bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescein-Guided Neuroendoscopy for Intraventricular Lesions: A Case Series
Authors: Fiorindi Alessandro , Boaro Alessandro , Del Moro Giulia , Longatti Pierluigi 
Published: March 2017

Abstract

BACKGROUND: The benefits of neuroendoscopy in the pathological diagnosis of intra- and paraventricular tumors have already been shown in many neurosurgical studies. However, most authors agree that neuroendoscopic biopsies are not infrequently inconclusive due to small or inadequate samples, prompting the need for new diagnostic strategies.

OBJECTIVE: To describe a technique not previously reported in the literature, combining neuroendoscopy with angiofluorescein guidance for the pathological diagnosis of intra- and paraventricular tumors.

METHODS: The 4-mm steerable fiberscope used was equipped with dual observation modes for white light and fluorescein. Access was by the classical precoronal burr hole. After inspecting the ventricular system in white light, a 10-mg/kg dose of fluorescein sodium (FS) was administered intravenously to the patient. The endoscope was then switched to the blue light fluorescent mode to better localize the pathological tissue. The protocol had been submitted to the local ethics committee.

RESULTS: From September 2011 to March 2015, 9 consecutive patients (aged 1-56 yr) harboring intra- and paraventricular lesions prospectively underwent angiofluorescein-guided endoscopy. In all cases, a pathological diagnosis was obtained without complications. In 5 patients, an endoscopic third ventriculostomy, and, in 1 patient, a septostomy was performed during the same procedure. Fluorescein guidance definitely modified our site of biopsy in 4 cases.

CONCLUSION: In our experience, FS has proven to be a strong enhancer of all ventricular lesions presenting with a disrupted blood–brain barrier, including inflammatory processes. Fluorescein-guided neuroendoscopy appears to be a safe, economic method to improve diagnostic potential in ventricular lesions.
MSH6, Past and Present and Muir–Torre Syndrome—Connecting the Dots
Authors: Mahalingam Meera 
Published: March 2017

Abstract:
Sebaceous neoplasms such as adenoma, sebaceoma, and carcinoma, although sporadic in their occurrence, are clinically significant because of their association with Muir–Torre syndrome (MTS). MTS is a rare autosomal dominant genodermatosis characterized by the occurrence of sebaceous neoplasms and/or keratoacanthomas and visceral malignancies. MTS is usually the result of germline mutations in the DNA mismatch repair genes MSH2 and, albeit less commonly, MLH1. Although less know, MSH6 is yet another key player. Evidence from Lynch syndrome indicates that pathogenic germline mutations in MSH6 are typically microsatellite stable and have a clinical presentation that differs from that associated with germline mutations in MSH2 and/or MLH1. Given this unique mutator phenotype of MSH6, the primary aim of this review was to underscore the clinical manifestations associated with pathogenic mutations in MSH6 in patients with MTS. As the current clinical and laboratory work-up of MTS is geared toward patients harboring a germline mutation in MSH2 and/or MLH1, an additional aim was to provide a scaffolding for the work-up of a patient presenting with an isolated germline mutation in MSH6.
Squared-Off Nuclei and “Appliqué” Pattern as a Histopathological Clue to Periocular Sebaceous Carcinoma: A Clinicopathological Study of 50 Neoplasms From 46 Patients
Authors: Broekaert Sigrid M. C. , Flux Katharina , Kyrpychova Liubov , Kacerovska Denisa , Ivan Doina , Schön Michael P. , Ströbel Philipp , Michal Michal , Denisjuk Natalja , Kerl Katrin , Kazakov Dmitry V. 
Published: March 2017

