bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis
Authors: Erdem Hakan , Cag Yasemin , Ozturk-Engin Derya , Defres Sylviane , Kaya Selcuk , Larsen Lykke , Poljak Mario , Barsic Bruno , Argemi Xavier , Sørensen Signe Maj , Bohr Anne Lisbeth , Tattevin Pierre , Gunst Jesper Damsgaard , Baštáková Lenka , Jereb Matjaž , Johansen Isik Somuncu , Karabay Oguz , Pekok Abdullah Umut , Sipahi Oguz Resat , Chehri Mahtab , Beraud Guillaume , Shehata Ghaydaa , Del Vecchio Rosa Fontana , Maresca Mauro , Karsen Hasan , Sengoz Gonul , Sunbul Mustafa , Yilmaz Gulden , Yilmaz Hava , Sharif-Yakan Ahmad , Kanj Souha Shararah , Parlak Emine , Pehlivanoglu Filiz , Korkmaz Fatime , Komur Suheyla , Kose Sukran , Ulug Mehmet , Bolukcu Sibel , Coskuner Seher Ayten , Ince Nevin , Akkoyunlu Yasemin , Halac Gulistan , Sahin-Horasan Elif , Tireli Hulya , Kilicoglu Gamze , Al-Mahdawi Akram , Nemli Salih Atakan , Inan Asuman , Senbayrak Seniha , Stahl Jean Paul , Vahaboglu Haluk 
Published: March 2015

ABSTRACT
Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.
The Omentum Is a Site of Protective IgM Production during Intracellular Bacterial Infection
Authors: Jones Derek D. , Racine Rachael , Wittmer Susan T. , Harston Louise , Papillion Amber M. , Dishaw Lisa M. , Randall Troy D. , Woodland David L. , Winslow Gary M. 
Published: March 2015

ABSTRACT

Infection of mice with the bacterium
Ehrlichia muris
elicits a protective T cell-independent (TI) IgM response mediated primarily by a population of CD11c-expressing plasmablasts in the spleen. Although splenic marginal zone (MZ) B cells are considered to be important for TI responses to blood-borne pathogens, MZ B cells were not responsible for generating plasmablasts in response to
Ehrlichia muris
. Moreover, antigen-specific serum IgM was decreased only modestly in splenectomized mice and in mice that lacked spleen, lymph nodes, and Peyer's patches (SLP mice). Both splenectomized and SLP mice were protected against lethal ehrlichial challenge infection. Moreover, we found a high frequency of
Ehrlichia
-specific plasmablasts in the omentum of both conventional and SLP mice. Omental plasmablasts elicited during
Ehrlichia
infection lacked expression of CD138 but expressed CD11c in a manner similar to that of their splenic counterparts. Selective ablation of CD11c-expressing B cells nearly eliminated the omental
Ehrlichia
-specific plasmablasts and reduced antigen-specific serum IgM, identifying the omental B cells as a source of IgM production in the SLP mice. Generation of the omental plasmablasts was route dependent, as they were detected following peritoneal infection but not following intravenous infection. Our data identify the omentum as an important auxiliary site of IgM production during intracellular bacterial infection.
Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection
Authors: Fox Barbara A. , Bzik David J. 
Published: March 2015

ABSTRACT

Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by
Toxoplasma gondii
. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δ
ku80
genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (
OMPDC
) and uridine phosphorylase (
UP
) genes. Deletion of
OMPDC
induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δ
ku80
Δ
ompdc
mutants stimulated a fully protective CD8
+
T cell-dependent immunity that prevented acute infection by type I and type II strains of
T. gondii
, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δ
ompdc
mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine.
Targeting Surface Protein SasX by Active and Passive Vaccination To Reduce Staphylococcus aureus Colonization and Infection
Authors: Liu Qian , Du Xin , Hong Xufen , Li Tianming , Zheng Bing , He Lei , Wang Yanan , Otto Michael , Li Min 
Published: March 2015

