bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic Investigation of Idiopathic Meningoencephalomyelitis in Dogs
Authors: Hoon‐Hanks L.L. , McGrath S. , Tyler K.L. , Owen C. , Stenglein M.D. 
Published: December 2017

BackgroundMeningoencephalomyelitis of unknown origin (MUO) is a common and life‐threatening neuroinflammatory disease in dogs. Features of the disease are suggestive of an underlying immune‐mediated process, but the association of this disease with a pathogen is still unknown.Hypothesis/ObjectivesTo search for candidate etiologic agent associated with cases if MUO using next generation metagenomic sequencing.AnimalsTwenty‐two dogs diagnosed with either MUO (11/22; 10 CSF and 3 brain), or noninflammatory CNS diseases inconsistent with MUO (11/22; 11 CSF and 2 brain) that served as negative controls.MethodsA case control study was performed by identifying MUO and non‐MUO cases. Samples were blindly processed and then unblinded for comparative analyses. Inclusion criteria for MUO cases included consistent MRI lesions and inflammatory CSF with a negative PCR panel for infectious agents or histopathologic diagnosis. Dogs with glucocorticoid therapy within 2 weeks of sample collection were excluded. Fresh‐frozen cerebrospinal fluid (CSF; 21) and brain (5) samples were collected and RNA and DNA were extracted separately for shotgun metagenomic sequencing. Known positive samples were used as controls to validate our sequencing and analysis pipelines and to establish limits of detection. Sequencing results were analyzed at a nucleotide and protein level for broad comparison to known infectious organisms.ResultsNo candidate etiologic agents were identified in dogs with MUO.Conclusions and Clinical ImportanceThese results support but do not prove the hypothesis that MUO is not associated with infectious agents and might be an autoimmune disease.
Geographic variation in life‐history traits: factors shaping energy investment in reproduction in a highland dwelling rodent
Authors: Sassi P. L. , Menéndez J. , Cuevas M. F. 
Published: December 2017

AbstractVariation in life‐history traits is shaped by intrinsic and extrinsic factors. Climate influences the availability of energy and nutrients in the environment, and thus animals’ energy balance, their allocation of resources to reproduction and ultimately, fitness. Temperature is reported as a prevailing influence on animals’ investment in reproduction, and diverse hypotheses propose mechanisms by which it occurs. Central and external limits to energy acquisition have been traditionally assumed. Hence, digestive limitations, periods of low food availability or demanding cold conditions would restrict this input. However, under warm conditions endotherms also face the need to dissipate heat from metabolic processes. From this perspective, a high metabolic rate process, such as lactation, would be restricted under increasing ambient temperatures (Ta). Our research addresses the variation in reproductive parameters in Phyllotis xanthopygus, a rodent species broadly distributed in the west highlands and southern parts of South America. Across a pronounced elevation gradient in the central Andes Mountains we found that litter size is comparatively smaller in pregnant females collected at lower elevations. This is congruent with expectations from the heat dissipation limit hypothesis. To disentangle the role of temperature on this pattern, we bred individuals under two thermal treatments. We recorded no changes in the litter size, but pups’ body mass was lower at higher Ta during lactation, also in agreement with decreased metabolism. Offspring size and number are relevant to a species’ fitness. The evidence suggests that in P. xanthopygus these traits vary geographically and are shaped by Ta in the laboratory. A species that evolved in high altitudes, inhabits cold and temperate areas and is sensitive to Ta increases in the laboratory, appears as an excellent candidate to further explore the ecophysiology‐thermal landscape interface, crucial to develop accurate predictive models of biodiversity dynamics.
Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft‐versus‐host disease: A pilot study
Authors: Motta ACF , Zhan Q , Larson A , Lerman M , Woo S‐B , Soiffer RJ , Murphy GF , Treister NS 
Published: December 2017

