bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-Neurosurgical Temporal Deformities: Various Techniques for Correction and Associated Complications
Authors: Santiago Gabriel F. , Terner Jordan , Wolff Amir , Teixeira Jeffrey , Brem Henry , Huang Judy , Gordon Chad R. 
Published: May 2018

Introduction:An irregular craniofacial contour along the temporal fossa, known commonly as "temporal hollowing deformity," (THD) can arise from multiple etiologies. In fact, up to half of all patients who undergo neurosurgical pterional dissections develop some form of temporal contour deformities. Unfortunately, temporal hollowing correction remains surgically challenging with many techniques resulting in high rates of failure and/or morbidity.Methods:Herein, we describe anatomy contributing to postsurgical temporal deformity as well as time-tested prevention and surgical correction techniques. In addition, a review of 25 articles summarizing various techniques and complication profiles associated with temporal hollowing correction are presented.Results:Complications included infection, implant malposition, revision surgery, pain, and implant removal because of implant-related complications Augmentation with either autologous fat or dermal filler is associated with the highest number of reported complications, including catastrophic events such as stroke, pulmonary embolism, and death. No such complications were reported with use of alloplastic material, use of autologous bone, or free tissue transfer. Furthermore, careful attention to adequate temporalis muscle resuspension and position remain paramount for stable restoration of craniofacial symmetry.Conclusions:Catastrophic complications were associated with injection augmentation of both fat and dermal filler in the temporal region. In contrast, use of alloplastic materials was not found to be associated with any catastrophic complications. As such, for the most severe cases of THD, we prefer to employ alloplastic reconstruction.
Lower extremity cooling reduces ischemia-reperfusion injury following Zone 3 REBOA in a porcine hemorrhage model
Authors: Simon Meryl A. , Tibbits Emily M. , Hoareau Guillaume L. , Davidson Anders J. , DeSoucy Erik S. , Faulconer E. Robert , Grayson J. Kevin , Neff Lucas P. , Johnson M. Austin , Williams Timothy K. 
Published: May 2018

BACKGROUND
New strategies to mitigate ischemia during REBOA and to prolong its maximal duration are needed. We hypothesized that simple external cooling of the hind limbs would decrease ischemia-reperfusion injury following prolonged Zone 3 REBOA.

METHODS
Twelve swine were anesthetized, instrumented, splenectomized, and then underwent 15% total blood volume hemorrhage. Animals were randomized to hypothermia or control followed by 4 hours of Zone 3 REBOA, resuscitation with shed blood, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Baseline and end-of-study muscle biopsies were obtained for histologic analysis.

RESULTS
There were no significant differences between groups at baseline or after hemorrhage. Maximum creatine kinase was significantly lower in the hypothermia group compared with the normothermia group (median [interquartile range] = 3,445 U/mL [3,380–4,402 U/mL] vs. 22,544 U/mL [17,030–24,981 U/mL]; p < 0.01). Maximum serum myoglobin was also significantly lower in the hypothermia group (1,792 ng/mL [1,250–3,668 ng/mL] vs. 21,186 ng/mL [14,181–24,779 ng/mL]; p < 0.01). Fascial compartment pressures were significantly lower during critical care in the hypothermia group (p = 0.03). No histologic differences were observed in hind limb skeletal muscle.

CONCLUSIONS
External cooling during prolonged Zone 3 REBOA decreased ischemic muscle injury and resulted in lower compartment pressures following reperfusion. Hypothermia may be a viable option to extend the tolerable duration of Zone 3 occlusion, beyond what is currently achievable. Future survival studies are required to assess functional outcomes.
A US military Role 2 forward surgical team database study of combat mortality in Afghanistan
Authors: Kotwal Russ S. , Staudt Amanda M. , Mazuchowski Edward L. , Gurney Jennifer M. , Shackelford Stacy A. , Butler Frank K. , Stockinger Zsolt T. , Holcomb John B. , Nessen Shawn C. , Mann-Salinas Elizabeth A. 
Published: May 2018

BACKGROUND
Timely and optimal care can reduce mortality among critically injured combat casualties. US military Role 2 surgical teams were deployed to forward positions in Afghanistan on behalf of the battlefield trauma system. They received prehospital casualties, provided early damage control resuscitation and surgery, and rapidly transferred casualties to Role 3 hospitals for definitive care. A database was developed to capture Role 2 data.

