bluuebunny/crossref_metadata_2025_split huggingface dataset:
Searching for a Potential Algorithm for Clostridium difficile Testing at a Tertiary Care Hospital: Does Toxin Enzyme Immunoassay Testing Help?
Authors: Theiss Angela M. , Balla Agnes , Ross Angie , Francis Denise , Wojewoda Christina 
Published: May 2018

ABSTRACTClostridium difficileis a major contributor to morbidity and mortality in the United States. Methods for identifying the organism in stool include molecular platforms, enzyme immunoassays (EIAs) for toxin, and culture. Controversy persists over whether molecular tests are too sensitive at identifyingC. difficile, and there are questions about how additional laboratory information could inform clinical management and reduce over treatment. The aim of this study was to assess whether clinical factors are related to the toxin status of patients and whether information about toxin status could potentially inform clinical management of patients. A total of 201 PCR-positiveC. difficilestool samples from adult patients at our institution underwent EIA toxin testing. Clinical and laboratory data were collected, and the percentage of PCR-positive/EIA-positive (PCR+/EIA+) patients and PCR+and EIA-negative (PCR+/EIA−) patients was calculated. Of the 201 samples, 47% were EIA positive and 53% were EIA negative. Although PCR+/EIA+patients were more likely to have had a priorC. difficileinfection (P= 0.015), there was no statistical difference between the additional data collected that correlated with a positive EIA result. We were unable to show that patients with an EIA+result had worse clinical parameters than those with EIA−results and concluded that establishing a testing algorithm that included both PCR and EIA testing would not change the clinical management of patients at our hospital.
Updates in the Language of
Histoplasma
Biodiversity
Authors: Gladieux Pierre 
Published: May 2018

ABSTRACT

In a recent article, Sepúlveda et al. (mBio 8:e01339-17, 2017,
https://doi.org/10.1128/mBio.01339-17
) investigated the genetic structure and evolutionary history of the human pathogen
Histoplasma
. Using whole-genome resequencing data, Sepúlveda et al. found that the
Histoplasma
genus is composed of at least four strongly differentiated lineages. Their tour de force is to use a smart combination of population genomic approaches to show that the advanced stage of intraspecific divergence observed within
Histoplasma
does not simply reflect population structure, but instead results from previously unidentified speciation events. The four independently evolving
Histoplasma
lineages are elevated to the species status and assigned names. The newly described species exhibit medically important differences in phenotype, and these findings, therefore, have important epidemiological implications. This work provides a blueprint for phylogenomic species recognition in fungi, opening the way for a new age of enlightenment in which fungal species are diagnosed using highly discriminatory tools within a hypothesis-testing framework.
A High Frequency of HIV-Specific Circulating Follicular Helper T Cells Is Associated with Preserved Memory B Cell Responses in HIV Controllers
Authors: Claireaux M. , Galperin M. , Benati D. , Nouël A. , Mukhopadhyay M. , Klingler J. , de Truchis P. , Zucman D. , Hendou S. , Boufassa F. , Moog C. , Lambotte O. , Chakrabarti L. A. 
Published: May 2018

ABSTRACTFollicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4+T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet+), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA−CXCR5+CD4+T cell population, proved more frequent in the controller group (P= 0.002). The frequency of PD-1 expression in Tet+cTfh was increased in both groups (median, >75%) compared to total cTfh (<30%), but the intensity of PD-1 expression per cell remained higher in the treated patient group (P= 0.02), pointing to the persistence of abnormal immune activation in treated patients. The function of cTfh, analyzed by the capacity to promote IgG secretion in cocultures with autologous memory B cells, did not show major differences between groups in terms of total IgG production but proved significantly more efficient in the controller group when measuring HIV-specific IgG production. The frequency of Tet+cTfh correlated with HIV-specific IgG production (R= 0.71 for Gag-specific andR= 0.79 for Env-specific IgG, respectively). Taken together, our findings indicate that key cTfh-B cell interactions are preserved in controlled HIV infection, resulting in potent memory B cell responses that may play an underappreciated role in HIV control.IMPORTANCEThe rare patients who spontaneously control HIV replication in the absence of therapy provide a unique model to identify determinants of an effective anti-HIV immune response. HIV controllers show signs of particularly efficient antiviral T cell responses, while their humoral response was until recently considered to play only a minor role in viral control. However, emerging evidence suggests that HIV controllers maintain a significant but “silent” antiviral memory B cell population that can be reactivated upon antigenic stimulation. We report that cTfh help likely contributes to the persistence of controller memory B cell responses, as the frequency of HIV-specific cTfh correlated with the induction of HIV-specific antibodies in functional assays. These findings suggest that T follicular help may contribute to HIV control and highlight the need for inducing such help in HIV vaccine strategies that aim at eliciting persistent B cell responses.
Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type Salmonella enterica Serovar Typhi
Authors: Zhang Yan , Brady Arthur , Jones Cheron , Song Yang , Darton Thomas C. , Jones Claire , Blohmke Christoph J. , Pollard Andrew J. , Magder Laurence S. , Fasano Alessio , Sztein Marcelo B. , Fraser Claire M. 
Published: May 2018

