bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clostridium perfringens Type A Enterotoxin Damages the Rabbit Colon
Authors: Garcia Jorge P. , Li Jihong , Shrestha Archana , Freedman John C. , Beingesser Juliann , McClane Bruce A. , Uzal Francisco A. 
Published: March 2014

ABSTRACT

Clostridium perfringens
enterotoxin causes the gastrointestinal (GI) symptoms of
C. perfringens
type A food poisoning and CPE-associated non-food-borne human GI diseases. It is well established that CPE induces fluid accumulation and severe tissue damage in ligated small intestinal loops of rabbits and other animals. However, a previous study had also reported that CPE binds to rabbit colonic cells yet does not significantly affect rabbit colonic loops. To the contrary, the current study determined that treatment with 50 or 100 μg/ml of CPE causes significant histologic lesions and luminal fluid accumulation in rabbit colonic loops. Interestingly, a CPE-neutralizing monoclonal antibody blocked the development of CPE-induced histologic damage but not luminal fluid accumulation in these loops. Similar luminal fluid accumulation, without significant histologic damage, also occurred after treatment of colonic loops with heat-inactivated CPE, antibody alone, or bovine serum albumin (BSA), indicating that increased osmolarity was causing or contributing to fluid accumulation in CPE-treated colonic loops. Comparative studies revealed the similar development of histologic damage and luminal fluid accumulation in both small intestinal loops and colonic loops after as little as a 1-h treatment with 50 μg/ml of CPE. Consistent with the CPE sensitivity of the small intestine and colon, Western blotting detected CPE binding and large-complex formation in both organs. In addition, Western blotting demonstrated the presence of the high-affinity CPE receptors claudin-3 and -4 in both organs of rabbits, consistent with the observed toxin binding. Collectively, these results offer support for the possible involvement of the colon in CPE-mediated GI disease.
Identification of an Outer Membrane Lipoprotein Involved in Nasopharyngeal Colonization by Moraxella catarrhalis in an Animal Model
Authors: Wang Wei , Joslin Stephanie N. , Pybus Christine , Evans Amanda S. , Lichaa Flora , Brautigam Chad A. , Hansen Eric J. 
Published: March 2014

ABSTRACT

Colonization of the human nasopharynx by
Moraxella catarrhalis
is presumed to involve attachment of this bacterium to the mucosa. DNA microarray analysis was used to determine whether attachment of
M. catarrhalis
to human bronchial epithelial (HBE) cells
in vitro
affected gene expression in this bacterium. Attachment affected expression of at least 454 different genes, with 163 being upregulated and 291 being downregulated. Among the upregulated genes was one (ORF113) previously annotated as encoding a protein with some similarity to outer membrane protein A (OmpA). The protein encoded by ORF113 was predicted to have a signal peptidase II cleavage site, and globomycin inhibition experiments confirmed that this protein was indeed a lipoprotein. The ORF113 protein also contained a predicted peptidoglycan-binding domain in its C-terminal half. The use of mutant and recombinant
M. catarrhalis
strains confirmed that the ORF113 protein was present in outer membrane preparations, and this protein was also shown to be at least partially exposed on the bacterial cell surface. A mutant unable to produce the ORF113 protein showed little or no change in its growth rate
in vitro
, in its ability to attach to HBE cells
in vitro
, or in its autoagglutination characteristics, but it did exhibit a reduced ability to survive in the chinchilla nasopharynx. This is the first report of a lipoprotein essential to the ability of
M. catarrhalis
to persist in an animal model.
Causes for the Persistence of Impact Factor Mania
Authors: Casadevall Arturo , Fang Ferric C. 
Published: March 2014

ABSTRACT
Numerous essays have addressed the misuse of the journal impact factor for judging the value of science, but the practice continues, primarily as a result of the actions of scientists themselves. This seemingly irrational behavior is referred to as “impact factor mania.” Although the literature on the impact factor is extensive, little has been written on the underlying causes of impact factor mania. In this perspective, we consider the reasons for the persistence of impact factor mania and its pernicious effects on science. We conclude that impact factor mania persists because it confers significant benefits to individual scientists and journals. Impact factor mania is a variation of the economic theory known as the “tragedy of the commons,” in which scientists act rationally in their own self-interests despite the detrimental consequences of their actions on the overall scientific enterprise. Various measures to reduce the influence of the impact factor are considered.

