bluuebunny/crossref_metadata_2025_split huggingface dataset:
Akkermansia muciniphila bacteria: a new perspective on the management of obesity: an updated review
Authors: Payahoo Laleh , Khajebishak Yaser , Ostadrahimi Alireza 
Published: December 2018

Background:
Obesity as a multifactorial disorder has shown a growing trend, in recent times. Considering the importance of obesity as a potent public health problem, finding a novel preventive approach for the management of obesity seems crucial. In addition to genetic and environmental factors, alteration in gut microbiota composition and inflammation are involved in the pathogenesis of obesity. The aim of the current study was to discuss the role of Akkermansia muciniphila in the management of obesity.

Method:
In this review article, all articles indexed in the scientific database using the keywords A. muciniphila, inflammation, gut microbiota, peroxisome proliferator-activated receptor-alpha (PPAR-α), overweight, and obesity were searched and discussed between 2000 and 2018.

Results:
Specific strains of gut microbiota such as A. muciniphila modify energy homeostasis in the body. In addition to degrading mucin and providing a desirable environment for the growth of other bacteria in the intestine, A. muciniphila participates in the management of obesity. Indeed, A. muciniphila increases the levels of Short chain fatty acids (SCFAs) and N-acylethanolamines as ligands of GPR41/GPR43 and G protein-coupled receptor119 (GPR119) receptors in L-cells, respectively, such that these receptors are involved in the various aspects of energy balance and appetite sensation. A. muciniphila also improves the low chronic inflammation observed in obese people through various mechanisms.

Conclusion:

A. muciniphila supplementation and the use of other approaches such as prebiotics or food components that increase the abundance of this bacterium in the gut microbiota population could be a novel valuable approach in the management of obesity.
Characteristics Associated With Human Immunodeficiency Virus Transmission Networks Involving Adolescent Girls and Young Women in Human Immunodeficiency Virus Prevention Trials Network 068 Study
Authors: Stoner Marie C.D. , Dennis Ann M. , Hughes James P. , Eshleman Susan H. , Sivay Mariya V. , Hudelson Sarah E. , Grabowski M. Kate , Gómez-Olivé F. Xavier , MacPhail Catherine , Piwowar-Manning Estelle , Kahn Kathleen , Pettifor Audrey 
Published: December 2018

Abstract
We combined behavioral survey data from the human immunodeficiency virus (HIV) Prevention Trials Network 068 study with phylogenetic information to determine if cluster membership was associated with characteristics of young women and their partners. Clusters were more likely to involve young women from specific villages and schools, indicating some localized transmission.
Supplemental digital content is available in the text.
Outcomes Analysis of Children Diagnosed With Hemophagocytic Lymphohistiocytosis in the PICU
Authors: Gregory Jillian , Greenberg Jay , Basu Sonali 
Published: December 2018

Objectives:
Describe a single center experience of hemophagocytic lymphohistiocytosis in a PICU over a 10-year period, to identify clinical features that may be associated with worse outcomes, including mortality, hospital and ICU length of stay, and functional and cognitive impairments on discharge.

Design:
Retrospective electronic medical record review, 2007–2017.

Setting:
PICU located in a large urban academic quaternary care children’s hospital.

Patients:
All children admitted with hemophagocytic lymphohistiocytosis to our PICU from 2007 to 2017.

Interventions:
None.

Measurements and Main Results:
All patients were identified utilizing International Classification of Diseases, 9th Revision and International Classification of Diseases, 10th Revision codes. Each chart was reviewed for demographic information, hemophagocytic lymphohistiocytosis diagnostic criteria, laboratory data, Pediatric Risk of Mortality Score III, clinical features and events of ICU stay, and PICU and hospital (length of stay). Mortality at 1 year and change in Functional Status Scale from admission to discharge were recorded. There were 42 admissions with 33 unique patients. Median Pediatric Risk of Mortality score at admission was 9 (interquartile range, 7–16). Median PICU length of stay was 7 days (interquartile range, 2–21 d) and hospital length of stay was 24 days (interquartile range, 14–37 d). During their ICU stay, 56% of patients received mechanical ventilation, 43% required vasoactives, 18% required continuous renal replacement therapy, and 5% received extracorporeal life support. Clinical factors related to increased PICU length of stay included Pediatric Risk of Mortality III score (p = 0.019), maximum lactate dehydrogenase (p = 0.017), maximum total bilirubin (p = 0.042), need for mechanical ventilation (p = 0.002), vasoactive use (p = 0.02), and secondary infection (p = 0.007). The most common therapies for hemophagocytic lymphohistiocytosis included steroids (93%), etoposide (55%), and anakinra (48%). Of the 26 patients who survived to hospital discharge, 19% had newly acquired morbidities. Overall 1-year mortality was 42%.