Abstract:
The histopathological diagnosis of periocular sebaceous carcinoma can be difficult in poorly differentiated cases showing few mature sebocytes. The authors examined 50 periocular sebaceous carcinomas from 46 patients to determine the frequency of 2 features seen in this neoplasm, namely cells with squared-off nuclei and so-called “appliqué” pattern (peritumoral subnecrosis of peripherally located neoplastic cells). Neoplastic cells with squared-off nuclei were found in varying numbers in both the intraepithelial and dermal (invasive) components in all neoplasms, whereas the appliqué pattern was observed in a third of the cases. It is concluded that these features, taken together, may serve as a clue for the diagnosis of periocular sebaceous carcinoma.
Supporting a Youth with Cerebellar Ataxia into Adolescence
Authors: Meneses Veronica , Gonzalez-Castillo Zurisadai , Edgar Veronica B. , Augustyn Marilyn 
Published: March 2017

CASE:
Zoe, a 13-year-old white girl, presents as a new patient to your pediatric clinic with complaints of frequent emesis, anxiety, and learning problems, and previous diagnosis of cerebellar ataxia. Parents accompany Zoe and state, “it is really hard for her to go out, she gets sick and falls easily.” She was born full term by vaginal delivery without complications. Given globally delayed milestones, she received early intervention services. Feeding problems began at infancy, including gastroesophageal reflux and aspiration pneumonia.
At age 2, Zoe saw a neurologist and brain MRI revealed cerebellar atrophy. She recently saw a geneticist and genetic studies are pending. Parents report receiving “little” information regarding prognosis; through their own research, they read about individuals having similar symptoms in adulthood, with a degenerative pattern. They worry that Zoe is “still very young and we do not know what her future will be like.”
Despite ongoing speech and feeding challenges, the parents report difficulty finding a speech and language therapist in their area. Zoe does see an otolaryngologist for frequent otitis media and hearing loss and an ophthalmologist for vision problems. Still, she continues to fall further behind in school. Furthermore, she is intensely afraid of falling at school and has few friends, resulting in the family being at a loss regarding “what to do about school.”
She lives with both parents and 2 healthy older sisters. Her mother has Crohn's disease and has been unable to work. Her maternal aunt is close to Zoe and has hypothyroidism. Her father works as an insurance agent and resources have been “tight.” Zoe's mother describes “making” Zoe go out to the movies, “otherwise she just stays home.” Zoe usually needs assistance to walk in public, to keep from stumbling. Parents share that simply being in a public place or meeting a new physician may trigger emesis. Zoe does enjoy interacting with neighborhood children and says she wants to be “normal,” wear nail polish, and date. She seeks independence, often refusing to use her wheelchair. Parents feel she requires more intensive occupational and physical therapy.
On examination, she is very slender with hypertelorism and nystagmus. Holding an emesis bag, she gags intermittently, producing clear secretions. She has a notable tremor and walks slightly stooped with wide-based gait. Her few words demonstrate articulation differences and cognitive expression characteristic of a younger child. She wears light make-up and age-appropriate clothes. She asks, “When can I go home?”
At the end of the visit, parents share their worry that Zoe is “so young and we do not know anything, what to expect, or what to tell her.” As the family's new medical home, they ask you to weigh in on what to do next to best support her? Where do you begin?
Cross-Talk Between Insulin Signaling and G Protein–Coupled Receptors
Authors: Fu Qin , Shi Qian , West Toni M. , Xiang Yang K. 
Published: March 2017

Abstract:
Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between 2 receptor signaling systems, and forming an integrated and dynamic network. Moreover, insulin can drive cardiac adrenergic desensitization via protein kinase A and G protein-receptor kinases phosphorylation of the β2AR, which compromises adrenergic regulation of cardiac contractile function. In this review, we will explore the current state of knowledge linking insulin and G protein–coupled receptor signaling, especially β-adrenergic receptor signaling in the heart, with emphasis on molecular insights regarding its role in diabetic cardiomyopathy.
Activity rhythms and clinical correlates in fibromyalgia
Authors: Neikrug Ariel B. , Donaldson Gary , Iacob Eli , Williams Sam L. , Hamilton Christopher A. , Okifuji Akiko 
Published: March 2017

