bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil‐To‐Lymphocyte Ratio: An Emerging Marker Predicting Prognosis in Elderly Adults with Community‐Acquired Pneumonia
Authors: Cataudella Emanuela , Giraffa Chiara M. , Di Marca Salvatore , Pulvirenti Alfredo , Alaimo Salvatore , Pisano Marcella , Terranova Valentina , Corriere Thea , Ronsisvalle Maria L. , Di Quattro Rosario , Stancanelli Benedetta , Giordano Mauro , Vancheri Carlo , Malatino Lorenzo
Published: April 2017

Objectives

To explore the performance of the neutrophil‐to‐lymphocyte ratio (NLR), an index of systemic inflammation that predicts prognosis of several diseases, in a cohort of elderly adults with community‐acquired pneumonia (CAP).

Design

Prospective clinical study from January 2014 to July 2016.

Setting

Unit of Internal Medicine, University of Catania, Catania, Italy.

Participants

Elderly adults admitted for CAP (N = 195).

Measurements

Clinical diagnosis of CAP was defined as the presence of a new infiltrate on plain chest radiography or chest computed tomography associated with one or more suggestive clinical features such as dyspnea, hypo‐ or hyperthermia, cough, sputum production, tachypnea (respiration rate >20 breaths per minute), altered breath sounds on physical examination, hypoxemia (partial pressure of oxygen <60 mmHg), leukocytosis (white blood cell count >10,000/μL). Clinical examination, traditional tests such as Pneumonia Severity Index (PSI); Confusion, Urea, Respiratory rate, Blood pressure, aged 65 and older (CURB‐65), and NLR were evaluated at admission. The accuracy and predictive value for 30‐day mortality of traditional scores and NLR were compared.

Results

NLR predicted 30‐day mortality (P < .001) and performed better than PSI (P < .05), CURB‐65, C‐reactive protein, and white blood cell count (P < .001) to predict prognosis. No deaths occurred in participants with a NLR of less than 11.12. Thirty‐day mortality was 30% in those with a NLR between 11.12% and 13.4% and 50% in those with a NLR between 13.4 and 28.3. All participants with a NLR greater than 28.3 died within 30 days.

Conclusions

These results would encourage early discharge of individuals with a NLR of less than 11.12, short‐term in‐hospital care for those with a NLR between 11.12 and 13.4, middle‐term hospitalization for those with a NLR between 13.4 and 28.3, and admission to a respiratory intensive care unit for those with a NLR greater than 28.3.
Determinants of board size in an emerging market
Authors: Min Byung S.
Published: April 2017

Drawing largely upon the selective adaptation paradigm, the resource dependence literature, and the capture argument, we examine determinants of board size using panel data set of Korean‐listed companies that have experienced dramatic changes in their governance system following the 1997 Asian crisis and regulatory reforms. Observing that the firm's compliance with statutory requirements reflects a strategic choice, our results also investigate the idea that the determinants of board size differ between firms actively and passively adapting to regulatory reforms. For actively adaptive firms, board size increases along with firm complexity but it varies inversely with the power of controlling shareholders (CSHs). In contrast, the roles of complexity andCSHs are not significant but seniority‐based promotion is an important factor to increase the size for the passive firms. Our results suggest that determinants of board size differ depending on corporate strategies to comply with statutory requirements in an emerging market where family business is dominant and corporate governance system has substantially changed.
The role of autophagy in pro‐inflammatory responses of microglia activation via mitochondrial reactive oxygen species in vitro
Authors: Ye Junli , Jiang Zhongxin , Chen Xuehong , Liu Mengyang , Li Jing , Liu Na
Published: April 2017

Microglia over‐activation contributes to neurodegenerative processes by neurotoxin factors and pro‐inflammatory molecules of pro‐inflammatory processes. Mitochondrial reactive oxygen species (ROS) and autophagy pathway might be involved in microglial activation, but the underlying mechanism is unclear. Here, we regulated autophagy pathway of microglia in vitro by autophagy inhibition (3‐methyladenine treatment, siRNA‐Beclin 1 or siRNA‐ATG5 transfection) or induction (rapamycin treatment) in murine microglial BV‐2 cells or cultured primary mouse microglial cells. And we found that autophagy inhibition could sensitize mitochondrial profile and microglial activation of cultured microglial cells, demonstrated by significant production of mitochondrial ROS, loss of mitochondrial membrane potential, secretion of pro‐inflammatory cytokines including interleukin 1β (IL‐1β), interleukin 6 (IL‐6), interleukin 12 (IL‐12) and tumor necrosis factor α and marked activation of mitogen‐activated proteinkinases (MAPKs) and nuclear factor κB (NF‐κB). These effects could be blocked by specific inhibitors of MAPK and NF‐κB or mitochondrial antioxidants, Mito‐TEMPO. Meanwhile, induction of autophagy with rapamycin treatment could significantly suppress microglial inflammatory responses, mitochondrial ROS production, activation of MAPKs and NF‐κB. Taken together, our in vitro results from primary cultured microglia and BV‐2 cell lines indicated that autophagy inhibition might participate in brain macrophage or microglia over‐activation and mitochondrial ROS generation might be involved in the regulatory microglial pro‐inflammatory responses.

