bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fucosyltransferase Gene Polymorphisms and Lewisb-Negative Status Are Frequent in Swedish Newborns, With Implications for Infectious Disease Susceptibility and Personalized Medicine
Authors: King Jovanka R , Varadé Jezabel , Hammarström Lennart 
Published: October 2018

Abstract

Background
Single-nucleotide polymorphisms (SNPs) in the fucosyltransferase genes FUT2 and FUT3 have been associated with susceptibility to various infectious and inflammatory disorders. FUT variations influence the expression of human histo-blood group antigens (HBGAs) (H-type 1 and Lewis), which are highly expressed in the gut and play an important role in microbial attachment, metabolism, colonization, and shaping of the microbiome. In particular, FUT polymorphisms confer susceptibility to specific rotavirus and norovirus genotypes, which has important global health implications.

Methods
We designed a genotyping method using a nested polymerase chain reaction approach to determine the frequency of SNPs in FUT2 and FUT3, thereby inferring the prevalence of Lewisb-positive, Lewisb-negative, secretor, and nonsecretor phenotypes in 520 Swedish newborns.

Results
There was an increased frequency of homozygotes for the minor allele for 1 SNP in FUT2 and 4 SNPs in FUT3. Overall, 37.3% of newborns were found to have Lewis b negative phenotypes (Le (a+b−) or Le (a−b−). Using our new, sensitive genotyping method, we were able to genetically define the Le (a−b−) individuals based on their secretor status and found that the frequency of Lewis b negative newborns in our cohort was 28%.

Conclusions
Given the high frequency of fucosyltransferase polymorphisms observed in our newborn cohort and the implications for disease susceptibility, FUT genotyping might play a future role in personalized health care, including recommendations for disease screening, therapy, and vaccination.
Stereotactic Brain Biopsy in Eloquent Areas Assisted by Navigated Transcranial Magnetic Stimulation: a Technical Case Report
Authors: Bartek Jiri , Cooray Gerald , Islam Mominul , Jensdottir Margret 
Published: October 2018

Abstract

BACKGROUND AND IMPORTANCE
Stereotactic brain biopsy (SB) is an important part of the neurosurgical armamentarium, with the possibility of achieving histopathological diagnosis in otherwise inaccessible lesions of the brain. Nevertheless, the procedure is not without the risk of morbidity, which is especially true for lesions in eloquent parts of the brain, where even a minor adverse event can result in significant deficits. Navigated transcranial magnetic stimulation (nTMS) is widely used to chart lesions in eloquent areas, successfully guiding maximal safe resection, while its potential role in aiding with the planning of a stereotactic biopsy is so far unexplored.

CLINICAL PRESENTATION
Magnetic resonance imaging of a 67-yr-old woman presenting with dysphasia revealed a noncontrast enhancing left-sided lesion in the frontal and parietal pars opercularis. Due to the location of the lesion, nTMS was used to chart both primary motor and language cortex, utilizing this information to plan a safe SB trajectory and sampling area according to the initial work-up recommendations from the multidisciplinary neuro-oncology board. The SB was uneventful, with histology revealing a ganglioglioma, WHO I. The patient was discharged the following day, having declined to proceed with tumor resection (awake surgery) due to the non-negligible risk of morbidity. Upon 1- and 3-mo follow-up, she showed no signs of any procedure-related deficits.

CONCLUSION
nTMS can be implemented to aid with the planning of a stereotactic biopsy procedure in eloquent areas of the brain, and should be considered part of the neurosurgical armamentarium.
Prediction of Spontaneous Lumbar Curve Correction After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis Lenke Type 1 Curves
Authors: Uehara Masashi , Takahashi Jun , Ikegami Shota , Kuraishi Shugo , Futatsugi Toshimasa , Oba Hiroki , Takizawa Takashi , Munakata Ryo , Koseki Michihiko , Kato Hiroyuki 
Published: October 2018

Study Design:
This is a retrospective single-center and single-surgeon study.

Objective:
The present study examined for preoperative parameters having the highest correlation with compensatory thoracolumbar/lumbar (TL/L) curve correction 2 years after surgery in adolescent idiopathic scoliosis (AIS) patients with Lenke type 1 curves.