Abstract
The primary aim of this study was to evaluate activity rhythms in fibromyalgia syndrome (FMS) and their association with FMS-related symptoms. We hypothesized that stronger and more consistent activity rhythms would be associated with reduced symptom severity and presentation in FMS. Two hundred ninety-two patients with FMS (mean age = 45.1 ± 11.1; 272 women) provided a 7-day actigraphy recording and responses to questionnaires addressing degree of pain, fatigue, mood, and physical impairment. Using a simple cosine model, we extracted Amplitude (activity range), Phi (time at maximum), Mesor (mean activity), and their variabilities (across days) from each participant's actigraphy. The clinical and actigraphic measures were operationally independent. There was a significant canonical relationship between activity rhythm parameters and clinical FMS measures (r = 0.376, R
2 = 0.14, P < 0.001). The set of Mesor, Amplitude, and Phi activity parameters remained associated with clinical measures when controlled statistically for both demographics and activity variability (P < 0.001). Each activity parameter provided unique discrimination of the clinical set by multivariate test (P = 0.003, 0.018, and 0.007 for Amplitude, Phi, and Mesor, respectively). These results revealed that better pain, fatigue, mood, physical impairment, and sleep outcomes were associated with higher activity range and more rhythmicity (Amplitude), increased mean activity (Mesor), and with earlier timing of peak activity (Phi). Exploratory analyses revealed significantly worse sleep for individuals with low Amplitude and more delayed Phi.
deStruct: Accurate Rearrangement Detection using Breakpoint Specific Realignment
Authors: McPherson Andrew , Shah Sohrab , Sahinalp S. Cenk 
Published: March 2017

AbstractWe propose that a breakpoint specific alignment procedure would improve breakpoint prediction. Our method, deStruct, uses multiple stages of realignment and clustering to progressively refine breakpoint prediction quality and accuracy. We show using simulated data that deStruct predicts breakpoints with higher sensitivity and specificity than existing breakpoint prediction tools.
Bacterial physiological adaptations to contrasting edaphic conditions identified using landscape scale metagenomics
Authors: Malik Ashish A. , Thomson Bruce C. , Whiteley Andrew S. , Bailey Mark , Griffiths Robert I. 
Published: March 2017

AbstractEnvironmental factors relating to soil pH are widely known to be important in structuring soil bacterial communities, yet the relationship between taxonomic community composition and functional diversity remains to be determined. Here, we analyze geographically distributed soils spanning a wide pH gradient and assess the functional gene capacity within those communities using whole genome metagenomics. Low pH soils consistently had fewer taxa (lower alpha and gamma diversity), but only marginal reductions in functional alpha diversity and equivalent functional gamma diversity. However, coherent changes in the relative abundances of annotated genes between pH classes were identified; with functional profiles clustering according to pH independent of geography. Differences in gene abundances were found to reflect survival and nutrient acquisition strategies, with organic-rich acidic soils harboring a greater abundance of cation efflux pumps, C and N direct fixation systems and fermentation pathways indicative of anaerobiosis. Conversely, high pH soils possessed more direct transporter-mediated mechanisms for organic C and N substrate acquisition. These findings show that bacterial functional versatility may not be constrained by taxonomy, and we further identify the range of physiological adaptations required to exist in soils of varying nutrient availability and edaphic conditions.
Brain connectivity-informed regularization methods for regression
Authors: Karas Marta , Brzyski Damian , Dzemidzic Mario , Goni Joaquin , Kareken David A. , Randolph Timothy W. , Harezlak Jaroslaw 
Published: March 2017

AbstractA challenging problem arising in brain imaging research is principled incorporation of information from different imaging modalities. Frequently each modality is analyzed separately using, for instance, dimensionality reduction techniques which result in a loss of mutual information. We propose a novel regularization method to estimate the association between the brain structure features and a scalar outcome within the linear regression framework. Our regularization technique provides a principled approach to utilizing external information arising from the structural brain connectivity to inform the estimation of the regression coefficients. Our proposal extends the classical Tikhonov regularization framework by defining a penalty term based on the structural connectivity-derived Laplacian matrix. In the work presented, we address both theoretical and computational issues. The approach is illustrated using simulated data and compared with other penalized regression methods. Finally, we apply our regularization method to study the associations between the alcoholism phenotypes and brain cortical thickness using a diffusion tensor imaging (DTI) derived measure of structural connectivity.
ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads
Authors: Hunt Martin , Mather Alison E. , Sánchez-Busó Leonor , Page Andrew J. , Parkhill Julian , Keane Jacqueline A. , Harris Simon R. 
Published: March 2017

