bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Metabolic Signatures Linked to Anti-Inflammatory Effects of Faecalibacterium prausnitzii
Authors: Miquel Sylvie , Leclerc Marion , Martin Rebeca , Chain Florian , Lenoir Marion , Raguideau Sébastien , Hudault Sylvie , Bridonneau Chantal , Northen Trent , Bowen Benjamin , Bermúdez-Humarán Luis G. , Sokol Harry , Thomas Muriel , Langella Philippe 
Published: April 2015

ABSTRACT

Faecalibacterium prausnitzii
is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring
F. prausnitzii
(A2-165) and
Escherichia coli
(K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested
in vitro
. We obtained stable
E. coli
and
F. prausnitzii
-diassociated mice in which
E. coli
primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of
F. prausnitzii
. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of
F. prausnitzii
after TNBS challenge. The protective effect of
F. prausnitzii
against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of
F. prausnitzii
, and the functional link was established
in vitro
for salicylic acid. We show for the first time that
F. prausnitzii
is a highly active commensal bacterium involved in reduction of colitis through
in vivo
modulation of metabolites along the GIT and in the peripheral blood.

IMPORTANCE
Inflammatory bowel diseases (IBD) are characterized by low proportions of
F. prausnitzii
in the gut microbiome. This commensal bacterium exhibits anti-inflammatory effects through still unknown mechanisms. Stable monoassociated rodents are actually not a reproducible model to decipher
F. prausnitzii
protective effects. We propose a new gnotobiotic rodent model providing mechanistic clues. In this model,
F. prausnitzii
exhibits protective effects against an acute colitis and a protective metabolic profile is linked to its presence along the digestive tract. We identified a molecule, salicylic acid, directly involved in the protective effect of
F. prausnitzii
. Targeting its metabolic pathways could be an attractive therapeutic strategy in IBD.
Extracellular Enzymes Facilitate Electron Uptake in Biocorrosion and Bioelectrosynthesis
Authors: Deutzmann Jörg S. , Sahin Merve , Spormann Alfred M. 
Published: April 2015

ABSTRACT

Direct, mediator-free transfer of electrons between a microbial cell and a solid phase in its surrounding environment has been suggested to be a widespread and ecologically significant process. The high rates of microbial electron uptake observed during microbially influenced corrosion of iron [Fe(0)] and during microbial electrosynthesis have been considered support for a direct electron uptake in these microbial processes. However, the underlying molecular mechanisms of direct electron uptake are unknown. We investigated the electron uptake characteristics of the Fe(0)-corroding and electromethanogenic archaeon
Methanococcus maripaludis
and discovered that free, surface-associated redox enzymes, such as hydrogenases and presumably formate dehydrogenases, are sufficient to mediate an apparent direct electron uptake. In genetic and biochemical experiments, we showed that these enzymes, which are released from cells during routine culturing, catalyze the formation of H
2
or formate when sorbed to an appropriate redox-active surface. These low-molecular-weight products are rapidly consumed by
M. maripaludis
cells when present, thereby preventing their accumulation to any appreciable or even detectable level. Rates of H
2
and formate formation by cell-free spent culture medium were sufficient to explain the observed rates of methane formation from Fe(0) and cathode-derived electrons by wild-type
M. maripaludis
as well as by a mutant strain carrying deletions in all catabolic hydrogenases. Our data collectively show that cell-derived free enzymes can mimic direct extracellular electron transfer during Fe(0) corrosion and microbial electrosynthesis and may represent an ecologically important but so far overlooked mechanism in biological electron transfer.