IMPORTANCE
Science and scientists are currently afflicted by an epidemic of mania manifested by associating the value of research with the journal where the work is published rather than the content of the work itself. The mania is causing profound distortions in the way science is done that are deleterious to the overall scientific enterprise. In this essay, we consider the forces responsible for the persistence of the mania and conclude that it is maintained because it disproportionately benefits elements of the scientific enterprise, including certain well-established scientists, journals, and administrative interests. Our essay suggests steps that can be taken to deal with this debilitating and destructive epidemic.
Comparative Analysis of
Salmonella
Genomes Identifies a Metabolic Network for Escalating Growth in the Inflamed Gut
Authors: Nuccio Sean-Paul , Bäumler Andreas J. 
Published: March 2014

ABSTRACT

The
Salmonella
genus comprises a group of pathogens associated with illnesses ranging from gastroenteritis to typhoid fever. We performed an
in silico
analysis of comparatively reannotated
Salmonella
genomes to identify genomic signatures indicative of disease potential. By removing numerous annotation inconsistencies and inaccuracies, the process of reannotation identified a network of 469 genes involved in central anaerobic metabolism, which was intact in genomes of gastrointestinal pathogens but degrading in genomes of extraintestinal pathogens. This large network contained pathways that enable gastrointestinal pathogens to utilize inflammation-derived nutrients as well as many of the biochemical reactions used for the enrichment and biochemical discrimination of
Salmonella
serovars. Thus, comparative genome analysis identifies a metabolic network that provides clues about the strategies for nutrient acquisition and utilization that are characteristic of gastrointestinal pathogens.

IMPORTANCE
While some
Salmonella
serovars cause infections that remain localized to the gut, others disseminate throughout the body. Here, we compared
Salmonella
genomes to identify characteristics that distinguish gastrointestinal from extraintestinal pathogens. We identified a large metabolic network that is functional in gastrointestinal pathogens but decaying in extraintestinal pathogens. While taxonomists have used traits from this network empirically for many decades for the enrichment and biochemical discrimination of
Salmonella
serovars, our findings suggest that it is part of a “business plan” for growth in the inflamed gastrointestinal tract. By identifying a large metabolic network characteristic of
Salmonella
serovars associated with gastroenteritis, our
in silico
analysis provides a blueprint for potential strategies to utilize inflammation-derived nutrients and edge out competing gut microbes.
Increased Survival in B-Cell-Deficient Mice during Experimental Cerebral Malaria Suggests a Role for Circulating Immune Complexes
Authors: de Oliveira Rosane B. , Wang Jennifer P. , Ram Sanjay , Gazzinelli Ricardo T. , Finberg Robert W. , Golenbock Douglas T. 
Published: March 2014

ABSTRACTThe pathogenesis of malaria, an insect-borne disease that takes millions of lives every year, is still not fully understood. Complement receptor 1 (CR1) has been described as a receptor forPlasmodium falciparum, which causes cerebral malaria in humans. We investigated the role of CR1 in an experimental model of cerebral malaria. Transgenic mice expressing human CR1 (hCR1+) on erythrocytes were infected withPlasmodium bergheiANKA and developed cerebral malaria. No difference in survival was observed in hCR1+mice compared to wild-type mice following infection withP. bergheiANKA; however, hCR1 detection was significantly diminished on erythrocytes between days 7 and 10 postinfection. hCR1 levels returned to baseline by day 17 postinfection in surviving animals. Immunoblot assays revealed that total erythrocyte hCR1 levels were diminished, confirming that immune complexes in association with erythrocyte hCR1 were likely removed from erythrocytesin vivoby clearance following immune adherence. Decreases in hCR1 were completely dependent on C3 expression, as mice treated with cobra venom factor (which consumes and depletes C3) retained hCR1 on erythrocytes during C3 depletion through day 7; erythrocyte hCR1 decreases were observed only when C3 levels recovered on day 9. B-cell-deficient mice exhibit a marked increase in survival following infection withP. bergheiANKA, which suggests that immune complexes play a central role in the pathogenesis of experimental cerebral malaria. Together, our findings highlight the importance of complement and immune complexes in experimental cerebral malaria.IMPORTANCECerebral malaria is a deadly complication of infection withPlasmodium falciparum. Despite its high prevalence, relatively little is understood about its pathogenesis. We have determined that immune complexes are generated and deposited on erythrocytes specifically expressing human complement receptor 1 in a mouse model of cerebral malaria. We also provide evidence demonstrating the importance of immunoglobulins in the pathogenesis of cerebral malaria in mice. These findings may have important implications in human cerebral malaria.
Biogeochemical Forces Shape the Composition and Physiology of Polymicrobial Communities in the Cystic Fibrosis Lung
Authors: Quinn Robert A. , Lim Yan Wei , Maughan Heather , Conrad Douglas , Rohwer Forest , Whiteson Katrine L. 
Published: March 2014