AbstractAntimicrobial resistance (AMR) is one of the major threats to human and animal health worldwide, yet few high-throughput tools exist to analyse and predict the resistance of a bacterial isolate from sequencing data. Here we present a new tool, ARIBA, that identifies AMR-associated genes and single nucleotide polymorphisms directly from short reads, and generates detailed and customisable output. The accuracy and advantages of ARIBA over other tools are demonstrated on three datasets from Gram-positive and Gram-negative bacteria, with ARIBA outperforming existing methods. ARIBA is available athttps://github.com/sanger-pathogens/ariba.
Estimating the proportion of disease heritability mediated by gene expression levels
Authors: O’Connor Luke J. , Gusev Alexander , Liu Xuanyao , Loh Po-Ru , Finucane Hilary K. , Price Alkes L. 
Published: March 2017

AbstractDisease risk variants identified by GWAS are predominantly noncoding, suggesting that gene regulation plays an important role. eQTL studies in unaffected individuals are often used to link disease-associated variants with the genes they regulate, relying on the hypothesis that noncoding regulatory effects are mediated by steady-state expression levels. To test this hypothesis, we developed a method to estimate the proportion of disease heritability mediated by the cis-genetic component of assayed gene expression levels. The method, gene expression co-score regression (GECS regression), relies on the idea that, for a gene whose expression level affects a phenotype, SNPs with similar effects on the expression of that gene will have similar phenotypic effects. In order to distinguish directional effects mediated by gene expression from non-directional pleiotropic or tagging effects, GECS regression operates on pairs of cis SNPs in linkage equilibrium, regressing pairwise products of disease effect sizes on products of cis-eQTL effect sizes. We verified that GECS regression produces robust estimates of mediated effects in simulations. We applied the method to eQTL data in 44 tissues from the GTEx consortium (average NeQTL = 158 samples) in conjunction with GWAS summary statistics for 30 diseases and complex traits (average NGWAS = 88K) with low pairwise genetic correlation, estimating the proportion of SNP-heritability mediated by the cis-genetic component of assayed gene expression in the union of the 44 tissues. The mean estimate was 0.21 (s.e. = 0.01) across 30 traits, with a significantly positive estimate (p < 0.001) for every trait. Thus, assayed gene expression in bulk tissues mediates a statistically significant but modest proportion of disease heritability, motivating the development of additional assays to capture regulatory effects and the use of our method to estimate how much disease heritability they mediate.
Molecular diagnosis of orthopaedic device infection direct from sonication fluid by metagenomic sequencing
Authors: Street Teresa L. , Sanderson Nicholas D. , Atkins Bridget L. , Brent Andrew J. , Cole Kevin , Foster Dona , McNally Martin A. , Oakley Sarah , Peto Leon , Taylor Adrian , Peto Tim E.A. , Crook Derrick W. , Eyre David W. 
Published: March 2017

