bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined and breed‐specific RIs for hematologic, biochemical, and hormonal analytes in Chios and Florina adult rams
Authors: Oikonomidis Ioannis L. , Brozos Christos , Kiossis Evangelos , Kritsepi‐Konstantinou Maria 
Published: April 2018

BackgroundClinical pathology investigations are essential to evaluate the health status and practice management of ruminants. Appropriate and accurate RIs are required for the interpretation of laboratory results. Despite substantial phenotypic differences and management‐related disparities between male and female sheep, RIs in rams are sparse and limited by small reference populations and outdated methods.ObjectivesThe purpose of this study was to establish RIs for hematologic, biochemical, and hormonal analytes in adult rams using controlled preanalytic and analytic procedures, and to investigate whether breed‐dependent partitioning of RIs is required.MethodsReference individuals were selected by a direct a priori method. Blood was collected from 128 healthy adult rams representing 2 Greek breeds (64 Chios and 64 Florina). Hematologic analysis was performed on the Advia 120, while differential WBC counts were manually performed on Giemsa‐stained blood smears. Flexor E, AVL 9180 Electrolyte Analyzer, and Immulite 1000 were used for biochemical and hormonal analyses, respectively. Combined and breed‐specific RIs were calculated using nonparametric and robust methods, respectively.ResultsFive outliers were detected based on laboratory results. Partitioning of RIs, based on both statistical and nonstatistical criteria, was recommended for some of the analytes.ConclusionsThe RIs are in some agreement with those in the literature. The observed differences may be attributed to preanalytic and analytic factors. The RIs determined in this study can be used as a guide for the interpretation of laboratory results in rams and can potentially be adopted by veterinary laboratories, provided that similar equipment and reagents are used.
A Phage Lysin Fused to a Cell-Penetrating Peptide Kills Intracellular Methicillin-Resistant Staphylococcus aureus in Keratinocytes and Has Potential as a Treatment for Skin Infections in Mice
Authors: Wang ZhaoFei , Kong LiCheng , Liu Yang , Fu Qiang , Cui ZeLin , Wang Jian , Ma JingJiao , Wang HengAn , Yan YaXian , Sun JianHe 
Published: April 2018

ABSTRACTStaphylococcus aureusis the main pathogen that causes skin and skin structure infections and is able to survive and persist in keratinocytes of the epidermis. Since the evolution of multidrug-resistant bacteria, the use of phages and their lysins has presented a promising alternative approach to treatment. In this study, a cell wall hydrolase (also called lysin) derived fromStaphylococcusphage JD007 (JDlys) was identified. JDlys showed strong lytic activity against methicillin-resistantStaphylococcus aureus(MRSA) strains from different sources and of different multilocus sequence typing (MLST) types. Furthermore, a fusion protein consisting of a cell-penetrating peptide derived from thetrans-activating transcription (Tat) factor fused to JDlys (CPPTat-JDlys) was used to kill MRSA bacteria causing intracellular infections. CPPTat-JDlys, in which the fusion of CPPTatto JDlys had almost no effect on the bacteriolytic activity of JDlys, was able to effectively eliminate intracellular MRSA bacteria and alleviate the inflammatory response and cell damage caused by MRSA. Specifically, CPPTat-JDlys was able to combat MRSA-induced murine skin infections and, consequently, expedite the healing of cutaneous abscesses. These data suggest that the novel antimicrobial CPP-JDlys may be a worthwhile candidate as a treatment for skin and skin structure infections caused by MRSA.IMPORTANCES. aureusis the main cause of skin and skin structure infections due to its ability to invade and survive in the epithelial barrier. Due to the overuse of antibiotics in humans and animals,S. aureushas shown a high capacity for acquiring and accumulating mechanisms of resistance to antibiotics. Moreover, most antibiotics are usually limited in their ability to overcome the intracellular persistence of bacteria causing skin and skin structure infections. So, it is critical to seek a novel antimicrobial agent to eradicate intracellularS. aureus. In this study, a cell-penetrating peptide fused to lysin (CPP-JDlys) was engineered. Our results show that CPP-JDlys can enter keratinocytes and effectively eliminate intracellular MRSA. Meanwhile, experiments with mice revealed that CPP-JDlys efficiently inhibits the proliferation of MRSA in murine skin and thus shortens the course of wound healing. Our results indicate that the CPP-fused lysin has potential for use for the treatment of skin infections caused by MRSA.
Quantitative Thresholds Enable Accurate Identification of Clostridium difficile Infection by the Luminex xTAG Gastrointestinal Pathogen Panel
Authors: Leal Sixto M. , Popowitch Elena B. , Levinson Kara J. , John Teny M. , Lehman Bethany , Rios Maria Bueno , Gilligan Peter H. , Miller Melissa B. 
Published: April 2018