METHODS
A retrospective review and descriptive analysis were conducted of battle-injured casualties transported to US Role 2 surgical facilities in Afghanistan from February 2008 to September 2014. Casualties were analyzed by mortality status and location of death (pretransport, intratransport, or posttransport), military affiliation, transport time, injury type and mechanism, combat mortality index–prehospital (CMI-PH), and documented prehospital treatment.

RESULTS
Of 9,557 casualties (median age, 25.0 years; male, 97.4%), most (95.1%) survived to transfer from Role 2 facility care. Military affiliation included US coalition forces (37.4%), Afghanistan National Security Forces (23.8%), civilian/other forces (21.3%), Afghanistan National Police (13.5%), and non-US coalition forces (4.0%). Mortality differed by military affiliation (p < 0.001). Among fatalities, most were Afghanistan National Security Forces (30.5%) civilian/other forces (26.0%), or US coalition forces (25.2%). Of those categorized by CMI-PH, 40.0% of critical, 11.2% of severe, 0.8% of moderate, and less than 0.1% of mild casualties died. Most fatalities with CMI-PH were categorized as critical (66.3%) or severe (25.9%), whereas most who lived were mild (56.9%) or moderate (25.4%). Of all fatalities, 14.0% died prehospital (pretransport, 5.8%; intratransport, 8.2%), and 86.0% died at a Role 2 facility (posttransport). Of fatalities with documented transport times (median, 53.0 minutes), most (61.7%) were evacuated within 60 minutes.

CONCLUSIONS
Role 2 surgical team care has been an important early component of the battlefield trauma system in Afghanistan. Combat casualty care must be documented, collected, and analyzed for outcomes and trends to improve performance.

LEVEL OF EVIDENCE
Therapeutic/Care Management, level IV.
Hereditary ataxias and paraparesias: clinical and genetic update
Authors: Parodi Livia , Coarelli Giulia , Stevanin Giovanni , Brice Alexis , Durr Alexandra 
Published: May 2018

Purpose of review
This review aims at updating the clinical and genetic aspects of hereditary spastic paraplegias (HSPs) and hereditary cerebellar ataxias (HCAs), focusing on the concept of spastic-ataxia phenotypic spectrum and on newly identified clinical overlaps with other neurological and nonneurological diseases.

Recent findings
Next-generation sequencing (NGS) has allowed the discovery of new genes involved in HSPs and HCAs. They include new HCAs genes such as GRM1 (SCA44), FAT2 (SCA45), PLD3 (SCA46), SCYL1 (SCAR21), UBA5 (SCAR24) and XRCC1 (SCAR26) as well as CAPN1 (SPG76) and CPT1C (SPG73) in HSPs. Furthermore, NGS allowed enriching known genes phenotype, reinforcing the overlap between HSPs and HCAs defining the spastic ataxia spectrum. Clear examples are the expanded phenotypes associated with mutations in SPG7, PNPLA6, GBA2, KIF1C, CYP7B1, FA2H, ATP13A2 and many others. Moreover, other genes not previously linked to HCAs and HSPs have been implicated in spastic or ataxic phenotypes.

Summary
The increase of HSPs and HCAs-related phenotypes and the continuous discovery of genes complicate clinical diagnostic in practice but, at the same time, it helps highlighting common pathological pathways, therefore opening new ways to the development of common therapeutic approaches.
Low incidence of plastic ingestion among three fish species significant for human consumption on the island of Newfoundland, Canada
Authors: Liboiron Max , Melvin Jessica , Richárd Natalie , Saturno Jacquelyn , Ammendolia Justine , Liboiron France , Charron Louis , Mather Charles 
Published: May 2018