Conclusions:
Hemophagocytic lymphohistiocytosis diagnosed in the PICU is a disease with high mortality. Patients who survive to discharge had relatively little morbidity, however, the mortality risk in the year following discharge continued to remain high.
FDG-PET/CT for Detecting an Infection Focus in Patients With Bloodstream Infection
Authors: Pijl Jordy P. , Glaudemans Andor W. J. M. , Slart Riemer H. J. A. , Yakar Derya , Wouthuyzen-Bakker Marjan , Kwee Thomas C. 
Published: December 2018

Purpose
To investigate the diagnostic performance of 18F-fluoro-2-deoxy-D-glucose (FDG) PET/ CT for the detection of an infection focus in patients with a bloodstream infection (BSI) and to identify factors influencing the diagnostic yield of FDG-PET/CT.

Methods
This retrospective single-center study included 185 consecutive patients with a BSI who underwent an FDG-PET/CT scan for the detection of an infection focus between 2010 and 2017. The final diagnosis at hospital discharge was used as reference standard. Diagnostic performance of FDG-PET/CT for the detection of an infection focus was assessed, and logistic regression analyses were performed to identify factors associated with FDG-PET/CT yield.

Results
An infection focus was identified on FDG-PET/CT in 120 (64.8%) of 185 patients. FDG-PET/CT achieved a sensitivity of 80.2%, specificity of 79.6%, positive predictive value of 90.8%, and a negative predictive value of 61.4% for detecting an infection focus in patients with a BSI. Blood cultures positive for enterococci (odds ratio, 0.14; P = 0.019) and days of antibiotic treatment before FDG-PET/CT (odds ratio, 0.94 per day increase; P = 0.014) were statistically significant independent predictors of a lower odds of detecting an infection focus on FDG-PET/CT. In patients who received antibiotics for less than 7 days before FDG-PET/CT, an infection focus was found in 71% (56/79). In patients who received antibiotics for 8 to 14 days before FDG-PET/CT, an infection focus was found in 52% (22/42). After 15 to 21 days of antibiotic treatment, an infection focus was found in 61% (8/13), and for 22 days or more, this declined to 38% (5/13).

Conclusions
FDG-PET/CT is a useful method for detecting an infection focus in patients with BSI. However, longer duration of antibiotic treatment before FDG-PET/CT and bacteremia with enterococci reduce the diagnostic yield of FDG-PET/CT. These factors should be taken into account when considering an FDG-PET/CT scan for this indication.
Voriconazole-Induced Periostitis After Allogeneic Stem Cell Transplantation
Authors: Haemels Maarten , Pans Steven , Schoemans Hélène , Goffin Karolien , Gheysens Olivier , Jentjens Sander 
Published: December 2018

Abstract
A 34-year-old man with history of Hodgkin lymphoma presented 7 months after allogeneic stem cell transplantation with an unexplained severe musculoskeletal pain syndrome. A 99mTc-MDP bone SPECTCT showed multiple foci with moderate to intense bone uptake across the axial and appendicular skeleton consistent with periostitis. The patient had been on voriconazole daily for 4 months to treat an Aspergillus pneumonia, and in the absence of other causes, a drug-induced periostitis was suspected. Voriconazole was changed to posaconazole with complete resolution of the musculoskeletal symptoms within 3 weeks.
Ischemic Complications After High-Grade Glioma Resection Could Interfere With Residual Tumor Detection With 18F-Fluorocholine PET/CT
Authors: García Vicente Ana María , Rodriguez Muñoz María José , Pena Pardo Francisco José , Martinez Madrigal Milton Miguel , Soriano Castrejón Angel 
Published: December 2018

Abstract
Ischemic complications after resection of high-grade glioma are frequent and may constitute potential cause of false-positive results in postsurgical evaluation using 18F-fluorocholine PET/CT. On the other hand, hypoxia caused by ischemia promotes invasive glioma growth. We present 3 cases of patients with different grades of ischemic injury after resection of high-grade glioma. The combined interpretation of diffusion-weighted imaging and apparent diffusion coefficient map on MRI, in this clinical setting, is mandatory to avoid PET/CT misinterpretations.
Systemic Changes Affecting the Morphology of Calvarial Bone
Authors: Yao Amy , Taub Justin S. , Gault Allison T. , Naidich Thomas P. , Taub Peter J. 
Published: December 2018

