bluuebunny/crossref_metadata_2025_split huggingface dataset:
The origin and phylogeny of Margaritiferidae (Bivalvia, Unionoida): a synthesis of molecular and fossil data
Authors: Araujo Rafael , Schneider Simon , Roe Kevin J. , Erpenbeck Dirk , Machordom Annie 
Published: September 2016

The family Margaritiferidae is a small but widely distributed group within the Unionoida, or freshwater mussels, whose taxonomy and systematics has been the subject of numerous publications. Despite several efforts, there is no consensus on which characters reliably diagnose this family. Herein, we present the results of a phylogenetic analysis of the most comprehensive data set for Margaritiferidae in terms of taxa and phylogenetic markers assembled to date, including eleven out of the twelve margaritiferid species currently considered valid. In addition, we review the fossil record of the family and attempt to integrate fossil andDNAsequence data to provide a diagnosis of Margaritiferidae, identify its origin and biogeographic patterns, and determine the systematic relationships of its constituent species and their taxonomic affinities. We assembled a molecular data set comprised of five markers:COI, 16S, 28S, 18S and histone 3 for a total of 59 specimens representing eleven species ofMargaritifera. Our results indicate that the family Margaritiferidae is a monophyletic group comprised of the single genusMargaritifera, which includes the following 12 species:M. dahurica,M. margaritifera,M. monodonta, M. middendorffi, M. laevis,M. marrianae, M. hembeli,M. falcata,M. laosensis, M. auriculariaandM. marocanaplus the unstudiedM. homsensis. Estimates of divergence times using fossil calibrations or mean substitution rates produced dramatically different results. Divergence estimates based on the fossil calibrations were 10 times higher than those obtained applying the mean substitution rates. The current distribution of the family implies dispersal across marine or brackish waters by their host fish, leaving a fossil record on four continents that dates to the Mesozoic. Margaritiferidae appear to be derived from putative ancestor in the Silesunionidae, with a likely origin in Asia. We suggest that Margaritiferidae had spread along the Tethys margins and crossed the Atlantic already in the Late Triassic or Early Jurassic. Further dispersal events, in the Late Cretaceous or Eocene, may be linked to salinity‐depleted coastal waters or freshwater layering.
Endosomal Trafficking Defects Can Induce Calcium-Dependent Azole Tolerance in Candida albicans
Authors: Luna-Tapia Arturo , Tournu Hélène , Peters Tracy L. , Palmer Glen E. 
Published: September 2016

ABSTRACT

The azole antifungals arrest fungal growth through inhibition of ergosterol biosynthesis. We recently reported that a
Candida albicans
vps21
Δ/Δ mutant, deficient in membrane trafficking through the late endosome/prevacuolar compartment (PVC), continues to grow in the presence of the azoles despite the depletion of cellular ergosterol. Here, we report that the
vps21
Δ/Δ mutant exhibits less plasma membrane damage upon azole treatment than the wild type, as measured by the release of a cytoplasmic luciferase reporter into the culture supernatant. Our results also reveal that the
vps21
Δ/Δ mutant has abnormal levels of intracellular Ca
2+
and, in the presence of fluconazole, enhanced expression of a calcineurin-responsive
RTA2-GFP
reporter. Furthermore, the azole tolerance phenotype of the
vps21
Δ/Δ mutant is dependent upon both extracellular calcium levels and calcineurin activity. These findings underscore the importance of endosomal trafficking in determining the cellular consequences of azole treatment and indicate that this may occur through modulation of calcium- and calcineurin-dependent responses.
Pharmacokinetics of the New Hepatitis C Virus NS3 Protease Inhibitor Narlaprevir following Single-Dose Use with or without Ritonavir in Patients with Liver Cirrhosis
Authors: Isakov V. , Koloda D. , Tikhonova N. , Kikalishvili T. , Krasavina E. , Lekishvili K. , Malaya I. , Ryska M. , Samsonov M. , Tolkacheva V. 
Published: September 2016