AbstractThis study reports the first baselines of plastic ingestion for three fish species that are common food fish in Newfoundland, Canada. Species collections occurred between 2015-2016 for Atlantic cod (Gadus morhua), Atlantic salmon (Salmo salar), and capelin (Mallotus villosus). The frequency of occurrence (%FO) of plastic ingestion for both spawning Atlantic salmon (n=69) and capelin (n=350) was 0%. Of the 1,010 Atlantic cod collected over two years, 17 individuals had ingested plastics, a %FO of 1.68%. This is the only multi-year investigation of plastic ingestion in Atlantic cod for the Northwest Atlantic, and the first for capelin and salmon in the region. Considering the ecological, economic, and cultural importance of these fish species, this study is the beginning of a longitudinal study of plastic ingestion to detect future changes in contamination levels.HighlightsIngestion rate (%FO) of plastics in Atlantic cod is 1.68%Ingestion rate (%FO) of plastics in Atlantic salmon and capelin is 0%First study of plastic ingestion rates in Atlantic salmon and capelinMulti-year baseline of plastic ingestion in Atlantic cod in the Northwest AtlanticPlastic ingestion rates for three food fish species in Newfoundland, Canada, are lowTermsFrequency of occurrence (%FO): the number of individuals in a population or group that have ingested plastics (not indicative of the number of particles ingested per individual)
Loss of the Wnt/β-catenin pathway in microglia of the developing brain drives pro-inflammatory activation leading to white matter injury
Authors: Van Steenwinckel Juliette , Schang Anne-Laure , Krishnan Michelle L , Degos Vincent , Delahaye-Duriez Andrée , Bokobza Cindy , Verdonk Franck , Montané Amélie , Sigaut Stéphanie , Hennebert Olivier , Lebon Sophie , Schwendimann Leslie , Le Charpentier Tifenn , Hassan-Abdi Rahma , Ball Gareth , Aljabar Paul , Saxena Alka , Holloway Rebecca K , Birchmeier Walter , Miron Veronique , Rowitch David , Chretien Fabrice , Leconte Claire , Besson Valérie C , Petretto Enrico G , Edwards A David , Hagberg Henrik , Soussi-Yanicostas Nadia , Fleiss Bobbi , Gressens Pierre 
Published: May 2018

SummaryMicroglia of the developing brain have unique functional properties but how their activation states is regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microglial activation in the developing brain with multiple models of neuroinflammation-mediated injury and primary human microglia we found that a reduction in Wnt/β-catenin signalling is necessary and sufficient to drive an oligodendrocyte-injurious microglial phenotype. We validated in a cohort of preterm born infants that genomic variation in the WNT pathway is associated with the levels of connectivity found in their brains. Using a Wnt agonist delivered by a BBB penetrant microglia-specific targeting nanocarrier we prevented in our animal model the pro-inflammatory microglial activation, white matter injury and behavioural deficits. Collectively, these data validate that the Wnt pathway regulates microglial activation, is critical in the evolution of an important form of human brain injury and is a viable therapeutic target.
Spatial RNA sequencing identifies robust markers of vulnerable and resistant human midbrain dopamine neurons and their expression in Parkinson’s Disease
Authors: Aguila Julio , Cheng Shangli , Kee Nigel , Cao Ming , Wang Menghan , Deng Qiaolin , Hedlund Eva 
Published: May 2018

ABSTRACTDefining transcriptional profiles of substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopamine neurons is critical to understanding their differential vulnerability in Parkinson’s Disease (PD). Here, we determine transcriptomes of human SNc and VTA dopamine neurons using LCM-seq on a large sample cohort. We apply a bootstrapping strategy as sample input to DESeq2 and identify 33 stably differentially expressed genes (DEGs) between these two subpopulations. We also compute a minimal sample size for identification of stable DEGs, which highlights why previous reported profiles from small sample sizes display extensive variability. Network analysis reveal gene interactions unique to each subpopulation and highlight differences in regulation of mitochondrial stability, apoptosis, neuronal survival, cytoskeleton regulation, extracellular matrix modulation and well as synapse integrity, which could explain the relative resilience of VTA dopamine neurons. Analysis of PD tissues showed that while identified stable DEGs can distinguish the subpopulations also in disease, the SNc markers SLIT1 and ATP2A3 were downregulated and thus appears to be biomarkers of disease. In summary, our study identifies human SNc and VTA marker profiles, which will be instrumental for studies aiming to modulate dopamine neuron resilience and to validate cell identity of stem cell-derived dopamine neurons.
Xanthine urolithiasis: Inhibitors of xanthine crystallization
Authors: Grases Felix , Costa-Bauza Antonia , Roig Joan , Rodriguez Adrian 
Published: May 2018