ObjectiveTo characterize the immunohistopathological features of oral chronic graft‐versus‐host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells.Material and MethodsPaired oral cGVHD biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c‐kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral lichen planus (OLP; n = 5), and normal tissues (n = 5).ResultsOral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+, CD4+, CD8+, CD103+, CD163+, and FoxP3+ cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4+ and CD103+ cells.ConclusionThe high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T‐cell‐driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.
Breastmilk cell trafficking induces microchimerism‐mediated immune system maturation in the infant
Authors: Molès Jean‐Pierre , Tuaillon Edouard , Kankasa Chipepo , Bedin Anne‐Sophie , Nagot Nicolas , Marchant Arnaud , McDermid Joann M. , Van de Perre Philippe 
Published: December 2017

AbstractInitiating breastfeeding within the first hour of life confers an important benefit in terms of child mortality and severe morbidity. Intestinal permeability to ingested macromolecules and immunoglobulins is limited to the first days of human life. These exchanges cease in the very early post‐partum period but may increase beyond the neonatal period in response to local inflammation or introduction of a weaning food. From animal‐ and limited human‐based observations, compelling evidence points out to breastmilk cells also trafficking from mother to infant mucosal tissues and participating to the maternal microchimerism. The precise nature of breastmilk cells that are involved is presently not known but likely includes progenitor/stem cells—representing up to 6% of breastmilk cells—with possible contribution of mature immune cells. Stem cell microchimerism may induce tolerance to non‐inherited maternal antigens (NIMAs), breastfeeding generating regulatory T cells (Treg) that suppress antimaternal immunity. Therefore, in complement to pregnancy‐induced microchimerism, breastfeeding‐induced microchimerism may be pivotal in infant immune development, intestinal tissue repair/growth and protection against infectious diseases. As a continuum of the gestational period, the neonatal gut may be considered as a temporary, but important developmental extension of the role played by the placenta during intrauterine life; breastmilk playing the role of maternal blood by delivering maternal soluble factors (macromolecules, Ig, cytokines) and immunologically active milk cells. A better understanding of breastfeeding‐induced maternal microchimerism would provide further evidence in support of public health messages that reinforce the importance of early initiation of breastfeeding.
Patient self‐care of periodontal pocket infections
Authors: Arweiler Nicole Birgit , Auschill Thorsten M. , Sculean Anton 
Published: December 2017

AbstractTreatment of periodontitis aims to control the infection caused by the periodontal pathogenic flora and includes mechanical debridement of root surfaces to disrupt the supragingival and subgingival biofilm. As periodontal pockets of ≤ 5 mm can be perform in a stable condition and may not need additional therapy, the ability and the willingness of the patient to perform good oral hygiene on a long‐term basis are of utmost importance for ensuring long‐term success of periodontal treatment. In this context, the aim of all home‐care measures must be the optimal control of plaque biofilm in order to prevent or treat gingival inflammation as a primary stage of periodontitis. Despite the fact that toothbrushing and other mechanical cleaning practices are the most important elements for preventing periodontal diseases or their progression, other factors, including education, motivation, manual dexterity and compliance with professional recommendation, provision of time and socio‐economic status, as well as risk factors, play a role. The present article provides an overview on the various possibilities for self‐care of residual pockets in patients with periodontitis.
Choriocapillaris flow deficit in Bietti crystalline dystrophy detected using optical coherence tomography angiography
Authors: Miyata Manabu , Oishi Akio , Hasegawa Tomoko , Ishihara Kenji , Oishi Maho , Ogino Ken , Sugahara Masako , Hirashima Takako , Hata Masayuki , Yoshikawa Munemitsu , Tsujikawa Akitaka 
Published: December 2017