ABSTRACT

In this study we sought to evaluate narlaprevir (NVR) pharmacokinetics (PK) after a single dose with or without ritonavir (RTV) in cirrhotic versus healthy subjects. NVR at 200 mg was administered to 8 healthy and 8 cirrhotic subjects, and NVR at 100 mg with RTV at 100 mg was administered to 8 healthy and 8 cirrhotic subjects. PK analysis was performed. The geometric mean maximum concentration of a drug in serum (
C
max
) and the area under the concentration-time curve from 0 to infinity (AUC
0–∞
) were 563.1 ng/ml and 4,701.8 ng · h/ml in cirrhotic patients versus 364.8 ng/ml and 1,917.1 ng · h/ml in healthy volunteers, respectively. The geometric mean ratios of the PK parameters of cirrhotic subjects to healthy volunteers were 1.54-fold (90% confidence interval [CI] = 1.05 to 2.27) for
C
max
and 2.45-fold (90% CI = 1.56 to 3.85) for AUC
0–∞
. The geometric mean
C
max
and AUC
0–∞
in cirrhotic and healthy subjects were similar: 1,225.7 ng/ml for
C
max
and 15,213.1 ng · h/ml for AUC
0–∞
in cirrhotic subjects and 1,178.9 ng/ml for
C
max
and 14,257.2 ng · h/ml for AUC
0–∞
in healthy volunteers. The corresponding geometric mean ratios were 1.04 (90% CI = 0.67 to 1.62) for
C
max
and 1.07 (90% CI = 0.72 to 1.58) for AUC
0–∞
. Higher exposures in cirrhotic subjects were safe and well tolerated. We found that NVR exposures after a 200-mg single dose were higher in cirrhotic subjects than in healthy subjects and that a 100-mg single dose of NVR boosted with RTV at 100 mg resulted in no significant PK differences between cirrhotic and healthy subjects.
Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation
Authors: Sharma-Chawla Niharika , Sender Vicky , Kershaw Olivia , Gruber Achim D. , Volckmar Julia , Henriques-Normark Birgitta , Stegemann-Koniszewski Sabine , Bruder Dunja 
Published: September 2016

ABSTRACT

Influenza A virus (IAV) and
Streptococcus pneumoniae
are major causes of respiratory tract infections, particularly during coinfection. The synergism between these two pathogens is characterized by a complex network of dysregulated immune responses, some of which last until recovery following IAV infection. Despite the high serotype diversity of
S. pneumoniae
and the serotype replacement observed since the introduction of conjugate vaccines, little is known about pneumococcal strain dependency in the enhanced susceptibility to severe secondary
S. pneumoniae
infection following IAV infection. Thus, we studied how preinfection with IAV alters host susceptibility to different
S. pneumoniae
strains with various degrees of invasiveness using a highly invasive serotype 4 strain, an invasive serotype 7F strain, and a carrier serotype 19F strain. A murine model of pneumococcal coinfection during the acute phase of IAV infection showed a significantly increased degree of pneumonia and mortality for all tested pneumococcal strains at otherwise sublethal doses. The incidence and kinetics of systemic dissemination, however, remained bacterial strain dependent. Furthermore, we observed strain-specific alterations in the pulmonary levels of alveolar macrophages, neutrophils, and inflammatory mediators ultimately affecting immunopathology. During the recovery phase following IAV infection, bacterial growth in the lungs and systemic dissemination were enhanced in a strain-dependent manner. Altogether, this study shows that acute IAV infection predisposes the host to lethal
S. pneumoniae
infection irrespective of the pneumococcal serotype, while the long-lasting synergism between IAV and
S. pneumoniae
is bacterial strain dependent. These results hold implications for developing tailored therapeutic treatment regimens for dual infections during future IAV outbreaks.
Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease
Authors: Balderas Miriam A. , Nguyen Chinh T. Q. , Terwilliger Austen , Keitel Wendy A. , Iniguez Angelina , Torres Rodrigo , Palacios Frederico , Goulding Celia W. , Maresso Anthony W. 
Published: September 2016