ABSTRACT

The cystic fibrosis (CF) lung contains thick mucus colonized by opportunistic pathogens which adapt to the CF lung environment over decades. The difficulty associated with sampling airways has impeded a thorough examination of the biochemical microhabitats these pathogens are exposed to. An indirect approach is to study the responses of microbial communities to these microhabitats, facilitated by high-throughput sequencing of microbial DNA and RNA from sputum samples. Microbial metagenomes and metatranscriptomes were sequenced from multiple CF patients, and the reads were assigned taxonomy and function through sequence homology to NCBI and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database hierarchies. For a comparison, saliva microbial metagenomes from the Human Microbiome Project (HMP) were also analyzed. These analyses identified that functions encoded and expressed by CF microbes were significantly enriched for amino acid catabolism, folate biosynthesis, and lipoic acid biosynthesis. The data indicate that the community uses oxidative phosphorylation as a major energy source but that terminal electron acceptors were diverse. Nitrate reduction was the most abundant anaerobic respiratory pathway, and genes for nitrate reductase were largely assigned to
Pseudomonas
and
Rothia
. Although many reductive pathways of the nitrogen cycle were present, the cycle was incomplete, because the oxidative pathways were absent. Due to the abundant amino acid catabolism and incomplete nitrogen cycle, the CF microbial community appears to accumulate ammonia. This finding was verified experimentally using a CF bronchiole culture model system. The data also revealed abundant sensing and transport of iron, ammonium, zinc, and other metals along with a low-oxygen environment. This study reveals the core biochemistry and physiology of the CF microbiome.

IMPORTANCE
The cystic fibrosis (CF) microbial community is complex and adapts to the environmental conditions of the lung over the lifetime of a CF patient. This analysis illustrates the core functions of the CF microbial community in the context of CF lung biochemistry. There are many studies of the metabolism and physiology of individual microbes within the CF lung, but none that collectively analyze data from the whole microbiome. Understanding the core metabolism of microbes that inhabit the CF lung can provide new targets for novel therapies. The fundamental processes that CF pathogens rely on for survival may represent an Achilles heel for this pathogenic community. Novel therapies that are designed to disrupt understudied survival strategies of the CF microbial community may succeed against otherwise untreatable or antibiotic-resistant microbes.
Identifying systems failures in the pathway to a catastrophic event: an analysis of national incident report data relating to vinca alkaloids
Authors: Franklin Bryony Dean , Panesar Sukhmeet S , Vincent Charles , Donaldson Liam J 
Published: March 2014

BackgroundCatastrophic errors in healthcare are rare, yet the consequences are so serious that where possible, special procedures are put in place to prevent them. As systems become safer, it becomes progressively more difficult to detect the remaining vulnerabilities. Using inadvertent intrathecal administration of vinca alkaloids as an example, we investigated whether analysis of incident report data describing low-harm events could bridge this gap.MethodsWe studied nine million patient safety incidents reported from England and Wales between November 2003 and May 2013. We searched for reports relating to administration of vinca alkaloids in patients also receiving intrathecal medication, and classified the failures identified against steps in the relevant national protocol.ResultsOf 38 reports that met our inclusion criteria, none resulted in actual harm. The stage of the medication process most commonly involved was ‘supply, transport and storage’ (15 cases). Seven cases related to dispensing, six to documentation, and four each to prescribing and administration. Defences most commonly breached related to separation of intravenous vinca alkaloids and intrathecal medication in timing (n=16) and location (n=8); potential for confusion due to inadequate separation of these drugs therefore remains. Problems involved in six cases did not align with the procedural defences in place, some of which represented major hazards.ConclusionsWe identified areas of concern even within the context of a highly controlled standardised national process. If incident reporting systems include and encourage reports of no-harm incidents in addition to actual patient harm, they can facilitate monitoring the resilience of healthcare processes. Patient safety incidents that produce the most serious harm are often rare, and it is difficult to know whether patients are adequately protected. Our approach provides a potential solution.
BRACHIAL PLEXUS INJURIES: DIAGNOSIS PERFORMANCE AND RELIABILITY OF EVERYDAY TOOLS
Authors: Caporrino F. A. , Moreira L. , Moraes V. Y. , Belloti J. C. , Gomes dos Santos J. B. , Faloppa F. 
Published: March 2014