IMPORTANCE
The intriguing trait of some microbial organisms to engage in direct electron transfer is thought to be widespread in nature. Consequently, direct uptake of electrons into microbial cells from solid surfaces is assumed to have a significant impact not only on fundamental microbial and biogeochemical processes but also on applied bioelectrochemical systems, such as microbial electrosynthesis and biocorrosion. This study provides a simple mechanistic explanation for frequently observed fast electron uptake kinetics in microbiological systems without a direct transfer: free, cell-derived enzymes can interact with cathodic surfaces and catalyze the formation of intermediates that are rapidly consumed by microbial cells. This electron transfer mechanism likely plays a significant role in various microbial electron transfer reactions in the environment.
Refractory polymyositis undergoing remission following antitubercular therapy
Authors: Misra Durga Prasanna , Edavalath Sukesh , Chowdhury Abhra Chandra , Agarwal Vikas 
Published: April 2015

Opportunistic infections pose a significant problem in patients receiving immunosuppressive therapy for autoimmune diseases. We present a case of a woman with polymyositis refractory to high-dose steroid and methotrexate, as a consequence of which she developed miliary tuberculosis. Her myositis went into remission after initiation of antitubercular therapy, in spite of bringing down the intensity of immunosuppression. This is the first reported case of myositis undergoing remission after treating intercurrent infection, and illustrates the complex relationship between autoimmune disease and host response to infection.
TFF2–CXCR4 Axis Is Associated with BRAF V600E Colon Cancer
Authors: Gala Manish K. , Austin Thomas , Ogino Shuji , Chan Andrew T. 
Published: April 2015

Abstract
Oncogene-induced senescence (OIS), a tumor-suppressive mechanism that is induced by the replicative and metabolic stress of oncogene activation, is a key barrier in the development of BRAF V600E colon cancer. Inhibition of this mechanism has been observed through epigenetic changes observed in sporadic serrated polyps, as well as through the germline mutations associated with those who develop serrated polyposis. We hypothesize that upregulated autocrine factors exist that are specific to the serrated pathway and also promote bypass of oncogene-induced senescence. To identify such autocrine factors, we integrate analyses of microarrays of sessile serrated polyps and two large colon cancer cohorts, the Cancer Genome Atlas (TCGA; n = 153), and French national Cartes d'Identité des Tumeurs (CIT) program (n = 462), with enhanced gene annotation through natural language processing techniques of the existing medical corpus. We reproducibly associate higher expression of the ligand–receptor axis of TFF2 and CXCR4 with BRAF V600E-mutant colon cancer (P = 3.0 × 10−3 and 0.077, respectively for TCGA; P = 3.0 × 10−8 and 5.1 × 10−7 for CIT). Given well-described oncogenic roles of TFF2 and CXCR4 in colon cancer, and availability of CXCR4 inhibitors for other clinical indications, this ligand–receptor axis may represent an actionable target for prevention and treatment of this molecular subtype of colorectal cancer. Cancer Prev Res; 8(7); 614–9. ©2015 AACR.
PolyI:C–Induced, TLR3/RIP3-Dependent Necroptosis Backs Up Immune Effector–Mediated Tumor Elimination In Vivo
Authors: Takemura Ryo , Takaki Hiromi , Okada Seiji , Shime Hiroaki , Akazawa Takashi , Oshiumi Hiroyuki , Matsumoto Misako , Teshima Takanori , Seya Tsukasa 
Published: April 2015

Abstract
Double-stranded RNA directly acts on fibroblast and myeloid lineages to induce necroptosis as in TNFα. Here, we investigated whether this type of cell death occurred in cancer cells in response to polyinosinic–polycytidylic acid (polyI:C) and the pan-caspase inhibitor z-Val-Ala-Asp fluromethyl ketone (zVAD). We found that the colon cancer cell line CT26 is highly susceptible to necroptosis, as revealed by staining with annexin V/propidium iodide. CT26 cells possess RNA sensors, TLR3 and MDA5, which are upregulated by interferon (IFN)-inducing pathways and linked to receptor-interacting protein kinase (RIP) 1/3 activation via TICAM-1 or MAVS adaptor, respectively. Although exogenously added polyI:C alone marginally induced necroptosis in CT26 cells, a combined regimen of polyI:C and zVAD induced approximately 50% CT26 necroptosis in vitro without secondary effects of TNFα or type I IFNs. CT26 necroptosis depended on the TLR3–TICAM-1–RIP3 axis in the tumor cells to produce reactive oxygen species, but not on MDA5, MAVS, or the caspases/inflammasome activation. However, the RNA-derived necroptosis was barely reproduced in vivo in a CT26 tumor–implanted Balb/c mouse model with administration of polyI:C + zVAD. Significant shrinkage of CT26 tumors was revealed only when polyI:C (100 μg) was injected intraperitoneally and zVAD (1 mg) subcutaneously into tumor-bearing mice that were depleted of cytotoxic T lymphocytes and natural killer cells. The results were confirmed with immune-compromised mice with no lymphocytes. Although necroptosis-induced tumor growth retardation appears mechanistically complicated and dependent on the injection routes of polyI:C and zVAD, anti-caspase reagent directed to tumor cells will make RNA adjuvant immunotherapy more effective by modulating the formation of the tumoricidal microenvironment and dendritic cell–inducing antitumor immune system. Cancer Immunol Res; 3(8); 902–14. ©2015 AACR.
Recognition of Incident Diabetes Mellitus During an Acute Myocardial Infarction
Authors: Arnold Suzanne V. , Stolker Joshua M. , Lipska Kasia J. , Jones Philip G. , Spertus John A. , McGuire Darren K. , Inzucchi Silvio E. , Goyal Abhinav , Maddox Thomas M. , Lind Marcus , Gumber Divya , Shore Supriya , Kosiborod Mikhail 
Published: April 2015

