bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indirect Effect of Azithromycin Use on the Intestinal Microbiome Diversity of Untreated Children: A Randomized Trial
Authors: Oldenburg Catherine E , Sié Ali , Coulibaly Boubacar , Ouermi Lucienne , Dah Clarisse , Tapsoba Charlemagne , Bärnighausen Till , Lebas Elodie , Arzika Ahmed M , Cummings Milo E , Zhong Lina , Lietman Thomas M , Keenan Jeremy D , Doan Thuy 
Published: February 2019

Abstract
Cohabiting children may share components of their intestinal microbiome. We evaluated whether receipt of azithromycin in one sibling confers changes to the intestinal microbiome in an untreated sibling compared with placebo in a randomized controlled trial. We found no evidence of an indirect effect of antibiotic use in cohabiting children.
Clinical Trials Registrations: NCT03187834.
A Quantitative Assessment of the Accuracy and Reliability of Robotically Guided Percutaneous Pedicle Screw Placement: Technique and Application Accuracy
Authors: Godzik Jakub , Walker Corey T , Hartman Cory , de Andrada Bernardo , Morgan Clinton D , Mastorakos George , Chang Steven , Turner Jay , Porter Randall W , Snyder Laura , Uribe Juan 
Published: February 2019

Abstract

BACKGROUND
Minimally invasive surgery (MIS) and anterior (ALIF), transforaminal (TLIF), or lateral lumbar interbody fusion (LLIF) often require percutaneous pedicle screw fixation (PSF) to achieve circumferential fusion. Robotic guidance technology may augment workflow to improve screw placement and decrease operative time.

OBJECTIVE
To report surgical experience with robotically assisted percutaneous screw placement following LLIF.

METHODS
Data from fusions with robotically assisted PSF in prone or lateral decubitus positions was reviewed. A CT-guided robotic guidance arm was used for screw placement (Excelsius GPS™, Globus Medical Inc, Audubon, Pennsylvania). Postoperative CT imaging facilitated screw localization. 3-dimensional and 2-dimensional coordinates of the screw tip and tail were calculated and compared with a target trajectory to calculate targeting errors. Breach was defined as a violation of the lateral or medial pedicle wall.

RESULTS
Robotic-guided screw placement was successful in 28/31 patients. In those patients, 116/116 screws were successfully implanted. The breach rate was 3.4% (4/116). Across 17 patients (70 screws), mean 3-D accuracy was 5.0 ± 2.4 mm, mean 2-D accuracy was 2.6 ± 1.1 mm, and mean angular offset was 5.6 ± 4.3° with corresponding intraclass correlation coefficients (ICC) of 0.775 and 0.693. 3-dimensional accuracy correlated with age (R = 0.306, P = .011) and BMI (R = 0.252, P = .038). Accuracy did not significantly differ among vertebral body levels (P > .22). Mean operative time for MIS-TLIF and percutaneous screws was 277 ± 52 and 183 ± 54 min, respectively. Operative time did not significantly decrease across either group (P > .187).

CONCLUSION
The Excelsius GPS™ robotic guidance system allows accurate PSF in most cases with 2 mm 2-D accuracy. Future studies are needed to demonstrate the utility of this novel guidance system and workflow improvement.
THC intoxication in a 16-month-old child
Authors: Burrows Kim , Williams Jennifer Ann 
Published: February 2019

Abstract
A 16-month-old previously healthy child with normal development presented with decreased level of consciousness, apneas, and seizure requiring intubation and treatment for status epilepticus. Investigations revealed no evidence of infection or trauma, normal head CT scan, and urine positive for tetrahydrocannabinol (THC) and negative for other substances. This report outlines the clinical presentation, approach to treatment, and potential seriousness of THC intoxication in young children. Mandatory reporting and monitoring of THC intoxication in children is recommended. The need for effective education of parents about the risks of unintentional THC poisoning and measures to safeguard young children is discussed.
Connectome-Based Patterns of First-Episode Medication-Naïve Patients With Schizophrenia
Authors: Cui Long-Biao , Wei Yongbin , Xi Yi-Bin , Griffa Alessandra , De Lange Siemon C , Kahn René S , Yin Hong , Van den Heuvel Martijn P 
Published: February 2019