ABSTRACTInsights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-typeSalmonella entericaserovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota. Metatranscriptome analysis of longitudinal stool samples collected from study subjects revealed two stable patterns of gene expression for the human gut microbiota, dominated by transcripts from eitherMethanobrevibacteror a diverse representation of genera in theFirmicutesphylum. Immunization with one of two live oral attenuated vaccines againstS. Typhi had minimal effects on the composition or function of the gut microbiota. It was observed that subjects harboring the methanogen-dominated transcriptome community at baseline displayed a lower risk of developing symptoms of typhoid following challenge with wild-typeS. Typhi. Furthermore, genes encoding antioxidant proteins, metal homeostasis and transport proteins, and heat shock proteins were expressed at a higher level at baseline or after challenge withS. Typhi in subjects who did not develop symptoms of typhoid. These data suggest that functional differences relating to redox potential and ion homeostasis in the gut microbiota may impact clinical outcomes following exposure to wild-typeS. Typhi.IMPORTANCES. Typhi is a significant cause of systemic febrile morbidity in settings with poor sanitation and limited access to clean water. It has been demonstrated that the human gut microbiota can influence mucosal immune responses, but there is little information available on the impact of the human gut microbiota on clinical outcomes following exposure to enteric pathogens. Here, we describe differences in the composition and function of the gut microbiota in healthy adult volunteers enrolled in a typhoid vaccine trial and report that these differences are associated with host susceptibility to or protection from typhoid after challenge with wild-typeS. Typhi. Our observations have important implications in interpreting the efficacy of oral attenuated vaccines against enteric pathogens in diverse populations.
Feasibility and effects of a home-based intervention using activity trackers on achievement of individual goals, quality of life and motor performance in patients with paediatric cancer
Authors: Götte Miriam , Kesting Sabine Verena , Gerss Joachim , Rosenbaum Dieter , Boos Joachim 
Published: May 2018

ObjectivesSupervised exercise interventions during inpatient care are feasible. The objective was to evaluate the usability of activity trackers and centralised monitoring to conduct a home-based exercise intervention during cancer treatment. The primary endpoint and confirmatory analysis was achievement of individual goals for daily steps, compared (A) in the intervention group (IG) over time and (B) between the IG and control group (CG). Secondary endpoints included achievement of goals for active minutes and effects on motor performance and health-related quality of life (hrQoL).MethodsForty patients treated for paediatric cancer (14.7±3.9 years) were included. The IG received a 6–8 week intervention during acute treatment (T1) and a 2-week intervention in transition to aftercare (T2). The CG only received the intervention at T2. Baseline tests to assess motor performance and physical activity were conducted prior to every intervention.ResultsIn the primary confirmatory analysis, the IG significantly improved achievement of individual step goals (p=0.04) whereas group analyses did not reveal significant differences. Achievement of active minutes remained low (p=0.23). IG scored higher in hrQoL than CG (p<0.01) and percentage of children scoring below normative value in strength tests was higher in CG. Of all participants, 94% rated the intervention as meaningful and 80% as motivational.ConclusionsResults of this study indicate that this intervention for home stays with centralised supervision is feasible and leads to increased achievement of individual step goals. Despite the positive effects on hrQoL, further strategies are needed to increase positive effects on motor performance.
A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review
Authors: Teodoro Tiago , Edwards Mark J , Isaacs Jeremy D 
Published: May 2018