Background—
Diabetes mellitus (DM) is common in patients hospitalized with an acute myocardial infarction (AMI), representing in some cases the first opportunity to recognize and treat DM. We report the incidence of new DM and its recognition among patients with AMI.

Methods and Results—

Patients in a 24-site US AMI registry (2005–08) had glycosylated hemoglobin assessed at a core laboratory, with results blinded to clinicians and local clinical measurements left to the discretion of the treating providers. Among 2854 AMI patients without known DM on admission, 287 patients (10%) met criteria for previously unknown DM, defined by a core laboratory glycosylated hemoglobin of ≥6.5%. Among these, 186 (65%) were unrecognized by treating clinicians, receiving neither DM education, glucose-lowering medications at discharge, nor documentation of DM in the chart (median glycosylated hemoglobin of unrecognized patients, 6.7%; range, 6.5–12.3%). Six months after discharge, only 5% of those not recognized as having DM during hospitalization had been initiated on glucose-lowering medications versus 66% of those recognized (
P
<0.001).

Conclusions—
Underlying DM that has not been previously diagnosed is common among AMI patients, affecting 1 in 10 patients, yet is recognized by the care team only one third of the time. Given its frequency and therapeutic implications, including but extending beyond the initiation of glucose-lowering treatment, consideration should be given to screening all AMI patients for DM during hospitalization. Inexpensive, ubiquitous, and endorsed as an acceptable screen for DM, glycosylated hemoglobin testing should be considered for this purpose.
Evaluating Forecast Impact of Assimilating Microwave Humidity Sounder (MHS) Radiances with a Regional Ensemble Kalman Filter Data Assimilation System
Authors: Newman Kathryn M. , Schwartz Craig S. , Liu Zhiquan , Shao Hui , Huang Xiang-Yu 
Published: April 2015

Abstract
This study examines the impact of assimilating Microwave Humidity Sounder (MHS) radiances in a limited-area ensemble Kalman filter (EnKF) data assimilation system. Two experiments spanning 11 August–13 September 2008 were run over a domain featuring the Atlantic basin using a 6-h full cycling analysis and forecast system. Deterministic 72-h forecasts were initialized at 0000 and 1200 UTC for a comparison of forecast impact. The two experiments were configured identically with the exception of the inclusion of the MHS radiances (AMHS) in the second to isolate the impacts of the MHS radiance data. The results were verified against several sources, and statistical significance tests indicate the most notable differences are in the midlevel moisture fields. Both configurations were characterized by high moisture biases when compared to the European Centre for Medium-Range Weather Forecasts interim reanalysis (ERA-Interim, also known as ERA-I) specific humidity fields, as well as precipitable water vapor from an observationally based product. However, the AMHS experiment has midlevel moisture fields closer to the ERA-I and observation datasets. When reducing the verification domain to focus on the subtropical and easterly wave regions of the North Atlantic Ocean, larger improvements in midlevel moisture at nearly all lead times is seen in the AMHS simulation. Finally, when considering tropical cyclone forecasts, the AMHS configuration shows improvement in intensity forecasts at several lead times as well as improvements at early to intermediate lead times for minimum sea level pressure forecasts.
Perceptions of ‘Evidence-Based Practice’ among the consumers of adolescent substance use treatment
Authors: Becker Sara J , Spirito Anthony , Vanmali Roshani 
Published: April 2015