ABSTRACT

SasX is a recently described surface protein of
Staphylococcus aureus
that is linked to the epidemic success of hospital-associated methicillin-resistant clones, in particular in Asia. It enhances nasal colonization and virulence in skin and lung infection models. Here, we evaluated the potential of SasX as a vaccine component in passive and active immunization efforts using mouse infection models. We found that SasX induced a specific immune response predominantly based on IgG1 antibodies. Active immunization with recombinant SasX or passive immunization with rabbit polyclonal anti-SasX IgG significantly decreased the size of lesions caused by
S. aureus
in a skin infection model. Furthermore, active immunization reduced acute lung injury in a lung infection model. Moreover, active or passive immunization significantly reduced
S. aureus
colonization in a nasal colonization model. Finally, anti-SasX IgG enhanced the susceptibility of
S. aureus
to killing by human neutrophils. We conclude that SasX is a potential target for therapeutics or vaccines designed to moderate colonization and infection by
sasX
-positive epidemic strains of
S. aureus
.
Activated Human Valvular Interstitial Cells Sustain Interleukin-17 Production To Recruit Neutrophils in Infective Endocarditis
Authors: Yeh Chiou-Yueh , Shun Chia-Tung , Kuo Yu-Min , Jung Chiau-Jing , Hsieh Song-Chou , Chiu Yen-Ling , Chen Jeng-Wei , Hsu Ron-Bin , Yang Chia-Ju , Chia Jean-San 
Published: March 2015

ABSTRACTThe mechanisms that underlie valvular inflammation in streptococcus-induced infective endocarditis (IE) remain unclear. We previously demonstrated that streptococcal glucosyltransferases (GTFs) can activate human heart valvular interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that activated VIC can enhance neutrophil infiltration through sustained IL-17 production, leading to valvular damage. To monitor cytokine and chemokine production, leukocyte recruitment, and the induction or expansion of CD4+CD45RA−CD25−CCR6+Th17 cells, primary human VIC were culturedin vitroand activated by GTFs. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by immunohistochemistry in infected valves from patients with IE. The expression of IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (Rorc) was upregulated in GTF-activated VIC, which may enhance the proliferation of memory Th17 cells in an IL-6-dependent manner. Many chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC, which might recruit neutrophils and CD4+T cells. Moreover, CXCL1 production in VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were increased in patients with IE compared to healthy donors. Furthermore, elevated serum IL-21 levels have been significantly associated with severe valvular damage, including rupture of chordae tendineae, in IE patients. Our findings suggest that VIC are activated by bacterial modulins to recruit neutrophils and that such activities might be further enhanced by the production of Th17-associated cytokines. Together, these factors can amplify the release of neutrophilic contentsin situ, which might lead to severe valvular damage.
Correlates between Models of Virulence for Mycobacterium tuberculosis among Isolates of the Central Asian Lineage: a Case for Lysozyme Resistance Testing?
Authors: Pardieu Claire , Casali Nicola , Clark Simon O. , Hooper Richard , Williams Ann , Velji Preya , Gonzalo Ximena , Drobniewski Francis 
Published: March 2015

ABSTRACT

Virulence factors (VFs) contribute to the emergence of new human
Mycobacterium tuberculosis
strains, are lineage dependent, and are relevant to the development of
M. tuberculosis
drugs/vaccines. VFs were sought within
M. tuberculosis
lineage 3, which has the Central Asian (CAS) spoligotype. Three isolates were selected from clusters previously identified as dominant in London, United Kingdom. Strain-associated virulence was studied in guinea pig, monocyte-derived macrophage, and lysozyme resistance assays. Whole-genome sequencing, single nucleotide polymorphism (SNP) analysis, and a literature review contributed to the identification of SNPs of interest. The animal model revealed borderline differences in strain-associated pathogenicity.
Ex vivo
, isolate C72 exhibited statistically significant differences in intracellular growth relative to C6 and C14. SNP candidates inducing lower fitness levels included 123 unique nonsynonymous SNPs, including three located in genes (
lysX
,
caeA
, and
ponA2
) previously identified as VFs in the laboratory-adapted reference strain H37Rv and shown to confer lysozyme resistance. C72 growth was most affected by lysozyme
in vitro
. A BLAST search revealed that all three SNPs of interest (C35F, P76Q, and P780R) also occurred in Tiruvallur, India, and in Uganda. Unlike C72, however, no single isolate identified through BLAST carried all three SNPs simultaneously. CAS isolates representative of three medium-sized human clusters demonstrated differential outcomes in models commonly used to estimate strain-associated virulence, supporting the idea that virulence varies within, not just across,
M. tuberculosis
lineages. Three VF SNPs of interest were identified in two additional locations worldwide, which suggested independent selection and supported a role for these SNPs in virulence. The relevance of lysozyme resistance to strain virulence remains to be established.
Efficient Assembly of Ribosomes Is Inhibited by Deletion of
bipA
in Escherichia coli
Authors: Choudhury Promisree , Flower Ann M. 
Published: March 2015