Summary of Background:
Several parameters have been considered to evaluate the flexibility of compensatory TL/L curve in AIS patients with Lenke type 1 curves. However, the imaging position with the strongest correlation with postoperative spontaneous TL/L curve correction is unknown.

Data:
In total, 37 patients with AIS Lenke type 1 curves who had undergone skip pedicle screw fixation were followed for a 2-year period were enrolled.

Materials and Methods:
TL/L Cobb angles measured at the standing posteroanterior view, supine position, supine position with maximum bending, supine position with traction, prone position, and prone-push position were determined before surgery. Using TL/L Cobb angles determined 2 years postoperatively, correlations between preoperative and postoperative Cobb angles were calculated for each position using the Spearman rank-correlation coefficient, linear regression analysis, and paired t tests.

Results:
Mean preoperative mean±SD TL/L Cobb angle was significantly improved from 31±9 to 13±8 degrees at the study end point. In analyses of correlations between postoperative TL/L Cobb angle and preoperative parameters, the supine position with traction was most strongly associated with TL/L curve correction rate at 2 years after surgery (r=0.72; P<0.01), with paired t tests revealing a significant mean difference of 3.1 degrees.

Conclusions:
Preoperative Cobb angle evaluated at the supine position with traction had the strongest correlation with spontaneously corrected TL/L curve Cobb angle after selective thoracic fusion for AIS Lenke type 1 curves. Accordingly, it may be sufficient to evaluate TL/L curve correction at this position only to reduce radiation exposure and operative time.
The association between multiple sclerosis and pain medications
Authors: Burkill Sarah , Montgomery Scott , Kockum Ingrid , Piehl Fredrik , Strid Pernilla , Hillert Jan , Alfredsson Lars , Olsson Tomas , Bahmanyar Shahram 
Published: October 2018

Abstract
Patients with multiple sclerosis (MS) are at greater risk of pain than people without the disease; however, the occurrence and characteristics of pain among these patients are incompletely described. We aimed to assess characteristics of pain amongst MS patients using MS patients who were recruited to participate in 3 studies in Sweden (n = 3877) and were matched with individuals without MS (n = 4548) by sex, year of birth, and region of residence. The Prescribed Drugs Register identified prescribed pain medication, overall and restricted to those given 4 or more prescriptions in 1 year to assess chronic pain. Anatomical therapeutic chemical codes classified whether pain was neuropathic, musculoskeletal, or migraine. Cox-proportional hazard models were used to estimate associations. Our findings showed patients with MS were at increased risk of pain treatment, with a hazard ratio (HR) of 2.52 (95% confidence interval 2.38-2.66). The largest magnitude HR was for neuropathic pain (5.73, 5.07-6.47) for which 34.2% (n = 1326) of the MS and 7.15% (n = 325) of the non-MS cohort were prescribed a treatment. The HR for chronic pain treatment was 3.55 (3.27-3.84), indicating an increased effect size relative to any pain treatment. Chronic neuropathic pain showed the largest HR at 7.43 (6.21-8.89). Neuropathic pain was shown to be the primary mechanism leading to increased risk of pain in patients with MS.
High-resolution Intracranial Vessel Wall Imaging in Monitoring Treatment Response in Primary CNS Angiitis
Authors: Tsivgoulis Georgios , Papadimitropoulos Georgios N. , Lachanis Stefanos , Palaiodimou Lina , Zompola Christina , Antonellou Roubina , Voumvourakis Konstantinos 
Published: October 2018

Introduction:
High-resolution vessel wall imaging (HR-VWI) is emerging as a tool of notable utility in the diagnosis of intracranial vessel pathology. Its role in monitoring vessel wall disease response to treatment, however, is less well-established.