ABSTRACT

Bacillus anthracis
is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (
nea
r-iron
t
ransporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of
B. anthracis
infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine.
Emergence of a Competence-Reducing Filamentous Phage from the Genome of Acinetobacter baylyi ADP1
Authors: Renda Brian A. , Chan Cindy , Parent Kristin N. , Barrick Jeffrey E. 
Published: September 2016

ABSTRACT

Bacterial genomes commonly contain prophage sequences as a result of past infections with lysogenic phages. Many of these integrated viral sequences are believed to be cryptic, but prophage genes are sometimes coopted by the host, and some prophages may be reactivated to form infectious particles when cells are stressed or mutate. We found that a previously uncharacterized filamentous phage emerged from the genome of
Acinetobacter baylyi
ADP1 during a laboratory evolution experiment. This phage has a genetic organization similar to that of the
Vibrio cholerae
CTXϕ phage. The emergence of the ADP1 phage was associated with the evolution of reduced transformability in our experimental populations, so we named it the
c
ompetence-
r
educing
a
cinetobacter phage (CRAϕ). Knocking out ADP1 genes required for competence leads to resistance to CRAϕ infection. Although filamentous bacteriophages are known to target type IV pili, this is the first report of a phage that apparently uses a competence pilus as a receptor.
A. baylyi
may be especially susceptible to this route of infection because every cell is competent during normal growth, whereas competence is induced only under certain environmental conditions or in a subpopulation of cells in other bacterial species. It is possible that CRAϕ-like phages restrict horizontal gene transfer in nature by inhibiting the growth of naturally transformable strains. We also found that prophages with homology to CRAϕ exist in several strains of
Acinetobacter baumannii
. These CRAϕ-like
A. baumannii
prophages encode toxins similar to CTXϕ that might contribute to the virulence of this opportunistic multidrug-resistant pathogen.

IMPORTANCE
We observed the emergence of a novel filamentous phage (CRAϕ) from the genome of
Acinetobacter baylyi
ADP1 during a long-term laboratory evolution experiment. CRAϕ is the first bacteriophage reported to require the molecular machinery involved in the uptake of environmental DNA for infection. Reactivation and evolution of CRAϕ reduced the potential for horizontal transfer of genes via natural transformation in our experiment. Risk of infection by similar phages may limit the expression and maintenance of bacterial competence in nature. The closest studied relative of CRAϕ is the
Vibrio cholerae
CTXϕ phage. Variants of CRAϕ are found in the genomes of
Acinetobacter baumannii
strains, and it is possible that phage-encoded toxins contribute to the virulence of this opportunistic multidrug-resistant pathogen.
Association between liver enzymes and incident type 2 diabetes in Singapore Chinese men and women
Authors: Wang Ye-Li , Koh Woon-Puay , Yuan Jian-Min , Pan An 
Published: September 2016

AimsTo assess the association between liver enzymes and the risk of type 2 diabetes (T2D) in a Chinese population.MethodsA nested case–control study comprising 571 T2D cases and 571 matched controls was conducted within the Singapore Chinese Health Study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were quantified in baseline plasma collected from them, while γ-glutamyltransferase (GGT) was assayed among 255 T2D cases with baseline hemoglobin A1c <6.5% and 255 matched controls. Participants were free of diagnosed diabetes, cardiovascular disease, and cancer at blood collections (1999–2004). Incident self-reported T2D cases were identified at follow-up II interview (2006–2010). Controls were matched to cases on age, sex, dialect group, and date of blood collection.ResultsHigher levels of ALT and GGT were significantly associated with increased risk of T2D (p for trend <0.001 for ALT, p for trend=0.03 for GGT), and the ORs (95% CIs) comparing highest versus lowest tertiles of ALT and GGT were 2.00 (1.01 to 3.96) and 2.38 (1.21 to 4.66), respectively. A null association was observed for AST, ALP, and LDH with T2D risk. Adding GGT (<23 vs ≥23 IU/L) or ALT (<21 vs ≥21 IU/L) to a prediction model resulted in significant gain in net reclassification improvement and integrated discrimination improvement of T2D prediction (all p<0.001).ConclusionsHigher levels of GGT and ALT are associated with increased T2D risk. GGT ≥23 IU/L and ALT ≥21 IU/L may identify people at higher risk of developing T2D in this Chinese population.
Patterns and injuries associated with orbital wall fractures in elderly patients who visited the emergency room: a retrospective case–control study
Authors: Kim Youn-Jung , Ahn Shin , Seo Dong-Woo , Sohn Chang Hwan , Lee Hyung-Joo , Park In-June , Yang Dong-Jin , Ryoo Seung Mok , Kim Won Young , Lim Kyung Soo 
Published: September 2016