Objective: Several national organisations in the USA have recently developed educational materials that encourage substance use disorder treatment consumers to seek out approaches supported by scientific evidence in order to promote the use of ‘evidence-based practice’ (EBP). This study aimed to explore how adolescents (young people aged 12–17 years) with substance use disorders and their caregivers perceive, understand and react to the concept of EBP. Methods: Qualitative focus groups and structured interviews were conducted with 29 caregivers and 24 adolescents with substance use disorders in the Northeastern USA. Discussions explored four themes: (a) familiarity with EBP, (b) assumptions about what EBP means, (c) impressions of EBP after reading a common definition and (d) recommended terms to describe EBP in educational materials. Participants’ responses were transcribed and qualitatively analysed by two independent coders. Results: Only 2 of the 53 participants had ever heard the term EBP, and only 1 was able to define it correctly. Common assumptions about the term ‘evidence-based’ were that it referred to treatment based on the patient’s medical history, legal evidence of substance use or the clinician’s prior experience. The misperception that EBP was associated with legal evidence was common among adolescents involved in the justice system. After reading a common definition of EBP, most participants thought that the approach sounded inflexible. Alternative terms the participants recommended to educate potential treatment consumers about EBP included proven, successful, better and therapy that works. Conclusion: Results suggest that future efforts to educate treatment consumers should use the phrase EBP with caution and emphasise the flexibility of the approach.
Shared performance targets for the horizontal coordination of public organizations: control theory and departmentalism in the United Kingdom’s Public Service Agreement system
Authors: James Oliver , Nakamura Ayako 
Published: April 2015

Coordinating organizations horizontally is a longstanding difficulty of public governance, often called departmentalism in central government systems. Several tools for horizontal coordination have previously been analysed but shared performance targets across departments have received relatively little attention. This article develops a control theory of shared performance target systems for horizontal coordination of departments consisting of ‘director’ (shared objective and target setting), ‘detector’ (shared monitoring of progress), and ‘effector’ (shared feedback to promote achievement of targets) components. The theory distinguishes between two kinds of shared targets: those promoting sequential coordination and simultaneous coordination among departments. The expectations of control theory are assessed for the Public Service Agreement (PSA) adopted in the United Kingdom. PSAs enabled a step change increase in discussion of shared policy objectives across departments. However, despite these benefits, the fundamentally separate broader ministerial and departmental accountability structures led to the setting of vague outcome targets, underdeveloped performance reporting, and fragmented delivery arrangements for shared targets. Points for practitioners The findings provide a cautionary tale for policy-makers seeking to implement horizontally shared targets across departmental organizations. The UK Government’s Public Service Agreement (PSA) system reveals that shared target systems for departments supervised by a finance ministry are a useful tool for incentivizing departments to collaborate with other departments in policy discussions and resource allocation. However, it was difficult for departments to set specific cross-cutting targets and to develop practical joint delivery and performance reporting strategies across existing departmental boundaries. The effects of the system were, for the most part, counteracted by departmentally focused resource and accountability structures. In some cases, broader structural reform to reorganize departmental structures to align with the formerly cross-cutting policy challenge was necessary rather than predominantly relying on shared targets to pursue policy goals.
Review of Anterior Cruciate Ligament Reconstruction Cost Variance Within a Regional Health Care System
Authors: Archibald-Seiffer Noah , Jacobs John C. , Saad Charles , Jevsevar David S. , Shea Kevin G. 
Published: April 2015