Case Report:
We report the case of a 45-year-old man with left middle and anterior cerebral artery infarcts and an National Institute of Health Stroke Scale (NIHSS) score of 2. Time-of-flight magnetic resonance angiography and digital subtraction angiography showed multifocal intracranial vessel pathology without extracranial vessel involvement. Comprehensive investigation with echocardiography and 24 hours Holter electrocardiography was unrevealing and the coagulation and routine autoimmune panel results were within normal limits. Cerebrospinal fluid showed mildly elevated protein and a diagnosis of probable primary central nervous system (PCNS) angiitis was made. The diagnosis was corroborated by intracranial HR-VWI, which showed homogenous, concentric enhancement of the left supraclinoid internal carotid artery (ICA) wall. The patient received high-dose IV methylprednisolone and cyclophosphamide. Repeat brain magnetic resonance imaging with HR-VWI at 3 and 9 months showed reduction and final resolution of vessel wall enhancement without recurrent infarcts. He has since remained clinically stable with an NIHSS score of 0 on low-dose oral glucocorticoids.

Conclusions:
Our report illustrates the utility of HR-VWI in diagnosing a case of PCNS angiitis through the demonstration of a vasculitic pattern of mural enhancement. Furthermore, it has provided evidence of disease response to treatment, assisting us in modifying treatment accordingly. Tracking disease activity and response to treatment in cases of central nervous system vasculitis can be another important use of HR-VWI in clinical practice besides assisting in establishing the diagnosis.
Characteristics and Outcomes of Liver Transplantation for Primary Biliary Cholangitis in Young Patients: Analysis of the United Network for Organ Sharing Database
Authors: Singh Amandeep , Fritze Danielle , Mansouri Mahsa , Lopez Rocio , Poordad Fred , Lawitz Eric , Cigarroa Francisco , Halff Glen , Alkhouri Naim 
Published: October 2018

Background.
Primary biliary cholangitis (PBC) in younger patients has been suggested to require liver transplantation (LT) in early adulthood, but data is limited on its outcomes. We aimed to evaluate the characteristics and outcome of LT in young patients with PBC in comparison with older adults.

Methods.
The United Network for Organ Sharing database was analyzed for all patients with PBC who underwent LT between 2000 and 2012. Based on age at the time of LT, subjects were divided into 2 groups: young patients (≤40 y) and older adults (≥41 y). Baseline demographics, clinical parameters, and outcomes of LT were then compared between the 2 groups. Univariable and multivariable analyses were performed to assess the factors associated with outcomes of LT.

Results.
A total of 2084 patients with PBC were included in the analysis with 158 young patients. Compared with older adults, younger patients were more likely to be male (27.2% versus 15.4%) and nonwhite (43.7% versus 21.5%), but they were less likely to have obesity, diabetes, or hypertension (P < 0.05) and had a lower mortality (8.2% versus 15.1%) but higher retransplantation rate (14.6% versus 4.7%) (P < 0.001). On multivariable analysis, older age, dialysis or ventilator use, and lower albumin were associated with high post-LT mortality.

Conclusions.
Compared with older adults, early-onset PBC in younger patients requiring LT had higher percentage of males and nonwhites and had a lower prevalence of metabolic comorbidities but higher retransplantation rates. Further studies are warranted to confirm these findings.
Heritability and genetic variance of dementia with Lewy bodies
Authors: Guerreiro Rita , Escott-Price Valentina , Hernandez Dena G. , Kun-Rodrigues Celia , Ross Owen A. , Orme Tatiana , Luis Neto Joao , Carmona Susana , Dehghani Nadia , Eicher John D. , Shepherd Claire , Parkkinen Laura , Darwent Lee , Heckman Michael G. , Scholz Sonja W. , Troncoso Juan C. , Pletnikova Olga , Dawson Ted , Rosenthal Liana , Ansorge Olaf , Clarimon Jordi , Lleo Alberto , Morenas-Rodriguez Estrella , Clark Lorraine , Honig Lawrence S , Marder Karen , Lemstra Afina , Rogaeva Ekaterina , George-Hyslop Peter St. , Londos Elisabet , Zetterberg Henrik , Barber Imelda , Braae Anne , Brown Kristelle , Morgan Kevin , Troakes Claire , Al-Sarraj Safa , Lashley Tammaryn , Holton Janice , Compta Yaroslau , Van Deerlin Vivianna , Serrano Geidy E , Beach Thomas G , Lesage Suzanne , Galasko Douglas , Masliah Eliezer , Santana Isabel , Pastor Pau , Diez-Fairen Monica , Aguilar Miquel , Tienari Pentti J. , Myllykangas Liisa , Oinas Minna , Revesz Tamas , Lees Andrew , Boeve Brad F , Petersen Ronald C. , Ferman Tanis J , Graff-Radford Neill , Cairns Nigel J. , Morris John C. , Pickering-Brown Stuart , Mann David , Halliday Glenda M. , Hardy John , Trojanowski John Q. , Dickson Dennis W. , Singleton Andrew ,   for the International Parkinson’s Disease Genomics Consortium, Stone David J. , Bras Jose 
Published: October 2018