AbstractCulture of multiple periprosthetic tissue samples is the current gold-standard for microbiological diagnosis of prosthetic joint infections (PJI). Additional diagnostic information may be obtained through sonication fluid culture of explants. However, current techniques can have relatively low sensitivity, with prior antimicrobial therapy and infection by fastidious organisms influencing results. We assessed if metagenomic sequencing of complete bacterial DNA extracts obtained direct from sonication fluid can provide an alternative rapid and sensitive tool for diagnosis of PJI.We compared metagenomic sequencing with standard aerobic and anaerobic culture in 97 sonication fluid samples from prosthetic joint and other orthopaedic device infections. Reads from Illumina MiSeq sequencing were taxonomically classified using Kraken. Using 50 samples (derivation set), we determined optimal thresholds for the number and proportion of bacterial reads required to identify an infection and validated our findings in 47 independent samples.Compared to sonication fluid culture, the species-level sensitivity of metagenomic sequencing was 61/69(88%,95%CI 77-94%) (derivation samples 35/38[92%,79-98%]; validation 26/31[84%,66-95%]), and genus-level sensitivity was 64/69(93%,84-98%). Species-level specificity, adjusting for plausible fastidious causes of infection, species found in concurrently obtained tissue samples, and prior antibiotics, was 85/97(88%,79-93%) (derivation 43/50[86%,73-94%], validation 42/47[89%,77-96%]). High levels of human DNA contamination were seen despite use of laboratory methods to remove it. Rigorous laboratory good practice was required to prevent bacterial DNA contamination.We demonstrate metagenomic sequencing can provide accurate diagnostic information in PJI. Our findings combined with increasing availability of portable, random-access sequencing technology offers the potential to translate metagenomic sequencing into a rapid diagnostic tool in PJI.
Identification, Isolation, and Characterization of Human LGR5-positive Colon Adenoma Cells
Authors: Dame Michael K. , Attili Durga , McClintock Shannon D. , Dedhia Priya H. , Ouilette Peter , Hardt Olaf , Chin Alana M , Xue Xiang , Laliberte Julie , Katz Erica L , Newsome Gina M. , Hill David R. , Miller Alyssa J. , Tsai Yu-Hwai , Agorku David , Altheim Christopher H , Bosio Andreas , Simon Becky , Samuelson Linda C , Stoerker Jay A , Appelman Henry D , Varani James , Wicha Max S. , Brenner Dean E. , Shah Yatrik M. , Spence Jason R , Colacino Justin A. 
Published: March 2017

ABSTRACTThe intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, while less is known about human intestinal stem cells due to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas, and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC) associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5. LGR5-positive cells were isolated from 4 adenoma organoid lines and were subjected to RNA-sequencing. We found that LGR5 expression in the epithelium and stroma was associated with tumor stage, and by integrating functional experiments with LGR5-sorted cell RNA-seq data from adenoma and normal organoids, we found correlations between LGR5 and CRC- specific genes, including DKK4 (dickkopf WNT signaling pathway inhibitor 4) and SMOC2 (SPARC related modular calcium binding 2). Collectively, this work provides resources, methods and new markers to isolate and study stem cells in human tissue homeostasis and carcinogenesis.
Electrically Conductive Pili from Pilin Genes of Phylogenetically Diverse Microorganisms
Authors: Walker David J.F. , Adhikari Ramesh Y. , Holmes Dawn E. , Ward Joy E. , Woodard Trevor L. , Nevin Kelly P. , Lovley Derek R. 
Published: March 2017

AbstractThe possibility that bacteria other thanGeobacterspecies might contain genes for electrically conductive pili (e-pili) was investigated by heterologously expressing pilin genes of interest inGeobacter sulfurreducens. Strains ofG. sulfurreducensproducing high current densities, which are only possible with e-pili, were obtained with pilin genes fromFlexistipes sinusarabici, Calditerrivibrio nitroreducens, andDesulfurivibrio alkaliphilus. The conductance of pili from these strains was comparable to nativeG. sulfurreducense-pili. The e-pili derived fromC. nitroreducens,andD. alkaliphiluspilin genes are the first examples of relatively long (> 100 amino acids) pilin monomers assembling into e-pili. The pilin gene fromDesulfofervidus auxiliidid not yield e-pili, suggesting that the hypothesis that this sulfate reducer wires itself to ANME-1 microbes with e-pili to promote anaerobic methane oxidation should be reevaluated. A high density of aromatic amino acids and a lack of substantial aromatic-free gaps along the length of long pilins may be important characteristics leading to e-pili. This study demonstrates a simple method to screen pilin genes from difficult-to-culture microorganisms for their potential to yield e-pili; reveals new potential sources for biologically based electronic materials; and suggests that a wide phylogenetic diversity of microorganisms may employ e-pili for extracellular electron exchange.