Abstract
Plastic surgeons are frequently consulted to evaluate concerns about a patient's skull. Imaging studies often reveal abnormalities in bone morphology, from increased porosity to sclerotic changes. While focal findings imply a benign or malignant neoplasm, the etiology of more diffuse findings can be more varied, making the correct diagnosis challenging. The present review summarizes the differential diagnosis of osseous lesions of the calvarium that affect the bone and contribute to changes seen on imaging studies.
Index Admission Emergency Laparoscopic Cholecystectomy and Common Bile Duct Exploration: Results From a Specialist Center in the United Kingdom
Authors: Deytrikh Andrew , Stewart Sabrina , Malone Nicholas , McTaggart Eleanor , Leeder Paul , Bhatti Imran , Awan Altaf 
Published: December 2018

Background:
The incidence of common bile duct (CBD) stones is between 10% to 18% in people undergoing cholecystectomy for gallstones. Laparoscopic exploration of the CBD is now becoming routine practice in the elective setting, however its safety and efficacy in emergencies is poorly understood.

Methods:
We analyzed our results for index emergency admission laparoscopic cholecystectomy within a specialist center in the United Kingdom. Data from all emergency cholecystectomies in our unit, between 2011 to 2016 were collected and analyzed retrospectively.

Results:
In total, 494 patients underwent emergency laparoscopic cholecystectomy; 53 (10.7%) patients underwent common bile duct exploration (CBDE), with 1 conversion and 1 bile leak. Indications for CBDE were based on preoperative imaging (41 cases, 81%) or intra-operative cholangiogram (44 cases, 83%) findings.

Conclusions:
Index admission laparoscopic cholecystectomy and concomitant CBDE is safe and should be the gold standard treatment for patients presenting with acute biliary complications, reducing readmissions and the need for a 2-stage procedure.
Examining the ocular fundus in neurology
Authors: Rodenbeck Stefanie J. , Mackay Devin D. 
Published: December 2018

Purpose of review
The funduscopic examination can be a technically difficult, and often omitted, portion of the neurologic examination, despite its great potential to influence patient care.

Recent findings
Medical practitioners are often first taught to examine the ocular fundus using a direct ophthalmoscope, however, this skill requires frequent practice. Nonmydriatic tabletop and portable fundus photography and even smartphone-based photography offer alternative and practical means for approaching examination of the ocular fundus. These alternative tools have been shown to be practical in a variety of settings including ambulatory clinics and emergency departments. Decreased retinal microvascular density detected with fundus photography has been linked to accelerated rates of cognitive decline. Research has also found optic disc pallor and retinopathy detected via fundus photography to be more prevalent in patients with recent stroke or transient ischemic attack.

Summary
Alternative methods of funduscopic examination based on fundus photography have the potential to improve the ease of use, portability, and availability of funduscopy. Recognition of changes in retinal microvasculature has the potential to noninvasively identify patients at the highest risk for cognitive impairment and cerebrovascular disease. However, further research is needed to determine the specific utility of measurements of retinal microvascular changes in clinical care. Innovative funduscopy techniques offer neurologists new approaches to this essential facet of the neurological examination.
Milestones in the development of a vestibular implant
Authors: Guyot Jean-Philippe , Perez Fornos Angelica 
Published: December 2018

Purpose of reviewBilateral vestibular deficits exist and their prevalence is more important than believed by the medical community. Their severe impact has inspired several teams to develop technical solutions in an attempt to rehabilitate patients. A particularly promising pathway is the vestibular implant. This article describes the main milestones in this field, mainly focusing on work conducted in human patients.Recent findingsThere have been substantial research efforts, first in animals and more recently in humans, toward the development of vestibular implants. Humans have demonstrated surprising adaptation capabilities to the artificial vestibular signal. Today, the possibility of restoring vestibular reflexes, particularly the vestibulo-ocular reflex, and even achieving useful function in close-to-reality tasks (i.e. improving visual abilities while walking) have been demonstrated in humans.SummaryThe vestibular implant opens new perspectives, not only as an effective therapeutic tool, but also pushes us to go beyond current knowledge and well-established clinical concepts.
Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules
Authors: Modi Nishit B. , Mittur Aravind , Rubens Robert , Khanna Sarita , Gupta Suneel 
Published: December 2018

Objective
IPX203 is an investigational oral extended-release capsule formulation of carbidopa-levodopa (CD-LD). The aim of this study was to characterize the single-dose pharmacodynamics, pharmacokinetics, and safety of IPX203 in subjects with advanced Parkinson disease compared with immediate-release (IR) CD-LD and extended-release CD-LD (Rytary).

