liver disease cirrhotic patients undergoing liver transplant in Ireland
Authors: El-Rayah El-Gaily A. , Twomey Patrick J. , Wallace Eleanor M. , McCormick Peter A. 
Published: January 2018

Objectives
Alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) are steatotic liver diseases and major causes of cirrhosis. Only a minority of patients with risk factors develop cirrhosis and genetic cofactors may be important in pathogenesis. Mutations in the Wilson’s and α-1-antitrypsin genes are not uncommon and we speculated that they may act as cofactors.

Methods
We investigated α-1-antitrypsin phenotyes and caeruloplasmin levels in patients undergoing elective liver transplantation. We compared patients with alcohol and NAFLD with nonsteatotic liver disease patients: viral hepatitis B or C, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis.

Results
Two hundred and thirty-one patients were included in the study. Pretransplant caeruloplasmin levels and α-1-antitrypsin phenotypes were available in 197 and 112 patients, respectively. α-1-Antitrypsin Z phenotypes were significantly more common in the alcohol and NAFLD group: 12/56 versus 3/56 (P<0.05). Serum caeruloplasmin (0.3±0.01 vs. 0.39±0.01 g/l, P<0.01) and serum copper levels (13.5±0.9 vs. 19.3±0.9 μmol/l, P<0.01) were significantly lower in the alcohol and NAFLD patients compared with the viral and autoimmune patients.

Conclusion
In this study, we found the α-1-antitrypsin Z phenotype was more common, and serum caeruloplasmin and copper levels were lower in patients with fatty liver diseases. We suggest that mutations in the α-1-antitrypsin and Wilson’s genes may act as cofactors in the pathogenesis of fatty liver diseases.
Renal Replacement Therapy in the Critically Ill Child*
Authors: Westrope Claire A. , Fleming Sarah , Kapetanstrataki Melpo , Parslow Roger C. , Morris Kevin P. 
Published: January 2018

Objectives:
Although renal replacement therapy is widely used in critically ill children, there have been few comprehensive population-based studies of its use. This article describes renal replacement therapy use, and associated outcomes, in critically ill children across the United Kingdom in the largest cohort study of this patient group.

Design:
A retrospective observational study using prospectively collected data.

Setting:
Data from the Pediatric Intensive Care Audit Network database which collects data on all children admitted to U.K. PICUs.

Patients:
Children (< 16 yr) in PICU who received renal replacement therapy between January 1, 2005, and December 31, 2012, were identified.

Interventions:
Individual-level data including age, underlying diagnosis, modality (peritoneal dialysis and continuous extracorporeal techniques [continuous renal replacement therapy]), duration of renal replacement therapy, PICU length of stay, and survival were extracted.

Measurements and Main Results:
Three-thousand eight-hundred twenty-five of 129,809 PICU admissions (2.9%) received renal replacement therapy in 30 of 33 centers. Volumes of renal replacement therapy varied considerably from 0% to 8.6% of PICU admissions per unit, but volume was not associated with patient survival. Overall survival to PICU discharge (73.8%) was higher than previous reports. Mortality risk was related to age, with lower risk in older children compared with neonates (odds ratio, 0.6; 95% CI, 0.5–0.8) although mortality did not increase over the age of 1 year; mode of renal replacement therapy, with lower risk in peritoneal dialysis than continuous renal replacement therapy methodologies (odds ratio, 0.7; 0.5–0.9); duration of renal replacement therapy (odds ratio, 1.02/d; 95% CI, 1.01–1.04); and primary diagnosis, with the lowest survival in liver disease patients (53.9%).

Conclusions:
This study describes current renal replacement therapy use across the United Kingdom and associated outcomes. We describe a number of factors associated with outcome, including age, underlying diagnosis, and renal replacement therapy modality which will need to be factored into future trial design.
Gadolinium Accumulation in the Deep Cerebellar Nuclei and Globus Pallidus After Exposure to Linear but Not Macrocyclic Gadolinium-Based Contrast Agents in a Retrospective Pig Study With High Similarity to Clinical Conditions
Authors: Boyken Janina , Frenzel Thomas , Lohrke Jessica , Jost Gregor , Pietsch Hubertus 
Published: January 2018

Objective
The aim of this retrospective study was to determine the gadolinium (Gd) concentration in different brain areas in a pig cohort that received repeated administration of Gd-based contrast agents (GBCAs) at standard doses over several years, comparable with a clinical setting.