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Drugs with antidepressant properties affect tryptophan metabolites differently in rodent models with depression‐like behavior
Authors: Eskelund Amanda , Li Yan , Budac David P. , Müller Heidi K. , Gulinello Maria , Sanchez Connie , Wegener Gregers
Published: April 2017

The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine, and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC‐MS/MS), in Flinders Sensitive Line rats, a genetic rat model of depression, and its controls: Flinders Sensitive Line and Sprague–Dawley rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains. Furthermore, effects of vortioxetine on tryptophan metabolites were assessed in the cortical regions of lupus mice (MRL/MpJ‐FasIpr), a murine model of increased depression‐like behavior associated with inflammation. Sustained vortioxetine or fluoxetine (at doses aimed to fully occupy serotonin transporter via food or drinking water for at least 14 days) reduced levels of the excitotoxin quinolinic acid (QUIN) in various brain regions in all rats. Furthermore, chronic vortioxetine reduced levels ofQUINinMRL/MpJ‐FasIprmice. Acute i.p. administration of fluoxetine (10 mg/kg) or vortioxetine (10 mg/kg) led to reduced brain 5‐hydroxyindoleacetic acid in Sprague–Dawley rats (2, 4, 6, and 8 h) and a similar trend was evident in Flinders Sensitive Line and Flinders Sensitive Line rats after 4 h. In contrast, single or repeated administration of ketamine (15 mg/kg i.p.) did not induce significant changes in metabolite levels. In conclusion, sustained vortioxetine and fluoxetine administration decreasedQUINindependent of species, while ketamine was ineffective. These results support the hypothesis that modulating tryptophan metabolism may be part of the mechanism of action for some antidepressants.

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Diagnostic criteria for temporomandibular disorders (DC/TMD): interexaminer reliability of the Finnish version of Axis I clinical diagnoses
Authors: Leskinen J. , Suvinen T. , Teerijoki‐Oksa T. , Kemppainen P. , Näpänkangas R. , Alstergren P. , Le Bell Y. , Forssell H. , Myllykangas R. , Tolvanen M. , Doepel M. , Sipilä K.
Published: April 2017

Recently, updated diagnostic criteria for temporomandibular disorders (DC/TMD) were published to assess TMD in a standardised way in clinical and research settings. The DC/TMD protocol has been translated into Finnish using specific cultural equivalency procedures. To assess the interexaminer reliability using the Finnish translations of the DC/TMD‐FIN Axis I clinical diagnostic assessment instruments. Reliability assessment data were collected during a 1‐day DC/TMD Examiner Training Course at the University of Turku, Finland, in collaboration with the International DC/TMD Training and Calibration Center in Malmö University. Clinical TMD examinations according to the Finnish pre‐final version of the DC/TMD Axis I assessment protocol were performed by four experienced TMD specialists on altogether 16 models. Kappa coefficient, overall percentage agreement (%A) as well as positive (PA) and negative (NA) agreements were used to define the reliability. Myofascial pain with referral, headache attributed to TMD and disc displacement (DD) without reduction without limited opening showed excellent kappa values (range 0·87–1·00). Fair‐to‐good reliability was observed for diagnoses of myalgia (k = 0·67), arthralgia (k = 0·71) and DD with reduction (k = 0·64). The PA was high for all pain‐related diagnoses and DD without reduction without limited opening (medians ≥83%), and acceptable for DD with reduction (median 67%). The NA was high (medians ≥87%) for all DC/TMD diagnoses, except for myalgia which showed acceptable NA (median 75%). The %A was high for all assessed diagnoses (medians >85%). The findings of this study showed DC/TMD‐FIN Axis I to demonstrate sufficiently high reliability for pain‐related TMD diagnoses.
The therapeutic role of mental health nurses in psychiatric intensive care: A mixed‐methods investigation in an inner‐city mental health service
Authors: McAllister S. , McCrae N.
Published: April 2017

Accessible summary

What is known on the subject?

Mental health services have been radically transformed since the 1990s, with an emphasis on care in the community. However, acute psychiatric wards remain an important component of service provision. Research shows that patients receive limited therapeutic interaction with nurses in such settings.

A recent review showed that just 4%‐12% of nurses' time was spent on activities that could be considered therapeutic.

What this study adds to existing knowledge?

Whereas nurses wanted more time for individual therapeutic activity, patients were content with brief interactions. However, such contact was not always available, partly due to workload pressures.

Both nurses and patients believed that a collaborative approach, involving the whole multidisciplinary team, was key to the success of therapeutic engagement.

The meaning of therapeutic engagement remains nebulous.

What are the implications for practice?

Nurse education, ward management and clinical supervision should have greater emphasis on therapeutic engagement.

Further research is needed to develop therapeutic engagement in acute psychiatric settings; such work should involve patients as active and equal partners.