Methods
This was a randomized, open-label, rater-blinded, multicenter, single-dose crossover study. Blinded clinicians assessed subject's motor state and Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores for up to 10 hours postdose. Duration of effect was determined using improvement thresholds in the MDS-UPDRS part III.

Results
Levodopa concentrations increased rapidly and similarly across all 3 treatments and were sustained for a longer duration after IPX203 dosing. All treatments exhibited a rapid onset of pharmacodynamic effect, whereas IPX203 had a significantly longer duration of effect based on MDS-UPDRS part III scores compared with IR CD-LD (P < 0.0001) and Rytary (P ≤ 0.0290). IPX203 had a 2.7-hour advantage over IR CD-LD (P < 0.0001) and a 0.9-hour advantage over Rytary in “off” time (P = 0.023) and in “good on” time (2.6 hours more than IR CD-LD, P < 0.0001; 0.9 hours more than Rytary, P = 0.0259) as measured by the Investigator Assessment of Subject's Motor State. Subjects were 77% more likely to require rescue following IR CD-LD treatment compared with IPX203 (hazard ratio, 0.23; P < 0.0001). More subjects reported treatment-emergent adverse effects during IR CD-LD (28.0%) and IPX203 (19.2%) than during Rytary (8.0%) treatment.

Conclusions
Compared with Rytary and IR CD-LD, IPX203 had a longer pharmacodynamic effect consistent with LD pharmacokinetics for the 3 treatments. The safety and tolerability of IPX203 were similar to those of IR CD-LD and Rytary.
Graphene Oxide as 2D Platform for Complexation and Intracellular Delivery of siRNA
Authors: Lázaro Irene de , Vranic Sandra , Marson Domenico , Rodrigues Artur Filipe , Buggio Maurizio , Esteban-Arranz Adrián , Mazza Mariarosa , Posocco Paola , Kostarelos Kostas 
Published: December 2018

AbstractThe development of efficient and safe nucleic acid delivery vectors remains an unmet need holding back translation of gene therapy approaches into bedside. Graphene oxide (GO) could help bypass such bottleneck thanks to its large surface area, versatile chemistry and biocompatibility, which could overall enhance transfection efficiency while abolishing some of the limitations linked to the use of viral vectors. Here, we aimed to assess the capacity of bare GO, without any further surface modification, to complex a short double-stranded nucleic acid of biological relevance (siRNA) and mediate its intracellular delivery. GO formed stable complexes with siRNA at 10:1, 20:1 and 50:1 GO:siRNA mass ratios. Complexation was further corroborated by atomistic molecular dynamics simulations. GO:siRNA complexes were promptly internalized in a primary mouse cell culture, as early as 4 h after exposure. At this time point, intracellular siRNA levels were comparable to those provided by a lipid-based transfection reagent that achieved significant gene silencing. Time-lapse tracking of internalized GO and siRNA evidenced a sharp decrease of intracellular siRNA from 4 to 12 h, while GO was sequestered in large vesicles, which may explain the lack of biological effect (i.e. gene silencing) achieved by GO:siRNA complexes. This study underlines the potential of non-surface modified GO flakes to act as 2D siRNA delivery platforms, without the need for cationic functionalization, but warrants further vector optimization to allow effective release of the nucleic acid and achieve efficient gene silencing.
Double Stranded DNA Breaks and Genome Editing Trigger Ribosome Remodeling and Translational Shutdown
Authors: Riepe Celeste , Zelin Elena , Wyman Stacia K. , Nguyen David N. , Liang Jin Rui , Frankino Phillip A. , Meacham Zuriah A. , Vu Jonathan T. , Marson Alexander , Ingolia Nicholas T. , Corn Jacob E. 
Published: December 2018