ObjectivesThis study aimed to determine orbital wall fracture (OWF) patterns and associated facial injuries in elderly patients and compare them with those in their younger adult counterparts.DesignA retrospective case–control study.SettingAn emergency department of a university-affiliated hospital located in an urban area.ParticipantsA total of 1378 adult patients with OWF diagnosed by CT from 1 January 2004 through 31 March 2014 were enrolled. Patients were categorised into elderly (≥65 years) and non-elderly (<65 years) groups.ResultsThe elderly group (n=146) had a mean age of 74.0 years compared with 37.5 years in the non-elderly group (n=1232). Slipping was the most common cause of OWF in the elderly group (43.8%, p<0.001), whereas violence was the most common cause in the non-elderly group (37.3%, p<0.001). The lateral orbital wall was the more common site of fracture in the elderly group, and their injuries were more often associated with concurrent facial bone fractures, including the mandible, maxilla and zygoma, compared with the non-elderly group. After adjusting for sex and the mechanism of injury, inclusion in the elderly group was a significant risk factor for fracture of the lateral wall (OR 1.658; 95% CI 1.074 to 2.560) and concomitant facial bone fractures of the maxilla (OR 1.625; 95% CI 1.111 to 2.377) and zygoma (OR 1.670; 95% CI 1.126 to 2.475).ConclusionsElderly patients were vulnerable to facial trauma, and concurrent facial bone fracture associated with OWF was more commonly observed in this age group. Therefore, a high index of suspicion and thorough investigation, including CT, for OWF-associated facial bone fractures are important.
Identifying patients with advanced chronic conditions for a progressive palliative care approach: a cross-sectional study of prognostic indicators related to end-of-life trajectories
Authors: Amblàs-Novellas J , Murray S A , Espaulella J , Martori J C , Oller R , Martinez-Muñoz M , Molist N , Blay C , Gómez-Batiste X 
Published: September 2016

Objectives2 innovative concepts have lately been developed to radically improve the care of patients with advanced chronic conditions (PACC): early identification of palliative care (PC) needs and the 3 end-of-life trajectories in chronic illnesses (acute, intermittent and gradual dwindling). It is not clear (1) what indicators work best for this early identification and (2) if specific clinical indicators exist for each of these trajectories. The objectives of this study are to explore these 2 issues.Setting3 primary care services, an acute care hospital, an intermediate care centre and 4 nursing homes in a mixed urban–rural district in Barcelona, Spain.Participants782 patients (61.5% women) with a positive NECPAL CCOMS-ICO test, indicating they might benefit from a PC approach.Outcome measuresThe characteristics and distribution of the indicators of the NECPAL CCOMS-ICO tool are analysed with respect to the 3 trajectories and have been arranged by domain (functional, nutritional and cognitive status, emotional problems, geriatric syndromes, social vulnerability and others) and according to their static (severity) and dynamic (progression) properties.ResultsThe common indicators associated with early end-of-life identification are functional (44.3%) and nutritional (30.7%) progression, emotional distress (21.9%) and geriatric syndromes (15.7% delirium, 11.2% falls). The rest of the indicators showed differences in the associations per illness trajectories (p<0.05). 48.2% of the total cohort was identified as advanced frailty patients with no advanced disease criteria.ConclusionsDynamic indicators are present in the 3 trajectories and are especially useful to identify PACC for a progressive PC approach purpose. Most of the other indicators are typically associated with a specific trajectory. These findings can help clinicians improve the identification of patients for a palliative approach.
Self-reported hypoglycaemia in patients with type 2 diabetes treated with insulin in the Hoorn Diabetes Care System Cohort, the Netherlands: a prospective cohort study
Authors: Rauh Simone P , Rutters Femke , Thorsted Brian L , Wolden Michael L , Nijpels Giel , van der Heijden Amber A W A , Walraven Iris , Elders Petra J , Heymans Martijn W , Dekker Jacqueline M 
Published: September 2016