Introduction

Despite indications that therapeutic interaction is beneficial for patients and for nurses' job satisfaction in acute psychiatric care, research shows a small amount of nurses' time is spent on such activity.

Aims

This study investigated the actual and potential therapeutic role of the mental health nurse in psychiatric intensive care, where admission is due to violence or aggression.

Methods

In a mixed‐methods concurrent triangulation design, clinician and patient activity was observed using a structured measurement tool, and qualitative interviews were conducted with four practitioners and six patients. Findings were generated using thematic analysis and descriptive statistics.

Results

Of the directly observed 234 clinician and 309 patient activities, 20.9% and 15.9%, respectively, were classified as therapeutic engagement. Interviews revealed that both clinicians and patients wanted more therapeutic contact, but whereas nurses wanted longer time to spend in individual sessions, patients preferred brief but more frequent interaction with nurses.

Discussion

This study shows disparity between actual and desirable levels of therapeutic interaction. Apart from organizational constraints, a fundamental problem is the lack of definition or established practices of therapeutic engagement.

Implications for Practice

There should be more emphasis on therapeutic engagement in nurse education, ward management and clinical supervision.
The effect of training on noise reduction in neonatal intensive care units
Authors: Calikusu Incekar Mujde , Balci Serap
Published: April 2017

Purpose

Noise, an environmental stimulus, is especially important in the neurobehavioral development of newborns and brain development of infants at high risk. Conditions in the neonatal intensive care units (NICUs) may cause certain sensory stimuli that are not appropriate for the development of newborns, especially preterm infants. This study was conducted in order to determine noise levels in the NICU and to evaluate the effect of training provided for noise control.

Design and Methods

This study was conducted as a pretest–posttest quasiexperimental design between September and November 2014 in a 30‐bed NICU of a tertiary hospital in Istanbul. A sample group consisting of 30 people (26 nurses, 4 care workers). Noise measurement devices were used in the Training Program of Noise Control.

Results

Of the health professionals, 96.7% were women, 86.7% were nurses, and 63.3% were university graduates. Some 36.7% of the health professionals had worked within the unit for more than 5 years. Noise measurements of full implementations were made over three 24‐h periods. Noise measurements were taken before and after the training on Monday, Friday, and Sunday. Noise levels after training diminished in all three measurements, and the decrease was found statistically significant (P < 0.01).

Practice Implications

Planned Noise Control Training for health professionals who work in NICUs is an effective way of reducing noise. We recommend that this training should be given to NICU health professionals and noise levels should be determined through measurements at specific times.
A review of early influences on physical activity and sedentary behaviors of preschool‐age children in high‐income countries
Authors: Lindsay Ana Cristina , Greaney Mary L. , Wallington Sherrie F. , Mesa Tatiana , Salas Carlos F.
Published: April 2017

Purpose

Promoting physical activity (PA) is a key component of preventing and controlling childhood obesity. Despite well‐documented benefits of PA, globally, rates of PA among young children have declined over the past decades, and most children are not accruing sufficient PA daily. Helping children develop the foundation for PA habits early in life is critical for the promotion of health in childhood and prevention of chronic diseases later in life, and will ultimately promote longer and healthier lives for individuals and the general population. The purpose of this review is to provide a synthesis of current evidence on influences on PA and sedentary behaviors of preschool‐age children in high‐income countries.

Design and Methods

A systematic review of three databases was performed. Studies conducted in high‐income countries and published from 2000 onward that addressed influences on PA and sedentary behaviors of preschool‐age children were identified and reviewed. Additionally, reference lists of identified articles and relevant published reviews were reviewed. Studies that met the following inclusion criteria were considered: (a) sample included preschoolers (age ≤5 years); (b) PA and/or sedentary behaviors or factors associated with PA and/or sedentary behaviors was assessed; (c) published in English; (d) used either quantitative or qualitative methods; and (e) conducted in a high‐income country. Data were extracted from selected studies to identify influences on PA and sedentary behaviors of preschool‐age children and organized using the social–ecological model according to multiple levels of influence.

Results

Results from included studies identify multiple factors that influence PA and sedentary behaviors of young children in high‐income countries at the various levels of the social–ecological model including intrapersonal, interpersonal, environmental, organizational, and policy.

Practice Implications

Given pediatric nurses’ role as primary care providers, and their frequent and continued contact with parents and their children throughout childhood through well‐child visits, immunization, and minor acute illnesses, they are well positioned to promote and support the development of early healthful PA habits of children starting in early childhood.
Effect of Intravenous or Perivascular Injection of Synthetic Adrenocorticotropic Hormone on Stimulation Test Results in Dogs
Authors: Johnson C.M. , Kass P.H. , Cohen T.A. , Feldman E.C.
Published: April 2017

Background

Standard protocols for adrenocorticotropic hormone (ACTH) stimulation testing (ACTHst) often involve intravenous (IV) injection of corticotropin.ACTHmight be unintentionally injected into the perivascular (PV) space.

Objective

To compare stimulation test results afterIVandPVinjections ofACTH.

Animals

Twenty privately owned dogs were studied: 10 healthy and 10 with trilostane‐treated naturally occurring hyperadrenocorticism (HAC).