SummaryDNA damage activates a robust transcriptional stress response, but much less is known about how DNA impacts translation. The advent of genome editing via a Cas9-induced DNA double-strand break has intensified interest in understanding cellular responses to DNA damage. Here we find that DNA double-strand breaks (DSBs) induced by Cas9 or other damaging agents lead to a reduction of core ribosomal proteins, RPS27A and RPL40, and that the loss of these proteins is post-transcriptional and p53-independent. DSBs furthermore lead to the shutdown of translation through phosphorylation of eukaryotic initiation factor 2 alpha, and altering these signals affects genome editing outcomes. This DSB translational response is widespread and precedes the transcriptional response. Our results demonstrate that even a single double-strand break can lead to ribosome remodeling and reduced translational output, and suggest caution in interpreting cellular phenotypes measured immediately after genome editing.
Pheophorbide a, a chlorophyll catabolite may regulate jasmonate signalling during dark-induced senescence in Arabidopsis
Authors: Aubry Sylvain , Fankhauser Niklaus , Ovinnikov Serguei , Zienkiewicz Krzysztof , Feussner Ivo , Hörtensteiner Stefan 
Published: December 2018

ABSTRACTChlorophyll degradation is one of the most visible landmarks of leaf senescence. During senescence, chlorophyll is degraded in the multi-step pheophorbide a oxygenase (PAO)/phyllobilin pathway, which is tightly regulated at the transcriptional level. This regulation allows a coordinated and efficient remobilisation of nitrogen towards sink organs. Taking advantage of combined transcriptome and metabolite analyses during dark-induced senescence of Arabidopsis thaliana mutants deficient in key steps of the PAO/phyllobilin pathway, we show an unanticipated role for one of the pathway intermediates, i.e. pheophorbide a. Both jasmonic acid-related gene expression and jasmonic acid precursors specifically accumulated in pao1, deficient in PAO. We propose that pheophorbide a, the last intact porphyrin intermediate of chlorophyll degradation and unique pathway ‘bottleneck’, has been recruited as a signalling molecule of the chloroplast metabolic status. Our work challenges the assumption that chlorophyll breakdown is merely a senescence output, but propose that the flux of pheophorbide a through the pathway acts in a feed-forward loop that remodels the nuclear transcriptome and controls the pace of chlorophyll degradation in senescing leaves.SummaryTranscriptome and metabolite profiles of key chlorophyll breakdown mutants reveal complex interplay between speed of chlorophyll degradation and jasmonic acid signallingFinancial sourcesThis work was supported by the European Union (Plant Fellow program), the Swiss National Foundation/ERA-NET (grant N° 163504) and the German Research Foundation (DFG, grant N° INST 186/822-1).
Alternative hydrogen uptake pathways suppress methane production in ruminants
Authors: Greening Chris , Geier Renae , Wang Cecilia , Woods Laura C. , Morales Sergio E. , McDonald Michael J. , Rushton-Green Rowena , Morgan Xochitl C. , Koike Satoshi , Leahy Sinead C. , Kelly William J. , Cann Isaac , Attwood Graeme T. , Cook Gregory M. , Mackie Roderick I. 
Published: December 2018

AbstractFarmed ruminants are the largest source of anthropogenic methane emissions globally. The methanogenic archaea responsible for these emissions use molecular hydrogen (H2), produced during bacterial and eukaryotic carbohydrate fermentation, as their primary energy source. In this work, we used comparative genomic, metatranscriptomic, and co-culture-based approaches to gain a system-wide understanding of the organisms and pathways responsible for ruminal H2metabolism. Two thirds of sequenced rumen bacterial and archaeal genomes encode enzymes that catalyze H2production or consumption, including 26 distinct hydrogenase subgroups. Metatranscriptomic analysis confirmed that these hydrogenases are differentially expressed in sheep rumen. Electron-bifurcating [FeFe]-hydrogenases from carbohydrate-fermenting Clostridia (e.g.Ruminococcus) accounted for half of all hydrogenase transcripts. Various H2uptake pathways were also expressed, including methanogenesis (Methanobrevibacter), fumarate reduction and nitrate ammonification (Selenomonas), and acetogenesis (Blautia). Whereas methanogenesis predominated in high methane yield sheep, alternative uptake pathways were significantly upregulated in low methane yield sheep. Complementing these findings, we observed significant differential expression and activity of the hydrogenases of the hydrogenogenic cellulose fermenterRuminococcus albusand the hydrogenotrophic fumarate reducerWolinella succinogenesin co-culture compared to pure culture. We conclude that H2metabolism is a more complex and widespread trait among rumen microorganisms than previously recognized. There is evidence that alternative hydrogenotrophs, including acetogens and selenomonads, can prosper in the rumen and effectively compete with methanogens for H2in low methane yield ruminants. Strategies to increase flux through alternative H2uptake pathways, including animal selection, dietary supplementation, and methanogenesis inhibitors, may lead to sustained methane mitigation.