Background/AimsThis study aimed to evaluate blood flow in the choriocapillaris in patients with Bietti crystalline dystrophy (BCD) with CYP4V2 mutations using optical coherence tomography angiography (OCTA), and to explore the parameters associated with visual function.MethodsThis prospective case-series study included 13 eyes of 13 consecutive patients with BCD with CYP4V2 mutations and 20 healthy eyes. Using OCTA, we obtained en face images of blood flow in the choriocapillaris. The residual choriocapillaris area on en face images in a 10°×10° macular cube was manually measured and graded according to whether the choriocapillaris remained at the subfovea. We also investigated factors associated with visual acuity (VA) and the mean deviation (MD) value using a Humphrey field analyser with a 10–2 Swedish Interactive Threshold Algorithm standard program among OCTA-derived parameters.ResultsChoriocapillaris blood flow deficit was observed in 12 eyes (92%), whereas this was observed in none of healthy eyes. The adjusted residual choriocapillaris area was 2.47±1.79 mm2. The presence of the choriocapillaris at the subfovea was significantly correlated with VA and the MD value (P=0.006, r=0.71; P=0.04, r=−0.59, respectively).ConclusionsUsing OCTA, choriocapillaris blood flow deficit could be observed in most patients with BCD with CYP4V2 mutations. The presence of the choriocapillaris at the subfovea was significantly correlated with visual function in these patients. Analysis of choriocapillaris blood flow using OCTA allows non-invasive assessment of the patient’s state.
Prehospital intravenous access for survival from out-of-hospital cardiac arrest: propensity score matched analyses from a population-based cohort study in Osaka, Japan
Authors: Fujii Tomoko , Kitamura Tetsuhisa , Kajino Kentaro , Kiyohara Kosuke , Nishiyama Chika , Nishiuchi Tatsuya , Hayashi Yasuyuki , Kawamura Takashi , Iwami Taku 
Published: December 2017

ObjectivesPrehospital intravenous access is a common intervention for patients with out-of-hospital cardiac arrest (OHCA). We aimed to assess the effectiveness of prehospital intravenous access and subsequent epinephrine administration on outcomes among OHCA patients.MethodsWe conducted a prospective cohort study of patients with OHCA from non-traumatic causes aged ≥18 years in Osaka, Japan from January 2005 through December 2012. The primary outcome was 1-month survival with favourable neurological outcome defined as a cerebral performance category of 1 or 2. The association between intravenous line placement and survival with favourable neurological outcome was evaluated by logistic regression, after propensity score matching for the intravenous access attempt stratified by initial documented rhythm of ventricular fibrillation (VF) or non-VF. The contribution of epinephrine administration to the outcome was also explored.ResultsAmong OHCA patients during the study period, 3208 VF patients and 38 175 non-VF patients were included in our analysis. Intravenous access attempt was negatively associated with 1-month survival with a favourable neurological outcome in VF group (OR 0.76, 95% CI 0.59 to 0.98), while no association was observed in the non-VF group (OR 1.06, 95% CI 0.84 to 1.34). Epinephrine administration had no positive association in the VF patients (OR 0.75, 95% CI 0.51 to 1.07) and positively associated in the non-VF patients (OR 1.52, 95% CI 1.08 to 2.08) with the favourable neurological outcome.ConclusionsIntravenous access attempt could be negatively associated with survival with a favourable neurological outcome after OHCA. Subsequent epinephrine administration might be effective for non-VF OHCAs.
Measurement of harms in community care: a qualitative study of use of the NHS Safety Thermometer
Authors: Brewster Liz , Tarrant Carolyn , Willars Janet , Armstrong Natalie 
Published: December 2017