Methods

Prospective study. Each of 20 dogs underwent 2ACTHst not <4 nor more than 14 days apart. Five healthy and 5HACdogs had anIV ACTHst first andPVsecond; 5 healthy and 5HACdogs had aPV ACTHst first andIVsecond. Blood samples for measurement of serum cortisol concentration were collected before and 1 hour afterACTHadministration.

Results

No significant difference in results was demonstrated when comparing serum cortisol concentrations afterIVandPV ACTHadministration in all 20 dogs (median μg/dL; interval μg/dL: 8.2; 1.4–17.4 versus 7.8; 0.9–16.9;P= .23). No significant difference in results was demonstrated when comparing serum cortisol concentrations afterIVandPV ACTHadministration in the 10 healthy dogs (median μg/dL; interval μg/dL: 10.9; 7.3–17.4 versus 10.6; 7.1–16.9;P= .54) or in the 10HACdogs (median μg/dL; interval μg/dL: 6.3; 1.4–8.6 versus 5.2; 0.9–8.7;P= .061).

Conclusions and Clinical Importance

Perivascular administration ofACTHdoes not significantly alter stimulation test results in healthy dogs or in dogs withHACundergoing therapy with trilostane.
Effect of Intravenous Small‐Volume Hypertonic Sodium Bicarbonate, Sodium Chloride, and Glucose Solutions in Decreasing Plasma Potassium Concentration in Hyperkalemic Neonatal Calves with Diarrhea
Authors: Trefz F.M. , Constable P.D. , Lorenz I.
Published: April 2017

Background

Hyperkalemia is a frequently observed electrolyte imbalance in dehydrated neonatal diarrheic calves that can result in skeletal muscle weakness and life‐threatening cardiac conduction abnormalities and arrhythmias.

Hypothesis

Intravenous administration of a small‐volume hypertonic NaHCO3solution is clinically more effective in decreasing the plasma potassium concentration (cK) in hyperkalemic diarrheic calves than hypertonic NaCl or glucose solutions.

Animals

Twenty‐two neonatal diarrheic calves withcK >5.8 mmol/L.

Methods

Prospective randomized clinical trial. Calves randomly received either 8.4% NaHCO3(6.4 mL/kg BW; n = 7), 7.5% NaCl (5 mL/kg BW; n = 8), or 46.2% glucose (5 mL/kg BW; n = 7) IV over 5 minutes and were subsequently allowed to suckle 2 L of an electrolyte solution. Infusions with NaHCO3and NaCl provided an identical sodium load of 6.4 mmol/kg BW.

Results

Hypertonic NaHCO3infusions produced an immediate and sustained decrease in plasmacK. Hypertonic glucose infusions resulted in marked hyperglycemia and hyperinsulinemia, butcK remained unchanged for 20 minutes. Between 30 and 120 minutes after initiation of treatment, the most marked decrements incK from baseline occurred in group NaHCO3, which were significantly (P< .05) larger during this period of time than in calves in group NaCl, but not group glucose. After 120 minutes, the mean decrease incK from baseline was −26 ± 10%, −9 ± 8%, and −22 ± 6% in groups NaHCO3, NaCl, and glucose, respectively.

Conclusions/Clinical Importance

Small‐volume hypertonic NaHCO3infusions appear to have clinical advantages for the rapid resuscitation of hyperkalemic diarrheic calves, compared to hypertonic NaCl or glucose solutions.
Biological Variability in Serum Cortisol Concentration Post‐adrenocorticotropic Hormone Stimulation in Healthy Dogs
Authors: Gal A. , Weidgraaf K. , Bowden J.P. , Lopez‐Villalobos N. , Cave N.J. , Chambers J.P. , Castillo‐Alcala F.
Published: April 2017

Background

The ACTH stimulation has low sensitivity for the diagnosis of hypercortisolism possibly as a result of biological and analytical variability.

Hypothesis/Objectives

To report the components of biological and analytical variability in serum cortisol concentration post‐ACTH stimulation ([cortisol]) in healthy dogs.

Animals

Fourteen healthy harrier hound dogs.

Methods

The data were extracted from a separate, prospective, randomized, double‐blinded, controlled discovery study in which dogs treated with vehicle control and 4 different doses of cortisone acetate (CA) for 7 days had an ACTH stimulation test performed to confirm the dose‐dependent effect of CA. The index of individuality (IoI), the critical difference between sequential measurements (CD), and the number of measurements required to assess the homeostatic set point (HSP) of [cortisol] with confidence intervals (CI) of 90 and 95% were estimated.

Results

The IoI was equal to 1.1 and the CD was 3.3 μg/dL (92 nmol/L). The number of measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were 3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in females (13.3 ± 4 μg/dL [366 ± 114 nmol/L] vs. 11.5 ± 2.5 μg/dL [318 ± 65 nmol/L], respectively; P = .046). As expected, treatment with CA resulted in a dose‐dependent suppression of [cortisol].