AbstractRecent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson’s disease (PD) or Alzheimer’s disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.
Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma
Authors: Noorani Ayesha , Goddard Martin , Crawte Jason , Alexandrov Ludmil B. , Li Xiaodun , Secrier Maria , Eldridge Matthew D. , Bower Lawrence , Weaver Jamie , Lao-Sirieix Pierre , Martincorena Inigo , Debiram-Beecham Irene , Grehan Nicola , MacRae Shona , Malhotra Shalini , Miremadi Ahmad , Thomas Tabitha , Galbraith Sarah , Petersen Lorraine , Preston Stephen D. , Gilligan David , Hindmarsh Andrew , Hardwick Richard H. ,   OCCAMS Consortium, Stratton Michael R. , Wedge David C. , Fitzgerald Rebecca C. 
Published: October 2018

AbstractContinual evolution of cancer makes it challenging to predict clinical outcomes. Highly varied and unpredictable patient outcomes in esophageal adenocarcinoma (EAC) prompted us to question the pattern and timing of metastatic spread. Whole genome sequencing and phylogenetic analysis of 396 samples across 18 EAC cases demonstrated a stellate pattern on the phylogenetic trees in 90% cases. The age-dependent trinucleotide signature, which can serve as a molecular clock, was absent or reduced in the stellate branches beyond the trunk in most cases (p<0.0001). Clustering of lymph nodes and distant metastases (n=250) demonstrated samples sharing a common clonal origin were widely dispersed anatomically. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time-points. We infer that metastasis occurs rapidly across multiple sites, constituting a model of metastatic spread we term clonal diaspora. This has implications for understanding metastatic progression, clinical staging and patient management.
The rat medial prefrontal cortex exhibits flexible neural activity states during the performance of an odor span task
Authors: De Falco E , An L , Sun N , Roebuck AJ , Greba Q , Lapish CC , Howland JG 
Published: October 2018

AbstractMedial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Towards this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased significantly earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states enable successful performance in dynamic environments placing strong demands on the substrates of working memory.
Characterization of α3 Glycine Receptors with Ginkgolide B and Picrotoxin
Authors: Chakrabarti Sampurna , Neelakantan Anil , Slaughter Malcolm M. 
Published: October 2018

AbstractGinkgolide B (GB) and picrotoxin (PTX) are antagonists of the major inhibitory receptors of the central nervous system: GABA and glycine receptors (GlyRs). GlyRs contain one or more of the four alpha subunit isoforms of which α1 and α2 have been extensively studied. This report compares GB and PTX block of α3 GlyRs expressed in HEK 293 cells, using whole-cell patch clamp techniques. In CNS, α3 exists as a heteropentamer in conjunction with beta subunits in a 2α:3β ratio. Thus, the nature of block was also tested in α3β heteromeric glycine receptors. GB and PTX blocked α3 GlyRs both in the presence (liganded state) and absence of glycine (unliganded state). This property is unique to α3 subunits; α1 and α2 subunits are only blocked in the liganded state. The GB block of α3 GlyRs is voltage-dependent (more effective when the cell is depolarized) and non-competitive, while the PTX block is competitive and not voltage-dependent. The heteromeric and homomeric α3 GlyRs recovered significantly faster from unliganded GB block compared to liganded GB block, but no such distinction was found for PTX block suggesting more than one binding site for GB. This study sheds light on features of the α3 GlyR that distinguish it from the more widely studied α1 and α2 subunits. Understanding these properties can help decipher the physiological functioning of GlyRs in the CNS and may permit development of subunit specific drugs.
Resource misallocation as a mediator of fitness costs in antibiotic resistance
Authors: Trauner Andrej , Banaei-Esfahani Amir , Gygli Sebastian M. , Warmer Philipp , Feldmann Julia , Shafieechashmi Seyedehsara , Eschbach Katja , Zampieri Mattia , Borrell Sonia , Collins Ben C. , Beisel Christian , Aebersold Ruedi , Gagneux Sebastien 
Published: October 2018