BackgroundOur aim was to study the prevalence of self-reported hypoglycaemic sensations and its association with mortality in patients with type 2 diabetes (T2D) treated with insulin in usual care.MethodsDemographics, clinical characteristics and mortality data were obtained from 1667 patients with T2D treated with insulin in the Hoorn Diabetes Care System Cohort (DCS), a prospective cohort study using clinical care data. Self-reported hypoglycaemic sensations were defined as either mild: events not requiring help; or severe: events requiring help from others (either medical assistance or assistance of others). The association between hypoglycaemic sensations and mortality was analysed using logistic regression analysis.ResultsAt baseline, 981 patients (59%) reported no hypoglycaemic sensations in the past year, 612 (37%) reported only mild sensations and 74 (4%) reported severe hypoglycaemic sensations. During a median follow-up of 1.9 years, 98 patients (5.9%) died. Reporting only mild hypoglycaemic sensations was associated with a lower mortality risk (OR 0.48, 95% CI 0.28 to 0.80), while reporting severe sensations was not significantly associated with mortality (OR 0.76, 95% CI 0.33 to 1.80), compared with reporting no hypoglycaemic sensations, and adjusting for demographic and clinical characteristics. Sensitivity analyses showed an OR of 1.38 (95% CI 0.31 to 6.11) for patients reporting severe hypoglycaemic sensations requiring medical assistance.ConclusionsSelf-reported hypoglycaemic sensations are highly prevalent in our insulin-treated T2D population. Patients reporting hypoglycaemic sensations not requiring medical assistance did not have an increased risk of mortality, suggesting that these sensations are not an indicator of increased short-term mortality risk in patients with T2D.
Understanding and overcoming barriers to timely discharge from the pediatric units
Authors: Mustafa Amira , Mahgoub Samar 
Published: September 2016

Delays in the discharge of hospital patients cause a backlog for new admissions from the Emergency Departments (ED), outpatient clinics, and transfers from the Intensive Care Units (ICU). A variety of initiatives have been reported on previously which aim to tackle this problem with variable success. In this quality improvement project, we aimed to increase the proportion of discharged patients who leave the paediatric unit by 12:00 Noon from 7% to 30% by May 2015.A baseline discharge process map was studied to understand the possible causes of the delays. A survey was conducted to look for the most likely cause for the delay. A data collection tool was designed to record the various steps in the discharge process for the pre-and post-intervention phases. Using a series of PDSA cycles, interventions were introduced.The average time for the discharge process was two hours and the baseline average percent of patients discharged by 12:00 Noon was 7% of all discharges. The leading cause for the delayed discharges was late orders by the physicians. Post-intervention, there was increase in the percentage of patients discharged by 12:00 Noon from 7% to 34%. 42% of discharged patients had appropriate reasons for afternoon discharge. By excluding these patients, the percentage of adjusted timely morning discharge has increased from 36% to 70%.Continuous monitoring and engagement of teams with regular feedback were the most important factors in achieving and sustaining improvement in the timely morning discharge of patients from our paediatric units.