AbstractOBJECTIVETo identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria.METHODSThe formation of xanthine crystals in synthetic urine and the effects of 10 potential crystallization inhibitors were assessed using a kinetic turbidimetric system with a photometer. The maximum concentration tested for each compound was: 20 mg/L for 3-methylxanthine (3-MX); 40 mg/L for 7-methylxanthine (7-MX), 1- methylxanthine (1-MX), theobromine (TB), theophylline, paraxanthine, and caffeine; 45 mg/L for 1-methyluric acid; 80 mg/L for 1,3-dimethyluric acid; and 200 mg/L for hypoxanthine. All crystals were examined by scanning electron microscopy.RESULTSOnly 7-MX, 3-MX, and 1-MX significantly inhibited xanthine crystallization at the tested concentrations. Mixtures of inhibitors had an additive effect rather than a synergistic effect on crystallization.CONCLUSIONTwo of the inhibitors identified here —7-MX and 3-MX — are major metabolites of TB. In particular, after TB consumption, 20% is excreted in the urine as TB, 21.5% as 3-MX, and 36 % as 7-MX. Thus, consumption of theobromine could protect patients with xanthinuria from the development of renal xanthine calculi. Clinical trials are necessary to demonstrate these effects in vivo.
The power of language: functional brain network topology of deaf and hearing in relation to sign language experience
Authors: Sinke Michel R.T. , Buitenhuis Jan W. , van der Maas Frank , Nwiboko Job , Dijkhuizen Rick M. , Diessen Eric van , Otte Willem M. 
Published: May 2018

AbstractProlonged auditory sensory deprivation leads to brain reorganization, indicated by functional enhancement in remaining sensory systems, a phenomenon known as cross-modal plasticity. In this study we investigated differences in functional brain network shifts from eyes-closed to eyes-open conditions between deaf and hearing people. Electroencephalography activity was recorded in deaf (N = 71) and hearing people (N = 122) living in rural Africa, which yielded a unique data-set of congenital, pre-lingual and post-lingual deaf people, with a divergent experience in American Sign Language. Functional networks were determined from the synchronization of electroencephalography signals between fourteen electrodes distributed over the scalp. We studied the synchronization between the auditory and visual cortex and performed whole-brain minimum spanning tree analysis based on the phase lag index of functional connectivity. This tree analysis accounts for variations in global network density and allows unbiased characterization of functional network backbones. We found increased functional connectivity between the auditory and visual cortex in deaf people during the eyes-closed condition in both the alpha and beta bands. Furthermore, we found functional network backbone shifts both in deaf and healthy people as they went from eyes-closed to eyes-open conditions. In both the alpha and beta band the deafs’ brain showed larger functional backbone-shifts in node strength compared to controls. In the alpha band this shift in network strength differed among deaf participants and depended on type of deafness: congenital, pre-lingual or post-lingual deafness. In addition, a correlation was found between functional backbone characteristics and experience of sign language. Our study revealed more insights in functional network reorganization specifically due to prolonged lack of auditory input, but might also be helpful for sensory deprivation and cross-modal plasticity in general. Global cortical network reorganization in deaf people supports the plastic capacities of the young brain. The differences between type of deafness stresses that etiology affects functional reorganization, whereas the association between network organization and acquired sign language experience reflects ongoing brain adaptation in people with hearing disabilities.
Removal of alleles by genome editing – RAGE against the deleterious load
Authors: Johnsson Martin , Gaynor R Chris , Jenko Janez , Gorjanc Gregor , de Koning Dirk-Jan , Hickey John M 
Published: May 2018

AbstractBackgroundIn this paper, we simulate deleterious load in an animal breeding program, and compare the efficiency of genome editing and selection for decreasing load. Deleterious variants can be identified by bioinformatics screening methods that use sequence conservation and biological prior information about protein function. Once deleterious variants have been identified, how can they be used in breeding?ResultsWe simulated a closed animal breeding population subject to both natural selection against deleterious load and artificial selection for a quantitative trait representing the breeding goal. Deleterious load was polygenic and due to either codominant or recessive variants. We compared strategies for removal of deleterious alleles by genome editing (RAGE) to selection against carriers. Each strategy varied in how animals and variants were prioritized for editing or selection.ConclusionsGenome editing of deleterious alleles reduces deleterious load, but requires simultaneous editing of multiple deleterious variants in the same sire to be effective when deleterious variants are recessive. In the short term, selection against carriers is a possible alternative to genome editing when variants are recessive. The dominance of deleterious variants affects both the efficiency of genome editing and selection against carriers, and which variant prioritization strategy is the most efficient. Our results suggest that in the future, there is the potential to use RAGE against deleterious load in animal breeding.
SCHiRM: Single Cell Hierarchical Regression Model to detect dependencies in read count data
Authors: Intosalmi Jukka , Mannerström Henrik , Hiltunen Saara , Lähdesmäki Harri 
Published: May 2018