Purpose: Determining the patterns of brachial plexus injuries is challenging. Diagnostic methods have been used to facilitate diagnosis, but there is no consensus regarding which tool best complements physical examination (PE). Magnetic resonance imaging (MRI) and nerve conduction studies (NCSs) are instruments with widespread use and feasibility for everyday assessment. In this study, we evaluated the diagnostic performance of these diagnostic instruments and PE. We also assessed the agreement in the PE and diagnostic instrument findings of two experienced and certified hand surgeons.Methods: We reviewed data gathered from medical records and compared these data with the results of operative findings. We divided data according to the site of injury and the root injury patterns for all three diagnostic instruments (PE, MRI, and NCSs).Results: We considered 102 assessments. We found poor inter-observer agreement for the PE assessments and poor agreement among the PE, NCS, and MRI assessments. Diagnostic performance was higher for PE: sensitivity = 97.8 [95% confidence interval (C.I.) = 92.1–99.7]; specificity = 30.8 [95% C.I. = 9.1–61.4], and NCSs (sensitivity = 98.9 [95% C.I. = 93.9–100]; specificity = 23.1 [95% C.I. = 5–53.8]. MRI had inferior performance for all measurements. Separate analysis using pre- and post-ganglionic injuries revealed that PE had the lowest sensitivity, 46.7 (95% C.I. = 21.3–73.4) despite having the highest specificity, 81.6 (95% C.I. = 71.9–89.1).Discussion: Low agreement among the findings using different diagnostic instruments demonstrated that PE is the most specific tool, despite its low sensitivity. Detailed PE is cornerstone for evaluating brachial plexus injuries and NCSs are better than MRI for scrutinizing injuries not found in PE.Clinical Relevance: In our study, NCSs exhibited superior performance to MRI, and should be considered a more reliable supporting tool after detailed PE.
Variants Associated with Susceptibility to Pancreatic Cancer and Melanoma Do Not Reciprocally Affect Risk
Authors: Wu Lang , Goldstein Alisa M. , Yu Kai , Yang Xiaohong Rose , Rabe Kari G. , Arslan Alan A. , Canzian Federico , Wolpin Brian M. , Stolzenberg-Solomon Rachael , Amundadottir Laufey T. , Petersen Gloria M. 
Published: March 2014

Abstract
Background: Melanoma cases may exist in pancreatic cancer kindreds, whereas there is increased risk of pancreatic cancer in familial melanoma. The two cancers may share genetic susceptibility variants in common.
Methods: Three dbGaP (datasets in Genotypes and Phenotypes)-deposited GWAS (genome-wide association study) datasets (MD Anderson melanoma, PanScan 1, and PanScan 2 for pancreatic cancer) were used. Thirty-seven melanoma susceptibility variants in 22 genomic regions from published GWAS, plus melanoma-related genes and pathways were examined for pancreatic cancer risk in the PanScan datasets. Conversely, nine known pancreatic cancer susceptibility variants were examined for melanoma risk in the MD Anderson dataset.
Results: In the PanScan data, initial associations were found with melanoma susceptibility variants in NCOA6 [rs4911442; OR, 1.32; 95% confidence interval (CI), 1.03–1.70; P = 0.03], YWHAZP5 (rs17119461; OR, 2.62; 95% CI, 1.08–6.35; P = 0.03), and YWHAZP5 (rs17119490; OR, 2.62; 95% CI, 1.08–6.34; P = 0.03), TYRP1 (P = 0.04), and IFNA13 (P = 0.04). In the melanoma dataset, two pancreatic cancer susceptibility variants were associated: NR5A2 (rs12029406; OR, 1.39; 95% CI, 1.01–1.92; P = 0.04) and CLPTM1L-TERT (rs401681; OR, 1.16; 95% CI, 1.01–1.34; P = 0.04). None of these associations remained significant after correcting for multiple comparisons.
Conclusion: Reported variants of melanoma genes and pathways do not play a role in pancreatic cancer predisposition. Reciprocally, pancreatic cancer susceptibility variants are not associated with melanoma risk.
Impact: Known melanoma-related genes and pathways, as well as GWAS-derived susceptibility variants of melanoma and pancreatic cancer, do not explain the shared genetic etiology of these two cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1121–4. ©2014 AACR.
Classifying Patients for Breast Cancer by Detection of Autoantibodies against a Panel of Conformation-Carrying Antigens
Authors: Evans Rick L. , Pottala James V. , Egland Kristi A. 
Published: March 2014