Abstract
Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P = .012, uncorrected), with rich club connection strength (P = .032, uncorrected) and SC-FC coupling (P < .001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder.
How (not) to change the (un)changeable?
Authors: Ronovská Kateřina , Pihera Vlastimil 
Published: February 2019

Abstract
The aim of this article is to outline how the current Czech legal doctrine deals with one of the most problematic issues in foundation law, namely the issue of making ex post facto changes to foundation deeds, including a change of purpose. When dealing with this topic, we need to consider the lack of clarity of the current regulation, which was inspired by various (sometimes antithetical) conceptual approaches. It is likely that the direction of the entire Czech foundation law will be dependent upon how such legal issues are addressed. With a view to the general nature of the issue, an analysis of the Czech situation is relevant for other countries as well. For that reason, the discussion is based on the general framework of the current trends in the development of foundation law in Europe.
Molecular epidemiology of Marek’s disease virus in central Pennsylvania, USA
Authors: Bell Andrew S , Kennedy David A , Jones Matthew J , Cairns Christopher L , Pandey Utsav , Dunn Patricia A , Szpara Moriah L , Read Andrew F 
Published: February 2019

AbstractThe evolution of Marek’s disease virus (MDV, Gallid herpesvirus 2) has threatened the sustainability of poultry farming in the past and its continued evolution remains a concern. Genetic diversity is key to understanding evolution, yet little is known about the diversity of MDV in the poultry industry. Here, we investigate the diversity of MDV on 19 Pennsylvanian poultry farms over a 3-year period. Using eight polymorphic markers, we found that at least twelve MDV haplotypes were co-circulating within a radius of 40 km. MDV diversity showed no obvious spatial clustering nor any apparent clustering by bird line: all of the virus haplotypes identified on the commercial farms could be found within a single, commonly reared bird line. On some farms, a single virus haplotype dominated for an extended period of time, while on other farms the observed haplotypes changed over time. In some instances, multiple haplotypes were found simultaneously on a farm, and even within a single dust sample. On one farm, co-occurring haplotypes clustered into phylogenetically distinct clades, putatively assigned as high and low virulence pathotypes. Although the vast majority of our samples came from commercial poultry farms, we found the most haplotype diversity on a noncommercial backyard farm experiencing an outbreak of clinical Marek’s disease. Future work to explore the evolutionary potential of MDV might therefore direct efforts toward farms that harbor multiple virus haplotypes, including both backyard farms and farms experiencing clinical Marek’s disease.
Effects of Mesenchymal Stem Cell Treatment on Systemic Cytokine Levels in a Phase 1 Dose Escalation Safety Trial of Septic Shock Patients*
Authors: Schlosser Kenny , Wang Jia-Pey , dos Santos Claudia , Walley Keith R. , Marshall John , Fergusson Dean A. , Winston Brent W. , Granton John , Watpool Irene , Stewart Duncan J. , McIntyre Lauralyn A. , Mei Shirley H. J. ,   on behalf of the Canadian Critical Care Trials Group and the Canadian Critical Care Translational Biology Group
Published: February 2019

Objectives:
Cellular Immunotherapy for Septic Shock is the first-in-human clinical trial evaluating allogeneic mesenchymal stem/stromal cells in septic shock patients. Here, we sought to determine whether plasma cytokine profiles may provide further information into the safety and biological effects of mesenchymal stem/stromal cell treatment, as no previous study has conducted a comprehensive analysis of circulating cytokine levels in critically ill patients treated with mesenchymal stem/stromal cells.

Design:
Phase 1 dose-escalation trial.

Patients:
The interventional cohort (n = 9) of septic shock patients received a single dose of 0.3, 1.0, or 3.0 million mesenchymal stem/stromal cells/kg body weight (n = 3 per dose). The observational cohort received no mesenchymal stem/stromal cells (n = 21).

Interventions:
Allogeneic bone marrow-derived mesenchymal stem/stromal cells.