AbstractMotivationModern single cell RNA sequencing (scRNA-seq) technologies have made it possible to measure the RNA content of individual cells. The scRNA-seq data provide us with detailed information about the cellular states but, despite several pioneering efforts, it remains an open research question how regulatory networks could be inferred from these noisy discrete read count data.ResultsHere, we introduce a hierarchical regression model which is designed for detecting dependencies in scRNA-seq and other count data. We model count data using the Poisson-log normal distribution and, by means of our hierarchical formulation, detect the dependencies between genes using linear regression model for the latent, cell-specific gene expression rate parameters. The hierarchical formulation allows us to model count data without artificial data transformations and makes it possible to incorporate normalization information directly into the latent layer of the model. We test the proposed approach using both simulated and experimental data. Our results show that the proposed approach performs better than standard regression techniques in parameter inference task as well as in variable selection task.AvailabilityAn implementation of the method is available athttps://github.com/jeintos/SCHiRM.Contactjukka.intosalmi@aalto.fi,harri.lahdesmaki@aalto.fi
Serotonin inhibits axonal regeneration of identifiable descending neurons after a complete spinal cord injury in lampreys
Authors: Sobrido-Cameán Daniel , Robledo Diego , Sánchez Laura , Rodicio María Celina , Barreiro-Iglesias Antón 
Published: May 2018

SummaryClassical neurotransmitters are mainly known for their roles as neuromodulators, but they also play important roles in the control of developmental and regenerative processes. Here, we used the lamprey model of spinal cord injury to study the effect of serotonin in axon regeneration at the level of individually identifiable descending neurons. Pharmacological and genetic treatments after a complete spinal cord injury showed that endogenous serotonin inhibits axonal regeneration in identifiable descending neurons through the activation of serotonin 1A receptors and a subsequent decrease in cAMP levels. RNA sequencing revealed that changes in the expression of genes that control axonal guidance could be a key factor on the serotonin effects during regeneration. This study provides new targets of interest for research in non-regenerating mammalian models of traumatic CNS injuries and extends the known roles of serotonin signalling during neuronal regeneration.
PCSK9 genetic variants, life-long lowering of LDL-cholesterol and cognition: a large-scale Mendelian randomization study
Authors: Lyall Donald M. , Ward Joey , Banach Maciej , Smith George Davey , Gill Jason G. , Pell Jill P. , Holmes Michael V , Sattar Naveed 
Published: May 2018

AbstractAimsPCSK9 inhibitors lower LDL cholesterol and are efficacious at reducing risk of vascular disease, however questions remain about potential adverse effects on cognitive function. We examined the association of LDL cholesterol-lowering genetic variants in PCSK9 with continuous measures of cognitive abilityMethods and ResultsSix independent SNPs in PCSK9 were used in up to 337,348 individuals from the UK Biobank who underwent measures of cognitive ability (fluid reasoning, reaction time, trial making test and digit symbol coding. Scaled to a 50mg/dL lower LDL cholesterol, the PCSK9 allele score was associated with a lower risk of CHD (odds ratio 0.73; 95% CI: 0.60 to 0.90, P = 0.003). The scaled PCSK9 allele score nominally associated with worse log reaction time (0.04 standard deviations; 95%CI: 0.00, 0.08; P=0.038). Although no strong associations of the PCSK9 allele score were identified with any cognitive trait, the imprecision around the estimates meant that we could not exclude a similar magnitude of effect of genetic inhibition of PCSK9 to that seen with established risk factors, including APOEe4 or smoking status for any of the individual cognition traits. Point estimates for the PCSK9 allele score and cognition traits were all on the harmful side of unity.ConclusionsUsing currently available data in UK Biobank, we are not able to rule out meaningful associations of PCSK9 genetic variants with cognition traits. These data highlight the need for further large-scale genetic analyses and, in parallel, continued pharmacovigilance for patients currently treated with PCSK9 inhibitors.