Material and Methods
Brain tissue was collected from 13 Göttingen mini pigs that had received repeated intravenous injections of gadopentetate dimeglumine (Gd-DTPA; Magnevist) and/or gadobutrol (Gadovist). The animals have been included in several preclinical imaging studies since 2008 and received cumulative Gd doses ranging from 7 to 129 mmol per animal over an extended period. Two animals with no history of administration of GBCA were included as controls. Brain autopsies were performed not earlier than 8 and not later than 38 months after the last GBCA application. Tissues from multiple brain areas including cerebellar and cerebral deep nuclei, cerebellar and cerebral cortex, and pons were analyzed for Gd using inductively coupled plasma mass spectrometry.

Results
Of the 13 animals, 8 received up to 48 injections of gadobutrol and Gd-DTPA and 5 received up to 29 injections of gadobutrol only. In animals that had received both Gd-DTPA and gadobutrol, a median (interquartile range) Gd concentration of 1.0 nmol/g tissue (0.44-1.42) was measured in the cerebellar nuclei and 0.53 nmol/g (0.29-0.62) in the globus pallidus. The Gd concentration in these areas in gadobutrol-only animals was 50-fold lower with median concentrations of 0.02 nmol/g (0.01-0.02) for cerebellar nuclei and 0.01 nmol/g (0.01-0.01) for globus pallidus and was comparable with control animals with no GBCA history. Accordingly, in animals that received both GBCAs, the amount of residual Gd correlated with the administered dose of Gd-DTPA (P ≤ 0.002) but not with the total Gd dose, consisting of Gd-DTPA and gadobutrol. The Gd concentration in cortical tissue and in the pons was very low (≤0.07 nmol/g tissue) in all animals analyzed.

Conclusion
Multiple exposure to macrocyclic gadobutrol is not associated with Gd deposition in brain tissue of healthy pigs. A single additional administration of linear Gd-DTPA is sufficient for Gd accumulation in the nucleus dentatus and globus pallidus, underlining the importance of obtaining a complete GBCA history in clinical studies.
Posterior Compartment Surgery Provides No Differential Benefit for Defecatory Symptoms Before or After Concomitant Mesh-Augmented Apical Suspension
Authors: Arunachalam Divya , Hale Douglass S. , Heit Michael H. 
Published: January 2018

Objectives
The aim of this study was to determine the value of posterior compartment surgery during concomitant mesh-augmented apical suspension by comparing obstructed defecatory symptoms after laparoscopic sacrocolpopexy (LSC) with LSC with posterior repair (LSC + PR) and laparoscopic sacrocolpoperineopexy (LSCP) procedures.

Methods
This was a retrospective cohort study of women who underwent LSC, LSC + PR, and LSCP between July 2007 and July 2016 at a tertiary referral center in Indianapolis, Ind. Our primary outcome was differential change in Colorectal-Anal Distress Inventory (CRADI-8) and Colorectal-Anal Impact Questionnaire (CRAIQ-7) scores between the groups including patient-specific symptoms of splinting, straining, incomplete emptying, and pain with defecation. Our secondary outcomes were the rates of postoperative persistent, new, and resolved obstructed defecation symptoms. Anatomic outcomes were also compared between the groups as measured by change in Pelvic Organ Prolapse Quantification System points Ap, GH, and PB.

Results
A total of 312 women were included in the study (47 LSC, 133 LSC + PR, and 132 LSCP), with a median follow-up time of 366 days. The majority of patients who underwent surgery had stage III pelvic organ prolapse (61%). Baseline demographics were similar between groups, including preoperative CRADI-8 and CRAIQ-7 scores. All surgical groups demonstrated improvement in CRADI-8 and CRAIQ-7 scores postoperatively (P < 0.001). However, despite differential change in Pelvic Organ Prolapse Quantification System points Ap, GH, and PB, there was no change in CRADI-8 and CRAIQ-7 scores or rates of persistent, new, and resolved symptoms of splinting to defecate, incomplete emptying, and pain with defecation between the groups. The only factor that seemed to be differentially improved by the addition of a posterior compartment repair was postoperative straining. There was a greater rate of de novo straining in the LSC group compared with LSCP (P = 0.01) (LSC + PR v LSCP, P = NS, for both).