ABSTRACT

Clostridium difficile
colonizes the gastrointestinal (GI) tract, resulting in either asymptomatic carriage or a spectrum of diarrheal illness. If clinical suspicion for
C. difficile
is low, stool samples are often submitted for analysis by multiplex molecular assays capable of detecting multiple GI pathogens, and some institutions do not report this organism due to concerns for high false-positive rates. Since clinical disease correlates with organism burden and molecular assays yield quantitative data, we hypothesized that numerical cutoffs could be utilized to improve the specificity of the Luminex xTAG GI pathogen panel (GPP) for
C. difficile
infection. Analysis of cotested liquid stool samples (
n
= 1,105) identified a GPP median fluorescence intensity (MFI) value cutoff of ≥1,200 to be predictive of two-step algorithm (2-SA; 96.4% concordance) and toxin enzyme immunoassay (EIA) positivity. Application of this cutoff to a second cotested data set (
n
= 1,428) yielded 96.5% concordance. To determine test performance characteristics, concordant results were deemed positive or negative, and discordant results were adjudicated via chart review. Test performance characteristics for the MFI cutoff of ≥150 (standard), MFI cutoff of ≥1,200, and 2-SA were as follows (respectively): concordance, 95, 96, and 97%; sensitivity, 93, 78, and 90%; specificity, 95, 98, and 98%; positive predictive value, 67, 82, and 81%;, and negative predictive value, 99, 98, and 99%. To capture the high sensitivity for organism detection (MFI of ≥150) and high specificity for active infection (MFI of ≥1,200), we developed and applied a reporting algorithm to interpret GPP data from patients (
n
= 563) with clinician orders only for syndromic panel testing, thus enabling accurate reporting of
C. difficile
for 95% of samples (514 negative and 5 true positives) irrespective of initial clinical suspicion and without the need for additional testing.
Introduction of Viral Hemorrhagic Septicemia Virus into Freshwater Cultured Rainbow Trout Is Followed by Bursts of Adaptive Evolution
Authors: Schönherz Anna A. , Forsberg Roald , Guldbrandtsen Bernt , Buitenhuis Albert J. , Einer-Jensen Katja 
Published: April 2018

ABSTRACTViral hemorrhagic septicemia virus(VHSV), a rhabdovirus infecting teleost fish, has repeatedly crossed the boundary from marine fish species to freshwater cultured rainbow trout. These naturally replicated cross-species transmission events permit the study of general and repeatable evolutionary events occurring in connection with viral emergence in a novel host species. The purpose of the present study was to investigate the adaptive molecular evolution of the VHSV glycoprotein, one of the key virus proteins involved in viral emergence, following emergence from marine species into freshwater cultured rainbow trout. A comprehensive phylogenetic reconstruction of the complete coding region of the VHSV glycoprotein was conducted, and adaptive molecular evolution was investigated using a maximum likelihood approach to compare different codon substitution models allowing for heterogeneous substitution rate ratios among amino acid sites. Evidence of positive selection was detected at six amino acid sites of the VHSV glycoprotein, within the signal peptide, the confirmation-dependent major neutralizing epitope, and the intracellular tail. Evidence of positive selection was found exclusively in rainbow trout-adapted virus isolates, and amino acid combinations found at the six sites under positive selection pressure differentiated rainbow trout- from non-rainbow trout-adapted isolates. Furthermore, four adaptive sites revealed signs of recurring identical changes across phylogenetic groups of rainbow trout-adapted isolates, suggesting that repeated VHSV emergence in freshwater cultured rainbow trout was established through convergent routes of evolution that are associated with immune escape.IMPORTANCEThis study is the first to demonstrate that VHSV emergence from marine species into freshwater cultured rainbow trout has been accompanied by bursts of adaptive evolution in the VHSV glycoprotein. Furthermore, repeated detection of the same adaptive amino acid sites across phylogenetic groups of rainbow trout-adapted isolates indicates that adaptation to rainbow trout was established through parallel evolution. In addition, signals of convergent evolution toward the maintenance of genetic variation were detected in the conformation-dependent neutralizing epitope or in close proximity to disulfide bonds involved in the structural conformation of the neutralizing epitope, indicating adaptation to immune response-related genetic variation across freshwater cultured rainbow trout.
Origin, Evolution, and Loss of Bacterial Small RNAs
Authors: Dutcher H. Auguste , Raghavan Rahul 
Published: April 2018