ObjectivesMeasurement is a vital part of improvement work. While it is known that the context of improvement work influences its success, less is known about how context affects measurement of underlying harms. We sought to explore the use of a harm measurement tool, the NHS Safety Thermometer (NHS-ST), designed for use across diverse healthcare settings in the particular context of community care.MethodsThis is a qualitative study of 19 National Health Service (NHS) organisations, 7 of which had community service provision. We conducted ethnographic observations of practice and interviews with front-line nursing and senior staff. Analysis was based on the constant comparison method.ResultsMeasurement in community settings presents distinct challenges, calling into question the extent to which measures can be easily transferred. The NHS-ST was seen as more appropriate for acute care, not least because community nurses did not have the same access to information. Data collection requirements were in tension with maintaining a relationship of trust with patients. The aim to collect data across care settings acted to undermine perceptions of the representativeness of community data. Although the tool was designed to measure preventable harms, care providers questioned their preventability within a community setting. Different harms were seen as priorities for measurement and improvement within community settings.ConclusionsMeasurement tools are experienced by healthcare staff as socially situated. In the community setting, there are distinct challenges to improving care quality not experienced in the acute sector. Strategies to measure harms, and use of any resulting data for improvement work, need to be cognisant of the complexity of an environment where healthcare staff often have little opportunity to monitor and influence patients.
Suramin increases cartilage proteoglycan accumulation in vitro and protects against joint damage triggered by papain injection in mouse knees in vivo
Authors: Guns Laura-An , Monteagudo Silvia , Kvasnytsia Maryna , Kerckhofs Greet , Vandooren Jennifer , Opdenakker Ghislain , Lories Rik J , Cailotto Frederic 
Published: December 2017

ObjectivesSuramin is an old drug used for the treatment of African sleeping sickness. We investigated therapeutic repositioning of suramin to protect against cartilage damage, as suramin may interact with tissue inhibitor of metalloproteinase-3 (TIMP3).MethodsIn vitro extracellular matrix (ECM) accumulation and turnover in the presence or absence of suramin were studied in the ATDC5 micromass model of chondrogenesis and in pellet cultures of human articular chondrocytes from osteoarthritis and control patients, by gene expression, protein analysis, colorimetric staining, immunoprecipitation, fluorimetric analysis and immunohistochemistry. To study suramin in vivo, the drug was injected intra-articularly in the papain model of joint damage. Disease severity was analysed by histology, immunohistochemistry and contrast-enhanced nanofocus CT.ResultsIn ATDC5 micromasses, suramin increased TIMP3 levels and decreased the activity of matrix metalloproteinases (MMPs) and aggrecanases. Suramin treatment resulted in increased glycosaminoglycans. This effect on the ECM was blocked by an anti-TIMP3 antibody. Direct interaction between suramin and endogenous TIMP3 was demonstrated in immunoprecipitates. Mice treated intra-articularly with suramin injections showed reduced cartilage damage compared with controls, with increased TIMP3 and decreased MMP and aggrecanase activity. Translational validation in human chondrocytes confirmed increased TIMP3 function and reduced cartilage breakdown after suramin treatment.ConclusionSuramin prevented loss of articular cartilage in a mouse model of cartilage damage. The effects appear to be mediated by a functional increase of TIMP3 and a subsequent decrease in the activity of catabolic enzymes. Thus, suramin repositioning could be considered to prevent progressive cartilage damage and avoid evolution toward osteoarthritis.
Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer
Authors: Strickler John H. , Loree Jonathan M. , Ahronian Leanne G. , Parikh Aparna R. , Niedzwiecki Donna , Pereira Allan Andresson Lima , McKinney Matthew , Korn W. Michael , Atreya Chloe E. , Banks Kimberly C. , Nagy Rebecca J. , Meric-Bernstam Funda , Lanman Richard B. , Talasaz AmirAli , Tsigelny Igor F. , Corcoran Ryan B. , Kopetz Scott 
Published: December 2017

Abstract
“Liquid biopsy” approaches analyzing cell-free DNA (cfDNA) from the blood of patients with cancer are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cohorts of patients with cancer can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based colorectal cancer sequencing compendia. Our analysis also identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed striking tumor heterogeneity, with 91% harboring multiple distinct resistance alterations (range, 1–13; median, 4). These results suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biological insights.
Significance: This study provides one of the first examples of how large-scale genomic profiling of cfDNA from patients with colorectal cancer can detect genomic alterations at frequencies comparable to those observed by direct tumor sequencing. Sequencing of cfDNA also generated insights into tumor heterogeneity and therapeutic resistance and identified novel EGFR ectodomain mutations. Cancer Discov; 8(2); 164–73. ©2017 AACR.
This article is highlighted in the In This Issue feature, p. 127
Towards a global initiative for fibrosis treatment (GIFT)
Authors: Molina-Molina Maria , Agusti Alvar , Crestani Bruno , Schwartz David A. , Königshoff Melanie , Chambers Rachel C. , Maher Toby M. , Faner Rosa , Mora Ana Lucia , Rojas Mauricio , Antoniou Katerina M. , Sellares Jacobo 
Published: December 2017