BackgroundFunctional cognitive disorder (FCD) describes cognitive dysfunction in the absence of an organic cause. It is increasingly prevalent in healthcare settings yet its key neuropsychological features have not been reported in large patient cohorts. We hypothesised that cognitive profiles in fibromyalgia (FM), chronic fatigue syndrome (CFS) and functional neurological disorders (FNDs) would provide a template for characterising FCD.MethodsWe conducted a systematic review of studies with cognition-related outcomes in FM, CFS and FND.ResultsWe selected 52 studies on FM, 95 on CFS and 39 on FND. We found a general discordance between high rates of subjective cognitive symptoms, including forgetfulness, distractibility and word-finding difficulties, and inconsistent objective neuropsychological deficits. Objective deficits were reported, including poor selective and divided attention, slow information processing and vulnerability to distraction. In some studies, cognitive performance was inversely correlated with pain, exertion and fatigue. Performance validity testing demonstrated poor effort in only a minority of subjects, and patients with CFS showed a heightened perception of effort.DiscussionThe cognitive profiles of FM, CFS and non-cognitive FND are similar to the proposed features of FCD, suggesting common mechanistic underpinnings. Similar findings have been reported in patients with mild traumatic brain injury and whiplash. We hypothesise that pain, fatigue and excessive interoceptive monitoring produce a decrease in externally directed attention. This increases susceptibility to distraction and slows information processing, interfering with cognitive function, in particular multitasking. Routine cognitive processes are experienced as unduly effortful. This may reflect a switch from an automatic to a less efficient controlled or explicit cognitive mode, a mechanism that has also been proposed for impaired motor control in FND. These experiences might then be overinterpreted due to memory perfectionism and heightened self-monitoring of cognitive performance.
Diagnostic accuracy of a two-stage model for detecting obstructive sleep apnoea in chronic tetraplegia
Authors: Graco Marnie , Schembri Rachel , Cross Susan , Thiyagarajan Chinnaya , Shafazand Shirin , Ayas Najib T , Nash Mark S , Vu Viet H , Ruehland Warren R , Chai-Coetzer Ching Li , Rochford Peter , Churchward Thomas , Green Sally E , Berlowitz David J 
Published: May 2018

BackgroundObstructive sleep apnoea (OSA) is highly prevalent in people with spinal cord injury (SCI). Polysomnography (PSG) is the gold-standard diagnostic test for OSA, however PSG is expensive and frequently inaccessible, especially in SCI. A two-stage model, incorporating a questionnaire followed by oximetry, has been found to accurately detect moderate to severe OSA (MS-OSA) in a non-disabled primary care population. This study investigated the accuracy of the two-stage model in chronic tetraplegia using both the original model and a modified version for tetraplegia.MethodsAn existing data set of 78 people with tetraplegia was used to modify the original two-stage model. Multivariable analysis identified significant risk factors for inclusion in a new tetraplegia-specific questionnaire. Receiver operating characteristic (ROC) curve analyses of the questionnaires and oximetry established thresholds for diagnosing MS-OSA. The accuracy of both models in diagnosing MS-OSA was prospectively evaluated in 100 participants with chronic tetraplegia across four international SCI units.ResultsInjury completeness, sleepiness, self-reported snoring and apnoeas were included in the modified questionnaire, which was highly predictive of MS-OSA (ROC area under the curve 0.87 (95% CI 0.79 to 0.95)). The 3% oxygen desaturation index was also highly predictive (0.93 (0.87–0.98)). The two-stage model with modified questionnaire had a sensitivity and specificity of 83% (66–93) and 88% (75–94) in the development group, and 77% (65–87) and 81% (68–90) in the validation group. Similar results were demonstrated with the original model.ConclusionImplementation of this simple alternative to full PSG could substantially increase the detection of OSA in patients with tetraplegia and improve access to treatments.Trial registration numberResults, ACTRN12615000896572 (The Australian and New Zealand Clinical Trials Registry) and pre-results, NCT02176928 (clinicaltrials.gov).
The Amazing Power of Dimensional Analysis: Quantifying Market Impact
Authors: Pohl Mathias , Ristig Alexander , Schachermayer Walter , Tangpi Ludovic 
Published: May 2018

This paper complements the inspiring work on dimensional analysis and market microstructure by Kyle and Obizhaeva (2017). Following closely these authors, our main result shows, by a similar argument as usually applied in physics, the following remarkable fact. If the market impact of a meta-order only depends on four well-defined and financially meaningful variables, and some obvious scaling relations as well as the assumption of leverage neutrality are satisfied, then there is only one possible form of this dependence. In particular, the market impact is proportional to the square-root of the size of the meta-order. This theorem can be regarded as a special case of a more general result of Kyle and Obizhaeva. These authors consider five variables which might have an influence on the size of the market impact. In this case, one finds a richer variety of possible functional relations which we precisely characterize. We also discuss the analogies to classical arguments from physics, such as the period of a pendulum.
TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type I to Promote Tumorigenesis
Authors: Deng Chengcheng , Lin Yu-Xin , Qi Xue-Kang , He Gui-Ping , Zhang Yuchen , Zhang Hao-Jiong , Xu Miao , Feng Qi-Sheng , Bei Jin-Xin , Zeng Yi-Xin , Feng Lin 
Published: May 2018