Measurements and Main Results:
Serial plasma samples were collected at study baseline prior to mesenchymal stem/stromal cell infusion (0 hr), 1 hour, 4 hours, 12 hours, 24 hours, and 72 hours after mesenchymal stem/stromal cell infusion/trial enrollment. Forty-nine analytes comprised mostly of cytokines along with several biomarkers were measured. We detected no significant elevations in a broad range of pro-inflammatory cytokines and biomarkers between the interventional and observational cohorts. Stratification of the interventional cohort by mesenchymal stem/stromal cell dose further revealed patient-specific and dose-dependent perturbations in cytokines, including an early but transient dampening of pro-inflammatory cytokines (e.g., interleukin-1β, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein 1), suggesting that mesenchymal stem/stromal cell treatment may alter innate immune responses and underlying sepsis biology.

Conclusions:
A single infusion of up to 3 million cells/kg of allogeneic mesenchymal stem/stromal cells did not exacerbate elevated cytokine levels in plasma of septic shock patients, consistent with a safe response. These data also offer insight into potential biological mechanisms of mesenchymal stem/stromal cell treatment and support further investigation in larger randomized controlled trials.
Multicolumn spinal cord stimulation for predominant back pain in failed back surgery syndrome patients: a multicenter randomized controlled trial
Authors: Rigoard Philippe , Basu Surajit , Desai Mehul , Taylor Rod , Annemans Lieven , Tan Ye , Johnson Mary Jo , Van den Abeele Carine ,   PROMISE Study Group, North Richard 
Published: February 2019

Abstract
Despite optimal medical management (OMM), low back pain (LBP) can be disabling, particularly after spinal surgery. Spinal cord stimulation (SCS) is effective in reducing neuropathic leg pain; however, evidence is limited for LBP. This prospective, open-label, parallel-group trial randomized (1:1) failed back surgery syndrome (FBSS) patients with predominant LBP to SCS plus OMM (SCS group) or OMM alone (OMM group) at 28 sites in Europe and the Americas. If trial stimulation was successful, a multicolumn SCS system was implanted. Outcomes were assessed at baseline (before randomization) and at 1, 3, 6, and 12 months after randomization. Patients could change treatment groups at 6 months. The primary outcome was the proportion of patients with ≥50% reduction in LBP (responder) at 6 months. Secondary outcomes included change in pain intensity, functional disability, and health-related quality of life (HRQoL). The results are posted at ClinicalTrials.gov under registration number NCT01697358. In the intent-to-treat analysis, there were more responders in the SCS group than in the OMM group (13.6%, 15/110 vs 4.6%, 5/108, difference 9% with 95% confidence interval 0.6%-17.5%, P = 0.036) at 6 months. The SCS group improved in all secondary outcomes compared with the OMM group. The OMM group only improved in HRQoL. In the SCS group, 17.6% (18/102) experienced SCS-related adverse events through 6 months, with 11.8% (12/102) requiring surgical reintervention. Adding multicolumn SCS to OMM improved pain relief, HRQoL, and function in a traditionally difficult-to-treat population of failed back surgery syndrome patients with predominant LBP. Improvements were sustained at 12 and 24 months.
The role of Nav1.7 in human nociceptors: insights from human induced pluripotent stem cell–derived sensory neurons of erythromelalgia patients
Authors: Meents Jannis E. , Bressan Elisangela , Sontag Stephanie , Foerster Alec , Hautvast Petra , Rösseler Corinna , Hampl Martin , Schüler Herdit , Goetzke Roman , Le Thi Kim Chi , Kleggetveit Inge Petter , Le Cann Kim , Kerth Clara , Rush Anthony M. , Rogers Marc , Kohl Zacharias , Schmelz Martin , Wagner Wolfgang , Jørum Ellen , Namer Barbara , Winner Beate , Zenke Martin , Lampert Angelika 
Published: February 2019