Conclusions and Clinical Importance

False‐negative test results in hypercortisolism could occur when [cortisol] is outside of the individual's HSP and within the reference interval. The large CD emphasizes the importance of assessing clinically relevant parameters in the diagnosis and monitoring of HC.
Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs
Authors: Hwang J.‐H. , Jeong J.‐W. , Song G.‐H. , Koo T.‐S. , Seo K.‐W.
Published: April 2017

Background

Esomeprazole is an S‐enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported.

Objective

To determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study).

Animals

Seven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively.

Methods

Both studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs.

Results

The bioavailability of esomeprazole administered as PO enteric‐coated granules and as SC injections was 71.4 and 106%, respectively. The half‐life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05).

Conclusion

The PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.
Validation of the BioPRYN enzyme‐linked immunosorbent assay for detection of pregnancy‐specific protein‐B (PSPB) and diagnosis of pregnancy in American bison (Bison bison)
Authors: Love DM , Mefford MT , Ramer JC
Published: April 2017

Contents

This study assessed the accuracy of the commercial BioPRYN® ELISA for the detection of pregnancy‐specific protein‐B (PSPB) using a single blood sample to determine pregnancy status in American bison (Bison bison). A total of 49 bison cows were used in the study, and sampled at two time‐points during the gestation period, fall and spring, correlating with early‐ to mid‐term gestation (average 62.9 days post‐mating) and mid‐ to late‐term gestation (average 229.2 days post‐mating), respectively. Sensitivity of the test during early‐ to mid‐term gestation sampling period (fall) was 87.1%, while specificity was 100%; sensitivity of the test during late‐term gestation sampling period (spring) was 96.3%, while specificity remained at 100%. In total, the test showed a total sensitivity of 91.4%, specificity of 100% and total accuracy of 93.8%, similar to domestic cattle. Use of the single‐sample BioPRYN® ELISA in American Bison for pregnancy diagnosis is economical and practical, minimizing animal handling time, frequency and subsequent stress while providing accurate results for pregnancy diagnosis at 62 days post‐mating. This method should be considered over more traditional pregnancy diagnosis methods for use in managed bison herds.
Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV‐infected adults in Dakar, Senegal
Authors: Byabene A. K. , Fortes‐Déguénonvo L. , Niang K. , Manga M. N. , Bulabula A. N. H. , Nachega J. B. , Seydi M.
Published: April 2017

Objective

To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV‐infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal.

Methods

Cross‐sectional study from 1 September 2013 to 30 January 2014. Outcomes: (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF.

Results

Of 98 HIV‐infected patients on ART, 68% were female. The median (IQR) age was 42 (20–50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI‐based first‐line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade‐off in Se (78.9%, 95% CI: 54.4–93.9%), Sp (20.0%, 95% CI: 11.1–31.7), PPV (22.4, 95% CI: 13.1–34.2%) and NPV (76.5%, 95% CI: 50.1–93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1–147.9; P = 0.04) and being a boosted PI‐based ART regimen ([aOR] = 27.0, 95% CI: 2.4–309.4; P = 0.008).

Conclusions

Optimal ART adherence is achievable in a high proportion of HIV‐infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low‐cost ART adherence monitoring tool in this setting.
N‐glycan maturation mutants in Lotus japonicus for basic and applied glycoprotein research
Authors: Pedersen Carina T. , Loke Ian , Lorentzen Andrea , Wolf Sara , Kamble Manoj , Kristensen Sebastian K. , Munch David , Radutoiu Simona , Spillner Edzard , Roepstorff Peter , Thaysen‐Andersen Morten , Stougaard Jens , Dam Svend
Published: April 2017

Studies of protein N‐glycosylation are important for answering fundamental questions on the diverse functions of glycoproteins in plant growth and development. Here we generated and characterised a comprehensive collection of Lotus japonicusLORE1 insertion mutants, each lacking the activity of one of the 12 enzymes required for normal N‐glycan maturation in the glycosylation machinery. The inactivation of the individual genes resulted in altered N‐glycan patterns as documented using mass spectrometry and glycan‐recognising antibodies, indicating successful identification of null mutations in the target glyco‐genes. For example, both mass spectrometry and immunoblotting experiments suggest that proteins derived from the α1,3‐fucosyltransferase (Lj3fuct) mutant completely lacked α1,3‐core fucosylation. Mass spectrometry also suggested that the Lotus japonicus convicilin 2 was one of the main glycoproteins undergoing differential expression/N‐glycosylation in the mutants. Demonstrating the functional importance of glycosylation, reduced growth and seed production phenotypes were observed for the mutant plants lacking functional mannosidase I, N‐acetylglucosaminyltransferase I, and α1,3‐fucosyltransferase, even though the relative protein composition and abundance appeared unaffected. The strength of our N‐glycosylation mutant platform is the broad spectrum of resulting glycoprotein profiles and altered physiological phenotypes that can be produced from single, double, triple and quadruple mutants. This platform will serve as a valuable tool for elucidating the functional role of protein N‐glycosylation in plants. Furthermore, this technology can be used to generate stable plant mutant lines for biopharmaceutical production of glycoproteins displaying relative homogeneous and mammalian‐like N‐glycosylation features.
MSH1 maintains organelle genome stability and genetically interacts with RECA and RECG in the moss Physcomitrella patens
Authors: Odahara Masaki , Kishita Yoshihito , Sekine Yasuhiko
Published: April 2017