AbstractGenetic susceptibility underlies the pathogenesis of cancer. We and others have previously identified a novel susceptibility gene TNFRSF19, which encodes an orphan member of the TNF receptor superfamily known to be associated with nasopharyngeal carcinoma (NPC) and lung cancer risk. Here, we show that TNFRSF19 is highly expressed in NPC and is required for cell proliferation and NPC development. However, unlike most of the TNF receptors, TNFRSF19 was not involved in NFκB activation or associated with TRAF proteins. We identified TGFβ receptor type I (TβRI) as a specific binding partner for TNFRSF19. TNFRSF19 bound the kinase domain of TβRI in the cytoplasm, thereby blocking Smad2/3 association with TβRI and subsequent signal transduction. Ectopic expression of TNFRSF19 in normal epithelial cells conferred resistance to the cell-cycle block induced by TGFβ, whereas knockout of TNFRSF19 in NPC cells unleashed a potent TGFβ response characterized by upregulation of Smad2/3 phosphorylation and TGFβ target gene transcription. Furthermore, elevated TNFRSF19 expression correlated with reduced TGFβ activity and poor prognosis in patients with NPC. Our data reveal that gain of function of TNFRSF19 in NPC represents a mechanism by which tumor cells evade the growth-inhibitory action of TGFβ.Significance:TNFRSF19, a susceptibility gene for nasopharyngeal carcinoma and other cancers, functions as a potent inhibitor of the TGFβ signaling pathway.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3469/F1.large.jpg. Cancer Res; 78(13); 3469–83. ©2018 AACR.
Long Noncoding RNA AB074169 Inhibits Cell Proliferation via Modulation of KHSRP-Mediated CDKN1a Expression in Papillary Thyroid Carcinoma
Authors: Gou Qiheng , Gao Linbo , Nie Xinwen , Pu Wenchen , Zhu Jingqiang , Wang Yichao , Liu Xuesha , Tan Shuangyan , Zhou Jian-Kang , Gong Yanqiu , He Juan , Wu Ke , Xie Yuxin , Zhao Wanjun , Dai Lunzhi , Liu Lunxu , Xiang Rong , Wei Yu-Quan , Zhang Lin , Peng Yong 
Published: May 2018

Abstract
Long noncoding RNAs (lncRNA) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here, we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell-cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis.
Significance: These findings identify a tumor-suppressive long noncoding RNA in papillary thyroid carcinoma.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4163/F1.large.jpg. Cancer Res; 78(15); 4163–74. ©2018 AACR.
Relation of RhoA in Peripheral Blood Mononuclear Cells With Severity of Aneurysmal Subarachnoid Hemorrhage and Vasospasm
Authors: González-Montelongo María del Carmen , Egea-Guerrero Juan José , Murillo-Cabezas Francisco , González-Montelongo Rafaela , Ruiz de Azúa-López Zaida , Rodríguez-Rodríguez Ana , Vilches-Arenas Angel , Castellano Antonio , Ureña Juan 
Published: May 2018

Background and Purpose—
Rho-kinase, an effector of RhoA, is associated with various cardiovascular diseases in circulating blood cells. However, the role of RhoA/Rho-kinase in peripheral blood mononuclear cells from patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) has not yet been studied in relation to the severity of this disease. Therefore, we analyzed the expression and activity of RhoA as a possible biomarker in aSAH.

Methods—
Twenty-four patients with aSAH and 15 healthy subjects were examined. Peripheral blood mononuclear cells were collected, and RhoA activity and expression were determined by RhoA activation assay kit (G-LISA) and enzyme-linked immunosorbent assay tests, respectively. The severity of aSAH was determined from the World Federation of Neurological Surgeon scale, and vasospasm was evaluated using clinical symptoms, arteriography, and sonography.

Results—

RhoA expression was significantly increased in peripheral blood mononuclear cells from patients on days 0, 2, and 4 after aSAH versus healthy subjects (
P
=0.036, 0.010, and 0.018, respectively, by
U
Mann–Whitney analysis). There was a significant correlation between RhoA expression and injury severity on days 2 and 4 (Spearman test, day 2:
r
=0.682, n=14,
P
=0.007; day 4:
r
=0.721, n=14,
P
=0.004). No significant correlation was observed on day 0 (day 0:
r
=0.131, n=6,
P
=0.805). Active RhoA was not significantly different in patients and healthy subjects on days 0, 2, and 4 (
P
=0.243, 0.222, and 0.600, respectively) nor did it increase significantly on days 0 and 2 in patients with vasospasm versus patients without vasospasm (
P
=0.064 and 0.519, respectively). In contrast, active RhoA was significantly higher on day 4 in patients who developed vasospasm versus patients without vasospasm (
P
=0.028).

Conclusions—
Our preliminary results indicate that RhoA expression and activity in peripheral blood mononuclear cells might be related with aSAH severity and cerebral vasospasm. RhoA is a potential biomarker of the risks associated with aSAH.