Conclusions
We cannot recommend posterior compartment surgery as providing any patient-centered benefit beyond improved cosmesis because the addition of perineal body stabilization either before (LSCP) or posterior repair after (LSC + PR) concomitant mesh-augmented apical suspension did not differentially affect bowel symptoms compared with LSC alone.
Targeted epigenomic changes to the maize methylome resulting from tissue culture
Authors: Han Zhaoxue , Crisp Peter A. , Stelpflug Scott , Kaeppler Shawn M. , Li Qing , Springer Nathan M. 
Published: January 2018

AbstractDNA methylation can contribute to the maintenance of genome integrity and regulation of gene expression. In most situations, DNA methylation patterns are inherited quite stably. However, changes in DNA methylation can occur at some loci as a result of tissue culture resulting in somaclonal variation. A sequence-capture bisulfite sequencing approach was implemented to monitor context-specific DNA methylation patterns in ~15Mb of the maize genome for a population of plants that had been regenerated from tissue culture. Plants that have been regenerated from tissue culture exhibit gains and losses of DNA methylation at a subset of genomic regions. There was evidence for a high rate of homozygous changes to DNA methylation levels that occur consistently in multiple independent tissue culture lines suggesting the existence of a targeted process for altering epigenetic state during tissue culture. The consistent changes induced by tissue culture include both gains and losses of DNA methylation and can affect CG, CHG or both contexts within a region. The majority of changes in DNA methylation exhibit stable inheritance although there is some evidence for stochastic reacquisition of the initial epigenetic state in some individuals. This study provides insights into the susceptibility of some loci and potential mechanisms that could contribute to altered DNA methylation and epigenetic state that occur during tissue culture in plant species.
Whole body transcriptomes and new insights into the biology of the tick Ixodes ricinus
Authors: Charrier N. Pierre , Couton Marjorie , Voordouw Maarten J. , Rais Olivier , Durand-Hermouet Axelle , Hervet Caroline , Plantard Olivier , Rispe Claude 
Published: January 2018

AbstractBackgroundIxodes ricinus is the most important vector of tick-borne-diseases in Europe. A better knowledge of its genome and transcriptome is important for developing control strategies. Previous transcriptomic studies of I. ricinus have focused on gene expression during the blood meal in specific tissues. To obtain a broader picture of changes in gene expression during the blood meal, our study analysed the transcriptome at the level of the whole body for both nymphal and adult ticks. I. ricinus ticks from a highly inbred colony at the University of Neuchâtel were used. We also analysed previously published RNAseq studies to compare the genetic variation between three wild strains and three lab strains, including the strain from Neuchâtel.ResultsRNA was extracted from whole tick bodies and the cDNA was sequenced, producing 162,872,698 paired-end reads. Our reference transcriptome contained 179,682 contigs, of which 31% were annotated using Trinotate. Gene expression was compared between ticks that differed with respect to stage (nymph, adult), sex (female, male), and feeding status (unfed, partially fed). We found that blood feeding in nymphs and female adult ticks increased the expression of cuticle-associated genes. Using a set of 5,422 single nucleotide polymorphisms to calculate the heterozygosity, we found that the wild tick populations of I. ricinus had much higher levels of heterozygosity than the three lab populations.ConclusionUsing high throughput strand-oriented sequencing for whole ticks in different stages and feeding conditions, we obtained a de novo assembly that significantly increased the genomic resources available for I. ricinus. Our study illustrates the importance of analysing the transcriptome at the level of the whole body to gain additional insights into how gene expression changes over the life cycle of an organism. Our comparison of several RNAseq datasets shows the power of transcriptomic data to accurately characterize genetic polymorphism and for comparing different populations or sources of sequencing material.