Chloroplast and mitochondrial DNA encodes genes that are essential for photosynthesis and respiration, respectively. Thus, loss of integrity of the genomic DNA of organelles leads to a decline in organelle function and alteration of organelle genetic information. RECA (RECA1 and RECA2) and RECG, which are homologs of bacterial homologous recombination repair (HRR) factors RecA and RecG, respectively, play an important role in the maintenance of integrity of the organelle genome by suppressing aberrant recombination between short dispersed repeats (SDRs) in the moss Physcomitrella patens. On the other hand, MutS homolog 1 (MSH1), a plant‐specific MSH with a C‐terminal GIY‐YIG endonuclease domain, is involved in the maintenance of integrity of the organelle genome in the angiosperm Arabidopsis thaliana. Here, we address the role of the duplicated MSH1 genes, MSH1A and MSH1B, in P. patens, in which MSH1A lacks the C‐terminal endonuclease domain. MSH1A and MSH1B localized to both chloroplast and mitochondrial nucleoids in protoplast cells. Single and double knockout (KO) mutants of MSH1A and MSH1B showed no obvious morphological defects; however, MSH1B KO and double KO mutants, as well as MSH1B GIY‐YIG deletion mutants, exhibited genomic instability due to recombination between SDRs in chloroplasts and mitochondria. Creating double KO mutations of each combination of MSH1B, RECA2 and RECG synergistically increased recombination between SDRs in chloroplasts and mitochondria. These results show the role of MSH1 in the maintenance of integrity of the organelle genome and the genetic interaction between MSH1 and homologs of HRR factors in the basal land plant P. patens.
Sound localization models as evaluation tools for tactical communication and protective systems
Authors: Joubaud Thomas , Zimpfer Véronique , Garcia Alexandre , Langrenne Christophe
Published: April 2017

Tactical Communication and Protective Systems (TCAPS) are hearing protection devices that sufficiently protect the listener's ears from hazardous sounds and preserve speech intelligibility. However, previous studies demonstrated that TCAPS still deteriorate the listener's situational awareness, in particular, the ability to locate sound sources. On the horizontal plane, this is mainly explained by the degradation of the acoustical cues normally preventing the listener from making front-back confusions. As part of TCAPS development and assessment, a method predicting the TCAPS-induced degradation of the sound localization capability based on electroacoustic measurements would be more suitable than time-consuming behavioral experiments. In this context, the present paper investigates two methods based on Head-Related Transfer Functions (HRTFs): a template-matching model and a three-layer neural network. They are optimized to fit human sound source identification performance in open ear condition. The methods are applied to HRTFs measured with six TCAPS, providing identification probabilities. They are compared with the results of a behavioral experiment, conducted with the same protectors, and which ranks the TCAPS by type. The neural network predicts realistic performances with earplugs, but overestimates errors with earmuffs. The template-matching model predicts human performance well, except for two particular TCAPS.
Speech recognition in one- and two-talker maskers in school-age children and adults: Development of perceptual masking and glimpsing
Authors: Buss Emily , Leibold Lori J. , Porter Heather L. , Grose John H.
Published: April 2017

Children perform more poorly than adults on a wide range of masked speech perception paradigms, but this effect is particularly pronounced when the masker itself is also composed of speech. The present study evaluated two factors that might contribute to this effect: the ability to perceptually isolate the target from masker speech, and the ability to recognize target speech based on sparse cues (glimpsing). Speech reception thresholds (SRTs) were estimated for closed-set, disyllabic word recognition in children (5–16 years) and adults in a one- or two-talker masker. Speech maskers were 60 dB sound pressure level (SPL), and they were either presented alone or in combination with a 50-dB-SPL speech-shaped noise masker. There was an age effect overall, but performance was adult-like at a younger age for the one-talker than the two-talker masker. Noise tended to elevate SRTs, particularly for older children and adults, and when summed with the one-talker masker. Removing time-frequency epochs associated with a poor target-to-masker ratio markedly improved SRTs, with larger effects for younger listeners; the age effect was not eliminated, however. Results were interpreted as indicating that development of speech-in-speech recognition is likely impacted by development of both perceptual masking and the ability recognize speech based on sparse cues.
Personalized tumor vaccines keep cancer in check
Authors: Kaiser Jocelyn
Published: April 2017

A new approach enlists a tumor's own mutated proteins.
Epidemic Insurance
Authors: Cohen Jon
Published: April 2017

Caught short by Ebola, the world gets ready for the next outbreak.
Architecture of a transcribing-translating expressome
Authors: Kohler R. , Mooney R. A. , Mills D. J. , Landick R. , Cramer P.
Published: April 2017

Coupling transcription and translation

In bacteria, the transcription of DNA into mRNA by RNA polymerase is coupled to the translation of that mRNA into protein by the ribosome. How this coupling is achieved has been unclear. Kohler
et al.
show that RNA polymerase and the ribosome from
Escherichia coli
can form a so-called expressome complex. Electron microscopy structural analysis, together with functional experiments, revealed details of the coupled complex. The coupling could allow translation to prevent transcriptional pausing, backtracking, and termination.