ABSTRACT

The bacterial BipA protein belongs to the EF-G family of translational GTPases and has been postulated to be either a regulatory translation factor or a ribosome assembly factor. To distinguish between these hypotheses, we analyzed the effect of
bipA
deletion on three phenotypes associated with ribosome assembly factors: cold sensitivity, ribosome subunit distribution, and rRNA processing. We demonstrated that a Δ
bipA
strain exhibits a cold-sensitive phenotype that is similar to, and synergistic with, that of a strain with a known ribosome assembly factor,
deaD
. Additionally, the
bipA
deletion strain displayed a perturbed ribosome subunit distribution when grown at low temperature, similar to that of a
deaD
mutant, and again, the double mutant showed additive effects. The primary ribosomal deficiency noted was a decreased level of the 50S subunit and the appearance of a presumed pre-50S particle. Finally, deletion of
bipA
resulted in accumulation of pre23S rRNA, as did deletion of
deaD
. We further found that deletion of
rluC
, which encodes a pseudouridine synthase that modifies the 23S rRNA at three sites, suppressed all three phenotypes of the
bipA
mutant, supporting and extending previous findings. Together, these results suggest that BipA is important for the correct and efficient assembly of the 50S subunit of the ribosome at low temperature but when unmodified by RluC, the ribosomes become BipA independent for assembly.

IMPORTANCE
The ribosome is the complex ribonucleoprotein machine responsible for protein synthesis in all cells. Although much has been learned about the structure and function of the ribosome, we do not fully understand how it is assembled or the accessory proteins that increase efficiency of biogenesis and function. This study examined one such protein, BipA. Our results indicate that BipA either directly or indirectly enhances the formation of the 50S subunit of the ribosome, particularly at low temperature. In addition, ribosomes contain a large number of modified nucleosides, including pseudouridines. This work demonstrates that the function of BipA is tied to the modification status of the ribosome and may help us understand why these modifications have been retained.
Structure-Function Analysis of Peptide Signaling in the Clostridium perfringens Agr-Like Quorum Sensing System
Authors: Ma Menglin , Li Jihong , McClane Bruce A. 
Published: March 2015

ABSTRACT

The accessory growth regulator (Agr)-like quorum sensing (QS) system of
Clostridium perfringens
controls the production of many toxins, including beta toxin (CPB). We previously showed (J. E. Vidal, M. Ma, J. Saputo, J. Garcia, F. A. Uzal, and B. A. McClane, Mol Microbiol 83:179–194, 2012,
http://dx.doi.org/10.1111/j.1365-2958.2011.07925.x
) that an 8-amino-acid, AgrD-derived peptide named 8-R upregulates CPB production by this QS system. The current study synthesized a series of small signaling peptides corresponding to sequences within the
C. perfringens
AgrD polypeptide to investigate the
C. perfringens
autoinducing peptide (AIP) structure-function relationship. When both linear and cyclic ring forms of these peptides were added to
agrB
null mutants of type B strain CN1795 or type C strain CN3685, the 5-amino-acid peptides, whether in a linear or ring (thiolactone or lactone) form, induced better signaling (more CPB production) than peptide 8-R for both
C. perfringens
strains. The 5-mer thiolactone ring peptide induced faster signaling than the 5-mer linear peptide. Strain-related variations in sensing these peptides were detected, with CN3685 sensing the synthetic peptides more strongly than CN1795. Consistent with those synthetic peptide results, Transwell coculture experiments showed that CN3685 exquisitely senses native AIP signals from other isolates (types A, B, C, and D), while CN1795 barely senses even its own AIP. Finally, a
C. perfringens
AgrD sequence-based peptide with a 6-amino-acid thiolactone ring interfered with CPB production by several
C. perfringens
strains, suggesting potential therapeutic applications. These results indicate that AIP signaling sensitivity and responsiveness vary among
C. perfringens
strains and suggest
C. perfringens
prefers a 5-mer AIP to initiate Agr signaling.

IMPORTANCE
Clostridium perfringens
possesses an Agr-like quorum sensing (QS) system that regulates virulence, sporulation, and toxin production. The current study used synthetic peptides to identify the structure-function relationship for the signaling peptide that activates this QS system. We found that a 5-mer peptide induces optimal signaling. Unlike other Agr systems, a linear version of this peptide (in addition to thiolactone and lactone versions) could induce signaling. Two
C. perfringens
strains were found to vary in sensitivity to these peptides. We also found that a 6-mer peptide can inhibit toxin production by some strains, suggesting therapeutic applications.
‘Engage me in taking care of my heart’: a grounded theory study on patient–cardiologist relationship in the hospital management of heart failure
Authors: Barello Serena , Graffigna Guendalina , Vegni Elena , Savarese Mariarosaria , Lombardi Federico , Bosio A Claudio 
Published: March 2015