SummaryAntimicrobial resistance poses a threat to global health and the economy. It is widely accepted that, in the absence of antibiotics, drug resistance mutations carry a fitness cost. In the case of rifampicin resistance in fast-growing bacteria, this cost stems from a reduced transcription rate of the RNA polymerase resulting in slower ribosome biosynthesis. However, this relationship does not apply in the slow-growingMycobacterium tuberculosis, where the true mechanism of fitness cost of rifampicin resistance as well as the impact of compensatory evolution remain unknown. Here we show, using global transcriptomic and proteomic profiling of selectedM. tuberculosismutants and clinical strains, that the fitness cost of rifampicin resistance inM. tuberculosisis the result of the physiological burden caused by aberrant gene expression. We further show that the perceived burden can be increased, effectively suppressing the emergence of drug resistance.
Complementary networks of cortical somatostatin interneurons enforce layer specific control
Authors: Naka Alexander , Veit Julia , Shababo Ben , Chance Rebecca K. , Risso Davide , Stafford David , Snyder Benjamin , Egladyous Andrew Y. , Chu Desi , Sridharan Savitha , Paninski Liam , Ngai John , Adesnik Hillel 
Published: October 2018

AbstractThe neocortex is organized into discrete layers of excitatory neurons: layer 4 receives the densest ‘bottom up’ projection carrying external sensory data, while layers 2/3 and 5 receive ‘top down’ inputs from higher cortical areas that may convey sensory expectations and behavioral goals. A subset of cortical somatostatin (SST) neurons gate top down input and control sensory computation by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5. However, it is unknown whether an analogous inhibitory mechanism separately and specifically controls activity in layer 4. We hypothesized that distinct SST circuits might exist to inhibit specific cortical layers. By enforcing layer-specific inhibition, distinct SST subnetworks could mediate pathway-specific gain control, such as regulating the balance between bottom up and top down input. Employing a combination of high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal distinct and complementary SST circuits that specifically and reciprocally interconnect with excitatory cells in either layer 4 or layers 2/3 and 5. Our data further define a transcriptionally distinct SST neuronal sub-class that powerfully gates bottom up sensory activity during active sensation by regulating layer 4 activity. This integrated paradigm further represents a potentially generalizable approach to identify and characterize neuronal cell types and reveal their in vivo function.
Pregnancy-associated plasma protein-aa promotes neuron survival by regulating mitochondrial function
Authors: Alassaf Mroj , Daykin Emily , Wolman Marc 
Published: October 2018

AbstractA neuron’s longevity is regulated by both extracellular molecular factors and the regulation of its intracellular functions, including mitochondrial activity. It remains poorly understood which extracellular factors promote neuron survival by influencing mitochondrial function. Through zebrafish mutant analysis, we reveal a novel extracellular neuronal survival factor: Pregnancy-associated plasma protein-aa (Pappaa). Neurons inpappaamutant larvae die precociously and exhibit multiple mitochondrial defects, including elevated mitochondrial calcium, membrane potential, and reactive oxygen species production (ROS). Inpappaamutants, neuron loss is exacerbated by stimulation of mitochondrial calcium load or ROS production and suppressed by exposure to a mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates local insulin-like growth factor 1 (IGF1) signaling; a known regulator of mitochondrial function and neuron survival. Inpappaamutants, neurons show reduced IGF1-receptor activity and neuron loss is attenuated by stimulation of IGF1 signaling. These results suggest Pappaa-IGF1 signaling promotes neuron survival by regulating mitochondrial function.