Science
, this issue p.
194
Semantics derived automatically from language corpora contain human-like biases
Authors: Caliskan Aylin , Bryson Joanna J. , Narayanan Arvind
Published: April 2017

Machines learn what people know implicitly

AlphaGo has demonstrated that a machine can learn how to do things that people spend many years of concentrated study learning, and it can rapidly learn how to do them better than any human can. Caliskan
et al.
now show that machines can learn word associations from written texts and that these associations mirror those learned by humans, as measured by the Implicit Association Test (IAT) (see the Perspective by Greenwald). Why does this matter? Because the IAT has predictive value in uncovering the association between concepts, such as pleasantness and flowers or unpleasantness and insects. It can also tease out attitudes and beliefs—for example, associations between female names and family or male names and career. Such biases may not be expressed explicitly, yet they can prove influential in behavior.

Science
, this issue p.
183
; see also p.
133
Detecting molecular hydrogen on Enceladus
Authors: Seewald Jeffrey S.
Published: April 2017

Cassini spacecraft detects molecular hydrogen on one of Saturn's moons
ToxoplasmaEffectors Targeting Host Signaling and Transcription
Authors: Hakimi Mohamed-Ali , Olias Philipp , Sibley L. David
Published: April 2017

Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions. In parallel, studies on host-pathogen interactions identified many host signaling pathways that were mysteriously altered by infection. It was only with the advent of forward and reverse genetic strategies that the connections between individual parasite effectors and the specific host pathways that they targeted finally became clear. The current repertoire of parasite effectors includes ROP kinases and pseudokinases that are secreted during invasion and that block host immune pathways. Similarly, many secretory GRA proteins alter host gene expression by activating host transcription factors, through modification of chromatin, or by inducing small noncoding RNAs. These effectors highlight novel mechanisms by whichT. gondiihas learned to harness host signaling to favor intracellular survival and will guide future studies designed to uncover the additional complexity of this intricate host-pathogen interaction.
Development and Validation of a Lateral Flow Immunoassay for Rapid Detection of NDM-Producing Enterobacteriaceae
Authors: Boutal Hervé , Naas Thierry , Devilliers Karine , Oueslati Saoussen , Dortet Laurent , Bernabeu Sandrine , Simon Stéphanie , Volland Hervé
Published: April 2017

The global spread of carbapenemase-producing
Enterobacteriaceae
(CPE) that are often resistant to most, if not all, classes of antibiotics is a major public health concern. The NDM-1 carbapenemase is among the most worrisome carbapenemases given its rapid worldwide spread. We have developed and evaluated a lateral flow immunoassay (LFIA) (called the NDM LFIA) for the rapid and reliable detection of NDM-like carbapenemase-producing
Enterobacteriaceae
from culture colonies. We evaluated the NDM LFIA using 175 reference enterobacterial isolates with characterized β-lactamase gene content and 74 nonduplicate consecutive carbapenem-resistant clinical isolates referred for expertise to the French National Reference Center (NRC) for Antibiotic Resistance during a 1-week period (in June 2016). The reference collection included 55 non-carbapenemase producers and 120 carbapenemase producers, including 27 NDM producers. All 27 NDM-like carbapenemase producers of the reference collection were correctly detected in less than 15 min by the NDM LFIA, including 22 strains producing NDM-1, 2 producing NDM-4, 1 producing NDM-5, 1 producing NDM-7, and 1 producing NDM-9. All non-NDM-1 producers gave a negative result with the NDM LFIA. No cross-reaction was observed with carbapenemases (VIM, IMP, NDM, KPC, and OXA-48-like), extended-spectrum β-lactamases (ESBLs) (TEM, SHV, and CTX-M), AmpCs (CMY-2, DHA-2, and ACC-1), and oxacillinases (OXA-1, -2, -9, and -10). Similarly, among the 74 referred nonduplicate consecutive clinical isolates, all 7 NDM-like producers were identified. Overall, the sensitivity and specificity of the assay were 100% for NDM-like carbapenemase detection with strains cultured on agar. The NDM LFIA was efficient, rapid, and easy to implement in the routine workflow of a clinical microbiology laboratory for the confirmation of NDM-like carbapenemase-producing
Enterobacteriaceae
.
Antifungal Susceptibility Testing of Aspergillus spp. by Using a Composite Correlation Index (CCI)-Based Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Method Appears To Not Offer Benefit over Traditional Broth Microdilution Testing
Authors: Gitman Melissa R. , McTaggart Lisa , Spinato Joanna , Poopalarajah Rahgavi , Lister Erin , Husain Shahid , Kus Julianne V.
Published: April 2017