ABSTRACT

Despite the central role of bacterial noncoding small RNAs (sRNAs) in posttranscriptional regulation, little is understood about their evolution. Here we compile what has been studied to date and trace a life cycle of sRNAs—from their mechanisms of emergence, through processes of change and frequent neofunctionalization, to their loss from bacterial lineages. Because they possess relatively unrestrictive structural requirements, we find that sRNA origins are varied, and include
de novo
emergence as well as formation from preexisting genetic elements via duplication events and horizontal gene transfer. The need for only partial complementarity to their mRNA targets facilitates apparent rapid change, which also contributes to significant challenges in tracing sRNAs across broad evolutionary distances. We document that recently emerged sRNAs in particular evolve quickly, mirroring dynamics observed in microRNAs, their functional analogs in eukaryotes. Mutations in mRNA-binding regions, transcriptional regulator or sigma factor binding sites, and protein-binding regions are all likely sources of shifting regulatory roles of sRNAs. Finally, using examples from the few evolutionary studies available, we examine cases of sRNA loss and describe how these may be the result of adaptive in addition to neutral processes. We highlight the need for more-comprehensive analyses of sRNA evolutionary patterns as a means to improve novel sRNA detection, enhance genome annotation, and deepen our understanding of regulatory networks in bacteria.
Internal workload and non-contact injury: a one-season study of five teams from the UEFA Elite Club Injury Study
Authors: McCall Alan , Dupont Gregory , Ekstrand Jan 
Published: April 2018

BackgroundInternal workload (ie, from training and matches) is considered one of the most important injury risk factors for elite European football teams, however there is little published evidence to support this belief.ObjectiveWe examined the association and predictive power of internal workload and non-contact injuries.MethodsFive elite European teams, 171 players (age: 25.1±4.9 years; height: 181.6±6.7 cm; body mass: 77.5±7.2 kg) participated over one full competitive season. Using the session-rating of perceived exertion (s-RPE) method player’s internal workloads were calculated for acute week, week-to-week changes, cumulated weeks, chronic weeks and acute:chronic ratios and analysed for association with non-contact injury (using generalised estimating equations (GEE)). Associated variables from GEE analysis were categorised into very low to very high workload zones and checked for increased relative risks (RRs). Associated workload variables were also analysed for predictive power (receiver operating characteristics).ResultsAcute:chronic workload ratios at 1:3 and 1:4 weeks were associated with non-contact injury (P<0.05). Specifically, a greater risk of injury was found for players with an acute:chronic workload at 1:4 weeks of 0.97 to 1.38 (RR 1.68; 95% CI 1.02 to 2.78, likely harmful) and >1.38 (RR 2.13; 95% CI 1.21 to 3.77, very likely harmful) compared with players whose acute:chronic workload was 0.60 to 0.97. An acute:chronic workload 1:3 of >1.42 compared with 0.59 to 0.97 displayed a 1.94 times higher risk of injury (RR 1.90; 95% CI 1.08 to 3.36, very likely harmful). Importantly, acute:chronic workload at both 1:4 and 1:3 showed poor predictive power (area under the curve 0.53 to 0.58) despite previous reports and beliefs that it can predict injury.ConclusionsThis study provides evidence for the acute:chronic internal workload (measured using s-RPE) as a risk factor for non-contact injury in elite European footballers. However the acute:chronic workload, in isolation, should not be used to predict non-contact injury.
Dabigatran persistence and adherence in New Zealand: a nationwide retrospective observational study
Authors: Harper Paul , Pollock Daryl , Stephens Matt 
Published: April 2018