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterised by increased scarring of lung tissue. Despite the recent introduction of novel drugs that slow disease progression, IPF remains a deadly disease, and the benefits of these new drugs differ markedly between patients.Human diseases arise due to alterations in an almost limitless network of interconnected genes, proteins, metabolites, cells and tissues, in direct relationship with a continuously changing macro- or microenvironment. Systems biology is a novel research strategy that seeks to understand the structure and behaviour of the so-called “emergent properties” of complex systems, such as those involved in disease pathogenesis, which are most often overlooked when just one element of disease pathogenesis is observed in isolation.This article summarises the debate that took place during a European Respiratory Society research seminar in Barcelona, Spain on December 15–16, 2016, which focused on how systems biology could generate new data by integrating the different IPF pathogenic levels of complexity. The main conclusion of the seminar was to create a global initiative to improve IPF outcomes by integrating cutting-edge international research that leverages systems biology to develop a precision medicine approach to tackle this devastating disease.
High-quality draft genome sequence of Aquidulcibacter paucihalophilus TH1–2T isolated from cyanobacterial aggregates in a eutrophic lake
Authors: Cai Haiyuan , Zeng Yonghui 
Published: December 2017

AbstractAquidulcibacter paucihalophilus TH1–2T is a member of the family Caulobacteraceae within Alphaproteobacteria isolated from cyanobacterial aggregates in a eutrophic lake. The draft genome comprises 3,711,627 bp and 3489 predicted protein-coding genes. The genome of strain TH1–2T has 270 genes encoding peptidases. And metallo and serine peptidases were found most frequently. A high number of genes encoding carbohydrate active enzymes (141 CAZymes) also present in strain TH1–2T genome. Among CAZymes, 47 glycoside hydrolase families, 37 glycosyl transferase families, 38 carbohydrate esterases families, nine auxiliary activities families, seven carbohydrate-binding modules families, and three polysaccharide lyases families were identified. Accordingly, strain TH1–2T has a high number of transporters (91), the dominated ones are ATP-binding cassette transporters (61) and TonB-dependent transporters (28). Major TBDTs are Group I, which consisted of transporters for various types of dissolved organic matter. These genome features indicate adaption to cyanobacterial aggregates microenvironments.
COMPRENSIÓN DE NOCIONES DEL SISTEMA MÉTRICO DECIMAL MEDIADA POR LA LSM EN EL AULA DE SORDOS [17-21]: ESTUDIO DE CASOS
Authors: Barojas Gómez Andrea , Garnica Dovala Ignacio 
Published: December 2017

Un problema central de la enseñanza de las matemáticas del Sordo es la comunicación entre docente y aprendiz, situación que exige reconocer las Lenguas de Señas como naturales. Nuestra investigación parte de este principio y se orienta a la comprensión de la Lengua de Señas Mexicana (LSM) en su relación con nociones matemáticas que se desarrollan en el aula de Sordos, específicamente a la de su gramática y a la construcción de Señas relativas a nociones del sistema métrico decimal (SMD). Se propone un modelo de comunicación para desarrollar tres procesos en el aula: enseñanza, indagación e investigación que propició la constitución de Señas pertinentes a cada una de nueve nociones: siete de matemáticas y dos de instrumentos de medición. Se realizó en condiciones de tiempo real en el aula con ocho jóvenes Sordos. Los resultados evidencian la relevancia del reconocimiento antes descrito y la necesaria presencia de la lengua escrita.