Aspergillus
spp. cause serious invasive lung infections, and
Aspergillus fumigatus
is the most commonly encountered clinically significant species. Voriconazole is considered to be the drug of choice for treating
A. fumigatus
infections; however, rising resistance rates have been reported. We evaluated a matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS)-based method for the differentiation between wild-type and non-wild-type isolates of 20
Aspergillus
spp. (including 2 isolates of
Aspergillus ustus
and 1 of
Aspergillus calidoustus
that were used as controls due their intrinsic low azole susceptibility with respect to the
in vitro
response to voriconazole). At 30 and 48 h of incubation, there was complete agreement between Cyp51A sequence analysis, broth microdilution, and MALDI-TOF MS classification of isolates as wild type or non-wild type. In this proof-of-concept study, we demonstrated that MALDI-TOF MS can be used to accurately detect
A. fumigatus
strains with reduced voriconazole susceptibility. However, rather than proving to be a rapid and simple method for antifungal susceptibility testing, this particular MS-based method showed no benefit over conventional testing methods.
Evaluation of a TaqMan Array Card for Detection of Central Nervous System Infections
Authors: Onyango Clayton O. , Loparev Vladimir , Lidechi Shirley , Bhullar Vinod , Schmid D. Scott , Radford Kay , Lo Michael K. , Rota Paul , Johnson Barbara W. , Munoz Jorge , Oneko Martina , Burton Deron , Black Carolyn M. , Neatherlin John , Montgomery Joel M. , Fields Barry
Published: April 2017

Infections of the central nervous system (CNS) are often acute, with significant morbidity and mortality. Routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-Saharan Africa. We developed a TaqMan array card (TAC) that detects multiple pathogens simultaneously from cerebrospinal fluid. The 21-pathogen CNS multiple-pathogen TAC (CNS-TAC) assay includes two parasites (
Balamuthia mandrillaris
and
Acanthamoeba
), six bacterial pathogens (
Streptococcus pneumonia
e,
Haemophilus influenzae
,
Neisseria meningitidis
,
Mycoplasma pneumoniae
,
Mycobacterium tuberculosis
, and
Bartonella
), and 13 viruses (parechovirus, dengue virus, Nipah virus, varicella-zoster virus, mumps virus, measles virus, lyssavirus, herpes simplex viruses 1 and 2, Epstein-Barr virus, enterovirus, cytomegalovirus, and chikungunya virus). The card also includes human RNase P as a nucleic acid extraction control and an internal manufacturer control, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). This CNS-TAC assay can test up to eight samples for all 21 agents within 2.5 h following nucleic acid extraction. The assay was validated for linearity, limit of detection, sensitivity, and specificity by using either live viruses (dengue, mumps, and measles viruses) or nucleic acid material (Nipah and chikungunya viruses). Of 120 samples tested by individual real-time PCR, 35 were positive for eight different targets, whereas the CNS-TAC assay detected 37 positive samples across nine different targets. The CNS-TAC assays showed 85.6% sensitivity and 96.7% specificity. Therefore, the CNS-TAC assay may be useful for outbreak investigation and surveillance of suspected neurological disease.
Molecular Evolution and Emergence of H5N6 Avian Influenza Virus in Central China
Authors: Du Yingying , Chen Mingyue , Yang Jiayun , Jia Yane , Han Shufang , Holmes Edward C. , Cui Jie
Published: April 2017

H5N6 avian influenza virus (AIV) has posed a potential threat to public health since its emergence in China in 2013. To understand the evolution and emergence of H5N6 AIV in the avian population, we performed molecular surveillance of live poultry markets (LPMs) in Wugang Prefecture, Hunan Province, in central China, during 2014 and 2015. Wugang Prefecture is located on the Eastern Asian-Australian migratory bird flyway, and a human death due to an H5N6 virus was reported in the prefecture on 21 November 2016. In total, we sampled and sequenced the complete genomes of 175 H5N6 AIVs. Notably, our analysis revealed that H5N6 AIVs contain at least six genotypes arising from segment reassortment, including a rare variant that possesses an HA gene derived from H5N1 clade 2.3.2 and a novel NP gene that has its origins with H7N3 viruses. In addition, phylogenetic analysis revealed that genetically similar H5N6 AIVs tend to cluster according to their geographic regions of origin. These results help to reveal the evolutionary behavior of influenza viruses prior to their emergence in humans.

IMPORTANCE
The newly emerged H5N6 influenza A virus has caused more than 10 human deaths in China since 2013. In November 2016, a human death due to an H5N6 virus, in Wugang Prefecture, Hunan Province, was confirmed by the WHO. To better understand the evolution and emergence of H5N6 viruses, we surveyed live poultry markets (LPMs) in Wugang Prefecture before the reported human death, with a focus on revealing the diversity and genomic origins of H5N6 in birds during 2014 and 2015. In general, H5N6 viruses in this region were most closely related to H5N1 clade 2.3.4.4, with the exception of one virus with an HA gene derived from clade 2.3.2 such that it represents a novel reassortant. Clearly, the ongoing surveillance of LPMs is central to monitoring the emergence of pathogenic influenza viruses.