Abstract
Patients with breast cancer elicit an autoantibody response against cancer proteins, which reflects and amplifies the cellular changes associated with tumorigenesis. Detection of autoantibodies in plasma may provide a minimally invasive mechanism for early detection of breast cancer. To identify cancer proteins that elicit a humoral response, we generated a cDNA library enriched for breast cancer genes that encode membrane and secreted proteins, which are more likely to induce an antibody response compared with intracellular proteins. To generate conformation-carrying antigens that are efficiently recognized by patients' antibodies, a eukaryotic expression strategy was established. Plasma from 200 patients with breast cancer and 200 age-matched healthy controls were measured for autoantibody activity against 20 different antigens designed to have conformational epitopes using ELISA. A conditional logistic regression model was used to select a combination of autoantibody responses against the 20 different antigens to classify patients with breast cancer from healthy controls. The best combination included ANGPTL4, DKK1, GAL1, MUC1, GFRA1, GRN, and LRRC15; however, autoantibody responses against GFRA1, GRN, and LRRC15 were inversely correlated with breast cancer. When the autoantibody responses against the 7 antigens were added to the base model, including age, BMI, race and current smoking status, the assay had the following diagnostic capabilities: c-stat (95% CI), 0.82 (0.78–0.86); sensitivity, 73%; specificity, 76%; and positive likelihood ratio (95% CI), 3.04 (2.34–3.94). The model was calibrated across risk deciles (Hosmer–Lemeshow, P = 0.13) and performed well in specific subtypes of breast cancer including estrogen receptor positive, HER-2 positive, invasive, in situ and tumor sizes &gt;1 cm. Cancer Prev Res; 7(5); 545–55. ©2014 AACR.
Incomplete Stent Apposition Causes High Shear Flow Disturbances and Delay in Neointimal Coverage as a Function of Strut to Wall Detachment Distance
Authors: Foin Nicolas , Gutiérrez-Chico Juan Luis , Nakatani Shimpei , Torii Ryo , Bourantas Christos V. , Sen Sayan , Nijjer Sukhjinder , Petraco Ricardo , Kousera Chrysa , Ghione Matteo , Onuma Yoshinobu , Garcia-Garcia Hector M. , Francis Darrel P. , Wong Philip , Di Mario Carlo , Davies Justin E. , Serruys Patrick W. 
Published: March 2014

Background—
Lack of re-endothelialization and neointimal coverage on stent struts has been put forward as the main underlying mechanism leading to late stent thrombosis. Incomplete stent apposition (ISA) has been observed frequently in patients with very late stent thrombosis after drug eluting stent implantation, suggesting a role of ISA in the pathogenesis of this adverse event. The aim of this study was to evaluate the impact of different degrees of ISA severity on abnormal shear rate and healing response with coverage, because of its potential implications for stent optimization in clinical practice.

Methods and Results—

We characterized flow profile and shear distribution in different cases of ISA with increasing strut-wall detachment distance (ranging from 100 to 500 μm). Protruding strut and strut malapposed with moderate detachment (ISA detachment distance <100 μm) have minimal disturbance to blood flow as compared with floating strut that has more significant ISA distance. In vivo impact on strut coverage was assessed retrospectively using optical coherence tomography evaluation on 72 stents (48 patients) sequentially at baseline and after 6-month follow-up. Analysis of coverage revealed an important impact of baseline strut-wall ISA distance on the risk of incomplete strut coverage at follow-up. Malapposed segments with an ISA detachment <100 μm at baseline showed complete strut coverage at follow-up, whereas segments with a maximal ISA detachment distance of 100 to 300 μm and >300 μm had 6.1% and 15.7% of their struts still uncovered at follow-up, respectively (
P
<0.001).

Conclusions—
Flow disturbances and risk of delayed strut coverage both increase with ISA detachment distance. Insights from this study are important for understanding malapposition as a quantitative, rather than binary phenomenon (present or absent) and to define the threshold of ISA detachment that might benefit from optimization during stent implantation.