Background: Examination of value in health care has become a national priority in the United States. Regional variation in health care costs is an area of focus among national policy experts. Procedural cost data can be used to provide physicians with information to evaluate costs and value. Purpose: To perform a cost review for anterior cruciate ligament (ACL) surgery to document the degree of variation in costs for ACL reconstruction. Study Design: Economic and decision analysis; Level of evidence, 4. Methods: A procedural cost review was performed for isolated ACL reconstructions within a 22-surgeon, 7-hospital system. Five consistent cost categories under the influence of the surgeon were identified and were analyzed for cost variation among surgeons: tibial fixation, femoral fixation, graft choice, sutures, and tools or disposable instruments. Results: For these 5 categories, the total costs to perform an ACL reconstruction (in 2013 US dollars) ranged from $392.80 to $4670.31, a difference of $4277.51 and a mean of $2039.09. Tibial fixation costs ranged from $95.00 to $760.00 (mean, $293.52). Femoral fixation ranged from $95.00 to $865.00 (mean, $367.14). The graft cost ranged from $1275.00 to $2545.75 (mean, $1976.43). Suture prices for each individual suture varied from $1.19 to $46.00 (mean, $18.26). Tools and disposable supplies ranged from $40.10 to $2136.00 (mean, $452.33). Conclusion: There were substantial differences in ACL reconstruction costs in the implant and disposable instruments categories. As health systems and physicians collaborate to improve health care quality and value for patients, information on cost variation will be important. Rational variation in health care cost is appropriate, reflecting variation due to the unique requirements of procedures and patient-centered care. Irrational variations in procedural costs are those that do not add additional value.
UV-activated 7-dehydrocholesterol-coated titanium implants promote differentiation of human umbilical cord mesenchymal stem cells into osteoblasts
Authors: Satué María , Ramis Joana M , Monjo Marta 
Published: April 2015

Vitamin D metabolites are essential for bone regeneration and mineral homeostasis. The vitamin D precursor 7-dehydrocholesterol can be used after UV irradiation to locally produce active vitamin D by osteoblastic cells. Furthermore, UV-irradiated 7-dehydrocholesterol is a biocompatible coating for titanium implants with positive effects on osteoblast differentiation. In this study, we examined the impact of titanium implants surfaces coated with UV-irradiated 7-dehydrocholesterol on the osteogenic differentiation of human umbilical cord mesenchymal stem cells. First, the synthesis of cholecalciferol (D3) was achieved through the incubation of the UV-activated 7-dehydrocholesterol coating for 48 h at 23℃. Further, we investigated in vitro the biocompatibility of this coating in human umbilical cord mesenchymal stem cells and its potential to enhance their differentiation towards the osteogenic lineage. Human umbilical cord mesenchymal stem cells cultured onto UV-irradiated 7-dehydrocholesterol-coated titanium implants surfaces, combined with osteogenic supplements, upregulated the gene expression of several osteogenic markers and showed higher alkaline phosphatase activity and calcein blue staining, suggesting increased mineralization. Thus, our results show that the use of UV irradiation on 7-dehydrocholesterol -treated titanium implants surfaces generates a bioactive coating that promotes the osteogenic differentiation of human umbilical cord mesenchymal stem cells, with regenerative potential for improving osseointegration in titanium-based bone anchored implants.
Ethical dilemmas facing chief nurses in Japan
Authors: Ito Chiharu , Natsume Mikiko 
Published: April 2015

Background: Chief nurses are most likely to take the lead in discussing and working to resolve ethical dilemmas, creating an ethical culture within their organization that results in effective ethics training. As the first step in this process, there is a need to define the kinds of ethical dilemmas that chief nurses grapple with on a regular basis as a target for future study. Research design: Anonymous written questionnaires and semi-structured interviews. Ethical considerations: All research procedures were approved by the Chubu University Ethics Review Board, the research institution to which the authors belong (authorization no. 250016). Findings and discussion: Responses from four chief nurses indicated that ethical dilemmas could be categorized as either those related to patient dignity or those related to management (unique to their roles as administrators). It was also learned that chief nurses struggle with the fact that although they consult with their superiors and others, these efforts do not lead to resolution. The expectation is that going forward, chief nurses will play a central role in acting as coordinators with physicians to promote better communication as well as lead group discussions aimed at providing care that respects patient dignity.