ObjectiveIn approaching the study and practice of heart failure (HF) management, authors recognise that the patient–doctor relationship has a central role in engaging patients in their care. This study aims at identifying the features and the levers of HF patient engagement and suggestions for orienting clinical encounters.DesignUsing a grounded theory approach, we conducted 22 in-depth interviews (13 patients with HF, 5 physicians and 4 caregivers). Data were collected and analysed using open, axial and selective coding procedures according to the grounded theory principles.SettingsAll interviews were conducted in an office in a university hospital located in a metropolitan area of Milan, Italy.ParticipantsThe data comprised a total of 22 patient, hospital cardiologist and caregiver interviews. Patients aged ≥18 years with New York Heart Association (NYHA) Functional Class of II or III were eligible to take part. Patients were recruited primarily through their referral cardiologist.ResultsThe HF patient engagement process develops in four main phases that are characterised by different patients’ emotional, cognitive and behavioural dynamics that contribute to shape the process of a patient's meaning making towards health and illness regarding their care. The emerging model illustrates that HF patient engagement entails a meaning-making process enacted by the patient after the critical event. This implies patients’ ability to give sense to their care experience and to their disease, symptomatology and treatments, and their changes along their illness course. Doctors are recognised as crucial in fostering patients’ engagement along all the phases of the process as they contribute to providing patients with self-continuity and give new meaning to their illness experience.ConclusionsThis study identifies the core experiential domains and the main levers involved in driving patients with HF to effectively engage in their disease management. The model emerging from this study may help clinicians think in a fresh way about encounters with patients and their role in fostering their patients’ health engagement.
Overweight and obesity on the island of Ireland: an estimation of costs
Authors: Dee Anne , Callinan Aoife , Doherty Edel , O'Neill Ciaran , McVeigh Treasa , Sweeney Mary Rose , Staines Anthony , Kearns Karen , Fitzgerald Sarah , Sharp Linda , Kee Frank , Hughes John , Balanda Kevin , Perry Ivan J 
Published: March 2015

ObjectivesThe increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches.MethodsCosts were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality.ResultsThe healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease.ConclusionsThe costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs.
Yang–Mills mass gap at large-N, noncommutative YM theory, topological quantum field theory and hyperfiniteness
Authors: Bochicchio Marco 
Published: March 2015

We review a number of old and new concepts in quantum gauge theories, some of which are well-established but not widely appreciated, some are most recent, that may have analogs in gauge formulations of quantum gravity, loop quantum gravity, and their topological versions, and may be of general interest. Such concepts involve noncommutative gauge theories and their relation to the large-N limit, loop equations and the change to the anti-selfdual (ASD) variables also known as Nicolai map, topological field theory (TFT) and its relation to localization and Morse–Smale–Floer homology, with an emphasis both on the mathematical aspects and the physical meaning. These concepts, assembled in a new way, enter a line of attack to the problem of the mass gap in large-NSU(N) Yang–Mills (YM), that is reviewed as well. Algebraic considerations furnish a measure of the mathematical complexity of a complete solution of large-NSU(N) YM: In the large-N limit of pure SU(N) YM the ambient algebra of Wilson loops is known to be a type II1 nonhyperfinite factor. Nevertheless, for the mass gap problem at the leading 1/N order, only the subalgebra of local gauge-invariant single-trace operators matters. The connected two-point correlators in this subalgebra must be an infinite sum of propagators of free massive fields, since the interaction is subleading in [Formula: see text], a vast simplification. It is an open problem, determined by the growth of the degeneracy of the spectrum, whether the aforementioned local subalgebra is in fact hyperfinite. Moreover, the sum of free propagators that occurs in the two-point correlators in the aforementioned local subalgebra must be asymptotic for large momentum to the result implied by the asymptotic freedom and the renormalization group: This fundamental constraint fixes asymptotically the residues of the poles of the propagators in terms of the mass spectrum and of the anomalous dimensions of the local operators. For the mass gap problem, in the search of a hyperfinite subalgebra containing the scalar sector of large-N YM, a major role is played by the existence of a TFT underlying the large-N limit of YM, with twisted boundary conditions on a torus or, which is the same by Morita duality, on a noncommutative torus. The TFT is trivial at the leading large-N order and localized on a set of critical points by means of a quantum version of Morse–Smale–Floer homology, that involves loop equations in the ASD variables. A hyperfinite sector arises by fluctuations around the trivial TFT, in which the joint spectrum of scalar and pseudoscalar glueballs is linear in the square of the masses [Formula: see text] with degeneracy k = 1, 2,…, and the two-point correlator satisfies the aforementioned fundamental constraint arising by the asymptotic freedom and the renormalization group.