ObjectiveTo determine the effect of age and gender on persistence and adherence in patients taking dabigatran for atrial fibrillation.DesignA retrospective observational study over 4 years using refill prescription data from the National Pharmaceutical Database.SettingAll patients in New Zealand who received dabigatran from July 2011 to September 2015.Population43 339 people filled at least one prescription of dabigatran.Main outcome measuresThe proportion of patients with good adherence (treatment available at least 80% of the time), and the proportion at risk of thrombosis (a break in treatment of more than 2 days) measured 6-monthly for 3 years. Medication persistence recorded over 3 years.ResultsPersistence was highest in older patients and showed a significant correlation with age (p<0.001); 24% over 70 years had discontinued treatment by 6 months compared with 50% under 50 years. Adherence was highest in the elderly (p<0.001) with 90% of patients over 80 years with good adherence at 12 months compared with 70% in patients aged 50–60 years and less than 60% in those under 50 years. The time at risk of thrombosis showed a similar pattern with 25% below 60 years with inadequate anticoagulation more than 20% of the time. Adherence dropped during the first 18 months of treatment with the most marked fall in those under 50 years. Adherence shows that breaks in treatment are common with 30% of men under 60 years with a break in treatment of at least 28 days during the first 12 months.ConclusionAdherence and persistence correlate with the patient’s age. Those over 70 years have high adherence consistent over time whereas younger patients have significantly worse adherence which declines over the first 18 months, with the lowest rate in those under 50 years. Adherence in our study is lower than reported in clinical trials, therefore the benefit of dabigatran in stroke prevention may not be realised in clinical practice especially in younger patients.
Acceptability and effectiveness of using mobile applications to promote HIV and other STI testing among men who have sex with men in Barcelona, Spain
Authors: Alarcón Gutiérrez Miguel , Fernández Quevedo Manuel , Martín Valle Silvia , Jacques-Aviñó Constanza , Díez David Elia , Caylà Joan A , García de Olalla Patricia 
Published: April 2018

ObjectiveTo evaluate the acceptability and effectiveness of a pilot intervention programme using gay geosocial mobile applications (apps) to offer rapid HIV and other STI tests to men who have sex with men (MSM) in Barcelona between December 2015 and March 2016.MethodologyWe offered rapid HIV, syphilis and hepatitis C testing by sending private messages on apps for sexual and social encounters. Acceptance was defined as the proportion of users who favourably responded to the message and effectiveness was defined as the proportion of users who attended our facilities among those who were interested in attending. To identify variables associated with the response to the messages, multivariate logistic regression was used. Adjusted OR (ORa) and 95% CIs were calculated. We collected information on sociodemographics, sexual behaviours and app usage from the contacted user profiles and from users who attended our facilities. A descriptive analysis was carried out.Results2656 individual messages were sent. Overall, a 38.4% response rate was obtained, 83.0% of them found it acceptable to receive the unsolicited message, and 73.2% effectiveness was obtained. Responders had higher odds of being 45 years or older (ORa=1.48; 95% CI 1.06 to 2.08), being connected at the moment the message was sent or during the previous hour (ORa=1.92; 95% CI 1.38 to 2.68), having a profile photo not exposing bare chest or abdomen (ORa=1.44; 95% CI 1.07 to 1.92) and using the Grindr app (ORa=1.39; 95% CI 1.12 to 1.73). Of those who were tested and took the survey (n=77), 45.5% had not taken an HIV test in over a year, 24.7% had had a previous STI diagnosis, 51.4% had reported anal sex without condom and 52% had consumed alcohol or drugs for sex.ConclusionsThe response rate, acceptance and effectiveness observed in this study indicate that this strategy could be a useful tool for promoting STI testing among high-risk MSM population.
Determining the reliability of craniocervical flexion test in asymptomatic individuals
Authors: Kotwani Seema , Bid D. N. , Ghatamaneni Dinesh , Alahmari Khalid A , Ramalingam Thangamani , Paul Silvian S. 
Published: April 2018

Background: The inter-rater reliability of the craniocervical flexion test (CCFT) has not been established.Objective: To investigate the intra-rater and inter-rater reliabilities of the CCFT in asymptomatic subjects.Methods: Sixty asymptomatic subjects were randomly selected for the study. The CCFT was measured on each subject by two testers for inter-rater reliability and by one of the testers after a gap of seven days for the intra-rater reliability. Before testing, the participants were trained for the movement and compensations were corrected.Results: The CCFT has high inter-rater reliability (intra-class correlation coefficient [Formula: see text] 0.907, standard error of mean [Formula: see text] 0.735) and high intra-rater reliability (intra-class correlation coefficient [Formula: see text] 0.986, standard error of mean [Formula: see text] 0.287). A Bland & Altman limits of agreement analysis has confirmed the high inter- and intra-rater reliabilities of the test.Conclusion: The CCFT has high inter-rater and intra-rater reliabilities in asymptomatic subjects.
Tumor necrosis factor alpha reduces intestinal vitamin C uptake: a role for NF-κB-mediated signaling
Authors: Subramanian Veedamali S. , Sabui Subrata , Subramenium Ganapathy A. , Marchant Jonathan S. , Said Hamid M. 
Published: April 2018