Abstract
The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (NaV) 1.7. Still, recent studies targeting NaV1.7 in clinical trials have provided conflicting results. Here, we differentiated induced pluripotent stem cells from IEM patients with the NaV1.7/I848T mutation into sensory nociceptors. Action potentials in these IEM nociceptors displayed a decreased firing threshold, an enhanced upstroke, and afterhyperpolarization, all of which may explain the increased pain experienced by patients. Subsequently, we investigated the voltage dependence of the tetrodotoxin-sensitive NaV activation in these human sensory neurons using a specific prepulse voltage protocol. The IEM mutation induced a hyperpolarizing shift of NaV activation, which leads to activation of NaV1.7 at more negative potentials. Our results indicate that NaV1.7 is not active during subthreshold depolarizations, but that its activity defines the action potential threshold and contributes significantly to the action potential upstroke. Thus, our model system with induced pluripotent stem cell–derived sensory neurons provides a new rationale for NaV1.7 function and promises to be valuable as a translational tool to profile and develop more efficacious clinical analgesics.
Cisplatin educates CD8+ T cells to prevent and resolve chemotherapy-induced peripheral neuropathy in mice
Authors: Laumet Geoffroy , Edralin Jules D. , Dantzer Robert , Heijnen Cobi J. , Kavelaars Annemieke 
Published: February 2019

Abstract
The mechanisms responsible for the persistence of chemotherapy-induced peripheral neuropathy (CIPN) in a significant proportion of cancer survivors are still unknown. Our previous findings show that CD8+ T cells are necessary for the resolution of paclitaxel-induced mechanical allodynia in male mice. In this study, we demonstrate that CD8+ T cells are not only essential for resolving cisplatin-induced mechanical allodynia, but also to normalize spontaneous pain, numbness, and the reduction in intraepidermal nerve fiber density in male and female mice. Resolution of CIPN was not observed in Rag2
−/− mice that lack T and B cells. Reconstitution of Rag2
−/− mice with CD8+ T cells before cisplatin treatment normalized the resolution of CIPN. In vivo education of CD8+ T cells by cisplatin was necessary to induce resolution of CIPN in Rag2

−/−
mice because adoptive transfer of CD8+ T cells from naive wild-type mice to Rag2
−/− mice after completion of chemotherapy did not promote resolution of established CIPN. The CD8+ T-cell-dependent resolution of CIPN does not require epitope recognition by the T-cell receptor. Moreover, adoptive transfer of cisplatin-educated CD8+ T cells to Rag2
−/− mice prevented CIPN development induced by either cisplatin or paclitaxel, indicating that the activity of the educated CD8+ T is not cisplatin specific. In conclusion, resolution of CIPN requires in vivo education of CD8+ T cells by exposure to cisplatin. Future studies should examine whether ex vivo CD8+ T cell education could be applied as a therapeutic strategy for treating or preventing CIPN in patients.
Nociceptin/orphanin FQ receptor modulates painful and fatigue symptoms in a mouse model of fibromyalgia
Authors: Dagnino Ana Paula Aquistapase , da Silva Rodrigo Braccini Madeira , Chagastelles Pedro Cesar , Pereira Talita Carneiro Brandão , Venturin Gianina Teribele , Greggio Samuel , Costa da Costa Jaderson , Bogo Maurício Reis , Campos Maria Martha 
Published: February 2019

AbstractGeneralized pain and fatigue are both hallmarks of fibromyalgia, a syndrome with an indefinite etiology. The treatment options for fibromyalgia are currently limited, probably because of its intricate pathophysiology. Thus, further basic and clinical research on this condition is currently needed. This study investigated the effects of nociceptin/orphanin FQ (N/OFQ) receptor (NOPr) ligands and the modulation of the NOP system in the preclinical mouse model of reserpine-induced fibromyalgia. The effects of administration of the natural agonist N/OFQ and the selective NOPr antagonists (UFP-101 and SB-612111) were evaluated in fibromyalgia-related symptoms in reserpine-treated mice. The expression of prepronociceptin/orphanin FQ and NOPr was assessed in central and peripheral sites at different time points after reserpine administration. Nociceptin/orphanin FQ displayed dual effects in the behavioral changes in the reserpine-elicited fibromyalgia model. The peptide NOPr antagonist UFP-101 produced analgesic and antifatigue effects, by preventing alterations in brain activity and skeletal muscle metabolism, secondary to fibromyalgia induction. The nonpeptide NOPr antagonist SB-612111 mirrored the favorable effects of UFP-101 in painful and fatigue alterations induced by reserpine. A time-related up- or downregulation of prepronociceptin/orphanin FQ and NOPr was observed in supraspinal, spinal, and peripheral sites of reserpine-treated mice. Our data shed new lights on the mechanisms underlying the fibromyalgia pathogenesis, supporting a role for N/OFQ-NOP receptor system in this syndrome.
Experimental evaluation of central pain processes in young women with primary dysmenorrhea
Authors: Payne Laura A. , Seidman Laura C. , Sim Myung-Shin , Rapkin Andrea J. , Naliboff Bruce D. , Zeltzer Lonnie K. 
Published: February 2019