Sodium-dependent vitamin C transporter-1 (SVCT-1) is the major transporter mediating intestinal vitamin C uptake. Intestinal inflammation and prolonged infection are associated with increased serum and intestinal mucosa levels of tumor necrosis factor-α (TNF-α), which also exerts profound effects on the intestinal absorption process. Elevated levels of TNF-α have been linked to the pathogenesis of inflammatory bowel disease (IBD) and malabsorption of nutrients, and patients with this condition have low levels of vitamin C. To date, little is known about the effect of TNF-α on intestinal absorption of vitamin C. We studied the impact of TNF-α on ascorbic acid (AA) transport using a variety of intestinal preparations. The expression level of human SVCT-1 mRNA is significantly lower in patients with IBD. TNF-α treated Caco-2 cells and mice showed a significant inhibition of intestinal14C-AA uptake. This inhibition was associated with significant decreases in SVCT-1 protein, mRNA, and heterogeneous nuclear RNA levels in TNF-α treated Caco-2 cells, mouse jejunum, and enteroids. Also, TNF-α caused a significant inhibition in the SLC23A1 promoter activity. Furthermore, treatment of Caco-2 cells with celastrol (NF-κB inhibitor) blocked the inhibitory effect caused by TNF-α on AA uptake, SVCT-1 protein, and mRNA expression, as well as the activity of SLC23A1 promoter. Treatment of TNF-α also led to a significant decrease in the expression of hepatocyte nuclear factor-1-α, which drives the basal activity of SLC23A1 promoter, and this effect was reversed by celastrol. Together, these findings show that TNF-α inhibits intestinal AA uptake, and this effect is mediated, at least in part, at the level of transcription of the SLC23A1 gene via the NF-κB pathway.NEW & NOTEWORTHY Our findings show that tumor necrosis factor-α inhibits intestinal ascorbic acid uptake in both in vitro and in vivo systems, and this inhibitory effect is mediated, at least in part, at the level of transcription of the SLC23A1 (sodium-dependent vitamin C transporter-1) gene via the NF-κB pathway.
Incidence, Risk Factors, and Clinical Characteristics of Peripartum Cardiomyopathy in South Korea
Authors: Lee Sunki , Cho Geum Joon , Park Geun U. , Kim Log Young , Lee Tae-Seon , Kim Do Young , Choi Suk-Won , Youn Jong-Chan , Han Seong Woo , Ryu Kyu-Hyung , Na Jin Oh , Choi Cheol Ung , Seo Hong Seog , Kim Eung Ju 
Published: April 2018

Background:
Peripartum cardiomyopathy (PPCM) is a rare disorder associated with pregnancy that can lead to life-threatening conditions. The incidence and clinical characteristics of this condition remain poorly understood.

Methods and Results:

We aimed to perform the first population-based study of PPCM in South Korea, using the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Patients who fulfilled predefined diagnostic criteria for PPCM from January 1, 2010, to December 31, 2012, were identified from
International Classification of Diseases, Tenth Revision, Clinical Modification
codes. To discriminate PPCM from other causes of heart failure, we excluded subjects who already had heart failure-related
International Classification of Diseases, Tenth Revision, Clinical Modification
codes at least 1 year before delivery. During the study period, there were 1 404 551 deliveries in South Korea, and we excluded 20 159 patients who already had heart failure. In those, a total of 795 cases were identified as PPCM. Patients with PPCM were older, had a higher prevalence of preeclampsia and gestational diabetes mellitus, and were more likely to be primiparous and have multiple pregnancies. Moreover, cesarean section and pregnancy-related complications and in-hospital death were also more common in patients with PPCM. Intriguingly, a considerable number of heart failure cases (n=64; 8.1% of total PPCM) were noted between 5 and 12 months after delivery.

Conclusions:
The incidence of PPCM was 1 in 1741 deliveries in South Korea. Patients with PPCM were older, were more associated with primiparity and multiple pregnancy, had more pregnancy-related complications, and revealed higher in-hospital mortality than controls. The number of cases diagnosed as PPCM were decreased over time after delivery; however, a large number of patients were still noted through 12 months after delivery.