Abstract
Primary dysmenorrhea (PD; menstrual pain without an underlying medical condition) is associated with enhanced pain sensitivity and temporal summation (TS) in adult women, which may reflect the presence of central pain processes. Research in this area has been limited by focusing on only adult populations and incomplete assessments of central sensitization. The current study explored both excitatory and inhibitory measures of pain processing in girls and young adult women with and without PD. Thirty-two young women with PD and 34 healthy controls underwent laboratory pain testing during each of 3 menstrual cycle phases (menstrual, ovulatory, and midluteal), which included measures of pain tolerance and threshold, TS, and conditioned pain modulation. Results indicated enhanced pain sensitivity in young women with PD as measured by heat pain tolerance and Average Pain50 (P50), compared with healthy controls. These group differences were evident at all phases of the menstrual cycle. No group differences in cold pain tolerance, TS, or conditioned pain modulation were evident at any phase of the menstrual cycle. These data suggest some evidence of central sensitization in young women with PD, although no evidence of enhanced excitatory or deficient inhibitory mechanisms were observed. Future research should focus on identifying other potential phenotypes for PD to determine those at risk of developing other pain problems.
Donor-Specific Human Leukocyte Antigen Antibody Formation After Distal Tibia Allograft and Subsequent Graft Resorption
Authors: Liwski Christopher R. , Dillman Daryl , Liwski Robert S. , Wong Ivan H. 
Published: February 2019

Abstract:
The association between donor-specific human leukocyte antigen (HLA) antibody formation and small bone allograft resorption has not been studied. We present the case of a patient treated for glenoid bone loss using a distal tibial allograft with Bankart repair who formed donor-specific HLA antibodies against the allograft and had subsequent graft resorption. X-ray and computed tomography (CT) scans were performed before and after surgery at standard checkpoints. Patient blood and serum samples were collected before and after surgery for HLA typing and HLA antibody testing. Human leukocyte antigen antibodies against the donor-specific HLA-A2 antigens were identified 6 weeks after surgery and were still detected at 5 months after surgery. At 6 months after surgery, a CT arthrogram revealed significant graft resorption. This case shows a temporal correlation between HLA antibody formation and clinical findings, potentially suggesting an association between HLA antibody formation and graft resorption. Further study is required to confirm this.
Liver fibrosis is associated with risk for colorectal adenoma in patients with nonalcoholic fatty liver disease
Authors: Kim Min Cheol , Park Jung Gil , Jang Byung Ik , Lee Heon Ju , Lee Won Kee 
Published: February 2019

Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with risks for developing colorectal adenoma. This study aimed to evaluate the association between advanced fibrosis in NAFLD and the risk for colorectal adenoma.
We retrospectively analyzed the data of 6332 adults who underwent abdominal ultrasound and 1st-time colonoscopy on the same day in a health screening program at a single center. We evaluated the presence of advanced fibrosis in NAFLD using various noninvasive score, which also analyzed the detection rate of colorectal adenoma according to the presence of advanced fibrosis in NAFLD.
The subjects with NAFLD had a higher prevalence of colorectal adenoma. In the multivariate analysis, NAFLD was an independent risk factor for colorectal adenoma (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 1.02–1.30), advanced adenoma (adjusted OR, 1.50; 95% CI, 1.12–2.01), and multiple adenomas (adjusted OR, 1.32; 95% CI, 1.01–1.73). When NAFLD was further stratified based on the stage of fibrosis using the noninvasive score models, the subjects with NAFLD and advanced fibrosis had a significantly higher risk for colorectal adenoma, advanced adenoma, and multiple adenomas than those with NAFLD without advanced fibrosis.
NAFLD with advanced fibrosis might be risk factor for colorectal adenoma compared with NAFLD without advanced fibrosis.